Additional file 1: of Effect of blood pressure and total cholesterol measurement on risk prediction using the Systematic COronary Risk Evaluation (SCORE)

Table S1. Differences in total cholesterol (mmol/l) between the cardio-preventive screening and the clinical examination program. Results from total cholesterol measurement at the cardio-preventive screening program, and at clinical examination program, analyzed separately for general practice patients, job agency clients, and health insurance members. (DOCX 14 kb

Additional file 2: of Effect of blood pressure and total cholesterol measurement on risk prediction using the Systematic COronary Risk Evaluation (SCORE)

Table S2. Differences in systolic blood pressure (mmHg) and total cholesterol (mmol/l) between the cardio-preventive screening and the clinical examination program according to the setting of recruitment. Results from blood pressure measurement a the the cardio-preventive screening program, and at clinical examination program, analyzed separately for general practice patients, job agency clients, and health insurance members. (DOCX 20 kb

Associations of androgens with depressive symptoms and cognitive status in the general population

<div><p>Objectives</p><p>Associations between androgens and depressive symptoms were mostly reported from cross-sectional and patient-based studies.</p><p>Study design/main outcome measures</p><p>Longitudinal data from 4,110 participants of the Study of Health in Pomerania were used to assess <b>se</b>x-specific associations of baseline total and free testosterone, androstenedione and sex hormone-binding globulin with incident depressive symptoms and cognitive status at 5- and 10-year follow-up.</p><p>Results</p><p>Despite sex-specific differences in depressive symptoms prevalence at baseline (women: 17.4%, men: 8.1%), cross-sectional analyses showed no associations between sex hormones and depressive symptoms. In age-adjusted longitudinal analyses, total testosterone was associated with incident depressive symptoms (relative risk at 5-year follow-up: 0.73, 95% confidence interval: 0.58–0.92). Similarly, age-adjusted analyses showed a positive association between sex hormone-binding globulin and cognitive status in men (β-coefficient per standard deviation: 0.44, 95% confidence interval: 0.13–0.74). In women, age-adjusted associations of androstenedione with baseline depressive symptoms (relative risk: 0.88, 95% confidence interval: 0.77–0.99) were found. None of the observed associations remained after multivariable adjustment.</p><p>Conclusions</p><p>The present population-based, longitudinal study revealed inverse associations between sex hormones and depressive symptoms. However, the null finding after multivariable adjustment suggests, that the observed associations were not independent of relevant confounders including body mass index, smoking and physical inactivity. Furthermore, the low number of incident endpoints in our non-clinical population-based sample limited the statistical power and reduced the chance to detect a statistically significant effect.</p></div

Associations of sex hormones and SHBG with change in mini mental status in linear regression models, separately in men and women.

<p>Associations of sex hormones and SHBG with change in mini mental status in linear regression models, separately in men and women.</p

Baseline characteristics of the study population, stratified by sex.

<p>Baseline characteristics of the study population, stratified by sex.</p

Associations of sex hormones and SHBG with depressive symptoms in Poisson regression models, separately in men and women.

<p>Associations of sex hormones and SHBG with depressive symptoms in Poisson regression models, separately in men and women.</p

Depressive symptoms prevalence at baseline by specific subgroups.

<p>Low total testosterone was defined as <10.4 nmol/L. TT, total testosterone; T2DM, type 2 diabetes mellitus.</p

EMT drives GLS1 dependence in two independent NSCLC models.

<p>(<b>A</b>) A427 cells were transfected with non-targeting (NT) or β-catenin targeting siRNAs and treated with the indicated concentrations of BPTES (left panel). Growth rates were normalized to DMSO treated cells transfected with NT siRNAs. The right panel depicts the effects of the β-catenin siRNAs on growth of DMSO treated cells. <b>(B</b>) Immunoblot of A427 protein extracts collected from cells 72 hrs post transfection. (<b>C</b>) NCI-H358 cells were treated with 25ng/ml TGF-ß for 4 wks. Induction of EMT was confirmed by the loss of E-cadherin and gain of vimentin. EMT was accompanied by an increase in GAC relative to PC protein levels (results representative of 2 independent experiments). Actin levels indicated for protein normalization. (<b>D</b>) NCI-H358 parental and 6wk TGF-ß treated cells were treated in triplicate with BPTES for 72 hrs and cell growth assessed by CTG. Results are representative of 3 independent experiments and are plotted as average growth rates (+/−SD) compared to DMSO treated cells.</p

Datasheet1_Metabolic remodeling in cardiac hypertrophy and heart failure with reduced ejection fraction occurs independent of transcription factor EB in mice.pdf

BackgroundA metabolic shift from fatty acid (FAO) to glucose oxidation (GO) occurs during cardiac hypertrophy (LVH) and heart failure with reduced ejection fraction (HFrEF), which is mediated by PGC-1α and PPARα. While the transcription factor EB (TFEB) regulates the expression of both PPARGC1A/PGC-1α and PPARA/PPARα, its contribution to metabolic remodeling is uncertain.MethodsLuciferase assays were performed to verify that TFEB regulates PPARGC1A expression. Cardiomyocyte-specific Tfeb knockout (cKO) and wildtype (WT) male mice were subjected to 27G transverse aortic constriction or sham surgery for 21 and 56 days, respectively, to induce LVH and HFrEF. Echocardiographic, morphological, and histological analyses were performed. Changes in markers of cardiac stress and remodeling, metabolic shift and oxidative phosphorylation were investigated by Western blot analyses, mass spectrometry, qRT-PCR, and citrate synthase and complex II activity measurements.ResultsLuciferase assays revealed that TFEB increases PPARGC1A/PGC-1α expression, which was inhibited by class IIa histone deacetylases and derepressed by protein kinase D. At baseline, cKO mice exhibited a reduced cardiac function, elevated stress markers and a decrease in FAO and GO gene expression compared to WT mice. LVH resulted in increased cardiac remodeling and a decreased expression of FAO and GO genes, but a comparable decline in cardiac function in cKO compared to WT mice. In HFrEF, cKO mice showed an improved cardiac function, lower heart weights, smaller myocytes and a reduction in cardiac remodeling compared to WT mice. Proteomic analysis revealed a comparable decrease in FAO- and increase in GO-related proteins in both genotypes. A significant reduction in mitochondrial quality control genes and a decreased citrate synthase and complex II activities was observed in hearts of WT but not cKO HFrEF mice.ConclusionsTFEB affects the baseline expression of metabolic and mitochondrial quality control genes in the heart, but has only minor effects on the metabolic shift in LVH and HFrEF in mice. Deletion of TFEB plays a protective role in HFrEF but does not affect the course of LVH. Further studies are needed to elucidate if TFEB affects the metabolic flux in stressed cardiomyocytes.</p

Oxygen consumption rates differentially altered upon drug perturbation in sensitive compared to insensitive cells.

<p>(A) NCI-H358 epithelial and mesenchymal lines or (B) NCI-H1703 (BPTES sensitive) and NCI-H1563 (BPTES insensitive) cells were treated with DMSO or 8 µM BPTES and oxygen consumption rate (OCR) was monitored over a 20 hr treatment. Data normalized to OCR at time zero (100%) and presented as mean values +/−SEM. <i>P</i> = 0.024 comparing changes in oxygen consumption with BPTES in the epithelial vs mesenchymal line; <i>P</i> = 0.00017 comparing NCI-H1703 and NCI-H1563 cells. (C) OCR following treatment with the indicated drugs to perturb mitochondrial respiration. Data normalized to OCR measurement prior to oligomycin treatment. (D) Addition of pyruvate to media restores the impaired FCCP response in the mesenchymal line. Average values +/−SEM indicated. Results representative of 2–3 independent experiments.</p