Intake of the different types of dairy products, genetic predisposition, and the risks of nonalcoholic fatty liver disease and cirrhosis: a prospective cohort study.

Background: The association of dairy product consumption with nonalcoholic fatty liver disease (NAFLD) and cirrhosis remains controversial. This study aimed to prospectively investigate the associations between the consumption of the different types of dairy products, genetic predisposition, and the risks of NAFLD and cirrhosis. Methods: This cohort study included 190 145 participants from the UK Biobank Study. The consumption of the different types of dairy products was assessed based on the Oxford WebQ at baseline and defined as the sum of milk, yogurt, and cheese. NAFLD and cirrhosis were evaluated using hospital inpatient records and death data in the UK Biobank. The weighted genetic risk score (GRS) for NAFLD and cirrhosis was constructed using 5 and 6 single-nucleotide variants (SNVs), respectively. Cox proportional hazards regression models were utilized to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between genetic factors and different types of dairy products with the incidence of NAFLD and cirrhosis. Results: During a median follow-up of 11.6 years, 1512 NAFLD and 556 cirrhosis cases were ascertained. After adjusting for several potential confounders, the HRs (95% CIs) (Q4 vs. Q1) of NAFLD were 0.86 (0.74, 0.995) for total dairy products, 0.96 (0.84, 1.09) for high-fat dairy products, 0.78 (0.67, 0.92) for low-fat dairy products, 0.86 (0.74, 0.99) for unfermented dairy products, and 0.79 (0.68, 0.91) for fermented dairy products. The multivariable-adjusted HRs (95% CIs) (Q4 vs. Q1) of cirrhosis were 0.75 (0.59, 0.96) for total dairy products, 0.97 (0.78, 1.19) for high-fat dairy products, 0.67 (0.51, 0.89) for low-fat dairy products, 0.75 (0.59, 0.96) for unfermented dairy products, and 0.71 (0.56, 0.90) for fermented dairy products. The associations of high-fat dairy products and fermented dairy products with NAFLD and cirrhosis were found to be nonlinear (P for nonlinear <0.05). No interaction was observed between dairy product consumption and NAFLD or cirrhosis genetic susceptibility. Conclusions: Higher consumption of dairy products, except for high-fat dairy, was correlated with lower risks of NAFLD and cirrhosis, regardless of their differences in genetic susceptibility.

Historical trends of breast cancer burden attributable to metabolic factors among Chinese women, 1990-2019: A population-based epidemiological study.

BACKGROUND:  This study aims to analyze breast cancer burden attributable to high body mass index (BMI) and high fasting plasma glucose (FPG) in China from 1990 to 2019. METHODS: Data were obtained from the Global Burden of Disease (GBD) study 2019. Deaths and disability-adjusted life years (DALYs) were used for attributable burden, and age-period-cohort (APC) model was used to evaluate the independent effects of age, period and birth cohort. RESULTS: In 2019, the age-standardized mortality and DALY rates of breast cancer attributable to high BMI were 1.107 (95% UI: 0.311, 2.327) and 29.990 (8.384, 60.713) per 100 000, and mortality and DALY rates attributable to high FPG were 0.519 (0.095, 1.226) and 13.662 (2.482, 32.425) per 100 000. From 1990 to 2019, the age-standardized mortality and DALY rates of breast cancer attributable to high BMI increased by 1.192% and 1.180%, and the trends of high FPG were not statistically significant. The APC results showed that the age effects of high BMI and high FPG-mortality and DALY rates increased, with the highest rates in the age group over 80 years. The birth cohort effects of high BMI showed "inverted V" shapes, while high FPG showed downward trends. CONCLUSIONS: Age was the main reason for the increase of attributable burden, and postmenopausal women were the high-risk groups. Therefore, targeted prevention measures should be developed to improve postmenopausal women's awareness and effectively reduce the prevalence of obesity and diabetes, thereby reducing the breast cancer burden caused by metabolic factors in China.

A simulation training of family management for parents of children with epilepsy: a randomized clinical trial.

BACKGROUND: Epilepsy is a chronic neurological disorder that is more likely to be diagnosed in children. The main treatment involves long-term use of anti-epileptic drugs and above all, home care is of great importance. As there has not been a widely accepted home care protocols, simulating a home care environment is necessary for caregivers to develop skills of proper home care. This study aims to evaluate the effectiveness of a simulation training of family management style (STOFMS) for parents of children with epilepsy in China. METHODS: A randomized controlled trial was conducted on 463 children with epilepsy and their families. They were recruited from March 2020 to November 2022 and randomly assigned to the STOFMS group or the conventional group in a 1:1 ratio. Scores of family management measures, 8-item of Morisky Medication Adherence and epilepsy clinical symptom of both groups were collected at three points of time: within 24 h after admission (T0), 3 months after discharge (T1), and 6 months after discharge (T2). Changes due to intervention were compared across groups by repeated-measures ANOVA. The study report followed the CONSORT 2010 checklist. RESULTS: There were statistically significant differences between the two groups at T2. A considerable increase over the baseline was observed in the total management level score and subscale scores in the STOFMS group at T1, compared with essentially no change in the control group. In terms of medication adherence, the STOFMS group performance improved greatly at T1 and T2 compared with the control group. The same result was also found in clinical efficacy at T2 (p < 0.05). CONCLUSION: STOFMS is an effective intervention to improve family management level, treatment adherence and clinical efficacy for children with epilepsy. TRIAL REGISTRATION: The registration number is ChiCTR2200065128. Registered at 18 October 2022, http://www.medresman.org.cn.

Long-term exposure to ambient air pollution and risk of microvascular complications among patients with type 2 diabetes: a prospective study.

BACKGROUND: Patients with type 2 diabetes (T2D) may disproportionately suffer the adverse cardiovascular effects of air pollution, but relevant evidence on microvascular outcome is lacking. We aimed to examine the association between air pollution exposure and the risk of microvascular complications among patients with T2D. METHODS: This prospective study included 17 995 participants with T2D who were free of macro- and micro-vascular complications at baseline from the UK Biobank. Annual average concentrations of particulate matter (PM) with diameters <2.5 µm (PM2.5), <10 µm (PM10), nitrogen dioxide (NO2) and nitrogen oxides (NOx) were assessed using land use regression models. Cox proportional hazards regression was used to estimate the associations of air pollution exposure with incident diabetic microvascular complications. The joint effects of the air pollutant mixture were examined using quantile-based g-computation in a survival setting. RESULTS: In single-pollutant models, the adjusted hazard ratios (95% confidence intervals) for composite diabetic microvascular complications per interquartile range increase in PM2.5, PM10, NO2 and NOx were 1.09 (1.04-1.14), 1.06 (1.01-1.11), 1.07 (1.02-1.12) and 1.04 (1.00-1.08), respectively. Similar significant results were found for diabetic nephropathy and diabetic neuropathy, but not for diabetic retinopathy. The associations of certain air pollutants with composite microvascular complications and diabetic nephropathy were present even at concentrations below the World Health Organization limit values. Multi-pollutant analyses demonstrated that PM2.5 contributed most to the elevated risk associated with the air pollutant mixture. In addition, we found no interactions between air pollution and metabolic risk factor control on the risk of diabetic microvascular complications. CONCLUSIONS: Long-term individual and joint exposure to PM2.5, PM10, NO2 and NOx, even at low levels, was associated with an increased risk of diabetic microvascular complications, with PM2.5 potentially being the main contributor.

Dissection of quantitative trait nucleotides and candidate genes associated with agronomic and yield-related traits under drought stress in rapeseed varieties: integration of genome-wide association study and transcriptomic analysis.

Introduction: An important strategy to combat yield loss challenge is the development of varieties with increased tolerance to drought to maintain production. Improvement of crop yield under drought stress is critical to global food security. Methods: In this study, we performed multiomics analysis in a collection of 119 diverse rapeseed (Brassica napus L.) varieties to dissect the genetic control of agronomic traits in two watering regimes [well-watered (WW) and drought stress (DS)] for 3 years. In the DS treatment, irrigation continued till the 50% pod development stage, whereas in the WW condition, it was performed throughout the whole growing season. Results: The results of the genome-wide association study (GWAS) using 52,157 single-nucleotide polymorphisms (SNPs) revealed 1,281 SNPs associated with traits. Six stable SNPs showed sequence variation for flowering time between the two irrigation conditions across years. Three novel SNPs on chromosome C04 for plant weight were located within drought tolerance-related gene ABCG16, and their pleiotropically effects on seed weight per plant and seed yield were characterized. We identified the C02 peak as a novel signal for flowering time, harboring 52.77% of the associated SNPs. The 288-kbps LD decay distance analysis revealed 2,232 candidate genes (CGs) associated with traits. The CGs BIG1-D, CAND1, DRG3, PUP10, and PUP21 were involved in phytohormone signaling and pollen development with significant effects on seed number, seed weight, and grain yield in drought conditions. By integrating GWAS and RNA-seq, 215 promising CGs were associated with developmental process, reproductive processes, cell wall organization, and response to stress. GWAS and differentially expressed genes (DEGs) of leaf and seed in the yield contrasting accessions identified BIG1-D, CAND1, and DRG3 genes for yield variation. Discussion: The results of our study provide insights into the genetic control of drought tolerance and the improvement of marker-assisted selection (MAS) for breeding high-yield and drought-tolerant varieties.

Vitamin D status, vitamin D receptor polymorphisms, and risk of type 2 diabetes: A prospective cohort study.

CONTEXT: Vitamin D status has been associated with risk of type 2 diabetes (T2D), but evidence is scarce regarding whether such relation differs by glycemic status. OBJECTIVE: To prospectively investigate the association between serum 25-hydroxyvitamin D [25(OH)D] and risk of incident T2D across the glycemic spectrum and the modification effect of genetic variants in vitamin D receptor (VDR). METHODS: This prospective study included 379,699 participants without T2D at baseline from the UK Biobank. Analyses were performed according to glycemic status and HbA1c levels. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs. RESULTS: During a median of 14.1 years of follow-up, 6,315 participants with normoglycemia and 9,085 prediabetes patients developed T2D. Compared to individuals with 25(OH)D <25 nmol/L, the multivariable-adjusted hazard ratios (95% CIs) of incident T2D for those with 25(OH)D ≥75 nmol/L was 0.62 (0.56, 0.70) among the normoglycemia and 0.64 (0.58, 0.70) among the prediabetes. A significant interaction was observed between 25(OH)D and VDR polymorphisms among participants with prediabetes (Pinteraction=0.017), whereby the reduced HR of T2D associated with higher 25(OH)D was more prominent in those carrying T allele of rs1544410. Triglycerides levels mediated 26% and 34% of the association between serum 25(OH)D and incident T2D among participants with normoglycemia and prediabetes. CONCLUSIONS: Higher serum 25(OH)D concentrations were associated with lower T2D risk across the glycemic spectrum below the threshold for diabetes, and the relations in prediabetes were modified by VDR polymorphisms. Improving lipid profile, mainly triglycerides, accounted for part of the favorable associations.

Cytoreductive surgery plus hyperthermic intraoperative peritoneal chemotherapy for people with peritoneal metastases from colorectal, ovarian or gastric origin: A systematic review of randomized controlled trials.

BACKGROUND: There is uncertainty in the relative benefits and harms of hyperthermic intraoperative peritoneal chemotherapy (HIPEC) when added to cytoreductive surgery (CRS) +/- systemic chemotherapy or systemic chemotherapy alone in people with peritoneal metastases from colorectal, gastric, or ovarian cancers. METHODS: We searched randomized controlled trials (RCTs) in the medical literature until April 14, 2022 and applied methods used for high-quality systematic reviews. FINDINGS: We included a total of eight RCTs (seven RCTs included in quantitative analysis as one RCT did not provide data in an analyzable format). All comparisons other than ovarian cancer contained only one trial. For gastric cancer, there is high uncertainty about the effect of CRS + HIPEC + systemic chemotherapy. For stage III or greater epithelial ovarian cancer undergoing interval cytoreductive surgery, CRS + HIPEC + systemic chemotherapy probably decreases all-cause mortality compared to CRS + systemic chemotherapy. For colorectal cancer, CRS + HIPEC + systemic chemotherapy probably results in little to no difference in all-cause mortality and may increase the serious adverse events proportions compared to CRS +/- systemic chemotherapy, but probably decreases all-cause mortality compared to fluorouracil-based systemic chemotherapy alone. INTERPRETATION: The role of CRS + HIPEC in gastric peritoneal metastases is uncertain. CRS + HIPEC should be standard of care in women with stage III or greater epithelial ovarian cancer undergoing interval CRS. CRS + systemic chemotherapy should be standard of care for people with colorectal peritoneal metastases, with HIPEC given only as part of a RCT focusing on subgroups and regimes. PROSPERO REGISTRATION: CRD42019130504.

Brazilin Actuates Ferroptosis in Breast Cancer Cells via p53/SLC7A11/GPX4 Signaling Pathway.

OBJECTIVE: To investigate the mechanism of induction of ferroptosis by brazilin in breast cancer cells. METHODS: Breast cancer 4T1 cells were divided into 6 groups: control, brazilin 1/2 half maximal inhibitory concentration (IC50), IC50, 2×IC50, erastin (10 µg/mL) and capecitabine (10 µg/mL) groups. The effect of brazilin on the proliferation of 4T1 cells was detected by cell counting kit-8 assay, and the treatment dose of brazilin was screened. The effect of brazilin on the mitochondrial morphology of 4T1 cells, and the mitochondrial damage was evaluated under electron microscopy. The levels of Fe2+, reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH) and glutathione peroxidase 4 (GPX4) were estimated using various detection kits. The invasion and migration abilities of 4T1 cells were detected by scratch assay and transwell assay. The expressions levels of tumor protein p53, solute carrier family 7 member 11 (SLC7A11), GPX4 and acyl-CoA synthetase long-chain family member 4 (ACSL4) proteins were quantified by Western blot assay. RESULTS: Compared to the control group, the 10 (1/2 IC50), 20 (IC50) and 40 (2×IC50) µg/mL brazilin, erastin, and capecitabine groups showed a significant decrease in the cell survival rate, invasion and migration abilities, GSH, SLC7A11 and GPX4 protein expression levels, and mitochondrial volume and ridge (P<0.05), and a significant increase in the mitochondria membrane density, Fe2+, ROS and MDA levels, and p53 and ACSL4 protein expression levels (P<0.05). CONCLUSIONS: Brazilin actuated ferroptosis in breast cancer cells, and the underlying mechanism is mainly associated with the p53/SLC7A11/GPX4 signaling pathway.

An endogenous promoter LpSUT2 discovered in duckweed: a promising transgenic tool for plants.

Promoters are one of the most critical elements in regulating gene expression. They are considered essential biotechnological tools for heterologous protein production. The one most widely used in plants is the 35S promoter from cauliflower mosaic virus. However, our study for the first time discovered the 35S promoter reduced the expression of exogenous proteins under increased antibiotic stress. We discovered an endogenous strong promoter from duckweed named LpSUT2 that keeps higher initiation activity under antibiotic stress. Stable transformation in duckweed showed that the gene expression of eGFP in the LpSUT2:eGFP was 1.76 times that of the 35S:eGFP at 100 mg.L-1 G418 and 6.18 times at 500 mg.L-1 G418. Notably, with the increase of G418 concentration, the gene expression and the fluorescence signal of eGFP in the 35S:eGFP were weakened, while the LpSUT2:eGFP only changed slightly. This is because, under high antibiotic stress, the 35S promoter was methylated, leading to the gene silencing of the eGFP gene. Meanwhile, the LpSUT2 promoter was not methylated and maintained high activity. This is a previously unknown mechanism that provides us with new insights into screening more stable promoters that are less affected by environmental stress. These outcomes suggest that the LpSUT2 promoter has a high capacity to initiate the expression of exogenous proteins. In conclusion, our study provides a promoter tool with potential application for plant genetic engineering and also provides new insights into screening promoters.

B7-H3 in acute myeloid leukemia: From prognostic biomarker to immunotherapeutic target.

ABSTRACT: B7-H3 (CD276), an immune checkpoint protein of the B7 family, exhibits significant upregulation in solid tumors and hematologic malignancies, exerting a crucial role in their pathophysiology. The distinct differential expression of B7-H3 between tumors and normal tissues and its multifaceted involvement in tumor pathogenesis position it as a promising therapeutic target for tumors. In the context of acute myeloid leukemia (AML), B7-H3 is prominently overexpressed and closely associated with unfavorable prognoses, yet it has remained understudied. Despite various ongoing clinical trials demonstrating the potential efficacy of immunotherapies targeting B7-H3, the precise underlying mechanisms responsible for B7-H3-mediated proliferation and immune evasion in AML remain enigmatic. In view of this, we comprehensively outline the current research progress concerning B7-H3 in AML, encompassing in-depth discussions on its structural attributes, receptor interactions, expression profiles, and biological significance in normal tissues and AML. Moreover, we delve into the protumor effects of B7-H3 in AML, examine the intricate mechanisms that underlie its function, and discuss the emerging application of B7-H3-targeted therapy in AML treatment. By juxtaposing B7-H3 with other molecules within the B7 family, this review emphasizes the distinctive advantages of B7-H3, not only as a valuable prognostic biomarker but also as a highly promising immunotherapeutic target in AML.

A dense matching method for remote sensing images fused with CPS denoising.

Dense matching of remote sensing images is crucial for 3D reconstruction. This study proposes an enhanced dense matching method employing the CPS image denoising algorithm, aiming to boost the SGM algorithm's accuracy and efficiency in remote sensing image matching. The stereo image pair's quality is evaluated using the PSNR index, and a decision-making criterion based on the CPS algorithm is incorporated to determine the need for denoising. Preprocessing steps, including image cropping and pixel coordinate transformation, significantly reduce computational requirements. An epipolar line model, minimizing the disparity between two pixels, is used for calculations. This model is employed to construct an epipolar image, enhancing the accuracy and efficiency of the process. The study conducted experimental validation and analysis of the mismatch rate, running time, and denoising effect of the algorithm using the Middlebury 2021 stereo datasets. Additionally, the matching results of the World-View3 satellite stereo image pairs were visualized and analyzed. The experimental results indicate that the proposed algorithm reduces the average mismatch rate by 13.1% and increases the running speed by about 3 to 4 times compared to the SGBM algorithm. Specifically, the denoising effect reduces the mismatch rate of the reconstructed image by an average of 8.97%. The results indicate that the CPS method effectively addresses dense matching challenges in the presence of image blur and noise, thereby improving the operational efficiency and accuracy of the dense matching algorithm.

Structural characterization and anti-inflammatory activities of a purified polysaccharide from fruits remnants of Alpinia zerumbet (Pers.) Burtt. et Smith.

We reported here an interesting source of Alpinia zerumbet Polysaccharides (named AZPs) from the residues after extracting essential oil by steam distillation from Alpinia zerumbet fructus. After a series of purifications, a homogeneous polysaccharide (AZP-2) of molecular weight 1.25 × 105 Da was obtained. Structure, anti-inflammatory activity, and anti-inflammatory mechanism were investigated. AZP-2 was mainly composed of galactose, arabinose, xylopyranose, glucose, and galacturonic acid. The main linkage structure of AZP-2 was determined after integrating the nuclear magnetic resonance (NMR) and methylation analysis, and the structure was comparatively complex. The results indicated that AZP-2 significantly decreased the production of NO and ROS in the inflammatory model established by lipopolysaccharide (LPS) stimulated RAW264.7, particularly at the concentration of 200 µg/mL. Furthermore, AZP-2 significantly modulated the secretion of both pro-inflammatory and anti-inflammatory cytokines. Notably, the mechanism of AZP-2 exhibiting inhibitory effects was related to regulating the NF-κB signaling pathway. Overall, AZP-2 could be used as a potential anti-inflammatory agent for further in-depth studies.

Stanniocalcin 2 regulates autophagy and ferroptosis in mammary epithelial cells of dairy cows through the mTORC1 pathway.

BACKGROUND: Stanniocalcin 2 (STC2), a glycoprotein hormone, is extensively expressed in various organs and tissues, particularly in the mammary gland. STC2 plays a crucial role in enabling cells to adapt to stress conditions and avert apoptosis. The efficiency of milk production is closely linked to both the quantity and quality of mammary cells. Yet there remains a dearth of research on the impact of STC2 on mammary cells activity in dairy cows. OBJECTIVE: The objective of this study was to investigate the effects of STC2 on the viability of mammary epithelial cells in dairy cows and to elucidate the underlying mechanisms. METHODS: Firstly, the GEPIA database was employed to perform survival analysis on STC2 expression in relation to prognosis using TCGA and GETx data. Subsequently, the basic physical and chemical properties, gene expression, and potential signaling pathways involved in the growth of dairy cow mammary epithelial cells were determined using STC2 knockdown. RESULTS: STC2 knockdown significantly suppressed autophagy in mammary epithelial cells of dairy cows. Moreover, STC2 knockdown upregulated GPX4 protein expression, elicited an elevation in Lipid ROS levels, and inhibited the mTORC1 signaling pathway, consequently repressing downstream genes involved in lipid synthesis regulated by mTORC1 and ultimately inducing ferroptosis. CONCLUSIONS: The findings of our study suggest that STC2 suppresses autophagy and ferroptosis through the activation of mTORC1. Mechanically, STC2 exerts an inhibitory effect on ferroptosis by activating antioxidative stress-related proteins, such as GPX4, to suppress Lipid ROS production and stimulating the mTORC1 signaling pathway to enhance the expression of genes associated with lipid synthesis.

Integration of metal organic framework nanoparticles into sodium alginate biopolymer-based three-dimensional membrane capsules for the efficient removal of toxic metal cations from water and real sewage.

Sodium alginate (SA) biopolymer has been recognized as an efficient adsorbent material owing to their unique characteristics, including biodegradability, non-toxic nature, and presence of abundant hydrophilic functional groups. Accordingly, in the current research work, UiO-66-OH and UiO-66-(OH)2 metal organic framework (MOF) nanoparticles (NPs) have been integrated into SA biopolymer-based three-dimensional (3-D) membrane capsules (MCs) via a simple and facile approach to remove toxic metal cations (Cu2+ and Cd2+) from water and real sewage. The newly configured capsules were characterized by FTIR, SEM, XRD, EDX and XPS analyses techniques. Exceptional sorption properties of the as-developed capsules were ensured by evaluation of the pertinent operational parameters, i.e., contents of MOF-NPs (1-100 wt%), adsorbent dosage (0.001-0.05 g), content time (0-360 h), pH (1-8), initial concentration of metal cations (5-1000 mg/L) and reaction temperature (298.15-333.15 K) on the eradication of Cu2+ and Cd2+ metal cations. It was found that hydrophilic functional groups (-OH and -COOH) have performed an imperative role in the smooth loading of MOF-NPs into 3-D membrane capsules via intra/inter-molecular hydrogen bonding and van der waals potencies. The maximum monolayer uptake capacities (as calculated by the Langmuir isotherm model) of Cd2+ and Cu2+ by 3-D SGMMCs-OH were 940 and 1150 mg/g, respectively, and by 3-D SGMMCs-(OH)2 were 1375 and 1575 mg/g, respectively, under optimum conditions. The as-developed capsules have demonstrated superior selectivity against targeted metal cations under designated pH and maintained >80 % removal efficiency up to six consecutive treatment cycles. Removal mechanisms of metal cations by the 3-D SGMMCs-OH/(OH)2 was proposed, and electrostatic interaction, ion-exchange, inner-sphere coordination bonds/interactions, and aromatic ligands exchange were observed to be the key removal mechanisms. Notably, FTIR and XPS analysis indicated that hydroxyl groups of Zr-OH and BDC-OH/(OH)2 aromatic linkers played vital roles in Cu2+ and Cd2+ adsorption by participating in inner-sphere coordination interactions and aromatic ligands exchange mechanisms. The as-prepared capsules indicated >70 % removal efficiency of Cu2+ from real electroplating wastewater in the manifestation of other competitive metal ions and pollutants under selected experimental conditions. Thus, it was observed that newly configured 3-D SGMMCs-OH/(OH)2 have offered a valuable discernment into the development of MOFs-based water decontamination 3-D capsules for industrial applications.

Habitual Short Sleep Duration, Diet, and Development of Type 2 Diabetes in Adults.

Importance: Understanding the interplay between sleep duration, dietary habits, and the risk of developing type 2 diabetes (T2D) is crucial for public health and diabetes prevention strategies. Objective: To investigate the associations of type of diet and duration of sleep with the development of T2D. Design, Setting, and Participants: Data derived from the UK Biobank baseline investigation (2006-2010) were analyzed for this cohort study between May 1 and September 30, 2023. The association between sleep duration and healthy dietary patterns with the risk of T2D was investigated during a median (IQR) follow-up of 12.5 (11.8-13.2) years (end of follow-up, September 30, 2021). Exposure: For the analysis, 247 867 participants were categorized into 4 sleep duration groups: normal (7-8 hours per day), mild short (6 hours per day), moderate short (5 hours per day), and extreme short (3-4 hours per day). Their dietary habits were evaluated based on population-specific consumption of red meat, processed meat, fruits, vegetables, and fish, resulting in a healthy diet score ranging from 0 (unhealthiest) to 5 (healthiest). Main Outcomes and Measures: Cox proportional hazards regression analysis was used to calculate hazard ratios (HRs) and 95% CIs for the development of T2D across various sleep duration groups and healthy diet scores. Results: The cohort comprised 247 867 participants with a mean [SD] age of 55.9 [8.1] years, of whom 52.3% were female. During the follow-up, 3.2% of participants were diagnosed with T2D based on hospital registry data. Cox regression analysis, adjusted for confounding variables, indicated a significant increase in the risk of T2D among participants with 5 hours or less of daily sleep. Individuals sleeping 5 hours per day exhibited a 1.16 adjusted HR (95% CI, 1.05-1.28), and individuals sleeping 3 to 4 hours per day exhibited a 1.41 adjusted HR (95% CI, 1.19-1.68) compared with individuals with normal sleep duration. Furthermore, individuals with the healthiest dietary patterns had a reduced risk of T2D (HR, 0.75 [95% CI, 0.63-0.88]). The association between short sleep duration and increased risk of T2D persisted even for individuals following a healthy diet, but there was no multiplicative interaction between sleep duration and healthy diet score. Conclusions and Relevance: In this cohort study involving UK residents, habitual short sleep duration was associated with increased risk of developing T2D. This association persisted even among participants who maintained a healthy diet. To validate these findings, further longitudinal studies are needed, incorporating repeated measures of sleep (including objective assessments) and dietary habits.

Birth weight, ideal cardiovascular health metrics in adulthood, and incident cardiovascular disease.

BACKGROUND: Prenatal and postnatal factors may have joint effects on cardiovascular health, and we aimed to assess the joint association of birth weight and ideal cardiovascular health metrics (ICVHMs) prospectively in adulthood with incident cardiovascular disease (CVD). METHODS: In the UK Biobank, 227,833 participants with data on ICVHM components and birth weight and without CVD at baseline were included. The ICVHMs included smoking, body mass index, physical activity, diet information, total cholesterol, blood pressure, and hemoglobin A1c. The Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) in men and women. RESULTS: Over a median follow-up period of 13.0 years (2,831,236 person-years), we documented 17,477 patients with incident CVD. Compared with participants with birth weights of 2.5-4.0 kg, the HRs [95% CIs] of CVD among those with low birth weights was 1.08 (1.00-1.16) in men and 1.23 (95% CI: 1.16-1.31) in women. The association between having a birth weight <2.5 kg and CVD risk in men was more prominent for those aged <50 years than for those of older age (P for interaction = 0.026). Lower birth weight and non-ideal cardiovascular health metrics were jointly related to an increased risk of CVD. Participants with birth weights <2.5 kg and ICVHMs score 0-1 had the highest risk of incident CVD (HR [95% CI]: 3.93 [3.01-5.13] in men; 4.24 [3.33-5.40] in women). The joint effect (HR [95% CI]: 1.36 [1.17-1.58]) could be decomposed into 24.7% (95% CI: 15.0-34.4%) for a lower birth weight, 64.7% (95% CI: 56.7-72.6%) for a lower ICVHM score, and 10.6% (95% CI: 2.7-18.6%) for their additive interaction in women. CONCLUSIONS: Birth weight and ICVHMs were jointly related to CVD risk. Attaining a normal birth weight and ideal ICVHMs may reduce the risk of CVD, and a simultaneous improvement of both prenatal and postnatal factors could further prevent additional cases in women.

Association of combined healthy lifestyle with risk of adverse outcomes in patients with prediabetes.

OBJECTIVE: Prediabetes and lifestyle factors have been associated with the risks of multiple adverse outcomes, but the effect of a healthy lifestyle on prediabetes-related complications remains unknown. We aimed to investigate whether the risks of multiple adverse outcomes including incident type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and chronic kidney disease (CKD) among individuals with prediabetes can be offset by a broad combination of healthy lifestyle factors. METHODS: This prospective study used data from the UK Biobank cohort. An overall lifestyle score ranging from 0 to 6 was created with 1 point for each of the 6 healthy lifestyle factors: no current smoking, moderate alcohol consumption, regular physical activity, healthy diet, no overweight or obese, and adequate sleep duration. T2DM, CVD, and CKD were ascertained during a median follow-up of 14 years. Cox proportional hazard regression models were used to estimate the associations. Sensitivity analyses were performed to test the robustness of the results. RESULTS: We included 202,993 participants without T2DM, CVD, and CKD at baseline (mean age 55.5 years [SD 8.1]; 54.7% were women). Among these participants, 6,745, 16,961, and 6,260 participants eventually developed T2DM, CVD, and CKD, respectively. Compared with the participants with normoglycaemia, those with prediabetes showed a higher risk of these adverse outcomes. In addition, those prediabetic participants with a lifestyle score of 0-1 had a significantly higher risk of T2DM (hazard ratio [HR] 16.73, 95% CI 14.24, 19.65), CVD (HR 1.96, 95% CI 1.74, 2.21), and CKD (HR 1.92, 95% CI 1.58, 2.34) compared with those with no prediabetes and a score of 5-6. Moreover, among the participants with prediabetes, the HRs for T2DM, CVD, and CKD comparing a lifestyle score of 5-6 versus 0-1 decreased to 0.43 (95% CI 0.36, 0.51), 0.52 (95% CI 0.44, 0.62), and 0.60 (95% CI 0.46, 0.79), respectively. CONCLUSIONS: Combined healthy lifestyle factors were associated with a significantly lower risk of multiple adverse outcomes, including T2DM, CVD, and CKD. This indicates that prioritising multifactorial approaches to behavioural lifestyle modification is crucial for preventing and postponing the development of complications related to prediabetes.

Sweetened Beverages, Genetic Susceptibility, and Incident Atrial Fibrillation: A Prospective Cohort Study.

BACKGROUND: An association between sweetened beverages and several cardiometabolic diseases has been reported, but their association with atrial fibrillation (AF) is unclear. We aimed to investigate the associations between consumption of sugar-sweetened beverages (SSB), artificially sweetened beverages (ASB), and pure fruit juice (PJ) and risk of consumption with AF risk and further evaluate whether genetic susceptibility modifies these associations. METHODS: A total of 201 856 participants who were free of baseline AF, had genetic data available, and completed a 24-hour diet questionnaire were included. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 9.9 years, 9362 incident AF cases were documented. Compared with nonconsumers, individuals who consumed >2 L/wk of SSB or ASB had an increased risk of AF (HR, 1.10 [95% CI, 1.01-1.20] and HR, 1.20 [95% CI, 1.10-1.31]) in the multivariable-adjusted model. A negative association was observed between the consumption of ≤1 L/wk of PJ and the risk of AF (HR, 0.92 [95% CI, 0.87-0.97]). The highest HRs (95% CIs) of AF were observed for participants at high genetic risk who consumed >2 L/wk of ASB (HR, 3.51 [95% CI, 2.94-4.19]), and the lowest HR were observed for those at low genetic risk who consumed ≤1 L/wk of PJ (HR, 0.77 [95% CI, 0.65-0.92]). No significant interactions were observed between the consumption of SSB, ASB, or PJ and genetic predisposition to AF. CONCLUSIONS: Consumption of SSB and ASB at >2 L/wk was associated with an increased risk for AF. PJ consumption ≤1 L/wk was associated with a modestly lower risk for AF. The association between sweetened beverages and AF risk persisted after adjustment for genetic susceptibility to AF. This study does not demonstrate that consumption of SSB and ASB alters AF risk but rather that the consumption of SSB and ASB may predict AF risk beyond traditional risk factors.