Metabolic and lifestyle factors in relation to senile cataract: a Mendelian randomization study

We conducted a Mendelian randomization study to determine the associations of body mass index (BMI), type 2 diabetes (T2D), systolic blood pressure (SBP), coffee and alcohol consumption and smoking initiation with senile cataract. Independent single nucleotide polymorphisms associated with the metabolic and lifestyle factors at the p < 5 × 10–8 were selected as instrument variables. Summary-level data for senile cataract were obtained from the FinnGen consortium (20,157 cases and 154,905 non-cases) and UK Biobank study (6332 cases and 354,862 non-cases). Higher genetically predicted BMI and SBP and genetic predisposition to T2D and smoking initiation were associated with an increased risk of senile cataract. The combined odds ratios were 1.19 (95% confidence interval (CI) 1.09–1.29; p < 0.001) per one standard deviation increase in BMI (~ 4.8 kg/m2), 1.13 (95% CI 1.04–1.23; p = 0.004) per 10 mmHg increase in SBP, 1.06 (95% CI 1.03–1.09; p < 0.001) per one unit increase in log-transformed odds ratio of T2D, and 1.19 (95% CI 1.10–1.29; p < 0.001) per one standard deviation increase in prevalence of smoking initiation. Genetically predicted coffee consumption showed a suggestive association with senile cataract (odds ratio per 50% increase, 1.18, 95% CI 1.00–1.40; p = 0.050). This study suggests causal roles of obesity, T2D, SBP and smoking in senile cataract.

Assessment of bidirectional relationships between 98 genera of the human gut microbiota and amyotrophic lateral sclerosis: a 2-sample Mendelian randomization study

Background Growing evidence suggests a mutual interaction between gut microbiome alterations and ALS pathogenesis. However, previous studies were susceptible to potential confounding factors and reverse causation bias, likely leading to inconsistent and biased results. Objectives To decipher the potentially mutual relationship between gut microbiota and ALS, we used a bidirectional two-sample MR approach to examine the associations between the gut microbiome and ALS. Results Using the inverse variance-weighted method, OTU10032 unclassified Enterobacteriaceae species-level OTU and unclassified Acidaminococcaceae were associated with a higher risk of ALS (per relative abundance: OR, 1.04; 95% CI, 1.01–1.07; P = 0.011 and OR, 1.02; 95% CI, 1.01–1.04; P = 0.009, respectively). Importantly, Gamma-Glu-Phe was showed potential deleterious effects on the risk of ALS (genetically predicted per a 1-standard deviation increase in the level of Gamma-Glu-Phe: OR, 1.96; 95% CI, 1.50–2.55; P = 0.012). Sensitivity analysis of the two candidate genera and metabolites using the MR-Egger and weighted-median methods produced similar estimates, and no horizontal pleiotropy or outliers were observed. Intriguingly, genetically predicted ALS was associated with an increase in the relative abundance of OTU4607_Sutterella (per 1-unit higher log odds: β, 2.23; 95% CI, 1.27–3.18; P = 0.020) and Lactobacillales_ORDER (per 1-unit higher log odds: β, 0.51; 95% CI, 0.09–0.94; P = 0.019). Conclusions Our findings provide novel evidence supporting the bidirectional relationship between the gut microbiota and ALS. These results may contribute to designing microbiome- and microbiome-dependent metabolite interventions in future ALS clinical trials.

Corruption News and Corporate Investment: Evidence from China

We examine whether corporate corruption scrutiny affects corporate investment in China. A corruption news index (CNI) containing firm-specific measures of corruption scrutiny was developed by tracking all articles in the press about corruption for all firms trading on the Shanghai and Shenzhen stock exchanges between 2000 and 2016. We found that a standard deviation increase in CNI is associated with a modest and short-lived decline in investment, ranging from 2 to 10 percent, with a stronger effect among SOEs. We explore two channels that can explain the CNI-investment effect: (i) a shift in the cost of external finance and (ii) a rise in political uncertainty connected with corporate corruption scrutiny. Our results indicate that CNI lowers the cost of external finance, pointing to a beneficial aspect of corruption cleanup. However, the effect of CNI on investment is amplified in the presence of provincial political turnover, providing support for the political uncertainty channel. The results also indicate that the negative effect of CNI on investment has significantly declined since 2013, supporting the proposition that the long-term benefits of corruption cleanup outweigh the short-term costs associated with policy uncertainty.

Course of lactate, pH and base excess for prediction of mortality in medical intensive care patients

Introduction As base excess had shown superiority over lactate as a prognostic parameter in intensive care unit (ICU) surgical patients we aimed to evaluate course of lactate, base excess and pH for prediction of mortality of medical ICU patients. Materials and methods For lactate, pH and base excess, values at the admission to ICU, at 24 ± 4 hours, maximum or minimum in the first 24 hours and in 24–48 hours after admission were collected from all patients admitted to the Medical ICU of the University Hospital Tübingen between January 2016 until December 2018 (N = 4067 at admission, N = 1715 with ICU treatment > 48 h) and investigated for prediction of in-hospital-mortality. Results Mortality was 22% and significantly correlated with all evaluated parameters. Strongest predictors of mortality determined by ROC were maximum lactate in 24 h (AUROC 0.74, cut off 2.7 mmol/L, hazard ratio of risk group with value > cut off 3.20) and minimum pH in 24 h (AUROC 0.71, cut off 7.31, hazard ratio for risk group 2.94). Kaplan Meier Curves stratified across these cut offs showed early and clear separation. Hazard ratios per standard deviation increase were highest for maximum lactate in 24 h (HR 1.65), minimum base excess in 24 h (HR 1.56) and minimum pH in 24 h (HR 0.75). Conclusion Lactate, pH and base excess were all suitable predictors of mortality in internal ICU patients, with maximum / minimum values in 24 and 24–48 h after admission altogether stronger predictors than values at admission. Base excess and pH were not superior to lactate for prediction of mortality.

Polygenic Risk Score Prediction for Endometriosis

Endometriosis is a major health care challenge because many young women with endometriosis go undetected for an extended period, which may lead to pain sensitization. Clinical tools to better identify candidates for laparoscopy-guided diagnosis are urgently needed. Since endometriosis has a strong genetic component, there is a growing interest in using genetics as part of the clinical risk assessment. The aim of this work was to investigate the discriminative ability of a polygenic risk score (PRS) for endometriosis using three different cohorts: surgically confirmed cases from the Western Danish endometriosis referral Center (249 cases, 348 controls), cases identified from the Danish Twin Registry (DTR) based on ICD-10 codes from the National Patient Registry (140 cases, 316 controls), and replication analysis in the UK Biobank (2,967 cases, 256,222 controls). Patients with adenomyosis from the DTR (25 cases) and from the UK Biobank (1,883 cases) were included for comparison. The PRS was derived from 14 genetic variants identified in a published genome-wide association study with more than 17,000 cases. The PRS was associated with endometriosis in surgically confirmed cases [odds ratio (OR) = 1.59, p = 2.57× 10−7] and in cases from the DTR biobank (OR = 1.50, p = 0.0001). Combining the two Danish cohorts, each standard deviation increase in PRS was associated with endometriosis (OR = 1.57, p = 2.5× 10−11), as well as the major subtypes of endometriosis; ovarian (OR = 1.72, p = 6.7× 10−5), infiltrating (OR = 1.66, p = 2.7× 10−9), and peritoneal (OR = 1.51, p = 2.6 × 10−3). These findings were replicated in the UK Biobank with a much larger sample size (OR = 1.28, p &lt; 2.2× 10−16). The PRS was not associated with adenomyosis, suggesting that adenomyosis is not driven by the same genetic risk variants as endometriosis. Our results suggest that a PRS captures an increased risk of all types of endometriosis rather than an increased risk for endometriosis in specific locations. Although the discriminative accuracy is not yet sufficient as a stand-alone clinical utility, our data demonstrate that genetics risk variants in form of a simple PRS may add significant new discriminatory value. We suggest that an endometriosis PRS in combination with classical clinical risk factors and symptoms could be an important step in developing an urgently needed endometriosis risk stratification tool.

Modeling Prenatal Adversity/Advantage: Effects on Birth Weight

Importance: How maternal experiences of adversity/advantage during pregnancy impact the developing fetus remains unclear. Objective: Using prospective data about experiences of adversity/advantage and other factors known to impact fetal developmental, we explored how these risk and protective factors relate to each other and impact infant birth weight by gestational age. Design: A prospective study that collected data on of forms of social advantage/disadvantage, and psychological factors from pregnant women during each trimester of pregnancy that accounted for maternal medical and nutritional status. We aimed to determine the differential impact of social advantage/disadvantage and adversity and psychological factors on infant birthweight accounting for gestational age. Structural Equation Modeling (SEM) was used to investigate the relationship of these forms of adversity as latent constructs on infant outcome. The follow-up of children is ongoing as a part of the Early Life Adversity Biological Embedding and Risk for Developmental Precursors of Mental Disorders (eLABE). Data collection was conducted from 2017-2020. Setting: An academic medical center. Participants: Pregnant women who were participants in a study of preterm birth within the Prematurity Research Center at Washington University in St. Louis with negative drug screens (other than cannabis) and without known pregnancy complications or known fetal congenital problems, were invited for participation. N=395 mothers were included in the analysis and N=268 eligible subjects declined participation. N=399 singleton offspring were included. Main Outcome(s) and Measure(s): Birthweight accounting for gestational age. Results: The study included N=395 pregnant women and their N=399 singleton offspring. The Social Advantage latent factor significantly predicted the residual birthweight after accounting for gestational age (p=.006) representing a 2.57% increase in residual gestational age-adjusted birthweight for each one standard deviation increase in the Social Advantage. The only other significant predictor was pre-pregnancy BMI (p=.019) which was associated with increased birthweight by gestational age while the Psychosocial Stress factor was no longer significant when other factors were accounted for. Conclusions and Relevance: Findings elucidate the significant effects of social adversity on the developing fetus and underscore the need to protect pregnant women in this risk group.

Men’s Attitude Towards Contraception and Sexuality, Women’s Empowerment, and Demand Satisfied for Family Planning in India

Whilst the prevalence of unmet need and contraceptive use remained unchanged for 10 years (between 2005–2015) in India, gender restrictive norms and power imbalances also have persisted, preventing married women from meeting their family planning desires. Data for this study are from the 2015–6 National Family Household Survey, which contains information on fertility preferences and family planning for women in reproductive age. As a proxy for men’s attitudinal norms, we aggregated men’s perceptions regarding contraception (contraception is women’s business, women who use contraception may become promiscuous) and control over their wife (if his wife refuses to have sex, men have the right to deny financial support, have sex with another woman, or beat wife) at district level. Using a three-level random intercepts model, we assessed individual and contextual-level associations of men’s attitudinal norms and met need for contraception among sexually active women (aged 15–49) with any demand for family planning, while adjusting for women’s empowerment indicators [education, job status, and adult marriage] and individual demographic factors. Our results indicate that men’s attitudinal norms are negatively associated with women’s contraceptive use; for instance, a 1 standard deviation increase in the proportion of men who believe that contraception is women’s business was associated with a 12% reduced likelihood of contraceptive use (OR = 0.88, 95% CI 0.82–0.95). Similar associations remained or were stronger after considering only modern methods, or when excluding female sterilization. Furthermore, our contextual effects analysis revealed that women’s higher education or wealth did not improve contraceptive uptake in communities with strong attitudinal norms, but working women or women married as children were more likely to use contraception in those communities. Our results suggest that men’s attitudinal norms may be dominating over women’s empowerment regarding family planning choices among reproductive age women. However, employment appeared to play a strong protective role associated with women’s contraceptive use. It is important for programs seeking to transform gender equality and empower women in making contraceptive choices to consider women’s employment opportunities and to also address male attitudinal norms in the context of the ecosystem in which men and women coexist and interact.

Associations of Mental Health and Chronic Physical Illness During Childhood With Major Depression in Later Life

While poor health in childhood has implications for mental health years later, less is known regarding its long-term impact. We determined whether childhood chronic physical illness burden was associated with major depression (MD) in later life (i.e., &gt;50 years), and tested mediation by childhood mental health status using path analysis. Data came from the 2016 U.S. Health and Retirement Study (n=18,047). One standard deviation increase in childhood chronic physical illness burden was associated with 1.21 (95% CI = 1.12, 1.30) times higher odds of MD in later life. Childhood mental health status explained 57.8% (95% CI: 35.2, 80.4) of this association. Results indicated that the relationship of chronic physical illness burden in childhood with MD in later life was mediated by childhood mental health status. Whether greater screening for psychiatric-related symptoms in childhood or review of health histories in later life can reduce the burden of MD requires further study.

Body Mass Index: An Effective Predictor of Ejection Fraction Improvement in Heart Failure

Background: Heart failure patients with higher body mass index (BMI) exhibit better clinical outcomes. Therefore, we assessed whether the BMI can predict left ventricular ejection fraction (EF) improvement following heart failure.Methods and Results: We included 184 patients newly diagnosed with dilated cardiomyopathy and reduced EF in our center and who underwent follow-up examination of EF via echocardiography after 6 months. The EF improved at 6 months in 88 participants, who were included in the heart failure with recovered EF (HFrecEF) subgroup. Patients in whom the EF remained reduced were included in the heart failure with persistently reduced EF (persistent HFrEF) subgroup. Our analyses revealed that EF increase correlated with age (r = −0.254, P = 0.001), left ventricular diastolic dimension (LVDD; r = −0.210, P = 0.004), diabetes (P = 0.034), brain natriuretic peptide (r = −0.199, P = 0.007), and BMI grade (P = 0.000). BMI grade was significantly associated with elevated EF after adjustment for other variables (P = 0.001). On multivariable analysis, compared to patients with persistent HFrEF, those with HFrecEF had higher BMI [odds ratio (OR) = 2.342 per one standard deviation increase; P = 0.001] and lower LVDD (OR = 0.466 per one standard deviation increase; P = 0.001). ROC-curve analysis data showed that BMI &gt; 22.66 kg/m2 (sensitivity 84.1%, specificity 59.4%, AUC 0.745, P = 0.000) indicate high probability of EF recovery in 6 months.Conclusions: Our data suggest that higher BMI is strongly correlated with the recovered EF and that BMI is an effective predictor of EF improvement in patients with heart failure and reduced EF.

John Henryism and Cognitive Function and Decline

Older Black adults in the US have higher prevalence and incidence of dementia and perform lower on cognitive tests than whites. Some of these differences have been attributed to facets of structural racism such as access to and quality of education and fewer socioeconomic resources. Here, we consider whether John Henryism (JH), a measure of self-perceived high-effort coping in the face of chronic environmental and psychosocial stressors, is associated with cognitive function and decline. JH has been associated with adverse cardiovascular health outcomes among African-Americans, especially those with fewer socioeconomic resources. Using data from MARS, we assessed whether JH, measured with an 8-item questionnaire (mean=16.9, sd=4.8, range: 4-27), was associated with level of cognitive function and rate of cognitive decline. We found one standard deviation increase in JH was associated with lower average cognitive function (□=-0.05, 95% CI: -0.09, -0.01). Higher JH was not associated with rate of cognitive decline.