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BACKGROUND AND AIMS: Childlessness and infertility represent a frequent and important issue in inflammatory bowel disease (IBD) patients. Nevertheless, until now epidemiological data remains scarce. Therefore, main objectives of this study were to evaluate the rate of childlessness and the cumulative probability of reproduction in female and male IBD patients within the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS), a large prospective multicenter nationwide cohort. METHODS: Prospectively collected data of SIBDCS was used, comprising more than 3,300 patients with Crohn's disease (CD) and ulcerative colitis (UC). We analyzed the following groups of patients: 1) female IBD patients aged ≥40 years and diagnosed before age of 30 years with at least one follow-up, 2) female IBD patients who reported actively trying to conceive, with IBD diagnosed <35 years and with age at enrolment <45 years (longitudinal observation), with at least one follow-up, and 3) childless males who actively tried to conceive. RESULTS: A total of 1,412 female patients from the SIBDCS [843 CD, 539 UC, 30 indeterminate colitis (IC)] with available data were included in our analyses. Out of those 184 females (70.1% CD and 29.9 % UC) were aged ≥ 40 years and have been diagnosed with IBD before the age of 30 years. Among these, 184 women 32.1% were childless. The portion of childless females (36.4%) was significantly higher in CD vs. UC (36.4% vs. 21.8%; p=0.026), equaling a relative risk of childlessness of 1.7 in CD vs. UC. and higher than in the Swiss general population (21%). The mean number of children per female patient was 1.32 (median 1, min 0, max 6), per female with CD 1.12 (median 1, min 0, max 4), per female with UC/IC 1.78 (median 2, min 0, max 6; P=0.001). The longitudinal analysis of female IBD patients trying to conceive revealed that one out of two women neither were pregnant nor had born a child five years after first trying to conceive. CONCLUSIONS: The rate of childlessnes

Pericytes facilitate blood–brain barrier (BBB) integrity; however, the mechanisms involved remain unclear. Hence, using co-cultures of human cerebral microvascular endothelial cells (ECs) and vascular pericytes (PCs) in different spatial arrangements, as well as PC conditioned media, we investigated the impact of PC-EC orientation and PC-derived soluble factors on EC barrier function. We provide the first evidence that barrier-inducing properties of PCs require basolateral contact with ECs. Gene expression analysis (GEA) in ECs co-cultured with PCs versus ECs alone showed significant upregulation of 38 genes and downregulation of 122 genes. Pathway enrichment analysis of modulated genes showed significant regulation of several pathways, including transforming growth factor-β and interleukin-1 regulated extracellular matrix, interferon and interleukin signaling, immune system signaling, receptor of advanced glycation end products (RAGE), and cytokine–cytokine receptor interaction. Transcriptomic analysis showed a reduction in molecules such as pro-inflammatory cytokines and chemokines, which are known to be induced during BBB disruption. Moreover, cytokine proteome array confirmed the downregulation of key pro-inflammatory cytokines and chemokines on the protein level. Other molecules which influence BBB and were favorably modulated upon EC-PC co-culture include IL-18 binding protein, kallikrein-3, CSF2 CSF3, CXCL10, CXCL11 (downregulated) and IL-1-R4; HGF, PDGF-AB/BB, PECAM, SERPIN E1 (upregulated). In conclusion, we provide the first evidence that (1) basolateral contact between ECs and PCs is essential for EC barrier function and integrity; (2) in ECs co-cultured with PCs, the profile of BBB disrupting pro-inflammatory molecules and cytokines/chemokines is downregulated; (3) PCs significantly modulate EC mechanisms known to improve barrier function, including TGF-β regulated ECM pathway, anti-inflammatory cytokines, growth factors and matrix proteins. This human P

STUDY QUESTION Is fatigue a frequent symptom of endometriosis? SUMMARY ANSWER Fatigue is an underestimated symptom of endometriosis as it affects the majority of women with endometriosis, but it is not widely discussed in literature. WHAT IS KNOWN ALREADY Fatigue can be a symptom of endometriosis causing major distress impacting the daily activities and quality of life of women with endometriosis. However, few studies with large sample sizes have investigated fatigue as a symptom of endometriosis. STUDY DESIGN, SIZE, DURATION The study was designed as a multi-center matched case-control study. Recruitment took place at hospitals and private practices in Switzerland, Germany and Austria between 2010 and 2016. Data was collected from 1120 women, 560 of them with endometriosis. The women with endometriosis were matched to 560 control women in regard to age ±3 years and ethnic background. PARTICIPANTS/MATERIALS, SETTING, METHODS Diagnosis of women with endometriosis had to be surgically and histologically confirmed. Surgical exclusion or absence of any endometriosis-identifying symptoms was required for control subjects. Materials included surgical and histological reports as well as data retrieved from a self-administered questionnaire. This study focused on the symptom fatigue in endometriosis. Relationships of variables were established by regression analysis and associations were quantified as odds ratios. MAIN RESULTS AND THE ROLE OF CHANCE Frequent fatigue was experienced by a majority of women diagnosed with endometriosis (50.7% versus 22.4% in control women, P < 0.001). Fatigue in endometriosis was associated with insomnia (OR: 7.31, CI: 4.62-11.56, P < 0.001), depression (OR: 4.45, CI: 2.76-7.19, P < 0.001), pain (OR: 2.22, CI: 1.52-3.23, P < 0.001), and occupational stress (OR: 1.45, CI: 1.02-2.07, P = 0.037), but was independent of age, time since first diagnosis and stage of the disease. LIMITATIONS, REASONS FOR CAUTION Women with asymptomatic endom

Objectives: Endometriosis is a gynaecological disease most commonly causing severe and chronic pelvic pain as well as an impaired quality of life. The aim of this study was to investigate if and how endometriosis affects choices regarding professional life as well as the quality of daily working life. Design, setting and participants: In the context of a multicentre case–control study, we collected data from 505 women with surgically/histologically confirmed diagnosis of endometriosis and 505 matched controls. Study participants were recruited prospectively in hospitals and doctors’ practices in Switzerland, Germany and Austria. Using a detailed questionnaire, the study investigated work–life and career choices of study participants. Main outcome measures Associations between endometriosis/disease symptoms and limitations in career development as well as ability to work. Results: Women with endometriosis were less often able to work in their desired profession than women from the control group (adjusted OR=1.84, 95% CI: 1.15 to 2.94, R2=0.029, p=0.001) and they had to take health-related limitations into consideration in their career decisions to a significantly higher degree than women in the control group (OR=4.79, 95% CI: 2.30 to 9.96, R2=0.063, p<0.001). Among women with endometriosis, chronic pain was significantly associated with increased sick leave (OR=3.52, 95% CI: 2.02 to 6.13, R2=0.072, p<0.001) as well as with loss of productivity at work (OR=3.08, 95% CI: 2.11 to 4.50, R2=0.087, p<0.001). Conclusions: Endometriosis is associated with impairment of professional life, in particular with regard to career choices. Further research to develop strategies to support endometriosis-affected women in realising professional opportunities is recommended.