Association between Protein Intake and Diabetes Complications Risk Following Incident Type 2 Diabetes: The EPIC-Potsdam Study.

Our knowledge about the connection between protein intake and diabetes-related complications comes largely from studies among those already diagnosed with type 2 diabetes (T2D). However, there is a lack of information on whether changing protein intake after diabetes diagnosis affects complications risk. We aimed to explore the association between protein intake (total, animal, and plant) and vascular complications in incident T2D patients considering pre-diagnosis intake and changes in intake after diagnosis. This prospective cohort study included 1064 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort who developed T2D during follow-up (physician-verified). Dietary protein intake was measured with a food frequency questionnaire at baseline and follow-up. We included physician-reported incident diabetes complications (myocardial infarction, stroke, nephropathy, and neuropathy). A total of 388 participants developed complications, 82 macrovascular complications, and 343 microvascular complications. Substituting carbohydrates with protein showed a trend towards lower complications risk, although this association was not statistically significant (hazard ratio (HR) for 5% energy (E) substitution: 0.83; 95% confidence intervals (CI): 0.60-1.14). Increasing protein intake at the expense of carbohydrates after diabetes diagnosis was not associated with total and microvascular complications (HR for 5% E change substitution: 0.98; 95% CI: 0.89-1.08 and HR for 5% E change substitution: 1.02; 95% CI: 0.92-1.14, respectively). Replacing carbohydrates with protein did not elevate the risk of diabetes complications in incident T2D cases.

Joint Associations of Diet and Device-measured Physical Activity with Mortality and Incident CVD and Cancer: a prospective analysis of the UK Biobank Study.

BACKGROUND: We examined the joint associations of diet and device-measured intensity-specific PA with all-cause mortality (ACM), cardiovascular disease (CVD) and cancer incidence. METHODS: We used data from 79,988 participants from the UK Biobank, a population-based prospective cohort study. Light PA (LPA), moderate-to-vigorous PA (MVPA), vigorous PA (VPA) and total PA (TPA) were measured using a wrist-worn accelerometer. Diet Quality Score (DQS) was based on 10 foods and ranged from 0 (unhealthiest) to 100 (healthiest) points. We derived joint PA and diet variables. Outcomes were all-cause mortality, CVD and cancer incidence including PA, diet and adiposity-related (PDAR) cancer. RESULTS: During a median follow-up of 8 years, 2,863 deaths occurred, 11,053 participants developed CVD, 7,005 developed cancer and 3,400 developed PDAR cancer. Compared with the least favourable referent group (bottom PA tertile/low DQS), participants with middle and high (total and intensity specific) PA, except for LPA, had lower all-cause mortality risk and incident CVD risk, regardless of DQS. For example, among middle and high VPA and high DQS groups, CVD HR were 0.79 (95%CI 0.74-0.86) and 0.75 (95%CI 0.69-0.82), respectively. The pattern of cancer results was less pronounced but in agreement with the ACM and CVD incidence findings (e.g. HR 0.90, 95%CI 0.81-0.99; 0.88,0.79-0.98 and 0.82,0.74-0.92 among high VPA for low, moderate and high DQS group, respectively). CONCLUSIONS: Device-measured PA reveals novel joint associations with diet on health outcomes. IMPACT: Our results emphasize the crucial role of PA in addition to a healthy diet for reducing chronic diseases and mortality risk.

Intracranial granuloma in a patient with granulomatosis with polyangiitis under rituximab maintenance: A case report.

BACKGROUND: Rituximab (RTX) is being used for both induction and maintenance of anti-neutrophil cytoplasmic antibody (ANCA) -associated vasculitis. However, the efficacy of RTX for the granulomatous findings of granulomatosis with polyangiitis (GPA) has not been demonstrated as clearly as its vasculitic manifestations. CASE SUMMARY: A 46-year-old man was diagnosed in 2019 with GPA with constitutional symptoms, bilateral mastoiditis, prostatic necrosis, nodules in both lungs, pauci-immune necrotizing glomerulonephritis and high level of PR3-ANCA. He reached clinical remission after induction with high-dose corticosteroids and intravenous cyclophosphamide pulses at the 3rd month. Two months following the second cycle of RTX as maintenance, he developed multiple cranial mass lesions, and excisional biopsy revealed necrotizing vasculitis with granuloma formation. Remission was achieved with long-term high-dose corticosteroid therapy after surgical excision. CONCLUSION: We observed a relapse of GPA with intracranial granulomatous lesions in a patient under RTX maintenance. Limited efficacy of RTX should be considered for mainly granulomatous manifestations in patients with GPA.

Modification of incident cancer risk with changes in metabolic syndrome status: A prospective cohort study in Taiwan.

PURPOSE: We aimed to investigate the effect of altered metabolic syndrome (MetS) status on cancer risk. METHODS: From 2002 through 2008 of the Taiwan MJ cohort, there were 111,616 adults who had repeated MetS measurements performed 3.3 years apart and were followed up for cancer incidence over 11.8 years. Cancer was confirmed based on histopathological reports. RESULTS: Participants were categorized as MetS-free (n = 80,409; no MetS at the first or last health screening), MetS-developed (n = 9833; MetS absence at the first screening and presence at the last screening), MetS-recovered (n = 8958; MetS presence at the first screening and absence at the last screening), and MetS-persisted (n = 12,416; MetS presence at the first and last screenings). We used the Fine-Gray sub-distribution method, with death as competing risk, to determine the association between MetS changes and incident cancer risk. During 1320,796 person-years of follow-up, 5862 individuals developed cancer. The incidence rate of cancer per 1000 person-years was 3.89 in the MetS-free, 5.26 in MetS-developed, 4.61 in MetS-recovered, and 7.33 in MetS-persisted groups (P < .001). Compared with the MetS-free group, MetS-persisted individuals had a higher risk of incident cancer. CONCLUSIONS: Persistent MetS was found to be associated with a high risk of incident cancer.

Body mass index and cancer risk among adults with and without cardiometabolic diseases: evidence from the EPIC and UK Biobank prospective cohort studies.

BACKGROUND: Whether cancer risk associated with a higher body mass index (BMI), a surrogate measure of adiposity, differs among adults with and without cardiovascular diseases (CVD) and/or type 2 diabetes (T2D) is unclear. The primary aim of this study was to evaluate separate and joint associations of BMI and CVD/T2D with the risk of cancer. METHODS: This is an individual participant data meta-analysis of two prospective cohort studies, the UK Biobank (UKB) and the European Prospective Investigation into Cancer and nutrition (EPIC), with a total of 577,343 adults, free of cancer, T2D, and CVD at recruitment. We used Cox proportional hazard regressions to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between BMI and incidence of obesity-related cancer and in turn overall cancer with a multiplicative interaction between BMI and the two cardiometabolic diseases (CMD). HRs and 95% CIs for separate and joint associations for categories of overweight/obesity and CMD status were estimated, and additive interaction was quantified through relative excess risk due to interaction (RERI). RESULTS: In the meta-analysis of both cohorts, BMI (per ~ 5 kg/m2) was positively associated with the risk of obesity-related cancer among participants without a CMD (HR: 1.11, 95%CI: 1.07,1.16), among participants with T2D (HR: 1.11, 95% CI: 1.05,1.18), among participants with CVD (HR: 1.17, 95% CI: 1.11,1.24), and suggestively positive among those with both T2D and CVD (HR: 1.09, 95% CI: 0.94,1.25). An additive interaction between obesity (BMI ≥ 30 kg/m2) and CVD with the risk of overall cancer translated into a meta-analytical RERI of 0.28 (95% CI: 0.09-0.47). CONCLUSIONS: Irrespective of CMD status, higher BMI increased the risk of obesity-related cancer among European adults. The additive interaction between obesity and CVD suggests that obesity prevention would translate into a greater cancer risk reduction among population groups with CVD than among the general population.

Association between vegetarian diet and gouty arthritis: A retrospective cohort study.

BACKGROUND AND AIMS: A vegetarian diet is rich in vegetables, fruits, and soy products. Although vegetarian diet is beneficial for improving the health outcomes such as body mass index, metabolic syndrome, cardiovascular disease, and mortality rate, the association between a vegetarian diet and gout incidence is not well known. METHODS AND RESULTS: We linked the MJ Health Survey Data and MJ Biodata 2000 with the National Health Insurance Research Database (NHIRD) and the National Registration of Death (2000-2018). Information on the diet was collected from the MJ Health Survey Data, and the incidence of gouty arthritis was confirmed using the NHIRD. The Kaplan-Meier survival curve and log-rank test were used to compare the differences between vegetarian and non-vegetarian participants. Cox regression models were used to estimate the risk of the incidence of gouty arthritis. Among 76,972 participants, 37,297 (48.46%) were men, 2488 (3.23%) were vegetarians and the mean age was 41.65 ± 14.13 years. The mean baseline uric acid level was 6.14 ± 1.65 mg/dL. A total of 16,897 participants developed gouty arthritis, including 16,447 (22.08%) non-vegetarians and 450 (18.9%) vegetarians over a mean follow-up of 19 years. Significant differences were observed in the Kaplan-Meier survival curves between vegetarians and non-vegetarians (log-rank p < 0.001). Vegetarians had a significantly decreased incidence of gouty arthritis compared with non-vegetarians (hazard ratio = 0.87, 95% confidence interval = 0.78-0.98, p = 0.02) after adjusting for potential confounders. CONCLUSION: People with a vegetarian diet had a significantly decreased risk of developing gouty arthritis compared with non-vegetarians in Taiwan.

Development and validation of a comprehensive food frequency questionnaire that assesses the dietary intake related with dental health in children: A pilot study.

BACKGROUND AND AIMS: This study aimed to develop a validated and reliable food frequency questionnaire (FFQ) that assess dietary intake related with dental health in children. METHODS: Children, two-to-nine-years old, who consulted to a paediatric dental clinic for any reason, were recruited to complete the FFQ and 24-h recall, inquired oral hygiene habits, performed oral examinations, recorded dmft(s)/DMFT(S) index, and taken anthropometric measurements. The statistical methods used for validation were Wilcoxon signed rank test, Spearman ranked correlations, weighted kappa statistic and Bland-Altman graphs were drawn. Besides, intraclass and spearman correlation coefficients calculated for the reliability. RESULTS: A total of 120 children participated in to the first stage of the study while 70 participants completed the 4-month period. The Spearman correlation coefficient and weighted kappa values confirmed that the FFQ had moderate validation against the food records for lactose, calcium and phosphorus. Dietary fat, fibre, lactose, calcium, potassium, fluoride, magnesium, phosphorus and zinc intakes were negatively and statistically significantly correlated with DMFT and DMFS according to both FFQ and 24-h (p < 0.05, for each). Furthermore, a positive correlation between DMFT/S and dietary carbohydrate, starch, polysaccharide and sucrose intakes was obtained. CONCLUSIONS: These results provide the preliminary evidence for the moderated reliability and validity of the FFQ; the higher DMFT and DMFS scores might be linked to lower dietary intakes of fat, fibre, lactose, calcium, potassium, fluorine, magnesium, phosphorus and zinc; and probably higher dietary intakes of carbohydrate, starch, polysaccharide and sucrose in children.

Are associations of leisure-time physical activity with mortality attenuated by high levels of chronic ambient fine particulate matter (PM2.5) in older adults? A prospective cohort study.

BACKGROUND AND PURPOSE: Although leisure-time physical activity (PA) has established health benefits in older adults, it is equivocal if exercising in environments with high levels of PM2.5 concentrations is equally beneficial for them. To explore the independent and joint associations of ambient PM2.5 and PA with all-cause mortality among adults aged 60 or older and to assess the modifying effect of age (60-74 years vs. 75+ years) on the joint associations. METHODS: A prospective cohort study based on the MJ Cohort repeat examinations (2005-2016) and the Taiwan Air Quality Monitoring Network and death registry linkages (2005-2022). We included MJ Cohort participants aged 60 or more at baseline who attended the health check-ups at least twice (n = 21,760). Metabolic equivalent hours per week (MET-h/week) of leisure-time PA were computed. Multivariable adjusted associations were examined using time-varying Cox proportional hazard models. RESULTS: There were 3539 all-cause deaths over a mean follow-up of 12.81 (SD = 3.67) years. Ambient PM2.5 and physical inactivity are both independently associated with all-cause mortality. The joint associations of PA and PM2.5 concentrations with all-cause mortality differed in the young-old (60-74 years) and the older-old (75+ years) (P for interaction = 0.01); Higher levels of long-term PM2.5 exposures (≥25 µg/m3) had little influence on the associations between PA and mortality in the young-old (HR = 0.68 (0.56-0.83) and HR = 0.72 (0.59-0.88) for participants with 7.5-<15 and 15+ MET-h/week respectively) but eliminated associations between exposure and outcome in the older-old (HR = 0.91 (0.69-01.21) and HR = 1.02 (0.76-1.38) for participants with 7.5-<15 and 15+ MET-h/week). CONCLUSION: Long-term exposures to higher PM2.5 concentrations may eliminate the beneficial associations of PA with all-cause mortality among adults aged 75 and over.

Associations of changes in physical activity and diet with incident obesity and changes in adiposity: Longitudinal findings from the UK Biobank.

We examined the association of changes in physical activity and diet with obesity development and changes in body fat percentage, body mass index, and waist circumference. 31,344 adults without obesity at baseline (age = 56.0 ± 7.5 years; female = 49.1%) from the UK Biobank were included. Physical activity was categorised based on public health guidelines as: inactive; insufficient; and sufficient. Diet category was assigned based on an established composited score that included consumption of fruits, vegetables, fish, red meat (unprocessed), and processed meat. Diet was categorised as: poor; reasonable; and good. Physical activity and diet changes were categorised based on changes in category: worsened; stable; increased (physical activity)/improved (diet). During a mean follow up of 6.8 (SD = ±2.3) years, 1354 (4.3%) participants developed obesity. Compared to stable physical activity-diet, increasing physical activity was associated with the lowest obesity odds, across diet changes (e.g., OR [95%CI]: diet worsened (0.89 [0.69, 1.15]); diet improved (0.65 [0.48, 0.89])). Increasing physical activity with improved diet was associated with the largest difference in body fat percentage (ß:-0.62 [-0.82, -0.41]), body mass index (-0.37 [-0.47, -0.28]), and waist circumference (-1.21 [-1.63, -0.79]). Excluding adults with a history of smoking, or major illness, lowered obesity odds among participants with increased physical activity by an additional 11%-21%. In those who decreased physical activity obesity was attenuated when combined with diet improvement. Improvements in physical activity or diet mutually attenuated the deleterious associations of the other behaviour's deterioration. In most analyses, increases in physical activity conferred consistent positive associations against the development of obesity, across dietary change groups.

Modification of the all-cause and cardiovascular disease related mortality risk with changes in the metabolic syndrome status: a population-based prospective cohort study in Taiwan.

AIM: To examine whether changes in metabolic syndrome (MetS) status over time are associated with risk of all-cause and cardiovascular disease related (CVD) mortality. METHODS: This prospective cohort study consisted of 544,749 individuals who participated in a self-funded comprehensive health surveillance program offered by Taiwan MJ Health Management Institution between 1998 and 2016. We included 236,216 adults who had at least two repeated MetS measures 5.9 (4.6) years apart and were followed up for mortality over 18.8 (5.2) years. Participants were classified according to the change in their MetS status as follows: MetS-free at both time points (n = 173,116), MetS-developed (n = 22,607), MetS-recovered (n = 13,616), and MetS-persistent (n = 26,877). Multivariable Cox proportional hazards model was used to determine the association between change in MetS status and risk of all-cause and CVD mortality. RESULTS: Over the 4,436,842 person-years follow-up period, 14,226 participants died, including 2671 (19%) of CVD-related causes. The crude CVD mortality rate per 1000 person-years in the study groups were MetS-free, 0.32; MetS-developed, 0.75; MetS-recovered, 1.22; and MetS-persistent, 2.00 (P < 0.001). Compared to the persistent MetS group, participants in the MetS-recovered group had a lower risk of all-cause (adjusted hazard ratio [aHR], 0.87; 95%CI, 0.82-0.92) and CVD mortality (aHR, 0.81; 95% confidence interval [CI], 0.71-0.93). Development of MetS increased the risk for all-cause (aHR, 1.11; 95%CI, 1.05-1.17) and CVD mortality (aHR, 1.22; 95%CI, 1.07-1.39), compared to the MetS-free group. CONCLUSION: Recovery from MetS was significantly associated with a lower risk of all-cause and CVD mortality, whereas development of MetS was associated with increased risk.

Joint association of alcohol consumption and adiposity with alcohol- and obesity-related cancer in a population sample of 399,575 UK adults.

Obesity and alcohol consumption are both important modifiable risk factors for cancer. We examined the joint association of adiposity and alcohol consumption with alcohol- and obesity-related cancer incidence. This prospective cohort study included cancer-free UK Biobank participants aged 40-69 years. Alcohol consumption was categorised based on current UK guidelines into four groups. We defined three markers of adiposity: body fat percentage (BF %), waist circumference and BMI and categorised each into three groups. We derived a joint alcohol consumption and adiposity marker variable with twelve mutually exclusive categories. Among 399 575 participants, 17 617 developed alcohol-related cancer and 20 214 developed obesity-related cancer over an average follow-up of 11·8 (SD 0·9) years. We found relatively weak evidence of independent associations of alcohol consumption with cancer outcomes. However, the joint association analyses showed that across all adiposity markers, above guideline drinkers who were in the top two adiposity groups had elevated cancer incidence risk (e.g. HR for alcohol-related cancer was 1·53 (95 % CI (1·24, 1·90)) for within guideline drinkers and 1·61 (95 % CI (1·30, 2·00)) for above guideline drinkers among participants who were in the top tertile BF %. Regardless of alcohol consumption status, the risk of obesity-related cancer increased with higher adiposity in a dose-response manner within alcohol consumption categories. Our study provides guidance for public health priorities aimed at lowering population cancer risk via two key modifiable risk factors.

Body shape phenotypes of multiple anthropometric traits and cancer risk: a multi-national cohort study.

BACKGROUND: Classical anthropometric traits may fail to fully represent the relationship of weight, adiposity, and height with cancer risk. We investigated the associations of body shape phenotypes with the risk of overall and site-specific cancers. METHODS: We derived four distinct body shape phenotypes from principal component (PC) analysis on height, weight, body mass index (BMI), waist (WC) and hip circumferences (HC), and waist-to-hip ratio (WHR). The study included 340,152 men and women from 9 European countries, aged mostly 35-65 years at recruitment (1990-2000) in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: After a median follow-up of 15.3 years, 47,110 incident cancer cases were recorded. PC1 (overall adiposity) was positively associated with the risk of overall cancer, with a HR per 1 standard deviation (SD) increment equal to 1.07 (95% confidence interval 1.05 to 1.08). Positive associations were observed with 10 cancer types, with HRs (per 1 SD) ranging from 1.36 (1.30-1.42) for endometrial cancer to 1.08 (1.03-1.13) for rectal cancer. PC2 (tall stature with low WHR) was positively associated with the risk of overall cancer (1.03; 1.02-1.04) and five cancer types which were not associated with PC1. PC3 (tall stature with high WHR) was positively associated with the risk of overall cancer (1.04; 1.03-1.05) and 12 cancer types. PC4 (high BMI and weight with low WC and HC) was not associated with overall risk of cancer (1.00; 0.99-1.01). CONCLUSIONS: In this multi-national study, distinct body shape phenotypes were positively associated with the incidence of 17 different cancers and overall cancer.

Alcohol Consumption and Adiposity: A Longitudinal Analysis of 45,399 UK Biobank Participants.

The evidence on the association between alcohol consumption and adiposity is inconsistent and fragmented. We investigated the longitudinal association between alcohol consumption pattern and four different adiposity markers with repeated measures of adiposity and obesity incidence. We categorized current drinkers based on the sex-specific quartiles of their weekly alcohol consumption and the UK alcohol drinking guidelines. We used multivariable adjusted generalised linear models. With the exception of a direct association between alcohol volume and body fat percentage (BF%) in women (B = 0.42%; 95%CI: 0.04, 0.80% for women in the top quartile), we found no associations between alcohol consumption and adiposity markers for either sex. Red wine and champagne/white wine consumption were inversely associated with waist circumference (WC) for both sexes (B = -0.58 cm, 95%CI: -0.77, -0.38 cm and B= -0.49 cm, 95%CI: -0.68, -0.29 cm, respectively, for women; B = -0.28 cm, 95%CI: -0.47, -0.08 cm and B = -0.23 cm, 95%CI: -0.42, -0.04 cm, respectively, for men). Female and male spirit drinkers had higher WC than non-spirit drinkers. Alcohol consumption was associated with a lower risk of obesity incidence in women (OR:0.60, 95%CI:0.45, 0.80 for the 2nd quartile, OR:0.53, 95%CI: 0.40, 0.70 for the 3rd quartile and OR:0.61, 95%CI:0.46, 0.80 for the 4th quartile). We found limited evidence of longitudinal associations between alcohol intake and adiposity. The few statistically significant associations we observed are unlikely to be of clinical importance.

YouTube: Is It a Reliable Source of Nutrition Information on COVID-19 Pandemic?

Data on the nutrition-related misinformation about COVID-19 are limited. This study analysed the quality and accuracy of the nutrition information available on YouTube about current COVID-19 pandemic as well as assessed the content of the videos. YouTube was searched using the terms "nutrition and COVID-19" in Turkish on 1 February 2021. Videos were filtered according to relevancy, and the first 280 videos were analysed. A total of 218 videos were reviewed and classified as "misleading" or "relevant" depending on the information provided. The transparency, utility, reliability, and accuracy of video contents were assessed. The videos attracted a cumulative 6,258,694 views. There were 178 (81.7%) fully relevant and 40 (18.3%) misleading videos. Approximately 80% of the videos shared by health professionals were relevant videos. Government organisations only shared relevant videos. Relevant videos had higher reliability, accuracy, and quality than misleading videos. The nutrition-related content of COVID-19 videos is suboptimal on YouTube. As the COVID-19 pandemic worsens, and nutrition could improve immunity, health professionals and educational and government organisations need to engage more in the spread of nutrition-related COVID-19 information to Internet platforms based on nutrition guidelines and the latest scientific evidence. This will be a practical and immediately implementable public health strategy to effectively spread the right information.

Changes in physical activity and adiposity with all-cause, cardiovascular disease, and cancer mortality.

BACKGROUND: The relationship between joint changes in physical activity and adiposity with mortality is not well understood. We examined the association of changes in these two established risk factors with all-cause (ACM), cardiovascular disease (CVD), and cancer mortality. METHODS: We used longitudinal data from Taiwan's MJ Cohort, comprising 116,228 general population adults recruited from 1998-2013 with repeated measures 4.6 y (2.5) apart and followed up for mortality for 11.9 y (3.5). Physical activity, body mass index (BMI), waist circumference (WC), and body fat percentage (BF%) groups and changes were based on public health and clinical guidelines. RESULTS: Compared to stable-insufficient physical activity, increasing physical activity from any baseline level was associated with lower ACM (HR [95%CI]): 0.85 [0.74, 0.96]) and CVD mortality (0.72 [0.55, 0.93]) risk. This was approximately equal to meeting physical activity guidelines at both timepoints (eg: 0.71 [0.58, 0.88] for CVD mortality). Compared to stable-overweight/moderate adiposity, decreasing adiposity level attenuated but did not offset mortality risk for all three outcomes (eg: BMI = 0.95 [0.76, 1.16] for CVD mortality). Only maintaining a healthy adiposity level at both timepoints offset mortality risk (BMI = 0.75 [0.61, 0.89]) for CVD mortality). In the joint changes analyses, lower mortality risk was a consequence of increases in physical activity across adiposity change groups (eg: WC decrease = 0.57 [0.48, 0.67]; WC stability = 0.73 [0.66, 0.80], WC increase = 0.83 [0.72, 0.97] for ACM). Decreasing adiposity attenuated the negative associations of decreased physical activity (BF% = 1.13 [0.95, 1.35] for ACM). CONCLUSIONS: We found a lower risk for ACM, CVD, and cancer mortality from increasing physical activity and an attenuation from decreasing adiposity regardless of baseline levels. The beneficial associations of joint changes were primarily driven by physical activity, suggesting lower mortality risk may be more immediate through physical activity improvements compared to adiposity improvements alone.

Migratory and anti-fibrotic programmes define the regenerative potential of human cardiac progenitors.

Heart regeneration is an unmet clinical need, hampered by limited renewal of adult cardiomyocytes and fibrotic scarring. Pluripotent stem cell-based strategies are emerging, but unravelling cellular dynamics of host-graft crosstalk remains elusive. Here, by combining lineage tracing and single-cell transcriptomics in injured non-human primate heart biomimics, we uncover the coordinated action modes of human progenitor-mediated muscle repair. Chemoattraction via CXCL12/CXCR4 directs cellular migration to injury sites. Activated fibroblast repulsion targets fibrosis by SLIT2/ROBO1 guidance in organizing cytoskeletal dynamics. Ultimately, differentiation and electromechanical integration lead to functional restoration of damaged heart muscle. In vivo transplantation into acutely and chronically injured porcine hearts illustrated CXCR4-dependent homing, de novo formation of heart muscle, scar-volume reduction and prevention of heart failure progression. Concurrent endothelial differentiation contributed to graft neovascularization. Our study demonstrates that inherent developmental programmes within cardiac progenitors are sequentially activated in disease, enabling the cells to sense and counteract acute and chronic injury.

Epicardium-derived cells organize through tight junctions to replenish cardiac muscle in salamanders.

The contribution of the epicardium, the outermost layer of the heart, to cardiac regeneration has remained controversial due to a lack of suitable analytical tools. By combining genetic marker-independent lineage-tracing strategies with transcriptional profiling and loss-of-function methods, we report here that the epicardium of the highly regenerative salamander species Pleurodeles waltl has an intrinsic capacity to differentiate into cardiomyocytes. Following cryoinjury, CLDN6+ epicardium-derived cells appear at the lesion site, organize into honeycomb-like structures connected via focal tight junctions and undergo transcriptional reprogramming that results in concomitant differentiation into de novo cardiomyocytes. Ablation of CLDN6+ differentiation intermediates as well as disruption of their tight junctions impairs cardiac regeneration. Salamanders constitute the evolutionarily closest species to mammals with an extensive ability to regenerate heart muscle and our results highlight the epicardium and tight junctions as key targets in efforts to promote cardiac regeneration.

Alcohol intake and mortality risk of COVID-19, pneumonia, and other infectious diseases: An analysis of 437191 UK biobank participants.

This study aims to investigate the association between alcohol consumption and COVID-19, infectious diseases, and pneumonia mortality. This is a prospective analysis of 437,191 UK Biobank participants (age 56.3 years, 54% female). The main exposure was self-reported alcohol consumption. In addition to never and previous drinkers, we applied quartiles-based and UK guidelines-based criteria to divide current drinkers by weekly consumption into four groups. Outcomes included COVID-19, infectious diseases, and pneumonia mortality, obtained from the national death registries until May 2020. After an 11-year follow-up, compared to never drinkers, previous drinkers had higher mortality risks of infectious diseases and pneumonia (adjusted HR: 1.29 [95% CI 1.06-1.57] and 1.35 [1.07-1.70], respectively), but not COVID-19. There was a curvilinear association of alcohol consumption with infectious diseases and pneumonia mortality. Drinking within-guidelines (<14 UK units/wk) and amounts up to double the recommendation (14 to < 28 UK units/wk) was associated with the lowest mortality risks of infectious diseases (0.70 [0.59-0.83] and 0.70 [0.59-0.83], respectively) and pneumonia (0.71 [0.58-0.87] and 0.72 [0.58-0.88], respectively). Alcohol consumption was associated with lower risks of COVID-19 mortality (e.g., drinking within-guidelines: 0.53 [0.33-0.86]). Drinkers reporting multiples of the recommended alcohol drinking amounts did not have higher mortality risks of COVID-19 and other infectious diseases than never drinkers. Despite the well-established unfavorable effects on general health, we found no deleterious associations between alcohol consumption and the risk of infectious diseases, including COVID-19. Future research with other study designs is needed to confirm the causality.

Prospective Associations of Accelerometer-Assessed Physical Activity With Mortality and Incidence of Cardiovascular Disease Among Adults With Hypertension: The UK Biobank Study.

Background Despite the well-established capacity of physical activity to reduce blood pressure, the associations between physical activity with cardiovascular disease (CVD) incidence and mortality in people living with hypertension are not well understood. We examine the dose-response associations of device-assessed physical activity with all-cause and CVD mortality and CVD incidence (total, stroke, and coronary heart disease) in adults with hypertension. Methods and Results This prospective study included data from 39 294 participants with hypertension in the UK Biobank study who had valid accelerometry data and for whom mortality and CVD followed-up data were available. We categorized moderate-to-vigorous physical activity and total physical activity volume into 4 categories based on the 10th, 50th, and 90th percentiles and used Cox regressions to estimate their associations with CVD mortality and incidence outcomes. Splines were used to assess the dose-response associations. During a median follow-up of 6.25 years (241 418 person-years), 1518 deaths (549 attributable to CVD) and 4933 CVD (fatal and nonfatal) incident events were registered. Compared with the lowest category of moderate-to-vigorous physical activity, the relative risks (hazard ratios and 95% CIs) of all-cause mortality for increasing categories were 0.53 (0.46-0.61), 0.41 (0.34-0.49), and 0.36 (0.26-0.49). We found associations of similar magnitude for total CVD incidence, stroke, and coronary heart disease; and for total physical activity volume across all outcomes. For all outcomes, there were linear or nearly linear inverse dose-response relationships with no evidence of harms with high levels of physical activity. Results were robust to removing participants who died within the first 2 years. Conclusions Our findings underscore the importance of physical activity for people living with hypertension and provide novel insights to support the development of physical activity guideline recommendations for this high-risk group.

Effect of severe compared with moderate energy restriction on physical activity among postmenopausal female adults with obesity: a prespecified secondary analysis of the Type of Energy Manipulation for Promoting optimum metabolic health and body composition in Obesity (TEMPO) Diet randomized controlled Trial.

BACKGROUND: An under-explored strategy for increasing physical activity is the dietary treatment of obesity, but empirical evidence is lacking. OBJECTIVES: We aimed to compare the effects of weight loss via severe as opposed to moderate energy restriction on physical activity over 36 mo. METHODS: A total of 101 postmenopausal female adults (45-65 y, BMI 30-40 kg/m2, <180 min/wk of structured exercise) were randomly assigned to either 12 mo of moderate energy restriction (25%-35% of energy requirement) with a food-based diet, or a severe intervention involving 4 mo of severe energy restriction (65%-75% of energy requirement) with a total meal replacement diet, followed by 8 mo of moderate energy restriction. Physical activity was encouraged, but no tailored or supervised exercise prescription was provided. Physical activity was assessed with an accelerometer worn for 7 d before baseline (0 mo) and 0.25, 1, 4, 6, 12, 24, and 36 mo after intervention commencement. RESULTS: Compared with the moderate group, the severe group exhibited greater mean: total volume of physical activity; duration of moderate-to-vigorous-intensity physical activity (MVPA); duration of light-intensity physical activity; step counts, as well as lower mean duration of sedentary time. All these differences (except step counts) were apparent at 6 mo [e.g., 1006 metabolic equivalent of task (MET)-min/wk; 95% CI: 564, 1449 MET-min/wk for total volume of physical activity], and some were also apparent at 4 and/or 12 mo. There were no differences between groups in the 2 other outcomes investigated (self-efficacy to regulate exercise; and proportion of participants meeting the WHO's 2020 Physical Activity Guidelines for MVPA). When the analyses were adjusted for weight at each time point, the differences between groups were either attenuated or abolished. CONCLUSIONS: Among female adults with obesity, including a dietary component to reduce excess body weight-notably one involving severe energy restriction-could potentially enhance the effectiveness of physical activity interventions.This trial was registered at www.anzctr.org.au as ACTRN12612000651886.