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  1. It seems to me perfectly natural that the lab would be located near where the https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome originated. And where its cousin COVID-19 would originate naturally.
  2. You are correct, and this was largely the focus of the vaccination programs at the beginning, but there are going to be so-called "break-through" infections in some of the at-risk people and some of the at-risk people who cannot be vaccinated. Getting at much as possible of the total population, including as young as possible for young children, of the country, and even the whole world, vaccinated, is the way to go.
  3. As I said before, these incidents seem to me to be very likely to be very costly in terms of health and healthcare, and it makes COVID-19 very distinct from a cold or flu in having the illness go on and on, leaving many patients even not being able to go back to work any time soon. The brain fog sounds quite distressing, for example.
  4. Mortality From Drug Overdoses, Homicides, Unintentional Injuries, Motor Vehicle Crashes, and Suicides During the Pandemic, March-August 2020. Faust JS, Du C, Mayes KD, Li SX, Lin Z, Barnett ML, Krumholz HM. JAMA. 2021 Jul 6;326(1):84-86. doi: 10.1001/jama.2021.8012. PMID: 34019096 https://jamanetwork.com/journals/jama/fullarticle/2780436 Abstract This study uses national death certificate data to characterize trends in death and excess mortality from drug overdoses, homicides, unintentional injuries, motor vehicle crashes, and suicide during the first 6 months of the pandemic in the US. [The initial COVID-19 outbreak in the US caused disruptions in usual behavioral patterns.1-3 To assess associated changes in external causes of death, we analyzed monthly trends from 2015 to 2020 in deaths resulting from drug overdoses, homicide, unintentional injuries, motor vehicle crashes, and suicide in the first 6 months of the pandemic. Methods We measured monthly excess mortality (the gap between observed and expected deaths) from 5 external causes using provisional national-level underlying cause death certificate data published by the National Center for Health Statistics (NCHS) through August 2020 (released March 2021). Data from March to August 2020 were aggregated by the NCHS into 5 groups: drug overdose (all intents), assault (homicide), unintentional injuries, motor vehicle crashes, and intentional self-harm (suicide) (see the Supplement for ICD-10 codes).4,5 To forecast all-cause and cause-specific expected monthly deaths from March to August 2020, we used seasonal autoregressive integrated moving average (sARIMA) models developed with cause-specific monthly mortality counts and US population data from January 2015 to February 2020. We plotted observed and expected deaths monthly with 95% CIs estimated from sARIMA models. We estimated the contribution of individual cause-specific mortality to all-cause non–COVID-19 excess mortality by dividing cause-specific mortality by total non–COVID-19 excess mortality from March to August 2020 (see the Supplement). Confidence intervals for the percent contribution to non–COVID-19 excess mortality were determined by subtracting the observed number of deaths from the upper and lower 95% thresholds for the expected number of deaths. For excess mortality counts, any figure not crossing 0 was considered statistically significant. For observed-to-expected ratios (OERs) of cause-specific mortality, statistical significance was defined as a 95% CI that excluded the null value of 1.00. Analyses were conducted using R version 4.0.2. This study used publicly available data and was not subject to institutional review approval per HHS regulation 45 CFR 46.101(c). Results From March to August 2020, there were 256 635 (95% CI, 161 450-351 823) all-cause excess deaths (1 661 271 observed; 1 404 634 expected) and 174 334 COVID-19 deaths (underlying cause). For the study period, OERs for 3 external causes of death were significantly higher than expected (drug overdoses, homicides, unintentional injuries), 1 unchanged (motor vehicle crashes), and 1 lower (suicides) (Table). There were 10 443 excess drug overdoses (95% CI, 6115 to 14 771; Figure, A), accounting for 12.7% of non–COVID-19 excess mortality (95% CI, 7.4% to 17.9%); 2014 excess homicide deaths (95% CI, 1086 to 2942) (Figure, B), accounting for 2.4% of non–COVID-19 excess mortality (95% CI, 1.3% to 3.6%); and 7497 excess deaths due to unintentional injuries (95% CI, 694 to 14 300) (Figure, C), accounting for 9.1% of non–COVID-19 excess mortality (95% CI, 0.8% to 17.4%). There was no significant change in motor vehicle crash deaths overall (725; 95% CI, −1090 to 2540) but fewer than expected motor vehicle crash deaths occurred in April (−523; 95% CI, −815 to −231), and significant increases were recorded monthly from June to August (1550; 95% CI, 611 to 2489) (Figure, D). Suicide deaths were statistically significantly lower than projected by 2432 deaths (95% CI, 1071 to 3792 fewer deaths) (Figure, E). Discussion Provisional mortality data showed that deaths from some but not all external causes increased during the pandemic, representing thousands of lives lost and exceeding prepandemic trends. Explanations for these changes are unknown. Drug overdoses and homicides may have been related to economic stress. Pandemic-associated changes in access to substance use disorder treatments may have exacerbated mortality from overdoses.6 Decreases in motor vehicle crash deaths in April coincided with less traffic, despite increases in drivers testing positive for drugs and alcohol and lower seatbelt use.3 Increases in motor vehicle crash deaths in June to August occurred as traffic increased (though still below 2019 levels), likely reflecting higher-risk behaviors.3 Lower than projected suicide deaths are paradoxical with reported increases in depressive and other mental health symptoms during the pandemic. Additional data are needed to understand the mechanism behind this finding. This study has limitations, including death certificate accuracy and that 2020 data published by NCHS are considered preliminary. However, substantial changes to March to August 2020 data are unlikely. Also, the true number of non–COVID-19 medical deaths may have been lower than projected during the pandemic period, as evidenced by the observation that in May, the total excess deaths due to drug overdoses, assaults, and unintentional injuries exceeded the apparent number of all non–COVID-19 excess deaths.]
  5. I really do think that you are exaggerating the risks and underestimating the benefits of the vaccines. I put my confidence in the decision makers. I am unaware of any examples for any of the many vaccines for different diseases where this issue you raise has been found. Vaccinating a greater fraction of the total population will greatly reduce the natural development of harmful mutations. I strongly feel that none of the variants of concern would have developed had the people in which they developed been vaccinated, and, if there had been herd immunity, the variants would not have spread to others.
  6. Serum albumin and risks of hospitalization and death: Findings from the Atherosclerosis Risk in Communities study. Shannon CM, Ballew SH, Daya N, Zhou L, Chang AR, Sang Y, Coresh J, Selvin E, Grams ME. J Am Geriatr Soc. 2021 Jul 23. doi: 10.1111/jgs.17313. Online ahead of print. PMID: 34298583 Abstract Objectives: To determine whether lower serum albumin in community-dwelling, older adults is associated with increased risk of hospitalization and death independent of pre-existing disease. Design: Prospective cohort study of participants in the fifth visit of the Atherosclerosis Risk in Communities (ARIC) study. Baseline data were collected from 2011 to 2013. Follow-up was available to December 31, 2017. Replication was performed in Geisinger, a health system in rural Pennsylvania. Setting: For ARIC, four US communities: Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and suburbs of Minneapolis, Minnesota. Participants: A total of 4947 community-dwelling men and women aged 66 to 90 years. Exposure: Serum albumin. Main outcomes: Incident all-cause hospitalization and death. Results: Among the 4947 participants, mean age was 75.5 years (SD: 5.12) and mean baseline serum albumin concentration was 4.05 g/dL (SD: 0.30). Over a median follow-up period of 4.42 years (interquartile interval: 4.16-5.05), 553 participants (11.2%) died and 2457 participants (49.7%) were hospitalized at least once. The total number of hospitalizations was 5725. In analyses adjusted for demographics and numerous clinical characteristics, including tobacco use, obesity, frailty, cardiovascular disease, kidney disease, diabetes C-reactive protein (CRP), cognitive status, alcohol use, medication use, respiratory disease, and systolic blood pressure, 1 g/dL lower baseline serum albumin concentration was associated with higher risk of both hospitalization (incidence rate ratio [IRR]: 1.58; 95% confidence interval [CI]: 1.36-1.82; p < 0.001) and death (hazard ratio {HR}: 1.67; 95% CI: 1.24-2.24; p < 0.001). Associations were weaker with older age but not different by frailty status or level of high-sensitivity CRP. Associations between serum albumin, hospitalizations, and death were also similar in a real-world cohort of primary care patients. Conclusions: Lower baseline serum albumin was significantly associated with increased risk of both all-cause hospitalization and death, independent of pre-existing disease. Older adults with low serum albumin should be considered a high-risk population and targeted for interventions to reduce the risk of adverse outcomes. Keywords: bromocresol purple; death; frailty; hospitalization; serum albumin. Meta-regression of randomized control trials with antithrombotics: weak correlation between net clinical benefit and all cause-mortality. Kilo R, Laporte S, Arab R, Mainbourg S, Provencher S, Grenet G, Bertoletti L, Villeneuve L, Cucherat M, Lega JC; META-EMBOL Group. Sci Rep. 2021 Jul 19;11(1):14728. doi: 10.1038/s41598-021-94160-1. PMID: 34282198 Abstract This study aimed to explore the validity of the use of the net clinical benefit (NCB), i.e. the sum of major bleeding and thrombotic events, as a potential surrogate for all-cause mortality in clinical trials assessing antithrombotics. Published randomized controlled trials testing anticoagulants in the prevention or treatment of venous thromboembolism (VTE) and non-valvular atrial fibrillation (NVAF) were systematically reviewed. The validity of NCB as a surrogate endpoint was estimated by calculating the strength of correlation of determination (R2) and its 95% confidence interval (CI) between the relative risks of NCB and all-cause mortality. Amongst the 125 trials retrieved, the highest R2trial values were estimated for NVAF (R2trial = 0.41, 95% CI [0.03; 0.48]), and acute VTE (R2trial = 0.30, 95% CI [0.04; 0.84]). Conversely, the NCB did not correlate with all-cause mortality in prevention studies with medical (R2trial = 0.12, 95% CI [0.00; 0.36]), surgical (R2trial = 0.05, 95% CI [0.00; 0.23]), and cancer patients (R2trial = 0.006, 95% CI [0.00; 1.00]). A weak correlation between NCB and all cause-mortality was found in NVAF and acute VTE, whereas no correlation was observed in clinical situations where the mortality rate was low. Consequently, NCB should not be considered a surrogate outcome for all cause-mortality in anticoagulation trials. Active and receptive arts participation and their association with mortality among adults in the United States: a longitudinal cohort study. Story KM, Yang Z, Bravata DM. Public Health. 2021 Jul 15;196:211-216. doi: 10.1016/j.puhe.2021.05.034. Online ahead of print. PMID: 34274695 Abstract Objectives: The aim of the study was to explore associations between active and receptive arts participation and all-cause mortality among adults in the United States population. Study design: This was a prospective cohort study. Methods: Data were derived from the Health and Retirement Study. Separate Cox proportional hazards models were constructed for two cohorts (2012 and 2014) to examine associations between arts participation and mortality. Results: Independent of sociodemographic and health factors, participants aged ≥65 years had a higher mortality risk if they did not engage in music listening, hazard ratio (HR) 1.39 (95% confidence interval [CI]: 1.12-1.71); singing/playing an instrument, HR 1.49 (95% CI: 1.07-2.0); or doing arts and crafts, HR 1.39 (95% CI: 1.00-1.92). For participants aged <65 years, there was a higher mortality risk if they did not listen to music, HR 1.79 (95% CI: 1.07-3.01). Older participants from the 2014 cohort had a higher mortality risk if they did not engage in active arts, HR 1.73 (95% CI: 1.08-2.77). Conclusions: Engagement in the arts was associated with lower risk of mortality even after risk adjustment, especially for adults aged ≥65 years. Greater access and integration of arts in everyday life is recommended. Keywords: Adults; Arts participation; Mortality; Music listening. Effects of lycopene intake on HDL-cholesterol and triglyceride levels: A systematic review with meta-analysis. Inoue T, Yoshida K, Sasaki E, Aizawa K, Kamioka H. J Food Sci. 2021 Jul 15. doi: 10.1111/1750-3841.15833. Online ahead of print. PMID: 34268742 Review. Abstract Lycopene is a lipophilic unsaturated carotenoid and has a very strong singlet oxygen-quenching ability. Increased serum or plasma lycopene levels have been reported to be associated with a lower risk of metabolic syndrome. We aimed to investigate the effects of lycopene intake on blood HDL-cholesterol (HCL-c) and triglyceride (TG) levels, which are metabolic syndrome biomarkers, by systematic review and meta-analyses of human interventional trials. We searched 15 databases and included studies that assessed the effects of oral lycopene intake on blood HDL-c and TG levels of participants ≥18 years of age. Three reviewers independently selected applicable studies, then assessed study qualities. Data were pooled as standardized mean difference (SMD) and analyzed by random-effects model. Heterogeneity was assessed by I2 statistics. Meta-analysis including 12 trial arms (n = 781) revealed a significantly increased HDL-c level in the lycopene group compared with that in the control group (SMD = 0.33 [95% CI: 0.12, 0.54], p = 0.002) and moderate heterogeneity (I2 = 45%). Most subgroup meta-analyses (restricted to study design, test food type, intake period, and participants' characteristics) showed similar results for HDL-c level. On the other hand, meta-analysis including 11 studies (n = 854) revealed no significant difference in TG level between the lycopene and control groups. Most studies which met eligibility criteria had moderate risk of bias. Funnel plots for HDL-c and TG suggested an absence of publication bias. In conclusion, this systematic review and meta-analyses suggested that lycopene intake significantly improved blood HDL-c levels but not TG levels.
  7. AlPater

    Al's CR updates

    Chronic food restriction enhances dopamine-mediated intracranial self-stimulation. Gnazzo FG, Mourra D, Guevara CA, Beeler JA. Neuroreport. 2021 Jul 19. doi: 10.1097/WNR.0000000000001700. Online ahead of print. PMID: 34284450 Abstract Dopamine-mediated reinforcement and behavioral adaptation is essential to survival. Here, we test the effects of food restriction on dopamine-mediated learning and reinforcement using optical intracranial self-stimulation (oICSS), an optogenetic version of conventional electrical ICSS (also known as brain stimulation reward, BSR). Using mouse genetic lines to express channelrhodopsin selectively in midbrain dopamine neurons, we demonstrate that genetically expressed channelrhodopsin can mediate optically evoked dopamine release and support self-stimulation in a lever-pressing paradigm. Using this midbrain dopamine oICSS preparation, we compare acquisition and rate of pressing in ad libitum versus food restricted mice. Food restriction facilitated both more rapid acquisition of self-stimulation behavior and higher rates of responding; reversing food status after acquisition modulated response vigor in already established behavior. These data suggest that food restriction enhances both the acquisition and expression of dopamine-reinforced self-stimulation responding. These data demonstrate the utility of oICSS for examining changes in reinforcement learning concomitant to neuroadaptations induced in dopamine signaling by experimental manipulations such as food restriction. Caloric restriction inhibits renal artery ageing by reducing endothelin-1 expression. Wang XH, Ao QG, Cheng QL. Ann Transl Med. 2021 Jun;9(12):979. doi: 10.21037/atm-21-2218. PMID: 34277779 Free PMC article. Abstract Background: The renal artery plays a central role in renal perfusion and is critical for proper renal function. Ageing is an independent risk factor for both impaired renal function and vascular disorders, and associated with an increase in the expression of the vasoconstrictor endothelin-1 (ET-1), and caloric restriction (CR) without malnutrition has been shown to be an effective inhibitor of renal dysfunction induced by ageing. The objective of this study was to determine whether CR-mediated alleviation of renal dysfunction is mediated by ET-1 expression. Methods: The young (2 months, 2 M) and old (12 months, 12 M) Sprague-Dawley male rats were used and fed ad libitum. The 12-month-old rats were further divided into 12 M and 12 M-caloric restriction (CR) (30% calorie restriction). After 8 weeks, the renal tissues were showed by PAS staining, and age-related metabolic parameters and renal functions were detected in each group of rats. The inflammatory cytokines of interleukin (IL)-6, IL-1β, tumor necrosis factor alpha (TNF-α), and transforming growth factor beta 1 (TGF-β1) were analyzed using ELISA. The mRNA and protein expression in the renal artery were analysis by qRT-PCR and Immunoblot analysis. Results: Ageing was associated with significant increases in 24 h urine protein content and serum triglyceride and cholesterol in 12 M rats, both of which were significantly inhibited in 12 M-CR. The mRNA expression and the secretion of IL-6, IL-1β, TNF-α, and TGF-β1 in the renal artery was significantly increased with ageing and inhibited by CR. CR also inhibited ageing-induced Edn1 (encoding ET-1) mRNA and protein expression in the renal artery. In addition, CR could regulate ET-1 expression by inhibiting the activation of NF-κB signaling and activation and induction in the expression of NF-E2-related factor 2 (Nrf2) and histone deacetylase and gene repressor sirtuin 1 (SIRT1), both of which play a central role in mitigating oxidative stress in young rats. Conclusions: Moderate CR can reverse the ageing related kidney dysfunction by reducing the ET-1 expression. CR might be used as an alternative to prevent the ageing induced renal artery dysfunction. Keywords: Caloric restriction (CR); NF-κB signaling; ageing; endothelin-1 (ET-1); renal artery.
  8. Since much vaccine hesitancy resides in blood-injection-injury cluster of fears https://www.cambridge.org/core/journals/psychological-medicine/article/injection-fears-and-covid19-vaccine-hesitancy/A70D5D859CC25804B7AC4FB3AD54F68D it may help that there be development of COVID/flu nasal spray vaccines http://outbreaknewstoday.com/nasal-spray-combined-vaccine-for-covid-and-flu-shows-protection-99139/ .
  9. From The New York Times: https://www.nytimes.com/2021/07/21/us/american-life-expectancy-report.html U.S. Life Expectancy Dropped 1.5 Years in 2020, Largely From the Pandemic The 18-month decline was the steepest since World War II, according to federal statistics. Black and Hispanic Americans were disproportionately affected. The sheer magnitude of the drop has left researchers reeling as it wiped away decades of progress, but it is not likely to be permanent.
  10. The regulation of healthspan and lifespan by dietary amino acids. Babygirija R, Lamming DW. Transl Med Aging. 2021;5:17-30. doi: 10.1016/j.tma.2021.05.001. Epub 2021 May 24. PMID: 34263088 Free PMC article. Abstract As a key macronutrient and source of essential macromolecules, dietary protein plays a significant role in health. For many years, protein-rich diets have been recommended as healthy due to the satiety-inducing and muscle-building effects of protein, as well as the ability of protein calories to displace allegedly unhealthy calories from fats and carbohydrates. However, clinical studies find that consumption of dietary protein is associated with an increased risk of multiple diseases, especially diabetes, while studies in rodents have demonstrated that protein restriction can promote metabolic health and even lifespan. Emerging evidence suggests that the effects of dietary protein on health and longevity are not mediated simply by protein quantity but are instead mediated by protein quality - the specific amino acid composition of the diet. Here, we discuss how dietary protein and specific amino acids including methionine, the branched chain amino acids (leucine, isoleucine, and valine), tryptophan and glycine regulate metabolic health, healthspan, and aging, with attention to the specific molecular mechanisms that may participate in these effects. Finally, we discuss the potential applicability of these findings to promoting healthy aging in humans. Keywords: aging; amino acids; branched-chain amino acids; methionine; protein restriction. Association of dietary zinc intake with coronary artery calcium progression: the Multi-Ethnic Study of Atherosclerosis (MESA). Gao JW, Zhang SL, Hao QY, Huang FF, Liu ZY, Zhang HF, Yan L, Wang JF, Liu PM. Eur J Nutr. 2021 Aug;60(5):2759-2767. doi: 10.1007/s00394-020-02452-5. Epub 2021 Jan 4. PMID: 33394121 Abstract Purpose: Zinc is considered protective against atherosclerosis; however, the association between dietary zinc intake and cardiovascular disease remains debated. We investigated whether dietary zinc intake was associated with coronary artery calcium (CAC) progression in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: This analysis included 5186 participants aged 61.9 ± 10.2 years (48.8% men; 41.3% white, 25.0% black, 21.6% Hispanic, and 12.1% Chinese American) from the MESA. Dietary zinc intake was assessed by a self-administered, 120-item food frequency questionnaire at baseline (2000-2002). Baseline and follow-up CAC were measured by computed tomography. CAC progression was defined as CAC > 0 at follow-up for participants with CAC = 0 at baseline; and an annualized change of 10 or percent change of ≥ 10% for those with 0 < CAC < 100 or CAC ≥ 100 at baseline, respectively. Results: Dietary zinc intake was 8.4 ± 4.5 mg/day and 2537 (48.9%) of the included participants had CAC at baseline. Over a median follow-up of 3.4 years (25th-75th percentiles = 2.0-9.1 years), 2704 (52.1%) participants had CAC progression. In the fully adjusted model, higher dietary zinc was associated with a lower risk of CAC progression in both men (hazard ratio {HR}) 0.697, 95% confidence interval [CI] 0.553-0.878; p = 0.002) and women (HR 0.675; 95% CI 0.496-0.919; p = 0.012, both comparing extreme groups). Furthermore, such an inverse association was attributable to dietary zinc intake from non-red meat (p < 0.05), rather than red meat sources (p > 0.05). Conclusions: In this multiethnic population free of clinically apparent cardiovascular disease, higher dietary zinc intake from non-red meat sources was independently associated with a lower risk of CAC progression. Keywords: Cardiovascular disease; Coronary artery calcium progression; Dietary zinc intake; Risk factors. Strain-specific metabolic responses to long-term caloric restriction in female ILSXISS recombinant inbred mice. Mulvey L, Wilkie SE, Griffiths K, Sinclair A, McGuinness D, Watson DG, Selman C. Mol Cell Endocrinol. 2021 Jul 8:111376. doi: 10.1016/j.mce.2021.111376. Online ahead of print. PMID: 34246728 Review. Abstract The role that genetic background may play in the responsiveness of organisms to interventions such as caloric restriction (CR) is underappreciated but potentially important. We investigated genetic background on a suite of metabolic parameters in female recombinant inbred ILSXISS mouse strains previously reported to show divergent lifespan responses to 40% CR (TejJ89-lifespan extension; TejJ48-lifespan unaffected; TejJ114-lifespan shortening). Body mass was reduced across all strains following 10 months of 40% CR, although this loss (relative to ad libitum controls) was greater in TejJ114 relative to the other strains. Gonadal white adipose tissue (gWAT) mass was similarly reduced across all strains following 40% CR, but brown adipose tissue (BAT) mass increased only in strains TejJ89 and TejJ48. Surprisingly, glucose tolerance was improved by CR only in TejJ114, while strains TejJ89 and TejJ114 were relatively hyperinsulinemic following CR relative to their AL controls. We subsequently undertook an unbiased metabolomic approach in gWAT and BAT tissue from strains TejJ89 and TejJ114 mice under AL and 40% CR. gWAT from TejJ89 showed a significant reduction in several long chain unsaturated fatty acids following 40% CR, but gWAT from TejJ114 appeared relatively unresponsive to CR, with far fewer metabolites changing. Phosphatidylethanoloamine lipids within the BAT were typically elevated in TejJ89 following CR, while some phosphatidylglycerol lipids were decreased. However, BAT from strain TejJ114 again appeared unresponsive to CR. These data highlight strain-specific metabolic differences exist in ILSXISS mice following CR. We suggest that precisely how different fat depots respond dynamically to CR may be an important factor in the variable longevity under CR observed in these mice. Keywords: Dietary restriction; Genetic heterogeneity; Metabolomics; White adipose tissue; brown adipose tissue. Single-oocyte transcriptome analysis reveals aging-associated effects influenced by life stage and calorie restriction. Mishina T, Tabata N, Hayashi T, Yoshimura M, Umeda M, Mori M, Ikawa Y, Hamada H, Nikaido I, Kitajima TS. Aging Cell. 2021 Jul 10:e13428. doi: 10.1111/acel.13428. Online ahead of print. PMID: 34245092 Abstract Chromosome segregation errors in oocytes lead to the production of aneuploid eggs, which are the leading cause of pregnancy loss and of several congenital diseases such as Down syndrome. The frequency of chromosome segregation errors in oocytes increases with maternal age, especially at a late stage of reproductive life. How aging at various life stages affects oocytes differently remains poorly understood. In this study, we describe aging-associated changes in the transcriptome profile of mouse oocytes throughout reproductive life. Our single-oocyte comprehensive RNA sequencing using RamDA-seq revealed that oocytes undergo transcriptome changes at a late reproductive stage, whereas their surrounding cumulus cells exhibit transcriptome changes at an earlier stage. Calorie restriction, a paradigm that reportedly prevents aging-associated egg aneuploidy, promotes a transcriptome shift in oocytes with the up-regulation of genes involved in chromosome segregation. This shift is accompanied by the improved maintenance of chromosomal cohesin, the loss of which is a hallmark of oocyte aging and causes chromosome segregation errors. These findings have implications for understanding how oocytes undergo aging-associated functional decline throughout their reproductive life in a context-dependent manner. Keywords: aging; chromosome segregation; cohesin; oocyte; transcriptome. Triiodothyronine (T3) enhances lifespan and protects against oxidative stress via activation of Klotho in Caenorhabditis elegans. Mohanty SK, Suchiang K. Biogerontology. 2021 Aug;22(4):397-413. doi: 10.1007/s10522-021-09923-0. Epub 2021 Apr 13. PMID: 33851304 Abstract Age predisposes individuals to significant diseases, and the biological processes contributing to aging are currently under intense investigation. Klotho is an anti-aging protein with multifaceted roles and is an essential component of the endocrine fibroblast growth factor. In Caenorhabditis elegans (C. elegans), there are two prospective orthologs of α-Klotho, C50F7.10, and E02H9.5, identified. The two orthologs' products are homologous to the highly conserved KL1 domain of human and mouse Klotho protein. Considering the endocrine system's major involvement in an organism's homeostasis and that thyroid disorders increase with advancing age, the molecular mechanisms underlying its impact on different endocrine components during the aging process remain poorly characterized. In this study, we sought to determine the regulatory role of Triiodothyronine (T3) on homologs genes of klotho and its impact on different parameters of aging in the C. elegans model organism. We showed that T3 could increase the mRNA expressions of the klotho homologous genes in C. elegans. Moreover, T3 could also extend a worm lifespan and modulate oxidative stress resistance and aging biomarkers significantly and positively. Further investigations employing different mutant and transgenic strains reveal that these observed effects are mediated through the EGL-17/EGL-15 pathway via Klotho activation along with the involvement of transcription factor DAF-16. In conclusion, these findings have revealed an unexpected link between T3 and Klotho and how this link can modulate the aging process in C. elegans via activation of klotho. This study will help understand the crosstalk and regulations of different endocrine components and their consequences on the aging process in multiple species. Keywords: Aging; DAF-16; EGL-15; Klotho; Oxidative stress; Triiodothyronine. Relationship of higher-level functional capacity with long-term mortality in Japanese older people: NIPPON DATA90. Nagata H, Miura K, Tanaka S, Kadota A, Hayakawa T, Kondo K, Fujiyoshi A, Takashima N, Kita Y, Okayama A, Okamura T, Ueshima H. J Epidemiol. 2021 Jul 10. doi: 10.2188/jea.JE20210077. Online ahead of print. PMID: 34248110 Abstract Background: Basic and instrumental activities of daily living (BADL, IADL) are known predictors of mortality. However, the relationship between higher-level functional capacity (HLFC) and mortality and related sex differences have rarely been investigated. Methods: A prospective population-based cohort study was conducted in 1,824 older residents (≥65 years) with independent BADL from 300 randomly selected areas in Japan from 1995, and the participants were followed up until 2010. Using the Cox proportional hazards model, the relationship between HLFC and mortality risk was investigated with adjustment for possible confounders. HLFC was assessed using the Tokyo Metropolitan Institute of Gerontology Index of Competence. Baseline data were collected using a questionnaire or by home-visit interviews. esults: During an average 12.2-year follow-up, all-cause death was observed in 836 (45.8%) participants. Impaired HLFC was significantly associated with mortality (hazard ratio {HR}) 1.37; 95% confidence interval [CI], 1.13-1.65). Lower social role was significantly associated with higher mortality risk in men (HR 1.38; 95% CI, 1.13-1.68). Lower IADL and intellectual activity were significantly associated with higher mortality risk in women (HR 1.50; 95% CI, 1.15-1.95; HR 1.46; 95% CI, 1.19-1.79). The relationship between HLFC and mortality risk showed a similar tendency among cardiovascular diseases, stroke, cancer, and pneumonia. onclusion: Impaired HLFC was associated with a high risk of all-cause mortality among community-dwelling older people with independent BADL. In particular, social role in men and IADL and intellectual activity in women were associated with long-term mortality risk. Keywords: disease-specific; higher-level functional capacity; mortality; older people; sex difference.
  11. AlPater

    Cell phones and cancer -- redux

    Your paper examined case-control studies, but their reference "6" was a prospective study. Tumors were associated with the side of the head the phones were used on. 6. Cell phones and brain tumors: a review including the long-term epidemiologic data. Khurana VG, Teo C, Kundi M, Hardell L, Carlberg M. Surg Neurol. 2009 Sep;72(3):205-14; discussion 214-5. doi: 10.1016/j.surneu.2009.01.019. Epub 2009 Mar 27. PMID: 19328536 Abstract Background: The debate regarding the health effects of low-intensity electromagnetic radiation from sources such as power lines, base stations, and cell phones has recently been reignited. In the present review, the authors attempt to address the following question: is there epidemiologic evidence for an association between long-term cell phone usage and the risk of developing a brain tumor? Included with this meta-analysis of the long-term epidemiologic data are a brief overview of cell phone technology and discussion of laboratory data, biological mechanisms, and brain tumor incidence. Methods: In order to be included in the present meta-analysis, studies were required to have met all of the following criteria: (i) publication in a peer-reviewed journal; (ii) inclusion of participants using cell phones for > or = 10 years (ie, minimum 10-year "latency"); and (iii) incorporation of a "laterality" analysis of long-term users (ie, analysis of the side of the brain tumor relative to the side of the head preferred for cell phone usage). This is a meta-analysis incorporating all 11 long-term epidemiologic studies in this field. Results: The results indicate that using a cell phone for > or = 10 years approximately doubles the risk of being diagnosed with a brain tumor on the same ("ipsilateral") side of the head as that preferred for cell phone use. The data achieve statistical significance for glioma and acoustic neuroma but not for meningioma. Conclusion: The authors conclude that there is adequate epidemiologic evidence to suggest a link between prolonged cell phone usage and the development of an ipsilateral brain tumor.
  12. Renal markers and risks of all cause and cardiovascular mortality from the Taichung community based cohort study. Lin CC, Chen TY, Li CI, Liu CS, Lin CH, Wang MC, Yang SY, Li TC. Sci Rep. 2021 Jul 8;11(1):14143. doi: 10.1038/s41598-021-93627-5. PMID: 34239018 Abstract This study aimed to explore the associations between renal-related and arterial stiffness biomarkers with all-cause and expanded cardiovascular disease (CVD) mortality in a general Taiwanese population. This prospective community-based cohort study included 4883 subjects aged ≥ 20 years who were followed up until December 31, 2016. Renal-related biomarkers consisted of blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), and urine albumin-to-creatinine ratio (UACR). Arterial stiffness biomarker consisted of brachial-ankle pulse wave velocity (baPWV). The death status of the subjects was ascertained by matching information from death records with the identification number and date of birth of the subjects. Cox proportional hazard models with restricted cubic splines estimated the hazard ratios and 95% confidence intervals for all-cause mortality and expanded CVD mortality. During a mean 8.3 years of follow up, 456 deaths were recorded, 146 of which were due to expanded CVD mortality. The multivariable-adjusted hazard ratios of all-cause mortality was 1.53 (95% CI 1.21-1.94) for BUN (≥ 20 mg/dL vs. < 20 mg/dL), 1.57 (1.15-2.14) for eGFR (< 90 mL/min/1.73 m2 vs. ≥ 90 mL/min/1.73 m2), 1.55 (1.25-1.92) for UACR (≥ 30 mg/g vs. < 30 mg/g), and 1.75 (1.14-2.67) for baPWV (≥ 1400 cm/s vs. < 1400 cm/s). The expanded CVD mortality was 1.89 (95% CI 1.30-2.73) for BUN (≥ 20 mg/dL vs. < 20 mg/dL), 2.28 (1.13-4.57) for eGFR (< 90 mL/min/1.73 m2 vs. ≥ 90 mL/min/1.73 m2), 2.13 (1.52-2.99) for UACR (≥ 25 mg/g vs. < 25 mg/g), and 15.73 (2.14-115.61) for baPWV (≥ 1400 cm/s vs. < 1400 cm/s). High levels of BUN, UACR, and baPWV and low levels of eGFR showed high risks with all-cause and expanded CVD mortality. Our study provides insights into screening tests to target populations at high risk of premature death due to CVD. The energy allocation trade-offs underlying life history traits in hypometabolic strepsirhines and other primates. Simmen B, Morino L, Blanc S, Garcia C. Sci Rep. 2021 Jul 9;11(1):14196. doi: 10.1038/s41598-021-93764-x. PMID: 34244546 Abstract Life history, brain size and energy expenditure scale with body mass in mammals but there is little conclusive evidence for a correlated evolution between life history and energy expenditure (either basal/resting or daily) independent of body mass. We addressed this question by examining the relationship between primate free-living daily energy expenditure (DEE) measured by doubly labeled water method (n = 18 species), life history variables (maximum lifespan, gestation and lactation duration, interbirth interval, litter mass, age at first reproduction), resting metabolic rate (RMR) and brain size. We also analyzed whether the hypometabolic primates of Madagascar (lemurs) make distinct energy allocation tradeoffs compared to other primates (monkeys and apes) with different life history traits and ecological constraints. None of the life-history traits correlated with DEE after controlling for body mass and phylogeny. In contrast, a regression model showed that DEE increased with increasing RMR and decreasing reproductive output (i.e., litter mass/interbirth interval) independent of body mass. Despite their low RMR and smaller brains, lemurs had an average DEE remarkably similar to that of haplorhines. The data suggest that lemurs have evolved energy strategies that maximize energy investment to survive in the unusually harsh and unpredictable environments of Madagascar at the expense of reproduction. Investigating the association of testosterone with survival in men and women using a Mendelian randomization study in the UK Biobank. Schooling CM, Zhao JV. Sci Rep. 2021 Jul 7;11(1):14039. doi: 10.1038/s41598-021-93360-z. PMID: 34234209 Abstract Life expectancy in the developed West is currently stagnated and remains shorter in men than women. Well-established evolutionary biology theory suggests lifespan trades-off against reproductive success, possibly sex-specifically. We examined whether a key driver of reproductive success, testosterone, affected survival using a Mendelian randomization longevity study in the UK Biobank to obtain unbiased estimates, along with control exposures. We applied published genetic instruments for testosterone to obtain inverse variance weighted estimates of associations with survival to (i.e., age at) recruitment, in 167,020 men and 194,174 women. We similarly obtained estimates for a positive control (smoking initiation), and a negative control (absorbate), a marker of vitamin C metabolism. Testosterone was associated with poorer survival (0.10 years younger at recruitment per effect size of testosterone, 95% confidence interval (CI) 0.004 to 0.20). As expected, smoking initiation was also associated with poorer survival (0.37 years younger, 95% CI 0.25 to 0.50), but not absorbate (0.01 years younger, 95% CI - 0.09 to 0.11). Several aspects of a healthy lifestyle (low animal fat diet) and several widely used medications (statins, metformin, dexamethasone and possibly aspirin) may modulate testosterone. Explicitly designing interventions sex-specifically based on these insights might help address stagnating life expectancy and sexual disparities. Prognostic value of Neutrophil-to-lymphocyte ratio in COVID-19 patients: A systematic review and meta-analysis. Ulloque-Badaracco JR, Salas-Tello WI, Al-Kassab-Córdova A, Alarcón-Braga EA, Benites-Zapata VA, Maguiña JL, Hernandez AV. Int J Clin Pract. 2021 Jul 6:e14596. doi: 10.1111/ijcp.14596. Online ahead of print. PMID: 34228867 Abstract Background: Neutrophil-to-lymphocyte ratio (NLR) is an accessible and widely used biomarker. NLR may be used as an early marker of poor prognosis in patients with COVID-19. Objective: To evaluate the prognostic value of the NLR in patients diagnosed with COVID-19. Methods: We conducted a systematic review and meta-analysis. Observational studies that reported the association between baseline NLR values (i.e. at hospital admission) and severity or all-cause mortality in COVID-19 patients were included. The quality of the studies was assessed using the Newcastle-Ottawa Scale (NOS). Random effects models and inverse variance method were used for meta-analyses. The effects were expressed as odds ratios (OR) and their 95% confidence intervals (CI). Small study effects were assessed with the Egger's test. Results: We analyzed sixty-one studies (n=15522 patients), 58 cohorts and three case-control. An increase of one unit of NLR was associated with a higher odds of severity (OR 6.22; 95%CI 4.93 to 7.84; p<0.001) and higher odds of all-cause mortality (OR 12.6; 95%CI 6.88 to 23.06; p<0.001). In our sensitivity analysis, we found that 41 studies with low risk of bias and moderate heterogeneity (I2 =53% and 58%) maintained strong association between NLR values and both outcomes (severity: OR 5.36; 95% CI 4.45 to 6.45; p<0.001; mortality: OR 10.42 95%CI 7.73 to 14.06; p=0.005). Conclusions: Higher values of NLR were associated with severity and all-cause mortality in hospitalized COVID-19 patients. Keywords: COVID-19; Mortality; NLR; Prognosis; Severity. Nut, corn, and popcorn consumption and the incidence of diverticular disease. Strate LL, Liu YL, Syngal S, Aldoori WH, Giovannucci EL. JAMA. 2008 Aug 27;300(8):907-14. doi: 10.1001/jama.300.8.907. PMID: 18728264 Free PMC article. Abstract Context: Patients with diverticular disease are frequently advised to avoid eating nuts, corn, popcorn, and seeds to reduce the risk of complications. However, there is little evidence to support this recommendation. Objective: To determine whether nut, corn, or popcorn consumption is associated with diverticulitis and diverticular bleeding. Design and setting: The Health Professionals Follow-up Study is a cohort of US men followed up prospectively from 1986 to 2004 via self-administered questionnaires about medical (biennial) and dietary (every 4 years) information. Men reporting newly diagnosed diverticulosis or diverticulitis were mailed supplemental questionnaires. Participants: The study included 47,228 men aged 40 to 75 years who at baseline were free of diverticulosis or its complications, cancer, and inflammatory bowel disease and returned a food-frequency questionnaire. Main outcome measures: Incident diverticulitis and diverticular bleeding. Results: During 18 years of follow-up, there were 801 incident cases of diverticulitis and 383 incident cases of diverticular bleeding. We found inverse associations between nut and popcorn consumption and the risk of diverticulitis. The multivariate hazard ratios for men with the highest intake of each food (at least twice per week) compared with men with the lowest intake (less than once per month) were 0.80 (95% confidence interval, 0.63-1.01; P for trend = .04) for nuts and 0.72 (95% confidence interval, 0.56-0.92; P for trend = .007) for popcorn. No associations were seen between corn consumption and diverticulitis or between nut, corn, or popcorn consumption and diverticular bleeding or uncomplicated diverticulosis. Conclusions: In this large, prospective study of men without known diverticular disease, nut, corn, and popcorn consumption did not increase the risk of diverticulosis or diverticular complications. The recommendation to avoid these foods to prevent diverticular complications should be reconsidered.
  13. Does exercise prevent major non-communicable disease and premature mortality? A critical review based on results from randomized controlled trials. Ballin M, Nordström P. J Intern Med. 2021 Jul 9. doi: 10.1111/joim.13353. Online ahead of print. PMID: 34242442 Review. Abstract Observational studies show that physical activity is strongly associated with reduced risk of premature mortality and major non-communicable diseases (NCDs). We reviewed to which extent these associations have been confirmed in randomized controlled trials (RCTs) for the outcomes of mortality, cardiovascular disease (CVD), type 2 diabetes (T2D), and fracture. The results show that exercise does not reduce all-cause mortality and incident CVD in older adults or in people with chronic conditions, based on RCTs comprising ∼50,000 participants. The results also indicate a lack of effect on cardiovascular mortality in people with chronic conditions, based on RCTs comprising ∼11,000 participants. Furthermore, there is inconsistent evidence regarding the effect of exercise on fractures in older adults, based on RCTs comprising ∼40,000 participants. Finally, based on RCTs comprising ∼17,000 participants, exercise reduces T2D incidence in people with prediabetes when combined with dietary modification, although evidence for the individual effect of exercise is lacking. Identified shortcomings of the current evidence include risks of publication bias, lack of high-quality studies in certain high-risk populations, and inconstant evidence with respect to some outcomes. Thus, additional large trials would be of value, especially with fracture as primary outcome. In conclusion, according to current RCT evidence, exercise can prevent T2D assuming it is combined with a dietary intervention. However, the evidence show that exercise does not prevent premature mortality or CVD, with inconsistent evidence for fractures. Keywords: Exercise; Health; Morbidity; Mortality; Physical activity.
  14. Dietary protein intake, kidney function, and survival in a nationally representative cohort. Narasaki Y, Okuda Y, Moore LW, You AS, Tantisattamo E, Inrig JK, Miyagi T, Nakata T, Kovesdy CP, Nguyen DV, Kalantar-Zadeh K, Rhee CM. Am J Clin Nutr. 2021 Jul 1;114(1):303-313. doi: 10.1093/ajcn/nqab011. PMID: Abstract Background: High-protein diets (e.g., Paleo, Atkins, South Beach, ketogenic) have gained popularity as a means to promote weight loss and avoid excess carbohydrate consumption. Yet in chronic kidney disease (CKD) patients, evidence suggests low dietary protein intake (DPI) leads to attenuation of kidney function decline, although concerns remain for risk of protein-energy wasting. Objectives: To examine associations of DPI with mortality in a nationally representative cohort of US adults, stratified by kidney function. Methods: We examined the association between daily DPI scaled to actual body weight (ABW), ascertained by 24-h dietary recall, with all-cause mortality among 27,604 continuous NHANES adult participants (1999-2010), stratified according to impaired versus normal kidney function (estimated glomerular filtration rates <60 compared with ≥60 ml/min/1.72 m2, respectively), using multivariable Cox models. We also examined the relation between high biological value (HBV) protein consumption with mortality. Results: In participants with impaired kidney function, a high DPI of ≥1.4 g/kg ABW/day was associated with higher mortality, while lower DPI levels were not associated with mortality (reference, 0.6 to <1.0 g/kg ABW/day): the adjusted HRs (aHRs) were 1.09 (95% CI: 0.90, 1.32), 1.03 (95% CI: 0.82, 1.29), and 1.37 (95% CI: 1.02, 1.85) for DPI <0.6, 1.0 to <1.4, and ≥1.4 g/kg ABW/day, respectively. Yet in participants with normal kidney function, a low DPI of <0.6 g/kg ABW/day was associated with higher mortality, whereas higher DPI levels were not associated with death: the aHRs were 1.18 (95% CI: 1.04, 1.34), 0.92 (95% CI: 0.81, 1.04), and 0.99 (95% CI: 0.85, 1.16) for DPI <0.6, 1.0 to <1.4, and ≥1.4 g/kg ABW/day, respectively. The highest 2 tertiles of HBV consumption were associated with higher mortality in participants with impaired kidney function. Conclusions: Among participants with impaired kidney function, a higher DPI and greater HBV consumption were associated with higher mortality, whereas a lower DPI was associated with higher mortality in those with normal kidney function. Further studies are needed to elucidate the specific pathways between higher DPI and mortality in CKD. Keywords: chronic kidney disease; dietary protein; kidney function; mortality; survival, NHANES. Meat consumption and risk of incident dementia: cohort study of 493,888 UK Biobank participants. Zhang H, Greenwood DC, Risch HA, Bunce D, Hardie LJ, Cade JE. Am J Clin Nutr. 2021 Jul 1;114(1):175-184. doi: 10.1093/ajcn/nqab028. PMID: 33748832 Free PMC article. Abstract Background: Worldwide, the prevalence of dementia is increasing and diet as a modifiable factor could play a role. Meat consumption has been cross-sectionally associated with dementia risk, but specific amounts and types related to risk of incident dementia remain poorly understood. Objective: We aimed to investigate associations between meat consumption and risk of incident dementia in the UK Biobank cohort. Methods: Meat consumption was estimated using a short dietary questionnaire at recruitment and repeated 24-h dietary assessments. Incident all-cause dementia comprising Alzheimer disease (AD) and vascular dementia (VD) was identified by electronic linkages to hospital and mortality records. HRs for each meat type in relation to each dementia outcome were estimated in Cox proportional hazard models. Interactions between meat consumption and the apolipoprotein E (APOE) ε4 allele were additionally explored. Results: Among 493,888 participants included, 2896 incident cases of all-cause dementia, 1006 cases of AD, and 490 cases of VD were identified, with mean ± SD follow-up of 8 ± 1.1 y. Each additional 25 g/day intake of processed meat was associated with increased risks of incident all-cause dementia (HR: 1.44; 95% CI: 1.24, 1.67; P-trend < 0.001) and AD (HR: 1.52; 95% CI: 1.18, 1.96; P-trend = 0.001). In contrast, a 50-g/d increment in unprocessed red meat intake was associated with reduced risks of all-cause dementia (HR: 0.81; 95% CI: 0.69, 0.95; P-trend = 0.011) and AD (HR: 0.70; 95% CI: 0.53, 0.92; P-trend = 0.009). The linear trend was not significant for unprocessed poultry and total meat. Regarding incident VD, there were no statistically significant linear trends identified, although for processed meat, higher consumption categories were associated with increased risks. The APOE ε4 allele increased dementia risk by 3 to 6 times but did not modify the associations with diet significantly. Conclusion: These findings highlight processed-meat consumption as a potential risk factor for incident dementia, independent of the APOE ε4 allele. Keywords: Alzheimer disease; UK Biobank; dementia; meat consumption; processed meat; vascular dementia. Tea consumption and long-term risk of type 2 diabetes and diabetic complications: a cohort study of 0.5 million Chinese adults. Nie J, Yu C, Guo Y, Pei P, Chen L, Pang Y, Du H, Yang L, Chen Y, Yan S, Chen J, Chen Z, Lv J, Li L. Am J Clin Nutr. 2021 Jul 1;114(1):194-202. doi: 10.1093/ajcn/nqab006. PMID: 33709113 Free PMC article. Abstract Background: Evidence from epidemiological studies remains inconsistent or limited about the associations of tea consumption with incident diabetes and risk of diabetic complications and death among patients with diabetes. Objectives: We aimed to investigate the associations of tea consumption with long-term risk of developing type 2 diabetes (T2D) and risks of diabetic complications and death among patients with diabetes. Methods: This study included 482,425 diabetes-free participants and 30,300 patients with diabetes aged 30-79 y at study enrollment from the China Kadoorie Biobank. Tea consumption information was collected at baseline by interviewer-administered questionnaires. Incidences of diabetes, diabetic complications, and death were identified by linkages to the National Health Insurance system, disease registries, and death registries. Cox proportional hazard regression models were used to estimate HRs and 95% CIs. Results: The mean ± SD age of participants free of diabetes was 51.2 ± 10.5 y and 41% were male. The mean ± SD age of patients with diabetes was 58.2 ± 9.6 y and 39% were male. Of all daily tea consumers, 85.8% preferred green tea. In the diabetes-free population, 17,434 participants developed incident T2D during 11.1 y of follow-up. Compared with participants who never consumed tea in the past year, the HR (95% CI) of T2D for daily consumers was 0.92 (0.88, 0.97). In patients with diabetes, we identified 6572 deaths, 12,677 diabetic macrovascular cases, and 2441 diabetic microvascular cases during follow-up. Compared with patients who never consumed tea in the past year, the HRs (95% CIs) of all-cause mortality and risk of microvascular complications for daily consumers were 0.90 (0.83, 0.97) and 0.88 (0.78, 1.00), respectively. Tea consumption was not associated with risk of macrovascular complications among patients with diabetes. With regard to tea consumed, the inverse associations between daily tea consumption and risks of T2D and all-cause mortality in patients with diabetes were only observed among daily green tea drinkers. Conclusions: In Chinese adults, daily green tea consumption was associated with a lower risk of incident T2D and a lower risk of all-cause mortality in patients with diabetes, but the associations for other types of tea were less clear. In addition, daily tea consumption was associated with a lower risk of diabetic microvascular complications, but not macrovascular complications. Keywords: China Kadoorie Biobank; death; diabetic complications; prospective cohort study; tea consumption; type 2 diabetes. Nighttime ambulatory pulse pressure predicts cardiovascular and all-cause mortality among middle-aged participants in the 21-year follow-up. Lempiäinen PA, Ylitalo A, Huikuri H, Kesäniemi YA, Ukkola OH. J Clin Hypertens (Greenwich). 2021 Jul 3. doi: 10.1111/jch.14317. Online ahead of print. PMID: 34216537 Abstract Office pulse pressure (PP) is a predictor for cardiovascular (CV) events and mortality. Our aim was to evaluate ambulatory PP as a long-term risk factor in a random cohort of middle-aged participants. The Opera study took place in years 1991-1993, with a 24-h ambulatory blood pressure measurement (ABPM) performed to 900 participants. The end-points were non-fatal and fatal CV events, and deaths of all-causes. Follow-up period, until the first event or until the end of the year 2014, was 21.1 years (mean). Of 900 participants, 22.6% died (29.6% of men/15.6% of women, p<.001). A CV event was experienced by 208 participants (23.1%), 68.3% of them were male (p<.001). High nighttime ambulatory PP predicted independently CV mortality (hazard ratio {HR} 2.60; 95% confidence interval [CI 95%] 1.08-6.31, p=.034) and all-cause mortality in the whole population (HR 1.72; Cl 95% 1.06-2.78, p=.028). In males, both 24-h PP and nighttime PP associated with CV mortality and all-cause mortality (24-h PP HR for CV mortality 2.98; CI 95% 1.11-8.04, p=.031 and all-cause mortality HR 2.40; CI 95% 1.32-4.37, p=.004). Accordingly, nighttime PP; HR for CV mortality 3.13; CI 95% 1.14-8.56, p=.026, and for all-cause mortality HR 2.26; CI 95% 1.29-3.96, p=.004. Cox regression analyses were adjusted by sex, CV risk factors, and appropriate ambulatory mean systolic BP. In our study, high ambulatory nighttime PP was detected as a long-term risk factor for CV and all-cause mortality in middle-aged individuals. Keywords: all-cause mortality; ambulatory pulse pressure; cardiovascular mortality; follow-up; nighttime pulse pressure. Trajectory patterns of blood pressure change up to six years and the risk of dementia: a nationwide cohort study. Cheng G, He S, He Q, Xie X, Tang C, Xie Q, Wu X, Jiang N, Li C, Min X, Yan Y. Aging (Albany NY). 2021 Jul 1;13. doi: 10.18632/aging.203228. Online ahead of print. PMID: 34198262 Abstract The present study aimed to investigate the associations between the trajectory of blood pressure (BP) change and the risk of subsequent dementia and to explore the differences in age, gender, and hypertension subgroups. We included 10,660 participants aged ≥ 60 years from 1998 to 2018 waves of the Chinese Longitudinal Healthy Longevity Survey. Latent growth mixture models were used to estimate BP trajectories. Cox-proportional hazard models were used to analyze the effects of BP trajectories on the risk of dementia. According to the results, stabilized systolic BP (SBP) was found to be associated with a higher risk of dementia compared with normal SBP [adjusted hazard ratio (aHR): 1.62; 95% confidence interval (CI): 1.27-2.07] and elevated SBP (aHR: 2.22; 95% CI: 1.51-3.28) in and only in the subgroups of the oldest-old, women, and subjects without hypertension at baseline. Similarly, stabilized pulse pressure (PP) was associated with a higher risk of dementia compared with normal PP (aHR: 1.52; 95% CI: 1.24-1.88) and elevated PP (aHR: 2.12; 95% CI: 1.48-3.04) in and only in the subgroups of the oldest-old, women, and subjects with hypertension at baseline. These findings suggest that stabilized SBP and PP have predictive significance for the occurrence of dementia in late life, and the factors of age, gender, and late-life hypertension should be considered when estimating the risk of BP decline on dementia. Keywords: blood pressure; dementia; late-life; pulse pressure; trajectory. Prognostic power of conventional echocardiography in individuals without history of cardiovascular diseases: A systematic review and meta-analysis. Fernandes LP, Barreto ATF, Neto MG, Câmara EJN, Durães AR, Roever L, Aras-Júnior R. Clinics (Sao Paulo). 2021 Jun 28;76:e2754. doi: 10.6061/clinics/2021/e2754. eCollection 2021. PMID: 34190849 Abstract Echocardiographic abnormalities are associated with a higher incidence of adverse cardiovascular outcomes. This systematic review and meta-analysis aimed to evaluate whether echocardiographic abnormalities are predictors of cardiovascular events in individuals without previous cardiovascular diseases. The PubMed, Scopus, and SciELO databases were searched for longitudinal studies investigating the association between echocardiographic abnormalities and cardiovascular events among individuals without known cardiovascular diseases. Two independent reviewers analyzed data on the number of participants, age and sex, echocardiographic alterations, follow-up time, and cardiovascular outcomes. The meta-analysis estimated the risk ratio (RR) and 95% confidence interval (CI). Heterogeneity was assessed using I2 test. Twenty-two longitudinal studies met the eligibility criteria, comprising a total of 55,603 patients. Left ventricular hypertrophy (LVH) was associated with non-fatal cardiovascular events (RR 2.16; 95% CI 1.22-3.84), death from cardiovascular disease (RR 2.58; 95% CI 1.83- 3.64), and all-cause mortality (RR 2.02; 95% CI 1.34-3.04). Left ventricular diastolic dysfunction (LVDD) and left atrial dilation (LA) were associated with fatal and non-fatal cardiovascular events (RR 2.01; 95% CI 1.32-3.07) and (RR 1.78; 95% CI 1.16-2.73), respectively. Aortic root dilation was associated with non-fatal cardiovascular events (RR 1.25; 95% CI 1.09-1.43). In conclusion, LVH, LVDD, dilations of the LA, and of the aortic root were associated with an increased risk of adverse events in individuals without previous cardiovascular diseases. This study suggests that simple data obtained on conventional echocardiography can be an important predictor of cardiovascular outcomes in a low-risk population. Epidemiology of dementia onset captured in Canadian primary care electronic medical records. Pham ANQ, Voaklander D, Wagg A, Drummond N. Fam Pract. 2021 Jun 28:cmab056. doi: 10.1093/fampra/cmab056. Online ahead of print. PMID: 34180503 Abstract Background: Dementia is an increasing concern in many countries, especially in those experiencing rapid growth in the proportion of older adults in their population. Objective: This study aims to describe trends and demographic characteristics of incident dementia cases in community-dwelling older adults managed by primary care physicians. Methods: We used electronic medical records from the Canadian Primary Care Sentinel Surveillance Network database to conduct a retrospective analysis to determine the number of, and trends for, incident diagnoses of dementia. Age-standardized annual incidence rates were calculated. Participants in our cohort are Canadian community dwelling seniors aged 65+ years who were not diagnosed with dementia before baseline with at least six years of record at their primary care clinics. Results: The cohort consisted of 39 067 patients of whom 57% were females; the mean (SD) follow-up was 8.4 (1.5) years. During follow-up, 4935 patients were diagnosed with dementia. The risk for dementia diagnosis increased with increasing age but decreased in the last four years among people aged 80 and older at baseline (P < 0.001). People with dementia were more likely to be females (P = 0.001) and urban residents (P < 0.001), they are less likely to be classified into the least deprived group (P = 0.012). Conclusions: The incidence of dementia diagnosis increased with age except in the oldest old in both sexes. This may be attributed to the effect of mortality competing risk. Future research on the association between risk factors and dementia should consider studying dementia among the oldest old separately to minimize bias. Keywords: Aging; dementia; electronic health record; epidemiology; geriatric; primary care. Prospective Analysis of Fruit and Vegetable Variety on Health Outcomes in Community-Dwelling Chinese Older Adults. Yeung SSY, Zhu ZLY, Chan RSM, Kwok T, Woo J. J Nutr Health Aging. 2021;25(6):735-741. doi: 10.1007/s12603-021-1605-7. PMID: 34179926 Abstract Objectives: Evidence on the topic regarding fruit and vegetable (FV) variety and health outcomes among older adults is limited. This study explored the prospective association of fruit variety, vegetable variety and combined FV variety with the risk of sarcopenia, frailty, all-cause and cause-specific mortality in community-dwelling Chinese older adults. Design: Prospective cohort study. Setting: Community. Participants: Community-dwelling Chinese older adults aged ≥65 years in Hong Kong. Measurements: Fruit variety, vegetable variety and combined FV variety at baseline were assessed using a validated food frequency questionnaire and the variety scores were stratified into tertiles. Sarcopenia (Asian Working Group for Sarcopenia 2019), frailty (Cardiovascular Health Study) and all-cause and cause-specific mortality (retrieved from an official database) were assessed at 14-year follow-up. Adjusted binary logistic regression or Cox proportional hazards model were performed to examine the association of fruit variety, vegetable variety and combined FV variety with each health outcome. Data are presented as hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Baseline dietary data of 3992 participants (median age: 72 years (interquartile range: 68-76), 49.9% women) was available. There were 436 and 371 participants who were newly identified as having sarcopenia and frailty respectively, and 1654 all-cause mortality, 367 cardiovascular diseases (CVD) mortality and 534 cancer mortality over 14-year. Tertiles of fruit variety, vegetable variety and combined FV variety were not associated with sarcopenia, frailty, CVD mortality and cancer mortality. Participants in the highest tertile of fruit variety (HR 0.81, 95% CI 0.70-0.95, p-trend 0.010), vegetable variety (HR 0.77, 95% CI 0.67-0.89, p-trend <0.001) and combined FV variety (HR 0.77, 95% CI 0.67-0.89. p-trend <0.001) showed lower risk of all-cause mortality compared with participants in the lowest tertile. Conclusion: Among community-dwelling Chinese older adults, FV variety was not associated with sarcopenia, frailty, CVD mortality and cancer mortality over 14-year. Higher fruit variety, vegetable variety and combined FV variety were associated with a lower risk of all-cause mortality. Promoting a wide FV variety might be recommended to benefit the health and longevity of this population. Keywords: Aged; fruit; mortality; variety; vegetables.