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Higher milk intake has been associated with a lower stroke risk, but not with risk of CHD. Residual confounding or reverse causation cannot be excluded. Therefore, we estimated the causal association of milk consumption with stroke and CHD risk through instrumental variable (IV) and gene-outcome analyses. IV analysis included 29 328 participants (4611 stroke; 9828 CHD) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD (eight European countries) and European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) case-cohort studies. rs4988235, a lactase persistence (LP) SNP which enables digestion of lactose in adulthood was used as genetic instrument. Intake of milk was first regressed on rs4988235 in a linear regression model. Next, associations of genetically predicted milk consumption with stroke and CHD were estimated using Prentice-weighted Cox regression. Gene-outcome analysis included 777 024 participants (50 804 cases) from MEGASTROKE (including EPIC-CVD), UK Biobank and EPIC-NL for stroke, and 483 966 participants (61 612 cases) from CARDIoGRAM, UK Biobank, EPIC-CVD and EPIC-NL for CHD. In IV analyses, each additional LP allele was associated with a higher intake of milk in EPIC-CVD (β = 13·7 g/d; 95 % CI 8·4, 19·1) and EPIC-NL (36·8 g/d; 95 % CI 20·0, 53·5). Genetically predicted milk intake was not associated with stroke (HR per 25 g/d 1·05; 95 % CI 0·94, 1·16) or CHD (1·02; 95 % CI 0·96, 1·08). In gene-outcome analyses, there was no association of rs4988235 with risk of stroke (OR 1·02; 95 % CI 0·99, 1·05) or CHD (OR 0·99; 95 % CI 0·95, 1·03). Current Mendelian randomisation analysis does not provide evidence for a causal inverse relationship between milk consumption and stroke or CHD risk. [ABSTRACT FROM AUTHOR]

Background: The accelerated aging process worldwide is placing a heavy burden on countries. PM 2.5 particulate matter exposure is a significant factor affecting human health and is crucial in the aging process., Methods: We utilized data from China Health and Retirement Longitudinal Study (CHARLS) and the Survey of Health, Aging, and Retirement in Europe (SHARE) to study the relationship between PM 2.5 exposure and the frailty index. Acquire PM 2.5 exposure data for China and Europe, match them according to geographic location within the database. Our study used frailty index to evaluate frailty, which comprises 29 items. We examined the association between PM 2.5 and frailty index using fixed-effects regression models and Mendelian randomization (MR) analysis., Results: We first examined the association between PM 2.5 and frailty index using fixed-effects regression models, revealing a notable positive link across populations in China (coefficient = 0.0003, P = 0.0380) and Europe (Coefficient = 0.0019, P < 0.0001). This suggests that PM 2.5 exposure is a significant risk factor for frailty, leading to accelerated frailty. Moreover, our MR analysis uncovered a possible causal association (OR = 1.2933, 95%CI: 1.2045-1.3820, P < 0.0001) between PM 2.5 exposure and the frailty index., Conclusions: Our findings indicate that long-term exposure to PM 2.5 in the environment is a risk factor for physical frailty and may have a potential causal relationship. Given the rapid global aging trend, public health measures are needed to reduce PM 2.5 concentrations and prevent frailty., Competing Interests: Declarations. Ethical approval: CHARLS received ethical approval from the Biomedical Ethics Review Committee of Peking University (IRB00001052-11015) and all participants provided informed written consent. SHARE received ethical approval from the Ethics Council of the Max Planck Society and all participants provided informed written consent. GWAS summary data and air pollution data are public data and do not require ethical approval. Consent for publication: All authors approved the final manuscript and the submission to this journal. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

More than 100 species of annual herb genus Suaeda widely distribute (Asia, North America, northern Africa and Europe), are rich in resources (about hundreds of millions of tons/Y) and have a long historical application. Most of them are mainly used for traditional food, feed and medicine. Recently, they have been employed to repair saline-alkali land and beautify the environment. So far, only 27 species have been reported on the bioactivity diversity, broad spectrum and effectiveness in clinical practice. Therefore, the in-depth and extensive research of Suaeda has become a research hotspot around the world. However, only one review summarized the nutritional, chemical and biological values of Suaeda. By searching the international authoritative databases (ACS Publications, ScienceDirect, PubMed, Springer, web of Science and Bing International etc.) and collecting 103 literatures closely related to Suaeda (1895-2021), herewith a comprehensive and systematic review was conducted on the phytology, chemistry, pharmacology and clinical application, enveloping the classification evolution between Amaranthaceae and Chenopodiaceae, distribution and common botanical characteristics; involving 9 chemical categories of 163 derivatives covering 14 new and 6 first-isolated ones, and appraising the content determination of 6 categories of components; mainly including the pharmacology of 13 species in vivo and vitro; estimating the clinical application of 16 species cured the related diseases of eight human physiological system except for the motor system. It is expected that this paper will provide forward-looking scientific ideas and literature support for the further modern research, development and utilization of the genus., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Polybrominated diphenyl ethers (PBDEs) are a class of flame-retardants that are found throughout the human body. However, global trends and diversity of the concentrations in human body and the potential risks remain largely unresolved. Based on published data during 2000-2019, we conducted a systematic meta-analysis to understand the burden and risks of PBDEs in humans and their spatiotemporal variations. The report provides a global picture of PBDE concentrations in human blood and breast milk. We found the levels of body PBDE burden in the North American population were higher than those from Asia and Europe. However, high concentrations of blood PBDEs in occupational population from Asia were observed, largely because of poorly controlled e-waste recycling operations. Penta- and deca-BDE were the main contributors in North America and Asia, respectively, reflecting the difference in the production and use of these chemicals. On a global scale, no substantial decreases in the concentrations of PBDEs in the blood and breast milk were observed, although most of the chemicals have been phased out. The results suggested that humans will be exposed to PBDEs with relatively high concentrations in a certain period because of the legacy in products and the environmental media. And the potential health risks necessitate careful study in the future. Our results also remind that the uses of degradation-resistant chemicals should be attached great importance to their safety., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: Advanced glycation end products (AGEs) can be formed in foods by the reaction of reducing sugars with proteins, and have been shown to induce insulin resistance and obesity in experimental studies. We examined the association between dietary AGEs intake and changes in body weight in adults over an average of 5 years of follow-up., Methods: A total of 255,170 participants aged 25-70 years were recruited in ten European countries (1992-2000) in the PANACEA study (Physical Activity, Nutrition, Alcohol, Cessation of smoking, Eating out of home in relation to Anthropometry), a sub-cohort of the EPIC (European Prospective Investigation into Cancer and Nutrition). Body weight was measured at recruitment and self-reported between 2 and 11 years later depending on the study center. A reference database for AGEs was used containing UPLC-MS/MS-measured N ε -(carboxymethyl)-lysine (CML), N ε -(1-carboxyethyl)-lysine (CEL), and N δ -(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) in 200 common European foods. This reference database was matched to foods and decomposed recipes obtained from country-specific validated dietary questionnaires in EPIC and intake levels of CEL, CML, and MG-H1 were estimated. Associations between dietary AGEs intake and body weight change were estimated separately for each of the three AGEs using multilevel mixed linear regression models with center as random effect and dietary AGEs intake and relevant confounders as fixed effects., Results: A one-SD increment in CEL intake was associated with 0.111 kg (95% CI 0.087-0.135) additional weight gain over 5 years. The corresponding additional weight gain for CML and MG-H1 was 0.065 kg (0.041-0.089) and 0.034 kg (0.012, 0.057), respectively. The top six food groups contributing to AGEs intake, with varying proportions across the AGEs, were cereals/cereal products, meat/processed meat, cakes/biscuits, dairy, sugar and confectionary, and fish/shellfish., Conclusion: In this study of European adults, higher intakes of AGEs were associated with marginally greater weight gain over an average of 5 years of follow-up.

Objectives: To assess the association between periodontal disease and Helicobacter pylori (H. pylori) infection in oral cavity., Materials and Methods: We searched PubMed, Embase, Web of Science, Cochrane library, Gray literature, and clinicaltrials.gov for eligible studies up to September 25, 2019. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The random-effects model was used with the software STATA 13.0. The Newcastle-Ottawa-Scale was used for quality evaluation., Results: Twelve observational studies (eight from Asia, one from Europe, and three from the South America) involving 2727 participants were included in the meta-analysis. The overall pooled results showed that H. pylori infection in oral cavity was associated with periodontal disease (OR 2.53, 95% CI 1.86-3.44, P < 0.05). No significant heterogeneity among the articles was observed (I 2  = 44.3%, P < 0.05). The sensitivity analysis indicated that the result of our meta-analysis was generally stable. The Begg test and the Egger test both showed no publication bias was observed (P = 0.45 and P = 0.18 respectively)., Conclusions: Based on current available evidence, it seemed there was a correlation between oral H. pylori infection and the occurrence of periodontal disease. However, since most of the data comes from Asia, more large-scale investigations with high quality from all over the world are needed to confirm the association., Clinical Relevance: H. pylori infection in oral may have a positive association with the prevalence of periodontal disease mainly in Asian populations.

Background: Ambient air pollution has recently been related to type 2 diabetes mellitus (T2DM), a disease that has caused an economic and health burden worldwide. Evidence of an association between air pollution and T2DM was reported in the United States and Europe. However, few studies have focused on the association with high levels of air pollutants in a developing country., Objectives: We conducted a 12-year cohort study to assess the incidence and mortality of T2DM associated with long-term exposure to PM 10 , SO 2 , and NO 2 ., Methods: A retrospective cohort with participants from four cities in northern China was conducted to assess mortality and incidence of T2DM from 1998 to 2009. Incidence of T2DM was self-reported, and incident intake of an antidiabetic drug or injection of insulin simultaneously and mortality of T2DM was obtained from a family member and double checked against death certificates provided from the local center for disease control and prevention. Individual pollution exposures were the mean concentrations of pollutants estimated from the local environmental monitoring centers over the survival years. Hazard ratios (HRs) were estimated using Cox regression models after adjusting for potential confounding factors., Results: A total of 39 054 participants were recruited into the mortality cohort, among which 59 subjects died from T2DM; 38 529 participants were analyzed in the incidence cohort, and 1213 developed new cases of T2DM. For each 10 μg/m 3 increase in PM 10 , SO 2 , and NO 2 , the adjusted HRs and 95% confidence interval (CI) for diabetic incidence were 1.831 (1.778, 1.886), 1.287 (1.256, 1.318), and 1.472 (1.419, 1.528), respectively. Similar results can be observed in the analysis of diabetic mortality with HRs (95% CI) up to 2.260 (1.732, 2.950), 1.130 (1.042, 1.225), and 1.525 (1.280, 1.816), respectively., Conclusions: Our results suggested that long-term exposure to high levels of PM 10 , SO 2 , and NO 2 increase risk of incident and mortality of T2DM in China., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To evaluate the dose-response relationships between alcohol consumption and functional limitations in older European men, and explore the role of muscle strength as a mediator of these relationships., Design: Cross-sectional study of older men participating in the Survey of Health, Aging and Retirement in Europe (SHARE)., Setting: Urban and rural households in 17 European countries and Israel., Participants: A total of 17 870 men aged 65 years and older from the SHARE (Wave 6, 2015) were included in this study., Measurements: Outcome variables were functional limitations: mobility limitation, arm function limitation, and fine motor limitation. Main exposure variable was alcohol consumption. Mediating factor was grip strength. Basic demographics, life habits, and health status were considered as potential confounders. Dose-response analyses with restricted cubic splines and the Karlson/Holm/Breen method were conducted., Results: A total of 17 870 participants were included in this study. Dose-response analyses revealed that moderate alcohol consumption was related to the lower odds of reporting mobility limitation (≤35 units/wk) and arm function limitation (≤41 units/wk), with a minimum odds ratio (OR) occurring at 10 units/week drinks for mobility limitation (OR = .71; 95% confidence interval [CI] = .62-.81) and arm function limitation (OR = .66; 95% CI = .59-.75). The odds of reporting the fine motor limitation monotonically increased with alcohol consumption when alcohol consumption was beyond 15 units/week. No significant mediating effect of grip strength on the relationships between alcohol consumption and mobility limitation and arm function limitation was found., Conclusion: Moderate alcohol consumption has a protective role in mobility and arm function limitation in older European men. Grip strength is not the main mediator of these associations, suggesting that the protective effect is independent of muscle strength. Alcohol consumption is associated with higher odds of reporting fine motor limitation in older European men. J Am Geriatr Soc 67:2331-2337, 2019., (© 2019 The American Geriatrics Society.)

Microplastics have been detected in freshwaters all over the world in almost all samples, and ecotoxicological studies have shown adverse effects of microplastics on organisms. However, no risk assessment of microplastics has been performed specifically in freshwater so far. The aim of the present study was therefore to review all exposure and ecotoxicity data available for microplastics in freshwaters and to perform a preliminary probabilistic risk assessment. The exposure probability distribution was based on 391 concentrations measured in Asia, Europe, and North America. Because exposure data are mainly available in particle number-based metrics but results from hazard studies are mostly mass-based, the hazard results were converted into particle number concentrations. A statistical analysis of the hazard data showed that there was no significant influence of particle shape or type of polymer on the no-observed-effect concentration. The predicted-no-effect concentration (PNEC) was calculated as the fifth percentile of the probabilistic species sensitivity distribution, based on 53 values from 14 freshwater species, to have a mode of 7.4 × 10 5 particles · m -3 (25th and 75th quantiles of 6.1 × 10 5 and 1.3 × 10 6 particles · m -3 , respectively). The exposure probability distribution was divided by the PNEC probability distribution to calculate risk characterization ratios (RCRs), with modes of 1.3 × 10 -6 in North America, 3.3 × 10 -6 in Europe, and 4.6 × 10 -3 in Asia. Probability distributions associated with the RCRs showed that ecological risks cannot be entirely excluded in Asia, where 0.4% of the RCR values were above 1. Environ Toxicol Chem 2019;38:436-447. © 2018 SETAC., (© 2018 SETAC.)

Objectives: To estimate the effects of baseline grip strength and cognition on the trajectory of functional limitation over time., Design: Longitudinal study of older adults participating in the Survey of Health, Ageing and Retirement in Europe (SHARE)., Setting: Urban and rural households in 11 European countries and Israel., Participants: Individuals aged 50 and older from SHARE (2004-2015) (N=14,073; 52.5% female)., Measurements: Outcomes were functional limitation scores from five panel wave. Main exposure variables were grip strength and cognitive measures including memory, verbal fluency, and numeracy at baseline. Basic demographic characteristics, life habits, and health status were considered as potential confounders. Mixed-effect linear regression models were fitted., Results: Functional limitation increased significantly over time (follow-up range 0.9-11.6 years) (β = 0.051, P < .001). Mixed-effect linear regression models identified significant interactions between grip strength (β = -0.001, P < .001), numeracy (β = -0.012, P < .001), verbal fluency (β = -0.003, P < .001), word recall (β = -0.006, P < .001) and time on functional limitation., Conclusion: Stronger baseline grip strength and better cognition predicted a slower rate of increase in functional limitation over time in older adults. Grip strength and cognitive function appeared to be useful indicators of the functional limitation process and attested to their value in monitoring functional change in European older adults. J Am Geriatr Soc 67:93-99, 2019., (© 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.)

In the past two decades, avian influenzas have posed an increasing international threat to human and livestock health. In particular, highly pathogenic avian influenza H5N1 has spread across Asia, Africa, and Europe, leading to the deaths of millions of poultry and hundreds of people. The two main means of international spread are through migratory birds and the live poultry trade. We focus on the role played by the live poultry trade in the spread of H5N1 across three regions widely infected by the disease, which also correspond to three major trade blocs: the European Union (EU), the Economic Community of West African States (ECOWAS), and the Association of Southeast Asian Nations (ASEAN). Across all three regions, we found per-capita GDP (a proxy for modernization, general biosecurity, and value-at-risk) to be risk reducing. A more specific biosecurity measure-general surveillance-was also found to be mitigating at the all-regions level. However, there were important inter-regional differences. For the EU and ASEAN, intra-bloc live poultry imports were risk reducing while extra-bloc imports were risk increasing; for ECOWAS the reverse was true. This is likely due to the fact that while the EU and ASEAN have long-standing biosecurity standards and stringent enforcement (pursuant to the World Trade Organization's Agreement on the Application of Sanitary and Phytosanitary Measures), ECOWAS suffered from a lack of uniform standards and lax enforcement., Competing Interests: The authors have declared that no competing interests exist.

Background: Exposure to air pollution during pregnancy may increase attention-deficit/hyperactivity disorder (ADHD) symptoms in children, but findings have been inconsistent. We aimed to study this association in a collaborative study of eight European population-based birth/child cohorts, including 29,127 mother-child pairs., Methods: Air pollution concentrations (nitrogen dioxide [NO2] and particulate matter [PM]) were estimated at the birth address by land-use regression models based on monitoring campaigns performed between 2008 and 2011. We extrapolated concentrations back in time to exact pregnancy periods. Teachers or parents assessed ADHD symptoms at 3-10 years of age. We classified children as having ADHD symptoms within the borderline/clinical range and within the clinical range using validated cutoffs. We combined all adjusted area-specific effect estimates using random-effects meta-analysis and multiple imputations and applied inverse probability-weighting methods to correct for loss to follow-up., Results: We classified a total of 2,801 children as having ADHD symptoms within the borderline/clinical range, and 1,590 within the clinical range. Exposure to air pollution during pregnancy was not associated with a higher odds of ADHD symptoms within the borderline/clinical range (e.g., adjusted odds ratio [OR] for ADHD symptoms of 0.95, 95% confidence interval [CI] = 0.89, 1.01 per 10 µg/m increase in NO2 and 0.98, 95% CI = 0.80, 1.19 per 5 µg/m increase in PM2.5). We observed similar associations for ADHD within the clinical range., Conclusions: There was no evidence for an increase in risk of ADHD symptoms with increasing prenatal air pollution levels in children aged 3-10 years. See video abstract at, http://links.lww.com/EDE/B379.

Aims: The objective of this study was to evaluate the efficacy, safety, and tolerability of LY3015014 (LY), a neutralizing antibody of proprotein convertase subtilisin/kexin type 9 (PCSK9), administered every 4 or 8 weeks in patients with primary hypercholesterolaemia, when added to a background of standard-of-care lipid-lowering therapy, including statins., Methods and Results: Double-blind, placebo-controlled trial randomized 527 patients with primary hypercholesterolaemia from June 2013 to January 2014 at 61 community and academic centres in North America, Europe, and Japan. Patients were randomized to subcutaneous injections of LY 20, 120, or 300 mg every 4 weeks (Q4W); 100 or 300 mg every 8 weeks (Q8W) alternating with placebo Q4W; or placebo Q4W. The primary endpoint was percentage change from baseline in low-density lipoprotein cholesterol (LDL-C) by beta quantification at Week 16. The mean baseline LDL-C by beta quantification was 136.3 (SD, 45.0)mg/dL. LY3015014 dose-dependently decreased LDL-C, with a maximal reduction of 50.5% with 300 mg LY Q4W and 37.1% with 300 mg LY Q8W compared with a 7.6% increase with placebo maintained at the end of the dosing interval. There were no treatment-related serious adverse events (AEs). The most common AE terms (>10% of any treatment group) reported more frequently with LY compared with placebo were injection site (IS) pain and IS erythema. No liver or muscle safety issues emerged., Conclusions: LY3015014 dosed every 4 or 8 weeks, resulted in robust and durable reductions in LDL-C. No clinically relevant safety issues emerged with the administration of LY. The long-term effects on cardiovascular outcomes require further investigation., (© The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Attention deficit/hyperactivity disorder (ADHD) is often poorly understood, and treatment practices are variable. This 12-month, prospective, observational study provides information about the diagnosis, co-morbidities, treatment patterns, and quality of life (QOL) of patients aged 6-17 years with ADHD symptoms from eastern Asia and central and eastern Europe. Here, we present baseline data for the 1068 enrolled and eligible patients in the study (median age 8 years, 82.2% male). Patients were grouped into two cohorts based on whether they were prescribed psycho- and/or pharmacotherapy (n = 794) or not (n = 274) at study entry. On average, patients receiving treatment were significantly older (9.1 vs. 8.4 years, p < 0.001), more severely ill (Clinical Global Impressions [CGI]-ADHD-S, 4.6 vs. 4.2, p < 0.001; Child Symptom Inventory-4 Parent Checklist (CSI-4) ADHD:C, 35.2 vs. 31.9, p < 0.001), and had significantly higher CSI-4 symptom severity scores relating to various co-morbidities than patients not receiving treatment. At study initiation, patient's health-related QOL was significantly impaired as measured on the Child Health and Illness Profile-Child Edition (CHIP-CE) rating scale, with significantly more impairment in the treated group of patients for the Comfort, Risks Avoidance, and Achievement domains. These results provide a description of ADHD and treatment practices in these regions and establish a baseline for gauging changes over time in the study sample.

The American Cancer Society's Department of Epidemiology and Statistics reports its 29th annual compilation of cancer incidence, survival and mortality data for the United States and around the world.