AlPater Posted December 22, 2017 Author Report Share Posted December 22, 2017 Hydralazine induces stress resistance and extends C. elegans lifespan by activating the NRF2/SKN-1 signalling pathway. Dehghan E, Zhang Y, Saremi B, Yadavali S, Hakimi A, Dehghani M, Goodarzi M, Tu X, Robertson S, Lin R, Chudhuri A, Mirzaei H. Nat Commun. 2017 Dec 20;8(1):2223. doi: 10.1038/s41467-017-02394-3. PMID: 29263362 Abstract Nuclear factor (erythroid-derived 2)-like 2 and its Caenorhabditis elegans ortholog, SKN-1, are transcription factors that have a pivotal role in the oxidative stress response, cellular homeostasis, and organismal lifespan. Similar to other defense systems, the NRF2-mediated stress response is compromised in aging and neurodegenerative diseases. Here, we report that the FDA approved drug hydralazine is a bona fide activator of the NRF2/SKN-1 signaling pathway. We demonstrate that hydralazine extends healthy lifespan (~25%) in wild type and tauopathy model C. elegans at least as effectively as other anti-aging compounds, such as curcumin and metformin. We show that hydralazine-mediated lifespan extension is SKN-1 dependent, with a mechanism most likely mimicking calorie restriction. Using both in vitro and in vivo models, we go on to demonstrate that hydralazine has neuroprotective properties against endogenous and exogenous stressors. Our data suggest that hydralazine may be a viable candidate for the treatment of age-related disorders. Longitudinal Assessment of PTH in Community-Dwelling Older Women-Elevations Are Not Associated With Mortality. Buchebner D, Malmgren L, Christensson A, McGuigan F, Gerdhem P, Ridderstråle M, Åkesson K. J Endocr Soc. 2017 Apr 19;1(6):615-624. doi: 10.1210/js.2017-00104. eCollection 2017 Jun 1. PMID: 29264515 https://academic.oup.com/jes/article/1/6/615/3743773 https://watermark.silverchair.com/js.2017-00104.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAakwggGlBgkqhkiG9w0BBwagggGWMIIBkgIBADCCAYsGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMeCxzcXSWzPHOnZ0VAgEQgIIBXHkLp_-vzPgagRHicaqs0u7XSK77gDoggn6_tkPOCUN2VXqF4oIPVICFShvKHZS4a4s-V6NUkKQjMVKJRNCeoiSu_Zv0F_8x9bivXUtdFDSenf0VEiVgGUoEujoXVLDj56ceq6InB3Vo2texqH3rxouK_hxSVpoW88m0WpzDjpO-UzHDU8pf4gMJfH39JimM8kWuK24M9TkPfJzYBN_5xwIQEQiABUqe-IvW1jwJYxhrE1VsX1rO1zNfA6aBq4ZDfXbloNDk9cYKA8lnJ0W3PkT3ynfNwmDFs8bva8ngqzqVGwJD0jVF1BVAgH1s1HnU_RiZbGkWojRH2IM9dFGrXtd8nrRvajViX_eqwQuJ2UiqeuCV4TKeR-ughMnLezHkZP53I5a8FO2dcWhi-sI2vmeewjj5DWrMd8qH8_M8vYYoGn_o_KzqXIB5-FpkY3BBwu0mh6npF9HE0PFqBQ Abstract CONTEXT: In older women, the magnitude of elevated parathyroid hormone (PTH) and its consequence is unclear. OBJECTIVE: To describe normal PTH profiles over time and the association with mortality. DESIGN AND PARTICIPANTS: There were 1044 community-dwelling women in the Malmö Osteoporosis Prospective Risk Assessment cohort (OPRA) who attended baseline (age 75 years). Follow-ups were attended by 715 (age 80 years) and 382 (age 85 years). MAIN OUTCOME MEASURES: PTH, estimated glomerular filtration rate (eGFR), 25-hydroxyvitamin D (25OHD) and mortality. RESULTS: At age 75 years, PTH levels for most (n = 877, 88%) were within the normal reference range (NRR) (i.e., <6.9 pmol/L). Longitudinally, between ages 75 and 80 years, PTH increased in 60% of all women (n = 390) but increases of up to 50% above baseline values (64%; n=250) still resulted in PTH levels within the NRR. These women had lower 25OHD levels (74 vs 83 nmol/L, P = 0.001). Only when increases were >50% was PTH elevated beyond the NRR (mean 7.1 ± 3.3). Here, a pronounced decline in eGFR (56 vs 61 mL/min/1.73 m2, P = 0.002) was found, despite no further changes in 25OHD. Extending the observational period until age 85 years gave similar results. Baseline PTH levels above NRR were associated with mortality (hazard ratio, 1.4; 95% confidence interval (CI), 1.1-1.8; P = 0.007), although not after adjustment for covariates (P = 0.082). CONCLUSIONS: Most women remained within normal PTH ranges despite large increases of up to 50%. PTH elevated above normal is not independently associated with mortality; impaired kidney function and low 25OHD status may be more prognostic in the very old. KEYWORDS: PTH; elderly women; kidney function; mortality; vitamin D Restoration of metabolic health by decreased consumption of branched-chain amino acids. Cummings NE, Williams EM, Kasza I, Konon EN, Schaid MD, Schmidt BA, Poudel C, Sherman DS, Yu D, Arriola Apelo SI, Cottrell SE, Geiger G, Barnes ME, Wisinski JA, Fenske RJ, Matkowskyj KA, Kimple ME, Alexander CM, Merrins MJ, Lamming DW. J Physiol. 2017 Dec 19. doi: 10.1113/JP275075. [Epub ahead of print] PMID: 29266268 Abstract Obesity and diabetes are increasing problems around the world, and while even moderate weight loss can improve metabolic health, reduced calorie diets are notoriously difficult to sustain. Branched-chain amino acids (BCAAs; leucine, isoleucine, and valine) are elevated in the blood of obese, insulin-resistant humans and rodents. We recently demonstrated that specifically reducing dietary levels of BCAAs has beneficial effects on the metabolic health of young, growing mice, improving glucose tolerance and modestly slowing fat mass gain. Here, we examine the hypothesis that reducing dietary BCAAs will promote weight loss, reduce adiposity, and improve blood glucose control in diet-induced obese mice with pre-existing metabolic syndrome. We find that specifically reducing dietary BCAAs rapidly reverses diet-induced obesity and improves glucoregulatory control in diet-induced obese mice. Most dramatically, mice eating an otherwise unhealthy high-calorie, high-sugar Western diet with reduced levels of BCAAs lost weight and fat mass rapidly until regaining a normal weight. Importantly, this normalization of weight was mediated not by caloric restriction or increased activity, but by increased energy expenditure, and was accompanied by a transient induction of the energy balance regulating hormone FGF21. Consumption of a Western diet reduced in BCAAs was also accompanied by a dramatic improvement in glucose tolerance and insulin resistance. Our results link dietary BCAAs to the regulation of metabolic health and energy balance in obese animals, and suggest that specifically reducing dietary BCAAs may represent a highly translatable option for the treatment of obesity and insulin resistance. The Scientist » News & Opinion » Daily News Study Pinpoints Potential “Master Regulator” of Age-Related Cognitive Decline Upping a gene’s expression in rat brains made them better learners and normalized the activity of hundreds of other genes to resemble the brains of younger animals. By Shawna Williams | December 18, 2017 https://www.the-scientist.com/?articles.view/articleNo/51199/title/Study-Pinpoints-Potential--Master-Regulator--of-Age-Related-Cognitive-Decline/&utm_source=hs_email&utm_medium=email&utm_content=59498324&_hsenc=p2ANqtz-8LNzLy6tZYewfWyh_sRdehno0HDMzac-J-yp28cY4PpD5OhUke7REmNngULcVVlKu2V80vETI3KaByBWFJwCC2wYNBNw&_hsmi=59498324 >>>>>>>>>>>>>>>>>>>>>>>> FK506-Binding Protein 12.6/1b, a negative regulator of [Ca<sup>2+</sup>], rescues memory and restores genomic regulation in the hippocampus of aging rats. Gant JC, Blalock EM, Chen KC, Kadish I, Thibault O, Porter NM, Landfield PW. J Neurosci. 2017 Dec 18. pii: 2234-17. doi: 10.1523/JNEUROSCI.2234-17.2017. [Epub ahead of print] PMID: 29255009 Abstract Hippocampal overexpression of FK506-binding protein 12.6/1b (FKBP1b), a negative regulator of ryanodine receptor Ca2+ release, reverses aging-induced memory impairment and neuronal Ca2+ dysregulation. Here, we test the hypothesis that FKBP1b also can protect downstream transcriptional networks from aging-induced dysregulation. We gave hippocampal microinjections of FKBP1b-expressing viral vector to male rats at either 13-months-of-age (long-term) or 19-months-of-age (short-term) and tested memory performance in the Morris water maze at 21-months-of-age. Aged rats treated short- or long-term with FKBP1b substantially outperformed age-matched vector controls and performed similarly to each other and young controls. Transcriptional profiling in the same animals identified 2342 genes whose hippocampal expression was up-/down-regulated in aged controls vs. young controls (the aging effect). Of these aging-dependent genes, 876 (37%) also showed altered expression in aged FKBP1b-treated rats compared to aged controls, with FKBP1b restoring expression of essentially all such genes (872/876, 99.5%) in the direction opposite the aging effect and closer to levels in young controls. This inverse relationship between the aging and FKBP1b effects suggests that the aging effects arise from FKBP1b deficiency. Functional category analysis revealed that genes downregulated with aging and restored by FKBP1b associated predominantly with diverse brain structure categories, including cytoskeleton, membrane channels and extracellular region. Conversely, genes upregulated with aging but not restored by FKBP1b associated primarily with glial-neuroinflammatory, ribosomal and lysosomal categories. Immunohistochemistry confirmed aging-induced rarefaction, and FKBP1b-mediated restoration, of neuronal microtubular structure. Thus, a previously-unrecognized genomic network modulating diverse brain structural processes is dysregulated by aging and restored by FKBP1b overexpression.SIGNIFICANCE STATEMENTPreviously, we found that hippocampal overexpression of FK506-binding protein 12.6/1b (FKBP1b), a negative regulator of intracellular Ca2+ responses, reverses both aging-related Ca2+ dysregulation and cognitive impairment. Here, we test whether hippocampal FKBP1b overexpression also counteracts aging changes in gene transcriptional networks. In addition to reducing memory deficits in aged rats, FKBP1b selectively counteracted aging-induced expression changes in 37% of aging-dependent genes, with cytoskeletal and extracellular structure categories highly associated with the FKBP1b-rescued genes. Our results indicate that, in parallel with cognitive processes, a novel transcriptional network coordinating brain structural organization is dysregulated with aging and restored by FKBP1b. The Adiponectin Paradox for All-Cause and Cardiovascular Mortality. Menzaghi C, Trischitta V. Diabetes. 2018 Jan;67(1):12-22. doi: 10.2337/dbi17-0016. PMID: 29263167 Abstract Basic science studies have shown beneficial effects of adiponectin on glucose homeostasis, chronic low-grade inflammation, apoptosis, oxidative stress, and atherosclerotic processes, so this molecule usually has been considered a salutary adipokine. It was therefore quite unexpected that large prospective human studies suggested that adiponectin is simply a marker of glucose homeostasis, with no direct favorable effect on the risk of type 2 diabetes and cardiovascular disease. But even more unforeseen were data addressing the role of adiponectin on the risk of death. In fact, a positive, rather than the expected negative, relationship was reported between adiponectin and mortality rate across many clinical conditions, comprising diabetes. The biology underlying this paradox is unknown. Several explanations have been proposed, including adiponectin resistance and the confounding role of natriuretic peptides. In addition, preliminary genetic evidence speaks in favor of a direct role of adiponectin in increasing the risk of death. However, none of these hypotheses are based on robust data, so further efforts are needed to unravel the elusive role of adiponectin on cardiometabolic health and, most important, its paradoxical association with mortality rate. Nutrients and bioactives in green leafy vegetables and cognitive decline: Prospective study. Morris MC, Wang Y, Barnes LL, Bennett DA, Dawson-Hughes B, Booth SL. Neurology. 2017 Dec 20. pii: 10.1212/WNL.0000000000004815. doi: 10.1212/WNL.0000000000004815. [Epub ahead of print] PMID: 29263222 Abstract OBJECTIVE: To increase understanding of the biological mechanisms underlying the association, we investigated the individual relations to cognitive decline of the primary nutrients and bioactives in green leafy vegetables, including vitamin K (phylloquinone), lutein, β-carotene, nitrate, folate, kaempferol, and α-tocopherol. METHODS: This was a prospective study of 960 participants of the Memory and Aging Project, ages 58-99 years, who completed a food frequency questionnaire and had ≥2 cognitive assessments over a mean 4.7 years. RESULTS: In a linear mixed model adjusted for age, sex, education, participation in cognitive activities, physical activities, smoking, and seafood and alcohol consumption, consumption of green leafy vegetables was associated with slower cognitive decline; the decline rate for those in the highest quintile of intake (median 1.3 servings/d) was slower by β = 0.05 standardized units (p = 0.0001) or the equivalent of being 11 years younger in age. Higher intakes of each of the nutrients and bioactives except β-carotene were individually associated with slower cognitive decline. In the adjusted models, the rates for the highest vs the lowest quintiles of intake were β = 0.02, p = 0.002 for phylloquinone; β = 0.04, p = 0.002 for lutein; β = 0.05, p < 0.001 for folate; β = 0.03, p = 0.02 for α-tocopherol; β = 0.04, p = 0.002 for nitrate; β = 0.04, p = 0.003 for kaempferol; and β = 0.02, p = 0.08 for β-carotene. CONCLUSIONS: Consumption of approximately 1 serving per day of green leafy vegetables and foods rich in phylloquinone, lutein, nitrate, folate, α-tocopherol, and kaempferol may help to slow cognitive decline with aging. Weight change and 15 year mortality: results from the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) cohort study. Mulligan AA, Lentjes MAH, Luben RN, Wareham NJ, Khaw KT. Eur J Epidemiol. 2017 Dec 20. doi: 10.1007/s10654-017-0343-y. [Epub ahead of print] PMID: 29264789 https://link.springer.com/article/10.1007%2Fs10654-017-0343-y https://link.springer.com/content/pdf/10.1007%2Fs10654-017-0343-y.pdf Abstract Studies have reported a higher mortality risk associated with weight loss, particularly in middle-aged and older adults, although some of these studies did find that gaining weight was also associated with an increased mortality risk. We examined changes in weight in relation to mortality in a prospective population-based cohort study of men and women, resident in Norfolk, UK. Participants were assessed at baseline (1993-1997) and at a second examination (1998-2000), as part of the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk) study, and followed up to 2015 for mortality. Participants with a self-reported history of cancer or cardiovascular disease, body mass index < 18.5 kg/m2 or missing data on adjustment variables, at either time-point were excluded, leaving 12,580 participants, aged 39-78 in 1993-1997, eligible for analyses. Cox proportional hazards models were used to determine Hazard Ratios (HRs) for all-cause (2603 deaths), cardiovascular (749 deaths), cancer (981 deaths), respiratory (226 deaths) and other causes of mortality (647 deaths) by categories of weight change. After multivariate adjustment, the HRs (95% CIs) for all-cause mortality for men and women who lost more than 5 kg were 1.85 (1.48-2.31) and 1.64 (1.31-2.05) respectively. Higher hazards were also found for specific causes of mortality and weight loss > 5 kg. Similar associations were observed after excluding deaths in the first 5 years of follow-up. Results for weight gain were inconclusive. We conclude that objectively measured weight loss, but not weight gain, was associated with subsequent higher mortality risk in this population-based study of middle-aged and elderly men and women. However, undiagnosed, pre-existing disease and the inability to account for weight cycling need to be remembered when interpreting these results. Unravelling the causal pathways underlying this association will require more detailed studies, including that of changes in body composition. KEYWORDS: All-cause mortality; CVD mortality; Cancer mortality; EPIC-Norfolk; Weight change; Weight loss Quote Link to comment Share on other sites More sharing options...
AlPater Posted December 23, 2017 Author Report Share Posted December 23, 2017 Opioid overdoses reducing overall U.S. life expectancy No comparable information available for Canada The Associated Press Posted: Dec 21, 2017 http://www.cbc.ca/news/health/opioid-overdoses-reduce-life-expectancy-in-us-1.4460280 Configuration and validation of a novel prostate disease nomogram predicting prostate biopsy outcome: A prospective study correlating clinical indicators among Filipino adult males with elevated PSA level. Chua ME, Tanseco PP, Mendoza JS, Castillo JC, Morales ML Jr, Luna SL Jr. Asian J Urol. 2015 Apr;2(2):114-122. doi: 10.1016/j.ajur.2015.04.023. Epub 2015 Apr 21. PMID: 29264129 https://www.sciencedirect.com/science/article/pii/S2214388215000557 https://ac.els-cdn.com/S2214388215000557/1-s2.0-S2214388215000557-main.pdf?_tid=2b60a88c-e804-11e7-a341-00000aab0f6b&acdnat=1514049215_2336340f3996ae3490508991916d6d17 Abstract OBJECTIVE: To configure and validate a novel prostate disease nomogram providing prostate biopsy outcome probabilities from a prospective study correlating clinical indicators and diagnostic parameters among Filipino adult male with elevated serum total prostate specific antigen (PSA) level. METHODS: All men with an elevated serum total PSA underwent initial prostate biopsy at our institution from January 2011 to August 2014 were included. Clinical indicators, diagnostic parameters, which include PSA level and PSA-derivatives, were collected as predictive factors for biopsy outcome. Multiple logistic-regression analysis involving a backward elimination selection procedure was used to select independent predictors. A nomogram was developed to calculate the probability of the biopsy outcomes. External validation of the nomogram was performed using separate data set from another center for determination of sensitivity and specificity. A receiver-operating characteristic (ROC) curve was used to assess the accuracy in predicting differential biopsy outcome. RESULTS: Total of 552 patients was included. One hundred and ninety-one (34.6%) patients had benign prostatic hyperplasia, and 165 (29.9%) had chronic prostatitis. The remaining 196 (35.5%) patients had prostate adenocarcinoma. The significant independent variables used to predict biopsy outcome were age, family history of prostate cancer, prior antibiotic intake, PSA level, PSA-density, PSA-velocity, echogenic findings on ultrasound, and DRE status. The areas under the receiver-operating characteristic curve for prostate cancer using PSA alone and the nomogram were 0.688 and 0.804, respectively. CONCLUSION: The nomogram configured based on routinely available clinical parameters, provides high predictive accuracy with good performance characteristics in predicting the prostate biopsy outcome such as presence of prostate cancer, high Gleason prostate cancer, benign prostatic hyperplasia, and chronic prostatitis. KEYWORDS: Benign prostatic hyperplasia; Nomogram; Prostate cancer; Prostatitis High Dietary Saturated Fat is Associated with a Low Risk of Intracerebral Hemorrhage and Ischemic Stroke in Japanese but not in Non-Japanese: A Review and Meta-Analysis of Prospective Cohort Studies. Muto M, Ezaki O. J Atheroscler Thromb. 2017 Dec 20. doi: 10.5551/jat.41632. [Epub ahead of print] PMID: 29269706 Abstract AIM: The associations between dietary saturated fatty acids and the risks of stroke subtypes in cohort studies were examined by a meta-analysis of separate ethnic Japanese and non-Japanese cohorts, and causes of their difference were elucidated. METHOD: Log hazard ratio (HR) with 95% confidence interval (CI) of the highest versus the lowest saturated fat intake from cohort studies were weighed by an inverse variance method to combine HRs. RESULTS: Five studies of intracerebral hemorrhage and 11 studies/comparisons of ischemic stroke were selected. A meta-analysis of intracerebral hemorrhage excluding subarachnoid hemorrhage showed a strong inverse association in Japanese (n=3, HR=0.55, 95% CI 0.32-0.94) but not in non-Japanese (n=2, HR=0.98, 95% CI 0.62-1.53). A meta-analysis of ischemic stroke showed a mild inverse association in Japanese (n=4, HR=0.82, 95% CI 0.71-0.93) but not in non-Japanese (n=7, HR= 0.93, 95% CI 0.84-1.03). The effect size of saturated fat in reducing the risk of stroke in Japanese was stronger for intracerebral hemorrhage (45% reduction) than for ischemic stroke (18% reduction). CONCLUSIONS: In Japanese but not in non-Japanese, a diet high in saturated fat is associated with a low risk of intracerebral hemorrhage and ischemic stroke. This may be due to differences in the range of intake of saturated fat, genetic susceptibility, incidence of lacunar infarction, and/or confounding factors such as dietary proteins. An intervention study targeting Japanese will be required to verify the causality. KEYWORDS: Brain infarction; Hemorrhagic stroke; Relative risk; Saturated fatty acid Smoking, alcohol, and diet in relation to risk of pancreatic cancer in China: a prospective study of 0.5 million people. Pang Y, Holmes MV, Guo Y, Yang L, Bian Z, Chen Y, Iona A, Millwood IY, Bragg F, Chen J, Li L, Kartsonaki C, Chen Z. Cancer Med. 2017 Dec 22. doi: 10.1002/cam4.1261. [Epub ahead of print] PMID: 29271112 Abstract In China, the incidence of pancreatic cancer (PC) has increased in recent decades. However, little is known about the relevance to PC risk of lifestyle and behavioral factors such as smoking, alcohol drinking, and diet. The China Kadoorie Biobank prospective study recruited 512,891 adults (210,222 men, 302,669 women) aged 30-79 (mean 52) years from 10 diverse areas during 2004-08. During ~9 years of follow-up, 688 incident cases of PC were recorded among those who had no prior history of cancer at baseline. Cox regression yielded adjusted hazard ratios (HR) for PC associated with smoking, alcohol and selected dietary factors. Overall, 74% of men were ever-regular smokers and 33% of men drank at least weekly, compared with only 3% and 2% of women, respectively. Among men, current regular smoking was associated with an adjusted HR of 1.25 (95% CI 1.08-1.44) for PC, with greater excess risk in urban than rural areas (1.46 [1.19-1.79] vs 1.04 [0.86-1.26]). Heavy, but not light to moderate, alcohol drinking (i.e. ≥420 g/week) was associated with significant excess risk (1.69 [1.21-2.37]), again more extreme in urban than rural areas (1.93 [1.29-2.87] vs 1.35 [0.74-2.48]). Overall, regular consumption of certain foodstuffs was associated with PC risk, with adjusted daily vs never/rare consumption HRs of 0.66 (0.56-0.79) for fresh fruit and 1.16 (1.01-1.33) for red meat. In China, smoking and heavy alcohol drinking were independent risk factors for PC in men. Lower fresh fruit and higher red meat consumption were also associated with higher risk of PC. KEYWORDS: Alcohol; Chinese; fresh fruit; meat; pancreatic cancer; smoking Quote Link to comment Share on other sites More sharing options...
AlPater Posted December 25, 2017 Author Report Share Posted December 25, 2017 (edited) Sensing and signaling mechanisms linking dietary methionine restriction to the behavioral and physiological components of the response. Forney LA, Stone KP, Wanders D, Gettys TW. Front Neuroendocrinol. 2017 Dec 21. pii: S0091-3022(17)30094-8. doi: 10.1016/j.yfrne.2017.12.002. [Epub ahead of print] Review. PMID: 29274999 Abstract Dietary methionine restriction (MR) is implemented using a semi-purified diet that reduces methionine by ∼80% and eliminates dietary cysteine. Within hours of its introduction, dietary MR initiates coordinated series of transcriptional programs and physiological responses that include increased energy intake and expenditure, decreased adiposity, enhanced insulin sensitivity, and reduction in circulating and tissue lipids. Significant progress has been made in cataloguing the physiological responses to MR in males but not females, but identities of the sensing and communication networks that orchestrate these responses remain poorly understood. Recent work has implicated hepatic FGF21 as an important mediator of MR, but it is clear that other mechanisms are also involved. The goal of this review is to explore the temporal and spatial organization of the responses to dietary MR as a model for understanding how nutrient sensing systems function to integrate complex transcriptional, physiological, and behavioral responses to changes in dietary composition. KEYWORDS: FGF21; amino acid sensing; insulin sensitivity; lipid metabolism; obesity Association of obstructive sleep apnoea with the risk of vascular outcomes and all-cause mortality: a meta-analysis. Xie C, Zhu R, Tian Y, Wang K. BMJ Open. 2017 Dec 22;7(12):e013983. doi: 10.1136/bmjopen-2016-013983. PMID: 29275335 http://bmjopen.bmj.com/content/7/12/e013983 http://bmjopen.bmj.com/content/bmjopen/7/12/e013983.full.pdf Abstract OBJECTIVE: This study aimed to conduct a meta-analysis to explore and summarise the evidence regarding the association between obstructive sleep apnoea (OSA) and the subsequent risk of vascular outcomes and all-cause mortality. METHODS: Electronic databases PubMed, Embase and the Cochrane Library were searched to identify studies conducted through May 2016. Prospective cohort studies that reported effect estimates with 95% CIs of major adverse cardiac events (MACEs), coronary heart disease (CHD), stroke, cardiac death, all-cause mortality and heart failure for different levels versus the lowest level of OSA were included. RESULTS: A total of 16 cohort studies reporting data on 24 308 individuals were included. Of these, 11 studies reported healthy participants, and the remaining five studies reported participants with different diseases. Severe OSA was associated with an increased risk of MACEs (relative risk (RR): 2.04; 95% CI 1.56 to 2.66; P<0.001), CHD (RR: 1.63; 95% CI 1.18 to 2.26; P=0.003), stroke (RR: 2.15; 95% CI 1.42 to 3.24; P<0.001), cardiac death (RR: 2.96; 95% CI 1.45 to 6.01; P=0.003) and all-cause mortality (RR: 1.54; 95% CI 1.21 to 1.97; P<0.001). Moderate OSA was also significantly associated with increased risk of MACEs (RR: 1.16; 95% CI 1.01 to 1.33; P=0.034) and CHD (RR: 1.38; 95% CI 1.04 to 1.83; P=0.026). No significant association was found between mild OSA and the risk of vascular outcomes or all-cause mortality (P>0.05). Finally, no evidence of a factor-specific difference in the risk ratio for MACEs among participants with different levels of OSA compared with those with the lowest level of OSA was found. CONCLUSIONS: Severe and moderate OSAs were associated with an increased risk of vascular outcomes and all-cause mortality. This relationship might differ between genders. Therefore, further large-scale prospective studies are needed to verify this difference. KEYWORDS: meta-analysis; mortality; obstructive sleep apnea; vascular outcome Red and processed meat consumption and breast cancer: UK Biobank cohort study and meta-analysis. Anderson JJ, Darwis NDM, Mackay DF, Celis-Morales CA, Lyall DM, Sattar N, Gill JMR, Pell JP. Eur J Cancer. 2017 Dec 21;90:73-82. doi: 10.1016/j.ejca.2017.11.022. [Epub ahead of print] PMID: 29274927 Abstract AIM: Red and processed meat may be risk factors for breast cancer due to their iron content, administration of oestrogens to cattle or mutagens created during cooking. We studied the associations in UK Biobank and then included the results in a meta-analysis of published cohort studies. METHODS: UK Biobank, a general population cohort study, recruited participants aged 40-69 years. Incident breast cancer was ascertained via linkage to routine hospital admission, cancer registry and death certificate data. Univariate and multivariable Cox proportional hazard models were used to explore the associations between red and processed meat consumption and breast cancer. Previously published cohort studies were identified from a systematic review using PubMed and Ovid and a meta-analysis conducted using a random effects model. RESULTS: Over a median of 7 years follow-up, 4819 of the 262,195 women developed breast cancer. The risk was increased in the highest tertile (>9 g/day) of processed meat consumption (adjusted hazard ratio 1.21, 95% confidence interval [CI] 1.08-1.35, p = 0.001). Collation with 10 previous cohort studies provided data on 40,257 incident breast cancers in 1.65 million women. On meta-analysis, processed meat consumption was associated with overall (relative risk [RR] 1.06, 95% CI 1.01-1.11) and post-menopausal (RR 1.09, 95% CI 1.03-1.15), but not pre-menopausal (RR 0.99, 95% CI 0.88-1.10), breast cancer. In UK Biobank and the meta-analysis, red meat consumption was not associated with breast cancer (adjusted HR 0.99 95% CI 0.88-1.12 and RR 1.03, 95% CI 0.99-1.08, respectively). CONCLUSIONS: Consumption of processed meat, but not red meat, may increase the risk of breast cancer. KEYWORDS: Breast cancer; Diet; Post-menopausal; Pre-menopausal; Processed meat; Red meat; UK Biobank Edited December 25, 2017 by AlPater Quote Link to comment Share on other sites More sharing options...
AlPater Posted December 26, 2017 Author Report Share Posted December 26, 2017 Association between coffee or caffeine consumption and fecundity and fertility: a systematic review and dose-response meta-analysis. Lyngsø J, Ramlau-Hansen CH, Bay B, Ingerslev HJ, Hulman A, Kesmodel US. Clin Epidemiol. 2017 Dec 15;9:699-719. doi: 10.2147/CLEP.S146496. eCollection 2017. Review. PMID: 29276412 Abstract OBJECTIVE: The aim was to investigate whether coffee or caffeine consumption is associated with reproductive endpoints among women with natural fertility (ie, time to pregnancy [TTP] and spontaneous abortion [sAB]) and among women in fertility treatment (ie, clinical pregnancy rate or live birth rate). DESIGN: This study was a systematic review and dose-response meta-analysis including data from case-control and cohort studies. METHODS: An extensive literature search was conducted in MEDLINE and Embase, with no time and language restrictions. Also, reference lists were searched manually. Two independent reviewers assessed the manuscript quality using the Newcastle-Ottawa Scale (NOS). A two-stage dose-response meta-analysis was applied to assess a potential association between coffee/caffeine consumption and the outcomes: TTP, SAB, clinical pregnancy, and live birth. Heterogeneity between studies was assessed using Cochrane Q-test and I2 statistics. Publication bias was assessed using Egger's regression test. RESULTS: The pooled results showed that coffee/caffeine consumption is associated with a significantly increased risk of SAB for 300 mg caffeine/day (relative risk [RR]: 1.37, 95% confidence interval [95% CI]: 1.19; 1.57) and for 600 mg caffeine/day (RR: 2.32, 95% CI: 1.62; 3.31). No association was found between coffee/caffeine consumption and outcomes of fertility treatment (based on two studies). No clear association was found between exposure to coffee/caffeine and natural fertility as measured by fecundability odds ratio (based on three studies) or waiting TTP (based on two studies). CONCLUSION: Results from this meta-analysis support the growing evidence of an association between coffee/caffeine intake and the risk of SAB. However, viewing the reproductive capacity in a broader perspective, there seems to be little, if any, association between coffee/caffeine consumption and fecundity. In general, results from this study are supportive of a precautionary principle advised by health organizations such as European Food Safety Authority (EFSA) and World Health Organization (WHO), although the advised limit of a maximum of two to three cups of coffee/200-300 mg caffeine per day may be too high. KEYWORDS: assisted reproduction; caffeine; coffee; fecundity; fertility; spontaneous abortion Association between Sleep Patterns and Health in Families with Exceptional Longevity. Klein L, Gao T, Barzilai N, Milman S. Front Med (Lausanne). 2017 Dec 8;4:214. doi: 10.3389/fmed.2017.00214. eCollection 2017. PMID: 29276708 Abstract BACKGROUND: Sleep patterns such as longer sleep duration or napping are associated with poor health outcomes. Although centenarians and their offspring demonstrate a delayed onset of age-related diseases, it is not known whether they have healthier sleep patterns or are protected against the negative effects of sleep disturbances. METHODS: Data on sleep patterns and health history were collected from Ashkenazi Jewish subjects of the Longevity Genes Project using standardized questionnaires. Participants included individuals with exceptional longevity (centenarians) with preserved cognition (n = 348, median age 97 years), their offspring (n = 513, median age 69 years), and controls (n = 199) age-matched to the offspring. Centenarians reported on their sleep patterns at age 70, while the offspring and controls on their current sleep patterns. Biochemical parameters were measured at baseline. Models were adjusted for age, sex, BMI, and use of sleep medication. RESULTS: The offspring and controls reported similar sleep patterns, with 33% sleeping ≥8 h and 17% napping in each group. At age 70, centenarians were more likely to have slept ≥8 h (55%) and to have napped (28%) compared with offspring and controls, p < 0.01. Among centenarians, no association was noted between sleep patterns and health outcomes. Sleeping for ≥8 h was associated with lower high-density lipoprotein cholesterol levels in the offspring and controls, and with insulin resistance in the offspring, but not with diabetes. Napping was associated with insulin resistance among the controls (p < 0.01), but not the offspring. Controls, but not offspring, who napped were 2.79 times more likely to have one or more of the following diseases: hypertension, myocardial infarction, stroke, or diabetes (OR 2.79, 95% CI 1.08-7.21, p = 0.04). CONCLUSION: Despite being more likely to exhibit risky sleep patterns at age 70 compared with the offspring and controls, the centenarians were protected from age-related morbidities. The offspring of centenarians did exhibit metabolic disturbances in association with less healthy sleep patterns; however, unlike the controls, they were much less likely to manifest age-related diseases. This suggests that offspring may have inherited resilience genotypes from their centenarian parents that protect them against the harmful effects of sleep disturbances. KEYWORDS: age-related diseases; aging; centenarians; longevity; nap; sleep The role of dietary patterns and exceptional parental longevity in healthy aging. Gubbi S, Barzilai N, Crandall J, Verghese J, Milman S. Nutr Healthy Aging. 2017 Dec 7;4(3):247-254. doi: 10.3233/NHA-170028. PMID: 29276794 Abstract BACKGROUND: Individuals with exceptional longevity and their offspring manifest a lower prevalence of age-related diseases than families without longevity. However, the contribution of dietary habits to protection from disease has not been systematically assessed in families with exceptional longevity. OBJECTIVE: The aim of this study is to compare dietary patterns between individuals with parental longevity and individals without parental longevity. METHODS: Dietary intake was evaluated using the Block Brief Food Frequency Questionnaire in 234 community dwelling Ashkenazi Jewish adults aged 65 years and older who were participants of the LonGenity study, which enrolls the offspring of parents with exceptional longevity (OPEL) and offspring of parents with usual survival (OPUS). RESULTS: OPEL constituted 38% of the subjects. The two groups had similar daily intake of total calories (1119 vs. 1218 kcal, p = 0.83), grams of cholesterol (141 g vs. 143 g, p = 0.19), and grams of sodium (1324 g vs.1475 g, p = 0.45), in OPEL vs. OPUS respectively. There were also no significant differences in the intake of other macronutrients, micronutrients, nutritional supplements and consumption of various food groups between OPEL and OPUS after adjustment for age and sex. DISCUSSION: A healthy diet is associated with a lower risk of several chronic diseases. Our study revealed that dietary intake did not differ between OPEL and OPUS; thus, pointing to the role of longevity genes in protecting from disease among individuals with familial longevity. CONCLUSION: The offspring of long-lived parents do not differ in their dietary patterns compared to individuals without parental longevity. KEYWORDS: Diet; aging; longevity; nutrition Quote Link to comment Share on other sites More sharing options...
AlPater Posted December 27, 2017 Author Report Share Posted December 27, 2017 Nutritional implications of dietary interventions for managing gastrointestinal disorders. Staudacher HM, Kurien M, Whelan K. Curr Opin Gastroenterol. 2017 Dec 22. doi: 10.1097/MOG.0000000000000421. [Epub ahead of print] PMID: 29278531 Abstract PURPOSE OF REVIEW: The aim of this review is to summarize some of the key dietary interventions recommended for common gastrointestinal disorders and to discuss recent evidence regarding their nutritional implications. RECENT FINDINGS: The gluten-free diet has been shown to negatively influence overall diet quality. The gluten-free diet is essential in celiac disease, although it is increasingly used for other perceived health benefits for which an analysis of perceived benefit should be weighed against any nutritional risks. Evidence from short-term controlled trials of a diet low in fermentable oligosaccharides, disaccharides, monosaccharide and polyols in irritable bowel syndrome suggests compromised intake of nutrients such as fiber, iron, and calcium, although findings vary across studies. Meanwhile long-term uncontrolled trials suggest dietary adequacy improves with reintroduction and personalization. Although high-fiber diets may be beneficial in diverticular disease and constipation, it may lead to reductions in energy intake and nutrient absorption in at-risk populations. SUMMARY: The role of therapeutic diets in the management of gastrointestinal disorders is increasingly recognized, but there are limited studies investigating their nutritional implications. The judicious use of dietetic expertise should minimize potential nutritional deficits, however further prospective trials are needed to identify the individuals and nutrients most at risk. Dietary Fiber and Metabolic Syndrome: A Meta-Analysis and Review of Related Mechanisms. Chen JP, Chen GC, Wang XP, Qin L, Bai Y. Nutrients. 2017 Dec 26;10(1). pii: E24. doi: 10.3390/nu10010024. Review. PMID: 29278406 Abstract (1) Background: Dietary fiber intake may provide beneficial effects on the components of metabolic syndrome (MetS); however, observational studies reported inconsistent results for the relationship between dietary fiber intake and MetS risk. We conducted a meta-analysis to quantify previous observational studies and a narrative review to summarize mechanisms involved in the potential relationship. (2) Methods: The literature was searched on PubMed and Web of Science until 28 November 2017. A random-effects model was used to calculate the summary risk estimates. Eleven cross-sectional studies and three cohort studies were included in the meta-analysis. Results from the original studies were reported as odds ratios (ORs) or relative ratios (RRs) of the MetS associated with different levels of dietary fiber intake, and the ORs/RRs comparing the highest with lowest categories of the intake were pooled. (3) Results: For the cross-sectional studies, the pooled OR was 0.70 (95% confidence interval (CI): 0.61-0.82) with evidence of high heterogeneity (I² = 74.4%, p < 0.001) and publication bias (p for Egger's test < 0.001). After removing four studies, results remained significant (OR = 0.67, 95% CI: 0.58-0.78) and the heterogeneity was largely reduced (I² = 32.4%, p = 0.181). For the cohort studies, the pooled RR was 0.86 (95% CI: 0.70-1.06). (4) Conclusion: Although the meta-analysis suggests an inverse association between dietary fiber intake and risk of MetS, and the association was supported by a wide range of mechanism studies, the findings are limited by insufficient cohort data. More prospective studies are needed to further verify the association between dietary fiber intake and the risk of MetS. KEYWORDS: dietary fiber; mechanisms; meta-analysis; metabolic syndrome Plasma levels of n-3 fatty acids and risk of coronary heart disease among Japanese: The Japan Public Health Center-based (JPHC) study. Hamazaki K, Iso H, Eshak ES, Ikehara S, Ikeda A, Iwasaki M, Hamazaki T, Tsugane S; JPHC Study Group. Atherosclerosis. 2017 Dec 8. pii: S0021-9150(17)31423-5. doi: 10.1016/j.atherosclerosis.2017.12.004. [Epub ahead of print] PMID: 29277442 Abstract BACKGROUND AND AIMS: Higher intake of fish or n-3 polyunsaturated fatty acids (PUFAs) has been associated with reduced risk of coronary heart disease (CHD). However, it is unclear whether increased blood levels of n-3 PUFAs are associated with reduced risk of CHD in the Japanese population. METHODS: The relationship between circulating levels of n-3 PUFAs (eicosapentaenoic acid + docosapentaenoic acid + docosahexaenoic acid) and risk of CHD was examined in a nested case-control study among participants in the Japan Public Health Center (JPHC)-based Study Cohort. Plasma n-3 PUFA phospholipid levels were measured at baseline by gas chromatography in 209 cases with CHD and 418 controls matched for sex, age, date of blood draw, time elapsed since last meal before blood collection, and study location. The CHD cases (n = 209) comprised 168 cases of myocardial infarction and 41 of sudden cardiac death, otherwise classified as 157 non-fatal and 52 fatal coronary events, respectively. Mean duration of follow-up was 13.5 years. RESULTS: Multivariate conditional logistic analysis showed no significant association between n-3 PUFAs and risk of total CHD. The odds ratio (OR) for the highest versus lowest quartiles of plasma n-3 PUFAs was 0.79 (95% confidence interval [95% CI]: 0.41-1.51, p for trend = 0.51). Subtype analysis of CHD revealed that the multivariate ORs for the highest versus lowest quartiles for n-3 PUFAs were 0.91 (95% CI: 0.43-1.89, p for trend = 0.90) for myocardial infarction, 0.08 (95% CI: 0.01-0.88, p for trend = 0.04) for sudden cardiac death, 0.89 (95% CI: 0.42-1.89, p for trend = 0.97) for nonfatal coronary events, and 0.12 (95% CI: 0.02-0.75, p for trend = 0.03) for fatal coronary events. CONCLUSIONS: Plasma n-3 PUFA levels were not associated with risk of total CHD but were inversely associated with risks of sudden cardiac death and fatal coronary events among middle-aged Japanese individuals. KEYWORDS: Coronary heart disease; Nested case-control study; n-3 polyunsaturated fatty acids Circadian regulation of metabolism and healthspan in Drosophila. Giebultowicz JM. Free Radic Biol Med. 2017 Dec 19. pii: S0891-5849(17)31275-3. doi: 10.1016/j.freeradbiomed.2017.12.025. [Epub ahead of print] Review. PMID: 29277395 Abstract Circadian clocks generate daily rhythms in gene expression, cellular functions, physiological processes and behavior. The core clock mechanism consists of transcriptional-translational negative feedback loops that turn over with an endogenous circa 24h period. Classical genetic experiments in the fly Drosophila melanogaster played an essential role in identification of clock genes that turned out to be largely conserved between flies and mammals. Like in mammals, circadian clocks in flies generate transcriptional rhythms in a variety of metabolic pathways related to feeding and detoxification. Given that rhythms pervade metabolism and the loss of metabolic homeostasis is involved in aging and disease, there is increasing interest in understanding how the clocks and the rhythms they control change during aging. The importance of circadian clocks for healthy aging is supported by studies reporting that genetic or environmental clock disruptions are associated with reduced healthspan and lifespan. For example, arrhythmia caused by mutations in core clock genes lead to symptoms of accelerated aging in both flies and mammals, including neurodegenerative phenotypes. Despite the wealth of descriptive data, the mechanisms by which functional clocks confer healthspan and lifespan benefits are poorly understood. Studies in Drosophila discussed here are beginning to unravel causative relationships between the circadian system and aging. In particular, recent data suggest that clocks may be involved in inducing rhythmic expression of specific genes late in life in response to age-related increase in oxidative stress. This review will summarize insights into links between circadian system and aging in Drosophila, which were obtained using powerful genetics tools available for this model organism and taking advantage of the short adult lifespan in flies that is measured in days rather than years. KEYWORDS: circadian clocks; longevity; metabolic rhythms Association of Short-term Exposure to Air Pollution With Mortality in Older Adults Qian Di, MS; Lingzhen Dai, ScD; Yun Wang, PhD; et al.JAMA. 2017;318(24):2446-2456. doi:10.1001/jama.2017.17923 This case-crossover study estimates the association between short-term exposures to ambient fine particulate matter and ozone and mortality in the continental United States. Key Points Question What is the association between short-term exposure to air pollution below current air quality standards and all-cause mortality? Finding In a case-crossover study of more than 22 million deaths, each 10-μg/m3 daily increase in fine particulate matter and 10–parts-per-billion daily increase in warm-season ozone exposures were associated with a statistically significant increase of 1.42 and 0.66 deaths per 1 million persons at risk per day, respectively. Meaning Day-to-day changes in fine particulate matter and ozone exposures were significantly associated with higher risk of all-cause mortality at levels below current air quality standards, suggesting that those standards may need to be reevaluated. Abstract Importance The US Environmental Protection Agency is required to reexamine its National Ambient Air Quality Standards (NAAQS) every 5 years, but evidence of mortality risk is lacking at air pollution levels below the current daily NAAQS in unmonitored areas and for sensitive subgroups. Objective To estimate the association between short-term exposures to ambient fine particulate matter (PM2.5) and ozone, and at levels below the current daily NAAQS, and mortality in the continental United States. Design, Setting, and Participants Case-crossover design and conditional logistic regression to estimate the association between short-term exposures to PM2.5 and ozone (mean of daily exposure on the same day of death and 1 day prior) and mortality in 2-pollutant models. The study included the entire Medicare population from January 1, 2000, to December 31, 2012, residing in 39 182 zip codes. Exposures Daily PM2.5 and ozone levels in a 1-km × 1-km grid were estimated using published and validated air pollution prediction models based on land use, chemical transport modeling, and satellite remote sensing data. From these gridded exposures, daily exposures were calculated for every zip code in the United States. Warm-season ozone was defined as ozone levels for the months April to September of each year. Main Outcomes and Measures All-cause mortality in the entire Medicare population from 2000 to 2012. Results During the study period, there were 22 433 862 million case days and 76 143 209 control days. Of all case and control days, 93.6% had PM2.5 levels below 25 μg/m3, during which 95.2% of deaths occurred (21 353 817 of 22 433 862), and 91.1% of days had ozone levels below 60 parts per billion, during which 93.4% of deaths occurred (20 955 387 of 22 433 862). The baseline daily mortality rates were 137.33 and 129.44 (per 1 million persons at risk per day) for the entire year and for the warm season, respectively. Each short-term increase of 10 μg/m3 in PM2.5 (adjusted by ozone) and 10 parts per billion (10−9) in warm-season ozone (adjusted by PM2.5) were statistically significantly associated with a relative increase of 1.05% (95% CI, 0.95%-1.15%) and 0.51% (95% CI, 0.41%-0.61%) in daily mortality rate, respectively. Absolute risk differences in daily mortality rate were 1.42 (95% CI, 1.29-1.56) and 0.66 (95% CI, 0.53-0.78) per 1 million persons at risk per day. There was no evidence of a threshold in the exposure-response relationship. Conclusions and Relevance In the US Medicare population from 2000 to 2012, short-term exposures to PM2.5 and warm-season ozone were significantly associated with increased risk of mortality. This risk occurred at levels below current national air quality standards, suggesting that these standards may need to be reevaluated. >>>>>>>>>>>>>>>>> Editorial Low-Level Air Pollution Associated With Death Policy and Clinical Implications Junfeng Zhang, PhD1,2,3 Author Affiliations JAMA. 2017;318(24):2431-2432. doi:10.1001/jama.2017.18948 Globally, an estimated 3.3 million annual premature deaths (5.86% of global mortality) are attributable to outdoor air pollution,1 although ambient air pollution has been regulated under national laws in many countries. In the United States under the Clean Air Act, the primary National Ambient Air Quality Standards (NAAQS) are intended to protect human health, with an adequate margin of safety, including sensitive populations such as children, older adults, and individuals with respiratory diseases. Under the Clean Air Act, the standards are reviewed every 5 years to account for new scientific evidence regarding their appropriateness and adequacy for protecting public health. Association Between Calcium or Vitamin D Supplementation and Fracture Incidence in Community-Dwelling Older AdultsA Systematic Review and Meta-analysis Jia-Guo Zhao, MD; Xian-Tie Zeng, MD; Jia Wang, MD1; Lin Liu, MD2 Abstract Full Text JAMA. 2017;318(24):2466-2482. doi:10.1001/jama.2017.19344 This meta-analysis summarizes the effects of calcium, vitamin D, or combined calcium and vitamin D supplements on fracture incidence among community-dwelling older adults. Key Points Question Is supplementation with calcium, vitamin D, or combined calcium and vitamin D associated with a lower fracture incidence in community-dwelling older adults? Findings In this meta-analysis of 33 randomized clinical trials that included 51 145 participants, the use of supplements that included calcium, vitamin D, or both was not associated with a significant difference in the risk of hip fractures compared with placebo or no treatment (risk ratio, 1.53, 1.21, and 1.09, respectively). Meaning These findings do not support the routine use of these supplements in community-dwelling older adults. Abstract Importance The increased social and economic burdens for osteoporosis-related fractures worldwide make the prevention of such injuries a major public health goal. Previous studies have reached mixed conclusions regarding the association between calcium, vitamin D, or combined calcium and vitamin D supplements and fracture incidence in older adults. Objective To investigate whether calcium, vitamin D, or combined calcium and vitamin D supplements are associated with a lower fracture incidence in community-dwelling older adults. Data Sources The PubMed, Cochrane library, and EMBASE databases were systematically searched from the inception dates to December 24, 2016, using the keywords calcium, vitamin D, and fracture to identify systematic reviews or meta-analyses. The primary randomized clinical trials included in systematic reviews or meta-analyses were identified, and an additional search for recently published randomized trials was performed from July 16, 2012, to July 16, 2017. Study Selection Randomized clinical trials comparing calcium, vitamin D, or combined calcium and vitamin D supplements with a placebo or no treatment for fracture incidence in community-dwelling adults older than 50 years. Data Extraction and Synthesis Two independent reviewers performed the data extraction and assessed study quality. A meta-analysis was performed to calculate risk ratios (RRs), absolute risk differences (ARDs), and 95% CIs using random-effects models. Main Outcomes and Measures Hip fracture was defined as the primary outcome. Secondary outcomes were nonvertebral fracture, vertebral fracture, and total fracture. Results A total of 33 randomized trials involving 51 145 participants fulfilled the inclusion criteria. There was no significant association of calcium or vitamin D with risk of hip fracture compared with placebo or no treatment (calcium: RR, 1.53 [95% CI, 0.97 to 2.42]; ARD, 0.01 [95% CI, 0.00 to 0.01]; vitamin D: RR, 1.21 [95% CI, 0.99 to 1.47]; ARD, 0.00 [95% CI, −0.00 to 0.01]. There was no significant association of combined calcium and vitamin D with hip fracture compared with placebo or no treatment (RR, 1.09 [95% CI, 0.85 to 1.39]; ARD, 0.00 [95% CI, −0.00 to 0.00]). No significant associations were found between calcium, vitamin D, or combined calcium and vitamin D supplements and the incidence of nonvertebral, vertebral, or total fractures. Subgroup analyses showed that these results were generally consistent regardless of the calcium or vitamin D dose, sex, fracture history, dietary calcium intake, and baseline serum 25-hydroxyvitamin D concentration. Conclusions and Relevance In this meta-analysis of randomized clinical trials, the use of supplements that included calcium, vitamin D, or both compared with placebo or no treatment was not associated with a lower risk of fractures among community-dwelling older adults. These findings do not support the routine use of these supplements in community-dwelling older people. Quote Link to comment Share on other sites More sharing options...
AlPater Posted December 28, 2017 Author Report Share Posted December 28, 2017 High-Protein Foods and Physical Activity Protect Against Age-Related Muscle Loss and Functional Decline. Bradlee ML, Mustafa J, Singer MR, Moore LL. J Gerontol A Biol Sci Med Sci. 2017 Dec 12;73(1):88-94. doi: 10.1093/gerona/glx070. PMID: 28549098 https://academic.oup.com/biomedgerontology/article/73/1/88/3854809 Abstract BACKGROUND: Skeletal muscle insulin resistance and reduced mitochondrial capacity have both been reported to be affected by aging. The purpose of this study was to compare the effects of calorie restriction-induced weight loss and exercise on insulin resistance, skeletal muscle mitochondrial content, and mitochondrial enzyme activities in older overweight to obese individuals. METHODS: Insulin-stimulated rates of glucose disposal (Rd) were determined using the hyperinsulinemic euglycemic clamp before and after completing 16 weeks of either calorie restriction to induce weight loss (N = 7) or moderate exercise (N = 10). Mitochondrial volume density, mitochondria membrane content (cardiolipin), and activities of electron transport chain (rotenone-sensitive NADH-oxidase), tricarboxylic acid (TCA) cycle (citrate synthase) and β-oxidation pathway (β-hydroxyacyl CoA dehydrogenase; β-HAD) were measured in percutaneous biopsies of the vastus lateralis before and after the interventions. RESULTS: Rd improved similarly (18.2% ± 9.0%, p < .04) with both weight loss and exercise. Moderate exercise significantly increased mitochondrial volume density (14.5% ± 2.0%, p < .05), cardiolipin content (22.5% ± 13.4%, p < .05), rotenone-sensitive NADH-oxidase (65.7% ± 13.2%, p = .02) and β-HAD (30.7% ± 6.8%, p ≤ .03) activity, but not citrate synthase activity (10.1% ± 4.0%). In contrast, calorie restriction-induced weight loss did not affect mitochondrial content, NADH-oxidase or β-HAD, yet increased citrate synthase activity (44.1% ± 21.1%, p ≤ .04). Exercise (increase) or weight loss (decrease) induced a remodeling of cardiolipin with a small (2%-3%), but significant change in the relative content of tetralinoleoyl cardiolipin. CONCLUSION: Exercise increases both mitochondria content and mitochondrial electron transport chain and fatty acid oxidation enzyme activities within skeletal muscle, while calorie restriction-induced weight loss did not, despite similar improvements in insulin sensitivity in overweight older adults. KEYWORDS: Caloric restriction; Glucose uptake; Human aging; Muscle metabolism; Obesity Genetic Predisposition to Obesity and Medicare Expenditures. Wehby GL, Domingue BW, Ullrich F, Wolinsky FD. J Gerontol A Biol Sci Med Sci. 2017 Dec 12;73(1):66-72. doi: 10.1093/gerona/glx062. PMID: 29240910 https://academic.oup.com/biomedgerontology/article/73/1/66/3811092 https://watermark.silverchair.com/glx062.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAb8wggG7BgkqhkiG9w0BBwagggGsMIIBqAIBADCCAaEGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQMIicLv7tPl_ZM4JuNAgEQgIIBcr6UHeghpbMmVTn5BaLPY5ONV_noo3L2TVOFsNLj8E0mEPvZ-S9KdFlB4HQF4gbwTNO8G9HAzzo6-TlrR-Puc1e8Z19mTUyOAPNONK-kn3aVuN8ggZU9HzNAyhRf8sJztNA1HuMDS5HonAA9hTeD2TbjQhiM_U-7v8uzGsU2G86rAStBOBLXOq2OxT8MgKvLrAuVOM7gt8F2x46UovPgMnsmJXD9fIZDGGJoYFPqBhB3EG3_D6hYR_9dNZGW3RDguoKa24gGt8b86mzxWSskEcmNv2U6VdEOWHY-fp9u6mpyLuBBObQ-DY8EjoI4g6pksWEYnmJQ2aToSOXneIssj09KrvnPF2VEoxWU4olJk-ouaRvIXZZVFGgTEXyH617GJ8_L6iY4eev0pJ4QGdTzi7fDhpBvSjs_4V3d4KsSMaNYehbpNI-1BqdBxUV_V-3KuLvBX2a77D1txg_4vqONPdu3RU4zKe1ozfxbxh2Nwnb0ufM Abstract BACKGROUND: The relationship between obesity and health expenditures is not well understood. We examined the relationship between genetic predisposition to obesity measured by a polygenic risk score for body mass index (BMI) and Medicare expenditures. METHODS: Biennial interview data from the Health and Retirement Survey for a nationally representative sample of older adults enrolled in fee-for-service Medicare were obtained from 1991 through 2010 and linked to Medicare claims for the same period and to Genome-Wide Association Study (GWAS) data. The study included 6,628 Medicare beneficiaries who provided 68,627 complete person-year observations during the study period. Outcomes were total and service-specific Medicare expenditures and indicators for expenditures exceeding the 75th and 90th percentiles. The BMI polygenic risk score was derived from GWAS data. Regression models were used to examine how the BMI polygenic risk score was related to health expenditures adjusting for demographic factors and GWAS-derived ancestry. RESULTS: Greater genetic predisposition to obesity was associated with higher Medicare expenditures. Specifically, a 1 SD increase in the BMI polygenic risk score was associated with a $805 (p < .001) increase in annual Medicare expenditures per person in 2010 dollars (~15% increase), a $370 (p < .001) increase in inpatient expenses, and a $246 (p < .001) increase in outpatient services. A 1 SD increase in the polygenic risk score was also related to increased likelihood of expenditures exceeding the 75th percentile by 18% (95% CI: 10%-28%) and the 90th percentile by 27% (95% CI: 15%-40%). CONCLUSION: Greater genetic predisposition to obesity is associated with higher Medicare expenditures. KEYWORDS: BMI; Healthcare costs; Polygenic risk score Iodine intake from supplements and diet during pregnancy and child cognitive and motor development: the INMA Mother and Child Cohort Study. Murcia M, Espada M, Julvez J, Llop S, Lopez-Espinosa MJ, Vioque J, Basterrechea M, Riaño I, González L, Alvarez-Pedrerol M, Tardón A, Ibarluzea J, Rebagliato M. J Epidemiol Community Health. 2017 Dec 26. pii: jech-2017-209830. doi: 10.1136/jech-2017-209830. [Epub ahead of print] PMID: 29279360 Abstract BACKGROUND: The effect of mild-to-moderate maternal iodine deficiency on the neuropsychological development of their offspring is uncertain. We aimed to assess the association between iodine status during pregnancy and the cognitive and motor development of children at 4-5 years. METHODS: We conducted a prospective cohort study in four Spanish regions with recruitment of pregnant women between 2003 and 2008 and follow-up of their children up to 4-5 years (mean (SD)=4.8 (0.6)). Cognitive and motor function was assessed in 1803 children using the McCarthy Scales of Children's Abilities. Dietary iodine and supplementation were measured through questionnaires twice during pregnancy. Urinary iodine concentration (UIC) was measured in spot samples. The residuals of a regression of UIC against creatinine were used to define a variable corrected for creatinine (UIC~Cr). RESULTS: Neither iodine supplements nor iodised salt consumption or maternal UIC were associated with cognitive or motor function. After adjusting for creatinine, children of women with UIC~Cr <100 µg/L had 3.93 (95% CI -6.18 to -1.69) general cognitive scores lower than the reference (150-249 µg/L). Dietary iodine was inversely associated with motor scores and milk but not other dairy products or seafood consumption accounted for this association (beta: -1.36; 95% CI -2.12 to -0.61; per one daily milk serving). CONCLUSIONS: We found an association between low maternal urinary iodine and lower cognitive scores in childhood, although only when corrected for creatinine, adding to the evidence that iodine deficiency may have potential harmful effects on neurodevelopment. Iodine supplementation does not appear to improve child's neurodevelopment at 4-5 years. KEYWORDS: longitudinal studies; nutrition; pregnancy; public health policy Effects of Diet and Exercise on Peripheral Vascular Disease. Hall JA, Dixson GH, Barnard RJ, Pritikin N. Phys Sportsmed. 1982 May;10(5):90-101. doi: 10.1080/00913847.1982.11947226. PMID: 29278187 Abstract In brief A 46-year-old man presented with symptoms of peripheral vascular disease in 1966. In 1976 arteriography revealed 100% occlusion of both femoral arteries at midthigh and some reconstitution of flow via collaterals into the popliteal region. His cholesterol level was initially 407 mg/100 ml, and his walking tolerance was 100 yards. After a 26-day stay at the Pritikin Longevity Center, his cholesterol dropped from 230 mg/100 ml to 130 mg/100 ml, and his walking tolerance increased to 3 miles in one hour with little leg pain. He has run more than 20 road races and completed a marathon. A recent exercise Doppler exam and a second arteriogram indicated a significant increase in blood flow due to dilation of deep femoral arteries and existing collateral vessels. Early puberty linked to depression in girls The younger the age at the first period, the stronger the risk of mental health problems Thomson Reuters Posted: Dec 27, 2017 http://www.cbc.ca/news/health/puberty-mental-health-girls-1.4021958 Quote Link to comment Share on other sites More sharing options...
AlPater Posted December 29, 2017 Author Report Share Posted December 29, 2017 (edited) Adolescent reserve capacity, socioeconomic status and school achievement as predictors of mortality in Finland - a longitudinal study. Acacio-Claro PJ, Koivusilta LK, Borja JR, Rimpelä AH. BMC Public Health. 2017 Dec 28;17(1):980. doi: 10.1186/s12889-017-4990-4. PMID: 29282033 Abstract BACKGROUND: Despite robust evidence on the inverse relationship between socioeconomic status (SES) and mortality, deviations from expected results have been observed likely due to school achievement and psychosocial resources, termed as "reserve capacity." Since adolescence is a critical period in developing sound psychological and behavioural patterns and adolescent markers of SES were seldom used, we determine if family SES in adolescence predicts later mortality. We also study how reserve capacity (perceived health, health-promoting behaviour and social support) and school achievement modify this relationship and reduce the negative effects of low SES. METHODS: A longitudinal study was designed by linking baseline data on 12 to 18 year-old Finns in 1985-95 (N = 41,833) from the Adolescent Health and Lifestyle Surveys with register data on mortality and SES from Statistics Finland. Average follow-up time was 18.4 years with a total of 770,161 person-years. Cox regression models, stratified by sex, were fitted to determine the effects of variables measured during adolescence: family SES, reserve capacity and school achievement on mortality risk. RESULTS: All reserve capacity dimensions significantly predicted mortality in boys. Perceived health and social support predicted that in girls. Adolescents with the lowest school achievement were more than twice at risk of dying compared to those with better school performance. Low SES increased the risk of death in boys (Hazard ratios: 1.6, 95% CI 1.1-2.4) but not in girls. Reserve capacity and school achievement weakened the effects of low SES on boys' risk of death. CONCLUSIONS: High reserve capacity and good school achievement in adolescence significantly reduce the risk of mortality. In boys, these also mitigate the negative effect of low SES on mortality. These findings underscore the roles of reserve capacity and school achievement during adolescence as likely causal or modifying factors in SES-health inequalities. KEYWORDS: Life course epidemiology; Mortality; Psychosocial resources; Reserve capacity; Socioeconomic status A Low-Fat Dietary Pattern and Diabetes: A Secondary Analysis From the Women's Health Initiative Dietary Modification Trial. Howard BV, Aragaki AK, Tinker LF, Allison M, Hingle MD, Johnson KC, Manson JE, Shadyab AH, Shikany JM, Snetselaar LG, Thomson CA, Zaslavsky O, Prentice RL. Diabetes Care. 2017 Dec 27. pii: dc170534. doi: 10.2337/dc17-0534. [Epub ahead of print] PMID: 29282203 Abstract OBJECTIVE: We performed a secondary analysis to evaluate the effect of the Women's Health Initiative dietary intervention on incident diabetes and diabetes treatment in postmenopausal women. RESEARCH DESIGN AND METHODS: A total of 48,835 women were randomized to a comparison group or an intervention group that underwent a behavioral/nutritional modification program to decrease fat and increase vegetable, fruit, and grain intake for an average of 8.1 years. Ninety-three percent of participants completed the intervention, and 71% participated in active follow-up through 30 September 2015 (median 17.3 years). We measured time to development of treated diabetes and progression from oral antihyperglycemic agents to insulin. Serum glucose and insulin were measured in a subsample of women (N = 2,324) at baseline and years 1, 3, and 6. RESULTS: During the trial, intervention group women had lower rates of initiation of insulin therapy (hazard ratio {HR} 0.74 [95% CI 0.59, 0.94]; P = 0.01). Moreover, women with baseline waist circumference ≥88 cm (P interaction = 0.01) and worse metabolic syndrome scores (P interaction = 0.02) had the greatest reduction in risk of initiating insulin therapy. The decreased risk from the intervention was present during the cumulative follow-up (HR 0.88 [95% CI 0.78, 0.99]; P = 0.04). In participants with measured biomarkers (5.8% subsample) who had baseline glucose <100 mg/dL, the intervention reduced the risk of developing glucose ≥100 mg/dL by 25% (odds ratio 0.75 [95% CI 0.61, 0.93]; P = 0.008). Adjustment for weight change did not alter the results. CONCLUSIONS: In this secondary analysis, a dietary intervention in postmenopausal women aimed at reducing fat and increasing intake of vegetables, fruits, and grains did not increase risk of diabetes and may have slowed progression. Protection by extra virgin olive oil against oxidative stress in vitro and in vivo. Chemical and biological studies on the health benefits due to a major component of the Mediterranean diet. Rossi M, Caruso F, Kwok L, Lee G, Caruso A, Gionfra F, Candelotti E, Belli SL, Molasky N, Raley-Susman KM, Leone S, Filipský T, Tofani D, Pedersen J, Incerpi S. PLoS One. 2017 Dec 28;12(12):e0189341. doi: 10.1371/journal.pone.0189341. eCollection 2017. PMID: 29283995 Abstract We report the results of in vivo studies in Caenorhabditis elegans nematodes in which addition of extra virgin olive oil (EVOO) to their diet significantly increased their life span with respect to the control group. Furthermore, when nematodes were exposed to the pesticide paraquat, they started to die after two days, but after the addition of EVOO to their diet, both survival percentage and lifespans of paraquat-exposed nematodes increased. Since paraquat is associated with superoxide radical production, a test for scavenging this radical was performed using cyclovoltammetry and the EVOO efficiently scavenged the superoxide. Thus, a linear correlation (y = -0.0838x +19.73, regression factor = 0.99348) was observed for superoxide presence (y) in the voltaic cell as a function of aliquot (x) additions of EVOO, 10 μL each. The originally generated supoeroxide was approximately halved after 10 aliquots (100 μL total). The superoxide scavenging ability was analyzed, theoretically, using Density Functional Theory for tyrosol and hydroxytyrosol, two components of EVOO and was also confirmed experimentally for the galvinoxyl radical, using Electron Paramagnetic Resonance (EPR) spectroscopy. The galvinoxyl signal disappeared after adding 1 μL of EVOO to the EPR cell in 10 minutes. In addition, EVOO significantly decreased the proliferation of human leukemic THP-1 cells, while it kept the proliferation at about normal levels in rat L6 myoblasts, a non-tumoral skeletal muscle cell line. The protection due to EVOO was also assessed in L6 cells and THP-1 exposed to the radical generator cumene hydroperoxide, in which cell viability was reduced. Also in this case the oxidative stress was ameliorated by EVOO, in line with results obtained with tetrazolium dye reduction assays, cell cycle analysis and reactive oxygen species measurements. We ascribe these beneficial effects to EVOO antioxidant properties and our results are in agreement with a clear health benefit of EVOO use in the Mediterranean diet. Edited December 29, 2017 by AlPater Quote Link to comment Share on other sites More sharing options...
AlPater Posted December 30, 2017 Author Report Share Posted December 30, 2017 President Trump's Mental Health - Is It Morally Permissible for Psychiatrists to Comment? Pouncey C. N Engl J Med. 2017 Dec 27. [Epub ahead of print] No abstract available. PMID: 29281801 http://www.nejm.org/doi/full/10.1056/NEJMp1714828?query=TOC >>>>>>>>>>>>>>>>>>>>>>> Rosemary K.M. Sword and Philip Zimbardo Ph.D. "The Dangerous Case of Donald Trump" A new book delves into the president’s mental health. Posted Sep 28, 2017 https://www.psychologytoday.com/blog/the-time-cure/201709/the-dangerous-case-donald-trump Effect of omega-3 fatty acids on cognition: an updated systematic review of randomized clinical trials. Rangel-Huerta OD, Gil A. Nutr Rev. 2017 Dec 12. doi: 10.1093/nutrit/nux064. [Epub ahead of print] PMID: 29240924 Abstract CONTEXT: The increasing number of studies on the effects of n-3 long-chain polyunsaturated fatty acids (LC-PUFAs) on health, particularly cognition, in the last 5 years reflects the growing interest in this area of research. OBJECTIVE: The aim for this systematic review was to evaluate the scientific evidence published in the last 5 years (2012-2017) on the effects of n-3 LC-PUFA intake on cognition, cognitive development, and cognitive decline to determine whether n-3 LC-PUFAs support cognitive development and prevent cognitive decline. DATA SOURCES: The PubMed database was searched. STUDY SELECTION: The 51 articles included in this systematic review reported on healthy individuals with mild or moderate cognitive impairment and patients with Alzheimer's disease. Risk of bias was assessed using Cochrane methodology. DATA EXTRACTION: The number of study participants, the type of study, the type and dose of n-3 LC-PUFAs, and the key results are reported here. RESULTS: Current evidence indicates that n-3 LC-PUFAs administered during pregnancy or breastfeeding have no effect on the skills or cognitive development of children in later stages of development. Evidence regarding the improvement of cognitive function during childhood and youth or in attention deficit/hyperactivity disorder is inconclusive. Moreover, it is still unclear if n-3 LC-PUFAs can improve cognitive development or prevent cognitive decline in young or older adults. KEYWORDS: cognition; cognitive development; omega-3; systematic review Intestinal absorption of vitamin D: a systematic review. Silva MC, Furlanetto TW. Nutr Rev. 2017 Aug 17. doi: 10.1093/nutrit/nux034. [Epub ahead of print] PMID: 29025082 Abstract Vitamin D is frequently prescribed as a supplement, yet its absorption remains poorly understood. This systematic review was performed to evaluate data on mechanisms involved in the intestinal absorption of vitamin D. PubMed, Embase, and Cochrane Library databases were searched. The following studies were included: experimental laboratory studies of vitamin D absorption through the enterocyte brush-border membrane; absorption tests that used radiolabeled vitamin D; and clinical trials in adults that investigated a single dose of cholecalciferol or ergocalciferol and reported at least 2 measurements of serum cholecalciferol, ergocalciferol, or 25-hydroxyvitamin D. From 2069 articles identified, 46 met the inclusion criteria. Different methods were employed to evaluate vitamin D absorption. Recent research suggests that vitamin D absorption is not an exclusive simple diffusion process. Vitamin D was better absorbed when it was consumed with fat-containing meals, but absorption also occurred without fat or oily vehicles. Factors that modified cholesterol absorption also altered vitamin D absorption. Vitamin D is probably absorbed through passive diffusion and a mechanism involving membrane carriers, especially cholesterol transporters, although data remain scarce. Some data suggest that fat, when consumed concomitantly with vitamin D, improves vitamin D absorption. KEYWORDS: absorption; bioavailability; enterocyte; membrane transport; vitamin D Review of the health effects of berries and their phytochemicals on the digestive and immune systems. Govers C, Berkel Kasikci M, van der Sluis AA, Mes JJ. Nutr Rev. 2017 Oct 25. doi: 10.1093/nutrit/nux039. [Epub ahead of print] PMID: 29087531 Abstract Berries are generally considered beneficial to health. This health-promoting potential has mainly been ascribed to berries' phytochemical and vitamin content, and little attention has been paid to the potential benefits of berries for the digestive tract, despite this being the first point of contact. In vivo studies that described the health effects of berries on individual parts of the digestive tract (ie, the mouth, esophagus, stomach, small and large intestine, microbiome, and immune system) were reviewed. Immune effects were included because a large part of the immune system is located in the intestine. Beneficial health effects were mainly observed for whole berry extracts, not individual berry components. These effects ranged from support of the immune system and beneficial microbiota to reduction in the number and size of premalignant and malignant lesions. These results demonstrate the potency of berries and suggest berries can serve as a strong adjuvant to established treatments or therapies for a variety of gastrointestinal and immune-related illnesses. KEYWORDS: berry; digestive system; immune system; in vivo; phytochemicals A longitudinal study of DNA methylation as a potential mediator of age-related diabetes risk. Grant CD, Jafari N, Hou L, Li Y, Stewart JD, Zhang G, Lamichhane A, Manson JE, Baccarelli AA, Whitsel EA, Conneely KN. Geroscience. 2017 Dec;39(5-6):475-489. doi: 10.1007/s11357-017-0001-z. Epub 2017 Nov 20. PMID: 29159506 Abstract DNA methylation (DNAm) has been found to show robust and widespread age-related changes across the genome. DNAm profiles from whole blood can be used to predict human aging rates with great accuracy. We sought to test whether DNAm-based predictions of age are related to phenotypes associated with type 2 diabetes (T2D), with the goal of identifying risk factors potentially mediated by DNAm. Our participants were 43 women enrolled in the Women's Health Initiative. We obtained methylation data via the Illumina 450K Methylation array on whole blood samples from participants at three timepoints, covering on average 16 years per participant. We employed the method and software of Horvath, which uses DNAm at 353 CpGs to form a DNAm-based estimate of chronological age. We then calculated the epigenetic age acceleration, or Δage, at each timepoint. We fit linear mixed models to characterize how Δage contributed to a longitudinal model of aging and diabetes-related phenotypes and risk factors. For most participants, Δage remained constant, indicating that age acceleration is generally stable over time. We found that Δage associated with body mass index (p = 0.0012), waist circumference (p = 0.033), and fasting glucose (p = 0.0073), with the relationship with BMI maintaining significance after correction for multiple testing. Replication in a larger cohort of 157 WHI participants spanning 3 years was unsuccessful, possibly due to the shorter time frame covered. Our results suggest that DNAm has the potential to act as a mediator between aging and diabetes-related phenotypes, or alternatively, may serve as a biomarker of these phenotypes. KEYWORDS: Aging; BMI; DNA methylation; biological age; biomarker; diabetes Quote Link to comment Share on other sites More sharing options...
AlPater Posted December 31, 2017 Author Report Share Posted December 31, 2017 Dietary acrylamide intake and risk of breast cancer: the Japan Public Health Center-based Prospective Study. Kotemori A, Ishihara J, Zha L, Liu R, Sawada N, Iwasaki M, Sobue T, Tsugane S; JPHC Study Group. Cancer Sci. 2017 Dec 30. doi: 10.1111/cas.13496. [Epub ahead of print] PMID: 29288560 Abstract Acrylamide forms during cooking and is classified as a probable carcinogen in humans, mandating the need for epidemiological studies of dietary acrylamide and cancers. However, the risk of dietary acrylamide exposure to breast cancer in Japanese women has not been assessed. We investigated the association between dietary acrylamide intake and risk of breast cancer in the Japan Public Health Center-based Prospective Study. The present study included 48,910 women aged 45-74 years who responded to a 5-year follow-up survey questionnaire. Dietary acrylamide intake was assessed using a validated food frequency questionnaire. Cox proportional hazards regression models were used to estimate hazard ratios and 95% confidence intervals. During an average of 15.4 years of follow up, 792 breast cancers were diagnosed. Energy-adjusted dietary acrylamide intake was not associated with the risk of breast cancer (adjusted hazard ratio for highest versus lowest tertile=0.95, 95% confidence intervals: 0.79-1.14, p-trend=0.58). Further, no significant associations were observed when stratified analyses were conducted by smoking status, coffee consumption, alcohol consumption, body mass index, menopausal status, estrogen receptor status, and progesterone receptor status. In conclusion, dietary acrylamide intake was not associated with the risk of breast cancer in this population-based prospective cohort study of Japanese women. This article is protected by copyright. All rights reserved. KEYWORDS: Asia; acrylamide; breast cancer; diet; epidemiology Quote Link to comment Share on other sites More sharing options...
AlPater Posted January 1, 2018 Author Report Share Posted January 1, 2018 Advanced aging causes diaphragm functional abnormalities, global proteome remodeling, and loss of mitochondrial cysteine redox flexibility in mice. Kelley RC, McDonagh B, Ferreira LF. Exp Gerontol. 2017 Dec 28. pii: S0531-5565(17)30553-3. doi: 10.1016/j.exger.2017.12.017. [Epub ahead of print] PMID: 29289553 Abstract AIM: Inspiratory muscle (diaphragm) function declines with age, contributing to exercise intolerance and impaired airway clearance. Studies of diaphragm dysfunction in rodents have focused on moderate aging (~24months); thus, the impact of advanced age on the diaphragm and potential mechanisms of dysfunction are less clear. Therefore, we aimed to define the effects of advanced age on the mechanics, morphology, and global and redox proteome of the diaphragm. METHODS: We studied diaphragm from young (6months) and very old male mice (30months). Diaphragm function was evaluated using isolated muscle bundles. Proteome analyses followed LC-MS/MS processing of diaphragm muscle. RESULTS: Advanced aging decreased diaphragm peak power by ~35% and maximal isometric specific force by ~15%, and prolonged time to peak twitch tension by ~30% (P<0.05). These changes in contractile properties were accompanied, and might be caused by decreases in abundance of calsequestrin, sarcoplasmic reticulum Ca2+-ATPase, sarcalumenin, and parvalbumin that were revealed by our label-free proteomics data. Advanced aging also increased passive stiffness (P<0.05), which might be a consequence of an upregulation of cytoskeletal and extracellular matrix proteins identified by proteomics. Analyses of cysteine redox state indicated that the main diaphragm abnormalities with advanced aging are in metabolic enzymes and mitochondrial proteins. CONCLUSION: Our novel findings are that the most pronounced impact of advanced aging on the diaphragm is loss of peak power and disrupted cysteine redox homeostasis in metabolic enzymes and mitochondrial proteins. KEYWORDS: Protein oxidation; Proteomics; Skeletal muscle; Stiffness; Weakness Zoledronic acid increases the prevalence of medication-related osteonecrosis of the jaw in a dose dependent manner in rice rats (Oryzomys palustris) with localized periodontitis. Messer JG, Mendieta Calle JL, Jiron JM, Castillo EJ, Van Poznak C, Bhattacharyya N, Kimmel DB, Aguirre JI. Bone. 2017 Dec 28. pii: S8756-3282(17)30485-4. doi: 10.1016/j.bone.2017.12.025. [Epub ahead of print] PMID: 29289789 Abstract OBJECTIVE: Investigate role of dose/duration of zoledronic acid (ZOL), a powerful anti-resorptive (pAR), on prevalence of medication-related osteonecrosis of the jaw (MRONJ) in rice rats (Oryzomys palustris), a species with natural susceptibility to food impaction-induced localized periodontitis (FILP). We hypothesize that ZOL induces MRONJ lesions in rice rats with FILP, and that the prevalence of MRONJ rises with increasing dose and duration of ZOL treatment. METHODS: We performed a toxicology experiment with clinically-relevant doses of ZOL in female rats (N=230) fed standard (STD) rodent chow. At age 4weeks (baseline), 12 rats were necropsied. The rest were randomized into five groups that began to receive 0, 8, 20, 50 or 125μg/kg ZOL IV/q 4weeks. After 12, 18, 24 and 30weeks, subgroups (N=9-16) from each of the dose groups were necropsied. High-resolution macroscopic photos of all jaw quadrants were given a gross quadrant grade (GQG) (0-4 or MRONJ) that classified FILP lesion severity and determined presence of gross MRONJ. Quadrants with GQG≥1 were examined histopathologically. Logistic regression analysis (ZOL dose/duration) of MRONJ prevalence was completed. RESULTS: We found: 1) 75% of 0μg/kg ZOL rats developed FILP lesions; 2) baseline rats and rats treated with 0μg/kg ZOL had no MRONJ; 3) 29 gross MRONJ cases were identified; 4) all gross MRONJ cases were confirmed histopathologically by the observation of exposed necrotic bone, and 53 new cases were discovered (total=82); 5) ZOL dose (P<0.001), but not duration (P=0.326), was a significant predictor of MRONJ prevalence; 6) 13% prevalence of gross MRONJ among all rats, with 22% prevalence among rats exposed to ZOL oncologic doses (20-125μg/kg); 7) 38% prevalence of histopathologic MRONJ among all rats, with 73% prevalence among rats exposed to ZOL oncologic doses. CONCLUSIONS: This is the first experiment to show a dose response relationship between clinically relevant doses of ZOL and MRONJ prevalence. KEYWORDS: Anti-resorptives; Duration; Periodontitis; Toxicology Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. Lean ME, Leslie WS, Barnes AC, Brosnahan N, Thom G, McCombie L, Peters C, Zhyzhneuskaya S, Al-Mrabeh A, Hollingsworth KG, Rodrigues AM, Rehackova L, Adamson AJ, Sniehotta FF, Mathers JC, Ross HM, McIlvenna Y, Stefanetti R, Trenell M, Welsh P, Kean S, Ford I, McConnachie A, Sattar N, Taylor R. Lancet. 2017 Dec 4. pii: S0140-6736(17)33102-1. doi: 10.1016/S0140-6736(17)33102-1. [Epub ahead of print] PMID: 29221645 Abstract BACKGROUND: Type 2 diabetes is a chronic disorder that requires lifelong treatment. We aimed to assess whether intensive weight management within routine primary care would achieve remission of type 2 diabetes. METHODS: We did this open-label, cluster-randomised trial (DiRECT) at 49 primary care practices in Scotland and the Tyneside region of England. Practices were randomly assigned (1:1), via a computer-generated list, to provide either a weight management programme (intervention) or best-practice care by guidelines (control), with stratification for study site (Tyneside or Scotland) and practice list size (>5700 or ≤5700). Participants, carers, and research assistants who collected outcome data were aware of group allocation; however, allocation was concealed from the study statistician. We recruited individuals aged 20-65 years who had been diagnosed with type 2 diabetes within the past 6 years, had a body-mass index of 27-45 kg/m2, and were not receiving insulin. The intervention comprised withdrawal of antidiabetic and antihypertensive drugs, total diet replacement (825-853 kcal/day formula diet for 3-5 months), stepped food reintroduction (2-8 weeks), and structured support for long-term weight loss maintenance. Co-primary outcomes were weight loss of 15 kg or more, and remission of diabetes, defined as glycated haemoglobin (HbA1c) of less than 6·5% (<48 mmol/mol) after at least 2 months off all antidiabetic medications, from baseline to 12 months. These outcomes were analysed hierarchically. This trial is registered with the ISRCTN registry, number 03267836. FINDINGS: Between July 25, 2014, and Aug 5, 2017, we recruited 306 individuals from 49 intervention (n=23) and control (n=26) general practices; 149 participants per group comprised the intention-to-treat population. At 12 months, we recorded weight loss of 15 kg or more in 36 (24%) participants in the intervention group and no participants in the control group (p<0·0001). Diabetes remission was achieved in 68 (46%) participants in the intervention group and six (4%) participants in the control group (odds ratio 19·7, 95% CI 7·8-49·8; p<0·0001). Remission varied with weight loss in the whole study population, with achievement in none of 76 participants who gained weight, six (7%) of 89 participants who maintained 0-5 kg weight loss, 19 (34%) of 56 participants with 5-10 kg loss, 16 (57%) of 28 participants with 10-15 kg loss, and 31 (86%) of 36 participants who lost 15 kg or more. Mean bodyweight fell by 10·0 kg (SD 8·0) in the intervention group and 1·0 kg (3·7) in the control group (adjusted difference -8·8 kg, 95% CI -10·3 to -7·3; p<0·0001). Quality of life, as measured by the EuroQol 5 Dimensions visual analogue scale, improved by 7·2 points (SD 21·3) in the intervention group, and decreased by 2·9 points (15·5) in the control group (adjusted difference 6·4 points, 95% CI 2·5-10·3; p=0·0012). Nine serious adverse events were reported by seven (4%) of 157 participants in the intervention group and two were reported by two (1%) participants in the control group. Two serious adverse events (biliary colic and abdominal pain), occurring in the same participant, were deemed potentially related to the intervention. No serious adverse events led to withdrawal from the study. INTERPRETATION: Our findings show that, at 12 months, almost half of participants achieved remission to a non-diabetic state and off antidiabetic drugs. Remission of type 2 diabetes is a practical target for primary care. Quote Link to comment Share on other sites More sharing options...
AlPater Posted January 3, 2018 Author Report Share Posted January 3, 2018 Lifespan leisure physical activity profile, brain plasticity and cognitive function in old age. Engeroff T, Vogt L, Fleckenstein J, Füzéki E, Matura S, Pilatus U, Schwarz S, Deichmann R, Hellweg R, Pantel J, Banzer W. Aging Ment Health. 2018 Jan 2:1-8. doi: 10.1080/13607863.2017.1421615. [Epub ahead of print] PMID: 29293024 Abstract OBJECTIVES: Despite the evidence suggesting physical activity (PA) as a major factor for the prevention of age-related cognitive decline, only a few studies have systematically investigated the impact of leisure PA during the lifespan (LLPA). This study investigates the effects of LLPA on cognitive function (CF) and brain plasticity (BP) in old age. METHOD: Participants' (n = 50, 72 ± 5 yrs, 27 females) LLPA energy expenditure and volume was assessed via a validated questionnaire investigating five epochs (14-80 yrs). Using current WHO PA recommendations as reference, participants were stratified into energy expenditure and volume groups. CF outcomes were attention, executive functions, working memory and memory. BP was assessed using magnetic resonance spectroscopy (MRSI) and brain derived neurotropic factor (BDNF). RESULTS: Correlation analysis revealed associations of mean LLPA energy expenditure with attention (CF) and N-acetylaspartate to choline ratios (NAA/Cho) (MRSI). ANOVA revealed higher interference control performance (CF) and NAA/Cho in participants complying with current PA recommendations (2-3 h per week) compared to non-compliers. Further CF and BP outcomes including BDNF were not associated with LLPA. CONCLUSION: Lifelong adherence to minimum recommended PA seems to be associated with markers of cognitive function and neuronal integrity in old age. KEYWORDS: Neuropsychology; brain derived neurotropic factor; brain metabolism; brain structure; exercise; lifelong; lifetime; neurobiology SCIENCE Fiber Is Good for You. Now Scientists May Know Why. Carl Zimmer MATTER JAN. 1, 2018 https://www.nytimes.com/2018/01/01/science/food-fiber-microbiome-inflammation.html?hpw&rref=health&action=click&pgtype=Homepage&module=well-region®ion=bottom-well&WT.nav=bottom-well >>>>>>>>>>> Fiber-Mediated Nourishment of Gut Microbiota Protects against Diet-Induced Obesity by Restoring IL-22-Mediated Colonic Health. Zou J, Chassaing B, Singh V, Pellizzon M, Ricci M, Fythe MD, Kumar MV, Gewirtz AT. Cell Host Microbe. 2017 Dec 12. pii: S1931-3128(17)30497-3. doi: 10.1016/j.chom.2017.11.003. [Epub ahead of print] PMID: 29276170 http://www.cell.com/cell-host-microbe/fulltext/S1931-3128(17)30497-3 Abstract Dietary supplementation with fermentable fiber suppresses adiposity and the associated parameters of metabolic syndrome. Microbiota-generated fiber-derived short-chain fatty acids (SCFAs) and free fatty acid receptors including GPR43 are thought to mediate these effects. We find that while fermentable (inulin), but not insoluble (cellulose), fiber markedly protected mice against high-fat diet (HFD)-induced metabolic syndrome, the effect was not significantly impaired by either inhibiting SCFA production or genetic ablation of GPR43. Rather, HFD decimates gut microbiota, resulting in loss of enterocyte proliferation, leading to microbiota encroachment, low-grade inflammation (LGI), and metabolic syndrome. Enriching HFD with inulin restored microbiota loads, interleukin-22 (IL-22) production, enterocyte proliferation, and antimicrobial gene expression in a microbiota-dependent manner, as assessed by antibiotic and germ-free approaches. Inulin-induced IL-22 expression, which required innate lymphoid cells, prevented microbiota encroachment and protected against LGI and metabolic syndrome. Thus, fermentable fiber protects against metabolic syndrome by nourishing microbiota to restore IL-22-mediated enterocyte function. KEYWORDS: germ-free mice; intestinal inflammation; metabolic syndrome; microbiota encroachment; short-chain fatty acids >>>>>>>>>>>>>>>>>>> Bifidobacteria or Fiber Protects against Diet-Induced Microbiota-Mediated Colonic Mucus Deterioration. Schroeder BO, Birchenough GMH, Ståhlman M, Arike L, Johansson MEV, Hansson GC, Bäckhed F. Cell Host Microbe. 2017 Dec 16. pii: S1931-3128(17)30498-5. doi: 10.1016/j.chom.2017.11.004. [Epub ahead of print] PMID: 29276171 http://www.cell.com/cell-host-microbe/fulltext/S1931-3128(17)30498-5 Abstract Diet strongly affects gut microbiota composition, and gut bacteria can influence the colonic mucus layer, a physical barrier that separates trillions of gut bacteria from the host. However, the interplay between a Western style diet (WSD), gut microbiota composition, and the intestinal mucus layer is less clear. Here we show that mice fed a WSD have an altered colonic microbiota composition that causes increased penetrability and a reduced growth rate of the inner mucus layer. Both barrier defects can be prevented by transplanting microbiota from chow-fed mice. In addition, we found that administration of Bifidobacterium longum was sufficient to restore mucus growth, whereas administration of the fiber inulin prevented increased mucus penetrability in WSD-fed mice. We hypothesize that the presence of distinct bacteria is crucial for proper mucus function. If confirmed in humans, these findings may help to better understand diseases with an affected mucus layer, such as ulcerative colitis. KEYWORDS: Bifidobacterium; Western style diet; colon; fiber; goblet cell; microbiota; mucin; mucus Body mass index as a biomarker for the evaluation of the "Obesity Paradox" among inpatients. Tojek K, Wustrau B, Czerniak B, Korzycka-Wilińska W, Winiarski P, Banaszkiewicz Z, Budzyński J. Clin Nutr. 2017 Dec 20. pii: S0261-5614(17)31425-5. doi: 10.1016/j.clnu.2017.12.005. [Epub ahead of print] PMID: 29291899 Abstract BACKGROUND: Overweight and obesity are, on the one hand, recognized as risk factors for many health-related disorders, and, on the other, as favorable prognostic factors in various patients treated for several different conditions; what is called the "obesity paradox". Until now, the existence of this phenomenon among a general population of consecutive inpatients has not been evaluated. We decided, therefore, to perform an evaluation. PATIENTS AND METHODS: Historical prospective analysis of the medical documentation of 23 603 hospitalizations during two consecutive years in one center was performed. The outcomes measured were as follows: length of stay, in-hospital all-cause mortality, and non-scheduled readmission in the 14-day, 30-day and one-year periods following discharge. RESULTS: Overweight and obese patients had a lower or similar prevalence of the measured outcomes than malnourished patients and those of normal weight. Adjustment of the standard WHO BMI ranges for patients aged ≥65 y (normal weight BMI range 23-33 kg/m2) made these differences more apparent. In logistic regression, the ratio of fat to fat-free body mass was a stronger and unfavorable risk factor compared with BMI for the measured outcomes. CONCLUSIONS: The greatest risk of all-cause in-hospital death and readmission concerned malnourished inpatients. Compared to patients with a normal BMI range, overweight and obesity had a lower or similar (but not greater) risk of the outcomes measured. However, due to several BMI limitations, our observations should be interpreted as suggesting a "BMI paradox", rather than an "obesity paradox". KEYWORDS: All-cause mortality; Body mass index; Hospitalized patients; Older adults; Prognosis Hypothetical interventions to prevent stroke: an application of the parametric g-formula to a healthy middle-aged population. Vangen-Lønne AM, Ueda P, Gulayin P, Wilsgaard T, Mathiesen EB, Danaei G. Eur J Epidemiol. 2018 Jan 2. doi: 10.1007/s10654-017-0344-x. [Epub ahead of print] PMID: 29294206 Abstract The effects of interventions on multiple lifestyle and metabolic risk factors, initiated in midlife or later in a healthy population, on the long-term risk of first-ever stroke is not known. A particular methodological challenge in observational studies is to estimate the unbiased effect of a time-varying exposure in presence of time-varying confounders, if those confounders are affected by prior exposure. In such cases, the parametric g-formula can be applied to estimate an unbiased effect. We applied the parametric g-formula to estimate the 18-years (1994-2012) cumulative stroke risk under different scenarios of hypothetical interventions on levels of blood pressure, cholesterol, weight, physical activity, smoking and alcohol intake; and compared these to the observed scenario, to calculate the population risk ratios and risk differences. Among 14,796 eligible participants in the prospective, population-based Tromsø study (baseline mean age 46.1 years, 51% women), the observed 18-years stroke risk was 5.9%. A feasible joint hypothetical intervention on six lifestyle and metabolic risk factors would reduce the 18-year stroke risk by 32% (95% confidence interval 16, 44). A combination of more intensive interventions reduced the estimated 18-years stroke risk by 64% (95% confidence interval 40, 80). Blood pressure reduction and quitting smoking significantly reduced the risk when applied separately. KEYWORDS: G-formula; Hypothetical interventions; Primary prevention; Risk factors; Stroke The Scientist » January 2018 Issue » Editorial Prizes and Penalties Life is filled with pleasure and pain. Science and society are struggling mightily with both. By Bob Grant | January 1, 2018 https://www.the-scientist.com/?articles.view/articleNo/51141/title/Prizes-and-Penalties/&utm_source=hs_email&utm_medium=email&utm_content=59732098&_hsenc=p2ANqtz--JXVpeRD8Ycv2kSTlzeYOQR3tCkMVScml7sKtEt_4Xk-JHjK-3wJukVBvITxikze29yJHh2AtXmxdN4dhWhGO_ZDQ_Kw&_hsmi=59732098 Quote Link to comment Share on other sites More sharing options...
AlPater Posted January 5, 2018 Author Report Share Posted January 5, 2018 Dynapenic Abdominal Obesity Increases Mortality Risk among English and Brazilian Older Adults: A 10-Year Follow-Up of the ELSA and SABE Studies. da Silva Alexandre T, Scholes S, Ferreira Santos JL, de Oliveira Duarte YA, de Oliveira C. J Nutr Health Aging. 2018;22(1):138-144. doi: 10.1007/s12603-017-0966-4. PMID: 29300433 Abstract BACKGROUND/OBJECTIVE: There is little epidemiological evidence demonstrating that dynapenic abdominal obesity has higher mortality risk than dynapenia and abdominal obesity alone. Our main aim was to investigate whether dynapenia combined with abdominal obesity increases mortality risk among English and Brazilian older adults over ten-year follow-up. DESIGN: Cohort study. SETTING: United Kingdom and Brazil. PARTICIPANTS: Data came from 4,683 individuals from the English Longitudinal Study of Ageing (ELSA) and 1,490 from the Brazilian Health, Well-being and Aging study (SABE), hence the final sample of this study was 6,173 older adults. MEASUREMENTS: The study population was categorized into the following groups: non-dynapenic/non-abdominal obese, abdominal obese, dynapenic, and dynapenic abdominal obese according to their handgrip strength (< 26 kg for men and < 16 kg for women) and waist circumference (> 102 cm for men and > 88 cm for women). The outcome was all-cause mortality over a ten-year follow-up. Adjusted hazard ratios by sociodemographic, behavioural and clinical characteristics were estimated using Cox proportional hazards models. RESULTS: The fully adjusted model showed that dynapenic abdominal obesity has a higher mortality risk among the groups. The hazard ratios (HR) were 1.37 for dynapenic abdominal obesity (95% CI = 1.12 - 1.68), 1.15 for abdominal obesity (95% CI = 0.98 - 1.35), and 1.23 for dynapenia (95% CI = 1.04 - 1.45). CONCLUSIONS: Dynapenia is an important risk factor for mortality but dynapenic abdominal obesity has the highest mortality risk among English and Brazilian older adults. KEYWORDS: Dynapenia ; handgrip; mortality; obesity; waist circumference Oral coenzyme Q10 supplementation in patients with migraine: Effects on clinical features and inflammatory markers. Dahri M, Tarighat-Esfanjani A, Asghari-Jafarabadi M, Hashemilar M. Nutr Neurosci. 2018 Jan 3:1-9. doi: 10.1080/1028415X.2017.1421039. [Epub ahead of print] PMID: 29298622 Abstract BACKGROUNDS AND AIMS: Migraine and inflammation are correlated. Coenzyme Q10 (CoQ10) as an anti-inflammatory agent has shown useful effects in other diseases. The present study aimed to assess the effect of CoQ10 supplementation on inflammation and clinical features of migraine. METHODS: This randomized double-blind placebo-controlled clinical trial was conducted among 45 non-menopausal women aged 18-50 years, diagnosed for episodic migraine according to the International Headache Society. After one month run-in period, subjects received CoQ10 (400 mg/day CoQ10, n = 23) or placebo (wheat starch, n = 22) for three months. All the patients got prophylactic medication too. Serum CoQ10 concentration, Calcitonin gene-related peptide (CGRP), interleukin (IL)-6, IL-10 and tumor necrosis factor-α (TNF-α) were measured at the beginning and end of the study. RESULTS: CoQ10 supplementation reduced CGRP and TNF-α significantly (p = 0.011 and p = 0.044, respectively), but there were no significant differences in serum IL-6 and IL-10 between the two groups. Significant increase in serum CoQ10 levels was evident with CoQ10 therapy (P < 0.001). A significant improvement was found in frequency (p = 0.018), severity (p = 0.001) and duration (p = 0.012) of migraine attacks in CoQ10 group compared to placebo. CONCLUSION: CoQ10 supplementation may decrease CGRP and TNF-α with no favorable effects on IL-6 and IL-10 in patients with migraine. KEYWORDS: CGRP; Coenzyme Q10; Inflammation; Migraine; Randomized controlled trial Associations of General and Central Adiposity With Incident Diabetes in Chinese Men and Women. Bragg F, Tang K, Guo Y, Iona A, Du H, Holmes MV, Bian Z, Kartsonaki C, Chen Y, Yang L, Sun Q, Dong C, Chen J, Collins R, Peto R, Li L, Chen Z; China Kadoorie Biobank (CKB) Collaborative Group. Diabetes Care. 2018 Jan 3. pii: dc171852. doi: 10.2337/dc17-1852. [Epub ahead of print] PMID: 29298802 Abstract OBJECTIVE: We assess associations of general and central adiposity in middle age and of young adulthood adiposity with incident diabetes in adult Chinese and estimate the associated population burden of diabetes. RESEARCH DESIGN AND METHODS: The prospective China Kadoorie Biobank enrolled 512,891 adults 30-79 years of age from 10 localities across China during 2004-2008. During 9.2 years of follow-up, 13,416 cases of diabetes were recorded among 482,589 participants without diabetes at baseline. Cox regression yielded adjusted hazard ratios (HRs) for incident diabetes associated with measures of general (e.g., BMI and BMI at 25 years) and central (e.g., waist circumference [WC]) adiposity. RESULTS: The mean (SD) BMI was 23.6 kg/m2 (3.4 kg/m2), and 3.8% had a BMI ≥30 kg/m2. Throughout the range examined (19-32 kg/m2), BMI showed a positive log-linear relationship with diabetes, with adjusted HRs per SD higher usual BMI greater in men (1.98; 95% CI 1.93-2.04) than in women (1.77; 1.73-1.81) (P for heterogeneity < 0.001). For WC, HRs per SD were 2.13 (95% CI 2.07-2.19) in men and 1.91 (1.87-1.95) in women (P for heterogeneity < 0.001). Mutual adjustment attenuated these associations, especially those of BMI. BMI at age 25 years was weakly positively associated with diabetes (men HR 1.09 [95% CI 1.05-1.12]; women 1.04 [1.02-1.07] per SD), which was reversed after adjustment for baseline BMI. In China, the increase in adiposity accounted for ∼50% of the increase in diabetes burden since 1980. CONCLUSIONS: Among relatively lean Chinese adults, higher adiposity-general and central-was strongly positively associated with the risk of incident diabetes. The predicted continuing increase in adiposity in China foreshadows escalating rates of diabetes. Prospective Study of Dietary Zinc Intake and Risk of Cardiovascular Disease in Women. Milton AH, Vashum KP, McEvoy M, Hussain S, McElduff P, Byles J, Attia J. Nutrients. 2018 Jan 4;10(1). pii: E38. doi: 10.3390/nu10010038. PMID: 29300299 http://www.mdpi.com/2072-6643/10/1/38/htm Abstract Several animal and human studies have shown that zinc is associated with cellular damage and cardiac dysfunction. This study aims to investigate dietary zinc and the zinc-iron ratio, as predictors of incident cardiovascular disease (CVD) in a large longitudinal study of mid-age Australian women (aged 50-61 years). Data was self-reported and validated food frequency questionnaires were used to assess dietary intake. Energy-adjusted zinc was ranked using quintiles and predictors of incident CVD were examined using stepwise logistic regression. After six years of follow-up, 320 incident CVD cases were established. A positive association between dietary zinc intake, zinc-iron ratio and risk of CVD was observed even after adjusting for potential dietary and non-dietary confounders. Compared to those with the lowest quintile of zinc, those in the highest quintile (Odds Ratio (OR) = 1.67, 95% Confidence Interval (CI) = 1.08-2.62) and zinc-iron ratio (OR = 1.72, 95% CI = 1.05-2.81) had almost twice the odds of developing CVD (p trend = 0.007). This study shows that high dietary zinc intake and zinc-iron ratio is associated with a greater incidence of CVD in women. Further studies are required detailing the source of zinc and iron in diet and their precise roles when compared to other essential nutrients. KEYWORDS: Australia; cardiovascular disease; cohort; diet; women; zinc Quote Link to comment Share on other sites More sharing options...
AlPater Posted January 6, 2018 Author Report Share Posted January 6, 2018 Protective and Detoxifying Effects Conferred by Dietary Selenium and Curcumin against AFB1-Mediated Toxicity in Livestock: A Review. Limaye A, Yu RC, Chou CC, Liu JR, Cheng KC. Toxins (Basel). 2018 Jan 2;10(1). pii: E25. doi: 10.3390/toxins10010025. Review. PMID: 29301315 Abstract Aflatoxin B1 (AFB1), among other aflatoxins of the aflatoxin family, is the most carcinogenic and hazardous mycotoxin to animals and human beings with very high potency leading to aflatoxicosis. Selenium is an essential trace mineral possessing powerful antioxidant functions. Selenium is widely reported as an effective antioxidant against aflatoxicosis. By preventing oxidative liver damage, suppressing pro-apoptotic proteins and improving immune status in AFB1 affected animals; selenium confers specific protection against AFB1 toxicity. Meticulous supplementation of animal feed by elemental selenium in the organic and inorganic forms has proven to be effective to ameliorate AFB1 toxicity. Curcumin is another dietary agent of importance in tackling aflatoxicosis. Curcumin is one of the major active ingredients in the tubers of a spice Curcuma longa L., a widely reported antioxidant, anticarcinogenic agent with reported protective potential against aflatoxin-mediated liver damage. Curcumin restricts the aflatoxigenic potential of Aspergillusflavus. Curcumin inhibits cytochrome P450 isoenzymes, particularly CYP2A6 isoform; thereby reducing the formation of AFB1-8, 9-epoxide and other toxic metabolites causing aflatoxicosis. In this review, we have briefly reviewed important aflatoxicosis symptoms among animals. With the main focus on curcumin and selenium, we have reviewed their underlying protective mechanisms in different animals along with their extraction and production methods for feed applications. KEYWORDS: aflatoxin B1; anti-AFB1 dietary supplement; antioxidant status; curcumin; selenium Eating at the same time every day may help combat dementia 0 BY TOBY MURPHY ON JANUARY 4, 2018 http://www.infosurhoy.com/cocoon/saii/xhtml/en_GB/health/eating-at-the-same-time-every-day-may-help-combat-dementia/ >>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>>> Time-Restricted Feeding Improves Circadian Dysfunction as well as Motor Symptoms in the Q175 Mouse Model of Huntington's Disease. Wang HB, Loh DH, Whittaker DS, Cutler T, Howland D, Colwell CS. eNeuro. 2018 Jan 3;5(1). pii: ENEURO.0431-17.2017. doi: 10.1523/ENEURO.0431-17.2017. eCollection 2018 Jan-Feb. PMID: 29302618 http://www.eneuro.org/content/5/1/ENEURO.0431-17.2017 http://www.eneuro.org/content/eneuro/5/1/ENEURO.0431-17.2017.full.pdf Abstract Huntington’s disease (HD) patients suffer from a progressive neurodegeneration that results in cognitive, psychiatric, cardiovascular, and motor dysfunction. Disturbances in sleep/wake cycles are common among HD patients with reports of delayed sleep onset, frequent bedtime awakenings, and fatigue during the day. The heterozygous Q175 mouse model of HD has been shown to phenocopy many HD core symptoms including circadian dysfunctions. Because circadian dysfunction manifests early in the disease in both patients and mouse models, we sought to determine if early intervention that improve circadian rhythmicity can benefit HD and delay disease progression. We determined the effects of time-restricted feeding (TRF) on the Q175 mouse model. At six months of age, the animals were divided into two groups: ad libitum (ad lib) and TRF. The TRF-treated Q175 mice were exposed to a 6-h feeding/18-h fasting regimen that was designed to be aligned with the middle of the time when mice are normally active. After three months of treatment (when mice reached the early disease stage), the TRF-treated Q175 mice showed improvements in their locomotor activity rhythm and sleep awakening time. Furthermore, we found improved heart rate variability (HRV), suggesting that their autonomic nervous system dysfunction was improved. Importantly, treated Q175 mice exhibited improved motor performance compared to untreated Q175 controls, and the motor improvements were correlated with improved circadian output. Finally, we found that the expression of several HD-relevant markers was restored to WT levels in the striatum of the treated mice using NanoString gene expression assays. KEYWORDS: Huntington’s disease; Q175; circadian rhythms; fast/feed cycle; time-restricted feeding Metabolic Responses to Carbohydrate Ingestion during Exercise: Associations between Carbohydrate Dose and Endurance Performance. Newell ML, Wallis GA, Hunter AM, Tipton KD, Galloway SDR. Nutrients. 2018 Jan 3;10(1). pii: E37. doi: 10.3390/nu10010037. PMID: 29301367 Abstract Carbohydrate (CHO) ingestion during exercise lasting less than three hours improves endurance exercise performance but there is still debate about the optimal dose. We utilised stable isotopes and blood metabolite profiles to further examine metabolic responses to CHO (glucose only) ingestion in the 20-64 g·h-1 range, and to determine the association with performance outcome. In a double-blind, randomized cross-over design, male cyclists (n = 20, mean ± SD, age 34 ± 10 years, mass 75.8 ± 9 kg, peak power output 394 ± 36 W, VO2max 62 ± 9 mL·kg-1·min-1) completed four main experimental trials. Each trial involved a two-hour constant load ride (185 ± 25 W) followed by a time trial, where one of three CHO beverages, or a control (water), were administered every 15 min, providing 0, 20, 39 or 64 g CHO·h-1. Dual glucose tracer techniques, indirect calorimetry and blood analyses were used to determine glucose kinetics, exogenous CHO oxidation (EXO), endogenous CHO and fat oxidation; and metabolite responses. Regression analysis revealed that total exogenous CHO oxidised in the second hour of exercise, and suppression of serum NEFA concentration provided the best prediction model of performance outcome. However, the model could only explain ~19% of the variance in performance outcome. The present data demonstrate that consuming ~40 g·h-1 of CHO appears to be the minimum ingestion rate required to induce metabolic effects that are sufficient to impact upon performance outcome. These data highlight a lack of performance benefit and few changes in metabolic outcomes beyond an ingestion rate of 39 g·h-1. Further work is required to explore dose-response effects of CHO feeding and associations between multiple metabolic parameters and subsequent performance outcome. KEYWORDS: exogenous; fat oxidation; fatty acids; glucose; hepatic glucose output The efficacy of probiotic supplementation in rheumatoid arthritis: a meta-analysis of randomized, controlled trials. Aqaeinezhad Rudbane SM, Rahmdel S, Abdollahzadeh SM, Zare M, Bazrafshan A, Mazloomi SM. Inflammopharmacology. 2018 Jan 4. doi: 10.1007/s10787-017-0436-y. [Epub ahead of print] PMID: 29302905 Abstract Probiotics are considered as -immunomodulatory agents; their efficacy as an adjunct therapy option for rheumatoid arthritis (RA), however, remains controversial. The main aim of the present meta-analysis, therefore, was to compare available data from the published randomized, controlled trials (RCTs) recruiting adults with RA which compared probiotics with placebo. The English literature search was performed using Ovid version of Medline, EmBase, Web of Science, and the Central Cochrane library through October 2016 and supplemented by hand searching reference lists. Among 240 citations identified, 4 RCTs (153 participants; 89% female) were included. All data were pooled using a standardized mean difference (SMD) with a 95% CI. Compared to the placebo, probiotics did not change the inflammatory parameters (erythrocyte sedimentation rate, tumor necrosis factor [TNF]-α, interleukin [iL]-1β, IL-6, IL-10, and IL-12) and oxidative stress indices (total antioxidant capacity and malondialdehyde) significantly. The borderline significant reduction as a result of probiotic administration was only determined in C-reactive protein [sDM - 0.32 (95% CI - 0.65 to 0.00)]. Among disease activity indices (disease activity score [DAS], tender joint count, and swollen joint count), DAS showed a significant improvement following probiotic treatment with a SMD (95% CI) of - 0.58 (- 0.97 to - 0.19). The number of trials was too small to determine if a strain-, dose-, or duration-response effect was present. Probiotics seem to be less effective in RA; however, to reach a firm conclusion, we need further evidence. KEYWORDS: Disease activity; Inflammatory factors; Meta-analysis; Probiotics; Randomized trial; Rheumatoid arthritis Environmental Risk Factors for Developing Type 2 Diabetes Mellitus: A Systematic Review. Dendup T, Feng X, Clingan S, Astell-Burt T. Int J Environ Res Public Health. 2018 Jan 5;15(1). pii: E78. doi: 10.3390/ijerph15010078. Review. PMID: 29304014 Abstract Different elements of the environment have been posited to influence type 2 diabetes mellitus (T2DM). This systematic review summarizes evidence on the environmental determinants of T2DM identified in four databases. It proposes a theoretical framework illustrating the link between environment and T2DM, and briefly discusses some methodological challenges and potential solutions, and opportunities for future research. Walkability, air pollution, food and physical activity environment and roadways proximity were the most common environmental characteristics studied. Of the more than 200 reported and extracted relationships assessed in 60 studies, 82 showed significant association in the expected direction. In general, higher levels of walkability and green space were associated with lower T2DM risk, while increased levels of noise and air pollution were associated with greater risk. Current evidence is limited in terms of volume and study quality prohibiting causal inferences. However, the evidence suggests that environmental characteristics may influence T2DM prevention, and also provides a reasonable basis for further investigation with better quality data and longitudinal studies with policy-relevant environmental measures. This pursuit of better evidence is critical to support health-orientated urban design and city planning. KEYWORDS: air pollution; environment; green space; noise; type 2 diabetes mellitus; walkability Serum selenium levels and the risk of progression of laryngeal cancer. Lubiński J, Marciniak W, Muszynska M, Jaworowska E, Sulikowski M, Jakubowska A, Kaczmarek K, Sukiennicki G, Falco M, Baszuk P, Mojsiewicz M, Kotsopoulos J, Sun P, Narod SA, Lubiński JA. PLoS One. 2018 Jan 5;13(1):e0184873. doi: 10.1371/journal.pone.0184873. eCollection 2018. PMID: 29304040 Abstract BACKGROUND: Observational studies have reported an inverse relationship between selenium status (blood or toenail) and the risk of laryngeal cancer; however, the impact of low serum selenium level on survival has not been evaluated. METHODS: We conducted a prospective study of 296 patients diagnosed with laryngeal cancer in Szczecin, Poland. Serum selenium was measured at diagnosis and prior to treatment. Patients were followed from the date of diagnosis to death at five years. Vital status was obtained by linkage to the Polish National Death Registry. RESULTS: The five-year survival after diagnosis was 82.0% (95% CI: 68% to 91%) for individuals in the highest quartile of serum selenium (> 66.8 μg/L) and was 28.6% (95% CI 19% to 42%) for individuals in the lowest quartile (<50.0 μg/L). In an age- and sex-adjusted analysis, the hazard ratio (HR) for death from all causes was 7.01 (95% CI 3.81 to 12.9) for patients in the lowest quartile of serum selenium, compared to those in the highest quartile. The corresponding multivariate HR was 3.07 (95% CI 1.59 to 5.94). CONCLUSIONS: This study suggests that a selenium level in excess of 70 μg/L is associated with improved outcome among patients undergoing treatment for laryngeal cancer. Further studies are needed to evaluate if selenium supplementation to achieve this level might improve overall prognosis. Quote Link to comment Share on other sites More sharing options...
AlPater Posted January 7, 2018 Author Report Share Posted January 7, 2018 Relationship between systolic blood pressure and all-cause mortality: a prospective study in a cohort of Chinese adults. Li C, Chen Y, Zheng Q, Wu W, Chen Z, Song L, An S, Li Z, Chen S, Wu SL. BMC Public Health. 2018 Jan 5;18(1):107. doi: 10.1186/s12889-017-4965-5. PMID: 29304766 https://bmcpublichealth.biomedcentral.com/track/pdf/10.1186/s12889-017-4965-5?site=bmcpublichealth.biomedcentral.com Abstract BACKGROUND: The association between systolic blood pressure (SBP) and all-cause mortality in Chinese adults remains unclear. This study aimed to identify the relationship of SBP with all-cause mortality in Chinese men and women. METHODS: One hundred twenty-one thousand eighty-two employees of the Kailuan Group Corporation, aged 18 or older, who participated in physical examination from 2006 to 2007 or from 2008 to 2009, were enrolled and followed up for all-cause mortality. The information used to ascertain the outcome of death during follow-up was extracted from provincial vital statistics offices, hospitalization records from the 11 hospitals, or medical records from medical insurance companies. RESULTS: The average age was 50.06 ± 12.85 in the overall sample. Over 7 years of follow-up, 5945 participants, including 5520 men and 425 women had all-cause mortality. After multivariate adjustment, men in SBP group of <100, 120-139, 140-159, 160-179 and ≥180 mmHg had hazard ratios (HR) of 1.46 (1.14-1.86), 1.14 (1.04-1.26), 1.29 (1.16-1.44), 1.57 (1.38-1.79) and 2.07 (1.76-2.43), respectively, and displayed significantly increased risk of all-cause mortality compared to those with SBP in the range of 100-119 mmHg. Compared with the group of 100-119 mmHg, women in SBP group of 140-159, 160-179 and ≥180 mmHg had significantly greater risk with HRs of 1.44 (95% CI, 1.01-2.07), 1.63 (95% CI, 1.04-2.55) and 2.31 (95% CI, 1.27-4.20). CONCLUSIONS: Either lower (<100 mmHg) or higher (>120 mmHg) SBP was associated with an increased all-cause mortality risk and a J-shaped relationship was observed between SBP and all-cause mortality in men. Only SBP exceeding 140 mmHg was related to a higher risk in women. The relationship between SBP and all-cause mortality among Chinese adults may differ by sex. KEYWORDS: All-cause mortality; J-shaped relationship; Prospective cohort study; Sex; Systolic blood pressure THIS WEEK IN SCIENCE Research in Science journals. SCIENCE05 JAN 2018 : 43 CANCER IMMUNOTHERAPY Good bacteria help fight cancer Priscilla N. Kelly http://science.sciencemag.org/content/359/6371/twis Resident gut bacteria can affect patient responses to cancer immunotherapy (see the Perspective by Jobin). Routy et al. show that antibiotic consumption is associated with poor response to immunotherapeutic PD-1 blockade. They profiled samples from patients with lung and kidney cancers and found that nonresponding patients had low levels of the bacterium Akkermansia muciniphila. Oral supplementation of the bacteria to antibiotic-treated mice restored the response to immunotherapy. Matson et al. and Gopalakrishnan et al. studied melanoma patients receiving PD-1 blockade and found a greater abundance of “good” bacteria in the guts of responding patients. Nonresponders had an imbalance in gut flora composition, which correlated with impaired immune cell activity. Thus, maintaining healthy gut flora could help patients combat cancer. >>>>>>>>>>>>>>>>>>> Science, this issue p. 91, >>>>>>>>>>>>>>>>>>>> Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillère R, Fluckiger A, Messaoudene M, Rauber C, Roberti MP, Fidelle M, Flament C, Poirier-Colame V, Opolon P, Klein C, Iribarren K, Mondragón L, Jacquelot N, Qu B, Ferrere G, Clémenson C, Mezquita L, Masip JR, Naltet C, Brosseau S, Kaderbhai C, Richard C, Rizvi H, Levenez F, Galleron N, Quinquis B, Pons N, Ryffel B, Minard-Colin V, Gonin P, Soria JC, Deutsch E, Loriot Y, Ghiringhelli F, Zalcman G, Goldwasser F, Escudier B, Hellmann MD, Eggermont A, Raoult D, Albiges L, Kroemer G, Zitvogel L. Science. 2018 Jan 5;359(6371):91-97. doi: 10.1126/science.aan3706. Epub 2017 Nov 2. PMID: 29097494 Abstract Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy (n = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples (n = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity (P < 0.01) and relative abundance of bacteria of the Ruminococcaceae family (P < 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors. >>>>>>>>>>>>>>>>>>>>>>>>>>>. p. 104, >>>>>>>>>>>>>>>>>>>>>>>>>>>> The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Matson V, Fessler J, Bao R, Chongsuwat T, Zha Y, Alegre ML, Luke JJ, Gajewski TF. Science. 2018 Jan 5;359(6371):104-108. doi: 10.1126/science.aao3290. PMID: 29302014 Abstract Anti-PD-1-based immunotherapy has had a major impact on cancer treatment but has only benefited a subset of patients. Among the variables that could contribute to interpatient heterogeneity is differential composition of the patients' microbiome, which has been shown to affect antitumor immunity and immunotherapy efficacy in preclinical mouse models. We analyzed baseline stool samples from metastatic melanoma patients before immunotherapy treatment, through an integration of 16S ribosomal RNA gene sequencing, metagenomic shotgun sequencing, and quantitative polymerase chain reaction for selected bacteria. A significant association was observed between commensal microbial composition and clinical response. Bacterial species more abundant in responders included Bifidobacterium longum, Collinsella aerofaciens, and Enterococcus faecium. Reconstitution of germ-free mice with fecal material from responding patients could lead to improved tumor control, augmented T cell responses, and greater efficacy of anti-PD-L1 therapy. Our results suggest that the commensal microbiome may have a mechanistic impact on antitumor immunity in human cancer patients. >>>>>>>>>>>>>>>>>>>>>> p. 97; >>>>>>>>>>>>>>>>>>>>>>> Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, Prieto PA, Vicente D, Hoffman K, Wei SC, Cogdill AP, Zhao L, Hudgens CW, Hutchinson DS, Manzo T, Petaccia de Macedo M, Cotechini T, Kumar T, Chen WS, Reddy SM, Szczepaniak Sloane R, Galloway-Pena J, Jiang H, Chen PL, Shpall EJ, Rezvani K, Alousi AM, Chemaly RF, Shelburne S, Vence LM, Okhuysen PC, Jensen VB, Swennes AG, McAllister F, Marcelo Riquelme Sanchez E, Zhang Y, Le Chatelier E, Zitvogel L, Pons N, Austin-Breneman JL, Haydu LE, Burton EM, Gardner JM, Sirmans E, Hu J, Lazar AJ, Tsujikawa T, Diab A, Tawbi H, Glitza IC, Hwu WJ, Patel SP, Woodman SE, Amaria RN, Davies MA, Gershenwald JE, Hwu P, Lee JE, Zhang J, Coussens LM, Cooper ZA, Futreal PA, Daniel CR, Ajami NJ, Petrosino JF, Tetzlaff MT, Sharma P, Allison JP, Jenq RR, Wargo JA. Science. 2018 Jan 5;359(6371):97-103. doi: 10.1126/science.aan4236. Epub 2017 Nov 2. PMID: 29097493 Abstract Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy (n = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples (n = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity (P < 0.01) and relative abundance of bacteria of the Ruminococcaceae family (P < 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors. >>>>>>>>>>>>>>>>>>> see also p. 32 >>>>>>>>>>>>>>>>>>>>>>> Precision medicine using microbiota. Jobin C. Science. 2018 Jan 5;359(6371):32-34. doi: 10.1126/science.aar2946. No abstract available. PMID: 29302001 Summary Accumulating evidence indicates that dysregulation of microbiota-host interactions associates with various diseases, including inflammatory bowel diseases (IBDs), colorectal cancer, diabetes, and liver cirrhosis (1). Recently, research has generated paradigm shifts in concepts about the interactions between bacteria and cancer therapeutic drugs. For example, bacteria modulate the antitumor efficacy in preclinical models of various chemotherapies (2–4) and immunotherapeutic agents (5, 6). Conceptually, these findings suggest that bacteria-mediated interactions with the immune system are essential for optimal drug efficacy. However, there is limited information regarding the functional impact of the composition of the human microbiome and therapeutic outcomes in cancer patients. On pages 91, 97, and 104 of this issue, Routy et al. (7), Gopalakrishnan et al. (8), and Matson et al. (9), respectively, address this important issue and demonstrate that patients can be stratified into responders and nonresponders to immunotherapy on the basis of the composition of their intestinal microbiomes, suggesting that microbiota should be considered when assessing therapeutic intervention. Quote Link to comment Share on other sites More sharing options...
AlPater Posted January 9, 2018 Author Report Share Posted January 9, 2018 Antihypertensive Medication Regimen Intensity and Incident Dementia in an Older Population. Tan ECK, Qiu C, Liang Y, Wang R, Bell JS, Fastbom J, Fratiglioni L, Johnell K. J Am Med Dir Assoc. 2018 Jan 3. pii: S1525-8610(17)30677-1. doi: 10.1016/j.jamda.2017.11.017. [Epub ahead of print] PMID: 29306604 Abstract OBJECTIVE: To investigate the association between antihypertensive medication regimen intensity and risk of incident dementia in an older population. DESIGN: Prospective, longitudinal cohort study. PARTICIPANTS/SETTING: A total of 1208 participants aged ≥78 years, free of dementia, and residing in central Stockholm at baseline (2001-2004). MEASUREMENTS: Participants were examined at 3- and 6-year follow-up to detect incident dementia. Data were collected through face-to-face interviews, clinical examinations, and laboratory tests. Data on antihypertensive use were obtained by a physician through patient self-report, visual inspection, or medical records. Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between time-varying antihypertensive regimen intensity and incident dementia after adjusting for potential confounders. RESULTS: During the follow-up period, 125 participants were diagnosed with dementia. Participants who developed dementia were more likely to have vascular disease at baseline (66.4% vs 55.3%, P = .02). In fully adjusted analyses, the number of antihypertensive classes (HR 0.68, 95% CI 0.55-0.84) and total prescribed daily dose (HR 0.70, 95% CI 0.57-0.86) were significantly associated with reduced dementia risk. After considering all-cause mortality as a competing risk, the number (HR 0.75, 95% CI 0.62-0.91) and doses (HR 0.71, 95% CI 0.59-0.86) of antihypertensive classes, and the independent use of diuretics (HR 0.66, 95% CI 0.44-0.99), were significantly associated with lower dementia risk. CONCLUSIONS: Greater intensity of antihypertensive drug use among older people may be associated with reduced incidence of dementia. KEYWORDS: Antihypertensive agents; cardiovascular diseases; dementia; longitudinal studies; prospective studies Observational study of the differential impact of time-varying depressive symptoms on all-cause and cause-specific mortality by health status in community-dwelling adults: the REGARDS study. Moise N, Khodneva Y, Jannat-Khah DP, Richman J, Davidson KW, Kronish IM, Shaffer J, Safford MM. BMJ Open. 2018 Jan 5;8(1):e017385. doi: 10.1136/bmjopen-2017-017385. PMID: 29306879 Free Article Abstract OBJECTIVE: To assess the association between time-varying depressive symptoms with all-cause and cause-specific mortality. DESIGN: The REGARDS (Reasons for Geographic and Racial Differences in Stroke) is a national, population-based longitudinal study conducted from 2003 to 2007. SETTING: General continental US communities. PARTICIPANTS: 29 491 black and white US adults ≥45 years randomly sampled within race-sex-geographical strata. EXPOSURE: Elevated depressive symptoms (Centre for Epidemiologic Studies Depression (CES-D) 4≥4) measured at baseline and on average 5 and 7 years later. MAIN OUTCOME MEASURES: Cox proportional hazard regression models assessed cancer, non-cardiovascular (cardiovascular disease (CVD)), CVD and all-cause mortality. RESULTS: The average age was 64.9 years; 55% were women; 41% black; 11.0% had elevated depressive symptoms; 54% had poor, fair or good health. Time-varying depressive symptoms were significantly associated with non-CVD (adjusted HR (aHR)=1.29, 95% CI 1.16 to 1.44) and all-cause (aHR=1.24, 95% CI 1.14 to 1.39), but not cancer (aHR=1.15, 95% CI 0.96 to 1.38) or CVD (aHR=1.13, 95% CI 0.98 to 1.32) death adjusting for demographics, chronic clinical diseases, behavioural risk factors and physiological factors. Depressive symptoms were related to all-cause (aHR=1.48, 95% CI 1.27 to 1.78), CVD (aHR=1.37, 95% CI 0.99 to 1.91), non-CVD (aHR=1.54, 95% CI 1.24 to 1.92) and cancer (aHR=1.36, 95% CI 0.97 to 1.91) death in those who reported excellent or very good health. The analyses of the association between one measure of baseline depressive symptoms and mortality analyses yielded similar results. CONCLUSIONS: Time-varying depressive symptoms confer an increased risk for all-cause mortality, CVD, non-CVD death and cancer death, particularly in those with excellent or very good health. These findings may have implications for timely treatment, regardless of health status. KEYWORDS: health status; mortality Change in Submaximal Cardiorespiratory Fitness and All-Cause Mortality. de Lannoy L, Sui X, Lavie CJ, Blair SN, Ross R. Mayo Clin Proc. 2018 Jan 4. pii: S0025-6196(17)30846-7. doi: 10.1016/j.mayocp.2017.11.020. [Epub ahead of print] PMID: 29307551 Abstract OBJECTIVE: To evaluate the relationship between change in submaximal cardiorespiratory fitness (sCRF) and all-cause mortality risk in adult men and women. PATIENTS AND METHODS: A prospective study with at least 2 clinical visits (mean follow-up time, 4.2±3.0 years) between April 1974 and January 2002 was conducted to assess the relationship between change in sCRF and mortality risk during follow-up. Participants were 6106 men and women. Submaximal CRF was determined using the heart rate obtained at the 5-minute mark of a graded maximal treadmill test used to determine maximal CRF (mCRF). Change in sCRF from baseline to follow-up was categorized into 3 groups: increased fitness (decreased heart rate, <-4.0 beats/min), stable fitness (heart rate, -4.0 to 3.0 beats/min), and decreased fitness (increased heart rate, >3.0 beats/min). RESULTS: The mean change in sCRF at follow-up for all 6106 study participants was -0.5±10.0 beats/min, and the mean change in mCRF was -0.3±1.4 metabolic equivalents. Change in sCRF was related to change in mCRF, though the variance explained was small (R2=0.21; P<.001). The hazard ratios (95% CIs) for all-cause mortality were 0.60 (0.38-0.96) for stable and 0.59 (0.35-1.00) for increased sCRF compared with decreased sCRF after adjusting for age, change in weight, and other common risk factors for premature mortality. The hazard ratios for changes in sCRF and mCRF were not significant after adjusting for changes in mCRF (P=.29) and sCRF (P=.60), respectively. CONCLUSION: A simple 5-minute submaximal test of CRF identified that adults who maintained or improved sCRF were less likely to die from all causes during follow-up than were adults whose sCRF decreased. Whom to Treat for High Blood Pressure-Time for a Precision Approach. Moran AE, Pletcher MJ, Bibbins-Domingo K. JAMA Intern Med. 2018 Jan 1;178(1):37-38. doi: 10.1001/jamainternmed.2017.7853. No abstract available. PMID: 29297011 For decades, the threshold blood pressure (BP) values of 140 mm Hg or higher systolic BP or 90 mm Hg or higher diastolic BP at more than 1 encounter have defined the diagnosis of hypertension for most patients. The 2017 American Heart Association/American College of Cardiology (AHA/ACC) hypertension treatment guidelines set lower treatment goals of 130 mm Hg systolic BP and 80 mm Hg diastolic BP for high cardiovascular risk patients.1 While threshold BPs simplify treatment decisions, a preponderance of observational evidence has established a continuous, log-linear relationship between BP and risk for cardiovascular disease events, at least down to systolic BPs in the range of 115 to 120 mm Hg and diastolic BP around 75 mm Hg. The question for clinical practice is whether BP treatment goals should be guided by this evidence, favoring ever-lower BPs until adverse event risks or treatment costs overwhelm expected benefits? Despite evidence from scores of high quality randomized clinical trials of pharmacological BP lowering, the answer to this question remains controversial. In this issue of JAMA Internal Medicine, Brunström and Carlberg2 add to the debate with a high-quality, study-level meta-analysis of 74 selected trials of pharmacological BP lowering treatment, representing over 300 000 participants and over 1 million person-years of observation. Overall, the authors found that relative benefit from BP lowering was dependent on baseline BP: for participants with baseline BP higher than 160 mm Hg, treatment was associated with a relative benefit for major cardiovascular events (relative risk [RR] 0.78; 95% CI, 0.70-0.87); for those with baseline BP below 140 mm Hg, relative benefit was uncertain (RR, 0.97; 95% CI, 0.90-1.04). In other words, the authors report a difference in the relative cardiovascular benefit from BP lowering that varies according to baseline blood pressure. The results of the Brunström and Carlberg analysis2 differ from those of past meta-analyses of the relative benefit of BP lowering, which concluded that blood-pressure lowering effects in clinical trials align quite well with the observational evidence.3,4 That is, the relative benefit of lowering BP is expected to be the same across patients with different baseline BPs. Those earlier analyses used different trial inclusion criteria and were performed on different samples of trials. Unlike Brunström and Carlberg, the authors of the other meta-analyses first adjusted individual trials’ RR reductions to a 10–mm Hg BP standard before pooling effect estimates. If we considering the findings of Brunström and Carlberg and the prior meta-analyses together for the relative benefit of BP treatment, the overall conclusion is that BP lowering in patients with pretreatment systolic BP of 140 mm Hg or higher is clearly beneficial, but the benefit in patients with pretreatment systolic BP lower than 140 mm Hg is more uncertain and dependent on trials included in the meta-analyses and the analytic approach. Is pretreatment BP alone sufficient information to guide hypertension treatment decisions in clinical practice? No, it is not. Medical history and multivariate global predictions of cardiovascular disease risk are both strong indicators of benefit from BP lowering, and the Brunström and Carlberg analysis2 did not account for the many baseline participant characteristics that may combine to explain the different relative benefit they observed at different baseline BPs (eg, lipid levels, kidney function, smoking status, dietary sodium and potassium intake, white coat or masked hypertension status, or genetic determinants of lifelong risk). Brunström and Carlberg did find a benefit from BP lowering in participants with prior coronary heart disease whose pretreatment BP was lower than 140 mm Hg (RR for major cardiovascular events, 0.90; 0.84-0.97). Broadly, this finding is consistent with the results of the SPRINT trial,5 which found reduced risk for major cardiovascular events with intensive systolic BP treatment in patients at high risk for cardiovascular disease, including those with baseline systolic BP below 140 mm Hg. Importantly, much of the benefit of intensive BP treatment in SPRINT came from reduced rate of acute heart failure events, an outcome excluded from the primary outcome defined for many other BP lowering trials. Meta-analyses of BP treatment are limited in their focus exclusively on RR reduction, ignoring absolute risk reduction, which is arguably the most important measure of treatment benefit and the greatest source of heterogeneity of treatment effect in clinical trials.6 Our research group’s past analysis of selection for statin treatment7 found that an absolute risk reduction–based approach (“number needed to treat”) was more efficient than selection based on absolute risk alone. Implicit in guidelines recommending statin treatment according to absolute risk (eg, 10-year atherosclerotic cardiovascular disease risk) is an emphasis on relative, not absolute risk reduction. Even if Brunström and Carlberg2 are correct, and relative benefit of BP lowering treatment is attenuated at lower baseline BPs, absolute risk reduction may be comparable between some patients with lower baseline BPs and others with high baseline BPs. For example, using the point estimates from Brunström and Carlberg, one achieves the same net health benefit of preventing 1 cardiovascular event over 10 years by treating 50 patients with baseline systolic BP of 160 mm Hg or higher, and a 10-year absolute cardiovascular disease risk of 11% (RR, 0.78), as by treating 50 patients with baseline systolic BP lower than 140 mm Hg and coronary heart disease (at a baseline 10-year absolute risk of 20%; RR, 0.90). An important omission in the Brunström and Carlberg analysis2 (and most other past meta-analyses) is a summary estimate of adverse event risk related to BP lowering in the trials. In decisions about BP-lowering treatment intensity, benefits must be balanced against concomitant treatment risks, particularly in older adults. Risk for serious fall injuries appears to be highest in the first 15 days after initiating or intensifying BP-lowering treatment in older patients,8 and frailty status is a strong predictor of risk for serious medication-related adverse events. Even in SPRINT,5 though there was no difference in overall serious adverse events related to treatment between the trial arms, intensive treatment led to a slight impairment in kidney function, and frail elderly participants experienced a greater risk of adverse events in both arms. Predictive modeling studies by Patel et al9 and several of the SPRINT Challenge analyses (https://challenge-nejm-org.qe2a-proxy.mun.ca/pages/winners) identified baseline characteristics of SPRINT participants that were associated with higher risk for serious treatment-related serious adverse events independent of randomization to intensive BP lowering, including age, active smoking, and markers of chronic kidney disease. The biggest challenge in clinical practice when deciding about BP treatment for the individual patient is to weigh the relative importance of the component benefits and risks. Ultimately patients’ values and preferences related to these benefits and risks must play a vital role in that process. In the era of electronic health records and precision medicine, decisions about BP-lowering treatment initiation and intensification should not be based on pretreatment BP alone. Expected RR reduction may vary according to numerous, non-BP factors available in the patient database; absolute risk reduction most certainly does. Research on clinical trials and patient data registries should be designed to inform a more tailored approach to BP-lowering decisions that considers these various factors of potential benefits and harms so that clinicians and patients can together make informed individual choices about BP treatment. What should practicing clinicians take away from the body of literature on hypertension and the controversies on where to assign a threshold for treatment? Two clinical implications are worth highlighting, the first more important than the second. First, clinicians should not allow the ongoing debate about targeting treatment for systolic BPs lower than 140 mm Hg to detract from the overwhelming evidence from decades of clinical trials, observational studies, and meta-analyses (including that of Brunström and Carlberg2) that supports cardiovascular benefit from treating systolic BP at or above 140 mm Hg. This point deserves to be underscored because current BP control rates in the United States are less than 50%, and recent evidence from the Centers for Disease Control and Prevention suggests that the improvements in national control rates since 1999 (from 32% to 54%) have slowed or declined over the last 6 years.10 Several strategies have been shown to result in higher control rates, but a key approach relevant to the current debate is the need for more accurate BP assessments, including ambulatory BP monitoring and home BP monitoring, both for diagnosis and to guide response to therapy. Second, clinicians should also understand the general points that underlie the current debate on targeting BP lower than 140 mm Hg. We do not know with certainty who will benefit from lower BP in this range, at least in part because we do not have good estimates of adverse effects of treatment. In the absence of firm evidence, the best approach for clinical decision making may be to align with the new AHA/ACC 2017 hypertension guidelines1 and to focus on those with the highest underlying cardiovascular risk, who may be more likely to benefit for all of the reasons discussed. In applying this guidance, however, clinicians must use their judgement and consider potential adverse effects of more aggressive treatment that is tailored to each patient and of course consider the patient preference for more aggressive treatment. >>>>>>>>>>>>>>>>>>>>>>>>>> Association of Blood Pressure Lowering With Mortality and Cardiovascular Disease Across Blood Pressure Levels: A Systematic Review and Meta-analysis. Brunström M, Carlberg B. JAMA Intern Med. 2018 Jan 1;178(1):28-36. doi: 10.1001/jamainternmed.2017.6015. PMID: 29131895 Abstract IMPORTANCE: High blood pressure (BP) is the most important risk factor for death and cardiovascular disease (CVD) worldwide. The optimal cutoff for treatment of high BP is debated. OBJECTIVE: To assess the association between BP lowering treatment and death and CVD at different BP levels. DATA SOURCES: Previous systematic reviews were identified from PubMed, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effect. Reference lists of these reviews were searched for randomized clinical trials. Randomized clinical trials published after November 1, 2015, were also searched for in PubMed and the Cochrane Central Register for Controlled Trials during February 2017. STUDY SELECTION: Randomized clinical trials with at least 1000 patient-years of follow-up, comparing BP-lowering drugs vs placebo or different BP goals were included. DATA EXTRACTION AND SYNTHESIS: Data were extracted from original publications. Risk of bias was assessed using the Cochrane Collaborations assessment tool. Relative risks (RRs) were pooled in random-effects meta-analyses with Knapp-Hartung modification. Results are reported according to PRISMA guidelines. MAIN OUTCOMES AND MEASURES: Prespecified outcomes of interest were all-cause mortality, cardiovascular mortality, major cardiovascular events, coronary heart disease (CHD), stroke, heart failure, and end-stage renal disease. RESULTS: Seventy-four unique trials, representing 306 273 unique participants (39.9% women and 60.1% men; mean age, 63.6 years) and 1.2 million person-years, were included in the meta-analyses. In primary prevention, the association of BP-lowering treatment with major cardiovascular events was dependent on baseline systolic BP (SBP). In trials with baseline SBP 160 mm Hg or above, treatment was associated with reduced risk for death (RR, 0.93; 95% CI, 0.87-1.00) and a substantial reduction of major cardiovascular events (RR, 0.78; 95% CI, 0.70-0.87). If baseline SBP ranged from 140 to 159 mm Hg, the association of treatment with mortality was similar (RR, 0.87; 95% CI, 0.75-1.00), but the association with major cardiovascular events was less pronounced (RR, 0.88; 95% CI, 0.80-0.96). In trials with baseline SBP below 140 mm Hg, treatment was not associated with mortality (RR, 0.98; 95% CI, 0.90-1.06) and major cardiovascular events (RR, 0.97; 95% CI, 0.90-1.04). In trials including people with previous CHD and mean baseline SBP of 138 mm Hg, treatment was associated with reduced risk for major cardiovascular events (RR, 0.90; 95% CI, 0.84-0.97), but was not associated with survival (RR, 0.98; 95% CI, 0.89-1.07). CONCLUSIONS AND RELEVANCE: Primary preventive BP lowering is associated with reduced risk for death and CVD if baseline SBP is 140 mm Hg or higher. At lower BP levels, treatment is not associated with any benefit in primary prevention but might offer additional protection in patients with CHD. Decreasing Blood Pressure in Older Patients. Goodwin JS. JAMA Intern Med. 2018 Jan 1;178(1):100-101. doi: 10.1001/jamainternmed.2017.7035. No abstract available. PMID: 29204654 One of my patients, a woman in her late 80s, has required 4 drugs at high doses for many years to keep her systolic blood pressure under 160 mm Hg. Over a 3-month period earlier this year, she went from 4 drugs to 1, with her systolic blood pressure now under 140 mm Hg. She and her family are ecstatic; I, less so. It has been known for many years that decreasing blood pressure in the elderly is a bad sign, unless related to more aggressive treatment.1 Decreases in blood pressure are a component of the so-called terminal decline, a constellation of signs and symptoms including decreases in activity, weight, cognition, and psychological outlook that often occur in the year or 2 before death, particularly death in very old age.2 Of these, blood pressure is the most noticeable, because it is numerical, frequently measured, and valued by patients and physicians. Weight loss is also a bad sign.3 We have all encountered octogenarian patients proud of finally shedding that excess 20 pounds after 50 years of failed attempts. Once again, not a good sign. Delgado et al4 now report that blood pressure actually starts a downward trajectory more than 10 years before death, when examined at a population level. They conducted 2 sets of analyses using a database of electronic medical records from 674 primary care practices. First, they plotted the blood pressure of 46 634 patients in the 20 years before death. Blood pressures started decreasing approximately 14 to 18 years before death, with steeper declines in those dying in their 80s and 90s, and with the steepest declines occurring in the 2 years prior to death. In the second study, they matched by age and sex each patient who died with a patient who survived at least 9 years longer, and compared the changes in blood pressure for the 2 groups in the period 10 to 2 years before death in the dying cohort. There were declines in blood pressure in both cohorts, but they were significantly steeper in those who died. One straightforward interpretation of these findings is that many people who die in old age have been on a dying trajectory for a decade or more. Something is happening to them that is not happening in people of the same age who are not going to die over the next decade. Are there other components of that trajectory, in addition to blood pressure decreases? The entire predeath trajectory was best illustrated in a brilliant and data-dense series of analyses of the Cardiovascular Health Study by Diehr and colleagues.5 They examined changes in body mass index, cognition, self-rated health, gait speed, distance walked, and activities of daily living over time, starting at different ages, for example, changes between age 75 and 80 years. They then stratified those changes based on when the participant ultimately died, for example, at 80 or 85 years or older than 87 years. This allowed them to distinguish the effect of being 1 year older from being 1 year closer to death. For all variables, there were clear decreases in the 7 years before death, independent of age. For most of the variables, the “effect” of being a year closer to death was larger than the “effect” of being a year older. The declines in functions in the decade before death suggest that epidemiological studies that examine the association of any of those functions with mortality are susceptible to reverse causation. The observational studies that show that high blood pressure has survival value in very old age may be because more individuals with lower pressures are in terminal decline. Similar biases would tend to show positive associations with high body mass index, or more physical activity, and survival. Epidemiologic studies describe average effects across populations or subpopulations. Physicians deal with individuals. How does the former activity inform the latter? An individual does not, on average, survive to 80 years. He or she dies at a specific age, with or without a preceding decline. The changes described by Delgado et al4 and by Diehr et al5 represent the averages of many different individuals. Perhaps one of them was hit by a car at the end of a 10-mile run on his 80th birthday. Another died after a 5-year struggle with metastatic breast cancer. Many died of “old age” or “natural causes,” diagnoses that do not appear on mortality statistics but are the most parsimonious ways to describe cause of death in many old people.6 It is the individuals dying of old age, or after many years with a serious chronic disease, that I picture when I read the graphs created by Delgado et al4 and the earlier ones by Diehr et al.5 Just because declines in function in the years before death are predictable does not mean that they are inevitable. It is reasonable to expect that gait speed and physical functioning and affect could all be improved with interventions in the decade before death. On the other hand, the much steeper decline in blood pressure in the last 2 years of life may have a different interpretation. This decline is the subject of recent reports from another research group using the same primary care database.7 The blood pressure decreases are not subtle, and they are accompanied by similar unsubtle decreases in physical activity, cognition, weight, and affect.2 The challenge for physicians treating the very elderly is when to “let go,” when to stop urging more social engagement, more exercise, more food, and to realize that our patients are near death. No physician wants to clutter the last 10 to 20 months of a person’s life with irrelevant concerns and activities. Surely an individual in the last year of life has more important things to think about. The clinical picture of the terminal decline may not meet hospice criteria. Perhaps death is still a year or 2 away. But the response should be similar, with a focus on supportive care. We do not much teach or study or talk about the various trajectories before death. This was not the case a century ago, when effective treatments were few and prognostication a valued activity. My interest in this topic was stimulated many years ago by another patient—a woman in her 80s with inoperable stomach cancer—who asked me what might happen to her. I realized that I had not thought about it. My understanding did not exceed the data on average survivals recorded by cancer registries. Surely I should be able to be more informative, to sketch out the different trajectories that in their total produced the average survival data. To me, that is the real value of the study by Delgado et al4 and of future studies using the same or similar databases. They should help us dissect out many different trajectories that end in death, to better inform physicians and their patients about what they might expect. >>>>>>>>>>>>>>>>>>>> Blood Pressure Trajectories in the 20 Years Before Death. Delgado J, Bowman K, Ble A, Masoli J, Han Y, Henley W, Welsh S, Kuchel GA, Ferrucci L, Melzer D. JAMA Intern Med. 2018 Jan 1;178(1):93-99. doi: 10.1001/jamainternmed.2017.7023. PMID: 29204655 Abstract IMPORTANCE: There is mixed evidence that blood pressure (BP) stabilizes or decreases in later life. It is also unclear whether BP trajectories reflect advancing age, proximity to end of life, or selective survival of persons free from hypertension. OBJECTIVE: To estimate individual patient BP for each of the 20 years before death and identify potential mechanisms that may explain trajectories. DESIGN, STUDY, AND PARTICIPANTS: We analyzed population-based Clinical Practice Research Datalink primary care and linked hospitalization electronic medical records from the United Kingdom, using retrospective cohort approaches with generalized linear mixed-effects modeling. Participants were all available individuals with BP measures over 20 years, yielding 46 634 participants dying aged at least 60 years, from 2010 to 2014. We also compared BP slopes from 10 to 3 years before death for 20 207 participants who died, plus 20 207 birth-year and sex-matched participants surviving longer than 9 years. MAIN OUTCOMES AND MEASURES: Clinically recorded individual patient repeated systolic BP (SBP) and diastolic BP (DBP). RESULTS: In 46 634 participants (51.7% female; mean [sD] age at death, 82.4 [9.0] years), SBPs and DBPs peaked 18 to 14 years before death and then decreased progressively. Mean changes in SBP from peak values ranged from -8.5 mm Hg (95% CI, -9.4 to -7.7) for those dying aged 60 to 69 years to -22.0 mm Hg (95% CI, -22.6 to -21.4) for those dying at 90 years or older; overall, 64.0% of individuals had SBP changes of greater than -10 mm Hg. Decreases in BP appeared linear from 10 to 3 years before death, with steeper decreases in the last 2 years of life. Decreases in SBP from 10 to 3 years before death were present in individuals not treated with antihypertensive medications, but mean yearly changes were steepest in patients with hypertension (-1.58; 95% CI, -1.56 to -1.60 mm Hg vs -0.70; 95% CI, -0.65 to -0.76 mm Hg), dementia (-1.81; 95% CI, -1.77 to -1.87 mm Hg vs -1.41; 95% CI, -1.38 to -1.43 mm Hg), heart failure (-1.66; 95% CI, -1.62 to -1.69 mm Hg vs -1.37; 95% CI, -1.34 to -1.39 mm Hg), and late-life weight loss. CONCLUSIONS AND RELEVANCE: Mean SBP and DBP decreased for more than a decade before death in patients dying at 60 years and older. These BP decreases are not simply attributable to age, treatment of hypertension, or better survival without hypertension. Late-life BP decreases may have implications for risk estimation, treatment monitoring, and trial design. 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AlPater Posted January 10, 2018 Author Report Share Posted January 10, 2018 Relationship Between Dietary Vitamin D and Deaths From Stroke and Coronary Heart Disease: The Japan Collaborative Cohort Study. Sheerah HA, Eshak ES, Cui R, Imano H, Iso H, Tamakoshi A. Stroke. 2018 Jan 8. pii: STROKEAHA.117.019417. doi: 10.1161/STROKEAHA.117.019417. [Epub ahead of print] PMID: 29311267 Abstract BACKGROUND AND PURPOSE: There is growing evidence about the importance of vitamin D for cardiovascular health. Therefore, we examined the relationship between dietary vitamin D intake and risk of mortality from stroke and coronary heart disease in Japanese population. METHODS: A prospective study encompassing 58 646 healthy Japanese adults (23 099 men and 35 547 women) aged of 40 to 79 years in whom dietary vitamin D intake was determined via a self-administered food frequency questionnaire. The median follow-up period was 19.3 years (1989-2009). The hazard ratios and 95% confidence intervals of mortality were calculated using categories of vitamin D intake. RESULTS: During 965 970 person-years of follow-up, 1514 stroke and 702 coronary heart disease deaths were documented. Vitamin D intake was inversely associated with risk of mortality from total stroke especially intraparenchymal hemorrhage but not from coronary heart disease; the multivariable hazard ratios (95% confidence intervals) for the highest (≥440 IU/d) versus lowest (<110 IU/D) categories of vitamin D intake were 0.70 (0.54-0.91; P for trend=0.04) for total stroke and 0.66 (0.46-0.96; P for trend=0.04) for intraparenchymal hemorrhage. CONCLUSIONS: Dietary vitamin D intake seems to be inversely associated with mortality from stroke. KEYWORDS: coronary disease; diet; stroke; surveys and questionnaires; vitamin D [The below paper is pdf-availed.] Co-morbidities only account for a small proportion of excess mortality after fracture: a record linkage study of individual fracture types. Chen W, Simpson JM, March LM, Blyth FM, Bliuc D, Tran T, Nguyen TV, Eisman JA, Center JR. J Bone Miner Res. 2018 Jan 4. doi: 10.1002/jbmr.3374. [Epub ahead of print] PMID: 29314242 Abstract BACKGROUND: Non-hip non-vertebral fractures (NHNV) constitute the majority of osteoporotic fractures but few studies have examined the association between these fractures, co-morbidity and mortality. OBJECTIVE: To examine the relationship between individual non-hip non-vertebral fractures, co-morbidities and mortality. METHODS: Prospective population-based cohort of 267,043 subjects (45 and Up Study, Australia) had baseline questionnaires linked to hospital administrative and all-cause mortality data from 2006 - 2013. Associations between fracture and mortality examined using multivariate, time dependent Cox models, adjusted for age, prior fracture, body mass index, smoking and co-morbidities (cardiovascular disease, diabetes, stroke, thrombosis and cancer) and survival function curves. Population attributable fraction calculated for each level of risk exposure. RESULTS: During 1,490,651 person-years, women and men experienced 7,571 and 4,571 fractures and 7,064 deaths and 11,078 deaths, respectively. In addition to hip and vertebral fractures, pelvis, humerus, clavicle, rib, proximal tibia/fibula, elbow and distal forearm fractures in both sexes, and ankle fractures in men, were associated with increased multivariable adjusted mortality hazard ratios ranging from 1.3 to 3.4. Co-morbidity independently added to mortality such that a woman with a humeral fracture and one co-morbidity had a similarly reduced 5 year survival to that of a woman with a hip fracture and no co-morbidities. Population mortality attributable to any fracture without co-morbidity was 9.2% in women and 5.3% in men. CONCLUSION: All proximal non-hip, non-vertebral fractures in women and men were associated with increased mortality risk. Co-existent co-morbidities independently further increased mortality. Population attributable risk for mortality for fracture was similar to cardiovascular disease and diabetes, highlighting their importance and potential benefit for early intervention and treatment. KEYWORDS: Aging; Epidemiology; Practice/ Policy-related issues A 24-year prospective study of dietary α-linolenic acid and lethal prostate cancer. Wu J, Wilson KM, Stampfer MJ, Willett WC, Giovannucci EL. Int J Cancer. 2018 Jan 8. doi: 10.1002/ijc.31247. [Epub ahead of print] PMID: 29315549 Abstract Several meta-analyses have attempted to determine the relations between intake of α-linolenic acid (ALA) and prostate cancer, but results were inconclusive. 47,885 men aged 40-75y without prior cancer in the Health Professionals Follow-up Study were prospectively followed from 1986 to 2010. Intake of ALA was determined from validated food frequency questionnaires every four years. We used multivariate Cox proportional hazards models to estimate hazard ratios (HR) with 95% confidence intervals (CIs) for lethal prostate cancer (distant metastasis or prostate cancer death). 386 lethal prostate cancers were diagnosed in the pre-PSA era (before February,1994) and 403 cancers in the PSA era. Intake of ALA was associated with increased risk of lethal prostate cancer in the pre-PSA era (comparing top to bottom quintile of intake, multivariate-adjusted HR =1.78; 95% CI = 1.22-2.06; p trend = 0.003), but not in the PSA era (HR =0.81; 95% CI = 0.56-1.17; p trend = 0.53), and the difference in associations was statistically significant (p for interaction = 0.02). Mayonnaise, a primary food source of ALA intake in our cohort, was likewise only significantly associated with lethal prostate cancer in the pre-PSA era. Among many other fatty acids that are correlated with ALA due to shared food sources, none was associated with lethal prostate cancer in the pre-PSA era. In conclusion, higher intake of ALA was associated with an increased risk of lethal prostate cancer in the pre-PSA era, but not in the PSA era. Potential reasons for the differential associations warrant further investigation. KEYWORDS: prospective cohort study; prostate cancer; α-linolenic acid Quote Link to comment Share on other sites More sharing options...
AlPater Posted January 11, 2018 Author Report Share Posted January 11, 2018 Effect of Restriction Vegan Diet's on Muscle Mass, Oxidative Status and Myocytes Differentiation: a Pilot Study. Vanacore D, Messina G, Lama S, Bitti G, Ambrosio P, Tenore GC, Messina A, Monda V, Zappavigna S, Boccellino M, Novellino E, Monda M, Stiuso P. J Cell Physiol. 2018 Jan 10. doi: 10.1002/jcp.26427. [Epub ahead of print] PMID: 29319158 Abstract This study was conceived to evaluate the effects of three different diets on body composition, metabolic parameters and serum oxidative status. We enrolled three groups of healthy men (omnivores, vegetarians and vegans) with similar age, weight and BMI and we observed a significant decrease in muscle mass index and lean body mass in vegan compared to vegetarian and omnivore groups, and higher serum homocysteine levels in vegetarians and vegans compared to omnivores. We studied whether serum from omnivore, vegetarian and vegan subjects affected oxidative stress, growth and differentiation of both cardiomyoblast cell line H9c2 and H-H9c2 (H9c2 treated with H2 O2 to induce oxidative damage). We demonstrated that vegan sera treatment of both H9c2 and H-H9c2 cells induced an increase of TBARS values and cell death and a decrease of free NO2- compared to vegetarian and omnivorous sera. Afterwards, we investigated the protective effects of vegan, vegetarian and omnivore sera on the morphological changes induced by H2 O2 in H9c2 cell line. We showed that the omnivorous sera had major antioxidant and differentiation properties compared to vegetarian and vegan sera. Finally, we evaluated the influence of the three different groups of sera on MAPKs pathway and our data suggested that ERK expression increased in H-H9c2 cells treated with vegetarian and vegan sera and could promote cell death. The results obtained in this study demonstrated that restrictive vegan diet could not prevent the onset of metabolic and cardiovascular diseases nor protect by oxidative damage. KEYWORDS: muscle mass; myocyte differentiation; oxidative stress; vegans diet The protected survivor model: Using resistant successful cognitive aging to identify protection in the very old. Silverman JM, Schmeidler J. Med Hypotheses. 2018 Jan;110:9-14. doi: 10.1016/j.mehy.2017.10.022. Epub 2017 Oct 31. PMID: 29317078 Abstract For some cardiovascular risk factors, association with risk for cognitive impairment observed in early old age is reduced, or paradoxically even reversed, as age of outcome increases. Successful cognitive aging is intact cognition in the oldest-old; we define resistant successful cognitive aging as successful cognitive aging despite high risk. The protected survivor model posits that a minority of the general population has a protective factor that mitigates the negative effect of a risk factor on successful cognitive aging for the unprotected majority. As age increases, differential failure rates increase the proportion of survivors with protection. Among the unprotected, the proportion with low risk increases, but among those with protection, high risk and low risk do not differ. Due to differential mortality, half the survivors are eventually protected - a majority among those with high risk, and a minority among those with low risk. According to the protective survivor model, an example of Simpson's paradox, the association of the risk factor with survival does not change within an individual, but the association in the surviving population changes as its age increases. We created quantitative illustrations of a simplified protected survivor model applied to successful cognitive aging to explain how the usual association of a risk factor with cognitive decline is reversed in the very old. In the illustrations, probability of subsequent survival was higher for survivors with high risk (mostly protected) than low risk (mostly not protected), an example of Simpson's paradox. Resistance to disease despite the presence of risk factors is consistent with the presence of countervailing protection. Based on the protected survivor model, we hypothesize that studies seeking protective factors against cognitive decline will be more effective by limiting a successful cognitive aging sample to resistant successful cognitive aging - to contrast with a sample without successful cognitive aging. Vitamin D Improves Neurogenesis and Cognition in a Mouse Model of Alzheimer's Disease. Morello M, Landel V, Lacassagne E, Baranger K, Annweiler C, Féron F, Millet P. Mol Neurobiol. 2018 Jan 9. doi: 10.1007/s12035-017-0839-1. [Epub ahead of print] PMID: 29318446 Abstract The impairment of hippocampal neurogenesis at the early stages of Alzheimer's disease (AD) is believed to support early cognitive decline. Converging studies sustain the idea that vitamin D might be linked to the pathophysiology of AD and to hippocampal neurogenesis. Nothing being known about the effects of vitamin D on hippocampal neurogenesis in AD, we assessed them in a mouse model of AD. In a previous study, we observed that dietary vitamin D supplementation in female AD-like mice reduced cognitive decline only when delivered during the symptomatic phase. With these data in hand, we wondered whether the consequences of vitamin D administration on hippocampal neurogenesis are stage-dependent. Male wild-type and transgenic AD-like mice (5XFAD model) were fed with a diet containing either no vitamin D (0VD) or a normal dose of vitamin D (NVD) or a high dose of vitamin D (HVD), from month 1 to month 6 (preventive arm) or from month 4 to month 9 (curative arm). Working memory was assessed using the Y-maze, while amyloid burden, astrocytosis, and neurogenesis were quantified using immunohistochemistry. In parallel, the effects of vitamin D on proliferation and differentiation were assayed on primary cultures of murine neural progenitor cells. Improved working memory and neurogenesis were observed when high vitamin D supplementation was administered during the early phases of the disease, while a normal dose of vitamin D increased neurogenesis during the late phases. Conversely, an early hypovitaminosis D increased the number of amyloid plaques in AD mice while a late hypovitaminosis D impaired neurogenesis in AD and WT mice. The observed in vivo vitamin D-associated increased neurogenesis was partially substantiated by an augmented in vitro proliferation but not an increased differentiation of neural progenitors into neurons. Finally, a sexual dimorphism was observed. Vitamin D supplementation improved the working memory of males and females, when delivered during the pre-symptomatic and symptomatic phases, respectively. Our study establishes that (i) neurogenesis is improved by vitamin D in a male mouse model of AD, in a time-dependent manner, and (ii) cognition is enhanced in a gender-associated way. Additional pre-clinical studies are required to further understand the gender- and time-specific mechanisms of action of vitamin D in AD. This may lead to an adaptation of vitamin D supplementation in relation to patient's gender and age as well as to the stage of the disease. KEYWORDS: Alzheimer’s disease; In vitro and in vivo neurogenesis; Memory; Mouse model; Sexual dimorphism; Vitamin D deficiency; Vitamin D supplementation U-shaped association between fertility and mortality in a community-based sample of Japanese women. Konishi S, Ng CFS, Watanabe C. J Epidemiol Community Health. 2018 Jan 9. pii: jech-2017-209809. doi: 10.1136/jech-2017-209809. [Epub ahead of print] PMID: 29317469 Abstract BACKGROUND: Prospective cohort studies of contemporary populations in both Western and Asian settings have reported a U-shaped association between fertility and mortality. We examined whether an association exists between fertility and all-cause and cause-specific mortality in a sample of Japanese women. METHODS: A prospective cohort study was conducted in one rural and one urban community in Gunma Prefecture, Japan, in 1993. A follow-up survey was conducted in the year 2000 in 4858 women aged 47-77 years, and information on demographic and lifestyle characteristics was collected. Mortality and migration data through December 2008 were obtained. A Cox proportional hazard model was used to examine the relationship between parity and mortality. RESULTS: Compared with women with 2-4 children (reference group), higher total mortality was observed among women with 0-1 or 5+ children. Low (HR 1.7, 95% CI 1.2 to 2.3) and high (HR 2.1, 95% CI 1.0 to 4.7) parities were both associated with higher all-cause mortality even after adjusting for potential confounders. Mortality due to ischaemic heart disease exhibited a significant association with parity; the HRs were 3.2 (95% CI 1.1 to 9.2) for women with 0-1 child and 8.7 (95% CI 1.7 to 45.5) for women with 5 or more children. No significant association was observed for mortality from malignancies, cancer of the digestive system, cardiovascular disease or cerebrovascular disease. CONCLUSIONS: There exists a U-shaped association between parity and all-cause mortality and cause-specific mortality due to ischaemic heart disease among Japanese women. KEYWORDS: cohort studies; fertility; ischaemic heart disease; mortality Effects of anti-hypertensive treatment on major cardiovascular events in populations within prehypertensive levels: a systematic review and meta-analysis. Hong Z, Wu T, Zhou S, Huang B, Wang J, Jin D, Geng D. J Hum Hypertens. 2018 Jan 9. doi: 10.1038/s41371-017-0026-x. [Epub ahead of print] PMID: 29317741 Abstract Uncertainties still remain in terms of the efficacy of anti-hypertensive treatment on the risk of major cardiovascular (CV) events within prehypertensive levels. This review aims to assess the efficacy and safety of anti-hypertensives on the CV risks in populations within prehypertensive levels. Randomized controlled trials (RCTs) concerning active treatment vs placebo in populations within prehypertensive levels were identified through electronic database and manual search. Outcomes included the first co-primary outcomes, stroke, heart failure (HF), myocardial infarction (MI), all-cause mortality, and cardiovascular mortality. The first co-primary outcomes were defined as composite cardiovascular disease (CVD) events in the included studies. A total of 29 RCTs involving 127,641 participants were identified. Pooled analysis showed active treatment was associated with a significant 7% reduction in risk of the first co-primary outcomes, 14% in stroke, and 10% in HF as compared to placebo (0.86, 0.77-0.96; 0.93, 0.89-0.98; and 0.90, 0.83-0.97). However, there were no significant reductions in risk of MI, all-cause mortality, and cardiovascular mortality. A significant reduction in risk of the first co-primary outcomes was observed in subpopulations with systolic blood pressure (SBP) 130-139 mmHg (0.94, 0.89-0.99) or prior CVDs (0.88, 0.82-0.94). Meta-regression analyses showed no significant relative risk reductions proportional to the magnitude of the mean baseline BP, mean on-treatment BP, the mean absolute change in BP, the proportion of patients with hypertension, and mean age. In summary, anti-hypertensive treatment has beneficial cardiovascular effects in populations within prehypertensive levels, especially in subpopulations with SBP 130-139 mmHg or prior CVDs. Fish consumption and risk of all-cause and cardiovascular mortality: a dose-response meta-analysis of prospective observational studies. Jayedi A, Shab-Bidar S, Eimeri S, Djafarian K. Public Health Nutr. 2018 Jan 10:1-10. doi: 10.1017/S1368980017003834. [Epub ahead of print] PMID: 29317009 Abstract OBJECTIVE: There are some indications of regional differences in the association between fish consumption and clinical outcomes. We aimed to test the linear and potential non-linear dose-response relationships between fish consumption and risk of all-cause and cardiovascular (CVD) mortality, and possible confounding by region. DESIGN: Systematic review and dose-response meta-analysis. SETTING: Systematic search using PubMed and Scopus, from inception up to September 2016. SUBJECTS: Prospective observational studies reporting the estimates of all-cause and CVD mortality in relation to three or more categories of fish intake were included. Random-effects dose-response meta-analysis was conducted. RESULTS: Fourteen prospective cohort studies (ten publications) with 911 348 participants and 75 451 incident deaths were included. A 20 g/d increment in fish consumption was significantly and inversely associated with the risk of CVD mortality (relative risk=0·96; 95 % CI 0·94, 0·98; I 2=0 %, n 8) and marginally and inversely associated with the risk of all-cause mortality (relative risk=0·98; 95 % CI 0·97, 1·00; I 2=81·9 %, n 14). Subgroup analysis resulted in a significant association only in the subgroup of Asian studies, compared with Western studies, in both analyses. Analysis of Western studies suggested a nearly U-shaped association, with a nadir at fish consumption of ~20 g/d in analysis of both outcomes. Meanwhile, the associations appeared to be linear in Asian studies. CONCLUSIONS: There was potential evidence of regional differences in the association between fish consumption and mortality. It may be helpful to examine the associations by considering types of fish consumed and methods of fish preparation. KEYWORDS: All-cause mortality; CHD; CVD; Fishes; Meta-analysis Urinary Calcium Excretion and Risk of Chronic Kidney Disease in the General Population. Taylor JM, Kieneker LM, de Borst MH, Visser ST, Kema IP, Bakker SJL, Gansevoort RT. Kidney Int Rep. 2016 Dec 31;2(3):366-379. doi: 10.1016/j.ekir.2016.12.007. eCollection 2017 May. PMID: 29318214 Abstract INTRODUCTION: High urinary calcium excretion (UCaE) has been shown to lead to accelerated renal function decline in individuals with renal tubular diseases. It is not known whether this association also exists in the general population. Therefore, we investigated whether high UCaE is associated with risk of developing chronic kidney disease (CKD) in community-dwelling subjects. METHODS: Urine samples of 5491 subjects who were free of CKD at baseline and participated in the Prevention of Renal and Vascular End-Stage Disease study (a prospective, observational, general population-based cohort of Dutch men and women aged 28-75 years) were examined for UCaE. UCa concentration was measured in two 24-hour urine samples at baseline (1997-1998) by indirect potentiometry. UCaE was treated as a continuous variable and a categorical variable grouped according to sex-specific quintiles for UCaE. UCaE was compared with de novo development of estimated glomerular filtration rate <60 ml/min per 1.73 m2 and/or albuminuria >30 mg/24 h. RESULTS: Baseline median UCaE was 4.13 mmol/24 h for men and 3.52 mmol/24 h for women. During a median follow-up of 10.3 years, 899 subjects developed CKD. After multivariable adjustment, every 1 mmol/24 h higher baseline UCaE was associated with a 6% lower risk for incident CKD during follow-up (hazard ratio: 0.94 [0.88-0.99], P = 0.02). The association was shown to be significantly nonlinear, with highest risk of CKD in the lowest quintile for UCaE (hazard ratio: 1.28 [0.97-1.68], P = 0.09). There was no association between UCaE and mortality or cardiovascular health during follow-up, suggesting that this association was not a reflection of poor nutritional intake due to bad health. DISCUSSION: These findings indicate that high UCaE does not increase risk of CKD, but rather that low UCaE may be harmful. KEYWORDS: calcium; chronic kidney disease; hypercalciuria; nutrition The effect of protein diets in postmenopausal women with osteoporosis: Systematic review of randomized controlled trials. Koutsofta I, Mamais I, Chrysostomou S. J Women Aging. 2018 Jan 10:1-23. doi: 10.1080/08952841.2018.1418822. [Epub ahead of print] PMID: 29319467 Abstract The main objective of this systematic review was to examine the effectiveness of protein supplementation through diet or dietary supplements on osteoporosis in postmenopausal women as evidenced by randomized controlled trials (RCTs). Five RCTs were included using dietary protein (N = 2), protein supplements (N = 2), and proteins through diet and supplements (N = 1). A total of 677 postmenopausal woman were included, all diagnosed with osteoporosis (T score < -2.5) and aged between 50 and 80 years. Results have found that combined protein administration through diet, mainly from animal sources and supplemental proteins (whey proteins, 86 g/d PRO including 6 g WPI), for a short period of time (up to 12 months) may positively affect osteoporosis in postmenopausal women. In addition, a positive effect can also be achieved by the single administration of a 250 mg/d supplement in which 10 g was WPI for a six-month period. In this review, it is shown that both combined administration of proteins through diet and supplements and single administration through protein supplements may reduce the risk of fracture in postmenopausal osteoporotic women. In contrast, dietary proteins alone, in doses similar to and/or higher than the RDA values, may not have any positive effect on treating osteoporosis. KEYWORDS: BMD; osteoporosis; postmenopausal women; protein diet; protein nutrient supplementation; systematic review Quote Link to comment Share on other sites More sharing options...
AlPater Posted January 13, 2018 Author Report Share Posted January 13, 2018 Dietary Resveratrol Does Not Affect Life Span, Body Composition, Stress Response, and Longevity-Related Gene Expression in Drosophila melanogaster. Staats S, Wagner AE, Kowalewski B, Rieck FT, Soukup ST, Kulling SE, Rimbach G. Int J Mol Sci. 2018 Jan 11;19(1). pii: E223. doi: 10.3390/ijms19010223. PMID: 29324667 Abstract In this study, we tested the effect of the stilbene resveratrol on life span, body composition, locomotor activity, stress response, and the expression of genes encoding proteins centrally involved in ageing pathways in the model organism Drosophila melanogaster. Male and female w1118 D. melanogaster were fed diets based on sucrose, corn meal, and yeast. Flies either received a control diet or a diet supplemented with 500 µmol/L resveratrol. Dietary resveratrol did not affect mean, median, and maximal life span of male and female flies. Furthermore, body composition remained largely unchanged following the resveratrol supplementation. Locomotor activity, as determined by the climbing index, was not significantly different between control and resveratrol-supplemented flies. Resveratrol-fed flies did not exhibit an improved stress response towards hydrogen peroxide as compared to controls. Resveratrol did not change mRNA steady levels of antioxidant (catalase, glutathione-S-transferase, NADH dehydrogenase, glutathione peroxidase, superoxide dismutase 2) and longevity-related genes, including sirtuin 2, spargel, and I'm Not Dead Yet. Collectively, present data suggest that resveratrol does not affect life span, body composition, locomotor activity, stress response, and longevity-associated gene expression in w1118 D. melanogaster. KEYWORDS: Drosophila; healthy ageing; life span; longevity; resveratrol Annual flu shot saves the lives of seniors By Dr. Brian Goldman http://www.cbc.ca/radio/whitecoat/blog/annual-flu-shot-saves-the-lives-of-seniors-1.4477030 >>>>>>>>>>>>>>>>>>>>>>>>>>> Repeated influenza vaccination for preventing severe and fatal influenza infection in older adults: a multicentre case-control study. Casado I, Domínguez Á, Toledo D, Chamorro J, Astray J, Egurrola M, Fernández-Sierra MA, Martín V, Morales-Suárez-Varela M, Godoy P, Castilla J; Project PI12/02079 Working Group. CMAJ. 2018 Jan 8;190(1):E3-E12. doi: 10.1503/cmaj.170910. PMID: 29311098 Abstract BACKGROUND: The effectiveness of repeated vaccination for influenza to prevent severe cases remains unclear. We evaluated the effectiveness of influenza vaccination on preventing admissions to hospital for influenza and reducing disease severity. METHODS: We conducted a case-control study in 20 hospitals in Spain during the 2013/14 and 2014/15 influenza seasons. Community-dwelling adults aged 65 years or older who were admitted to hospital for laboratory-confirmed influenza were matched with inpatient controls by sex, age, hospital and admission date. The effectiveness of vaccination in the current and 3 previous seasons in preventing influenza was estimated for inpatients with nonsevere influenza and for those with severe influenza who were admitted to intensive care units (ICUs) or who died. RESULTS: We enrolled 130 inpatients with severe and 598 with nonsevere influenza who were matched to 333 and 1493 controls, respectively. Compared with patients who were unvaccinated in the current and 3 previous seasons, adjusted effectiveness of influenza vaccination in the current and any previous season was 31% (95% confidence interval [CI] 13%-46%) in preventing admission to hospital for nonsevere influenza, 74% (95% CI 42%-88%) in preventing admissions to ICU and 70% (95% CI 34%-87%) in preventing death. Vaccination in the current season only had no significant effect on cases of severe influenza. Among inpatients with influenza, vaccination in the current and any previous season reduced the risk of severe outcomes (adjusted odds ratio 0.45, 95% CI 0.26-0.76). INTERPRETATION: Among older adults, repeated vaccination for influenza was twice as effective in preventing severe influenza compared with nonsevere influenza in patients who were admitted to hospital, which is attributable to the combination of the number of admissions to hospital for influenza that were prevented and reduced disease severity. These results reinforce recommendations for annual vaccination for influenza in older adults. Lifespan extension without fertility reduction following dietary addition of the autophagy activator Torin1 in Drosophila melanogaster. Mason JS, Wileman T, Chapman T. PLoS One. 2018 Jan 12;13(1):e0190105. doi: 10.1371/journal.pone.0190105. eCollection 2018. PMID: 29329306 Abstract Autophagy is a highly conserved mechanism for cellular repair that becomes progressively down-regulated during normal ageing. Hence, manipulations that activate autophagy could increase lifespan. Previous reports show that manipulations to the autophagy pathway can result in longevity extension in yeast, flies, worms and mammals. Under standard nutrition, autophagy is inhibited by the nutrient sensing kinase Target of Rapamycin (TOR). Therefore, manipulations of TOR that increase autophagy may offer a mechanism for extending lifespan. Ideally, such manipulations should be specific and minimise off-target effects, and it is important to discover additional methods for 'clean' lifespan manipulation. Here we report an initial study into the effect of up-regulating autophagy on lifespan and fertility in Drosophila melanogaster by dietary addition of Torin1. Activation of autophagy using this selective TOR inhibitor was associated with significantly increased lifespan in both sexes. Torin1 induced a dose-dependent increase in lifespan in once-mated females. There was no evidence of a trade-off between longevity and fecundity or fertility. Torin1-fed females exhibited significantly elevated fecundity, but also elevated egg infertility, resulting in no net change in overall fertility. This supports the idea that lifespan can be extended without trade-offs in fertility and suggest that Torin1 may be a useful tool with which to pursue anti-ageing research. >>>>>>>>>>>> "Torin-1 did not affect the survival of normal colon stem cells in vivo, suggesting its selectivity towards cancer cells." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3875761/ The J-curve between Diastolic Blood Pressure and Risk of All-cause and Cardiovascular Death. Kimm H, Mok Y, Lee SJ, Lee S, Back JH, Jee SH. Korean Circ J. 2018 Jan;48(1):36-47. doi: 10.4070/kcj.2017.0036. PMID: 29322696 https://synapse.koreamed.org/DOIx.php?id=10.4070/kcj.2017.0036&vmode=PUBREADER https://synapse.koreamed.org/Synapse/Data/PDFData/0054KCJ/kcj-48-36.pdf Abstract BACKGROUND AND OBJECTIVES: The J-curve phenomenon between diastolic blood pressure (DBP) and mortality has been reported repeatedly in treated patients. However, the baseline risk of low DBP has not been fully explored. This study was to examine the relationship between DBP and risk of mortality from all-cause, atherosclerotic vascular diseases (ASCVD), and ischemic heart disease (IHD) using a prospective cohort of general population. METHODS: We analyzed 1,234,435 participants of the Korean Cancer Prevention Study cohort (789,255 men, 30-95 years of age) who had a medical evaluation from 1992 to 1995 using Cox proportional hazards models. RESULTS: A total of 22.5 million person-years were followed up (mean age 46.6 years, deaths 193,903 cases). The hazard ratios of mortality from all-cause and ASCVD, among those with DBP <60 mmHg compared to 70-79 mmHg were 1.23 (95% confidence interval [CI], 1.16-1.30) and 1.37 (95% CI, 1.20-1.57), respectively, after adjustment for multivariable including systolic blood pressure. Increased risks of all-cause death in the lowest DBP category group were maintained in men or women, 30-59 or ≥60 years of age, smoker or non-smoker and diabetes mellitus (DM) or non-DM subgroups. The risk in DBP 60-69 mmHg groups increased in several subgroups. However, the risk for ASCVD death in 30-59 years and DM group, and risk for IHD death in most subgroups except for elderly (≥60 years) decreased. CONCLUSION: A J-curve relationship between low DBP and all-cause death was found consistently. The baseline risk in the general population may be considered for risk assessment, particularly in case of interventions that lower DBP below 60 mmHg. KEYWORDS: Blood pressure; Diastolic blood pressure; Hypertension; Mortality; Myocardial ischemia Frailty and leucocyte count are predictors of all-cause mortality and hospitalization length in non-demented institutionalized older women. Fernandez-Garrido J, Ruiz-Ros V, Navarro-Martínez R, Buigues C, Martínez-Martínez M, Verdejo Y, Sanantonio-Camps L, Mascarós MC, Cauli O. Exp Gerontol. 2018 Jan 8. pii: S0531-5565(17)30413-8. doi: 10.1016/j.exger.2018.01.007. [Epub ahead of print] PMID: 29326085 Abstract Alteration in the immune system such as the number of white blood cells count (WBC) has been associated with frailty syndrome but their role in institutionalized older individuals have been rarely investigated. We evaluated the relationships between white blood cell subtypes, geriatric assessment, depression and frailty syndrome based on the criteria of physical phenotype. In particular, we aimed to analyze by a two-year follow-up and prospective study the predictive value of alterations in WBC, frailty and functional impairment in terms of hospitalizations and all-cause mortality in institutionalized older women. There was a significant and inverse correlation between the frailty score and lymphocyte count at baseline but it did not display any predictive effect for the outcomes (hospitalizations and mortality). In contrast, monocytes count was significantly correlated with number of hospital stays and predicted hospitalizations in the follow-up. High frailty score directly and better functional status (Barthel score) inversely predicted mortality in the follow-up with an HR of 1.87 (95%CI: 1.04-3.35), and 0.97 (95% CI: 0.96-0.99) (p < .05 in both cases). Further investigation into the role of white blood cell subtypes in aging and its associated adverse outcomes in older adults is warranted. Physical phenotype of frailty besides general population, also predicted mortality in older institutionalized women and deserves specific intervention in this subgroup of older individuals. Adherence to Mediterranean Diet Reduces Incident Frailty Risk: Systematic Review and Meta-Analysis. Kojima G, Avgerinou C, Iliffe S, Walters K. J Am Geriatr Soc. 2018 Jan 11. doi: 10.1111/jgs.15251. [Epub ahead of print] Review. PMID: 29322507 Abstract OBJECTIVES: To conduct a systematic review of the literature on prospective cohort studies examining associations between adherence to a Mediterranean diet and incident frailty and to perform a meta-analysis to synthesize the pooled risk estimates. DESIGN: Systematic review and meta-analysis. SETTING: Embase, MEDLINE, CINAHL, PsycINFO, and Cochrane Library were systematically searched on September 14, 2017. We reviewed references of included studies and relevant review papers and performed forward citation tracking for additional studies. Corresponding authors were contacted for additional data necessary for a meta-analysis. PARTICIPANTS: Community-dwelling older adults (mean age ≥60). MEASUREMENTS: Incident frailty risk according to adherence to a Mediterranean diet. RESULTS: Two reviewers independently screened the title, abstract, and full text to ascertain the eligibility of 125 studies that the systematic search of the literature identified, and four studies were included (5,789 older people with mean follow-up of 3.9 years). Two reviewers extracted data from the studies independently. All four studies provided adjusted odds ratios (ORs) of incident frailty risk according to three Mediterranean diet score (MDS) groups (0-3, 4-5, and 6-9). Greater adherence to a Mediterranean diet was associated with significantly lower incident frailty risk (pooled OR = 0.62, 95% CI = 0.47-0.82, P = .001 for MDS 4-5; pooled OR = 0.44, 95% CI = 0.31-0.64, P < .001 for MDS 6-9) than poorer adherence (MDS 0-3). Neither significant heterogeneity (I2 = 0-16%, P = .30) nor evidence of publication bias was observed. CONCLUSION: Greater adherence to a Mediterranean diet is associated with significantly lower risk of incident frailty in community-dwelling older people. Future studies should confirm these findings and evaluate whether adherence to a Mediterranean diet can reduce the risk of frailty, including in non-Mediterranean populations. KEYWORDS: Mediterranean diet; frailty; meta-analysis; systematic review Quote Link to comment Share on other sites More sharing options...
AlPater Posted January 14, 2018 Author Report Share Posted January 14, 2018 Premature recruitment of oocyte pool and increased mTOR activity in Fmr1 knockout mice and reversal of phenotype with rapamycin. Mok-Lin E, Ascano M Jr., Serganov A, Rosenwaks Z, Tuschl T, Williams Z. Sci Rep. 2018 Jan 12;8(1):588. doi: 10.1038/s41598-017-18598-y. PMID: 29330421 Abstract While mutations in the fragile X mental retardation-1 (FMR1) gene are associated with varying reproductive outcomes in females, the effects of a complete lack of FMR1 expression are not known. Here, we studied the ovarian and reproductive phenotypes in an Fmr1 knockout (KO) mouse model and the role of mammalian target of rapamycin (mTOR) signaling. Breeding, histologic and mTOR signaling data were obtained at multiple time points in KO and wild type (WT) mice fed a control or rapamycin (mTOR inhibitor) diet. KO mice showed an earlier decline in ovarian reserve than WT mice with an increased proportion of activated follicles. mTOR and phosphorylated S6 kinase (p-S6K) levels, a measure of downstream mTOR signaling, were elevated in the KO ovaries. Rapamycin blocked these effects in KO mice, and increased the primordial follicle pool and age of last litter in WT mice. Our data demonstrates an early decline in reproductive capacity in Fmr1 KO mice and proposes that premature recruitment of the primordial pool via altered mTOR signaling may be the mechanism. Reversal of phenotypes and protein levels in rapamycin-treated KO mice, as well as increased reproductive lifespan of rapamycin-fed WT mice, suggest the mTOR pathway as a potential therapeutic target. A summary of meat intakes and health burdens. Yip CSC, Lam W, Fielding R. Eur J Clin Nutr. 2018 Jan;72(1):18-29. doi: 10.1038/ejcn.2017.117. Epub 2017 Aug 9. Review. PMID: 28792013 Abstract This review summarizes published meta-analysis outcomes on the associations between meat intakes and burden of diseases. A novel assessment process was developed, combining selected Cochrane Review measures, AMSTAR checklist, and other quality measures identified by authors during preliminary phases of the review process. Meat intakes have been found to be statistically significant associated with 21 burden of diseases. A total of 37 risk-outcome best dose-response estimations were identified, all were positively associated, and 21 of them with low to moderate, or insignificant heterogeneity. The highest dose-responses per 50 g increases in processed meat intake at 95% confident levels were 1.81 (1.32, 2.48) for esophageal cancer, 1.71 (1.34, 2.19) for stomach cancer, 1.42 (1.07, 1.89) for CHD, 1.32 (1.19, 1.48) for diabetes, and 1.24 (1.13, 1.35) for colon cancer incidences, and 1.24 (1.09, 1.40) for CVD mortality. The highest dose-responses per each 65 g increases in total red meat intake were 1.36 (1.16, 1.58) for endometrial cancer, 1.25 (1.10, 1.41) esophageal cancer, and 1.22 (1.16, 1.23) for lung cancer incidences. In addition, 14 statistically significant associations in terms of high vs low meat intake relative risks were also identified. Total red meat intakes were found negatively associated with CVD and cancer mortalities, and poultry meat intakes were found negatively associated with all-cause and cancer mortalities, and rectal cancer incidences in low meat consumption Asian countries. Current global and dietary Comparative Risk Assessments may underestimate burden of diseases attributed to meat intakes. More investigation is needed in low-meat consumption countries. Egg consumption, cardiovascular diseases and type 2 diabetes. Geiker NRW, Larsen ML, Dyerberg J, Stender S, Astrup A. Eur J Clin Nutr. 2018 Jan;72(1):44-56. doi: 10.1038/ejcn.2017.153. Epub 2017 Sep 27. Review. PMID: 28952608 Abstract Eggs are rich in nutrients and a source of essential fatty- and amino acids, and the food item with highest cholesterol content. Since the 1970s dietary recommendations have advised limiting egg intake to 2-4 a week for the healthy population, and in those diagnosed with cardiovascular disease (CVD) and type 2 diabetes (T2D) an even more restricted consumption. The aim of the present paper was to assess the recommendation to lower the dietary intake of cholesterol and especially the intake of egg to reduce the risk of CVD and T2D. We performed three web-based literature searches on human studies (observational and interventional) published within the past 10 years during spring 2015. High-quality intervention studies have found nonsignificant effects of increasing the consumption of eggs on risk markers for CVD and T2D in healthy subjects and subjects with T2D. The risk associations found in the observational studies are more likely to be attributed to a dietary pattern often accompanying high egg intake and/or the cluster of other risk factors in people with high egg consumption. Dietary patterns, physical activity and genetics affect the predisposition of CVD and T2D more than a single food item as eggs. In conclusion, up to seven eggs per week can safely be consumed, but in patients with established CVD or T2D only with special emphasis on a healthy lifestyle. Association of whole grain intake with all-cause, cardiovascular, and cancer mortality: a systematic review and dose-response meta-analysis from prospective cohort studies. Zhang B, Zhao Q, Guo W, Bao W, Wang X. Eur J Clin Nutr. 2018 Jan;72(1):57-65. doi: 10.1038/ejcn.2017.149. Epub 2017 Nov 1. Review. PMID: 29091078 Abstract BACKGROUND/OBJECTIVES: Whole grains are rich source of nutrients and have shown beneficial effects on human health. This study was designed to systematically review the existing results and quantitatively assess the dose-response relationship of whole grain intake with all-cause and cause-specific mortality. SUBJECTS/METHODS: We searched 'whole grain' or 'whole grains' in combination with 'mortality'' or 'cardiovascular disease' or 'cancer' through the Web of Science and PubMed databases till 20 January 2016. To be eligible for inclusion, publications should be prospective cohort studies and reported the influence of whole grain intake on human mortality. Relative risks (RRs) and 95% confidence intervals (CIs) from the included studies were pooled by a random effects model or fixed effect model. RESULTS: We included 19 cohort studies from 17 articles, with 1 041 692 participants and 96 710 deaths in total, in the analyses. We observed an inverse relationship of whole grain intake with risk of total, cardiovascular disease and cancer mortality. The pooled RR was 0.84 (95% CI 0.81-0.88, n=9) for total mortality, 0.83 (95% CI 0.79-0.86, n=8) for CVD mortality and 0.94 (95% CI 0.87-1.01, n=14) for cancer mortality, comparing the highest intake of whole grain with the lowest category. For dose-response analysis, we found a nonlinear relationship of whole grain intake with risk of total, cardiovascular and cancer mortality. Each 28 g/d intake of whole grains was associated with a 9% (pooled RR: 0.91 (0.90-0.93)) lower risk for total mortality, 14% (pooled RR: 0.86 (0.83-0.89)) lower risk for CVD mortality and 3% (pooled RR: 0.97 (0.95-0.99)) lower risk for cancer mortality. CONCLUSIONS: Our study shows that whole grain intake was inversely associated with risk of total, CVD and cancer mortality. Our results support current dietary guidelines to increase the intake of whole grains. Government officials, scientists and medical staff should take actions to promote whole grains intake. Associations between fruits, vegetables, vitamin A, β-carotene and flavonol dietary intake, and age-related macular degeneration in elderly women in Korea: the Fifth Korea National Health and Nutrition Examination Survey. Kim EK, Kim H, Kwon O, Chang N. Eur J Clin Nutr. 2018 Jan;72(1):161-167. doi: 10.1038/ejcn.2017.152. Epub 2017 Sep 27. PMID: 28952611 Abstract BACKGROUND/OBJECTIVES: Age-related macular degeneration (AMD) is one of the principal causes of blindness. This study investigated the association between diet and the prevalence of AMD in elderly Korean women. SUBJECTS/METHODS: Study subjects were women aged ⩾65 years (n=1008) from the Korea National Health and Nutrition Examination Survey (2010-2012). The presence of early- and late-onset AMD was determined on the basis of a fundus photograph from a health examination survey. Food intake was estimated using 24 h recall. RESULTS: The prevalence of AMD was 18.8% in elderly women in Korea. Multiple logistic regression analysis showed a significant negative association between vegetable intake and AMD (odds ratio (OR) 0.44, 95% confidence interval (CI) 0.25, 0.77, P for trend=0.002) after adjusting for age, body mass index, postmenopausal period, duration of hormone replacement therapy, residential area, education level, family income, smoking status, alcohol consumption, dietary supplement use and total energy intake. After adjusting for potential confounders, the ORs between extreme quartiles were 0.55 (95% CI 0.29, 1.05, P for trend=0.070) for fruit and vegetable intake, 0.38 (95% CI 0.21, 0.68, P for trend=0.001) for vitamin A, 0.36 (95% CI 0.19, 0.67, P for trend<0.001) for β-carotene and 0.45 (95% CI 0.25, 0.82, P for trend=0.008) for flavonols. CONCLUSIONS: These results suggest that higher consumption of fruits and vegetables containing antioxidant nutrients and phytochemicals may provide some protection against AMD. 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AlPater Posted January 15, 2018 Author Report Share Posted January 15, 2018 Supplemental Retinal Carotenoids Enhance Memory in Healthy Individuals with Low Levels of Macular Pigment in A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Power R, Coen RF, Beatty S, Mulcahy R, Moran R, Stack J, Howard AN, Nolan JM. J Alzheimers Dis. 2018;61(3):947-961. doi: 10.3233/JAD-170713. PMID: 29332050 https://content.iospress.com/articles/journal-of-alzheimers-disease/jad170713 https://content.iospress.com/download/journal-of-alzheimers-disease/jad170713?id=journal-of-alzheimers-disease%2Fjad170713 Abstract BACKGROUND: There is a biologically plausible rationale whereby the dietary carotenoids lutein (L), zeaxanthin (Z), and meso-zeaxanthin (MZ), which are collectively referred to as macular pigment (MP) in the central retina (macula), support the maintenance of cognition via their antioxidant and anti-inflammatory properties. OBJECTIVE: To investigate the impact of supplemental L, Z, and MZ on memory, executive function, and verbal fluency among healthy individuals with low MP levels. METHODS: In this double-blind, placebo-controlled, randomized clinical trial, subjects (n = 91; mean±SD age = 45.42±12.40; % male = 51.6) consumed a daily formulation of 10 mg L, 10 mg MZ, and 2 mg Z (n = 45) or placebo (n = 46) for 12 months. Cognitive domains assessed included verbal and visual learning, immediate and delayed memory, executive function, and verbal fluency. MP and serum carotenoid concentrations of L, Z, and MZ were also measured. RESULTS: Following 12-month supplementation, individuals in the active group exhibited statistically significant improvements in memory when compared to the placebo group (paired associated learning [PAL] memory score [rANOVA, p = 0.009]; PAL errors [rANOVA, p = 0.017]). Furthermore, the observed reduction in the number of errors made in the PAL task among those in the intervention group was positively and significantly related to observed increases in MP volume (p = 0.005) and observed increases in serum concentrations of L (p = 0.009). CONCLUSION: This randomized, double-blind, placebo-controlled clinical trial demonstrates a memory-enhancing effect of daily supplementation with L, Z, and MZ in healthy subjects with low MP at baseline. The implications of these findings for intellectual performance throughout life, and for risk of cognitive decline in later life, warrant further study. KEYWORDS: Brain; CANTAB; carotenoids; cognitive function; episodic memory; lutein; macular pigment; meso-zeaxanthin; paired associated learning; zeaxanthin Coffee consumption and risk of hypertension in the SUN Project. Navarro AM, Martinez-Gonzalez MA, Gea A, Ramallal R, Ruiz-Canela M, Toledo E. Clin Nutr. 2017 Dec 21. pii: S0261-5614(17)31429-2. doi: 10.1016/j.clnu.2017.12.009. [Epub ahead of print] PMID: 29331442 Abstract BACKGROUND & AIMS: Evidence on coffee consumption and its association with the incidence of hypertension is still inconsistent. The aim of this study was to examine the association of regular or decaffeinated coffee consumption with the risk of developing hypertension in a middle-aged Mediterranean cohort. METHODS: The SUN Project is a prospective open cohort with more than 22,500 Spanish university graduates. For the present study, we analyzed data from 13,374 participants initially free of hypertension (mean follow-up 9.1 years). The consumption of regular and decaffeinated coffee was obtained at baseline using a previously validated semi-quantitative food frequency questionnaire. Validated, self-reported medical diagnoses of hypertension were collected biennially. We used Cox regression models to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for incident hypertension according to baseline coffee consumption. We assessed the interaction with sex and baseline adherence to the Mediterranean diet. RESULTS: Among 121,397 person-years of follow-up, a total of 1757 participants developed hypertension. Overall, coffee consumption -either caffeinated or decaffeinated- was not significantly associated with the risk of hypertension. Only among women, higher consumption of regular coffee was associated with a 26% lower risk of hypertension (>=2 cups/d vs. never/seldom, 95% CI 9%-39%; p for interaction: 0.0236). Women with a low baseline adherence to the Mediterranean diet showed the strongest risk reduction (HR ≥ 2 cups/d vs. never/seldom 0.58, 95% CI (0.41-0.82) p for interaction = 0.0452). CONCLUSION: In the SUN project we found an inverse association between regular coffee consumption and the risk of hypertension in women, which was strongest among women with a suboptimal food pattern (low adherence to the Mediterranean diet). KEYWORDS: Blood pressure; Coffee; Hypertension; Mediterranean diet; Prospective cohort; SUN project Quote Link to comment Share on other sites More sharing options...
AlPater Posted January 16, 2018 Author Report Share Posted January 16, 2018 [The below paper is pdf-availed.] Pilot study of sleep and meal timing effects, independent of sleep duration and food intake, on insulin sensitivity in healthy individuals. Pizinger T, Kovtun K, RoyChoudhury A, Laferrère B, Shechter A, St-Onge MP. Sleep Health. 2018 Feb;4(1):33-39. doi: 10.1016/j.sleh.2017.10.005. Epub 2017 Nov 20. PMID: 29332677 Abstract This pilot study tested the independent and interactive effects of sleep and meal times, under identical sleep duration and feeding conditions, on insulin sensitivity (Si) in overweight adults. Participants underwent a 4-phase randomized crossover inpatient study differing in sleep times: normal (Ns: 0000-0800 hours) or late (Ls: 0330-1130 hours); and in meal times: normal (Nm: 1, 5, 11, and 12.5 hours after awakening) or late (Lm: 4.5, 8.5, 14.5, and 16 hours after awakening). An insulin-modified frequently sampled intravenous glucose tolerance test, at scheduled breakfast time, and a meal tolerance test, at scheduled lunch time, were performed to assess Si after 3 days in each condition. Six participants were enrolled (4 men, 2 women; mean age 25.1±[sD] 3.9 years, body mass index 29.2±2.7 kg/m2); only 1 failed to complete her last study phase. There were no effects of sleep and meal times or sleep × meal time interaction on Si (all P>.35), acute insulin response to intravenous glucose (all P>.20), and disposition index (all P>.60) after adjusting for sex and body mass index. Meal tolerance test glucose and insulin areas under the curve were lower during Nm (glucose P=.11; insulin P=.0088). There were a sleep × meal interaction and an effect of meal times on overnight glucose (P=.0040 and .012, respectively) and insulin (P=.0075 and .067, respectively). Sleep timing, without concomitant sleep restriction, does not adversely affect Si and glucose tolerance, but meal times may be relevant for health. Our results should be confirmed in a larger sample. KEYWORDS: Cortisol; Glucose tolerance; Insulin sensitivity; Meal timing; Melatonin; Sleep timing The Relationship between Habitual Dietary Intake and Gut Microbiota in Young Japanese Women. Seura T, Yoshino Y, Fukuwatari T. J Nutr Sci Vitaminol (Tokyo). 2017;63(6):396-404. doi: 10.3177/jnsv.63.396. PMID: 29332901 https://www.jstage.jst.go.jp/article/jnsv/63/6/63_396/_pdf Abstract Recent studies have shown that dietary content affects the health of the host by changing the gut microbiota. However, little is known about the association of microbiota composition with habitual diet in Japanese people. Here, we aimed to clarify the relationship between the fecal microbiota and habitual dietary intake of micronutrients, macronutrients and food groups in healthy young Japanese women. Analysis of fecal microbiota was performed by the terminal restriction fragment length polymorphism (T-RFLP) method, and a dietary survey was conducted over three consecutive days using a weighed food record method. T-RFLP pattern analysis divided the subjects into two clusters, where cluster A group had a high relative abundance of Bacteroides and Clostridium cluster IV, and cluster B group had a high relative abundance of Bifidobacterium and Lactobacillales. Cluster A group also had lower intakes of iron and vitamin K and higher intakes of mushrooms and snacks than cluster B group. Analysis of Spearman rank correlations found several significant relationships between fecal microbiota and intake of nutrients and food groups. Bifidobacterium was correlated with iron intake, and Clostridium cluster XI was negatively correlated with intakes of cholesterol and eggs. These results suggest that dietary habits may strongly affect Bifidobacterium, Bacteroides and Clostridium abundance in the gut microbiota of young Japanese women. This is the first study to show relationships between fecal microbiota and habitual dietary intake in Japanese people. Accumulation of results from similar studies will help to elucidate the relationships between dietary intake and diseases in Japanese people. KEYWORDS: cross-sectional study; gut microbiota; habitual dietary intake; young Japanese women Dietary L-Arginine Intakes and the Risk of Metabolic Syndrome: A 6-Year Follow-Up in Tehran Lipid and Glucose Study. Mirmiran P, Moghadam SK, Bahadoran Z, Ghasemi A, Azizi F. Prev Nutr Food Sci. 2017 Dec;22(4):263-270. doi: 10.3746/pnf.2017.22.4.263. Epub 2017 Dec 31. PMID: 29333377 Abstract This study was conducted to investigate whether regular dietary intake of L-arginine could affect the occurrence of metabolic syndrome (MetS). Eligible adult men and women (n=1,237), who participated in the Tehran Lipid and Glucose Study, were followed for a median of 6.3 years. Dietary intakes of L-arginine and serum nitrate and nitrite (NOx) concentration were assessed at baseline (2006~2008), and demographics, anthropometrics, and biochemical variables were evaluated at baseline and follow-up examinations. The occurrence of MetS was assessed in relation to total L-arginine, intakes of L-arginine from animal and plant sources, with adjustment of potential confounding variables. Participants who had higher intake of L-arginine also had higher serum NOx at baseline (35.0 vs. 30.5 μmol/L, P<0.05). After 6 years of follow-up, higher intakes of L-arginine from animal sources were accompanied with increased risk of MetS [odd ratios (OR)=1.49, 95% confidence interval (95% CI)=1.02~2.18]. Compared to the lowest, the highest intakes of L-arginine from plant sources were related to significantly reduced risk of MetS (OR=0.58, 95% CI=0.32~0.99). In conclusion, our findings suggest a potentially protective effect of plant derived L-arginine intakes against development of MetS and its phenotypes; moreover, higher intakes of L-arginine from animal sources could be a dietary risk factor for development of metabolic disorders. KEYWORDS: L-arginine; metabolic syndrome; nitric oxide Body mass index, abdominal adiposity, weight gain and risk of developing hypertension: a systematic review and dose-response meta-analysis of more than 2.3 million participants. Jayedi A, Rashidy-Pour A, Khorshidi M, Shab-Bidar S. Obes Rev. 2018 Jan 15. doi: 10.1111/obr.12656. [Epub ahead of print] Review. PMID: 29334692 Abstract OBJECTIVE: This study aimed to test the association between anthropometric measures and risk of developing hypertension. METHODS: We did a systematic search using PubMed and Scopus, from inception up to January 2017. Prospective cohort studies reporting the risk estimates of hypertension for three or more quantitative categories of indices of general and abdominal adiposity were included. Summary relative risks were calculated using random-effects models. RESULTS: Fifty-seven prospective cohort studies were included. Summary relative risks were 1.49 (95% confidence interval [CI]: 1.41, 1.58; I2 = 97.4%, n = 50) for a five-unit increment in body mass index, 1.27 (95%CI: 1.15, 1.39; I2 = 95.0%, n = 14) for a 10-cm increment in waist circumference, 1.16 (95%CI: 1.09, 1.23; I2 = 77.8%, n = 5) for weight gain equal to a one-unit increment in BMI, and 1.37 (95%CI: 1.24, 1.51; I2 = 76.4%, n = 8) and 1.74 (95%CI: 1.35, 2.13; I2 = 58.9%, n = 4) for a 0.1-unit increment in waist-to-hip ratio and waist-to-height ratio, respectively. The risk of hypertension increased continuously with increasing all anthropometric measures, and also along with weight gain. CONCLUSION: Being as lean as possible within the normal body mass index range may be the best suggestion in relation to primary prevention of hypertension. KEYWORDS: Abdominal obesity; body mass index; hypertension; meta-analysis [Papers' pdfs are availed for the issue.] January 16, 2018, Vol 319, No. 3, Pages 205-316 | Obesity In This Issue of JAMA https://jamanetwork.com/journals/jama/currentissue >>>>>>>>>>>>>>>>>>>> JAMA Infographic January 16, 2018 Medical Care Use and Expenditures Associated With Adult Obesity in the United States Adam I. Biener, PhD; Sandra L. Decker, PhD; for the Agency for Healthcare Research and Quality JAMA. 2018;319(3):218. doi:10.1001/jama.2017.21063 https://jamanetwork.com/journals/jama/fullarticle/2669713 Obesity is associated with several costly medical conditions. Based on data from 2010 through 2015, nearly half of obese adults had hypertension compared with 20% of normal-weight adults. Obese adults were 4 times as likely to have diabetes compared with normal-weight adults. From 2001 through 2015, increases in medical expenditures were greater for obese adults than for normal-weight adults. From 2010 through 2015, adults with a body mass index of 40 or higher incurred $7800 in annual medical expenditures on average, 76% more than normal-weight adults. Relative to adults with normal weight, obese adults were about twice as likely to have been prescribed a cardiovascular or gastrointestinal agent, nearly 70% more likely to have been prescribed a psychotherapeutic agent, and more than 4 times as likely to be prescribed an antidiabetic agent. Nearly 10% of obese adults were hospitalized annually resulting in 125.9 inpatient hospitalizations per 1000 people annually, compared with just 6% of normal weight-adults hospitalized, resulting in 77.9 stays per 1000 people each year. Nearly half of obese adults had at least 3 physician visits per year compared with 35.1% of normal-weight adults. Quote Link to comment Share on other sites More sharing options...
AlPater Posted January 18, 2018 Author Report Share Posted January 18, 2018 (edited) Predictors of overweight/obesity in a Brazilian cohort after 13 years of follow-up. Souza LG, Jardim TV, Rezende AC, Sousa ALL, Moreira HG, Perillo NB, de Souza SG, de Souza WKSB, Araújo YCL, do Rosário Gondim Peixoto M, Jardim PCBV. Nutr J. 2018 Jan 15;17(1):10. doi: 10.1186/s12937-018-0320-7. PMID: 29334952 https://nutritionj.biomedcentral.com/articles/10.1186/s12937-018-0320-7 https://nutritionj.biomedcentral.com/track/pdf/10.1186/s12937-018-0320-7?site=nutritionj.biomedcentral.com Abstract BACKGROUND: Obesity is a chronic complex disease with an increasing prevalence around the world. Prospective studies in adult cohorts are needed to provide information about predictors of new-onset overweight/obesity on population-based levels. The aim of this study was to identify factors associated with the risk of an adult individual become overweight/obese after 13 years of follow-up. METHODS: Second phase of an observational population-based prospective cohort study in a small town in the Midwest region of Brazil. A representative sample of the adult population (≥18 years) was assessed in 2002 (phase 1). Anthropometric, sociodemographic, dietary intake and lifestyle data were collected. After 13 years of follow-up (2015), the same variables were re-evaluated (phase 2). New-onset overweight/obesity was the outcome variable. RESULTS: A total of 685 subjects were included with a mean age in phase 1 of 42.7 ± 13.8 years and 56.1 ± 13.8 years in phase 2, the mean follow-up time was 13.2 years and female sex counted for 66.3% of the sample. Total weight gain was 5.9 ± 10.2 Kg, body mass index increased 2.6 ± 3.8 Kg/m2 and waist circumference (WC) values increased 8.0 ± 10.5 cm. The prevalence of overweight/obesity went from 49.1% in phase 1 to 69.8% in phase 2 (p < 0.001). The factors associated with a decreased risk of new-onset overweight/obesity were ages between 50 and 64 (RR 0.40; CI 0.24-0.67 - p = 0.001) and ≥65 years (RR 0.15; CI 0.06-0.35 - p < 0.001), being part of the second quartile of fat consumption (RR 0.59; CI 0.35-0.97 - p = 0.041), no alcohol consumption (RR 0.59; CI 0.37-0.93 - p = 0.024) and smoking (RR 0.58; CI 0.39-0.86 - p = 0,007) in phase 1. CONCLUSIONS: We identified in thirteen years of follow-up that older ages, a moderate fat consumption compared to low consumption, no alcohol consumption and smoking habit were related to a decreased risk of new-onset overweight/obesity. Obesity prevention actions must focus on subjects at younger ages and include policies to reduce alcohol consumption. KEYWORDS: Body mass index; Obesity; Waist circumference; Weight gain Insulin and Estrogen Independently and Differentially Reduce Macronutrient Intake in Healthy Men. Krug R, Mohwinkel L, Drotleff B, Born J, Hallschmid M. J Clin Endocrinol Metab. 2018 Jan 12. doi: 10.1210/jc.2017-01835. [Epub ahead of print] PMID: 29342258 Abstract CONTEXT: Insulin administration to the central nervous system inhibits food intake, but this effect has been found to be less pronounced in female compared to male organisms. This sex-specific pattern has been suggested to arise from a modulating influence of estrogen signaling on the insulin effect. OBJECTIVE: We assessed in healthy young men whether pre-treatment with transdermal estradiol interacts with the hypophagic effect of central nervous insulin administration via the intranasal pathway. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: According to a 2×2 design, two groups of men (each n=16) received a 3-day transdermal estradiol (100 µg/24 h) or placebo pre-treatment and on two separate mornings were intranasally administered 160 IU regular human insulin or placebo. MAIN OUTCOME MEASURES: We assessed free-choice ad-libitum calorie intake from a rich breakfast buffet and relevant blood parameters in samples collected before and after breakfast. RESULTS: Estrogen treatment induced a 3.5-fold increase in serum estradiol concentrations and suppressed serum testosterone concentrations by 70%. Independent of estradiol administration, intranasal insulin reduced the intake of carbohydrates during breakfast, attenuating in particular the consumption of sweet, palatable foods. Estradiol treatment per se decreased protein consumption. We did not find indicators of eating-related interactions between both hormones. CONCLUSIONS: Results indicate that in an acute setting, estrogen does not interact with central nervous insulin signaling in the control of eating behavior in healthy men. Insulin and estradiol rather exert independent inhibiting effects on macronutrient intake. Effect of vitamin A supplementation on iron status in humans: a systematic review and meta-analysis. da Cunha MSB, Campos Hankins NA, Arruda SF. Crit Rev Food Sci Nutr. 2018 Jan 16:0. doi: 10.1080/10408398.2018.1427552. [Epub ahead of print] PMID: 29336593 Abstract Anemia is a worldwide public health problem that can be related to many causes, including vitamin A deficiency. The aim of this study was to assess and estimate the effect of vitamin A supplementation (VAS) on iron status biomarkers and anemia in humans. Six databases, including Cochrane, EMBASE, LILACS, Pubmed, Scopus and Web of Science, were searched for clinical trials and cohort studies that investigated the effect of vitamin A supplementation alone on iron status and anemia, without time-restriction. The search yielded 23 eligible studies, 21 clinical trials and 2 cohort studies, with children, teenagers, pregnant or lactating women. The meta-analysis of the clinical trials showed that VAS reduces the risk of anemia by 26% and raises hemoglobin levels, compared to non-treated group, independent of the life stage. VAS did not alter the prevalence of iron deficiency among the clinical trials conducted with children and teenagers (RR 0.82, 95% CI 0.60 to 1.12, p = 0.204), whereas a significant increase in serum ferritin levels was observed in trials conducted with pregnant and lactating women (WMD 6.61 μg/L; 95% CI 6.00 to 7.21 μg/L; p < 0.001). Therefore, vitamin A supplementation alone may reduce the risk of anemia, by improving hemoglobin and ferritin levels in individuals with low serum retinol levels. KEYWORDS: Review; anemia; iron deficiency; iron status; supplementation; vitamin A supplementation Why your birth year may increase your risk of dying during a flu pandemic People born in 1957 during the Asian flu had a higher risk of dying during the Swine flu pandemic By Laura Clementson, CBC News Posted: Jan 16, 2018 http://www.cbc.ca/news/canada/hamilton/research-influenza-pandemic-1.4489315 >>>>>>>>>>>>>>>>>> Pandemic Paradox: Early Life H2N2 Pandemic Influenza Infection Enhanced Susceptibility to Death during the 2009 H1N1 Pandemic. Gagnon A, Acosta E, Hallman S, Bourbeau R, Dillon LY, Ouellette N, Earn DJD, Herring DA, Inwood K, Madrenas J, Miller MS. MBio. 2018 Jan 16;9(1). pii: e02091-17. doi: 10.1128/mBio.02091-17. PMID: 29339427 ABSTRACT Recent outbreaks of H5, H7, and H9 influenza A viruses in humans have served as a vivid reminder of the potentially devastating effects that a novel pandemic could exert on the modern world. Those who have survived infections with influenza viruses in the past have been protected from subsequent antigenically similar pandemics through adaptive immunity. For example, during the 2009 H1N1 “swine flu” pandemic, those exposed to H1N1 viruses that circulated between 1918 and the 1940s were at a decreased risk for mortality as a result of their previous immunity. It is also generally thought that past exposures to antigenically dissimilar strains of influenza virus may also be beneficial due to cross-reactive cellular immunity. However, cohorts born during prior heterosubtypic pandemics have previously experienced elevated risk of death relative to surrounding cohorts of the same population. Indeed, individuals born during the 1890 H3Nx pandemic experienced the highest levels of excess mortality during the 1918 “Spanish flu.” Applying Serfling models to monthly mortality and influenza circulation data between October 1997 and July 2014 in the United States and Mexico, we show corresponding peaks in excess mortality during the 2009 H1N1 “swine flu” pandemic and during the resurgent 2013–2014 H1N1 outbreak for those born at the time of the 1957 H2N2 “Asian flu” pandemic. We suggest that the phenomenon observed in 1918 is not unique and points to exposure to pandemic influenza early in life as a risk factor for mortality during subsequent heterosubtypic pandemics. IMPORTANCE The relatively low mortality experienced by older individuals during the 2009 H1N1 influenza virus pandemic has been well documented. However, reported situations in which previous influenza virus exposures have enhanced susceptibility are rare and poorly understood. One such instance occurred in 1918—when those born during the heterosubtypic 1890 H3Nx influenza virus pandemic experienced the highest levels of excess mortality. Here, we demonstrate that this phenomenon was not unique to the 1918 H1N1 pandemic but that it also occurred during the contemporary 2009 H1N1 pandemic and 2013–2014 H1N1-dominated season for those born during the heterosubtypic 1957 H2N2 “Asian flu” pandemic. These data highlight the heretofore underappreciated phenomenon that, in certain instances, prior exposure to pandemic influenza virus strains can enhance susceptibility during subsequent pandemics. These results have important implications for pandemic risk assessment and should inform laboratory studies aimed at uncovering the mechanism responsible for this effect. KEYWORDS: influenza virus; mortality; pandemics; susceptibility Association of a Low-Protein Diet With Slower Progression of CKD. Metzger M, Yuan WL, Haymann JP, Flamant M, Houillier P, Thervet E, Boffa JJ, Vrtovsnik F, Froissart M, Bankir L, Fouque D, Stengel B. Kidney Int Rep. 2017 Aug 30;3(1):105-114. doi: 10.1016/j.ekir.2017.08.010. eCollection 2018 Jan. PMID: 29340320 http://www.kireports.org/article/S2468-0249(17)30364-9/fulltext http://www.kireports.org/article/S2468-0249(17)30364-9/pdf Abstract INTRODUCTION: Reducing protein intake is recommended for slowing chronic kidney disease (CKD) progression, but assessment of its true effectiveness is sparse. METHODS: Using the Maroni formula, we assessed dietary protein intake (DPI) from 24-hour urinary urea excretion in 1594 patients (67% men and 33% women) with CKD, 784 of whom also had 7-day food records. Cause-specific hazard ratios (HRs) and 95% confidence intervals for the competing risks of DPI-associated end-stage renal disease (ESRD) or death were estimated in 1412 patients with baseline glomerular filtration rate ≥15 ml/min per 1.73 m2, measured by 51Cr-EDTA renal clearance (mGFR). RESULTS: Overall, mean DPI estimated from urea excretion was 1.09 ± 0.30 g/kg of body weight per day (range = 0.34-2.76); 20% of patients had values > 1.3 g/kg per day, and 1.9% had values < 0.6 g/kg per day. Urea excretion and food records produced similar estimates of mean DPI. The lower the mGFR, the lower the mean DPI. Over a median follow-up of 5.6 years, there were 319 ESRD events and 189 pre-ESRD deaths. After adjusting for relevant covariates, each 0.1 g/kg daily higher baseline urea excretion-based DPI or food record-based DPI was associated with an HR for ESRD of 1.05 (95% confidence interval 1.01-1.10) or 1.09 (95% confidence interval 1.04-1.14), respectively. HRs were stronger in patients with baseline mGFR < 30 ml/min per 1.73 m2. There was no association with mortality. The mean age of the patients was 59 ± 15 years, and mean body mass index was 26.6 ± 5.2 kg/m2. CONCLUSION: In this prospective observational study, the lower the baseline DPI, the slower the progression toward ESRD. Most importantly, the absence of threshold for the relation between DPI and ESRD risk indicates that there is no optimal DPI in the range observed in this cohort. KEYWORDS: dietary protein intake; end-stage renal disease; glomerular filtration rate; mortality; urinary urea excretion Edited January 18, 2018 by AlPater Quote Link to comment Share on other sites More sharing options...
AlPater Posted January 19, 2018 Author Report Share Posted January 19, 2018 (edited) Mobility Trajectories at the End of Life: Comparing Clinical Condition and Latent Class Approaches. Lunney JR, Albert SM, Boudreau R, Ives D, Satterfield S, Newman AB, Harris T; Health Aging and Body Composition Study. J Am Geriatr Soc. 2018 Jan 18. doi: 10.1111/jgs.15224. [Epub ahead of print] PMID: 29345750 Abstract OBJECTIVES: To assess mobility disability trajectories before death in a large sample of very old adults using two analytical approaches to determine how well they corresponded. DESIGN: Decedent sample from the Health, Aging and Body Composition (Health ABC) Study. Data were collected between 1997 and 2015. SETTING: Pittsburgh, Pennsylvania, and Memphis, Tennessee. PARTICIPANTS: Individuals randomly selected from well-functioning white Medicare beneficiaries and all black community residents meeting age criteria (70-79) (N = 3,075). MEASUREMENTS: Participants were interviewed in person or by phone at least every six months throughout the study. Of the 1,991 participants who died by the end of the study, 1,410 had been interviewed for 3 years before death, including an interview 6 months before dying. We analyzed self-reported mobility collected prospectively at 6-month intervals during the last 3 years of life. We derived trajectories in two ways: by averaging decline within decedent groups prespecified according to clinical conditions and by estimating trajectory models using maximum-likelihood semiparametric modeling. RESULTS: Ninety-eight percent of decedents were classified according to 4 prespecified clinical conditions (sudden death, terminal, organ failure, frailty), which produced groups with different characteristics. Five disability trajectories were identified: late decline, progressive disability, moderate disability, early decline, and persistent disability. Disability trajectory and clinical condition grouping confirmed previous research but were only marginally related. CONCLUSION: Derived disability trajectories and grouping according to clinical condition provide useful information about different facets of the end-of-life experience. The lack of fit between them suggests a need for greater attention to heterogeneity in disability in the period before death. KEYWORDS: disability; end of life; functional decline; mobility; trajectories Social and Behavioural Determinants of the Difference in Survival among Older Adults in Japan and England. Aida J, Cable N, Zaninotto P, Tsuboya T, Tsakos G, Matsuyama Y, Ito K, Osaka K, Kondo K, Marmot MG, Watt RG. Gerontology. 2018 Jan 18. doi: 10.1159/000485797. [Epub ahead of print] PMID: 29346791 https://www.karger.com/Article/FullText/485797 https://www.karger.com/Article/Pdf/485797 Abstract BACKGROUND: A rapidly ageing population presents major challenges to health and social care services. Cross-country comparative studies on survival among older adults are limited. In addition, Japan, the country with the longest life expectancy, is rarely included in these cross-country comparisons. OBJECTIVE: We examined the relative contributions of social and behavioural factors on the differences in survival among older people in Japan and England. METHODS: We used data from the Japan Gerontological Evaluation Study (JAGES; n = 13,176) and the English Longitudinal Study of Ageing (ELSA; n = 5,551) to analyse all-cause mortality up to 9.4 years from the baseline. Applying Laplace regression models, the 15th survival percentile difference was estimated. RESULTS: During the follow-up, 31.3% of women and 38.6% of men in the ELSA died, whereas 19.3% of women and 31.3% of men in the JAGES died. After adjusting for age and baseline health status, JAGES participants had longer survival than ELSA participants by 318.8 days for women and by 131.6 days for men. Family-based social relationships contributed to 105.4 days longer survival in JAGES than ELSA men. Fewer friendship-based social relationships shortened the JAGES men's survival by 45.4 days compared to ELSA men. Currently not being a smoker contributed to longer survival for JAGES women (197.7 days) and ELSA men (46.6 days), and having lower BMI reduced the survival of JAGES participants by 129.0 days for women and by 212.2 days for men. CONCLUSION: Compared to participants in England, Japanese older people lived longer mainly because of non-smoking for women and family-based social relationships for men. In contrast, a lower rate of underweight, men's better friendship-based social relationships, and a lower smoking rate contributed to survival among participants in England. KEYWORDS: Cohort study; Cross-country comparative study; Laplace regression; Mortality; Social relationships Modification of the Associations Between Duration of Oral Contraceptive Use and Ovarian, Endometrial, Breast, and Colorectal Cancers. Michels KA, Pfeiffer RM, Brinton LA, Trabert B. JAMA Oncol. 2018 Jan 18. doi: 10.1001/jamaoncol.2017.4942. [Epub ahead of print] PMID: 29346467 Abstract IMPORTANCE: Although oral contraceptive (OC) use is common, the influence of OC use on carcinogenesis is not fully understood. A recent Agency for Healthcare Research and Quality report identified a need to understand the consistency of OC use and cancer associations across subpopulations, including smokers and obese women. OBJECTIVE: To determine whether associations between duration of OC use and risk of specific cancers were modified by lifestyle characteristics. DESIGN, SETTING, AND PARTICIPANTS: The prospective NIH-AARP Diet and Health Study (enrolled 1995-1996, followed until 2011), with population-based recruitment of AARP members in 6 states and 2 metropolitan areas. All analyses included at least 100 000 women who reported OC use at enrollment. We identified 1241 ovarian, 2337 endometrial, 11 114 breast, and 3507 colorectal cancer cases during follow-up. Data analysis was performed between September 2016 and April 2017. EXPOSURES: Duration of OC use (never or <1 year [reference], 1-4, 5-9, or ≥10 years). MAIN OUTCOMES AND MEASURES: Development of ovarian, endometrial, breast, and colorectal cancers. We examined effect modification by modifiable lifestyle characteristics: cigarette smoking, alcohol consumption, body mass index (BMI), and physical activity. We used Cox models adjusted for age, race, age at menarche, and the modifiers of interest. RESULTS: The analytic population was aged 50 to 71 years (median, 62 years) at enrollment and largely white (91%) and postmenopausal (96%). For ovarian cancer, OC use-associated risk reductions strengthened with duration of use (long-term OC use [≥10 years] HR, 0.60; 95% CI, 0.47-0.76; P < .001 for trend) and were similar across modifiable lifestyle factors. Risk reductions for endometrial cancer strengthened with duration of use (long-term OC use HR, 0.66; 95% CI, 0.56-0.78; P < .001 for trend); the most pronounced reductions were among long-term OC users who were smokers (HR, 0.47; 95% CI, 0.25-0.88), had obese BMIs (0.36; 95% CI, 0.25-0.52), and who exercised rarely (HR, 0.40; 95% CI, 0.29-0.56). Associations between OC use and breast and colorectal cancers were predominantly null. CONCLUSIONS AND RELEVANCE: Long-term OC use is consistently associated with reduced ovarian cancer risk across lifestyle factors. We observed the greatest risk reductions for endometrial cancer among women at risk for chronic diseases (ie, smokers, obese BMI). Oral contraceptive use may be beneficial for chemoprevention for a range of women with differing baseline cancer risks. Association of Dietary Inflammatory Potential With Colorectal Cancer Risk in Men and Women. Tabung FK, Liu L, Wang W, Fung TT, Wu K, Smith-Warner SA, Cao Y, Hu FB, Ogino S, Fuchs CS, Giovannucci EL. JAMA Oncol. 2018 Jan 18. doi: 10.1001/jamaoncol.2017.4844. [Epub ahead of print] PMID: 29346484 Abstract IMPORTANCE: Inflammation is important in colorectal cancer development. Diet modulates inflammation and may thus be a crucial modifiable factor in colorectal cancer prevention. OBJECTIVE: To examine whether proinflammatory diets are associated with increased colorectal cancer risk by using an empirical dietary inflammatory pattern (EDIP) score based on a weighted sum of 18 food groups that characterizes dietary inflammatory potential based on circulating levels of inflammation biomarkers. DESIGN, SETTINGS, AND PARTICIPANTS: Cohort study of 46 804 men (Health Professionals Follow-up Study: 1986-2012) and 74 246 women (Nurses' Health Study: 1984-2012) followed for 26 years to examine associations between EDIP scores and colorectal cancer risk using Cox regression. We also examined associations in categories of alcohol intake and body weight. Data analysis began January 17, 2017, and was completed August 9, 2017. EXPOSURES: EDIP scores calculated from food frequency questionnaires administered every 4 years. MAIN OUTCOMES AND MEASURES: Incident colorectal cancer. RESULTS: We documented 2699 incident colorectal cancer cases over 2 571 831 person-years of follow-up. Compared with participants in the lowest EDIP quintile (Q) who had a colorectal cancer incidence rate (per 100 000 person-years) of 113 (men) and 80 (women), those in the highest Q had an incidence rate of 151 (men) and 92 (women), leading to an unadjusted rate difference of 38 and 12 more colorectal cancer cases, respectively, among those consuming highly proinflammatory diets. Comparing participants in the highest vs lowest EDIP Qs in multivariable-adjusted analyses, higher EDIP scores were associated with 44% (men: hazard ratio {HR}, 1.44; 95% CI, 1.19-1.74; P < .001 for trend), 22% (women: HR, 1.22; 95% CI, 1.02-1.45; P = .007 for trend), and 32% (men and women: pooled HR, 1.32; 95% CI, 1.12-1.55; P < .001 for trend) higher risk of developing colorectal cancer. In both men and women, associations were observed in all anatomic subsites except for the rectum in women. In subgroups (P ≤ .02 for all interactions), associations differed by alcohol intake level, with stronger associations among men (Q5 vs Q1 HR, 1.62; 95% CI, 1.05-2.49; P = .002 for trend) and women (Q5 vs Q1 HR, 1.33; 95% CI, 0.97-1.81; P = .03 for trend) not consuming alcohol; and by body weight, with stronger associations among overweight/obese men (Q5 vs Q1 HR, 1.48; 95% CI, 1.12-1.94; P = .008 for trend) and lean women (Q5 vs Q1 HR, 1.31; 95% CI, 0.99-1.74; P = .01 for trend). CONCLUSIONS AND RELEVANCE: Findings suggest that inflammation is a potential mechanism linking dietary patterns and colorectal cancer development. Interventions to reduce the adverse role of proinflammatory diets may be more effective among overweight/obese men and lean women or men and women who do not consume alcohol. Edited January 19, 2018 by AlPater Quote Link to comment Share on other sites More sharing options...
AlPater Posted January 20, 2018 Author Report Share Posted January 20, 2018 [Last time mine was checked it was 26.] The gamma gap predicts 4-year all-cause mortality among nonagenarians and centenarians. Yang M, Xie L, Liu X, Hao Q, Jiang J, Dong B. Sci Rep. 2018 Jan 18;8(1):1046. doi: 10.1038/s41598-018-19534-4. PMID: 29348636 https://www.nature.com/articles/s41598-018-19534-4 Abstract Recent studies have revealed the prognostic role of the gamma gap, the total serum proteins concentration minus the albumin concentration, for predicting all-cause mortality among adults. This study aims to investigate the relationship between the gamma gap and all-cause mortality among nonagenarians and centenarians via a secondary data analysis of a prospective observational study. The analysis included 801 participants (260 men and 541 women, mean age: 93.7 ± 3.5 years), 46 of which were lost at the 4-year follow-up. The mean gamma gap was 2.7 ± 0.5 g/dl. After adjusting for relevant confounders, the gamma gap was significantly associated with 4-year all-cause mortality (hazard ratio per 1-SD = 1.22, 95% confidential interval [CI]: 1.12-1.78). Using different cut-off points, the elevated gamma gap could be defined as ≥2.9, 3.0, 3.1, or 3.2 g/dl. The relevant HRs and 95% CIs of the elevated gamma gap for predicting mortality were 1.27 (1.12-1.90), 1.29 (1.03-1.78), 1.21 (1.23-1.66), and 1.26 (1.09-1.69), respectively. In conclusion, the gamma gap is an independent prognostic factor for long-term mortality in nonagenarians and centenarians. A value greater than or equal to 3.1 g/dl may define an elevated gamma gap, but further studies are required. The tyranny of the averages and the indiscriminate use of risk factors in public health: The case of coronary heart disease. Merlo J, Mulinari S, Wemrell M, Subramanian SV, Hedblad B. SSM Popul Health. 2017 Aug 18;3:684-698. doi: 10.1016/j.ssmph.2017.08.005. eCollection 2017 Dec. PMID: 29349257 https://www.sciencedirect.com/science/article/pii/S2352827317300757 https://ac.els-cdn.com/S2352827317300757/1-s2.0-S2352827317300757-main.pdf?_tid=b891692c-fe0b-11e7-88be-00000aab0f01&acdnat=1516471375_9cf6e09e868cced52dd4e42bb3f88d1c Abstract Modern medicine is overwhelmed by a plethora of both established risk factors and novel biomarkers for diseases. The majority of this information is expressed by probabilistic measures of association such as the odds ratio (OR) obtained by calculating differences in average "risk" between exposed and unexposed groups. However, recent research demonstrates that even ORs of considerable magnitude are insufficient for assessing the ability of risk factors or biomarkers to distinguish the individuals who will develop the disease from those who will not. In regards to coronary heart disease (CHD), we already know that novel biomarkers add very little to the discriminatory accuracy (DA) of traditional risk factors. However, the value added by traditional risk factors alongside simple demographic variables such as age and sex has been the subject of less discussion. Moreover, in public health, we use the OR to calculate the population attributable fraction (PAF), although this measure fails to consider the DA of the risk factor it represents. Therefore, focusing on CHD and applying measures of DA, we re-examine the role of individual demographic characteristics, risk factors, novel biomarkers and PAFs in public health and epidemiology. In so doing, we also raise a more general criticism of the traditional risk factors' epidemiology. We investigated a cohort of 6103 men and women who participated in the baseline (1991-1996) of the Malmö Diet and Cancer study and were followed for 18 years. We found that neither traditional risk factors nor biomarkers substantially improved the DA obtained by models considering only age and sex. We concluded that the PAF measure provided insufficient information for the planning of preventive strategies in the population. We need a better understanding of the individual heterogeneity around the averages and, thereby, a fundamental change in the way we interpret risk factors in public health and epidemiology. KEYWORDS: ACE, Average causal effect; AUC, Area under the ROC curve; CABG, Coronary artery bypass graft; CHD, Coronary heart disease; CRP, C-reactive protein; Coronary heart disease; DA, Discriminatory accuracy; Discriminatory accuracy; FPF, False positive fraction; HDL, High-density lipoprotein cholesterol; HR, Hazard ratios; ICE, Individual causal effect; Individual heterogeneity; LDL, Low-density lipoprotein cholesterol; Lp-PLA2, Lipoprotein-associated phospholipase A2; MDC study, The Malmö Diet and Cancer; Multilevel analysis; NTBNP, N-terminal pro–brain natriuretic peptide; OR, Odds ratio; Over-diagnosis; Overtreatment; PAF, Population attributable fraction; PAH, Phenylalanine hydroxylase; PCI, Percutaneous coronary intervention; PKU, Phenylketonuria; Population attributable fraction; RCT, Randomized clinical trial; ROC, Receiver operating characteristic; RR, Relative risk; Risk factors; TPF, True positive fraction Effect of swimming exercise on premenstrual syndrome. Maged AM, Abbassy AH, Sakr HRS, Elsawah H, Wagih H, Ogila AI, Kotb A. Arch Gynecol Obstet. 2018 Jan 19. doi: 10.1007/s00404-018-4664-1. [Epub ahead of print] PMID: 29350276 Abstract OBJECTIVE: To study the effectiveness of performing swimming on the severity of symptoms of premenstrual syndrome (PMS). MATERIALS AND METHODS: A randomized controlled trial that was conducted on 70 women diagnosed with PMS divided randomly into two equal groups: Group I included women who engaged into exercise and group II controls. Daily Symptoms Report was filled at the start and at end of the study. RESULTS: At the posttreatment evaluation, there was a highly significant difference between the study and control groups regarding anxiety (0 vs. 5), depression (3 vs. 12), tension (3 vs. 12), mood changes (0 vs. 7), feeling out of control (0 vs. 7), weak coordination (0 vs. 10), confusion (2 vs. 9), headache (3 vs. 15), tiredness (4 vs. 12), pains (5 vs. 11), tenderness of the breast (2 vs. 8), and cramps (6 vs. 17) (P < 0.001), but no such difference was found regarding irritability, insomnia, crying, swelling, or food craving. Regarding the percentage of symptoms changes, there was a highly significant difference between the study and control groups regarding anxiety (- 33.3 vs. 0), depression (- 79.29 vs. 15.56), tension (- 81.18 vs. - 6.79), mood changes (- 33.33 vs. 0), feeling out of control (- 91.67 vs. 0), weak coordination (- 100 vs. - 9.55), sleeplessness (- 71.43 vs. 0), confusion (- 84.17 vs. - 9.55), headache (- 77.78 vs. - 6.94), fatigue (- 65.69 vs. 0), pains (- 65.83 vs. - 8.93), breast tenderness (- 87.87 vs. 4.55), cramps (- 60.77 vs. 4.55), and swellings (- 55.05 vs. - 8.33), but no such difference was found regarding irritability, crying, or food craving. CONCLUSIONS: There is beneficial effect of swimming on most of the physical and psychological symptoms of PMS. KEYWORDS: Aerobic exercise; Premenstrual syndrome; Swimming Quote Link to comment Share on other sites More sharing options...
AlPater Posted January 21, 2018 Author Report Share Posted January 21, 2018 [i had said the next below paper's full-text was not free.] Diet has independent effects on the pace and shape of aging in Drosophila melanogaster. Ruth Archer C, Basellini U, Hunt J, Simpson SJ, Lee KP, Baudisch A. Biogerontology. 2018 Feb;19(1):1-12. doi: 10.1007/s10522-017-9729-1. Epub 2017 Sep 15. PMID: 28914388 https://link.springer.com/article/10.1007%2Fs10522-017-9729-1 Abstract Studies examining how diet affects mortality risk over age typically characterise mortality using parameters such as aging rates, which condense how much and how quickly the risk of dying changes over time into a single measure. Demographers have suggested that decoupling the tempo and the magnitude of changing mortality risk may facilitate comparative analyses of mortality trajectories, but it is unclear what biologically meaningful information this approach offers. Here, we determine how the amount and ratio of protein and carbohydrate ingested by female Drosophila melanogaster affects how much mortality risk increases over a time-standardised life-course (the shape of aging) and the tempo at which animals live and die (the pace of aging). We find that pace values increased as flies consumed more carbohydrate but declined with increasing protein consumption. Shape values were independent of protein intake but were lowest in flies consuming ~90 μg of carbohydrate daily. As protein intake only affected the pace of aging, varying protein intake rescaled mortality trajectories (i.e. stretched or compressed survival curves), while varying carbohydrate consumption caused deviation from temporal rescaling (i.e. changed the topography of time-standardised survival curves), by affecting pace and shape. Clearly, the pace and shape of aging may vary independently in response to dietary manipulation. This suggests that there is the potential for pace and shape to evolve independently of one another and respond to different physiological processes. Understanding the mechanisms responsible for independent variation in pace and shape, may offer insight into the factors underlying diverse mortality trajectories. KEYWORDS: Dietary restriction; Fruit flies; Geometric framework of nutrition; Gompertz; Pace; Shape Legume consumption and risk of all-cause, cardiovascular, and cancer mortality in the PREDIMED study. Papandreou C, Becerra-Tomás N, Bulló M, Martínez-González MÁ, Corella D, Estruch R, Ros E, Arós F, Schroder H, Fitó M, Serra-Majem L, Lapetra J, Fiol M, Ruiz-Canela M, Sorli JV, Salas-Salvadó J. Clin Nutr. 2018 Jan 9. pii: S0261-5614(17)31439-5. doi: 10.1016/j.clnu.2017.12.019. [Epub ahead of print] PMID: 29352655 Abstract BACKGROUND & AIMS: Limited prospective studies have examined the association between legumes consumption and mortality, whereas scarce, if at all, previous studies have evaluated such associations taking into consideration specific grain legumes. We aimed to investigate the association between total legumes consumption and grain legumes species (dry beans, chickpeas, lentils, and fresh peas) with all-cause, cardiovascular disease (CVD), cancer and other-cause mortality among elderly Mediterranean individuals at high CVD risk. METHODS: We prospectively assessed 7216 participants from the PREvención con DIeta MEDiterránea study. Dietary intake was assessed at baseline and yearly during follow-up by using a validated food frequency questionnaire. RESULTS: During a median follow-up of 6.0 years, 425 total deaths, 103 CVD deaths, 169 cancer deaths and 153 due to other-causes deaths occurred. Hazard ratios (HRs) [95% confidence interval (CI)] of CVD mortality were 1.52 (1.02-2.89) (P-trend = 0.034) and 2.23 (1.32-3.78) (P-trend = 0.002) for the 3rd tertile of total legumes and dry beans consumption, respectively, compared with the 1st tertile. When comparing extreme tertiles, higher total legumes and lentils consumption was associated with 49% (HR: 0.51; 95% CI: 0.31-0.84; P-trend = 0.009) and 37% (HR: 0.63; 95% CI: 0.40-0.98; P-trend = 0.049) lower risk of cancer mortality. Similar associations were observed for CVD death in males and for cancer death in males, obese and diabetic participants. CONCLUSIONS: These findings support the benefits of legumes consumption for cancer mortality prevention which may be counterbalanced by their higher risk for CVD mortality. KEYWORDS: Cancer; Cardiovascular; Legumes; Mortality; PREDIMED >>>>>>>>>>>>>>>>>>>>>>>>> Legume Consumption and All-Cause and Cardiovascular Disease Mortality. Li H, Li J, Shen Y, Wang J, Zhou D. Biomed Res Int. 2017;2017:8450618. doi: 10.1155/2017/8450618. Epub 2017 Nov 2. Review. PMID: 29230416 Free PMC Article https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5688364/ >>>>>>>>>>>>>>>>>>>>>>> Food groups and risk of all-cause mortality: a systematic review and meta-analysis of prospective studies. Schwingshackl L, Schwedhelm C, Hoffmann G, Lampousi AM, Knüppel S, Iqbal K, Bechthold A, Schlesinger S, Boeing H. Am J Clin Nutr. 2017 Jun;105(6):1462-1473. doi: 10.3945/ajcn.117.153148. Epub 2017 Apr 26. Review. PMID: 28446499 Free Article http://ajcn.nutrition.org/content/105/6/1462.full.pdf+html Because of a lapse in government funding, the information on this website may not be up to date, transactions submitted via the website may not be processed, and the agency may not be able to respond to inquiries until appropriations are enacted. The NIH Clinical Center (the research hospital of NIH) is open. For more details about its operating status, please visit cc.nih.gov. Updates regarding government operating status and resumption of normal operations can be found at USA.gov. 'Liquid biopsy' for cancer promises early detection. Kaiser J. Science. 2018 Jan 19;359(6373):259. doi: 10.1126/science.359.6373.259. No abstract available. PMID: 29348215 Combining DNA and protein markers brings researchers closer to a universal cancer screening test. Summary A team of researchers has taken a major step toward one of the hottest goals in cancer research: a blood test that can detect tumors early. Their new test, which examines cancer-related DNA and proteins in the blood, yielded a positive result about 70% of the time across eight common cancer types in 1005 patients whose tumors had not yet spread—among the best performances yet for a universal cancer blood test. It also narrowed down the form of cancer. The work, reported online today in Science, could one day lead to a tool for routinely screening people and catching tumors before they cause symptoms, when chances are best for a cure. Decreased opioid consumption and enhance recovery with the addition of IV Acetaminophen in colorectal patients: a prospective, multi-institutional, randomized, double-blinded, placebo-controlled study (DOCIVA study). Aryaie AH, Lalezari S, Sergent WK, Puckett Y, Juergens C, Ratermann C, Ogg C. Surg Endosc. 2018 Jan 19. doi: 10.1007/s00464-018-6062-y. [Epub ahead of print] PMID: 29352454 Abstract BACKGROUND: We hypothesized that administration of IV acetaminophen alone would reduce the opioid consumption in post-operative colorectal surgery and reduce the side effects of narcotics. METHODS: Patients were randomized to receive either IV acetaminophen or placebo in addition to opioid PCA. Primary endpoints evaluated were opioid consumption and pain visual analogue scale score (PVASS) during first 48 h post-operatively. Secondary endpoints evaluated were time of return of GI function (ROGIF), time to diet ordered (TTDO), length of hospital stay (LOHS), and occurrence of ileus. RESULTS: 105 patients were enrolled and 97 remained in the study after exclusion (control group n = 50; study group n = 47). Mean ± SEs of opioid consumption in the study group was 21.5 ± 1.8 mg of morphine equivalent (ME) and 35.0 ± 3.3 mg ME at 24 and 48 h, respectively, versus 36.4 ± 4.1 mg ME and 59.7 ± 6.7 mg ME in the control group (p = 0.002 and 0.002). PVASS levels were lower in the study group at all intervals at 3, 8, 24, and 48 h (p = 0.02, 0.006, < 0.01, and 0.02). ROGIF, TTDO, and LOHS were also found to be lower in the study group (p ≤ 0.01, < 0.01, and 0.002). The rate of ileus was reduced by using IV acetaminophen (22% vs 2.1%; p = 0.004). CONCLUSIONS: IV acetaminophen helps to reduce opioid consumption for patients undergoing colorectal surgery. Additionally, there appears to be a shortened length of hospital stay, better pain control, reduced time to return of bowel function, and lower rate of post-operative ileus in patients receiving IV acetaminophen. KEYWORDS: Colorectal surgery; ERAS; IV Tylenol; Ileus; Pain control Quote Link to comment Share on other sites More sharing options...
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