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Everything posted by AlPater

  1. AlPater

    Al's CR updates

    The email list system is broken. Posts cannot be searched. Many of the posts do not make it to the messages I receive individually and via the daily mailings. Therefore, I am sending this message, comprised of citations papers that seem to be appropriate to the room of the Forum. I will try to also provide full-text links and a very brief excerpt or within brackets my synopsis of the paper. I apologize for the fact some papers discuss results of studies on the overweight or obese, but feel that some benefits seen in such subjects bears on a continuum of benefits accrued by CR and provide incentive to folks who are overweight or obese. Below are today's papers. Altered consolidation of extinction-like inhibitory learning in genotype-specific dysfunctional coping fostered by chronic stress in mice. Campus P, Maiolati M, Orsini C, Cabib S. Behav Brain Res. 2016 Aug 6. pii: S0166-4328(16)30505-8. doi: 10.1016/j.bbr.2016.08.014. [Epub ahead of print] PMID: 27506654 http://linkinghub.elsevier.com.sci-hub.cc/retrieve/pii/S0166432816305058 These findings support the conclusion that an experience of reduced food availability strain-specifically affects persistence of newly acquired passive coping strategies by altering consolidation of extinction-like inhibitory learning. The interaction of fasting, caloric restriction, and diet-induced obesity with 17β-estradiol on the expression of KNDy neuropeptides and their receptors in the female mouse. Yang JA, Yasrebi A, Snyder M, Roepke TA. Mol Cell Endocrinol. 2016 Aug 6. pii: S0303-7207(16)30298-2. doi: 10.1016/j.mce.2016.08.008. [Epub ahead of print] PMID: 27507595 http://linkinghub.elsevier.com.sci-hub.cc/retrieve/pii/S0303720716302982 [This paper suggests that steroidal environment and energy state negatively regulate KNDy (Kisspeptin/Neurokinin B/Dynorphin) gene which plays an important role in the https://en.wikipedia.org/wiki/Hypothalamic%E2%80%93pituitary%E2%80%93gonadal_axis] Effects of dietary supplementation with EPA and/or α-lipoic acid on adipose tissue transcriptomic profile of healthy overweight/obese women following a hypocaloric diet. Huerta AE, Prieto-Hontoria PL, Fernández-Galilea M, Escoté X, Martínez JA, Moreno-Aliaga MJ. Biofactors. 2016 Aug 10. doi: 10.1002/biof.1317. [Epub ahead of print] PMID: 27507611 http://sci-hub.cc/doi/10.1002/biof.1317 α-lipoic acid, especially in combination with EPA, upregulated the expression of genes associated with lipid catabolism while downregulated genes involved in lipids storage. Association of the TNF-alpha -308 G/A polymorphisms with metabolic responses secondary to a high protein/low carbohydrate versus a standard hypocaloric diet. De Luis DA, Aller R, Izaola O, Romero E. Nutr Hosp. 2016 Jun 30;33(3):267. doi: 10.20960/nh.267. Spanish. PMID: 27513494 [i have no access to this paper's full texts.] Carriers of -308 GG promoter variant of TNF-alpha gene have a better metabolic response than -308 GA obese with a high protein hypocaloric diet.
  2. [Admin Note: I made this new thread as a collector for posts about the recently discovered and previously discussed apparent link between diet, micronutrients choline and carnitine, TMAO production by gut microbes that feed on these micronutrients, and elevated risk of cardiovascular disease. Four posts down is the new post (by me) on the topic. The first four posts come from a different thread. --Dean] In his post about supplements for vegetarians, Michael Rae said: For now, prudence seems to require that vegetarians err on the side of a generous and definitely supplemented intake of choline, ensuring that dietary (to the extent that it can be known) plus supplemental choline is meaningfully higher than the AI of 550 mg for men and 425 mg/day for women. Functional status is still tricky, but one obvious set of markers is the same panel used to establish signs of deficiency in Zeisel’s depletion-repletion study:iv a fivefold or more increase above normal of the muscle-damage enzyme creatine phosphokinase (CPK), or a one-and-a-half or more times normal reading of the liver enzymes aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), or lactate dehydrogenase (LD). Fatty liver, unfortunately, requires a harder-to-access MRI of fat deposits in the organ, to which your doctor is unlikely to consent. The below papers may be a reason dietary choline can be bad for us. NATURE | RESEARCH HIGHLIGHTS CARDIOVASCULAR BIOLOGY Gut microbes raise heart-attack risk Nature 531, 278 (17 March 2016) doi:10.1038/531278b Published online 16 March 2016 http://sci-hub.io/10.1038/531278b Subject terms: Microbiology Cardiovascular biology Gut microbes produce a chemical that enhances clotting in the arteries, increasing the risk of heart attack and stroke. Stanley Hazen of the Cleveland Clinic in Ohio and his colleagues treated human platelets, which form blood clots, with a compound called TMAO. This is made in the body from a waste product of gut microbes, and has been linked to heart disease. The team found that TMAO made the platelets form artery-blocking clots faster. The researchers increased blood TMAO levels in mice by feeding them a diet that was rich in choline, a TMAO precursor, and found that the animals formed clots faster than did those with lower TMAO levels. This effect was not seen in animals that lacked gut microbes or that were treated with antibiotics. When intestinal microbes from mice that produced high levels of TMAO were transplanted into mice with no gut microbes, the recipients' clotting risk increased. The results reveal a link between diet, gut microbes and heart-disease risk, the authors say. Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk. Zhu W, Gregory JC, Org E, Buffa JA, Gupta N, Wang Z, Li L, Fu X, Wu Y, Mehrabian M, Sartor RB, McIntyre TM, Silverstein RL, Tang WH, DiDonato JA, Brown JM, Lusis AJ, Hazen SL. Cell. 2016 Mar 9. pii: S0092-8674(16)30113-1. doi: 10.1016/j.cell.2016.02.011. [Epub ahead of print] PMID: 26972052 http://sci-hub.io/10.1016/j.cell.2016.02.011 Abstract Normal platelet function is critical to blood hemostasis and maintenance of a closed circulatory system. Heightened platelet reactivity, however, is associated with cardiometabolic diseases and enhanced potential for thrombotic events. We now show gut microbes, through generation of trimethylamine N-oxide (TMAO), directly contribute to platelet hyperreactivity and enhanced thrombosis potential. Plasma TMAO levels in subjects (n > 4,000) independently predicted incident (3 years) thrombosis (heart attack, stroke) risk. Direct exposure of platelets to TMAO enhanced sub-maximal stimulus-dependent platelet activation from multiple agonists through augmented Ca2+ release from intracellular stores. Animal model studies employing dietary choline or TMAO, germ-free mice, and microbial transplantation collectively confirm a role for gut microbiota and TMAO in modulating platelet hyperresponsiveness and thrombosis potential and identify microbial taxa associated with plasma TMAO and thrombosis potential. Collectively, the present results reveal a previously unrecognized mechanistic link between specific dietary nutrients, gut microbes, platelet function, and thrombosis risk.
  3. https://en.wikipedia.org/wiki/The_Epoch_Times A media/newspaper provider should have the integrity to exclude stories about QAnon and vaccinine misinfomation. The author's ideas have been presented in https://en.wikipedia.org/wiki/Great_Barrington_Declaration#Critical_commentaries and widely criticized by the scientific community.
  4. https://en.wikipedia.org/wiki/The_Epoch_Times
  5. AlPater

    Video vs. print/paper

    Video/audio requires too much of a time commitment when I am at my desktop and is a distraction when I am driving or walking.
  6. Biomarker-Calibrated Macronutrient Intake and Chronic Disease Risk among Postmenopausal Women. Prentice RL, Pettinger M, Neuhouser ML, Raftery D, Zheng C, Gowda GAN, Huang Y, Tinker LF, Howard BV, Manson JE, Wallace R, Mossavar-Rahmani Y, Johnson KC, Lampe JW. J Nutr. 2021 Aug 7;151(8):2330-2341. doi: 10.1093/jn/nxab091. PMID: 33880504 Abstract Background: Knowledge about macronutrient intake and chronic disease risk has been limited by the absence of objective macronutrient measures. Recently, we proposed novel biomarkers for protein, protein density, carbohydrate, and carbohydrate density, using established biomarkers and serum and urine metabolomics profiles in a human feeding study. Objectives: We aimed to use these biomarkers to develop calibration equations for macronutrient variables using dietary self-reports and personal characteristics and to study the association between biomarker-calibrated intake estimates and cardiovascular disease, cancer, and diabetes risk in Women's Health Initiative (WHI) cohorts. Methods: Prospective disease association analyses are based on WHI cohorts of postmenopausal US women aged 50-79 y when enrolled at 40 US clinical centers (n = 81,954). We used biomarker intake values in a WHI nutritional biomarker study (n = 436) to develop calibration equations for each macronutrient variable, leading to calibrated macronutrient intake estimates throughout WHI cohorts. We then examined the association of these intakes with chronic disease incidence over a 20-y (median) follow-up period using HR regression methods. Results: In analyses that included doubly labeled water-calibrated total energy, HRs for cardiovascular diseases and cancers were mostly unrelated to calibrated protein density. However, many were inversely related to carbohydrate density, with HRs (95% CIs) for a 20% increment in carbohydrate density of 0.81 (0.69, 0.95) and 0.83 (0.74, 0.93), respectively, for primary outcomes of coronary heart disease and breast cancer, as well as 0.74 (0.60, 0.91) and 0.87 (0.81, 0.93) for secondary outcomes of heart failure and total invasive cancer. Corresponding HRs (95% CIs) for type 2 diabetes incidence in relation to protein density and carbohydrate density were 1.17 (1.09, 1.75) and 0.73 (0.66, 0.80), respectively. Conclusions: At specific energy intake, a diet high in carbohydrate density is associated with substantially reduced risk of major chronic diseases in a population of US postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00000611. Keywords: biomarker; cancer; cardiovascular disease; diabetes; diet; macronutrient; measurement error; metabolomics. Citicoline and Memory Function in Healthy Older Adults: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Nakazaki E, Mah E, Sanoshy K, Citrolo D, Watanabe F. J Nutr. 2021 Aug 7;151(8):2153-2160. doi: 10.1093/jn/nxab119. PMID: 33978188 Free PMC article. Abstract Background: Supplementation of citicoline (CDP-choline), a naturally occurring mononucleotide, has shown beneficial effects on memory function and behavior in populations with a wide range of impairments. However, few studies have investigated its effect in healthy older populations. Objective: The objective of this study was to investigate the effects of citicoline (Cognizin®), on memory in healthy elderly populations with age-associated memory impairment (AAMI). Methods: A total of 100 healthy men and women aged between 50 and 85 y with AAMI participated in this randomized, double-blind, placebo-controlled trial. Participants were randomized to receive placebo (n = 51) or citicoline (n = 49; 500 mg/d) for 12 wk. Memory function was assessed at baseline and end of the intervention (12 wk) using computerized tests (Cambridge Brain Sciences, Ontario, Canada). Safety measurements included adverse events query, body weight, blood pressure, and hematology and metabolic panel. Intent-to-treat analysis was conducted using ANCOVA for the primary and secondary outcome variables with Bonferroni correction for multiple comparisons. Results: A total of 99 out of 100 participants completed the study in its entirety. After the 12-wk intervention, participants supplemented with citicoline showed significantly greater improvements in secondary outcomes of episodic memory (assessed by the Paired Associate test), compared with those on placebo (mean: 0.15 vs. 0.06, respectively, P = 0.0025). Composite memory (secondary outcome), calculated using the scores of 4 memory tests, also significantly improved to a greater extent following citicoline supplementation (mean: 3.78) compared with placebo (mean: 0.72, P = 0.0052). Conclusions: Dietary supplementation of citicoline for 12 wk improved overall memory performance, especially episodic memory, in healthy older males and females with AAMI. The findings suggest that regular consumption of citicoline may be safe and potentially beneficial against memory loss due to aging. Keywords: 5′-cytidine diphosphate choline; aging; brain; citicoline; memory loss. Dietary Acid Load and Mortality from All Causes, Cardiovascular Disease, and Cancer: results from the Golestan Cohort Study. Hejazi E, Emamat H, Sharafkhah M, Saidpour A, Poustchi H, Sepanlou SG, Sotoudeh M, Dawsey SM, Boffetta P, Abnet CC, Kamangar F, Etemadi A, Pourshams A, Fazeltabar-Malekshah A, Brennan P, Malekzadeh R, Hekmatdoost A. Br J Nutr. 2021 Aug 16:1-20. doi: 10.1017/S0007114521003135. Online ahead of print. PMID: 34392847 Abstract Given the limited studies, and controversial results on association between dietary acid load and mortality from cardiovascular disease (CVD) and cancers, we aimed to investigate this association in a large population cohort study in Middle-East, with a wide range of dietary acid load.The study was conducted on the platform of the Golestan Cohort Study (GCS), which enrolled 50,045 participants in 2004-2008. Dietary intake was assessed using a validated food frequency questionnaire (FFQ). Dietary potential renal acid load (PRAL) score was calculated from nutrient intake. Death and its causes were identified, and confirmed by two or three physicians. Cox proportional hazards regression was used to estimate HRs and 95% CIs for total and cause specific mortalities. Then, the associations were modeled using restricted cubic splines.PRAL range was -57.36 to +53.81 mEq/d for men and -76.70 to +49.08 for women. During 555,142 person-years of follow-up, we documented 6830 deaths, including 3070 cardiovascular deaths, 1502 cancer deaths and 2258 deaths from other causes. For overall deaths, in final model after adjustment for confounders, participants in the first and 5th quintiles of PRAL had a higher risk of mortality compared to the second quintile of PRAL (HR: 1.08; 95% CI:1.01-1.16 and HR: 1.07; 95% CI: 1.01-1.15, respectively); P for trend <0.05). Participants in the first and 5th quintiles of PRAL had a 12% higher risk of CVD mortality compared to the Q2 of PRAL (HR: 1.12; 95% CI: 1.01-1.25 and HR: 1.12; 95% CI: 1.01-1.26, respectively; P for trend <0.05). We found that all-cause and CVD mortality rates were higher in the lowest and highest PRAL values, in an approximately U-shaped relation (P-values for the overall association and the non-linear association of energy-adjusted PRAL with total mortality were <0.001 and <0.001, and with CVD mortality were 0.008 and 0.003, respectively).Our results highlight unfavorable associations of high acidity and alkalinity of diet with the increased total and CVD mortality risk. It may be important to consider a balanced acid-base diet as a protective strategy to prevent premature death, especially from CVD. Keywords: GCS; Mortality; cancer; cardiovascular; cohort. Estimating Under-recognized COVID-19 Deaths, United States, March 2020-May 2021 using an Excess Mortality Modelling Approach. Iuliano AD, Chang HH, Patel NN, Threlkel R, Kniss K, Reich J, Steele M, Hall AJ, Fry AM, Reed C. Lancet Reg Health Am. 2021 Jul 13:100019. doi: 10.1016/j.lana.2021.100019. Online ahead of print. PMID: 34386789 Free PMC article. Abstract Background: In the United States, Coronavirus Disease 2019 (COVID-19) deaths are captured through the National Notifiable Disease Surveillance System and death certificates reported to the National Vital Statistics System (NVSS). However, not all COVID-19 deaths are recognized and reported because of limitations in testing, exacerbation of chronic health conditions that are listed as the cause of death, or delays in reporting. Estimating deaths may provide a more comprehensive understanding of total COVID-19-attributable deaths. Methods: We estimated COVID-19 unrecognized attributable deaths, from March 2020-April 2021, using all-cause deaths reported to NVSS by week and six age groups (0-17, 18-49, 50-64, 65-74, 75-84, and ≥85 years) for 50 states, New York City, and the District of Columbia using a linear time series regression model. Reported COVID-19 deaths were subtracted from all-cause deaths before applying the model. Weekly expected deaths, assuming no SARS-CoV-2 circulation and predicted all-cause deaths using SARS-CoV-2 weekly percent positive as a covariate were modelled by age group and including state as a random intercept. COVID-19-attributable unrecognized deaths were calculated for each state and age group by subtracting the expected all-cause deaths from the predicted deaths. Findings: We estimated that 766,611 deaths attributable to COVID-19 occurred in the United States from March 8, 2020-May 29, 2021. Of these, 184,477 (24%) deaths were not documented on death certificates. Eighty-two percent of unrecognized deaths were among persons aged ≥65 years; the proportion of unrecognized deaths were 0•24-0•31 times lower among those 0-17 years relative to all other age groups. More COVID-19-attributable deaths were not captured during the early months of the pandemic (March-May 2020) and during increases in SARS-CoV-2 activity (July 2020, November 2020-February 2021). Discussion: Estimating COVID-19-attributable unrecognized deaths provides a better understanding of the COVID-19 mortality burden and may better quantify the severity of the COVID-19 pandemic. Keywords: COVID-19; Excess mortality; Mortality; SARS-CoV-2; Unrecognized deaths. METABOLISM CHANGES WITH AGE, JUST NOT WHEN YOU MIGHT THINK Researchers have precisely measured life’s metabolic highs and lows, from birth to old age, and the findings might surprise you. https://today.duke.edu/2021/08/metabolism-changes-age-just-not-when-you-might-think >>>>>>>>>>>>>>>>>>> Daily energy expenditure through the human life course. Pontzer H, Yamada Y, Sagayama H, Ainslie PN, Andersen LF, Anderson LJ, Arab L, Baddou I, Bedu-Addo K, Blaak EE, Blanc S, Bonomi AG, Bouten CVC, Bovet P, Buchowski MS, Butte NF, Camps SG, Close GL, Cooper JA, Cooper R, Das SK, Dugas LR, Ekelund U, Entringer S, Forrester T, Fudge BW, Goris AH, Gurven M, Hambly C, El Hamdouchi A, Hoos MB, Hu S, Joonas N, Joosen AM, Katzmarzyk P, Kempen KP, Kimura M, Kraus WE, Kushner RF, Lambert EV, Leonard WR, Lessan N, Martin C, Medin AC, Meijer EP, Morehen JC, Morton JP, Neuhouser ML, Nicklas TA, Ojiambo RM, Pietiläinen KH, Pitsiladis YP, Plange-Rhule J, Plasqui G, Prentice RL, Rabinovich RA, Racette SB, Raichlen DA, Ravussin E, Reynolds RM, Roberts SB, Schuit AJ, Sjödin AM, Stice E, Urlacher SS, Valenti G, Van Etten LM, Van Mil EA, Wells JCK, Wilson G, Wood BM, Yanovski J, Yoshida T, Zhang X, Murphy-Alford AJ, Loechl C, Luke AH, Rood J, Schoeller DA, Westerterp KR, Wong WW, Speakman JR; IAEA DLW Database Consortium. Science. 2021 Aug 13;373(6556):808-812. doi: 10.1126/science.abe5017. PMID: 34385400 Abstract Total daily energy expenditure ("total expenditure") reflects daily energy needs and is a critical variable in human health and physiology, but its trajectory over the life course is poorly studied. We analyzed a large, diverse database of total expenditure measured by the doubly labeled water method for males and females aged 8 days to 95 years. Total expenditure increased with fat-free mass in a power-law manner, with four distinct life stages. Fat-free mass-adjusted expenditure accelerates rapidly in neonates to ~50% above adult values at ~1 year; declines slowly to adult levels by ~20 years; remains stable in adulthood (20 to 60 years), even during pregnancy; then declines in older adults. These changes shed light on human development and aging and should help shape nutrition and health strategies across the life span.
  7. Below paper citations and full text links or availability include a short excerpt or my synopsis in square brackets. The email list system is broken. Posts cannot be searched. Many of the posts do not make it to the messages I receive individually and via the daily mailings. Therefore, I am sending this message, comprised of citations papers that seem to be appropriate to the room of the Forum. I will try to also provide full-text links and a very brief excerpt or within brackets my synopsis of the paper. I apologize for the fact some papers discuss results of studies on the overweight or obese, but feel that some benefits seen in such subjects bears on a continuum of benefits accrued by CR and provide incentive to folks who are overweight or obese. Below are today's papers.. The Lancet Volume 388, Issue 10045, 13–19 August 2016, Pages 640–642 Comment Air pollution and heart disease Bert Brunekreef, Barbara Hoffmann doi:10.1016/S0140-6736(16)30375-0 http://www.sciencedirect.com.qe2a-proxy.mun.ca/science/article/pii/S0140673616303750 Joel D Kaufman, Sara D Adar, R Graham Barr, Matthew Budoff, Gregory L Burke, Cynthia L Curl, Martha L Daviglus, Ana V Diez Roux, Amanda J Gassett, David R Jacobs Jr, Richard Kronmal, Timothy V Larson, Ana Navas-Acien, Casey Olives, Paul D Sampson, Lianne Sheppard, David S Siscovick, James H Stein, Adam A Szpiro, Karol E Watson Association between air pollution and coronary artery calcification within six metropolitan areas in the USA (the Multi-Ethnic Study of Atherosclerosis and Air Pollution): a longitudinal cohort study The Lancet, Volume 388, Issue 10045, 13–19 August 2016, Pages 696-704 http://sci-hub.cc/10.1016/s0140-6736(16)00378-0 Summary Background Long-term exposure to fine particulate matter less than 2·5 μm in diameter (PM2·5) and traffic-related air pollutant concentrations are associated with cardiovascular risk. The disease process underlying these associations remains uncertain. We aim to assess association between long-term exposure to ambient air pollution and progression of coronary artery calcium and common carotid artery intima-media thickness. Methods In this prospective 10-year cohort study, we repeatedly measured coronary artery calcium by CT in 6795 participants aged 45–84 years enrolled in the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air) in six metropolitan areas in the USA. Repeated scans were done for nearly all participants between 2002 and 2005, for a subset of participants between 2005 and 2007, and for half of all participants between 2010 and 2012. Common carotid artery intima-media thickness was measured by ultrasound in all participants at baseline and in 2010–12 for 3459 participants. Residence-specific spatio-temporal pollution concentration models, incorporating community-specific measurements, agency monitoring data, and geographical predictors, estimated concentrations of PM2·5 and nitrogen oxides (NOX) between 1999 and 2012. The primary aim was to examine the association between both progression of coronary artery calcium and mean carotid artery intima-media thickness and long-term exposure to ambient air pollutant concentrations (PM2·5, NOX, and black carbon) between examinations and within the six metropolitan areas, adjusting for baseline age, sex, ethnicity, socioeconomic characteristics, cardiovascular risk factors, site, and CT scanner technology. Findings In this population, coronary calcium increased on average by 24 Agatston units per year (SD 58), and intima-media thickness by 12 μm per year (10), before adjusting for risk factors or air pollutant exposures. Participant-specific pollutant concentrations averaged over the years 2000–10 ranged from 9·2–22·6 μg PM2·5/m3 and 7·2–139·2 parts per billion (ppb) NOX. For each 5 μg PM2·5/m3 increase, coronary calcium progressed by 4·1 Agatston units per year (95% CI 1·4–6·8) and for each 40 ppb NOX coronary calcium progressed by 4·8 Agatston units per year (0·9–8·7). Pollutant exposures were not associated with intima-media thickness change. The estimate for the effect of a 5 μg/m3 higher long-term exposure to PM2·5 in intima-media thickness was −0·9 μm per year (95% CI −3·0 to 1·3). For 40 ppb higher NOX, the estimate was 0·2 μm per year (−1·9 to 2·4). Interpretation Increased concentrations of PM2·5 and traffic-related air pollution within metropolitan areas, in ranges commonly encountered worldwide, are associated with progression in coronary calcification, consistent with acceleration of atherosclerosis. This study supports the case for global efforts of pollution reduction in prevention of cardiovascular diseases. Graham A Colditz, Karen M Emmons The role of universal health coverage in reducing cancer deaths and disparities The Lancet, Volume 388, Issue 10045, 13–19 August 2016, Pages 638-640 http://sci-hub.cc/10.1016/s0140-6736(16)30376-2 KME is employed by Kaiser Permanente, a US managed care consortium. Mahiben Maruthappu, Johnathan Watkins, Aisyah Mohd Noor, Callum Williams, Raghib Ali, Richard Sullivan, Thomas Zeltner, Rifat Atun Economic downturns, universal health coverage, and cancer mortality in high-income and middle-income countries, 1990–2010: a longitudinal analysis The Lancet, Volume 388, Issue 10045, 13–19 August 2016, Pages 684-695 http://sci-hub.cc/10.1016/s0140-6736(16)00577-8 Summary Background The global economic crisis has been associated with increased unemployment and reduced public-sector expenditure on health care (PEH). We estimated the effects of changes in unemployment and PEH on cancer mortality, and identified how universal health coverage (UHC) affected these relationships. Methods For this longitudinal analysis, we obtained data from the World Bank and WHO (1990–2010). We aggregated mortality data for breast cancer in women, prostate cancer in men, and colorectal cancers in men and women, which are associated with survival rates that exceed 50%, into a treatable cancer class. We likewise aggregated data for lung and pancreatic cancers, which have 5 year survival rates of less than 10%, into an untreatable cancer class. We used multivariable regression analysis, controlling for country-specific demographics and infrastructure, with time-lag analyses and robustness checks to investigate the relationship between unemployment, PEH, and cancer mortality, with and without UHC. We used trend analysis to project mortality rates, on the basis of trends before the sharp unemployment rise that occurred in many countries from 2008 to 2010, and compared them with observed rates. Results Data were available for 75 countries, representing 2·106 billion people, for the unemployment analysis and for 79 countries, representing 2·156 billion people, for the PEH analysis. Unemployment rises were significantly associated with an increase in all-cancer mortality and all specific cancers except lung cancer in women. By contrast, untreatable cancer mortality was not significantly linked with changes in unemployment. Lag analyses showed significant associations remained 5 years after unemployment increases for the treatable cancer class. Rerunning analyses, while accounting for UHC status, removed the significant associations. All-cancer, treatable cancer, and specific cancer mortalities significantly decreased as PEH increased. Time-series analysis provided an estimate of more than 40 000 excess deaths due to a subset of treatable cancers from 2008 to 2010, on the basis of 2000–07 trends. Most of these deaths were in non-UHC countries. Interpretation Unemployment increases are associated with rises in cancer mortality; UHC seems to protect against this effect. PEH increases are associated with reduced cancer mortality. Access to health care could underlie these associations. We estimate that the 2008–10 economic crisis was associated with about 260 000 excess cancer-related deaths in the Organisation for Economic Co-operation and Development alone. [OP.2A.09] SYSTOLIC BLOOD PRESSURE VARIATION DURING 6 YEARS AND MORTALITY: THE AGE AMPLIFIES THE IMPACT OF A SPONTANEOUS INCREASE OR REDUCTION OF PRESSURE AMONG HYPERTENSIVE: IPC COHORT. Thomas-Jean F, Pannier B, Hanon O, Czernichow S, Lemogne C, Simon T, Simon J, Danchin N. J Hypertens. 2016 Sep;34 Suppl 2:e18. doi: 10.1097/01.hjh.0000491374.01833.d7. PMID: 27508617 [The abstract is pdf-availed.] Among normotensives, increase SBP has a deleterious effect only among subjects before 55 years old [OP.LB.02.09] WHAT ANGIOTENSIN CONVERTING ENZYME GENOTYPE AND HIGH BLOOD PRESSURE HAVE IN COMMON IN PORTUGUESE CENTENARIANS? Pereira Da Silva A, Ramos Marques N, Matos A, Gil A, Gorjão Clara J, Bicho M. J Hypertens. 2016 Sep;34 Suppl 2:e80-1. doi: 10.1097/01.hjh.0000491545.64127.b0. PMID: 27508809 [The abstract is pdf-availed.] [Not a prospective study but they compared centenarians with those unlikely to get that old and found that it was but was not only genes that seem to get them there -- hypertension is a risk for the oldest old too.] Association between body mass index and mortality in a prospective cohort of Chinese adults. Sun H, Ren X, Chen Z, Li C, Chen S, Wu S, Chen Y, Yang X. Medicine (Baltimore). 2016 Aug;95(32):e4327. PMID: 27512844 http://journals.lww.com/md-journal/Fulltext/2016/08090/Association_between_body_mass_index_and_mortality.10.aspx lowest risk of all-cause mortality was seen among persons with a BMI of 24 to 28 kg/m in male ... in female, a high BMI was associated with increased mortality, and a BMI of <18.5 kg/m was associated with the lowest risk. Personalized risk prediction for type 2 diabetes: the potential of genetic risk scores. Läll K, Mägi R, Morris A, Metspalu A, Fischer K. Genet Med. 2016 Aug 11. doi: 10.1038/gim.2016.103. [Epub ahead of print] PMID: 27513194 http://biorxiv.org/content/biorxiv/early/2016/02/29/041731.full.pdf genetic risk score (GRS) that has the strongest association with type 2 diabetes (T2D) ... Adding GRS to the prediction model for 5-year T2D risk resulted in continuous net reclassification improvement of 0.324 (95% CI: 0.211-0.444). In addition, a significant effect of the GRS on all-cause and cardiovascular mortality was observed. [OP.1C.09] REPRODUCTIVE HISTORY OF WOMEN AS A DETERMINANT OF ARTERIAL STIFFNESS - THE MALMÖ DIET CANCER STUDY. Nilsson PM, Carlqvist E, Gottsäter M. J Hypertens. 2016 Sep;34 Suppl 2:e10. doi: 10.1097/01.hjh.0000491354.79923.fb. PMID: 27508557 carotid femoral pulse wave velocity (c-f PWV) ... Reproductive Risk Index (RRI) was created to capture the combined effect of separate reproductive variables (age at menarche, parity, and age at menopause). ... Age at menarche (beta = -0.040, p < 0.05) was inversely associated with logarithmic c-f PWV ... RRI was significantly associated (beta = 0.050, p < 0.05) with non-logarithm (supposedly non-linear) c-f PWV. Subjective mood and energy levels of healthy weight and overweight/obese healthy adults on high-and low-glycemic load experimental diets. Breymeyer KL, Lampe JW, McGregor BA, Neuhouser ML. Appetite. 2016 Aug 6. pii: S0195-6663(16)30322-1. doi: 10.1016/j.appet.2016.08.008. [Epub ahead of print] PMID: 27507131 http://sci-hub.cc/10.1016/j.appet.2016.08.008 In conclusion, a high-glycemic load diet was associated with higher depression symptoms, total mood disturbance, and fatigue compared to a low-glycemic load diet especially in overweight/obese, but otherwise healthy, adults. Lifetime grain consumption and breast cancer risk. Farvid MS, Cho E, Eliassen AH, Chen WY, Willett WC. Breast Cancer Res Treat. 2016 Aug 10. [Epub ahead of print] PMID: 27510186 http://sci-hub.cc/10.1007/s10549-016-3910-0 adult brown rice which was associated with lower risk of overall and premenopausal breast cancer (for each 2 servings/week: RR 0.94; 95 % CI 0.89-0.99 and RR 0.91; 95 % CI 0.85-0.99, respectively) and adult white bread intake which was associated with increased overall breast cancer risk (for each 2 servings/week: RR 1.02; 95 % CI 1.01-1.04), as well as breast cancer before and after menopause. Further, pasta intake was inversely associated with overall breast cancer risk. Vegetarian diet reduces the risk of hypertension independent of abdominal obesity and inflammation: a prospective study. Chuang SY, Chiu TH, Lee CY, Liu TT, Tsao CK, Hsiung CA, Chiu YF. J Hypertens. 2016 Aug 10. [Epub ahead of print] PMID: 27512965 [The below paper is pdf-availed.] Taiwanese vegetarians had lower incidence of hypertension than nonvegetarians. [OP.1B.04] ASSOCIATIONS OF 15-YEAR AVERAGE POTASSIUM INTAKE WITH LONG-TERM CARDIOVASCULAR AND RENAL OUTCOME IN THE OUTPATIENT CLINICAL SETTING. Van Noordenne N, Olde Engberink RH, Van Den Hoek TC, Van Den Born BJ, Vogt L. J Hypertens. 2016 Sep;34 Suppl 2:e6. doi: 10.1097/01.hjh.0000491339.74085.91. PMID: 27508744 [The abstract is pdf-availed.] high potassium intake is associated with renoprotection ... not ... CV disease and mortality. xx Blood pressure variability and cardiovascular disease: systematic review and meta-analysis. Stevens SL, Wood S, Koshiaris C, Law K, Glasziou P, Stevens RJ, McManus RJ. BMJ. 2016 Aug 9;354:i4098. doi: 10.1136/bmj.i4098. PMID: 27511067 http://www.bmj.com/content/354/bmj.i4098 http://www.bmj.com/content/bmj/354/bmj.i4098.full.pdf Increased long term variability in systolic blood pressure was associated with risk of all cause mortality (hazard ratio 1.15, 95% confidence interval 1.09 to 1.22), cardiovascular disease mortality (1.18, 1.09 to 1.28), cardiovascular disease events (1.18, 1.07 to 1.30), coronary heart disease (1.10, 1.04 to 1.16), and stroke (1.15, 1.04 to 1.27). Increased mid-term and short term variability in daytime systolic blood pressure were also associated with all cause mortality (1.15, 1.06 to 1.26 and 1.10, 1.04 to 1.16, respectively). Effects of the Mediterranean Diet on Cardiovascular Outcomes-A Systematic Review and Meta-Analysis. Liyanage T, Ninomiya T, Wang A, Neal B, Jun M, Wong MG, Jardine M, Hillis GS, Perkovic V. PLoS One. 2016 Aug 10;11(8):e0159252. doi: 10.1371/journal.pone.0159252. eCollection 2016. PMID: 27509006 Free Article http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0159252 http://journals.plos.org/plosone/article/asset?id=10.1371%2Fjournal.pone.0159252.PDF evidence is limited and highly variable. Results must be interpreted with caution. https://www.crsociety.org/topic/11225-metabolism-aging-cr-exercise/?hl=%2Bpeak+%2Boxygen+%2Bconsumption Circadian Characteristics of Older Adults and Aerobic Capacity. Dupont Rocher S, Bessot N, Sesboüé B, Bulla J, Davenne D. J Gerontol A Biol Sci Med Sci. 2016 Jun;71(6):817-22. doi: 10.1093/gerona/glv195. Epub 2015 Nov 23. PMID: 26602866 http://sci-hub.cc/10.1093/gerona/glv195 Abstract BACKGROUND: Alteration of circadian rhythmicity with aging might depend on physical aerobic capacity. METHODS: Three groups of participants were established based on their peak oxygen consumption (Group 1 < 20mL/min/kg; Group 2 > 20mL/min/kg and <30mL/min/kg; Group 3 > 30mL/min/kg). Each participant had an individual evaluation of their circadian rhythmicity characteristics through two well-known circadian rhythms: core temperature and rest/activity cycles. Nocturnal sleep was also recorded using actimetry and diurnal vigilance tested in a car driving simulator. RESULTS: The amplitude of the oral temperature fluctuations for Group 1 is significantly lower (p < .05) than that of Group 3. Group 2 (p < .01) and Group 3 (p < .05) were significantly more active during the day than Group 1. The index of inactivity during the night for Groups 2 (p < .05) and 3 (p < .01) was higher than Group 1. Results of the car driving simulation showed that for Group 1, the number of lane crossings was significantly higher than Groups 2 (p < .01) and 3 (p < .01). In addition, diurnal vigilance was lower in Group 1. CONCLUSIONS: The biological clock seems to be enhanced in older participants with a higher level of physical capacity. KEYWORDS: Exercise; Physical activity; Physical performance
  8. AlPater

    Al's CR updates

    Protective Features of Calorie Restriction on Cuprizone-induced Demyelination via Modulating Microglial Phenotype. Zarini D, Pasbakhsh P, Nekoonam S, Mojaverrostami S, Ghasemi S, Shabani M, Kashani IR. J Chem Neuroanat. 2021 Aug 12:102013. doi: 10.1016/j.jchemneu.2021.102013. Online ahead of print. PMID: 34391881 Abstract Multiple sclerosis (MS) is an immune-mediated demyelinating disorder in the central nervous system (CNS) with no definitive treatment, but it can be alleviated by changing life habits. Calorie restriction (CR) is effective in preventing or treating metabolic and autoimmune disorders. CR is one of the helpful approaches to control the progression of MS. In the present study, we investigated the preventive effect of caloric restriction on cuprizone induced-demyelination, a model of multiple sclerosis. To induce acute demyelination in C57/BL6 mice, we added 0.2% Cuprizone (CPZ) to their diet for 6 weeks. To induce calorie restriction, 10% Carboxymethyl cellulose (CMC) was added to the diet as a dietary cellulose fiber for 6 weeks. Remyelination was studied by luxol fast blue (LFB) staining. Microglia activity, M1 and M2 microglial/macrophage phenotypes were assessed by immunohistochemistry of Iba-1, iNOS and Arg-1, respectively. The expression of targeted genes was assessed by the real-time polymerase chain reaction. Luxol fast blue (LFB) staining showed that the CR regimen could decrease the cuprizone-induced demyelination process (p < 0.01). Moreover, the CR application could improve balance and motor performance in cuprizone-intoxicated mice by significantly enhancing protein and gene expression of Sirt1, M2 microglial phenotype marker (Arg-1) and Akt1 gene expression, also decreased M1 microglial phenotype marker (iNOS), Akt2 and P53 gene expressions (p < 0.05). Cumulatively, it can be concluded that caloric restriction was able to counteract MS symptoms through alleviating inflammatory responses. Keywords: Calorie restriction; Cuprizone; Demyelination; Microglia; Multiple Sclerosis. Lamin regulates the dietary restriction response via the mTOR pathway in Caenorhabditis elegans. Charar C, Metsuyanim-Cohen S, Bar DZ. J Cell Sci. 2021 Aug 12:jcs.258428. doi: 10.1242/jcs.258428. Online ahead of print. PMID: 34383046 Abstract Animals subjected to dietary restriction (DR) have reduced body size, low fecundity, slower development, lower fat content and longer life span. We identified lamin as a regulator of multiple dietary restriction phenotypes. Downregulation of lmn-1, the single Caenorhabditis elegans lamin gene, increased animal size and fat content, specifically in DR animals. The LMN-1 protein acts in the mTOR pathway, upstream to RAPTOR and S6K, key component and target of mTOR complex 1 (mTORC1), respectively. DR excludes the mTORC1 activator RAGC-1 from the nucleus. Downregulation of lmn-1 restores RAGC-1 to the nucleus, a necessary step for the activation of the mTOR pathway. These findings further link lamin to metabolic regulation. Keywords: Caenorhabditis elegans; Dietary restriction; Lamin; mTOR.
  9. AlPater

    Are potatoes wrongly vilified?

    I think potatoes are okay. They contain much less sugars than carrots and their nutritiondata rating for "Optimal health" is slightly better than carrots: https://nutritiondata.self.com/facts/vegetables-and-vegetable-products/2550/2 https://nutritiondata.self.com/facts/vegetables-and-vegetable-products/2383/2 But their GI is higher: https://lpi.oregonstate.edu/mic/food-beverages/glycemic-index-glycemic-load
  10. J Natl Med Assoc. 2002 Feb;94(2):88-99. Less is better Thomas T Samaras, Harold Elrick PMID: 11853051 PMCID: PMC2594131 Free PMC article Abstract The "more is better" credo is evaluated in terms of its harmful ramifications on human health, the environment, and the survival of the human race. The trend towards greater height and body weight in developed countries is evaluated in terms of its negative aspects on health and longevity. The benefits of reduced caloric intake are discussed. Countries that survive on lower food intakes are shown to have much less heart disease, such as South Africa, where rural blacks outlive whites and also have a higher percentage of centenarians. The risks of increasing birth weight are discussed in terms of promoting cancer and overweight in adulthood. Rapid childhood growth also is shown to have risks because rapid maturity is in conflict with the need to have more time to learn about our complex world before reaching reproductive capability. The increase in the average size of humans aggravates our burgeoning population numbers, placing even greater demands on our need for fresh water, energy, resources, and a clean invironment. Many good things come in large packages, such as elephants, whales, and trees. While Sumo wrestlers, football players, and basketball players play an important role in our world, their small numbers do not pose a threat to our survival. However, their body habitus should not be the goal for the average male of the future.
  11. Yes, I got two shots of Pfizer. BTW, my wife got COVID some months ago; I got my first shot on the same trip before she was tested and I was tested the next day when she got her results (I should have got tested when she did); I was surprised not to test positive the next day after she did, despite kissing her in her pre-symptomatic stage and until she tested positive after she had symptoms for a while; and my never having symptoms thereafter.
  12. I agree with you, Saul. This pandemic has brought out characteristics of quite a few people that surprise me in their susceptibility to misinformation, and their views on vaccines, some held even before this pandemic. I was skeptical that vaccines could be developed with the speed which with they were, but here we are with multiple vaccines that have been rigorously tested by the manufacturers and in the field. Infections, hospitalizations, ICU admissions, deaths and long COVID cases have diminished in parallel with vaccinations. All the while, some people are presenting scenarios for COVID vaccines that have not been found for vaccines for other diseases, some of which vaccines use similar methods for vaccine development.
  13. https://www.kff.org/policy-watch/covid-19-vaccine-breakthrough-cases-data-from-the-states/ gives the import of vaccination on cases, hospitalizations, and deaths for individual states. About half of Californians are vaccinated, and the vast majority of the sick are unvaccinated. And vaccinations are preventing many others from becoming infected, while the unvaccinated are like typhoid Mary.
  14. I strongly disagree with your opinions. I think selection is most likely to occur in individual infections. There are a huge number of virus particles produced in each infection in unvaccinated people, which are then met with an immune response which over many days kill off virus particles while they continue to propagate until the immune system wins or the host dies. The virus particles are in overwhelming numbers compared to the hosts once the infection gets going. Vaccines will cut the viral propagation short; vaccines are highly effective at preventing any kind of propagation at all. And, getting herd immunity stops the virus. It was done with small pox and polio. If worse comes to worse, modified vaccines can be readily generated, depending the degree intransidence of the unvaccinated in keeping this pestilence going.
  15. Alcohol use and cardiometabolic risk in the UK Biobank: A Mendelian randomization study. Lankester J, Zanetti D, Ingelsson E, Assimes TL. PLoS One. 2021 Aug 11;16(8):e0255801. doi: 10.1371/journal.pone.0255801. eCollection 2021. PMID: 34379647 Abstract Observational studies suggest alcohol use promotes the development of some adverse cardiometabolic traits but protects against others including outcomes related to coronary artery disease. We used Mendelian randomization (MR) to explore causal relationships between the degree of alcohol consumption and several cardiometabolic traits in the UK Biobank. Using the well-established ADH1B Arg47His variant (rs1229984) and up to 24 additional SNPs recently found to be associated with alcohol consumption in an independent dataset as instruments, we conducted two-stage least squares and inverse weighted variance MR analyses, both as one-sample analyses in the UK Biobank and as two-sample analyses in external consortia. In the UK Biobank inverse variance weighted analyses, we found that one additional drink of alcohol per day was positively associated with systolic blood pressure (beta = 2.65 mmHg [1.40, 3.89]), hemorrhagic stroke (OR = 2.25 [1.41, 3.60]), and atrial fibrillation (OR = 1.26 [1.07, 1.48]), which were replicated in multivariable analyses. Alcohol was also associated with all cardiovascular disease and all-cause death. A positive association with myocardial infarction did not replicate in multivariable analysis, with suggestive mediation through blood pressure; similarly, a positive association between alcohol use with type 2 diabetes was mitigated by BMI in multivariable analysis. Findings were generally null in replication with two-sample analyses. Alcohol was not protective for any disease outcome with any analysis method, dataset, or strata. Stratifications by sex and smoking in the UK Biobank revealed higher point estimates of risk for several outcomes for men and mixed results for smoking strata, but no statistically significant heterogeneity. Our results are consistent with an overall harmful and/or null effect of alcohol on cardiometabolic health at all levels of use and suggest that even moderate alcohol use should not be promoted as a part of a healthy diet and lifestyle. Revisiting the association of sedentary behavior and physical activity with all-cause mortality using a compositional approach: the Women's Health Study. Migueles JH, Lee IM, Sanchez CC, Ortega FB, Buring JE, Shiroma EJ. Int J Behav Nutr Phys Act. 2021 Aug 10;18(1):104. doi: 10.1186/s12966-021-01173-0. PMID: 34376213 Abstract Background: While physical activity has consistently been associated with decreased mortality rates, it remains unknown if there is a single "ideal" combination of time in physical activities of different intensities and sedentary behavior (SB) associated with the lowest rate. This study examined the associations of combinations of time in moderate-to-vigorous intensity (MVPA), higher-light intensity (HLPA), lower-light intensity activities (LLPA), and SB with mortality rates in older women. Methods: This prospective cohort study included 16,676 older women from throughout the United States enrolled in the Women's Health Study. Women wore accelerometers on their hip from 2011 to 2015 and were followed through 2017 (mean (SD) of 4.3 (1.1) years). Deaths were confirmed with medical records, death certificates, or the National Death Index. Compositional Cox regression models were used. Results: The mean (SD) age was 72 (5.7) years at accelerometer wear; 503 women died. Compared to the least active women (mean, 3 min/day MVPA, 27 min/day HLPA, 162 min/day LLPA, and 701 min/day SB): compositional models showed an inverse L-shaped dose-response association of MVPA replacing other behaviors with mortality rates mortality rates (P = .02); SB relative to LLPA, HLPA, and MVPA was directly associated with mortality rates in a curvilinear dose-response manner (P < .001); replacing 10 min of SB for MVPA (HR (95% CI) = .86 (.73-.98)) or for HLPA (HR (95% CI.94 (.88-1.00)) associated with 14 and 6% lower mortality rates, respectively; a 47% risk reduction (HR [95% CI] = .53 [.42-.64]) was observed among women meeting physical activity guidelines (mean, 36 min/day MVPA, 79 min/day HLPA, 227 min/day LLPA and 549 min/day SB); and similar mortality rate reductions of 43% (HR (95% CI) = .57 (.41-.73)) were observed with increases in HLPA and LLPA without increasing MVPA, e.g., reallocating SB to 90 min/day of HLPA plus 120 min/day of LLPA. Conclusions: There was no "ideal" combination of physical activities of different intensities and SB associated with the lowest mortality rates. Of particular relevance to older women, replacing SB with light intensity activity was associated with lower mortality rates, and "mixing and matching" times in different intensities yielded equivalent mortality risk reductions. Familial factors, diet, and risk of cardiovascular disease: a cohort analysis of the UK Biobank. Zhang H, Zeng Y, Yang H, Hu Y, Hu Y, Chen W, Ying Z, Sun Y, Qu Y, Li Q, Valdimarsdóttir UA, Song H. Am J Clin Nutr. 2021 Aug 10:nqab261. doi: 10.1093/ajcn/nqab261. Online ahead of print. PMID: 34375391 Abstract Background: Both diet and familial factors have a major role in the development of cardiovascular disease (CVD). However, it remains unclear whether familial predisposition to CVD modifies the association between dietary factors and CVD. Objectives: The aim was to assess whether the association between diet and CVD varies with familial predisposition to CVD. Methods: In this prospective cohort of the UK Biobank, 462,155 CVD-free participants were included in 2006-2010 and followed for CVD incidence until 2020. Food intake was measured using a short food-frequency questionnaire. Familial predisposition was measured by self-reported family history of CVD and by polygenic risk score (PRS) for CVD based on summary statistics of independent genome-wide association studies. Results: During a median follow-up of 11.2 y, 46,164 incident CVD cases were identified. A moderately higher risk of CVD was associated with more frequent processed-meat consumption, with an adjusted HR of 1.07 (95% CI: 1.03, 1.11; highest vs. lowest level). Conversely, intakes of fish, cheese, vegetables, and fruit were each associated with reduced CVD risk [HR (95% CI): 0.92 (0.89, 0.96), 0.90 (0.86, 0.94), 0.98 (0.95, 1.00), and 0.93 (0.89, 0.96), respectively]. Stratification analyses by family history of CVD and by PRS for CVD revealed an inverse association between CVD and intakes of fish and cheese, for both subgroups with and without a familial predisposition to CVD. Notably, while the association between processed-meat intake and CVD was restricted to individuals with a familial predisposition to CVD [e.g., HR: 1.11 (1.05, 1.16) and 1.03 (0.97, 1.10) for with and without a family history, respectively, P-interaction < 0.001], the risk reduction of CVD associated with vegetable and fruit intake was only noted among participants without a CVD familial predisposition [e.g., HR for fruit consumption: 1.00 (0.97, 1.03) and 0.91 (0.87, 0.95), respectively, P < 0.001]. Conclusions: Familial factors modify the association between diet and CVD, underscoring the need for personalized dietary guidelines for CVD prevention. Keywords: cardiovascular disease; family history of cardiovascular disease; food intake; modification effect; polygenic risk score; risk factor. Time-restricted feeding prevents metabolic diseases through the regulation of galanin/GALR1 expression in the hypothalamus of mice. Sun J, She Y, Fang P, Gu X, Zhang Z. Eat Weight Disord. 2021 Aug 9. doi: 10.1007/s40519-021-01280-8. Online ahead of print. PMID: 34370270 Abstract Purpose: Time-restricted feeding (TRF) reverses obesity and insulin resistance, yet the central mechanisms underlying its beneficial effects are not fully understood. Recent studies suggest a critical role of hypothalamic galanin and its receptors in the regulation of energy balance. It is yet unclear whether TRF could regulate the expression of galanin and its receptors in the hypothalamus of mice fed a high-fat diet. Methods: To test this effect, we subjected mice to either ad lib or TRF of a high-fat diet for 8 h per day. After 4 weeks, galanin and many neuropeptides associated with the function of metabolism were examined. Results: The present findings showed that mice under TRF consume equivalent calories from a high-fat diet as those with ad lib access, yet are protected against obesity and have improved glucose metabolism. Plasma galanin, orexin A, irisin and adropin levels were significantly reversed by TRF regimen. Besides, TRF regimen reversed the progression of metabolic disorders in mice by increasing GLUT4 and PGC-1α expression in skeletal muscles. Moreover, the levels of galanin and GALR1 expression were severely diminished in the hypothalamus of the TRF mice, whereas GALR2 was highly expressed. Conclusions: TRF diminished galanin and GALR1 expression, and increased GALR2 expression in the hypothalamus of mice fed a high-fat diet. The current studies provide additional evidence that TRF is effective in improving HFD-induced hyperglycemia and insulin resistance in mice, and this effect could be associated with TRF-induced changes of the galanin systems in the hypothalamus. Association between body mass index, its change and cognitive impairment among Chinese older adults: a community-based, 9-year prospective cohort study. Wu S, Lv X, Shen J, Chen H, Ma Y, Jin X, Yang J, Cao Y, Zong G, Wang H, Yuan C. Eur J Epidemiol. 2021 Aug 9. doi: 10.1007/s10654-021-00792-y. Online ahead of print. PMID: 34370136 Abstract To examine the association of baseline body mass index (BMI) and BMI change with cognitive impairment among older adults in China. The study included data from the Chinese Longitudinal Healthy Longevity Study, a national community-based prospective cohort study from 2002 to 2018. Baseline BMI and BMI change were available for 12,027 adults aged older than 65 years. Cognitive impairment was defined as Chinese version of the Mini Mental State Examination score lower than 18. Multivariable Cox proportional hazard model was used. Among 12,027 participants (mean age was 81.23 years old and 47.48% were male), the proportion of underweight, normal, overweight and obese at baseline was 33.87%, 51.39%, 11.39% and 3.34%, respectively. During an average of 5.9 years' follow-up, 3086 participants (4.35 per 100 person-years) with incident cognitive impairment were identified. Compared with normal weight group, adjusted hazard ratio (AHR) for cognitive impairment was 0.86 (95% CI 0.75-0.99) among overweight group, whereas corresponding AHR was 1.02 (95% CI 0.94-1.10) in underweight and 1.01 (95% CI 0.80-1.28) in obese participants. Large weight loss (< -10%) was significantly associated with an increased risk of cognitive impairment (AHR, 1.42, 95% CI 1.29-1.56), compared to stable weight status group (-5% ~ 5%). In the restricted cubic spline models, BMI change showed a reverse J-shaped association with cognitive impairment. BMI-defined overweight, but not obesity, was associated with a lower risk of cognitive impairment among elderly Chinese adults, while large weight loss was associated with an increased risk. These findings are consistent with weight loss in the prodromal phase of dementia. Keywords: BMI; BMI change; Chinese; Cognitive impairment; Cohort; Older adults. Associations of plasma metal concentrations with the risks of all-cause and cardiovascular disease mortality in Chinese adults. Shi L, Yuan Y, Xiao Y, Long P, Li W, Yu Y, Liu Y, Liu K, Wang H, Zhou L, Yang H, Li X, He M, Wu T. Environ Int. 2021 Aug 5;157:106808. doi: 10.1016/j.envint.2021.106808. Online ahead of print. PMID: 34365319 Abstract Background: Exposure to metals/metalloids from both the natural environment and anthropogenic sources have a complex influence on human health. However, relatively few studies have explored the relations of exposure to multiple metals/metalloids with mortality. Therefore, this prospective study aims to examine the relations of multiple metal/metalloids exposures with all-cause and cardiovascular disease (CVD) mortality. Methods: A total of 6155 participants within the Dongfeng-Tongji (DF-TJ) cohort were involved in this analysis, which were followed for mortality until December 31, 2018. We applied inductively coupled plasma mass spectrometry (ICP-MS) to measure baseline plasma concentrations of 23 metals. We utilized Cox regression models to calculate the hazard ratios (HRs) for all-cause and CVD mortality associated with metal concentrations. We proposed plasma metal score to assess the simultaneous exposure to multiple metals through summing each metal concentration weighted by the regression coefficients with all-cause mortality. Results: During the follow-up (mean duration, 9.8 years), we ascertained 876 deaths, including 416 deaths of CVD (157 deaths of coronary heart disease and 259 deaths of stroke). In the multiple-metals model, after adjusting for potential confounders, plasma copper, molybdenum, and vanadium were positively associated with all-cause mortality, whereas manganese, selenium, and thallium were negatively associated with the risk of all-cause mortality, with adjusted HRs (95% Confidence Interval, CI) of the fourth quartiles were 1.73 (1.42-2.11, P-trend < 0.001) for copper, 1.33 (1.09-1.63, P-trend = 0.005) for molybdenum, 1.43 (1.16-1.77, P-trend < 0.001) for vanadium, 0.74 (0.58-0.94, P-trend = 0.005) for manganese, 0.68 (0.56-0.83, P-trend < 0.001) for selenium, and 0.74 (0.59-0.92, P-trend = 0.002) for thallium, respectively. Positive associations were observed between plasma copper, molybdenum, vanadium concentrations and CVD mortality, whereas negative associations were found for plasma selenium and thallium concentrations with CVD mortality in the multiple-metals model. Compared with the first quartiles, the HRs of fourth quartiles were 1.94 (1.45-2.58, P-trend < 0.001) for copper, 1.72 (1.26-2.35, P-trend < 0.001) for molybdenum, 1.81 (1.32-2.47, P-trend < 0.001) for vanadium, 0.67 (0.50-0.89, P-trend = 0.003) for selenium, and 0.58 (0.41-0.81, P-trend < 0.001) for thallium, respectively. The plasma metal score was significantly associated with higher risks of all-cause and CVD death in dose-response fashions. When compared with the first quartiles of plasma metal score, the HRs of fourth quartiles were 2.16 (1.76-2.64; P-trend < 0.001) for all-cause mortality and 3.00 (2.24-4.02; P-trend < 0.001) for CVD mortality. Conclusions: The study indicated that several plasma metals/metalloids were key determinants and predictors of all-cause and CVD death in the Chinese population. Our findings highlighted the importance to comprehensively assess and monitor multiple metals/metalloids exposures. Keywords: All-cause mortality; CVD mortality; Manganese; Molybdenum; Plasma metal score; Prospective study.
  16. AlPater

    Spicy food and dementia risk?

    Holy hot hedes. 50 g chili/day. No wonder so few ate that much chili. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6566199/pdf/nutrients-11-01183.pdf
  17. On a quick read of your article, this sounds like another case of a beautiful theory slain by the ugly facts. Prostate cancer patients did not get more metastasis if they ate more peanuts, for example. “Reassuringly though, a large US study reported no significant impact of peanut consumption on cancer mortality. In another study, peanut consumption was reported to have no significant effect on prognosis in men with established prostate cancer.
  18. As I said, I hate videos. This paper was not previously posted: Relationship between serum B12 concentrations and mortality: experience in NHANES. Wolffenbuttel BHR, Heiner-Fokkema MR, Green R, Gans ROB. BMC Med. 2020 Oct 9;18(1):307. doi: 10.1186/s12916-020-01771-y. PMID: 33032595 Free PMC article. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545540/pdf/12916_2020_Article_1771.pdf Abstract Background: There is conflicting evidence in the literature on the association between (elevated) serum B12 concentrations and subsequent disease or mortality. We evaluated in the NHANES general population the association of serum B12 concentrations as well as vitamin B12 supplement intake with all-cause, cardiovascular, and cancer-related mortality, while taking into account demographic and lifestyle factors and significant other diseases which are known to be associated with poorer outcome. Methods: The main outcomes of our study were all-cause mortality, cardiovascular mortality, and cancer-related mortality. Mortality status and cause of death were determined by NHANES-linked National Death Index public access files through December 31, 2015. The association of serum B12 concentrations and vitamin B12 supplement intake with mortality was assessed with Cox proportional hazard (PH) models, with adjustment for a number of relevant demographic and lifestyle factors and comorbidity. Results: The final study population of 24,262 participants had a mean age of 48 (SD 19) years; 50.1% were males. The median follow-up duration was 109 months (range 1-201 months). On the census day of December 31, 2015, 3023 participants were determined as deceased (12.5%). The fully adjusted Cox PH model indicated that low serum B12 concentrations < 140 pmol/l were associated with a small increase in all-cause (hazard ratio, HR 1.39, 95% CI 1.08-1.78, p = 0.011) and cardiovascular (HR 1.64, 95% CI 1.08-2.47, p = 0.020) mortality. Similarly, high serum B12 concentrations > 700 pmol/l were associated with an increase in cardiovascular mortality only (HR 1.45, 95% CI 1.01-2.06, p = 0.042). Participants with a diagnosis of hypertension, dyslipidemia, CVD, and cancer more frequently used vitamin B12-containing supplements than those without these diagnoses. We could not demonstrate an association between vitamin B12 supplement intake and mortality, when adjusted for comorbidity. Conclusions: In the general population of NHANES, low serum B12 concentrations were associated with a moderate increase in all-cause mortality. There was a small but significant increase in cardiovascular mortality in the groups with low or high serum B12. High intake of vitamin B12 in the form of supplements was not associated with any adverse effect on mortality and therefore can be regarded as safe. Keywords: Epidemiology; Mortality; NHANES; Prognosis; Supplement; Vitamin B12.
  19. New Sci. 2021 Feb 27;249(3323):10-11. doi: 10.1016/S0262-4079(21)00303-1. Epub 2021 Mar 3. Children with long covid Helen Thomson PMID: 33686318 PMCID: PMC7927578 DOI: 10.1016/S0262-4079(21)00303-1 Free PMC article https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927578/ Abstract Almost half of children who contract covid-19 may have lasting symptoms, which should factor into decisions on reopening schools, reports Helen Thomson.
  20. NEW BioNTech shares surge as vaccine-maker's profits soar on booming outlook German pharmaceutical maker BioNTech, which developed the first widely used coronavirus vaccine with Pfizer, swung to a huge profit in the second quarter on record sales. https://www.cbc.ca/news/business/biontech-earnings-1.6134619
  21. Fasting may help ward off infections, study in mice suggests Date: August 5, 2021 Source: PLOS Summary: Fasting before and during exposure to Salmonella enterica bacteria protects mice from developing a full-blown infection, in part due to changes in the animals' gut microbiomes, according to new research. https://www.sciencedaily.com/releases/2021/08/210805140612.htm >>>>>>>>>>>>>> Fasting increases microbiome-based colonization resistance and reduces host inflammatory responses during an enteric bacterial infection. Graef FA, Celiberto LS, Allaire JM, Kuan MTY, Bosman ES, Crowley SM, Yang H, Chan JH, Stahl M, Yu H, Quin C, Gibson DL, Verdu EF, Jacobson K, Vallance BA. PLoS Pathog. 2021 Aug 5;17(8):e1009719. doi: 10.1371/journal.ppat.1009719. eCollection 2021 Aug. PMID: 34352037 Free PMC article. Abstract Reducing food intake is a common host response to infection, yet it remains unclear whether fasting is detrimental or beneficial to an infected host. Despite the gastrointestinal tract being the primary site of nutrient uptake and a common route for infection, studies have yet to examine how fasting alters the host's response to an enteric infection. To test this, mice were fasted before and during oral infection with the invasive bacterium Salmonella enterica serovar Typhimurium. Fasting dramatically interrupted infection and subsequent gastroenteritis by suppressing Salmonella's SPI-1 virulence program, preventing invasion of the gut epithelium. Virulence suppression depended on the gut microbiota, as Salmonella's invasion of the epithelium proceeded in fasting gnotobiotic mice. Despite Salmonella's restored virulence within the intestines of gnotobiotic mice, fasting downregulated pro-inflammatory signaling, greatly reducing intestinal pathology. Our study highlights how food intake controls the complex relationship between host, pathogen and gut microbiota during an enteric infection. Carrots vs. Russet Potato https://www.soupersage.com/compare-nutrition/carrots-vs-russet-potato [Al: It looks like they used data for peeled russet potatoes, since the usda data for baked or raw potatoes shows better nutrition.] >>>>>>>>>>>>>>>>>>> Frequency of Boiled Potato Consumption and All-Cause and Cardiovascular Disease Mortality in the Prospective Population-Based HUNT Study. Moholdt T, Nilsen TIL. Front Nutr. 2021 Jul 19;8:681365. doi: 10.3389/fnut.2021.681365. eCollection 2021. PMID: 34350204 Free PMC article. Abstract Few studies have assessed the association between potato consumption and mortality, especially cardiovascular disease (CVD) mortality. Our objective was to investigate the association between consumption of boiled potatoes and all-cause and CVD mortality in a Norwegian population. We used data from the population based HUNT3 study in Norway, with data on boiled potato consumption frequency in 2006-2008 from 49,926 males and females aged 20 years or above. All-cause and CVD mortality were identified during 10 years follow-up through the national Cause of Death Registry, which is virtually complete. We used Cox regression to estimate hazard ratio (HR) with a 95% confidence interval (CI) for death controlling for potential confounders, and conducted additional analyses stratified by sex, body mass index (BMI) ±25 kg/m2, and age ±65 years. There were 4,084 deaths and 1,284 of these were due to CVD. Frequency of boiled potato consumption was not associated with all-cause mortality, nor with CVD mortality. Compared to those individuals who consumed boiled potatoes less than once weekly, those who reported to consume boiled potatoes 1-3 times per week had an adjusted HR (95% CI) of 1.12 (0.89, 1.41) for all-cause mortality and 1.20 (0.78, 1.86) for CVD mortality. Individuals who consumed boiled potatoes 4-6 times per week had HRs of 0.97 (0.78, 1.21) and 1.03 (0.68, 1.55), for all-cause and CVD mortality, respectively, whereas those who consumed boiled potatoes more than once daily had HRs of 1.04 (0.83, 1.29) and 1.09 (0.73, 1.63) for all-cause and CVD mortality, respectively. There was no evidence of differential associations for males vs. females, nor between people with BMI ± 25 kg/m2. The associations between frequency of boiled potato consumption and all-cause mortality showed different patterns between those younger vs. older than 65 years, with a tendency of increased risk only in the oldest age group. In conclusion, frequency of consumption of boiled potatoes was not associated with all-cause or CVD mortality in the HUNT population in Norway. Keywords: diet; heart disease; nutrients; survival; vegetables. Association between dietary omega-3 fatty acid intake and depression in postmenopausal women. Chae M, Park K. Nutr Res Pract. 2021 Aug;15(4):468-478. doi: 10.4162/nrp.2021.15.4.468. Epub 2021 Mar 8. PMID: 34349880 Free PMC article. Abstract Background/objectives: This study aimed to analyze the association between dietary omega-3 fatty acid intake and depression in postmenopausal women using data from the Korea National Health and Nutrition Examination Survey (KNHANES) VI. Subjects/methods: The KNHANES is a cross-sectional nationwide health and nutrition survey. Dietary data, including omega-3 fatty acids, were assessed using the 24-h recall method. Depression was evaluated using a survey questionnaire. The association between dietary omega-3 fatty acids and depression was evaluated using multivariate logistic regression analysis. Depression, according to the dietary omega-3 fatty acid intake, was expressed as the odds ratio (OR) with a 95% confidence interval (CI). A total of 4,150 postmenopausal women were included in the analysis. Results: In the fully-adjusted model, the group with the highest dietary omega-3 fatty acid intake significantly showed lower prevalence of depression than the group with the lowest intake (OR, 0.52; 95% CI, 0.33-0.83); a significant linear trend was detected (P for trend = 0.04). According to the dose-response analysis using cubic restricted spline regression, this association was linear and monotonic (P for non-linearity = 0.32). Conclusions: In this study, the dietary omega-3 fatty acid intake in postmenopausal women was inversely proportional to depression in a dose-response manner. Large cohort studies are needed to verify the causality between omega-3 fatty acids and depression in Korean postmenopausal women. Keywords: Korea; Omega-3 fatty acids; depression; menopause; women. Terminal decline in objective and self-reported measures of motor function before death: 10 year follow-up of Whitehall II cohort study. Landré B, Fayosse A, Ben Hassen C, Machado-Fragua MD, Dumurgier J, Kivimaki M, Sabia S, Singh-Manoux A. BMJ. 2021 Aug 4;374:n1743. doi: 10.1136/bmj.n1743. PMID: 34348957 Abstract Objectives: To examine multiple objective and self-reported measures of motor function for their associations with mortality. Design: Prospective cohort study. Setting: UK based Whitehall II cohort study, which recruited participants aged 35-55 years in 1985-88; motor function component was added at the 2007-09 wave. Participants: 6194 participants with motor function measures in 2007-09 (mean age 65.6, SD 5.9), 2012-13, and 2015-16. Main outcome measures: All cause mortality between 2007 and 2019 in relation to objective measures (walking speed, grip strength, and timed chair rises) and self-reported measures (physical component summary score of the SF-36 and limitations in basic and instrumental activities of daily living (ADL)) of motor function. Results: One sex specific standard deviation poorer motor function in 2007-09 (cases/total, 610/5645) was associated with an increased mortality risk of 22% (95% confidence interval 12% to 33%) for walking speed, 15% (6% to 25%) for grip strength, 14% (7% to 23%) for timed chair rises, and 17% (8% to 26%) for physical component summary score over a mean 10.6 year follow-up. Having basic/instrumental ADL limitations was associated with a 30% (7% to 58%) increased mortality risk. These associations were progressively stronger when measures were drawn from 2012-13 (mean follow-up 6.8 years) and 2015-16 (mean follow-up 3.7 years). Analysis of trajectories showed poorer motor function in decedents (n=484) than survivors (n=6194) up to 10 years before death for timed chair rises (standardised difference 0.35, 95% confidence interval 0.12 to 0.59; equivalent to a 1.2 (men) and 1.3 (women) second difference), nine years for walking speed (0.21, 0.05 to 0.36; 5.5 (men) and 5.3 (women) cm/s difference), six years for grip strength (0.10, 0.01 to 0.20; 0.9 (men) and 0.6 (women) kg difference), seven years for physical component summary score (0.15, 0.05 to 0.25; 1.2 (men) and 1.6 (women) score difference), and four years for basic/instrumental ADL limitations (prevalence difference 2%, 0% to 4%). These differences increased in the period leading to death for timed chair rises, physical component summary score, and ADL limitations. Conclusion: Motor function in early old age has a robust association with mortality, with evidence of terminal decline emerging early in measures of overall motor function (timed chair rises and physical component summary score) and late in basic/instrumental ADL limitations. Fine Particulate Matter and Dementia Incidence in the Adult Changes in Thought Study. Shaffer RM, Blanco MN, Li G, Adar SD, Carone M, Szpiro AA, Kaufman JD, Larson TV, Larson EB, Crane PK, Sheppard L. Environ Health Perspect. 2021 Aug;129(8):87001. doi: 10.1289/EHP9018. Epub 2021 Aug 4. PMID: 34347531 Abstract Background: Air pollution may be associated with elevated dementia risk. Prior research has limitations that may affect reliability, and no studies have evaluated this question in a population-based cohort of men and women in the United States. Objectives: We evaluated the association between time-varying, 10-y average fine particulate matter ( PM2.5) exposure and hazard of all-cause dementia. An additional goal was to understand how to adequately control for age and calendar-time-related confounding through choice of the time axis and covariate adjustment. Methods: Using the Adult Changes in Thought (ACT) population-based prospective cohort study in Seattle, we linked spatiotemporal model-based PM2.5 exposures to participant addresses from 1978 to 2018. Dementia diagnoses were made using high-quality, standardized, consensus-based protocols at biennial follow-ups. We conducted multivariable Cox proportional hazards regression to evaluate the association between time-varying, 10-y average PM2.5 exposure and time to event in a model with age as the time axis, stratified by apolipoprotein E (APOE) genotype, and adjusted for sex, education, race, neighborhood median household income, and calendar time. Alternative models used calendar time as the time axis. Results: We report 1,136 cases of incident dementia among 4,166 individuals with nonmissing APOE status. Mean [mean ± standard deviation (SD)] 10-y average PM2.5 was 10.1 (±2.9)μg/m3. Each 1-μg/m3 increase in the moving average of 10-y PM2.5 was associated with a 16% greater hazard of all-cause dementia [1.16 (95% confidence interval: 1.03, 1.31)]. Results using calendar time as the time axis were similar. Discussion: In this prospective cohort study with extensive exposure data and consensus-based outcome ascertainment, elevated long-term exposure to PM2.5 was associated with increased hazard of all-cause dementia. We found that optimal control of age and time confounding could be achieved through use of either age or calendar time as the time axis in our study. Our results strengthen evidence on the neurodegenerative effects of PM2.5. Association between adiposity and cardiovascular outcomes: an umbrella review and meta-analysis of observational and Mendelian randomization studies. Kim MS, Kim WJ, Khera AV, Kim JY, Yon DK, Lee SW, Shin JI, Won HH. Eur Heart J. 2021 Aug 1:ehab454. doi: 10.1093/eurheartj/ehab454. Online ahead of print. PMID: 34333589 Abstract Aims: The aim of this study was to investigate the causal relationship and evidence of an association between increased adiposity and the risk of incident cardiovascular disease (CVD) events or mortality. Methods and results : Observational (informing association) and Mendelian randomization (MR) (informing causality) studies were assessed to gather mutually complementary insights and elucidate perplexing epidemiological relationships. Systematic reviews and meta-analyses of observational and MR studies that were published until January 2021 and evaluated the association between obesity-related indices and CVD risk were searched. Twelve systematic reviews with 53 meta-analyses results (including over 501 cohort studies) and 12 MR studies were included in the analysis. A body mass index (BMI) increase was associated with higher risks of coronary heart disease, heart failure, atrial fibrillation, all-cause stroke, haemorrhagic stroke, ischaemic stroke, hypertension, aortic valve stenosis, pulmonary embolism, and venous thrombo-embolism. The MR study results demonstrated a causal effect of obesity on all indices but stroke. The CVD risk increase for every 5 kg/m2 increase in BMI varied from 10% [relative risk (RR) 1.10; 95% confidence interval (CI) 1.01-1.21; certainty of evidence, low] for haemorrhagic stroke to 49% (RR 1.49; 95% CI 1.40-1.60; certainty of evidence, high) for hypertension. The all-cause and CVD-specific mortality risks increased with adiposity in cohorts, but the MR studies demonstrated no causal effect of adiposity on all-cause mortality. Conclusion : High adiposity is associated with increased CVD risk despite divergent evidence gradients. Adiposity was a causal risk factor for CVD except all-cause mortality and stroke. Half (49%; 26/53) of the associations were supported by high-level evidence. The associations were consistent between sexes and across global regions. This study provides guidance on how to integrate evidence from observational (association) and genetics-driven (causation) studies accumulated to date, to enable a more reliable interpretation of epidemiological relationships. Keywords: Cardiovascular disease; Coronary heart disease; Mendelian randomization study; Meta-analysis; Stroke; Umbrella review.
  22. Just some suggestions ... For the 2., first question, it is not needed in lieu of the 1. questions. For 1., you might include: "Are you partially or fully vaccinated?" For 2., people may have had a bad reaction to the first COVID shot, or had a bad previous reaction to vaccination for some other disease, leading them to forgo vaccination for COVID. It is said 10% of all people, a large fraction of the currently unvaccinated, have https://en.wikipedia.org/wiki/Fear_of_needles . So it could be another reason people may not get the vaccine.
  23. Something like what Eckhart Tolle describes here may be at work .... You crazy. No, you crazy. No, you crazy. No, every other one not like our group crazy. PS: By the way, have you read what https://en.wikipedia.org/wiki/Bild#Reception had to say about your "Top" newspaper? Sorry for Wiki, but something has to come through as valid. I enjoyed reading: '"Bild is not a harmless guilty pleasure", she wrote, but a "dangerous political instrument—not only a high-magnification telescope into the abyss but an evil creature".[21]'
  24. Al, again, attacking the source is not an argument. Bild is the largest news source in Germany and thus the most influential. As to Der Spiegel, it's a magazine. It leans heavily to the left and a few years ago had on its cover Trump beheading the Statue of Liberty. And its most recent claim to fame is a major scandal involving numerous fabricated stories. Again, and double entendre, "Top, my bottom". Keep politics out of it. And you mistook the magazine, https://www.spiegel.de/ for the news website, https://en.wikipedia.org/wiki/Der_Spiegel_(online) or https://www.spiegel.de/international/. And the Statue of Liberty cartoon was humerous. The fabricated stories were a crime against Der Spiegel (Online) and its readers, that their investigation found nobody else working independently for them were involved with or knew the stories were fabricated. But really, what do you think about the tabloid "telling children “that they were going to murder their grandma”"? That is "Fear-Driven COVID Coverage"? Not your typical "vaccines contain microchips" type of nonesense, and I could see it harms children's psyche, whether re COVID-19 or not.