Tea Consumption, Milk or Sweeteners Addition, Genetic Variation in Caffeine Metabolism, and Incident Venous Thromboembolism.

OBJECTIVE: The association between tea consumption and venous thromboembolism (VTE) remains unknown. We aimed to evaluate the association between tea consumption with different additives (milk and/or sweeteners) and incident VTE, and the modifying effects of genetic variation in caffeine metabolism on the association. METHODS: A total of 190,189 participants with complete dietary information and free of VTE at baseline in the UK Biobank were included. The primary outcome was incident VTE, including incident deep vein thrombosis and pulmonary embolism. RESULTS: During a median follow-up of 12.1 years, 4,485 (2.4%) participants developed incident VTE. Compared with non-tea drinkers, tea drinkers who added neither milk nor sweeteners (hazard ratio [HR]: 0.85; 95% confidence interval [95% CI]: 0.76-0.94), only milk (HR: 0.86; 95% CI: 0.80-0.93), and both milk and sweeteners to their tea (HR: 0.90; 95% CI: 0.81-0.99) had a lower risk of VTE, while those who added only sweeteners to their tea did not (HR: 0.94; 95% CI: 0.75-1.17). Moreover, there was an L-shaped relationship between tea consumption and incident VTE among tea drinkers who added neither milk nor sweeteners, only milk, and both milk and sweeteners to their tea, respectively. However, a nonsignificant association was found among tea drinkers who added only sweeteners to their tea. Genetic variation in caffeine metabolism did not significantly modify the association (p-interaction = 0.659). CONCLUSION: Drinking unsweetened tea, with or without added milk, was associated with a lower risk of VTE. However, there was no significant association between drinking tea with sweeteners and incident VTE.

Spatial transcriptomics reveals segregation of tumor cell states in glioblastoma and marked immunosuppression within the perinecrotic niche.

Glioblastoma (GBM) remains an untreatable malignant tumor with poor patient outcomes, characterized by palisading necrosis and microvascular proliferation. While single-cell technology made it possible to characterize different lineage of glioma cells into neural progenitor-like (NPC-like), oligodendrocyte-progenitor-like (OPC-like), astrocyte-like (AC-like) and mesenchymal like (MES-like) states, it does not capture the spatial localization of these tumor cell states. Spatial transcriptomics empowers the study of the spatial organization of different cell types and tumor cell states and allows for the selection of regions of interest to investigate region-specific and cell-type-specific pathways. Here, we obtained paired 10x Chromium single-nuclei RNA-sequencing (snRNA-seq) and 10x Visium spatial transcriptomics data from three GBM patients to interrogate the GBM microenvironment. Integration of the snRNA-seq and spatial transcriptomics data reveals patterns of segregation of tumor cell states. For instance, OPC-like tumor and NPC-like tumor significantly segregate in two of the three samples. Our differentially expressed gene and pathway analyses uncovered significant pathways in functionally relevant niches. Specifically, perinecrotic regions were more immunosuppressive than the endogenous GBM microenvironment, and perivascular regions were more pro-inflammatory. Our gradient analysis suggests that OPC-like tumor cells tend to reside in areas closer to the tumor vasculature compared to tumor necrosis, which may reflect increased oxygen requirements for OPC-like cells. In summary, we characterized the localization of cell types and tumor cell states, the gene expression patterns, and pathways in different niches within the GBM microenvironment. Our results provide further evidence of the segregation of tumor cell states and highlight the immunosuppressive nature of the necrotic and perinecrotic niches in GBM.

Association of accelerometer-measured physical activity and its change with progression to chronic kidney disease in adults with type 2 diabetes and overweight/obesity.

OBJECTIVE: To examine the long-term association of objectively measured moderate-to-vigorous physical activity (MVPA) and its longitudinal changes with progression to chronic kidney disease (CKD) in patients with type 2 diabetes (T2D) and overweight/obesity. METHODS: This study included 1746 participants in the Look AHEAD trial with baseline estimated glomerular filtration rate (eGFR)≥60 mL/min/1.73 m2. MVPA was measured at baseline, year 1, year 4 and year 8 using an RT3 accelerometer. The outcome was progression to CKD, defined as eGFR<60 mL/min per 1.73 m2 with a drop of ≥30% or end-stage kidney disease. Cox hazards models were fitted to examine the association between MVPA and outcomes. RESULTS: Over a median follow-up of 12.0 years, 567 participants experienced progression to CKD. Overall, there was a linear inverse association of cumulative average total MVPA (per 100 min/week higher amount, HR: 0.91; 95% CI: 0.86 to 0.96) and MVPA accumulated in bouts of ≥10 min (per 100 minutes/week higher amount, HR: 0.81; 95% CI: 0.72 to 0.91) with progression to CKD. Moreover, an increase in total MVPA from baseline to year 4 (the fourth quartile, ≥63.2 min/week) was associated with a 33% lower risk of progression to CKD compared with the largest MVPA reduction (the first quartile, <-198.3 min/week). A lower risk of progression to CKD was also observed for increases in MVPA accumulated in bouts of both <10 min and ≥10 min. CONCLUSIONS: Longer MVPA time and increases in MVPA was associated with a reduced risk of progression to CKD in adults with overweight/obesity and T2D.

J-shaped association between dietary thiamine intake and the risk of cognitive decline in cognitively healthy, older Chinese individuals.

Background: The prospective association of dietary thiamine intake with the risk of cognitive decline among the general older adults remains uncertain. Aims: To investigate the association between dietary thiamine intake and cognitive decline in cognitively healthy, older Chinese individuals. Methods: The study included a total of 3106 participants capable of completing repeated cognitive function tests. Dietary nutrient intake information was collected through 3-day dietary recalls and using a 3-day food-weighed method to assess cooking oil and condiment consumption. Cognitive decline was defined as the 5-year decline rate in global or composite cognitive scores based on a subset of items from the Telephone Interview for Cognitive Status-modified. Results: The median follow-up duration was 5.9 years. There was a J-shaped relationship between dietary thiamine intake and the 5-year decline rate in global and composite cognitive scores, with an inflection point of 0.68 mg/day (95% confidence interval (CI): 0.56 to 0.80) and a minimal risk at 0.60-1.00 mg/day of dietary thiamine intake. Before the inflection point, thiamine intake was not significantly associated with cognitive decline. Beyond the inflection point, each unit increase in thiamine intake (mg/day) was associated with a significant decrease of 4.24 (95% CI: 2.22 to 6.27) points in the global score and 0.49 (95% CI: 0.23 to 0.76) standard units in the composite score within 5 years. A stronger positive association between thiamine intake and cognitive decline was observed in those with hypertension, obesity and those who were non-smokers (all p<0.05). Conclusions: This study revealed a J-shaped association between dietary thiamine intake and cognitive decline in cognitively healthy, older Chinese individuals, with an inflection point at 0.68 mg/day and a minimal risk at 0.60-1.00 mg/day of dietary thiamine intake.

Relationship of dietary intake of food folate and synthetic folic acid intake from fortified foods with all-cause mortality in individuals with chronic kidney disease.

OBJECTIVE: To evaluate the association of the dietary intake of food folate (natural folate) and synthetic folic acid intake from fortified foods with the risk of all-cause mortality and end-stage kidney disease (ESKD) among the chronic kidney disease (CKD) population in regions with folic acid fortification. METHODS: 4028 individuals with established CKD in Chronic Renal Insufficiency Cohort (CRIC) were included. Diet was assessed using a validated diet history questionnaire at the baseline, year 2, and year 4, and nutrient intake, including food folate and folic acid from fortified foods, was estimated using the National Nutrient Database. The outcomes were all-cause mortality and ESKD. The results for all-cause mortality were further validated using the data from National Health and Nutrition Examination Surveys (NHANES). RESULTS: During a median follow-up of 11.1 years, 1155 deaths and 938 ESKD cases occurred. Compared with the first quartile of food folate intake, the third (HR: 0.74; 95% CI: 0.62, 0.90) and fourth (HR: 0.79; 95% CI: 0.63, 0.98) quartiles had a lower risk of all-cause mortality. Nevertheless, there was no significant association of synthetic folic acid intake from fortified foods with all-cause mortality. Similar results were observed for ESKD. Consistently, in NHANES, food folate intake and serum 5-methyltetrahydrofolate, but not folic acid intake, were inversely associated with all-cause mortality, while serum unmetabolized folic acid was positively associated with all-cause mortality in CKD participants. CONCLUSIONS: Higher intake of dietary natural folate, but not synthetic folic acid intake from fortified foods, was associated with lower risks of all-cause mortality and ESKD among CKD participants.

L-shaped association between dietary zinc intake and cognitive decline in Chinese older people.

BACKGROUND AND OBJECTIVE: The prospective association between dietary zinc (Zn) intake and cognitive decline remains uncertain. We aimed to assess the relationship of dietary Zn intake with the risk of cognitive decline in the Chinese older people, and examine the possible effect modifiers on this association. METHODS: A total of 3,106 older Chinese adults aged 55 years or older from China Health and Nutrition Survey were included. Dietary nutrients intake information was collected by combined 24-h dietary recalls with weighing food inventory. The cognitive decline was defined as the 5-year decline rate in global and composite cognitive scores, based on a subset of items from the Telephone Interview for Cognitive Status-modified. RESULTS: The median follow-up duration was 5.9 years. There was an L-shaped association between dietary Zn intake and the 5-year decline rates in global and composite cognitive scores, with an inflection point at 8.8 mg/day of dietary Zn. For the composite cognitive scores, compared with the first quantile (<7.9 mg/day) of dietary Zn intake, quantiles 2-6 (≥7.9 mg/day) had a significantly slower cognitive decline rate (ß: -0.24; 95% confidence interval: -0.40 to -0.07). Similar results were found for the global cognitive scores. Moreover, the inverse association between dietary Zn intake and cognitive decline in composite cognitive scores was significantly stronger in those with lower levels of physical activity (P-interactions = 0.041). CONCLUSION: Dietary Zn intake was negatively associated with cognitive decline in the older people. Maintaining appropriate dietary Zn levels may prevent cognitive decline.

Serum 25-Hydroxyvitamin D, Vitamin D Receptor, and Vitamin-D-Binding Protein Gene Polymorphisms and Risk of Dementia Among Older Adults With Prediabetes.

BACKGROUND: The association between vitamin D and dementia risk in those with prediabetes remains uncertain. We aimed to evaluate the association of serum 25-hydroxyvitamin D (25OHD) with incident dementia among older adults with prediabetes, and examine whether apolipoprotein E (APOE) genotypes, vitamin D receptor (VDR), and vitamin-D-binding protein (VDBP) gene polymorphisms may modify this association. METHODS: A total of 34 237 participants aged ≥60 with prediabetes (HbA1c <6.5% and ≥5.7%) and without dementia at baseline were included from the UK Biobank. Serum 25-hydroxyvitamin D (25OHD) was measured using chemiluminescent immunoassay method. The primary outcome was incident all-cause dementia. Secondary outcomes included incident Alzheimer's disease (AD) and vascular dementia, respectively. The VDR and VDBP gene polymorphisms included single nucleotide polymorphisms of rs7975232, rs1544410, rs2228570, rs731236, and rs7041, rs4588, respectively. RESULTS: During a median follow-up of 11.8 years, 941 (2.7%) participants developed incident all-cause dementia. Overall, serum 25OHD was inversely associated with all-cause dementia (per standard deviation increment, adjusted hazard ratio: 0.82; 95% confidence interval: 0.75, 0.89). Similar trends were found for incident AD and vascular dementia. Furthermore, there was a stronger inverse relationship between serum 25OHD and all-cause dementia among VDR rs7975232 C allele noncarriers (p-interaction < 0.05). However, APOE Ɛ4, other VDR, and VDBP gene polymorphisms did not significantly modify the relation of serum 25OHD with incident all-cause dementia (all p-interactions >.05). CONCLUSIONS: There was an inverse association between serum 25OHD and incident dementia among older adults with prediabetes, especially in VDR rs7975232 AA allele carriers.

Social isolation, loneliness, and the risk of incident acute kidney injury in middle-aged and older adults: A prospective cohort study.

OBJECTIVE: The relationships of social isolation and loneliness with acute kidney injury (AKI) risk remained uncertain. We aimed to investigate the associations of social isolation and loneliness with incident AKI. METHODS: 450,868 participants without prior AKI were included from the UK Biobank. The social isolation index was constructed based on living alone, social contact, and participation in social activities. Loneliness was assessed by asking about "Do you often feel lonely?". The study outcome was incident AKI. RESULTS: During a median follow-up of 12.0 years, 18,679 (4.1%) participants developed AKI, including 18,428 participants ascertained by hospital admission records with a median duration of hospitalization of 3 (25th-75th, 1-8) days. The hazard ratio for incident AKI for social isolation compared with no social isolation was 1.50 (95% CI: 1.44-1.55) after adjusting for age and race (minimally adjusted), and was 1.10 (95% CI: 1.06-1.14) after further adjusting for socioeconomic factors, health behaviors, biological and health-related factors, psychologic factors, and loneliness (fully adjusted). The minimally adjusted and fully adjusted hazard ratios for incident AKI for loneliness compared with no loneliness was 1.57 (95% CI: 1.52-1.62), and 1.10 (95% CI: 1.06-1.15), respectively. In the fully adjusted models, the highest risk of AKI was found in those with both social isolation and loneliness. Living alone and less social contact, rather than less participation in social activities, were significantly associated with a higher risk of incident AKI. CONCLUSIONS: Both social isolation and loneliness were independently and significantly associated with a higher risk of incident AKI.

Relationship among serum 25-hydroxyvitamin D, fibrosis stage, genetic susceptibility, and risk of severe liver disease.

OBJECTIVES: The prospective association between vitamin D and new-onset severe liver disease is still uncertain. The aim of this study was to assess the association of serum 25-hydroxyvitamin D (25(OH)D) with new-onset severe liver disease and to evaluate whether fibrosis stage, as assessed by the fibrosis- 4 (FIB-4) scores and genetic risk for liver cirrhosis may modify this association. METHODS: The study included 439 807 participants without liver diseases at baseline from the UK Biobank. Serum 25(OH)D concentrations were measured using the chemiluminescent immunoassay method. The primary outcome was new-onset severe liver disease, a composite definition of compensated or decompensated liver cirrhosis, liver failure, hepatocellular carcinoma, and liver-related death. RESULTS: During a median follow-up of 12 y, 4510 participants developed new-onset severe liver disease. Overall, there was an inverse association of serum 25(OH)D with new-onset severe liver disease (per SD increment, adjusted hazard ratio [HR], 0.87; 95% confidence interval, 0.84-0.91). Similarly, serum 25(OH)D (per SD increment) was significantly and inversely associated with new-onset compensated cirrhosis, decompensated cirrhosis, liver failure, and liver-related death, respectively, with HRs ranging from 0.75 to 0.87. No significant association was found for hepatocellular carcinoma. Furthermore, there was a stronger inverse association between serum 25(OH)D and severe liver disease among those with a higher FIB-4 score (≥2.67, 1.3 to <2.67, and <1.3; Pinteraction < 0.001). However, the genetic risks for liver cirrhosis, calculated using 12 related single nucleotide polymorphisms, did not significantly modify the association between serum 25(OH)D and severe liver disease (Pinteraction = 0.216). CONCLUSIONS: Lower serum 25(OH)D concentrations were significantly associated with a greater risk for new-onset severe liver disease, especially in participants with higher FIB-4 scores.

Social isolation, loneliness, and the risk of incident type 2 diabetes mellitus by glycemic status.

AIM: The modifying effect of prediabetic status on the association of social isolation and loneliness with the risk of type 2 diabetes mellitus (T2DM) remains uncertain. We aimed to explore whether prediabetic status modifies the association of social isolation and loneliness with incident T2DM. METHODS: 358,951 participants with random blood glucose < 11.1 mmol/l, hemoglobin A1c < 6.5 % and without diagnosis of diabetes from the UK Biobank were included. Prediabetes was defined by hemoglobin A1c level at 5.7-6.4 %. Social isolation and loneliness were assessed using self-reported questionnaires. The study outcome was incident T2DM. RESULTS: During a median follow-up of 12.5 years, 13,213 (3.7 %) incident T2DM cases were documented. Social isolation and loneliness in subjects with normoglycemia (adjusted HR [95 %CI]: social isolation: 1.14 [1.07;1.23]; loneliness: 1.33 [1.20;1.47]) were more strongly associated with increased risk of T2DM than in those with prediabetes (adjusted HR [95 %CI]: social isolation: 0.97 [0.91;1.03]; loneliness: 1.04 [0.95;1.13]) (Both P for interaction < 0.001). Among individuals with prediabetes, alcoholic consumption (30.9 %), household income (23.3 %), healthy sleep (17.1 %), loneliness (14.9 %), and physical activity (12.6 %) mediated most of the variance in the association between social isolation and incident T2DM, while body mass index (17.9 %) and healthy sleep (17.6 %) mediated most of the variance in the association between loneliness and incident T2DM. CONCLUSION: Social isolation and loneliness were independently associated with a higher risk of T2DM among individuals without prediabetes. Among those with prediabetes, the association of social isolation and loneliness with incident T2DM were mainly mediated by some socioeconomic and lifestyle factors.

Association of Body Weight Time in Target Range With the Risk of Kidney Outcomes in Patients With Overweight/Obesity and Type 2 Diabetes Mellitus.

OBJECTIVE: We assessed the relationship of body weight time in target range (TTR) with composite kidney outcome in people with overweight/obesity and type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: Included in this study were 3,601 participants with baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 from the Look AHEAD (Action for Health in Diabetes) trial. Body weight TTR was defined as the proportion of time during the first 4 years that body weight was within the weight loss target (a weight loss of ≥7% from baseline). The primary outcome was composite kidney outcome, defined as eGFR decline ≥30% from baseline and to a level <60 mL/min/1.73 m2 at follow-up visit, or end-stage kidney disease. RESULTS: During a median follow-up of 8.0 years, 435 cases of composite kidney outcome were documented. Body weight TTR during the first 4 years was inversely associated with the subsequent risk of composite kidney outcome (per SD increment; adjusted hazard ratio [HR] 0.81; 95% CI 0.70-0.93). Accordingly, the adjusted HRs (95% CI) of composite kidney outcome were 1.00 (reference), 0.73 (0.54-1.00), 0.71 (0.52-0.99), and 0.54 (0.36-0.80) for participants with body weight TTR of 0%, >0% to <29.9%, 29.9% to <69.7%, and 69.7% to <100%, respectively. Similar results were found for a doubling of the urine albumin to creatinine ratio (secondary outcome). CONCLUSIONS: A higher body weight TTR, with a weight loss target of losing ≥7% of initial weight, was associated with a lower risk of kidney outcomes in participants with overweight/obesity and T2DM.

Habitual fish oil supplementation, genetic susceptibility of kidney stones and the risk of new-onset kidney stones.

OBJECTIVE: We aimed to assess the association between habitual fish oil use and new-onset kidney stones in participants with different levels of genetic risks of kidney stones. METHODS: 477,311 participants free of kidney stones at baseline from the UK Biobank cohort were included. Fish oil use was collected by both food frequency questionnaires and 24-h dietary recalls. A genetic risk score (GRS) for kidney stones was calculated based on 20 single-nucleotide polymorphisms associated with kidney stones. The primary outcome was new-onset kidney stones. RESULTS: During a median follow-up of 12.0 years, 5,637 cases of kidney stones were documented. Participants with high genetic risks of kidney stones had a higher risk of new-onset kidney stones (vs. low or intermediate risks; adjusted HR, 1.52; 95 %CI:1.44-1.60). Compared with non-users, habitual use of fish oil was associated with a lower risk of new-onset kidney stones (adjusted HR, 0.84, 95 %CI, 0.78-0.92) in participants with low or intermediate genetic risks, but not in those with high genetic risks of kidney stones (adjusted HR, 1.02, 95 %CI, 0.93-1.12; P-interaction =0.001). Among those with low or intermediate genetic risks of kidney stones, compared with fish oil constant nonusers, the adjusted HRs (95 %CI) for kidney stones were 0.89 (0.75-1.06), 0.72 (0.58-0.90), and 0.79 (0.64-0.97), for fish oil occasional users, modestly constant users, and moderately and highly constant users (P for trend = 0.001), respectively. CONCLUSIONS: Habitual fish oil use was associated with a lower risk of new-onset kidney stones in participants with low or intermediate genetic risk of kidney stones.

Progress on the mechanism of natural products alleviating androgenetic alopecia.

Androgenetic alopecia (AGA) has become a widespread problem that leads to considerable impairment of the psyche and daily life. The currently approved medications for the treatment of AGA are associated with significant adverse effects, high costs, and prolonged treatment duration. Therefore, natural products are being considered as possible complementary or alternative treatments. This review aims to enhance comprehension of the mechanisms by which natural products treat AGA. To achieve this, pertinent studies were gathered and subjected to analysis. In addition, the therapeutic mechanisms associated with these natural products were organized and summarized. These include the direct modulation of signaling pathways such as the Wnt/ß-catenin pathway, the PI3K/AKT pathway, and the BMP pathway. Additionally, they exert effects on cytokine secretion, anti-inflammatory, and antioxidant capabilities, as well as apoptosis and autophagy. Furthermore, the review briefly discusses the relationship between signaling pathways and autophagy and apoptosis in the context of AGA, systematically presents the mechanisms of action of existing natural products, and analyzes the potential therapeutic targets based on the active components of these products. The aim is to provide a theoretical basis for the development of pharmaceuticals, nutraceuticals, or dietary supplements.

Different sedentary behaviors, genetic susceptibility of hypertension, and new-onset hypertension: Mediating effects of body mass index and grip strength.

BACKGROUND: The association between different sedentary behaviors and hypertension risk remains unclear. We aimed to explore the relationship between different domains of sedentary behaviors and new-onset hypertension, investigate whether genetic susceptibility to hypertension modifies the relationship, and examine the extent to which the relationship is mediated by body mass index (BMI) and grip strength. METHODS: 212 714 participants without baseline hypertension in the UK Biobank were enrolled. The three major sedentary behaviors (TV-watching, nonoccupational computer use, and driving) were measured using touch screen questionnaires. The primary outcome was new-onset hypertension. RESULTS: During a median follow-up of 11.9 years, 13 983 participants developed hypertension. There was a linear positive association between TV-watching time and new-onset hypertension (p for nonlinearity =0.868). A J-shaped association was found for nonoccupational computer use time and driving time with new-onset hypertension, with an inflection point of 0.5 h/day for both (both p for nonlinearity <0.001). Polygenetic risk scores for hypertension (based on 118 related single-nucleotide polymorphisms) did not significantly modify these associations (all p-interactions >0.05). Furthermore, the detrimental effects of long-term sedentary behaviors on hypertension were mediated by BMI by 21%-30%, and the beneficial effects of limited sitting time (within 0.5 h/day) for driving and nonoccupational computer use were mediated by grip strength by 6-25%. CONCLUSIONS: There was a positive association for hands-independence sedentary behavior (TV-watching), and a J-shaped association for hands-dependence sedentary behaviors (nonoccupational computer use and driving) with new-onset hypertension, regardless of genetic risks of hypertension. These relationships were partly mediated by BMI and grip strength.

Adding salt to foods and hazards of microvascular, cerebrovascular and cardiovascular diseases.

BACKGROUND: We aimed to examine the association of the frequency of adding salt to foods and the hazards of the incidence and mortality risks for a range of vascular outcomes, including microvascular, cerebrovascular, and cardiovascular diseases. METHODS: 438,307 participants from the UK Biobank who completed the questionnaire on the frequency of adding salt to foods and were free of vascular disease at baseline were enrolled. Information on the frequency of adding salt to foods (do not include salt used in cooking) was collected at baseline through a touch-screen questionnaire. The primary outcomes included incident microvascular diseases, cerebrovascular diseases, and cardiovascular diseases, respectively. The secondary outcomes included: (1) each component of these vascular diseases (10 components in total), (2) first occurrence of fatal and non-fatal vascular diseases. RESULTS: During a median follow-up of 12.1 years, a total of 17,169 (3.9%), 10,437 (2.4%), and 48,203 (11.0%) participants developed microvascular, cerebrovascular and cardiovascular diseases, respectively. Overall, the hazards of incident microvascular, cerebrovascular and cardiovascular diseases increased with the increasing frequency of adding salt to foods (all P for trend <0.001). Similar trends were found for the secondary outcomes. Moreover, the positive association of always adding salt to foods with hazard of cardiovascular diseases was stronger among current-smokers (P-interaction = 0.010), younger participants (P-interaction <0.001), and those with lower body mass index levels (P-interaction = 0.003). CONCLUSIONS: Higher frequency of adding salt to foods was associated with higher hazards of non-fatal and fatal microvascular, cerebrovascular and cardiovascular diseases, and each component of these vascular diseases.

Relationship of serum 25-hydroxyvitamin D, obesity with new-onset obstructive sleep apnea.

OBJECTIVE: The prospective association between vitamin D and obstructive sleep apnea (OSA) remains uncertain. We aimed to assess the association between serum 25-hydroxyvitamin D (25(OH)D), a major circulating form of vitamin D, and new-onset OSA, and examine the modifying effect of obesity. MATERIALS AND METHODS: This prospective cohort study included 444,975 participants from UK Biobank without prior OSA. The primary outcome was new-onset OSA. RESULTS: During a median follow-up duration of 12.0 years, 6051 (1.4%) participants occurred new-onset OSA. Overall, there was an inverse relation of serum 25(OH)D concentrations with the risk of new-onset OSA (per SD increment, HR, 0.92; 95%CI: 0.89-0.95). In the analysis of the interactions of serum 25(OH)D with the combination of BMI (<25, 25- < 30, and ≥30 kg/m2) and waist circumference (WC) (<90 and ≥90 cm) categories on new-onset OSA, the significantly inverse association of serum 25(OH)D and new-onset OSA was mainly found in participants with both BMI ≥ 25 kg/m2 and WC ≥ 90 cm (BMI 25-30 kg/m2 and WC ≥ 90 cm: per SD increment, HR, 0.90; 95%CI: 0.84-0.95; BMI ≥ 30 kg/m2 and WC ≥ 90 cm: per SD increment, HR, 0.85; 95%CI: 0.81-0.88), but not in other four groups with BMI < 25 kg/m2 or WC < 90 cm (P -interaction = 0.004). CONCLUSIONS: There was an inverse relation of serum 25(OH)D with the risk of new-onset OSA in participants with both BMI ≥ 25 kg/m2 and WC ≥ 90 cm. Our findings suggest the importance of maintaining a higher serum 25(OH)D concentration for primary prevention of OSA in a population with obesity.

Association of handgrip strength and walking pace with incident Parkinson's disease.

BACKGROUND: We aimed to quantify the association of handgrip strength and self-reported walking pace with incident Parkinson's disease (PD) in the general population. METHODS: A total of 419 572 participants (54.1% females, mean age: 56.1 years [SD, 8.2]) without prior PD were included from UK Biobank. Handgrip strength was assessed by dynamometer. Walking pace was self-reported as slow, average or brisk. The study outcome was incident PD, determined by self-report data, hospital admission records or death records. RESULTS: The mean handgrip strength was 23.5 (SD, 6.3) and 39.6 (SD, 8.9) kg for females and males, respectively. A total of 33 645 (8.0%), 221 682 (52.8%) and 164 245 (39.2%) participants reported slow, average and brisk walking pace, respectively. Over a median follow-up duration of 12.5 years, 2152 participants developed incident PD. When handgrip strength was assessed as sex-specific tertiles, compared with those in the third tertile, the adjusted hazard ratios (HRs) (95% confidence interval [CI]) of incident PD for participants in the second and first tertiles were 1.23 (1.09-1.39) and 1.60 (1.42-1.79), respectively. Compared with brisk walking pace, average (HR, 1.33; 95% CI: 1.20-1.47) or slow (HR, 1.84; 95% CI: 1.57-2.15) walking pace was associated with a higher risk of incident PD. A lower grip strength (Tertiles 1 and 2) and an average/slow walking pace accounted for 23.8% and 19.9% of PD cases, respectively. When handgrip strength and walking pace were considered together, the highest risk of incident PD was observed in participants with both lowest handgrip strength and slow walking pace (HR, 2.89; 95% CI: 2.30-3.64). Genetic risks of PD did not significantly modify the relation of handgrip strength (P for interaction = 0.371) or walking pace (P for interaction = 0.082) with new-onset PD. CONCLUSIONS: Low handgrip strength and slow walking pace were significantly associated with a higher risk of incident PD, regardless of the individuals' genetic risk profile.

Mobile Phone Use and Risks of Overall and 25 Site-Specific Cancers: A Prospective Study from the UK Biobank Study.

BACKGROUND: The association between mobile phone use and incident cancers remains uncertain. We aimed to investigate the relationships of mobile phone use with incident overall and 25 site-specific cancers in men and women. METHODS: A total of 431,861 participants ages 38 to 73 years without prior cancers were included from the UK Biobank. Of these, 46.7% were male. Participants who used a mobile phone at least once per week to make or receive calls were defined as mobile phone users. The study outcomes were incident overall and 25 site-specific cancers. RESULTS: During a median follow-up of 10.7 years, 35,401 (17.5%) men and 30,865 (13.4%) women developed overall cancer. Mobile phone use was significantly associated with higher risks of incident overall cancer [HR, 1.09; 95% confidence interval (CI): 1.06-1.12], nonmelanoma skin cancer (NMSC; HR, 1.08; 95% CI: 1.03-1.14), urinary tract cancer (HR, 1.18; 95% CI:1.05-1.32), and prostate cancer (HR, 1.19; 95% CI: 1.13-1.25) in men, and incident overall cancer (HR, 1.03; 95% CI: 1.00-1.06), NMSC (HR, 1.07; 95% CI: 1.01-1.13), and vulva cancer (HR, 1.74; 95% CI: 1.00-3.02) in women, but not with other cancers. Among mobile phone users, there was a dose-response relationship of length of mobile phone use with incident NMSC in men and women, and prostate cancer in men (all Ptrend < 0.05). CONCLUSIONS: There was a dose-response relationship of length of mobile phone use with incident NMSC in men and women, and prostate cancer in men. IMPACT: Our findings underscore the importance of limiting mobile phone use or keeping a distance from mobile phone for primary prevention of NMSC and prostate cancer.

Positive association between dietary manganese intake and new-onset hypertension: A nationwide cohort study in China.

BACKGROUND AND AIM: To date, few studies have investigated the association between dietary manganese intake and the risk of hypertension, so the prospective relationship of dietary manganese intake and new-onset hypertension remains uncertain. We aimed to investigate the association between dietary manganese intake and the risk of new-onset hypertension in the general Chinese population. METHODS AND RESULTS: This prospective cohort study included 12,177 participants who were free of hypertension at baseline from China Health and Nutrition Survey (CHNS). Dietary intake was measured by 3 consecutive 24-h dietary recalls combined with a household food inventory. The study outcome was new-onset hypertension, defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg or diagnosed by a physician or under antihypertensive treatment during the follow-up. During a median follow-up duration of 6.1 years, 4269 (44.9 per 1000 person-years) participants developed new-onset hypertension. Overall, there was a positive association between dietary manganese intake and new-onset hypertension. The adjusted HRs (95%CIs) of new-onset hypertension were 1.00 (reference), 0.97 (0.87, 1.08), 1.24 (1.10, 1.39) and 1.75 (1.52, 2.01) across the quartiles of dietary manganese intake, respectively. Accordingly, a significantly higher risk of new-onset hypertension (HR, 1.38; 95%CI: 1.27, 1.50) was found in participants in quartiles 3-4 of dietary manganese intake (≥6.0 mg/day), compared with those in quartiles 1-2 (<6.0 mg/day). CONCLUSIONS: In the general Chinese population, dietary manganese intake was positively associated with the risk of new hypertension, independent of sodium intake and other important covariates.

Association of accelerometer-measured physical activity intensity, sedentary time, and exercise time with incident Parkinson's disease.

Evidence regarding the association between physical activity and Parkinson's disease (PD) risk is generally limited due to the use of self-report questionnaires. We aimed to quantify the separate and combined effects of accelerometer-measured light physical activity (LPA), moderate-to-vigorous physical activity (MVPA), sedentary time and exercise timing with incident PD. 96,422 participants without prior PD and with usable accelerometer data were included from UK Biobank. Time spent in sedentary activity, LPA, MVPA, and exercise timing were estimated using machine learning models. The study outcome was incident PD. Over a median follow-up duration of 6.8 years, 313 participants developed PD. There was a L-shaped association for LPA and MVPA, and a reversed L-shaped association for sedentary time, with the risk of incident PD (all P for nonlinearity < 0.001). Similar trends were found across three time-windows (morning, midday-afternoon, and evening). Compared with those with both low LPA (<3.89 h/day) and low MVPA (<0.27 h/day), the adjusted HR (95% CI) of PD risk was 0.49 (0.36-0.66), 0.19 (0.36-0.66) and 0.13 (0.09-0.18), respectively, for participants with high MVPA only, high LPA only, and both high LPA and high MVPA. Moreover, participants with both low LPA and high sedentary time (≥9.41 h/day) (adjusted HR, 5.59; 95% CI: 4.10-7.61), and those with both low MVPA and high sedentary time (adjusted HR, 3.93; 95% CI: 2.82-5.49) had the highest risk of incident PD. In conclusion, regardless of exercise timing (morning, midday-afternoon, and evening), there was an inverse association for accelerometer-measured MVPA and LPA, and a positive association for sedentary time, with incident PD.