Diastereo- and Enantioselective Synthesis of Eight-Membered N-Heterocycles from Benzofuran-Derived Azadienes and Ynones.

Enantioselective synthesis of eight-membered N-heterocycles represents a long-standing challenge in organic synthesis. Here, by combining the squaramide and DBU catalysis, a sequential asymmetric conjugate addition/cyclization reaction between benzofuran-derived azadienes and ynones has been well-developed, providing straightforward access to chiral eight-membered N-heterocycles in high yields with stereoselectivities. This protocol features the use of a bifunctional squaramide catalyst for controlling the enantioselectivity of products, while the DBU is utilized to achieve intramolecular cyclization and improve the diastereoselectivity of products.

Benign prostatic hyperplasia and cardiovascular risk: a prospective study among Chinese men.

PURPOSE: To examine the prospective association of BPH with subsequent risk of CVD, including heart disease and stroke. METHODS: We used data from China Health and Retirement Longitudinal Study of 5242 Chinese men aged 45 years or older. During a follow-up of 7 years, we identified 613 cases of non-fatal CVD, including 417 heart diseases and 254 strokes. Cox proportional hazards models yielded hazard ratios (HRs) relating BPH to CVD, heart disease, and stroke incidence. RESULTS: Overall, 8.1% of men reported a history of BPH diagnosed by physicians at baseline. As compared with men without a history of BPH, those reporting a history of BPH had an increased risk of developing CVD (multivariable-adjusted HR = 1.43 [1.12, 1.83], heart disease (1.35 [1.00, 1.83]), and stroke (1.50 [1.03, 2.19]). The subgroup analysis by age at baseline (< 60 vs. ≥ 60 years) showed that the associations appeared to be evident among men < 60 years, particularly for CVD (1.82 [1.24, 2.69]) and heart disease (1.72 [1.06, 2.79]). However, interaction tests suggested the associations were not significantly modified by age (P for interaction > 0.10 for all outcomes). CONCLUSION: In Chinese men, BPH was associated with higher risks of CVD, heart disease and stroke, particularly among men aged < 60 years.

Meal frequency and incidence of type 2 diabetes: a prospective study.

Dietary habits play an important role in the development of obesity and type 2 diabetes. However, evidence on association between diet frequency and type 2 diabetes was limited and inconclusive. We aimed to examine the association between meal frequency and risk of type 2 diabetes. The cohort study used data from China Health and Retirement Longitudinal Study of 8874 community-dwelling people aged over 45 years. Participants were classified as eating two meals per day, three meals per day and four meals per day. Multiple Poisson regression models were used to examine risk of 4-year incident type 2 diabetes among people who ate more or less than three meals per day compared with people who ate three meals per day. We documented 706 type 2 diabetes cases during follow-up. After adjustment for known risk factors for type 2 diabetes, except for BMI, participants who ate four meals per day were at a lower risk of type 2 diabetes than those who ate three meals per day (relative risk(RR) = 0·73 (0·58, 0·92)). After further adjustment for baseline BMI, the association was slightly attenuated but remained statistically significant (RR = 0·76 (0·60, 0·97)). Subgroup analysis showed that the fully adjusted RR of type 2 diabetes for people eating four meals per day were 0·66 (0·48, 0·91) and 0·93 (0·65, 1·34) among those had a BMI < 25 and ≥ 25 kg/m2, respectively. Eating four meals per day, compared with eating three meals per day was associated with lower risk of developing type 2 diabetes in a Chinese population, particularly in those with a BMI < 25 kg/m2.

Dairy intake and the risk of pancreatic cancer: the Japan Collaborative Cohort Study (JACC Study) and meta-analysis of prospective cohort studies.

Dairy product intake was suggested to reduce the risk of gastrointestinal cancers. This study investigated the association between dairy product intake and the risk of pancreatic cancer (PAC) using a prospective cohort study and meta-analysis of prospective cohort studies. First, we included 59 774 people aged 40-79 years from the Japan Collaborative Cohort Study (JACC Study). The Cox regression was used to compute the hazard ratios (HR) and 95 % CI of incident PAC for individuals who reported the highest intakes of milk, cheese and yogurt compared with not consuming the corresponding dairy products. Then, we combined our results with those from other four prospective cohort studies that were eligible after searching several databases, in a meta-analysis, using the fixed-effects model before evaluating publication bias and heterogeneity across studies. In the JACC Study, the highest v. no intakes of milk, cheese and yogurt were not associated with the reduced risk of PAC after a median follow-up of 13·4 years: HR (95 % CI) = 0·93 (0·64, 1·33), 0·91 (0·51, 1·62) and 0·68 (0·38, 1·21), respectively. The results did not significantly change in the meta-analysis: 0·95 (0·82, 1·11) for milk, 1·16 (0·87, 1·55) for cheese and 0·91 (0·79, 1·05) for yogurt. The meta-analysis showed no signs of publication bias or heterogeneity across studies. To conclude, consumption of milk, cheese and yogurt was not associated with the risk of PAC either in the JACC Study or the meta-analysis.

Stable and Efficient Blue-Emitting CsPbBr3 Nanoplatelets with Potassium Bromide Surface Passivation.

Colloidal all-inorganic perovskites nanocrystals (NCs) have emerged as a promising material for display and lighting due to their excellent optical properties. However, blue emissive NCs usually suffer from low photoluminescence quantum yields (PLQYs) and poor stability, rendering them the bottleneck for full-color all-perovskite optoelectronic applications. Herein, a facile approach is reported to enhance the emission efficiency and stability of blue emissive perovskite nano-structures via surface passivation with potassium bromide. By adding potassium oleate and excess PbBr2 to the perovskite precursor solutions, potassium bromide-passivated (KBr-passivated) blue-emitting (≈450 nm) CsPbBr3 nanoplatelets (NPLs) is successfully synthesized with a respectably high PLQY of 87%. In sharp contrast to most reported perovskite NPLs, no shifting in emission wavelength is observed in these passivated NPLs even after prolonged exposures to intense irradiations and elevated temperature, clearly revealing their excellent photo- and thermal-stabilities. The enhancements are attributed to the formation of K-Br bonding on the surface which suppresses ion migration and formation of Br-vacancies, thus improving both the PL emission and stability of CsPbBr3 NPLs. Furthermore, all-perovskite white light-emitting diodes (WLEDs) are successfully constructed, suggesting that the proposed KBr-passivated strategy can promote the development of the perovskite family for a wider range of optoelectronic applications.

Consumption of flavonoid-rich fruits, flavonoids from fruits and stroke risk: a prospective cohort study.

We sought to examine the prospective associations of specific fruit consumption, in particular flavonoid-rich fruit (FRF) consumption, with the risk of stroke and subtypes of stroke in a Japanese population. A study followed a total of 39 843 men and 47 334 women aged 44-76 years, and free of CVD, diabetes and cancer at baseline since 1995 and 1998 to the end of 2009 and 2012, respectively. Data on total and specific FRF consumption for each participant were obtained using a self-administrated FFQ. The hazard ratios (HR) of stroke in relation to total and specific FRF consumption were estimated through Cox proportional hazards regression models. During a median follow-up of 13·1 years, 4091 incident stroke cases (2557 cerebral infarctions and 1516 haemorrhagic strokes) were documented. After adjustment for age, BMI, study area, lifestyles, dietary factors and other risk factors, it was found that total FRF consumption was associated with a significantly lower risk of stroke in women (HR = 0·70; 95 % CI 0·58, 0·84), while the association in men was not significant (HR = 0·93; 95 % CI 0·79, 1·09). As for specific FRF, consumptions of citrus fruits, strawberries and grapes were found associated with a lower stroke risk in women. Higher consumptions of FRF, in particular citrus fruits, strawberries and grapes, were associated with a lower risk of developing stroke in Japanese women.

Smoking Cessation, Weight Gain, Cardiovascular Risk, and All-Cause Mortality: A Meta-analysis.

INTRODUCTION: Quitting smoking usually results in weight gain, rising the concern that weight gain after smoking cessation may attenuate the benefits of smoking quitting on cardiovascular health. AIMS AND METHODS: We aimed to examine the risk of cardiovascular disease (CVD) among smoking quitters compared with smokers, stratified by post-cessation weight change. We searched PubMed, Scopus, and Web of Science for eligible studies published before September 2020. Cohort studies examining the relative risk of CVD among smoking quitters stratified by post-cessation weight change, with smokers being treated as the reference, were included. Two investigators extracted the key characteristics of each included study using a standard electronic form. RESULTS: We identified nine studies for this meta-analysis. Compared with smokers, the pooled RRs (95% confidence interval) of CVD among quitters with weight gain and among those without were 0.74 [0.66, 0.83] and 0.86 [0.80, 0.92], with no evidence of heterogeneity between studies being observed. Moreover, the associations appeared to be significantly stronger among quitters with weight gain than those without, particularly in the analysis of coronary heart disease (CHD) and stroke (pooled RRs = 0.65 [0.59, 0.71] vs. 0.79 [0.71, 0.88] for CHD and 0.67 [0.62, 0.73] vs. 0.76 [0.72, 0.81] for stroke, respectively; p for interaction <.05). CONCLUSIONS: Smoking cessation was associated with a significantly lower risk of CVD and all-cause mortality, regardless of post-cessation weight gain. A greater risk reduction among quitters with weight gain than those without merits further investigations. IMPLICATIONS: Quitting smoking usually results in weight gain and increases the risk of type 2 diabetes. We found that the risk reduction in CVD and all-cause mortality associated with smoking cessation was greater in quitters with weight gain than that in quitters without, especially in CHD and stroke. Despite weight gain and increased risk of type 2 diabetes, quitting smoking remains effective in the prevention of CVD.

Consumption of soy products and cardiovascular mortality in people with and without cardiovascular disease: a prospective cohort study of 0.5 million individuals.

PURPOSE: We sought to examine the association of soy product consumption with risk of cardiovascular death in Chinese individuals with and without a history of cardiovascular disease (CVD). METHODS: The current analysis included 487,034 individuals free of CVD and 22,923 individuals with a history of CVD at study baseline. Data on consumption of soy products were collected by a food frequency questionnaire. The Cox regression was used to obtain the hazard ratios (HRs) of cardiovascular mortality associated with soy product consumption among people with and without a history of CVD at baseline. RESULTS: During the period of follow-up, 12,582 and 2860 cardiovascular deaths were recorded among people without and with a history of CVD. Compared with those who never or rarely ate soy products, the multivariable HRs (95% CIs) were 1.02 (0.96, 1.08) for those who ate soy products monthly, 1.01 (0.95, 1.07) for those who ate soy products 1-3 days per week, 0.95 (0.88, 1.04) for those who ate soy products ≥ 4 days per week. For cause-specific mortality, soy product consumption was inversely associated with mortality from acute myocardial infarction (HR [95% CI] = 0.75 [0.61, 0.92]). Among people with a history of CVD, higher soy product consumption was not associated with cardiovascular mortality. CONCLUSIONS: Soy consumption ≥ 4 days per week was associated with a significantly lower risk of mortality from acute myocardial infarction in comparison with never or rarely consumption among people without a history of CVD. Among people with a history of CVD, higher soy product consumption was not associated with cardiovascular mortality.

Soy consumption and incidence of gestational diabetes mellitus: the Japan Environment and Children's Study.

BACKGROUND: Intervention studies have shown that isoflavone treatment improved glucose metabolism, indicating that soy intake may have a potential role in diabetes prevention. OBJECTIVES: We aimed to investigate the prospective association of soy isoflavone and soy food intakes with incidence of gestational diabetes mellitus (GDM) in a birth cohort study. METHODS: We recruited 97,454 pregnant women (median gestational age 12 weeks) between January 2011 and March 2014. Dietary intakes during the 12 months preceding study enrollment were assessed by a semi-quantitative food frequency questionnaire. The relative risks of GDM associated with soy isoflavone and soy food intakes were obtained by Poisson regression. Demographic information, histories of diseases, socioeconomic status, lifestyles, and dietary habits, obtained by a self-administrated questionnaire, were used for covariate adjustments. RESULTS: We identified 1904 cases of GDM (2.2%) among 84,948 women. Compared with those in the lowest quintile of soy isoflavone intake, women in the highest quintile were found to have experienced a significantly lower risk of GDM (multivariate relative risk = 0.82; 95% confidence interval: 0.70, 0.95; P for trend = 0.05). Similar results were observed for genistein and daidzein. Regarding soy foods, intakes of miso soup and natto were inversely associated with GDM incidence (both P for trend ≤ 0.01), whereas the association for tofu intake appeared to be nonlinear (P for trend = 0.74). CONCLUSIONS: Higher intakes of miso soup and natto before and during early pregnancy, compared with lower intakes, may be associated with a lower incidence of GDM.

The association between smoking and risk of skin cancer: a meta-analysis of cohort studies.

PURPOSE: The association between smoking and the risk of skin cancers has been studied without reaching consistent findings. This study aims to assess this association through an updated meta-analysis of cohort studies. METHODS: We retrieved cohort studies that investigated the temporal association between smoking and the risk of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and malignant melanoma (MM). Pooled relative risks (RRs) and confidence intervals (CIs) of the included articles were calculated for current, former, and heavy smoking compared with never smoking. Publication bias was detected using the Egger's regression. RESULTS: A total of 15 studies, published between 1990 and 2018, were included. Current smoking was associated with a higher risk of SCC (pooled RR = 1.32, 95% CI 1.15, 1.52) but with a lower risk of BCC (pooled RR = 0.85, 95% CI 0.75, 0.96) and MM (pooled RR = 0.72, 95% CI 0.64, 0.82). No publication bias was detected, and no single study had a substantial impact on the pooled results. Similar results were detected for heavy smoking, while former smoking was not associated with the risk of skin cancer. CONCLUSION: Current smoking and heavy smoking were associated with a higher risk of SCC but a decreased risk of BCC and MM, while former smoking was not associated with skin cancer risk.

Effects of strawberry intervention on cardiovascular risk factors: a meta-analysis of randomised controlled trials.

We conducted a meta-analysis of randomised controlled trials (RCT) to examine the effects of strawberry interventions on cardiovascular risk factors. We searched multiple databases including PubMed, Web of Science and Scopus to identify eligible studies published before 19 May 2019. The endpoints were blood pressure, total cholesterol (TC), HDL-cholesterol, LDL-cholesterol, TAG, fasting blood glucose, endothelial function and inflammatory factors. Pooled analyses were performed using random- or fixed-effects models according to a heterogeneity test. We also conducted sub-group analyses by baseline endpoint levels. We included eleven RCT in this meta-analysis (six for blood pressure, seven for lipid profile, seven for fasting blood glucose and six for C-reactive protein (CRP)). Overall, the strawberry interventions significantly reduced CRP levels by 0·63 (95 % CI -1·04, -0·22) mg/l but did not affect blood pressure, lipid profile or fasting blood glucose in the main analyses. Our analysis stratified by baseline endpoint levels showed the strawberry interventions significantly reduced TC among people with baseline levels >5 mmol/l (-0·52 (95 % CI -0·88, -0·15) mmol/l) and reduced LDL-cholesterol among people with baseline levels >3 mmol/l (-0·31 (95 % CI -0·60, -0·02) mmol/l). There was little evidence of heterogeneity in the analysis and no evidence of publication bias. In summary, strawberry interventions significantly reduced CRP levels and may improve TC and LDL-cholesterol in individuals with high baseline levels.

Consumption of flavonoid-rich fruits and risk of CHD: a prospective cohort study.

Although the association between fruit consumption and CHD risk has been well studied, few studies have focused on flavonoid-rich fruits (FRF), in particular strawberries and grapes. We aimed to verify the association of total and specific FRF consumption with risk of CHD by a large prospective cohort study. A total of 87 177 men and women aged 44-75 years who were free of CVD and cancer at study baseline were eligible for the present analysis. FRF consumption was assessed using a FFQ. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) of CHD in relation to FRF consumption with adjustment for potential risk factors and confounders. During a mean follow-up of 13·2 years, we identified 1156 incident CHD cases. After full adjustment for covariates including demographics, lifestyles and dietary factors, the HR were 0·93 (95 % CI 0·77, 1·11), 0·91 (95 % CI 0·75, 1·11), 0·84 (95 % CI 0·67, 1·04) and 0·78 (95 % CI 0·62, 0·99) for the second, third, fourth and fifth quintiles compared with the lowest quintile of FRF consumption. Regarding specific fruits, we observed a significant inverse association for citrus fruit consumption and a borderline inverse association for strawberry consumption, while no association was observed for apple/pear or grape consumption. Although the associations appeared to be stronger in women, they were not significantly modified by sex. Higher consumption of FRF, in particular, citrus fruits, may be associated with a lower risk of developing CHD.

Chocolate consumption and risk of gestational diabetes mellitus: the Japan Environment and Children's Study.

The association of chocolate consumption with risk of gestational diabetes has not been examined. We aimed to investigate the prospective association between chocolate consumption and risk of gestational diabetes in a large birth cohort in Japan. A total of 97 454 pregnant women with a median gestational age of 12 weeks were recruited from January 2011 to March 2014. Data on demographic information, disease history, socio-economic status, lifestyle and dietary habits were obtained at the study enrolment. Dietary intake during the past 12 months before study enrolment was assessed through a semi-quantitative FFQ. The logistic regression was used to obtain the OR of gestational diabetes in relation to chocolate consumption. Among 84 948 women eligible for the analysis, 1904 cases of gestational diabetes (2·2 %) were identified during the period of pregnancy. After controlling for potential confounding factors including age, smoking status, drinking status, education level, occupation, pre-pregnant BMI, depression, previous history of macrosomia babies, parity, physical activity and dietary factors, women in the highest quartile of chocolate consumption, compared with those in the lowest quartile, had a significantly lower risk of developing gestational diabetes (OR 0·78, 95 % CI 0·67, 0·90; P for trend = 0·002). Stratified analyses suggested that the association was not significantly modified by pre-pregnancy BMI, age, parity, smoking status or drinking status. The present prospective cohort study provided evidence that chocolate consumption was associated with a significant lower risk of gestational diabetes in Japanese women.

Mixed Two-Dimensional Organic-Inorganic Halide Perovskites for Highly Efficient and Stable Photovoltaic Application.

Solar cells made of hybrid organic-inorganic perovskite (HOIP) materials have attracted ever-increasing attention due to their high efficiency and easy fabrication. However, issues regarding their poor stability remain a challenge for practical applications. Engineering the composition and structure of HOIP can effectively enhance the thermal stability and improve the power conversion efficiency (PCE). In this work, mixed two-dimensional (2D) HOIPs are systematically investigated for solar-power harvesting using first-principles calculations. We find that their electronic properties depend strongly on the mixed atoms (Cs, Rb, Ge and Pb) and the formation energy is related to the HOIP's composition, where the atoms are more easily mixed in SnI-2D-HOIPs due to low formation energy at the same composition ratio. We further show that optimal solar energy harvesting can be achieved on the solar cells composed of mixed SnI-2D-HOIPs because of reduced bandgaps, enhanced mobility and improved stability. Importantly, we find that the mixed atoms (Cs, Rb, Ge and Pb) with the appropriate composition ratios can effectively enhance the solar-to-power efficiency and show greatly improved resistance to moisture. The findings demonstrate that mixed 2D-HOIPs can replace the bulk HOIPs or pure 2D-HOIPs for applications into solar cells with high efficiency and stability.

Multivitamin use and risk of stroke mortality: the Japan collaborative cohort study.

BACKGROUND AND PURPOSE: An effect of multivitamin supplement on stroke risk is uncertain. We aimed to examine the association between multivitamin use and risk of death from stroke and its subtypes. METHODS: A total of 72 180 Japanese men and women free from cardiovascular diseases and cancers at baseline in 1988 to 1990 were followed up until December 31, 2009. Lifestyles including multivitamin use were collected using self-administered questionnaires. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) of total stroke and its subtypes in relation to multivitamin use. RESULTS: During a median follow-up of 19.1 years, we identified 2087 deaths from stroke, including 1148 ischemic strokes and 877 hemorrhagic strokes. After adjustment for potential confounders, multivitamin use was associated with lower but borderline significant risk of death from total stroke (HR, 0.87; 95% confidence interval, 0.76-1.01), primarily ischemic stroke (HR, 0.80; 95% confidence interval, 0.63-1.01), but not hemorrhagic stroke (HR, 0.96; 95% confidence interval, 0.78-1.18). In a subgroup analysis, there was a significant association between multivitamin use and lower risk of mortality from total stroke among people with fruit and vegetable intake <3 times/d (HR, 0.80; 95% confidence interval, 0.65-0.98). That association seemed to be more evident among regular users than casual users. Similar results were found for ischemic stroke. CONCLUSIONS: Multivitamin use, particularly frequent use, was associated with reduced risk of total and ischemic stroke mortality among Japanese people with lower intake of fruits and vegetables.

Timing of clinic visits after health checks and risk of hospitalization for cardiovascular events and all-cause death among the high-risk population.

BACKGROUND AND AIMS: We aimed to examine the association between timing of clinic visits after health checks and risk of hospitalization for cardiovascular events and all-cause mortality among the high-risk population. METHODS: A total of 412,059 high-risk individuals from the health claims database of the Japan Health Insurance Association were divided into 4 groups according to the timing of clinic visits during 12 months after health checks (early: <3 months, intermediate: 4-6 months, late: 7-12 months, and none). Cox proportional hazard regression models were used to examine the associations between timing of clinic visits after health checks and risk of hospitalization for stroke, coronary heart disease, heart failure, or all-cause mortality. RESULTS: During a median follow-up of 4.3 years, we identified a total of 15,860 cases having composite outcomes of first hospitalization for stroke, coronary heart disease, heart failure, or all-cause mortality. Compared to high-risk adults without clinic visits after the health checks, the fully adjusted hazard ratios (95% confidence interval) of a composite outcome were 0.78 (0.74, 0.81), 0.84 (0.78, 0.89), and 0.94 (0.89, 1.00) for early, intermediate, and late clinic visits, respectively. Compared to no clinic visit, an early clinic visit was associated with lower risks of all individual endpoints, and the risk reductions appeared to be greater in the hospitalization for stroke and heart failure. CONCLUSIONS: The present study using real-world data provided evidence that an early clinic visit after health checks was associated with lower risks of hospitalization for major cardiovascular events and all-cause mortality among high-risk individuals.

Effects of high-protein diets on body weight, glycaemic control, blood lipids and blood pressure in type 2 diabetes: meta-analysis of randomised controlled trials.

High-protein diets are popular for weight management, but the health effects of such diets in diabetic persons are inconclusive. The aim of the present meta-analysis was to examine the effects of high-protein diets on body weight and metabolic risk factors in patients with type 2 diabetes. We searched the PubMed and Cochrane Library databases for relevant randomised trials up to August 2012. Either a fixed- or a random-effects model was used to combine the net changes in each outcome from baseline to the end of the intervention. Overall, nine trials including a total of 418 diabetic patients met our inclusion criteria. The study duration ranged from 4 to 24 weeks. The actual intake of dietary protein ranged from 25 to 32% of total energy in the intervention groups and from 15 to 20% in the control groups. Compared with the control diets, high-protein diets resulted in more weight loss (pooled mean difference: 22.08, 95% CI 23.25, 20.90 kg). High-protein diets significantly decreased glycated Hb A1C (HbA1C) levels by 0.52 (95% CI 20.90, 20.14) %, but did not affect the fasting blood glucose levels. There were no differences in lipid profiles. The pooled net changes in systolic and diastolic blood pressure were 23.13 (95% CI 26.58, 0.32)mmHg and 21.86 (95% CI 24.26, 0.56) mmHg, respectively. However, two studies reported a large influence on weight loss and HbA1C levels, respectively. In summary, high-protein diets (within 6 months) may have some beneficial effects on weight loss, HbA1C levels and blood pressure in patients with type 2 diabetes. However, further investigations are still required to draw a conclusion.

Effect of probiotic fermented milk on blood pressure: a meta-analysis of randomised controlled trials.

Previous studies have suggested that probiotic fermented milk may possess blood pressure (BP)-lowering properties. In the present study, we aimed to systematically examine the effect of probiotic fermented milk on BP by conducting a meta-analysis of randomised controlled trials. PubMed, Cochrane library and the ClinicalTrials.gov databases were searched up to March 2012 to identify eligible studies.The reference lists of the obtained articles were also reviewed. Either a fixed-effects or a random-effects model was used to calculate the combined treatment effect. Meta-analysis of fourteen randomised placebo-controlled trials involving 702 participants showed that probiotic fermented milk, compared with placebo, produced a significant reduction of 3·10 mmHg (95% CI 24·64, 21·56) in systolic BP and 1·09 mmHg (95% CI 22·11, 20·06) in diastolic BP. Subgroup analyses suggested a slightly greater effect on systolic BP in hypertensive participants than in normotensive ones (23·98 v. 22·09 mmHg). Analysis of trials conducted in Japan showed a greater reduction than those conducted in European countries for both systolic BP (26·12 v. 22·08 mmHg) and diastolic BP (23·45 v. 20·52 mmHg). Some evidence of publication bias was present, but sensitivity analysis excluding small trials that reported extreme results only affected the pooled effect size minimally. In summary, the present meta-analysis suggested that probiotic fermented milk has BP-lowering effects in pre-hypertensive and hypertensive subjects.

Art Engagement and Risk of Type 2 Diabetes: Evidence From the English Longitudinal Study of Ageing.

Objectives: To examine the prospective association between art engagement and the risk of type 2 diabetes. Methods: Adults aged ≥50 from the English Longitudinal Study of Ageing were asked about the frequency of art engagement, including going to the cinema, the art gallery or museum, and the theatre, a concert, or the opera. Cox proportional hazards regression models were used to examine the risk of type 2 diabetes associated with art engagement. Results: During a median follow-up of 12.2 years, we identified 350 cases of type 2 diabetes from 4,064 participants through interviews. After multivariable adjustment, compared with people who never went to the cinema, those going to the cinema frequently had a significantly lower risk of developing type 2 diabetes (HR = 0.61, 95% CI: 0.44-0.86). After further adjustment for socioeconomic factors, the association was slightly attenuated but remained statistically significant (HR = 0.65, 95% CI: 0.46-0.92). Similar results were found for going to the theatre, a concert, or the opera. Conclusion: Frequent art engagement may be associated with a lower risk of type 2 diabetes, which was independent of individuals' socioeconomic factors.

Polypharmacy, chronic kidney disease, and mortality among older adults: A prospective study of National Health and nutrition examination survey, 1999-2018.

Introduction: Polypharmacy might contribute to a range of adverse outcomes, which could get worse in the elderly with chronic kidney disease (CKD). Evidence on polypharmacy, CKD, and mortality is scarce. We aimed to investigate the prospective association between polypharmacy, CKD and all-cause and cause-specific mortality in adults aged ≥65 years. Methods: A total of 13,513 adults from the National Health and Nutrition Examination Surveys were included, following up from 1999 to 2018 until December 31, 2019. The simultaneous use of ≥5 medications by one individual was defined as polypharmacy. Survey-weighted Cox proportional hazard models were used to estimate the hazard ratio (HRs) for mortality from all-cause, cardiovascular diseases (CVD), and cancer after adjusting for potential confounding factors. Results: Among the elderly with CKD, we identified 3,825 total deaths (1,325 CVD and 714 cancer) during a median follow-up of 7.7 years. Participants with polypharmacy had a 27% (HR = 1.27 [1.15, 1.39]) and 39% (HR = 1.39 [1.19, 1.62]) higher risk of all-cause and CVD mortality, respectively, but not for cancer mortality. Compared with the elderly with no polypharmacy and no CKD, the corresponding HRs (95%CIs) for all-cause mortality were 1.04 (0.96, 1.14) for those with no polypharmacy but CKD, 1.24 (1.11, 1.39) for with polypharmacy but no CKD, and 1.34 (1.21, 1.49) for those with both polypharmacy and CKD. A similar pattern was detected for CVD mortality. Discussion: Polypharmacy was associated with elevated risks of all-cause and CVD mortality among the elderly CKD patients. More evidence-based approaches should be promoted for the appropriate deprescribing in the older adults with CKD.