AlanPater

The evolution of menopause in toothed whales. Ellis S, Franks DW, Nielsen MLK, Weiss MN, Croft DP. Nature. 2024 Mar 13. doi: 10.1038/s41586-024-07159-9. Online ahead of print. PMID: 38480878 Abstract Understanding how and why menopause has evolved is a long-standing challenge across disciplines. Females can typically maximize their reproductive success by reproducing for the whole of their adult life. In humans, however, women cease reproduction several decades before the end of their natural lifespan1,2. Although progress has been made in understanding the adaptive value of menopause in humans3,4, the generality of these findings remains unclear. Toothed whales are the only mammal taxon in which menopause has evolved several times5, providing a unique opportunity to test the theories of how and why menopause evolves in a comparative context. Here, we assemble and analyse a comparative database to test competing evolutionary hypotheses. We find that menopause evolved in toothed whales by females extending their lifespan without increasing their reproductive lifespan, as predicted by the 'live-long' hypotheses. We further show that menopause results in females increasing their opportunity for intergenerational help by increasing their lifespan overlap with their grandoffspring and offspring without increasing their reproductive overlap with their daughters. Our results provide an informative comparison for the evolution of human life history and demonstrate that the same pathway that led to menopause in humans can also explain the evolution of menopause in toothed whales. Relative intake of macronutrients impacts risk of mild cognitive impairment or dementia. Roberts RO, Roberts LA, Geda YE, Cha RH, Pankratz VS, O'Connor HM, Knopman DS, Petersen RC. J Alzheimers Dis. 2012;32(2):329-39. doi: 10.3233/JAD-2012-120862. PMID: 22810099 Free PMC article. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494735/ Abstract High caloric intake has been associated with an increased risk of cognitive impairment. Total caloric intake is determined by the calories derived from macronutrients. The objective of the study was to investigate the association between percent of daily energy (calories) from macronutrients and incident mild cognitive impairment (MCI) or dementia. Participants were a population-based prospective cohort of elderly persons who were followed over a median 3.7 years (interquartile range, 2.5–3.9) of follow-up. At baseline and every 15 months, participants (median age, 79.5 years) were evaluated using the Clinical Dementia Rating scale, a neurological evaluation, and neuropsychological testing for a diagnosis of MCI, normal cognition, or dementia. Participants also completed a 128-item food-frequency questionnaire at baseline; total daily caloric and macronutrient intakes were calculated using an established database. The percent of total daily energy from protein (% protein), carbohydrate (% carbohydrate), and total fat (% fat) was computed. Among 937 subjects who were cognitively normal at baseline, 200 developed incident MCI or dementia. The risk of MCI or dementia (hazard ratio [HR], [95% confidence interval]) was elevated in subjects with high % carbohydrate (upper quartile: 1.89 [1.17–3.06]; P for trend=0.004), but was reduced in subjects with high % fat (upper quartile: 0.56 [0.34–0.91]; P for trend=0.03), and high % protein (upper quartile 0.79 [0.52 – 1.20]; P for trend=0.03) in the fully adjusted models. A dietary pattern with relatively high caloric intake from carbohydrates and low caloric intake from fat and proteins may increase the risk of MCI or dementia in elderly persons. Keywords: Mild cognitive impairment, dementia, dietary proteins, dietary fats, dietary carbohydrates, caloric intake, energy intake, prospective studies, community-based >>>>>>>>>>>>>>>>>> Dietary Macronutrient Intake and Cardiovascular Disease Risk and Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies. Ma Y, Zheng Z, Zhuang L, Wang H, Li A, Chen L, Liu L. Nutrients. 2024 Jan 2;16(1):152. doi: 10.3390/nu16010152. PMID: 38201983 Free PMC article. Review. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10780780/pdf/nutrients-16-00152.pdf Abstract Many epidemiological studies have evaluated the intake of macronutrients and the risk of mortality and cardiovascular disease (CVD). However, current evidence is conflicting and warrants further investigation. Therefore, we carried out an umbrella review to examine and quantify the potential dose-response association of dietary macronutrient intake with CVD morbidity and mortality. Prospective cohort studies from PubMed, Embase, and CENTRAL were reviewed, which reported associations of macronutrients (protein, fat, and carbohydrate) with all-cause, CVD, cancer mortality, or CVD events. Multivariable relative risks (RR) were pooled, and heterogeneity was assessed. The results of 124 prospective cohort studies were included in the systematic review and 101 in the meta-analysis. During the follow-up period from 2.2 to 30 years, 506,086 deaths and 79,585 CVD events occurred among 5,107,821 participants. High total protein intake was associated with low CVD morbidity (RR 0.88, 95% confidence interval 0.82-0.94), while high total carbohydrate intake was associated with high CVD morbidity (1.08, 1.02-1.13). For fats, a high intake of total fat was associated with a decreased all-cause mortality risk (0.92, 0.85-0.99). Saturated fatty acid intake was only associated with cancer mortality (1.10, 1.06-1.14); Both monounsaturated fatty acid (MUFA) and polyunsaturated fatty acids (PUFA) intake was associated with all-cause mortality (MUFA: 0.92, 0.86-0.98; PUFA: 0.91, 0.86-0.96). This meta-analysis supports that protein intake is associated with a decreased risk of CVD morbidity, while carbohydrate intake is associated with an increased risk of CVD morbidity. High total fat intake is associated with a low risk of all-cause mortality, and this effect was different in an analysis stratified by the type of fat. Keywords: cardiovascular disease; macronutrient intake; meta-analysis; mortality. Persistent complement dysregulation with signs of thromboinflammation in active Long Covid. Cervia-Hasler C, Brüningk SC, Hoch T, Fan B, Muzio G, Thompson RC, Ceglarek L, Meledin R, Westermann P, Emmenegger M, Taeschler P, Zurbuchen Y, Pons M, Menges D, Ballouz T, Cervia-Hasler S, Adamo S, Merad M, Charney AW, Puhan M, Brodin P, Nilsson J, Aguzzi A, Raeber ME, Messner CB, Beckmann ND, Borgwardt K, Boyman O. Science. 2024 Jan 19;383(6680):eadg7942. doi: 10.1126/science.adg7942. Epub 2024 Jan 19. PMID: 38236961 https://www.science.org/doi/epdf/10.1126/science.adg7942 Abstract Long Covid is a debilitating condition of unknown etiology. We performed multimodal proteomics analyses of blood serum from COVID-19 patients followed up to 12 months after confirmed severe acute respiratory syndrome coronavirus 2 infection. Analysis of >6500 proteins in 268 longitudinal samples revealed dysregulated activation of the complement system, an innate immune protection and homeostasis mechanism, in individuals experiencing Long Covid. Thus, active Long Covid was characterized by terminal complement system dysregulation and ongoing activation of the alternative and classical complement pathways, the latter associated with increased antibody titers against several herpesviruses possibly stimulating this pathway. Moreover, markers of hemolysis, tissue injury, platelet activation, and monocyte-platelet aggregates were increased in Long Covid. Machine learning confirmed complement and thromboinflammatory proteins as top biomarkers, warranting diagnostic and therapeutic interrogation of these systems.

When one twin goes vegan and the other doesn’t What a plant-based diet can and cannot do for you, explained by Netflix’s You Are What You Eat. By Kenny Torrella@KennyTorrella Jan 12, 2024, 9:00am EST https://www.vox.com/future-perfect/24034578/vegan-twin-study-stanford-you-are-what-you-eat-netflix >>>>>>>>>>>>>>>>>>>>>>>> Cardiometabolic Effects of Omnivorous vs Vegan Diets in Identical Twins: A Randomized Clinical Trial. Landry MJ, Ward CP, Cunanan KM, Durand LR, Perelman D, Robinson JL, Hennings T, Koh L, Dant C, Zeitlin A, Ebel ER, Sonnenburg ED, Sonnenburg JL, Gardner CD. JAMA Netw Open. 2023 Nov 1;6(11):e2344457. doi: 10.1001/jamanetworkopen.2023.44457. PMID: 38032644 Free PMC article. Clinical Trial. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10690456/ Abstract Importance: Increasing evidence suggests that, compared with an omnivorous diet, a vegan diet confers potential cardiovascular benefits from improved diet quality (ie, higher consumption of vegetables, legumes, fruits, whole grains, nuts, and seeds). Objective: To compare the effects of a healthy vegan vs healthy omnivorous diet on cardiometabolic measures during an 8-week intervention. Design, setting, and participants: This single-center, population-based randomized clinical trial of 22 pairs of twins (N = 44) randomized participants to a vegan or omnivorous diet (1 twin per diet). Participant enrollment began March 28, 2022, and continued through May 5, 2022. The date of final follow-up data collection was July 20, 2022. This 8-week, open-label, parallel, dietary randomized clinical trial compared the health impact of a vegan diet vs an omnivorous diet in identical twins. Primary analysis included all available data. Intervention: Twin pairs were randomized to follow a healthy vegan diet or a healthy omnivorous diet for 8 weeks. Diet-specific meals were provided via a meal delivery service from baseline through week 4, and from weeks 5 to 8 participants prepared their own diet-appropriate meals and snacks. Main outcomes and measures: The primary outcome was difference in low-density lipoprotein cholesterol concentration from baseline to end point (week 8). Secondary outcome measures were changes in cardiometabolic factors (plasma lipids, glucose, and insulin levels and serum trimethylamine N-oxide level), plasma vitamin B12 level, and body weight. Exploratory measures were adherence to study diets, ease or difficulty in following the diets, participant energy levels, and sense of well-being. Results: A total of 22 pairs (N = 44) of twins (34 [77.3%] female; mean [SD] age, 39.6 [12.7] years; mean [SD] body mass index, 25.9 [4.7]) were enrolled in the study. After 8 weeks, compared with twins randomized to an omnivorous diet, the twins randomized to the vegan diet experienced significant mean (SD) decreases in low-density lipoprotein cholesterol concentration (-13.9 [5.8] mg/dL; 95% CI, -25.3 to -2.4 mg/dL), fasting insulin level (-2.9 [1.3] μIU/mL; 95% CI, -5.3 to -0.4 μIU/mL), and body weight (-1.9 [0.7] kg; 95% CI, -3.3 to -0.6 kg). Conclusions and relevance: In this randomized clinical trial of the cardiometabolic effects of omnivorous vs vegan diets in identical twins, the healthy vegan diet led to improved cardiometabolic outcomes compared with a healthy omnivorous diet. Clinicians can consider this dietary approach as a healthy alternative for their patients. What's the best time of the day to exercise? 6th January 2024, 08:00 CST By Annabel Bourne https://www.bbc.com/future/article/20240105-whats-the-best-time-of-the-day-to-exercise >>>>>>>>>>>>>>>>>>>>>>>>> Circadian rhythms and exercise - re-setting the clock in metabolic disease. Gabriel BM, Zierath JR. Nat Rev Endocrinol. 2019 Apr;15(4):197-206. doi: 10.1038/s41574-018-0150-x. PMID: 30655625 Review. Abstract Perturbed diurnal rhythms are becoming increasingly evident as deleterious events in the pathology of metabolic diseases. Exercise is well characterized as a crucial intervention in the prevention and treatment of individuals with metabolic diseases. Little is known, however, regarding optimizing the timing of exercise bouts in order to maximize their health benefits. Furthermore, exercise is a potent modulator of skeletal muscle metabolism, and it is clear that skeletal muscle has a strong circadian profile. In humans, mitochondrial function peaks in the late afternoon, and the circadian clock might be inherently impaired in myotubes from patients with metabolic disease. Timing exercise bouts to coordinate with an individual's circadian rhythms might be an efficacious strategy to optimize the health benefits of exercise. The role of exercise as a Zeitgeber can also be used as a tool in combating metabolic disease. Shift work is known to induce acute insulin resistance, and appropriately timed exercise might improve health markers in shift workers who are at risk of metabolic disease. In this Review, we discuss the literature regarding diurnal skeletal muscle metabolism and the interaction with exercise bouts at different times of the day to combat metabolic disease. Nighttime ambient temperature and sleep in community-dwelling older adults. Baniassadi A, Manor B, Yu W, Travison T, Lipsitz L. Sci Total Environ. 2023 Nov 15;899:165623. doi: 10.1016/j.scitotenv.2023.165623. Epub 2023 Jul 19. PMID: 37474050 Abstract This longitudinal study examines the association between bedroom nighttime temperature and sleep quality in a sample of community dwelling older adults. Using wearable sleep monitors and environmental sensors, we assessed sleep duration, efficiency, and restlessness over an extended period within participants' homes while controlling for potential confounders and covariates. Our findings demonstrated that sleep was most efficient and restful when nighttime ambient temperature ranged between 20 and 25 °C, with a clinically relevant 5-10 % drop in sleep efficiency when the temperature increased from 25 °C to 30 °C. The associations were primarily nonlinear, and substantial between-subject variations were observed. These results highlight the potential to enhance sleep quality in older adults by optimizing home thermal environments and emphasize the importance of personalized temperature adjustments based on individual needs and circumstances. Additionally, our study underscores the potential impact of climate change on sleep quality in older adults, particularly those with lower socioeconomic status, and supports increasing their adaptive capacity in the face of a changing climate. Keywords: Environment; Older adults; Sleep; Temperature; Wearable.

Organ aging signatures in the plasma proteome track health and disease. Oh HS, Rutledge J, Nachun D, Pálovics R, Abiose O, Moran-Losada P, Channappa D, Urey DY, Kim K, Sung YJ, Wang L, Timsina J, Western D, Liu M, Kohlfeld P, Budde J, Wilson EN, Guen Y, Maurer TM, Haney M, Yang AC, He Z, Greicius MD, Andreasson KI, Sathyan S, Weiss EF, Milman S, Barzilai N, Cruchaga C, Wagner AD, Mormino E, Lehallier B, Henderson VW, Longo FM, Montgomery SB, Wyss-Coray T. Nature. 2023 Dec;624(7990):164-172. doi: 10.1038/s41586-023-06802-1. Epub 2023 Dec 6. PMID: 38057571 Abstract Animal studies show aging varies between individuals as well as between organs within an individual1,2,3,4, but whether this is true in humans and its effect on age-related diseases is unknown. We utilized levels of human blood plasma proteins originating from specific organs to measure organ-specific aging differences in living individuals. Using machine learning models, we analysed aging in 11 major organs and estimated organ age reproducibly in five independent cohorts encompassing 5,676 adults across the human lifespan. We discovered nearly 20% of the population show strongly accelerated age in one organ and 1.7% are multi-organ agers. Accelerated organ aging confers 20–50% higher mortality risk, and organ-specific diseases relate to faster aging of those organs. We find individuals with accelerated heart aging have a 250% increased heart failure risk and accelerated brain and vascular aging predict Alzheimer’s disease (AD) progression independently from and as strongly as plasma pTau-181 (ref. 5), the current best blood-based biomarker for AD. Our models link vascular calcification, extracellular matrix alterations and synaptic protein shedding to early cognitive decline. We introduce a simple and interpretable method to study organ aging using plasma proteomics data, predicting diseases and aging effects.

Well said! Put another way: “a lie can travel halfway around the world while the truth is putting on its shoes.” >>>>>>>>>>>>>>>>>>>>>>>>>>>>> Pocket worthy Stories to fuel your mind The Golden Age of Junk Science Is Killing Us Misinformation is being spewed, weaponized, and consumed at a deadly rate. Fortunately, there's a way out. Here's how to make sense of what you're seeing. Men’s Health Timothy Caulfield https://getpocket.com/explore/item/the-golden-age-of-junk-science-is-killing-us?utm_source=pocket-newtab-en-us

I got the latest Pfizer COVID-19 vaccine, with about the same pain reaction as the fourth shot, as well as the flu shot, the day before yesterday. >>>>>>>>>>>>> Life expectancy for men in U.S. falls to 73 years — six years less than for women, per study By Annalisa Merelli Nov. 13, 2023 https://www.statnews.com/2023/11/13/life-expectancy-men-women/ "... according to new research published on Monday in JAMA Internal Medicine. At least partially as a consequence of over 1 million Covid-19 deaths, life expectancy in the U.S. has declined significantly over the past few years, falling from 78.8 years in 2019 to 77 in 2020 and 76.1 in 2022 — undoing over two decades of progress. This puts the country far behind its wealthy peers: Countries such as Japan, Korea, Portugal, the U.K., and Italy all enjoy a life expectancy of 80 years or more. Countries such as Turkey (78.6) and China (78.2) also fare better. ..." https://data.oecd.org/healthstat/life-expectancy-at-birth.htm

Can You Think Yourself Young? Research shows that a positive attitude to ageing can lead to a longer, healthier life, while negative beliefs can have hugely detrimental effects. The Guardian David Robson https://getpocket.com/explore/item/can-you-think-yourself-young?utm_source=pocket-newtab-en-us

Hear that? It’s the sound of leaf blower bans. As restrictions spread, neighborhoods are getting quieter — and cleaner. https://grist.org/solutions/leaf-blower-bans-air-pollution-noise/?utm_source=pocket-newtab-en-us Mystery of Why Humans Die Around 80 May Finally Be Solved Scientists have been studying the ageing processes of mammals, from humans to mice and giraffes. The Telegraph Sarah Knapton The mystery of why humans die at around 80, while other mammals live far shorter or longer lives, may finally have been solved by scientists. https://getpocket.com/explore/item/mystery-of-why-humans-die-around-80-may-finally-be-solved?utm_source=pocket-newtab-en-us >>>>>>>>>>>>>>>>>>>>>>>>>>>>> Somatic mutation rates scale with lifespan across mammals. Cagan A, Baez-Ortega A, Brzozowska N, Abascal F, Coorens THH, Sanders MA, Lawson ARJ, Harvey LMR, Bhosle S, Jones D, Alcantara RE, Butler TM, Hooks Y, Roberts K, Anderson E, Lunn S, Flach E, Spiro S, Januszczak I, Wrigglesworth E, Jenkins H, Dallas T, Masters N, Perkins MW, Deaville R, Druce M, Bogeska R, Milsom MD, Neumann B, Gorman F, Constantino-Casas F, Peachey L, Bochynska D, Smith ESJ, Gerstung M, Campbell PJ, Murchison EP, Stratton MR, Martincorena I. Nature. 2022 Apr;604(7906):517-524. doi: 10.1038/s41586-022-04618-z. Epub 2022 Apr 13. PMID: 35418684 Free PMC article. Pocket worthy Stories to fuel your mind ‘Too Many Antioxidants Can Give You Cancer,’ and Other Facts About the Misunderstood Molecules And free radicals aren’t always bad for you. Popular Science Sara Chodosh https://getpocket.com/explore/item/too-many-antioxidants-can-give-you-cancer-and-other-facts-about-the-misunderstood-molecules?utm_source=pocket-newtab-en-us By Zaria Gorvett 23rd August 2023 Weathered or unhealthy skin is emerging as a major risk factor for almost every single age-related disease, from Parkinson's to type 2 diabetes. https://www.bbc.com/future/article/20230823-the-curious-ways-your-skin-shapes-your-health Pocket worthyStories to fuel your mind The Hollywood HIV Doctor Who Was Secretly Peddling Eternal Youth How did a respected and beloved medical professional end up leading a multi-million-dollar anti-aging scheme—and staring down decades in prison? Jeffrey Arlo Brown https://getpocket.com/explore/item/the-hollywood-hiv-doctor-who-was-secretly-peddling-eternal-youth?utm_source=pocket-newtab-en-us Would You Want to Know if You’re Going to Get Alzheimer’s Disease? Advances in genetic research mean predicting who develops the condition is becoming more accurate, but that’s not necessarily a comfort. The Telegraph David Co https://getpocket.com/explore/item/would-you-want-to-know-if-you-re-going-to-get-alzheimer-s-disease?utm_source=pocket-newtab-en-us " phytoncides, antibacterial and antimicrobial substances that trees and other plants release into the air to help them fight diseases and harmful organisms. When humans breathe in these substances—typically by spending time in nature—their health can improve. Across several studies, phytoncides have been shown to boost immune function, increase anticancer protein production, reduce stress hormones, improve mood, and help people relax." >>>>>>>>>> https://getpocket.com/explore/item/the-simple-dutch-cure-for-stress?utm_source=pocket_collection_story

Applies more to Mom, 1923-2020; 98 years: >>> Those Winter Sundays By Robert Hayden Sundays too my father got up early and put his clothes on in the blueblack cold, then with cracked hands that ached from labor in the weekday weather made banked fires blaze. No one ever thanked him. I’d wake and hear the cold splintering, breaking. When the rooms were warm, he’d call, and slowly I would rise and dress, fearing the chronic angers of that house, Speaking indifferently to him, who had driven out the cold and polished my good shoes as well. What did I know, what did I know of love’s austere and lonely offices?

Open Access Published: 31 August 2023 Acute blood biomarker profiles predict cognitive deficits 6 and 12 months after COVID-19 hospitalization Maxime Taquet, Zuzanna Skorniewska, Adam Hampshire, James D. Chalmers, Ling-Pei Ho, Alex Horsley, Michael Marks, Krisnah Poinasamy, Betty Raman, Olivia C. Leavy, Matthew Richardson, Omer Elneima, Hamish J. C. McAuley, Aarti Shikotra, Amisha Singapuri, Marco Sereno, Ruth M. Saunders, Victoria C. Harris, Linzy Houchen-Wolloff, Neil J. Greening, Parisa Mansoori, Ewen M. Harrison, Annemarie B. Docherty, Nazir I. Lone, PHOSP-COVID Study Collaborative Group Nature Medicine (2023) Abstract Post-COVID cognitive deficits, including ‘brain fog’, are clinically complex, with both objective and subjective components. They are common and debilitating, and can affect the ability to work, yet their biological underpinnings remain unknown. In this prospective cohort study of 1,837 adults hospitalized with COVID-19, we identified two distinct biomarker profiles measured during the acute admission, which predict cognitive outcomes 6 and 12 months after COVID-19. A first profile links elevated fibrinogen relative to C-reactive protein with both objective and subjective cognitive deficits. A second profile links elevated D-dimer relative to C-reactive protein with subjective cognitive deficits and occupational impact. This second profile was mediated by fatigue and shortness of breath. Neither profile was significantly mediated by depression or anxiety. Results were robust across secondary analyses. They were replicated, and their specificity to COVID-19 tested, in a large-scale electronic health records dataset. These findings provide insights into the heterogeneous biology of post-COVID cognitive deficits. "reinfections were also linked to higher long COVID frequency and severity, compared to people who only had COVID-19 once" https://www.nih.gov/news-events/news-releases/large-study-provides-scientists-deeper-insight-into-long-covid-symptoms >>>>>>>>>>>>>>>>>>>>> Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection Tanayott Thaweethai, PhD1,2; Sarah E. Jolley, MD, MS3; Elizabeth W. Karlson, MD, MS4; et al Emily B. Levitan, ScD5; Bruce Levy, MD2,4; Grace A. McComsey, MD6; Lisa McCorkell, MPP7; Girish N. Nadkarni, MD, MPH8; Sairam Parthasarathy, MD9; Upinder Singh, MD10; Tiffany A. Walker, MD11; Caitlin A. Selvaggi, MS1; Daniel J. Shinnick, MS1; Carolin C. M. Schulte, PhD1; Rachel Atchley-Challenner, PhD12; Leora I. Horwitz, MD13; Andrea S. Foulkes, ScD1,2; RECOVER Consortium Authors; for the RECOVER Consortium JAMA. 2023;329(22):1934-1946. PMID: 37278994 PMCID: PMC10214179 DOI: 10.1001/jama.2023.8823 Abstract Importance: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals. Objective: To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections. Design, setting, and participants: Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling. Exposure: SARS-CoV-2 infection. Main outcomes and measures: PASC and 44 participant-reported symptoms (with severity thresholds). Results: A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months. Conclusions and relevance: A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.

“The amount of energy needed to refute bullshit is an order of magnitude bigger than to produce it,” the programmer, Alberto Brandolini, wrote in 2013.

Prospective Associations of Different Combinations of Aerobic and Muscle-Strengthening Activity With All-Cause, Cardiovascular, and Cancer Mortality. López-Bueno R, Ahmadi M, Stamatakis E, Yang L, Del Pozo Cruz B. JAMA Intern Med. 2023 Aug 7:e233093. doi: 10.1001/jamainternmed.2023.3093. Online ahead of print. PMID: 37548973 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2807854?guestAccessKey=aed32847-e929-4924-91f4-9bb7746726b8&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jamainternalmedicine&utm_term=mostread&utm_content=olf-widget_08142023 Abstract Importance: Studies examining the associations of different combinations of intensity-specific aerobic and muscle strengthening activity (MSA) with all-cause and cause-specific mortality are scarce; the few available estimates are disparate. Objective: To examine the prospective associations of different combinations of moderate aerobic physical activity (MPA), vigorous aerobic physical activity (VPA), and MSA with all-cause, cardiovascular (CVD), and cancer mortality. Design, setting, and participants: This nationwide prospective cohort study used data from the US National Health Interview Survey. A total of 500 705 eligible US adults were included in the study and followed up during a median of 10.0 years (5.6 million person-years) from 1997 to 2018. Data were analyzed from September 1 to September 30, 2022. Exposures: Self-reported cumulative bouts (75 weekly minutes) of MPA and VPA with recommended MSA guidelines (yes or no) to obtain 48 mutually exclusive exposure categories. Main outcomes and measures: All-cause, CVD, and cancer mortality. Participants were linked to the National Death Index through December 31, 2019. Results: Overall, 500 705 participants (mean [SD] age, 46.4 [17.3] years; 210 803 [58%] female; 277 504 [77%] White) were included in the study. Compared with the reference group (doing no MPA or VPA and less than recommended MSA), the category associated with the lowest hazard ratio (HR) for all-cause mortality was more than 0 to 75 minutes of MPA combined with more than 150 minutes of VPA and 2 or more MSA sessions per week (HR, 0.50; 95% CI, 0.42-0.59). The optimal combinations for CVD and cancer mortality risk reduction were more than 150 to 225 minutes of MPA, more than 0 to 75 minutes of VPA, and 2 or more MSA sessions per week (HR, 0.30; 95% CI, 0.15-0.57), and more than 300 minutes of MPA, more than 0 to 75 minutes of VPA, and 2 or more MSA sessions per week (HR, 0.44; 95% CI, 0.23-0.82), respectively. Adjusted mortality rates represented an approximately 50% lower mortality rate for all-cause and cancer mortality and an approximately 3-fold lower mortality rate for CVD mortality. Conclusions and relevance: This cohort study demonstrated that balanced levels of MPA, VPA, and MSA combined may be associated with optimal reductions of mortality risk. Higher-than-recommended levels of MPA and VPA may further lower the risk of cancer and all-cause mortality, respectively. A common allele of HLA is associated with asymptomatic SARS-CoV-2 infection. Augusto DG, Murdolo LD, Chatzileontiadou DSM, Sabatino JJ Jr, Yusufali T, Peyser ND, Butcher X, Kizer K, Guthrie K, Murray VW, Pae V, Sarvadhavabhatla S, Beltran F, Gill GS, Lynch KL, Yun C, Maguire CT, Peluso MJ, Hoh R, Henrich TJ, Deeks SG, Davidson M, Lu S, Goldberg SA, Kelly JD, Martin JN, Vierra-Green CA, Spellman SR, Langton DJ, Dewar-Oldis MJ, Smith C, Barnard PJ, Lee S, Marcus GM, Olgin JE, Pletcher MJ, Maiers M, Gras S, Hollenbach JA. Nature. 2023 Aug;620(7972):128-136. doi: 10.1038/s41586-023-06331-x. Epub 2023 Jul 19. PMID: 37468623 Free PMC article. Abstract Studies have demonstrated that at least 20% of individuals infected with SARS-CoV-2 remain asymptomatic1,2,3,4. Although most global efforts have focused on severe illness in COVID-19, examining asymptomatic infection provides a unique opportunity to consider early immunological features that promote rapid viral clearance. Here, postulating that variation in the human leukocyte antigen (HLA) loci may underly processes mediating asymptomatic infection, we enrolled 29,947 individuals, for whom high-resolution HLA genotyping data were available, in a smartphone-based study designed to track COVID-19 symptoms and outcomes. Our discovery cohort (n = 1,428) comprised unvaccinated individuals who reported a positive test result for SARS-CoV-2. We tested for association of five HLA loci with disease course and identified a strong association between HLA-B*15:01 and asymptomatic infection, observed in two independent cohorts. Suggesting that this genetic association is due to pre-existing T cell immunity, we show that T cells from pre-pandemic samples from individuals carrying HLA-B*15:01 were reactive to the immunodominant SARS-CoV-2 S-derived peptide NQKLIANQF. The majority of the reactive T cells displayed a memory phenotype, were highly polyfunctional and were cross-reactive to a peptide derived from seasonal coronaviruses. The crystal structure of HLA-B*15:01–peptide complexes demonstrates that the peptides NQKLIANQF and NQKLIANAF (from OC43-CoV and HKU1-CoV) share a similar ability to be stabilized and presented by HLA-B*15:01. Finally, we show that the structural similarity of the peptides underpins T cell cross-reactivity of high-affinity public T cell receptors, providing the molecular basis for HLA-B*15:01-mediated pre-existing immunity. How does the UK economy compare to other countries? https://www.bbc.com/news/business-66269947 We’re No. 1! Canada claims the most Top 10 liveable cities in the world By Michelle Butterfield Global News Posted June 23, 2023 https://globalnews.ca/news/9787103/canada-most-liveable-cities-top-10-2023/ A daytime nap is good for the brain By James Gallagher Regularly finding time for a little snooze is good for our brain and helps keep it bigger for longer, say University College London researchers. https://www.bbc.com/news/health-65950168 Pocket worthy Stories to fuel your mind Your Cotton Tote is Pretty Much the Worst Replacement for a Plastic Bag You have to use a cotton tote thousands of times to make up for its environmental impact. Quartz Zoë Schlanger https://getpocket.com/explore/item/your-cotton-tote-is-pretty-much-the-worst-replacement-for-a-plastic-bag?utm_source=pocket-newtab

The Irish Light: Woman abused by paper which falsely said vaccine killed her son https://www.bbc.com/news/world-europe-66424582 A grieving mother and her lawyer have been targeted by an extreme campaign of abuse after suing a conspiracy theory newspaper which falsely claimed her son died from a Covid vaccine.

Pocket worthyStories to fuel your mind Humans Could Live up to 150 Years A study counts blood cells and footsteps to predict a hard limit to our longevity. Scientific American Emily Willingham https://getpocket.com/explore/item/humans-could-live-up-to-150-years-new-research-suggests?utm_source=pocket-newtab >>>>>>>>>>>>>>>>>>>>> Longitudinal analysis of blood markers reveals progressive loss of resilience and predicts human lifespan limit. Pyrkov TV, Avchaciov K, Tarkhov AE, Menshikov LI, Gudkov AV, Fedichev PO. Nat Commun. 2021 May 25;12(1):2765. doi: 10.1038/s41467-021-23014-1. PMID: 34035236 Free PMC article. Abstract We investigated the dynamic properties of the organism state fluctuations along individual aging trajectories in a large longitudinal database of CBC measurements from a consumer diagnostics laboratory. To simplify the analysis, we used a log-linear mortality estimate from the CBC variables as a single quantitative measure of the aging process, henceforth referred to as dynamic organism state indicator (DOSI). We observed, that the age-dependent population DOSI distribution broadening could be explained by a progressive loss of physiological resilience measured by the DOSI auto-correlation time. Extrapolation of this trend suggested that DOSI recovery time and variance would simultaneously diverge at a critical point of 120 - 150 years of age corresponding to a complete loss of resilience. The observation was immediately confirmed by the independent analysis of correlation properties of intraday physical activity levels fluctuations collected by wearable devices. We conclude that the criticality resulting in the end of life is an intrinsic biological property of an organism that is independent of stress factors and signifies a fundamental or absolute limit of human lifespan.

The Steep Cost of Ron DeSantis’s Covid Vaccine Turnabout The Florida governor lost enthusiasm for the shot before the Delta wave. It’s a grim chapter he now leaves out of his retelling of his pandemic response. 12 min read https://www.nytimes.com/2023/07/22/us/politics/ron-desantis-covid.html Long-term cardiovascular outcomes of COVID-19. Xie Y, et al. Nat Med. 2022. PMID: 35132265 Free PMC article. Abstract The cardiovascular complications of acute coronavirus disease 2019 (COVID-19) are well described, but the post-acute cardiovascular manifestations of COVID-19 have not yet been comprehensively characterized. Here we used national healthcare databases from the US Department of Veterans Affairs to build a cohort of 153,760 individuals with COVID-19, as well as two sets of control cohorts with 5,637,647 (contemporary controls) and 5,859,411 (historical controls) individuals, to estimate risks and 1-year burdens of a set of pre-specified incident cardiovascular outcomes. We show that, beyond the first 30 d after infection, individuals with COVID-19 are at increased risk of incident cardiovascular disease spanning several categories, including cerebrovascular disorders, dysrhythmias, ischemic and non-ischemic heart disease, pericarditis, myocarditis, heart failure and thromboembolic disease. These risks and burdens were evident even among individuals who were not hospitalized during the acute phase of the infection and increased in a graded fashion according to the care setting during the acute phase (non-hospitalized, hospitalized and admitted to intensive care). Our results provide evidence that the risk and 1-year burden of cardiovascular disease in survivors of acute COVID-19 are substantial. Care pathways of those surviving the acute episode of COVID-19 should include attention to cardiovascular health and disease.

Ultra-processed food consumption and risk of dementia and Alzheimer's disease: Long-term results from the Framingham Offspring Study Kanran Wang, Weimin Tang, Xingchen Hao, Junhan Zhao First published: 03 July 2023 https://doi.org/10.1002/alz.13351 Abstract INTRODUCTION We aimed to assess the prospective associations between consumption of ultra-processed foods (UPF) and the risk of all-cause dementia and Alzheimer's disease (AD) dementia. METHOD This study included 2909 adult participants who were dementia free at baseline and had a follow-up. Dietary intakes were collected using the Food Frequency Questionnaire (FFQ). Proportional hazards models and cubic spline regression were used. RESULTS During a mean follow-up of 14.4 years, a total of 306 incident dementia events occurred, including 184 (60.1%) cases of AD. After multivariate adjustments, individuals in the highest quartile for energy-adjusted UPF consumption (over 9.1 servings per day) had a higher risk of all-cause dementia (hazard ratio [HR]: 1.61; 95% confidence interval [CI]: 1.09–2.16) and AD dementia (HR: 1.75; 95% CI: 1.04–2.71) compared to the lowest quartile. [Correction added on 24 July 2023, after first online publication: In the preceding sentence, the text ‘the highest quartiles for UPF consumption (> 7.5 servings per day)’ was revised to ‘the highest quartile for energy-adjusted UPF consumption (over 9.1 servings per day)’.] A nonlinear dose–response pattern was shown for all-cause dementia and AD dementia. CONCLUSIONS Higher consumption of UPF is associated with an increased risk of all-cause dementia and AD dementia.

Pocket worthy -- Stories to fuel your mind Walking Correctly Takes Work—Here’s How to Improve Every Step Experts explain how to make the most of your daily strolls. Popular Science Stan Horaczek https://getpocket.com/explore/item/walking-correctly-takes-work-here-s-how-to-improve-every-step?utm_source=pocket-newtab https://www.cbc.ca/radio/podcastnews/what-do-we-know-about-the-health-benefits-and-risks-of-cold-water-immersion-transcript-1.6868196 Common, inexpensive diabetes drug could cut long COVID risk, study finds Metformin reduced long COVID incidence among infected patients by 41 per cent Lauren Pelley · CBC News · Posted: Jun 10, 2023 https://www.cbc.ca/news/health/metformin-long-covid-1.6871654

There is too much emphasis on drugs: "Aging is “morally bad,” they argue, and it’s a problem that needs to be solved. They see existing regulations as roadblocks to progress and call for a different approach. Less red tape allows for more innovation, they say. People should be encouraged to self-experiment with unproven treatments if they wish. And companies shouldn’t be held back by national laws that limit how they develop and test drugs. Around 780 such people gathered at this “pop-up city” in Montenegro to work out how they might create such a state—a place where like-minded innovators can work together in an all-new jurisdiction that gives them free rein to self-experiment with unproven drugs." https://www.technologyreview.com/2023/05/31/1073750/new-longevity-state-rhode-island/?utm_source=pocket-newtab

Arch Gerontol Geriatr. 2023 Jan;104:104825. doi: 10.1016/j.archger.2022.104825. Epub 2022 Sep 26. A science-based review of the world's best-selling book on aging Charles Brenner PMID: 36183524 PMCID: PMC9669175 DOI: 10.1016/j.archger.2022.104825 Free PMC article No abstract available https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9669175/ "Do sirtuins extend lifespan in yeast, invertebrates and vertebrates? Has Sinclair discovered sirtuin activators? Based on 25 years of work by academic and industrial investigators, the clear answer to both questions is no (Brenner, 2022b). Whereas Lifespan claims that sirtuins are dominantly acting longevity genes from yeast to humans (Sinclair and LaPlante, 2019), analysis of the work reveals that in yeast, sirtuin genes help 1 in 5 million cells live longer in one model of aging whereas they shorten lifespan for the entire culture (Brenner, 2022b). Early reports of sirtuins extending lifespan in invertebrates could not be independently replicated. In 2011, researchers from 7 institutions published together that sirtuin genes do not extend lifespan in worms or flies (Burnett et al., 2011). We learned in 2016 that, just as it does in yeast, the fly sirtuin gene antagonizes lifespan extension in conditions of dietary restriction (Slade and Staveley, 2016). While all the positive results made global headlines and are described in Lifespan, the negative results have not been amplified by mass media."

Induction of a torpor-like hypothermic and hypometabolic state in rodents by ultrasound. Yang Y, Yuan J, Field RL, Ye D, Hu Z, Xu K, Xu L, Gong Y, Yue Y, Kravitz AV, Bruchas MR, Cui J, Brestoff JR, Chen H. Nat Metab. 2023 May 25. doi: 10.1038/s42255-023-00804-z. Online ahead of print. PMID: 37231250 Abstract Torpor is an energy-conserving state in which animals dramatically decrease their metabolic rate and body temperature to survive harsh environmental conditions. Here, we report the noninvasive, precise and safe induction of a torpor-like hypothermic and hypometabolic state in rodents by remote transcranial ultrasound stimulation at the hypothalamus preoptic area (POA). We achieve a long-lasting (>24 h) torpor-like state in mice via closed-loop feedback control of ultrasound stimulation with automated detection of body temperature. Ultrasound-induced hypothermia and hypometabolism (UIH) is triggered by activation of POA neurons, involves the dorsomedial hypothalamus as a downstream brain region and subsequent inhibition of thermogenic brown adipose tissue. Single-nucleus RNA-sequencing of POA neurons reveals TRPM2 as an ultrasound-sensitive ion channel, the knockdown of which suppresses UIH. We also demonstrate that UIH is feasible in a non-torpid animal, the rat. Our findings establish UIH as a promising technology for the noninvasive and safe induction of a torpor-like state.

Caloric restriction in humans reveals immunometabolic regulators of health span. Spadaro O, Youm Y, Shchukina I, Ryu S, Sidorov S, Ravussin A, Nguyen K, Aladyeva E, Predeus AN, Smith SR, Ravussin E, Galban C, Artyomov MN, Dixit VD. Science. 2022 Feb 11;375(6581):671-677. doi: 10.1126/science.abg7292. Epub 2022 Feb 10. PMID: 35143297 Abstract The extension of life span driven by 40% caloric restriction (CR) in rodents causes trade-offs in growth, reproduction, and immune defense that make it difficult to identify therapeutically relevant CR-mimetic targets. We report that about 14% CR for 2 years in healthy humans improved thymopoiesis and was correlated with mobilization of intrathymic ectopic lipid. CR-induced transcriptional reprogramming in adipose tissue implicated pathways regulating mitochondrial bioenergetics, anti-inflammatory responses, and longevity. Expression of the gene Pla2g7 encoding platelet activating factor acetyl hydrolase (PLA2G7) is inhibited in humans undergoing CR. Deletion of Pla2g7 in mice showed decreased thymic lipoatrophy, protection against age-related inflammation, lowered NLRP3 inflammasome activation, and improved metabolic health. Therefore, the reduction of PLA2G7 may mediate the immunometabolic effects of CR and could potentially be harnessed to lower inflammation and extend the health span.

JAMA Netw Open. 2023 Jan 3;6(1):e2247868. doi: 10.1001/jamanetworkopen.2022.47868. CYP1A2 Genetic Variation, Coffee Intake, and Kidney Dysfunction Sara Mahdavi 1 , Paolo Palatini 2 , Ahmed El-Sohemy 1 PMID: 36701157 PMCID: PMC9880799 DOI: 10.1001/jamanetworkopen.2022.47868 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2800839 Abstract Importance: Caffeine is detoxified by cytochrome P450 1A2 (CYP1A2), and genetic variation in CYP1A2 impacts the rate of caffeine clearance. Factors that may modify the association between coffee intake and kidney disease remain unclear. Objective: To assess whether CYP1A2 genotype modifies the association between coffee intake and kidney dysfunction. Design, setting, and participants: The Hypertension and Ambulatory Recording Venetia Study (HARVEST) was a prospective cohort study of individuals with stage 1 hypertension in Italy; HARVEST began on April 1, 1990, and follow-up is ongoing. The current study used data from April 1, 1990, to June 30, 2006, with follow-up of approximately 10 years. Blood pressure and biochemical data were collected monthly during the first 3 months, then every 6 months thereafter. Data were analyzed from January 2019 to March 2019. Participants were screened and recruited from general practice clinics. The present study included 1180 untreated participants aged 18 to 45 years with stage 1 hypertension; those with nephropathy, diabetes, urinary tract infection, and cardiovascular disease were excluded. Exposures: Coffee intake and CYP1A2 genotype rs762551 were exposures analyzed over a median follow-up of 7.5 (IQR, 3.1-10.9) years. Main outcomes and measures: Albuminuria (defined as an albumin level of ≥30 mg/24 h) and hyperfiltration (defined as an estimated glomerular filtration rate of ≥150 mL/min/1.73 m2) were the primary outcomes as indicators of kidney dysfunction. Results: Among 1180 participants, genotyping, lifestyle questionnaires, and urine analysis data were obtained from 604 individuals (438 [72.5%] male) with a mean (SD) age of 33.3 (8.5) years and a mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) of 25.4 (3.4). A total of 158 participants (26.2%) consumed less than 1 cup of coffee per day, 379 (62.7%) consumed 1 to 3 cups per day, and 67 (11.1%) consumed more than 3 cups per day. Genotype frequencies for rs762551 (260 participants [43.1%] with genotype AA, 247 participants [40.8%] with genotype AC, and 97 participants [16.1%] with genotype CC) did not differ between coffee intake categories. The level of risk of developing albuminuria, hyperfiltration, and hypertension, assessed by Cox regression and survival analyses, was not associated with coffee intake in the entire group or among fast metabolizers. The risks of albuminuria (adjusted hazard ratio [aHR], 2.74; 95% CI, 1.63-4.62; P < .001), hyperfiltration (aHR, 2.11; 95% CI, 1.17-3.80; P = .01), and hypertension (aHR, 2.81; 95% CI, 1.51-5.23; P = .001) increased significantly among slow metabolizers who consumed more than 3 cups per day. Conclusions and relevance: In this study, the risks of albuminuria, hyperfiltration, and hypertension increased with heavy coffee intake only among those with the AC and CC genotypes of CYP1A2 at rs762551 associated with slow caffeine metabolism, suggesting that caffeine may play a role in the development of kidney disease in susceptible individuals.

True to form, Ron. https://rationalwiki.org/wiki/Richard_Haier

https://www.aljazeera.com/news/2023/3/16/where-in-the-world-can-you-have-the-longest-retirement Saudi Arabia (26 years) Canada (15) United States (10) South Africa (2) Retirement measures mandatory and voluntary ages for a person who entered the labour force at age 22.