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OBJECTIVE: The objective of this study was to compare race- and ethnicity-specific BMI cutoffs for the three classes of obesity based on equivalent risk of type 2 diabetes (T2D). METHODS: Participants without T2D were included from the UK Biobank, the China Health and Nutrition Survey, and the Singapore Chinese Health Study. Poisson regressions with restricted cubic splines were applied to determine BMI cutoffs for each non-White race and ethnicity for equivalent incidence rates of T2D at BMI values of 30.0, 35.0, and 40.0 kg/m2 in White adults. RESULTS: During a median follow-up of 13.8 years among 507,763 individuals, 5.2% developed T2D. In women, BMI cutoffs for an equivalent incidence rate of T2D as observed at 40.0 kg/m2 in White adults were 31.6 kg/m2 in Black, 29.2 kg/m2 in British Chinese, 27.3 kg/m2 in South Asian, 26.9 kg/m2 in Native Chinese, and 25.1 kg/m2 in Singapore Chinese adults. In men, the corresponding BMI cutoffs were 31.9 kg/m2 in Black, 30.6 kg/m2 in British Chinese, 29.0 kg/m2 in South Asian, 29.6 kg/m2 in Native Chinese, and 27.6 kg/m2 in Singapore Chinese adults. The race and ethnicity order was consistent when equivalent BMI cutoffs were estimated for class I and II obesity. CONCLUSIONS: Establishing a race- and ethnicity-tailored classification of the three classes of obesity is urgently needed.

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OBJECTIVE: To investigate the associations between data-driven dietary patterns, immune function, and incident type 2 diabetes (T2D) and the mediating effects of immune function. METHODS: This study included 375,665 participants without diabetes at baseline in the UK Biobank study. Dietary patterns were derived through principal component analysis of food frequency questionnaire data. Immune function was assessed using 14 individual inflammatory markers and an integrated low-grade inflammation score (INFLA-score). Cox proportional hazard models were used to estimate the associations of dietary patterns or immune function with incident T2D. Linear regressions were used to estimate the associations of dietary patterns with immune function. Mediating effects of immune function were quantified. RESULTS: During a median 14.6-year follow-up, 13,932 participants developed T2D. Four dietary patterns were identified: prudent diet (high in whole grains, vegetables, fruits, fish), wheat/dairy/eggs restrictive diet (limiting these foods), meat-based diet (high in red/processed meat, salt), and full-cream dairy diet (preference for full cream milk or dairy products). The prudent diet was negatively (HRQ4 vs Q1, 0.69 [95% CI, 0.65-0.72]), while the wheat/dairy/eggs restrictive diet (HRQ4 vs Q1, 1.08 [95% CI, 1.03-1.13]), meat-based diet (HRQ4 vs Q1, 1.12 [95% CI, 1.06-1.17]), and full-cream dairy diet (HRQ4 vs Q1, 1.08 [95% CI, 1.03-1.12]) were positively associated with incident T2D (all p for trend ≤0.04). The prudent diet was negatively and the full-cream dairy diet was positively associated with most inflammatory markers. Most inflammatory markers, especially INFLA-score (HR, 1.18 [95% CI, 1.16-1.20]), were positively associated with incident T2D. INFLA-score mediated 13% of the association with incident T2D for the prudent diet and 34% for the full-cream dairy diet. CONCLUSIONS: This study identified four distinct dietary patterns and a range of inflammatory markers associated with incident T2D. A notable proportion of the associations between dietary patterns and T2D was mediated by immune function.

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Secondary fermentation in beer can result in undesirable consequences, such as off-flavors, increased alcohol content, hyperattenuation, gushing, and the spontaneous explosion of packaging. Strains of Saccharomyces cerevisiae var. diastaticus are a major contributor to such spoilage due to their production of extracellular glucoamylase enzyme encoded by the STA1 gene. Saccharomyces yeasts can naturally produce antifungal proteins named "killer" toxins that inhibit the growth of competing yeasts. Challenging diastatic yeasts with killer toxins revealed that 91% of strains are susceptible to the K1 killer toxin produced by S. cerevisiae. Screening of 192 killer yeasts identified novel K2 toxins that could inhibit all K1-resistant diastatic yeasts. Variant K2 killer toxins were more potent than the K1 and K2 toxins, inhibiting 95% of diastatic yeast strains tested. Brewing trials demonstrated that adding killer yeast during a simulated diastatic contamination event could prevent hyperattenuation. Currently, most craft breweries can only safeguard against diastatic yeast contamination by good hygiene and monitoring for the presence of diastatic yeasts. The detection of diastatic yeasts will often lead to the destruction of contaminated products and the aggressive decontamination of brewing facilities. Using killer yeasts in brewing offers an approach to safeguard against product loss and potentially remediate contaminated beer.IMPORTANCEThe rise of craft brewing means that more domestic beer in the marketplace is being produced in facilities lacking the means for pasteurization, which increases the risk of microbial spoilage. The most damaging spoilage yeasts are "diastatic" strains of Saccharomyces cerevisiae that cause increased fermentation (hyperattenuation), resulting in unpalatable flavors such as phenolic off-flavor, as well as over-carbonation that can cause exploding packaging. In the absence of a pasteurizer, there are no methods available that would avert the loss of beer due to contamination by diastatic yeasts. This manuscript has found that diastatic yeasts are sensitive to antifungal proteins named "killer toxins" produced by Saccharomyces yeasts, and in industrial-scale fermentation trials, killer yeasts can remediate diastatic yeast contamination. Using killer toxins to prevent diastatic contamination is a unique and innovative approach that could prevent lost revenue to yeast spoilage and save many breweries the time and cost of purchasing and installing a pasteurizer.

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CONTEXT: The investigation of the association between blood glucose within normal range and all-cause mortality among individuals without traditional risk factors is limited. OBJECTIVE: To determine the associations of 3 glycemic measures (fasting plasma glucose [FPG], hemoglobin A1c [HbA1c], and 2-h glucose) in the normal range with all-cause mortality among individuals without traditional risk factors. DESIGN: Retrospective cohort study. SETTING: US National Health and Nutrition Examination Survey in 1988-1994 and 1999-2018. PARTICIPANTS: Non-pregnant adults who had a measurement of 2-h glucose, FPG, and HbA1c, and absence of traditional risk factors were included. MAIN OUTCOME MEASURES: Cox proportional hazard models were performed to examine the associations of normal FPG (n=5793), normal HbA1c (n=8179), and normal 2-h glucose (n=3404) with all-cause mortality. RESULTS: The significant association was found between 2-h glucose within the normal range and all-cause mortality among those without traditional risk factors. Compared to participants with 2-h glucose <80 mg/dL, participants with a higher normal 2-h glucose level had a higher risk of all-cause mortality (110-139 mg/dL: HR, 1.80 [95% CI, 1.03-3.15]). In the subgroup analysis, significant associations were also found among people aged ≥60 years and men. No significant associations were found between normal FPG and HbA1c levels and all-cause mortality. CONCLUSIONS: Among US adults without traditional risk factors, high normal 2-h glucose level was positively associated with all-cause mortality. This result highlights the potential importance of maintaining a lower normal level of 2-h glucose for preventing mortality in individuals who are conventionally considered to be cardiovascular healthy.

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BACKGROUND: To investigate whether and what lifestyle factors in later life modify the associations of early-life smoking behaviors and genetic susceptibility with type 2 diabetes (T2D). METHODS: In the UK Biobank, in utero tobacco exposure (n = 354,493) and age of smoking initiation (n = 353,557) were self-reported. A composite lifestyle score was calculated based on diet, physical activity, nicotine exposure, sleep duration, and BMI. Hazard ratio (HR) and absolute risk difference (ARD) were used to estimate the associations of early-life smoking behaviors and genetic risk with incident T2D, as well as the effect modification of the lifestyle score. RESULTS: During a median follow-up of 14.6 years, the HRs (95 % CIs) of T2D for in utero tobacco exposure, and smoking initiation in adulthood, adolescence, and childhood, compared with no smoking behavior, were 1.19 (1.16-1.23), 1.34 (1.29-1.39), 1.58 (1.53-1.64), 2.22 (2.11-2.32), respectively (P for trend<0.001). Early-life smoking behaviors and high genetic risk (vs no smoking behavior and low genetic risk) were associated with a 302%-593 % higher T2D risk (P for additive interaction<0.05). Compared to participants with early-life smoking behaviors, high genetic risk, and an unfavorable lifestyle, those who adhered to a favorable lifestyle had a lower T2D risk in all subgroups (HRs from 0.05 to 0.36 and ARD from -14.97 % to -9.51 %), with the highest ARD attributable to lifestyle in participants with early-life smoking behaviors and high genetic risk. CONCLUSIONS: The T2D risk associated with early-life smoking behaviors and genetic risk was modified by a favorable lifestyle.

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Photosystem II (PS II) assembly is a stepwise process involving preassembly complexes or modules focused around four core PS II proteins. The current model of PS II assembly in cyanobacteria is derived from studies involving the deletion of one or more of these core subunits. Such deletions may destabilize other PS II assembly intermediates, making constructing a clear picture of the intermediate events difficult. Information on plastoquinone exchange pathways operating within PS II is also unclear and relies heavily on computer-aided simulations. Deletion of PsbX in [S. Biswas, J.J. Eaton-Rye, Biochim. Biophys. Acta - Bioenerg. 1863 (2022) 148519] suggested modified QB binding in PS II lacking this subunit. This study has indicated the phenotype of the ∆PsbX mutant arose by disrupting a conserved hydrogen bond between PsbX and the D2 (PsbD) protein. We mutated two conserved arginine residues (D2:Arg24 and D2:Arg26) to further understand the observations made with the ∆PsbX mutant. Mutating Arg24 disrupted the interaction between PsbX and D2, replicating the high-light sensitivity and altered fluorescence decay kinetics observed in the ∆PsbX strain. The Arg26 residue, on the other hand, was more important for either PS II assembly or for stabilizing the fully assembled complex. The effects of mutating both arginine residues to alanine or aspartate were severe enough to render the corresponding double mutants non-photoautotrophic. Our study furthers our knowledge of the amino-acid interactions stabilizing plastoquinone-exchange pathways while providing a platform to study PS II assembly and repair without the actual deletion of any proteins.

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OBJECTIVE: Whether genetic susceptibility to disease and dietary cholesterol (DC) absorption contribute to inconsistent associations of DC consumption with diabetes and cardiovascular disease (CVD) remains unclear. RESEARCH DESIGN AND METHODS: DC consumption was assessed by repeated 24-h dietary recalls in the UK Biobank. A polygenetic risk score (PRS) for DC absorption was constructed using genetic variants in the Niemann-Pick C1-Like 1 and ATP Binding Cassettes G5 and G8 genes. PRSs for diabetes, coronary artery disease, and stroke were also created. The associations of DC consumption with incident diabetes (n = 96,826) and CVD (n = 94,536) in the overall sample and by PRS subgroups were evaluated using adjusted Cox models. RESULTS: Each additional 300 mg/day of DC consumption was associated with incident diabetes (hazard ratio [HR], 1.17 [95% CI, 1.07-1.27]) and CVD (HR, 1.09 [95% CI, 1.03-1.17]), but further adjusting for BMI nullified these associations (HR for diabetes, 0.99 [95% CI, 0.90-1.09]; HR for CVD, 1.04 [95% CI, 0.98-1.12]). Genetic susceptibility to the diseases did not modify these associations (P for interaction ≥0.06). The DC-CVD association appeared to be stronger in people with greater genetic susceptibility to cholesterol absorption assessed by the non-high-density lipoprotein cholesterol-related PRS (P for interaction = 0.04), but the stratum-level association estimates were not statistically significant. CONCLUSIONS: DC consumption was not associated with incident diabetes and CVD, after adjusting for BMI, in the overall sample and in subgroups stratified by genetic predisposition to cholesterol absorption and the diseases. Nevertheless, whether genetic predisposition to cholesterol absorption modifies the DC-CVD association requires further investigation.

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BACKGROUND: Noninvasive and early assessment of liver fibrosis is of great significance and is challenging. We aimed to evaluate the predictive performance and cost-effectiveness of the LiverRisk score for liver fibrosis and liver-related and diabetes-related mortality in the general population. METHODS: The general population from the NHANES 2017-March 2020, NHANES 1999-2018, and UK Biobank 2006-2010 were included in the cross-sectional cohort (n = 3,770), along with the NHANES follow-up cohort (n = 25,317) and the UK Biobank follow-up cohort (n = 17,259). The cost-effectiveness analysis was performed using TreeAge Pro software. Liver stiffness measurements ≥10 kPa were defined as compensated advanced chronic liver disease (cACLD). FINDINGS: Compared to conventional scores, the LiverRisk score had significantly better accuracy and calibration in predicting liver fibrosis, with an area under the receiver operating characteristic curve (AUC) of 0.76 (0.72-0.79) for cACLD. According to the updated thresholds of LiverRisk score (6 and 10), we reclassified the population into three groups: low, medium, and high risk. The AUCs of LiverRisk score for predicting liver-related and diabetes-related mortality at 5, 10, and 15 years were all above 0.8, with better performance than the Fibrosis-4 score. Furthermore, compared to the low-risk group, the medium-risk and high-risk groups in the two follow-up cohorts had a significantly higher risk of liver-related and diabetes-related mortality. Finally, the cost-effectiveness analysis showed that the incremental cost-effectiveness ratio for LiverRisk score compared to FIB-4 was USD $18,170 per additional quality-adjusted life-year (QALY) gained, below the willingness-to-pay threshold of $50,000/QALY. CONCLUSIONS: The LiverRisk score is an accurate, cost-effective tool to predict liver fibrosis and liver-related and diabetes-related mortality in the general population. FUNDING: The National Natural Science Foundation of China (nos. 82330060, 92059202, and 92359304); the Key Research and Development Program of Jiangsu Province (BE2023767a); the Fundamental Research Fund of Southeast University (3290002303A2); Changjiang Scholars Talent Cultivation Project of Zhongda Hospital of Southeast University (2023YJXYYRCPY03); and the Research Personnel Cultivation Program of Zhongda Hospital Southeast University (CZXM-GSP-RC125).

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OBJECTIVE: This study aimed to assess the association of shift work with blood glucose and the mediating role of oxidative stress. METHODS: Fasting plasma glucose (FPG) and urinary concentrations of oxidative stress biomarkers (8-hydroxy-2'-deoxyguanosine [8-OHdG], 4-hydroxy-2-nonenal-mercapturic acid, and 8-iso-prostaglandin F2α [8-isoPGF2α ]) were measured among 831 participants. RESULTS: Positive dose-response relationships among shift work duration,  FPG (ptrend < 0.001), and abnormal glucose regulation (AGR; ptrend = 0.035) were found. Compared with participants without shift work, three-shift work was associated with a higher level of FPG (percentage change: 6.49%, 95% CI: 4.21%-8.83%) and a higher prevalence of impaired fasting glucose (odds ratio: 1.886, 95% CI: 1.114-3.192) and AGR (odds ratio: 1.929, 95% CI: 1.197-3.111). A dose-response relationship was found between shift work duration and 8-OHdG (ptrend = 0.002) and 8-isoPGF2α (ptrend = 0.019). Urinary 8-OHdG and 8-isoPGF2α partially mediated the association between shift work duration and FPG levels and the prevalence of impaired fasting glucose and AGR, with mediating proportions ranging from 4.77% to 20.76%. CONCLUSIONS: These findings suggest that shift work is positively associated with blood glucose, and the association is partially mediated by oxidative stress.

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Background Cardiometabolic health has been worsening among young adults, but the prevalence of lifestyle risk factors and cardiometabolic diseases is unclear. Methods and Results Adults aged 18 to 44 years were included from the National Health and Nutrition Examination Survey, 2011 to 2018. Age-standardized prevalence of lifestyle risk factors and cardiometabolic diseases was estimated overall and by demographic and social risk factors. A set of multivariable logistic regressions was sequentially performed by adjusting for age, sex, social risk factors, and lifestyle factors to determine whether racial and ethnic disparities in the prevalence of cardiometabolic diseases may be attributable to differences in social risk factors and lifestyle factors. Appropriate weights were used to ensure national representativeness of the estimates. A total of 10 405 participants were analyzed (median age, 30.3 years; 50.8% women; 32.3% non-Hispanic White). The prevalence of lifestyle risk factors ranged from 16.3% for excessive drinking to 49.3% for poor diet quality. The prevalence of cardiometabolic diseases ranged from 4.3% for diabetes to 37.3% for dyslipidemia. The prevalence of having ≥2 lifestyle risk factors was 45.2% and having ≥2 cardiometabolic diseases was 22.0%. Racial and ethnic disparities in many cardiometabolic diseases persisted but were attenuated after adjusting for social risk factors and lifestyle factors. Conclusions The prevalence of lifestyle risk factors and cardiometabolic diseases was high among US young adults and varied by race and ethnicity and social risk factors. Racial and ethnic disparities in the prevalence of cardiometabolic diseases were not fully explained by differences in social risk factors and lifestyle factors.

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BACKGROUND: Nationwide achievement of guideline-recommended diabetes care targets has not been comprehensively assessed in China. OBJECTIVE: To estimate the proportions of adults with diabetes achieving major clinical risk factor control, body mass index (BMI), lifestyle, and dietary targets specified in the Chinese diabetes guidelines. DESIGN: Nationwide cross-sectional survey. SETTING: China, 2015 to 2017. PARTICIPANTS: A national sample of 8401 adults with self-reported diabetes and a subset of 3531 with dietary data. MEASUREMENTS: The assessed targets included 1) ABC targets (individualized hemoglobin A1c [HbA1c] target; blood pressure [BP] <130/80 mm Hg; and low-density lipoprotein cholesterol [LDL-C] level <2.6 or <1.8 mmol/L [<100 or <70 mg/dL], depending on the presence of atherosclerotic cardiovascular disease), 2) BMI below 24 kg/m2, 3) lifestyle targets (not currently smoking or drinking, guideline-recommended leisure time activity level, and sleep duration of 7 to 8 hours), and 4) dietary targets (50% to 65% of energy from carbohydrate, 15% to 20% from protein, 20% to 30% from fat, ≥14 g of fiber per 1000 kcal, and <2000 mg of sodium per day). RESULTS: The proportion of adults with self-reported diabetes achieving each ABC target was 64.1% (95% CI, 61.4% to 66.8%) for HbA1c, 22.2% (CI, 20.2% to 24.1%) for BP, and 23.9% (CI, 21.9% to 25.9%) for LDL-C. The proportion achieving a BMI below 24 kg/m2 was 32.2% (CI, 30.3% to 34.2%). The proportion achieving each lifestyle target was 75.8% (CI, 73.9% to 77.7%) for smoking, 66.7% (CI, 64.4% to 69.1%) for drinking, 17.9% (CI, 15.8% to 20.1%) for leisure time activity, and 52.0% (CI, 49.6% to 54.3%) for sleep duration. The proportion achieving each dietary target was 39.1% (CI, 36.0% to 42.2%) for carbohydrate, 20.1% (CI, 16.9% to 23.3%) for protein, 20.5% (CI, 17.6% to 23.4%) for fat, 9.0% (CI, 7.0% to 10.9%) for sodium, and 2.5% (CI, 1.3% to 3.6%) for fiber. Only 4.4% (CI, 3.5% to 5.2%) of participants achieved all 3 ABC targets, 5.1% (CI, 4.3% to 6.0%) achieved all 4 lifestyle targets, and 4 participants achieved all 5 dietary targets. LIMITATIONS: Self-reported data and age of the data. CONCLUSION: Achievement of guideline-recommended diabetes care targets in Chinese adults with self-reported diabetes was exceedingly low. The findings highlight the need for immediate national health actions to improve diabetes care. PRIMARY FUNDING SOURCE: Shanghai Municipal Education Commission, National Key R&D Program of the People's Republic of China, and the National Health Commission of the People's Republic of China.

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BACKGROUND: Poor diet quality is a risk factor for type 2 diabetes and cardiovascular disease. However, knowledge of metabolites marking adherence to Dietary Guidelines for Americans (2015 version) are limited. OBJECTIVES: The goal was to determine a pattern of metabolites associated with the Healthy Eating Index (HEI)-2015, which measures adherence to the Dietary Guidelines for Americans. METHODS: The analysis examined 3557 adult men and women from the longitudinal cohort Multiethnic Study of Atherosclerosis (MESA), without known cardiovascular disease and with complete dietary data. Fasting serum specimens and diet and demographic questionnaires were assessed at baseline. Untargeted 1H 1-dimensional nuclei magnetic resonance spectroscopy (600 MHz) was used to generate metabolomics and lipidomics. A metabolome-wide association study specified each spectral feature as outcomes, HEI-2015 score as predictor, adjusting for age, sex, race, and study site in linear regression analyses. Subsequently, hierarchical clustering defined the discrete groups of correlated nuclei magnetic resonance features associated with named metabolites, and the linear regression analysis assessed for associations with HEI-2015 total and component scores. RESULTS: The sample included 50% women with an mean age of 63 years, with 40% identifying as White, 23% as Black, 24% as Hispanic, and 13% as Chinese American. The mean HEI-2015 score was 66. The metabolome-wide association study identified 179 spectral features significantly associated with HEI-2015 score. The cluster analysis identified 7 clusters representing 4 metabolites; HEI-2015 score was significantly associated with all. HEI-2015 score was associated with proline betaine [ß = 0.12 (SE = 0.02); P = 4.70 × 10-13] and was inversely related to proline [ß = -0.13 (SE = 0.02); P = 4.45 × 10-14], 1,5 anhydrosorbitol [ß = -0.08 (SE = 0.02); P = 4.37 × 10-7] and unsaturated fatty acyl chains [ß = 0.08 (SE = 0.02); P = 8.98 × 10-7]. Intake of total fruit, whole grains, and seafood and plant proteins was associated with proline betaine. CONCLUSIONS: Diet quality is significantly associated with unsaturated fatty acyl chains, proline betaine, and proline. Further analysis may clarify the link between diet quality, metabolites, and pathogenesis of cardiometabolic disease.

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Introduction: No study has comprehensively quantified the individual and collective contributions of various risk factors to the growing burden of diabetes in the United States. Methods: This study aimed to determine the extent to which an increase in the prevalence of diabetes was related to concurrent changes in the distribution of diabetes-related risk factors among US adults (aged 20 years or above and not pregnant). Seven cycles of series of cross-sectional National Health and Nutrition Examination Survey data between 2005-2006 and 2017-2018 were included. The exposures were survey cycles and seven domains of risk factors, including genetic, demographic, social determinants of health, lifestyle, obesity, biological, and psychosocial domains. Using Poisson regressions, percent reduction in the ß coefficient (the logarithm used to calculate the prevalence ratio for prevalence of diabetes in 2017-2018 vs. 2005-2006) was computed to assess the individual and collective contribution of the 31 prespecified risk factors and seven domains to the growing burden of diabetes. Results: Of the 16,091 participants included, the unadjusted prevalence of diabetes increased from 12.2% in 2005-2006 to 17.1% in 2017-2018 [prevalence ratio: 1.40 (95% CI, 1.14-1.72)]. Individually, genetic domain [17.3% (95% CI, 5.4%-40.8%)], demographic domain [41.5% (95% CI, 24.4%-76.8%)], obesity domain [35.3% (95% CI, 15.8%-70.2%)], biological domain [46.2% (95% CI, 21.6%-79.1%)], and psychosocial domain [21.3% (95% CI, 9.5%-40.1%)] were significantly associated with a different percent reduction in ß. After adjusting for all seven domains, the percent reduction in ß was 97.3% (95% CI, 62.7%-164.8%). Conclusion: The concurrently changing risk factors accounted for the increasing diabetes prevalence. However, the contribution of each risk factor domain varied. Findings may inform planning cost-effective and targeted public health programs for diabetes prevention.

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OBJECTIVES: To describe the epidemiological, clinical, and household transmission characteristics of pediatric COVID-19 cases in Shanghai, China. METHODS: Pediatric patients with COVID-19 hospitalized in Shanghai from March-May 2022 were enrolled in this retrospective, multicenter cohort study. The symptoms and the risk factors associated with disease severity were analyzed. RESULTS: In total, 2620 cases (age range, 24 days-17 years) were enrolled in this study. Of these, 1011 (38.6%) were asymptomatic, whereas 1415 (54.0%), 190 (7.3%), and 4 (0.2%) patients developed mild, moderate, and severe illnesses, respectively. Household infection rate was negatively correlated with household vaccination coverage. Children aged 0-3 years, those who are unvaccinated, those with underlying diseases, and overweight/obese children had a higher risk of developing moderate to severe disease than children aged 12-17 years, those who were vaccinated, those without any underlying disease, and those with normal weight, respectively (all P <0.05). A prolonged duration of viral shedding was associated with disease severity, presence of underlying diseases, vaccination status, and younger age (all P <0.05). CONCLUSION: Children aged younger than 3 years who were not eligible for vaccination had a high risk of developing moderate to severe COVID-19 with a prolonged duration of viral shedding. Vaccination could protect children from COVID-19 at the household level.

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BACKGROUND: longitudinal evidence concerning frailty phenotype and the risk of cardiovascular disease (CVD) remained insufficient, and whether CVD preventive strategies exert low CVD risk on frail adults is unclear. OBJECTIVES: we aimed to prospectively evaluate the association of frailty phenotype, adherence to ideal cardiovascular health (CVH) and their joint associations with the risk of CVD. METHODS: a total of 314,093 participants from the UK Biobank were included. Frailty phenotype was assessed according to the five criteria of Fried et al.: weight loss, exhaustion, low physical activity, slow gait speed and low grip strength. CVH included four core health behaviours (smoking, physical activity and diet) and three health factors (weight, cholesterol, blood pressure and glycaemic control). The outcome of interest was incident CVD, including coronary heart disease, heart failure and stroke. RESULTS: compared with the non-frail people whose incident rate of overall CVD was 6.54 per 1,000 person-years, the absolute rate difference per 1,000 person-years was 1.67 (95% confidence interval, CI: 1.33, 2.02) for pre-frail and 5.00 (95% CI: 4.03, 5.97) for frail. The ideal CVH was significantly associated with a lower risk of all CVD outcomes. For the joint association of frailty and CVH level with incident CVD, the highest risk was observed among frailty accompanied by poor CVH with an HR of 2.92 (95% CI: 2.68, 3.18). CONCLUSIONS: our findings indicate that physical frailty is associated with CVD incidence. Improving CVH was significantly associated with a considerable decrease in CVD risk, and such cardiovascular benefits remain for the frailty population.

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BACKGROUND AND AIMS: Although lower lean mass is associated with greater diabetes prevalence in cross-sectional studies, prospective data specifically in middle-aged Black and White adults are lacking. Relative appendicular lean mass (ALM), such as ALM adjusted for body mass index (BMI), is important to consider since muscle mass is associated with overall body size. We investigated whether ALM/BMI is associated with incident type 2 diabetes in the Coronary Artery Risk Development in Young Adults study. METHODS AND RESULTS: 1893 middle-aged adults (55% women) were included. ALM was measured by DXA in 2005-06. Incident type 2 diabetes was defined in 2010-11 or 2015-16 as fasting glucose ≥7 mmol/L (126 mg/dL), 2-h glucose on OGTT ≥11.1 mmol/L (200 mg/dL) (2010-11 only), HbA1C ≥48 mmol/mol (6.5%) (2010-11 only), or glucose-lowering medications. Cox regression models with sex stratification were performed. In men and women, ALM/BMI was 1.07 ± 0.14 (mean ± SD) and 0.73 ± 0.12, respectively. Seventy men (8.2%) and 71 women (6.8%) developed type 2 diabetes. Per sex-specific SD higher ALM/BMI, unadjusted diabetes risk was lower by 21% in men [HR 0.79 (0.62-0.99), p = 0.04] and 29% in women [HR 0.71 (0.55-0.91), p = 0.008]. After adjusting for age, race, smoking, education, physical activity, and waist circumference, the association was no longer significant. Adjustment for waist circumference accounted for the attenuation in men. CONCLUSION: Although more appendicular lean mass relative to BMI is associated with lower incident type 2 diabetes in middle-aged men and women over 10 years, its effect may be through other metabolic risk factors such as waist circumference, which is a correlate of abdominal fat mass.

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