Perceived Taste and Olfactory Dysfunctions and Subsequent Stroke Risk.

Background: Taste and olfactory dysfunction are commonly associated with neurodegenerative diseases and cardiovascular risk factors, but their specific associations with stroke risk remain uncertain. Objectives: The purpose of this paper was to explore whether perceived taste and olfactory dysfunctions were associated with stroke risk. Methods: Included were 85,656 participants (mean age 51.0 ± 15.3 years) of the Kailuan study. Perceived olfactory and taste dysfunctions were assessed via a questionnaire at baseline (in 2014-2016). Incident stroke cases were confirmed by review of medical records. Cox proportional hazards models were used to investigate associations of perceived olfactory and taste dysfunctions with stroke risk, and mediation analysis was used to estimate the mediating effect of chronic disease statuses. Results: We documented 2,198 incident stroke cases during a mean of 5.6 years of follow-up. Perceived taste dysfunction was associated with a doubled risk of developing total stroke (adjusted HR: 2.03; 95% CI: 1.36-3.04; P < 0.001) even with adjustment of lifestyle factors, biomarkers (ie, blood lipids, blood glucose, blood pressure, and uric acid), and other potential confounders. However, perceived olfactory dysfunction (adjusted HR: 1.22; 95% CI: 0.79-1.90; P = 0.34) was not significantly associated with a high risk of total stroke. Similar results of both perceived taste and olfactory dysfunctions were observed for ischemic stroke. Presence of chronic diseases, including hypertension, diabetes, chronic kidney disease, and overweight/obesity, mediated 4% to 5% of the association of perceived taste dysfunction with both total stroke and ischemic stroke. Conclusions: In this large cohort study, perceived taste dysfunction was associated with a high risk of developing stroke.

Identification of autism spectrum disorder using multiple functional connectivity-based graph convolutional network.

Presently, the combination of graph convolutional networks (GCN) with resting-state functional magnetic resonance imaging (rs-fMRI) data is a promising approach for early diagnosis of autism spectrum disorder (ASD). However, the prevalent approach involves exclusively full-brain functional connectivity data for disease classification using GCN, while overlooking the prior information related to the functional connectivity of brain subnetworks associated with ASD. Therefore, in this study, the multiple functional connectivity-based graph convolutional network (MFC-GCN) framework is proposed, using not only full brain functional connectivity data but also the established functional connectivity data from networks of key brain subnetworks associated with ASD, and the GCN is adopted to acquire complementary feature information for the final classification task. Given the heterogeneity within the Autism Brain Imaging Data Exchange (ABIDE) dataset, a novel External Attention Network Readout (EANReadout) is introduced. This design enables the exploration of potential subject associations, effectively addressing the dataset's heterogeneity. Experiments were conducted on the ABIDE dataset using the proposed framework, involving 714 subjects, and the average accuracy of the framework was 70.31%. The experimental results show that the proposed EANReadout outperforms the best traditional readout layer and improves the average accuracy of the framework by 4.32%.

Association Between Bowel Movement Pattern and Cognitive Function: Prospective Cohort Study and a Metagenomic Analysis of the Gut Microbiome.

BACKGROUND AND OBJECTIVES: Little is known regarding the association between intestinal motility patterns and cognitive function in individuals who are baseline cognitively healthy. The gut microbiome may contribute to the association. We examined the association between bowel movement (BM) pattern and cognitive function and explored the role of the gut microbiome in explaining this association. METHODS: In this prospective study, we leveraged 3 cohort studies, Nurses' Health Study (NHS), NHSII, and Health Professionals Follow-Up Study (HPFS). Participants reported BM frequency and subjective cognitive function. In a subset of NHSII participants, we assessed cognitive function using an objective neuropsychological battery. We profiled the gut microbiome in a subset of participants using whole-genome shotgun metagenomics. General linear models, Poisson regression, and logistic regression were used to quantify the association of BM frequency with different cognitive measurements. RESULTS: We followed 112,753 men and women (women: 87.6%) with a mean age of 67.2 years at baseline (NHS: 76 years, NHSII: 59 years, HPFS: 75 years) for a median follow-up of 4 years (NHSII and HPFS: 4 years, NHS: 2 years). Compared with those with BM once daily, participants with BM frequency every 3+ days had significantly worse objective cognitive function, equivalent to 3.0 (95% confidence interval [CI],1.2-4.7) years of chronological cognitive aging. We observed similar J-shape dose-response relationships of BM frequency with the odds of subjective cognitive decline and the likelihood of having more subsequent subjective cognitive complaints (both p nonlinearity < 0.001). BM frequencies of every 3+ days and ≥twice/day, compared with once daily, were associated with the odds ratios of subjective cognitive decline of 1.73 (95% CI 1.60-1.86) and 1.37 (95% CI 1.33-1.44), respectively. BM frequency and subjective cognitive decline were significantly associated with the overall gut microbiome configuration (both p < 0.005) and specific microbial species in the 515 participants with microbiome data. Butyrate-producing microbial species were depleted in those with less frequent BM and worse cognition, whereas a higher abundance of proinflammatory species was associated with BM frequency of ≥twice/day and worse cognition. DISCUSSION: Lower BM frequency was associated with worse cognitive function. The gut microbial dysbiosis may be a mechanistic link underlying the association.

Germline Genetic Variants Associated with Somatic TMPRSS2:ERG Fusion Status in Prostate Cancer: A Genome-Wide Association Study.

BACKGROUND: The prostate cancer subtype defined by the presence of TMPRSS2:ERG has been shown to be molecularly and epidemiologically distinct. However, few studies have investigated germline genetic variants associating with TMPRSS2:ERG fusion status. METHODS: We performed a genome-wide association study with 396 TMPRSS2:ERG(+) cases, 390 TMPRSS2:ERG(-) cases, and 2,386 cancer-free controls from the Physicians' Health Study (PHS), the Health Professionals Follow-up Study (HPFS), and a Seattle-based Fred Hutchinson (FH) Cancer Center Prostate Cancer Study. We applied logistic regression models to test the associations between ∼5 million SNPs with TMPRSS2:ERG fusion status accounting for population stratification. RESULTS: We did not identify genome-wide significant variants comparing the TMPRSS2:ERG(+) to the TMPRSS2:ERG(-) prostate cancer cases in the meta-analysis. When comparing TMPRSS2:ERG(+) prostate cancer cases with controls without prostate cancer, 10 genome-wide significant SNPs on chromosome 17q24.3 were observed in the meta-analysis. When comparing TMPRSS2:ERG(-) prostate cancer cases with controls without prostate cancer, two SNPs on chromosome 8q24.21 in the meta-analysis reached genome-wide significance. CONCLUSIONS: We observed SNPs at several known prostate cancer risk loci (17q24.3, 1q32.1, and 8q24.21) that were differentially and exclusively associated with the risk of developing prostate tumors either with or without the gene fusion. IMPACT: Our findings suggest that tumors with the TMPRSS2:ERG fusion exhibit a different germline genetic etiology compared with fusion negative cases.

Free PSA and Clinically Significant and Fatal Prostate Cancer in the PLCO Screening Trial.

PURPOSE: We studied whether adding percent free PSA to total PSA improves prediction of clinically significant prostate cancer and fatal prostate cancer. MATERIALS AND METHODS: A total of 6,727 men within the intervention arm of PLCO (Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial) had baseline percent free PSA. Of this cohort, 475 had clinically significant prostate cancer and 98 had fatal prostate cancer. Cumulative incidence and Cox analyses were conducted to evaluate the association between percent free PSA/PSA and clinically significant prostate cancer/fatal prostate cancer. Harrell's C index evaluated predictive ability. Kaplan-Meier analysis assessed survival. RESULTS: Median follow-up was 19.7 years, median baseline PSA was 1.19 ng/mL, median percent free PSA was 18%. Cumulative incidence of fatal prostate cancer for men with baseline PSA ≥2 ng/mL and percent free PSA ≤10 was 3.2% and 6.1% at 15 and 25 years, respectively, compared to 0.03% and 1.1% for men with percent free PSA >25%. In younger men (55-64 years) with baseline PSA 2-10 ng/mL, C index improved from 0.56 to 0.60 for clinically significant prostate cancer and from 0.53 to 0.64 for fatal prostate cancer with addition of percent free PSA. In older men (65-74 years), C index improved for clinically significant prostate cancer from 0.60 to 0.66, with no improvement in fatal prostate cancer. Adjusting for age, digital rectal exam, family history of prostate cancer, and total PSA, percent free PSA was associated with clinically significant prostate cancer (HR 1.05, P < .001) per 1% decrease. Percent free PSA improved prediction of clinically significant prostate cancer and fatal prostate cancer for all race groups. CONCLUSIONS: In a large U.S. screening trial, the addition of percent free PSA to total PSA in men with baseline PSA ≥2 ng/mL improved prediction of clinically significant prostate cancer and fatal prostate cancer. Free PSA should be used to risk-stratify screening and decrease unnecessary prostate biopsies.

Oxic effects of Pb-Ce compound pollution on Chinese cabbage and programmed cell death in root tip cells.

Heavy metal pollution is increasing, and rare earth elements (REE) play an important role in the environmental impact of heavy metals. Mixed heavy metal pollution is a major issue with complex effects. Despite substantial research on single heavy metal pollution, relatively few studies have focused on pollution from rare earth heavy metal composites. We studied the effects of different concentrations of Ce-Pb on the antioxidant activity in root tip cells and biomass of Chinese cabbage. We also used the integrated biomarker response (IBR) to evaluate the toxic effects of rare earth-heavy metal pollution on Chinese cabbage. We used programmed cell death (PCD) for the first time to reflect the toxicological effects of heavy metals and rare earths and studied the interaction between Ce and Pb in root tip cells in depth. Our results showed that Ce-Pb compound pollution can induce PCD in the root cells of Chinese cabbage, and the toxicity of compound pollutants is greater than that of single pollutants. Our analyses also provide the first evidence that Ce and Pb exert interaction effects in the cell. Ce induces Pb transfer in plant cells. The Pb content in the cell wall decreases from 58% to 45%. Additionally, Pb induced Ce valence changes. Ce (III) decreased from 50% to 43%, while Ce (IV) increased from 50% to 57%, directly resulting in PCD in the roots of Chinese cabbage. These findings improve our understanding of the harmful effects of compound pollution with rare earth metals and heavy metals on plants.

Multi-walled carbon nanotube induced liver injuries possibly by promoting endoplasmic reticulum stress in Cyprinus carpio.

The mass production and discharge of carbon nanotubes (CNTs) to the water environment are of great concern since they threaten the health of organisms in the aquatic ecosystem. CNTs induce multi-organ injuries in fish, but limited literature is available regarding the mechanisms involved. In the present study, juvenile common carp (Cyprinus carpio) were exposed to multi-walled carbon nanotubes (MWCNTs) (0.25 mg L-1 and 2.5 mg L-1) for four weeks. MWCNTs caused dose-dependent alterations in the pathological morphology of liver tissues. Ultrastructural changes manifested as nuclear deformation, chromatin condensation, endoplasmic reticulum (ER) disorderly arrangement, mitochondria vacuolation, and mitochondrial membrane destruction. TUNEL analysis indicated that the apoptosis rate in hepatocytes markedly increased upon exposure to MWCNTs. Moreover, the apoptosis was confirmed by significant upregulation of mRNA levels of apoptosis-related genes (Bcl-2, XBP1, Bax, and caspase3) in MWCNTs-exposure groups, except for Bcl-2 expression which was not significantly changed in HSC groups (2.5 mg L-1 MWCNTs). Furthermore, real-time PCR assay indicated the increased expression of ER stress (ERS) marker genes (GRP78, PERK, and eIF2α) in the exposure groups compared to the control groups, suggesting that the PERK/eIF2α signaling pathway involved in the injuries of the liver tissue. Overall, the results above indicate that MWCNTs induce ERS by activating the PERK/eIF2α pathway in the liver of common carp, and resulted in the initiation of apoptosis procedure.

Addition of a Genetic Risk Score for Identification of Men with a Low Prostate-specific Antigen Level in Midlife at Risk of Developing Lethal Prostate Cancer.

Men with a low prostate-specific antigen (PSA) level (<1 ng/ml) in midlife may extend the rescreening interval (if aged 40-59 yr) or forgo future PSA screening (if aged >60 yr) owing to their low risk of aggressive prostate cancer (PCa). However, there is a subset of men who develop lethal PCa despite low baseline PSA. We investigated how a PCa polygenic risk score (PRS) in addition to baseline PSA impacts the prediction of lethal PCa among 483 men aged 40-70 yr from the Physicians' Health Study followed over a median of 33 yr. We examined the association of the PRS with the risk of lethal PCa (lethal cases vs controls) using logistic regression adjusted for baseline PSA. The PCa PRS was associated with risk of lethal PCa (odds ratio per 1 standard deviation in PRS [OR] 1.79, 95% confidence interval [CI] 1.28-2.49). The association between the PRS and lethal PCa was stronger for those with PSA <1 ng/ml (OR 2.23, 95% CI 1.19-4.21) than for men with PSA ≥1 ng/ml (OR 1.61, 95% CI 1.07-2.42). Our PCa PRS improved the identification of men with PSA <1 ng/ml at greater risk of future lethal PCa who should consider ongoing PSA testing. Patient summary: A subset of men develop fatal prostate cancer despite having low prostate-specific antigen (PSA) levels in middle age. A risk score based on multiple genes can help in predicting men who may be at risk of developing lethal prostate cancer and who should be advised to have regular PSA measurements.

Fluorescent labeling and tracing of immobilized efficient degrading bacterium DNB-S1 and its remediation efficiency of DBP contaminated soil.

Dibutyl phthalate (DBP) is an organic pollutant frequently detected in soil, and is a reproductive poison that harms animals both before and after birth and has mutagenic, teratogenic, and carcinogenic effects. DBP removal from farmland has been the subject of extensive research in recent years. Efficient DBP degrading bacterial strains were screened in the laboratory. GFP (Green fluorescent protein) labeled degradation strain GFP-DNB-S1 was analyzed for its activity and dynamics. Using sodium alginate (SA) and nano-hydroxyapatite (n-HAP) as carrier materials and CaCl2 as a cross-linking agent, the immobilized microbial agent n-HAP/SA + DNB-S1 was prepared by embedding cross-linking immobilization technology to study the remediation effect of DBP contaminated soil. The best formation effect of immobilized materials (n-HAP/SA) was found when the SA to n-HAP ratio was 3:2. When compared to single SA immobilized bacteria, n-HAP/SA immobilized bacteria improved the surface roughness and porosity of the microspheres. After 70 days, LED light revealed that the immobilized bacteria's GFP green fluorescent protein expression was stable. At 70 days, the initial DBP concentration of 500 mg ∙ L-1 degraded at a rate of 69.9%. The degrading bacteria had no effect on DBP degradation before and after being labeled with GFP. The n-HAP/SA immobilized bacteria offered a better living environment for microorganisms due to their rougher surface and a greater number of pores. This protected the microorganisms and increased the efficiency of DBP degradation. When the concentration of DBP in contaminated soil was set to 20 mg ∙ kg-1 and the n-HAP/SA + DNB-S1 immobilized bacterial agent was applied to the soil, the rate of DBP degradation was determined to be 93.34%. The degradation process followed First-order degradation kinetics, which improved the physical and chemical properties of the soil as well as its fertility.

The Prostate Stromal Transcriptome in Aggressive and Lethal Prostate Cancer.

Prostate cancer has a heterogeneous prognosis. Most previous studies have focused on the identification of prognostic biomarkers in the prostate cancer tumor. However, it is increasingly recognized that the tumor microenvironment contributes to prostate cancer aggressiveness and progression. We therefore examined whole transcriptome expression of the prostate stroma and associations with aggressive and lethal prostate cancer. We performed RNA sequencing (Illumina TruSeq Exome Capture) of 272 tumor-adjacent and 120 benign-adjacent macrodissected prostate stromal samples from 293 men with prostate cancer from the Health Professionals Follow-up Study and Physicians' Health Study. We performed differential expression analysis comparing gene expression and pathways by Gleason score and lethal outcome. We also tested a previously developed stromal gene signature of Gleason score in these datasets. Comparing high- with low-Gleason score cancers, 26 genes (P < 0.001) and 12 pathways (FDR < 0.20) were significantly differentially expressed in tumor-adjacent stroma, including pathways related to stroma composition remodeling and DNA repair, with 73 genes and 65 pathways significant in benign-adjacent stroma. Comparing lethal with nonlethal prostate cancer, 11 genes were differentially expressed in tumor-adjacent and 15 genes in benign-adjacent stroma, and pathways involved in inflammatory response were differentially enriched in both tumor and benign-adjacent stroma. In addition, our previously identified Gleason stromal gene signature was validated to be associated with Gleason score in these data. Implications: Our study uncovers stroma-specific genes and pathways that are differentially enriched with high Gleason score and lethal prostate cancer, demonstrating that the molecular investigation of the tumor microenvironment can provide additional information about prostate cancer prognosis.

Application of the deep learning algorithm in nutrition research - using serum pyridoxal 5'-phosphate as an example.

BACKGROUND: Multivariable linear regression (MLR) models were previously used to predict serum pyridoxal 5'-phosphate (PLP) concentration, the active coenzyme form of vitamin B6, but with low predictability. We developed a deep learning algorithm (DLA) to predict serum PLP based on dietary intake, dietary supplements, and other potential predictors. METHODS: This cross-sectional analysis included 3778 participants aged ≥20 years in the National Health and Nutrition Examination Survey (NHANES) 2007-2010, with completed information on studied variables. Dietary intake and supplement use were assessed with two 24-hour dietary recalls. We included potential predictors for serum PLP concentration in the models, including dietary intake and supplement use, sociodemographic variables (age, sex, race-ethnicity, income, and education), lifestyle variables (smoking status and physical activity level), body mass index, medication use, blood pressure, blood lipids, glucose, and C-reactive protein. We used a 4-hidden-layer deep neural network to predict PLP concentration, with 3401 (90%) participants for training and 377 (10%) participants for test using random sampling. We obtained outputs after sending the features of the training set and conducting forward propagation. We then constructed a loss function based on the distances between outputs and labels and optimized it to find good parameters to fit the training set. We also developed a prediction model using MLR. RESULTS: After training for 105 steps with the Adam optimization method, the highest R2 was 0.47 for the DLA and 0.18 for the MLR model in the test dataset. Similar results were observed in the sensitivity analyses after we excluded supplement-users or included only variables identified by stepwise regression models. CONCLUSIONS: DLA achieved superior performance in predicting serum PLP concentration, relative to the traditional MLR model, using a nationally representative sample. As preliminary data analyses, the current study shed light on the use of DLA to understand a modifiable lifestyle factor.

Circulating Insulin-Like Growth Factor 1-Related Biomarkers and Risk of Lethal Prostate Cancer.

Background: Experimental and epidemiologic evidence supports the role of circulating insulin-like growth factor-1 (IGF-1) levels with the risk of prostate cancer. Most circulating IGF-1 is bound to specific binding proteins, and only about 5% circulates in a free form. We explored the relation of free IGF-1 and other components of the IGF system with lethal prostate cancer. Methods: Using prospectively collected samples, we undertook a nested case-only analysis among 434 men with lethal prostate cancer and 524 men with indolent, nonlethal prostate cancer in the Physicians' Health Study and the Health Professionals Follow-up Study. Prediagnostic plasma samples were assayed for free IGF-1 and total IGF-1, acid labile subunit, pregnancy-associated plasma protein A (PAPP-A), and intact and total IGF binding protein 4. We estimated odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the associations between IGF-1-related biomarkers and lethal prostate cancer using unconditional logistic regression models adjusted for age, height, and body mass index. Results: Men in the highest quartile of PAPP-A levels had 42% higher odds of lethal prostate cancer (pooled adjusted OR = 1.42, 95% CI = 1.04 to 1.92) compared with men in the lowest 3 quartiles. There were no statistically significant differences in the other plasma analytes. The positive association between PAPP-A and lethal prostate cancer was present among men with intact PTEN but not among those with tumor PTEN loss (2-sided P interaction = .001). Conclusions: Our study provides suggestive evidence that among men who later develop prostate cancer, higher plasma PAPP-A levels measured prior to diagnosis are associated with increased risk of lethal compared with indolent disease.

High-dose vitamin C ameliorates cardiac injury in COVID-19 pandemic: a retrospective cohort study.

BACKGROUND: Cardiac injury is common and associated with poor clinical outcomes in COVID-19. Data are lacking whether high-dose intravenous vitamin C (HIVC) could help to ameliorate myocardial injury in the pandemic. METHODS: The retrospective cohort study included consecutive severe and critically ill COVID-19 patients with cardiac injury receiving symptomatic supportive treatments alone or together with HIVC. Troponin I and inflammatory markers were collected at admission and day 21 during hospitalization from the electronic medical records. RESULTS: The patients (n = 113) were categorized into the ameliorated cardiac injury (ACI) group (n = 70) and the non-ameliorated cardiac injury (NACI) group (n = 43). Overall, fifty-one (45.1%) patients were administered with HIVC, the percentages of patients with HIVC were higher in the ACI group than those in the NACI group. Logistic regression analysis revealed that HIVC was independently associated with the improvement of myocardial injury. Further analysis showed that inflammatory markers levels significantly decreased at day 21 during hospitalization in patients with HIVC therapy compared to those administered with symptomatic supportive treatments alone. Meanwhile, similar results were also observed regarding changes in inflammatory markers levels from baseline to day 21 during hospitalization in the patients treated with HIVC. CONCLUSIONS: HIVC can ameliorate cardiac injury through alleviating hyperinflammation in severe and critically ill patients with COVID-19.

Restless legs syndrome and perceived olfactory and taste dysfunction: A community-based study.

BACKGROUND AND PURPOSE: Restless legs syndrome (RLS) has been suggested as a prodromal symptom of Parkinson disease (PD). Olfactory or taste dysfunction can also occur preceding PD diagnosis. However, whether RLS is associated with chemosensory dysfunction remains unknown. We thus aim to investigate the association between RLS and perceived olfactory and taste dysfunction. METHODS: We performed a cross-sectional analysis including 90,337 Chinese adults free of neurodegenerative diseases in the Kailuan study in 2016. Presence of RLS was defined using revised RLS diagnostic criteria or the Cambridge-Hopkins questionnaire for RLS. Perceived olfactory and taste dysfunction was collected via a questionnaire. The association between RLS and perceived olfactory and taste dysfunction was assessed using logistic regression model, adjusting for potential cofounders such as age, sex, and medical history. RESULTS: RLS was associated with high odds of having perceived olfactory and/or taste dysfunction (adjusted odds ratio = 5.92, 95% confidence interval = 3.11-11.3). The significant association persisted when using the Cambridge-Hopkins questionnaire (adjusted odds ratio = 5.55, 95% confidence interval = 2.37-13.0) or when excluding participants with major chronic diseases. CONCLUSIONS: RLS was associated with increased odds of perceived olfactory and taste dysfunction.

Hyper-Inflammatory Response Involves in Cardiac Injury Among Patients With Coronavirus Disease 2019.

BACKGROUND: Inflammation can facilitate development of coronavirus disease 2019 (COVID-19) and cardiac injury is associated with worse clinical outcomes. However, data are relatively scarce on the association between hyper-inflammatory response and cardiac injury among COVID-19 patients. METHODS: The study was designed based on severe and critically ill patients with COVID-19. Information on clinical characteristics and laboratory examinations was collected from the electronic medical records and analyzed. RESULTS: There were 32.4% (n = 107) of patients with cardiac injury. The median age was 67 years, and 48.8% (n = 161) of patients were men. Hypertension was the most common in 161 (48.8%) patients, followed by diabetes (16.7%, n = 55) and coronary heart disease (13.3%, n = 44). Compared to cases without cardiac injury, those with cardiac injury were older, had higher proportions of coronary heart disease, and leukocyte counts, significantly elevated concentrations of N-terminal pro-B-Type natriuretic peptide, high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-α, interleukin-2 receptor (IL-2R), IL-6, and IL-8, but lower lymphocyte counts. A significant positive correlation was observed between high-sensitivity troponin I and inflammatory cytokines. Logistic regression analysis showed that hs-CRP, TNF-α and IL-6 were independent risk factors for cardiac injury. CONCLUSIONS: Cardiac injury was associated with elevated levels of inflammatory cytokines among severe and critically ill patients with COVID-19, suggesting that hyper-inflammatory response may involve in cardiac injury.

Treating Restless Legs Syndrome Was Associated With Low Risk of Cardiovascular Disease: A Cohort Study With 3.4 Years of Follow-Up.

Background Restless legs syndrome (RLS) is associated with higher cardiovascular disease (CVD) risk. However, it remains unknown whether treatment of RLS lowers the cardiovascular risk associated with RLS. Methods and Results All data were collected retrospectively, but subjects were prospectively followed forward in time to determine outcomes of interest. We used the Truven Health MarketScan Commercial Claims and Encounters database from January 1, 2006, through December 31, 2014. Participants were 169 393 individuals, which included 24 199 nonpregnant participants with an RLS diagnosis (16 694 receiving treatments for RLS and 7505 without treatment) during 2006 to 2008 and 145 194 age- and sex-matched participants without RLS. All participants were free of CVD before January 1, 2009 (analysis baseline). Incident CVD cases (myocardial infarction, angina, stroke, atrial fibrillation, and heart failure) were identified. We adjusted for potential confounders, such as presence of chronic conditions and medication use. We identified 16 574 incident CVD cases during 2009 to 2014. Relative to the non-RLS group, the adjusted hazard ratio (HR) for future CVD was 1.26 (95% CI, 1.20-1.32) (P<0.001) for the RLS with treatment group, and 1.53 (95% CI, 1.42-1.65) (P<0.001) for the RLS without treatment group. Significant lower CVD risk was observed for all different RLS treatments, including dopaminergics, anticonvulsants, benzodiazepines, and opiates (adjusted HRs range, 0.71-0.84; P<0.001 for all), except for ergot-dopamine use. Conclusions RLS was associated with higher future CVD risk. However, RLS was associated with statistically significantly less future cardiovascular risk in RLS patients with treatment than in those without treatment.

Alcohol consumption and sleep quality: a community-based study.

OBJECTIVE: To assess the association between total alcohol intake, specific alcoholic beverages and sleep quality in a community-based cohort. DESIGN: A cross-sectional study. SETTING: The Kailuan community, China. PARTICIPANTS: Included were 11 905 participants who were free of a history of CVD, cancer, Parkinson's disease, dementia and head injury in or prior to 2012. Alcohol consumption (amount and frequency intake) and alcoholic beverage type were collected in 2006 (baseline) and 2012. Participants were grouped into non-, light- (women: 0-0·4 serving/d; men: 0-0·9 serving/d), moderate- (women: 0·5-1·0 serving/d; men: 1·0-2·0 servings/d) and heavy- (women: >1·0 servings/d; men: >2·0 servings/d) drinkers. Overall sleep quality was measured in 2012 and included four sleep parameters (insomnia, daytime sleepiness, sleep duration, snoring/obstructive sleep apnoea). RESULTS: We observed a dose-response association between higher alcohol consumption in 2006 and worse sleep quality in 2012 (Ptrend < 0·001), after adjusting for age, sex, socio-economic status, smoking status, physical activity, obesity, plasma lipid profiles, diabetes and hypertension. A similar association was observed when alcohol consumption in 2012 was used as exposure. Alcohol was associated with higher odds of having short sleep duration (adjusted OR for heavy- v. non-drinkers = 1·31; 95 % CI: 1·09, 1·57) and snoring (adjusted OR for heavy- v. non-drinkers: 1·38; 95 % CI: 1·22, 1·57). Consumption of hard liquor, but not beer or wine, was significantly associated with poor sleep quality. CONCLUSIONS: Higher alcohol consumption was associated with poorer sleep quality and higher odds of having snoring and short sleep duration.