Determinants of career development in cardiology – results from a Swiss national survey

BACKGROUND: Despite the rising proportion of female medical students and specialised female doctors in Switzerland, the field of cardiology remains one of the most male-dominated. OBJECTIVES: The goal of this study was to identify determinants of and obstacles to career development for cardiologists with special regard to an academic and interventional career. METHODS: Under the direction of the Swiss working group Women in Cardiology (IG-WIC), an online survey was conducted among Swiss cardiologists and cardiologists in training. RESULTS: 140 participants (43.6% female, 56.4% male; median age 45.0) were included. Women were more often single (27.9% vs 10.1%, p = 0.013) and less likely to have children (52.5% vs 70.9%, p = 0.034). If they had children, they were more likely to provide childcare themselves (37.5% vs 10.7%, p = 0.006) or to have interrupted their work in favour of parenting (40.6% vs 8.9%, p <0.001). A majority of women indicated a negative impact of their gender on their career development (78.7%), and 36.3% reported sexual harassment at their workplace. Women felt less supported in their professional training, especially concerning research activities. As a hindrance for pursuit of a career in academic medicine, both sexes stated lack of compatibility of work and family (44.6%) and the competitive work environment (55.4%) being most important. Women also identified gender-specific disadvantages as one of the main reasons for not choosing an academic or interventional career. CONCLUSIONS: The overall satisfaction among Swiss cardiologists is high regarding training in health care and the working atmosphere. However, women and men plead for better compatibility of work and family and better structured training curricula. Several gender-specific aspects hindering women from advancing in cardiology training should be addressed

Gender score development in the Berlin Aging Study II: A retrospective approach

In addition to biological sex, gender, defined as the sociocultural dimension of being a woman or a man, plays a central role in health. However, there are so far few approaches to quantify gender in a retrospective manner in existing study datasets. We therefore aimed to develop a methodology that can be retrospectively applied to assess gender in existing cohorts. We used baseline data from the Berlin Aging Study II (BASE-II), obtained in 2009-2014 from 1869 participants aged 60 years and older. We identified 13 gender-related variables and used them to construct a gender score by using primary component and logistic regression analyses. Of these, nine variables contributed to a gender score: chronic stress, marital status, risk-taking behaviour, personality attributes: agreeableness, neuroticism, extraversion, loneliness, conscientiousness, and level of education. Females and males differed significantly in the distribution of the gender score, but a significant overlap was also found. Thus, we were able to develop a gender score in a retrospective manner from already collected data that characterized participants in addition to biological sex. This approach will allow researchers to introduce the notion of gender retrospectively into a large number of studies

Hotline sessions presented at the American College of Cardiology Congress 2009

The article summarizes the results of clinical trials in the field of cardiovascular medicine, which were presented during the Hotline Sessions at the annual meeting of the American College of Cardiology in Orlando, USA, from 28th March to 31st March 2009. The data were presented by leading experts in the field with relevant positions within the trials. Unpublished reports should be considered as preliminary data as the analysis may change in the final publications. The summaries presented in the manuscript were generated from the oral presentations and provide the readers with the comprehensive information on the results of the latest clinical trials in cardiovascular medicine

ESC core curriculum for the general cardiologist (2013)

[No abstract available

Sex-specific pathways in early cardiac response to pressure overload in mice

Pressure overload (PO) first causes cardiac hypertrophy and then heart failure (HF), which are associated with sex differences in cardiac morphology and function. We aimed to identify genes that may cause HF-related sex differences. We used a transverse aortic constriction (TAC) mouse model leading to hypertrophy without sex differences in cardiac function after 2 weeks, but with sex differences in hypertrophy 6 and 9 weeks after TAC. Cardiac gene expression was analyzed 2 weeks after surgery. Deregulated genes were classified into functional gene ontology (GO) categories and used for pathway analysis. Classical marker genes of hypertrophy were similarly upregulated in both sexes (α-actin, ANP, BNP, CTGF). Thirty-five genes controlling mitochondrial function (PGC-1, cytochrome oxidase, carnitine palmitoyl transferase, acyl-CoA dehydrogenase, pyruvate dehydrogenase kinase) had lower expression in males compared to females after TAC. Genes encoding ribosomal proteins and genes associated with extracellular matrix remodeling exhibited relative higher expression in males (collagen 3, matrix metalloproteinase 2, TIMP2, and TGFβ2, all about twofold) after TAC. We confirmed 87% of the gene expression by real-time polymerase chain reaction. By GO classification, female-specific genes were related to mitochondria and metabolism and males to matrix and biosynthesis. Promoter studies confirmed the upregulation of PGC-1 by E2. Less downregulation of metabolic genes in female hearts and increased protein synthesis capacity and deregulation of matrix remodeling in male hearts characterize the sex-specific early response to PO. These differences could contribute to subsequent sex differences in cardiac function and HF

B‐cell receptors of EBV‐negative Burkitt lymphoma bind modified isoforms of autoantigens

Burkitt lymphoma (BL) represents the most aggressive B‐cell‐lymphoma. Beside the hallmark of IG‐MYC‐translocation, surface B‐cell receptor (BCR) is expressed, and mutations in the BCR pathway are frequent. Coincidental infections in endemic BL, and specific extra‐nodal sites suggest antigenic triggers. To explore this hypothesis, BCRs of BL cell lines and cases were screened for reactivities against a panel of bacterial lysates, lysates of Plasmodium falciparum, a custom‐made virome array and against self‐antigens, including post‐translationally modified antigens. An atypically modified, SUMOylated isoform of Bystin, that is, SUMO1‐BYSL was identified as the antigen of the BCR of cell line CA46. SUMO1‐BYSL was exclusively expressed in CA46 cells with K139 as site of the SUMOylation. Secondly, an atypically acetylated isoform of HSP40 was identified as the antigen of the BCR of cell line BL41. K104 and K179 were the sites of immunogenic acetylation, and the acetylated HSP40 isoform was solely present in BL41 cells. Functionally, addition of SUMO1‐BYSL and acetylated HSP40 induced BCR pathway activation in CA46 and BL41 cells, respectively. Accordingly, SUMO1‐BYSL‐ETA’ immunotoxin, produced by a two‐step intein‐based conjugation, led to the specific killing of CA46 cells. Autoantibodies directed against SUMO1‐BYSL were found in 3 of 14 (21.4%), and autoantibodies against acetylated HSP40 in 1/14(7.1%) patients with sporadic Burkitt‐lymphoma. No reactivities against antigens of the infectious agent spectrum could be observed. These results indicate a pathogenic role of autoreactivity evoked by immunogenic post‐translational modifications in a subgroup of sporadic BL including two EBV‐negative BL cell lines

Sexually dimorphic gene expression in the heart of mice and men

The prevalence and clinical manifestation of several cardiovascular diseases vary considerably with sex and age. Thus, a better understanding of the molecular basis of these differences may represent a starting point for an improved gender-specific medicine. Despite the fact that sex-specific differences have been observed in the cardiovascular system of humans and animal models, systematic analyses of sexual dimorphisms at the transcriptional level in the healthy heart are missing. Therefore we performed gene expression profiling on mouse and human cardiac samples of both sexes and young as well as aged individuals and verified our results for a subset of genes using real-time polymerase chain reaction in independent left ventricular samples. To tackle the question whether sex differences are evolutionarily conserved, we also compared sexually dimorphic genes between both species. We found that genes located on sex chromosomes were the most abundant ones among the sexually dimorphic genes. Male-specific expression of Y-linked genes was observed in mouse hearts as well as in the human myocardium (e.g. Ddx3y, Eif2s3y and Jarid1d). Higher expression levels of X-linked genes were detected in female mice for Xist, Timp1 and Car5b and XIST, EIF2S3X and GPM6B in women. Furthermore, genes on autosomal chromosomes encoding cytochromes of the monoxygenase family (e.g. Cyp2b10), carbonic anhydrases (e.g. Car2 and Car3) and natriuretic peptides (e.g. Nppb) were identified with sex- and/or age-specific expression levels. This study underlines the relevance of sex and age as modifiers of cardiac gene expression

Androgens Contribute to Sex Differences in Myocardial Remodeling under Pressure Overload by a Mechanism Involving TGF-β

Background: In clinical studies, myocardial remodeling in aortic valve stenosis appears to be more favorable in women than in men, even after menopause. In the present study, we assessed whether circulating androgens contribute to a less favorable myocardial remodeling under pressure overload in males. We examined sex-related differences in one-year-old male and female mice. Whereas male mice at this age exhibited circulating androgen levels within the normal range for young adults, the circulating estrogens in females were reduced. The contribution of gonadal androgens to cardiac remodeling was analyzed in a group of same-age castrated mice. Methodology/Principal Findings: Animals were subjected to transverse aortic constriction (TAC). Echocardiography was performed 2 weeks after TAC and myocardial mRNA levels of TGF-bs, Smads 2 and 3, collagens, fibronectin, b-myosin heavy chain and a-myosin heavy chain were determined by q-PCR. Protein detection of p-SMAD2/3 was performed by Western Blot. Histological staining of fibrosis was performed with picrosirius red and Masson’s trichrome. Compared with females, males developed more severe tissue fibrosis, LV dilation and hemodynamic dysfunction. TAC-males showed higher myocardial expression levels of TGF-bs and the treatment with a neutralizing antibody to TGF-b prevented myocardial fibrosis development. Orchiectomy diminished TAC-induced up-regulation of TGF-bs and TGF-b target genes, and it also reduced fibrosis and hemodynamic dysfunction. The capability of androgens to induce TGF-b expression was confirmed i