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Introduction: A recent multiregional whole-exome sequencing of 48 tumour samples from 9 gastric adenocarcinomas discovered PCLO mutations in 23 (47.9%) tumour samples. Based on that unexpected high prevalence of PCLO mutations, we hypothesized a tumour biological significance of PCLO in gastric cancer (GC)., Methods: Tumour samples (whole tissue sections) obtained from 466 patients resected for therapy-naive GC were stained with an anti-PCLO antibody. The histoscore for tumour cells and the presence of immunostaining of stromal cells and tumour vessels was documented for each case. An algorithm for PCLO immunopositivity was formed and correlated with clinicopathological patient characteristics., Results: 175 GCs were classified as PCLO positive within tumour cells, and 291 as negative. Stromal cells were positive for PCLO in 106 cases and tumour vessels in 84. PCLO-positive GCs more often showed an intestinal phenotype, a lower T category and were more commonly associated with Helicobacter pylori infection. A separate analysis of PCLO expression in intestinal and diffuse type GCs, respectively, showed no significant correlations. Patients with PCLO negative/low tumour cells showed a shortened overall (14.0 ± 1.4 vs. 16.0 ± 1.8 months) and tumour-specific survival (15.0 ± 1.6 months vs. 17.9 ± 3.6). Comparison of PCLOs genotype with its phenotype in 48 tumour samples obtained from nine cases showed no direct correlations with missense mutations., Conclusion: Our data provide evidence that PCLO is differentially expressed in GC and might delay tumour progression., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: The bearded vulture is sparsely distributed across a wide geographic range that extends over three continents (Africa, Europe and Asia). Restriction to high-altitude mountainous habitats, low breeding rates, lack of food and a heightened level of persecution have left many local populations severely diminished or extinct. Understanding the genetic connectivity and population structure of this threatened vulture species is critical for accurately assessing their conservation status, and for appropriately managing local populations through captive breeding programmes or translocations. Previous genetic assessments of the species were mainly focused on the European and Asian populations and included limited representation of the geographically isolated southern African population. A single mitochondrial study, which focused on the African populations of the bearded vulture, detected limited genetic differentiation between populations in Ethiopia and southern Africa, with reduced haplotype diversity in the southern Africa population. In this study, we extend the previous genetic assessments of the species by examining the phylogeography and genetic connectivity of global G. barbatus populations using a panel of 14 microsatellite loci., Results: Analyses revealed spatially correlated genetic differentiation between regional populations and low levels of gene flow between these population fragments. In contrast to the mitochondrial data, the microsatellite data support the management of genetically different populations as separate entities., Conclusions: Low genetic diversity and geographic isolation are known to adversely affect the evolutionary potential of a species in the long-term. The high inbreeding found in the southern African G. barbatus and, to a lesser extent, the northern African populations highlights the need for conservation programmes to effectively manage populations of this species and maintain extant genetic diversity.

Evidence-based decisions on indicated prevention in early psychosis require large-scale studies on the pathways to care in high-risk subjects. EPOS (The European Prediction of Psychosis Study), a prospective multi-center, naturalistic field study in four European countries (Finland, Germany, The Netherlands and England), was designed to acquire accurate knowledge about pathways to care and delay in obtaining specialized high risk care. Our high risk sample (n=233) reported on average 2.9 help-seeking contacts, with an average delay between onset of relevant problems to initial help-seeking contact of 72.6 weeks, and between initial help-seeking contact and reaching specialized high risk care of 110.9 weeks. This resulted in a total estimated duration of an unrecognized risk for psychosis of 3 ½ years. Across EPOS EU regions, about 90% of care pathway contacts were within professional health care sectors. Between EPOS regions, differences in the pathways parameters including early detection and health-care systems were often very pronounced. High-risk participants who later made transition to a full psychotic disorder had significantly longer delays between initial help-seeking and receiving appropriate interventions. Our study underlines the need for regionally adapted implementation of early detection and intervention programs within respective mental health and health care networks, including enhancing public awareness of early psychosis., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Epidemiologic data and animal models suggest that, despite the predominant role of human papillomavirus infection, sex steroid hormones are also involved in the etiology of invasive cervical carcinoma (ICC)., Methods: Ninety-nine ICC cases, 121 cervical intraepithelial neoplasia grade 3 (CIN3) cases and 2 control women matched with each case for center, age, menopausal status and blood collection-related variables, were identified in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Circulating levels of testosterone (T) and estradiol (E(2)); dehydroepiandrosterone sulfate (DHEAS); progesterone (premenopausal women); and sex hormone-binding globulin (SHBG) were measured using immunoassays. Levels of free (f) T and E(2) were calculated from absolute concentrations of T, E(2), and SHBG. Odds ratios (ORs) and 95% confidence intervals (CI) were computed using regularized conditional logistic regression., Results: Among premenopausal women, associations with ICC were observed for fT (OR for highest vs. lowest tertile = 5.16, 95% CI, 1.50-20.1). SHBG level was associated with a significant downward trend in ICC risk. T, E(2), fE(2), and DHEAS showed nonsignificant positive association with ICC. Progesterone was uninfluential. Among postmenopausal women, associations with ICC were found for T (OR = 3.14; 95% CI, 1.21-9.37), whereas E(2) and fT showed nonsignificant positive association. SHBG level was unrelated to ICC risk in postmenopausal women. No associations between any hormone and CIN3 were detected in either pre- or postmenopausal women., Conclusions: Our findings suggest for the first time that T and possibly E(2) may be involved in the etiology of ICC., Impact: The responsiveness of cervical tumors to hormone modulators is worth exploring.

The 2009 European Guidelines on Pulmonary Hypertension did not cover only pulmonary arterial hypertension (PAH) but also some aspects of pulmonary hypertension (PH) in chronic lung disease. The European Guidelines point out that the drugs currently used to treat patients with PAH (prostanoids, endothelin receptor antagonists and phosphodiesterase-5 inhibitors) have not been sufficiently investigated in other forms of PH. Therefore, the European Guidelines do not recommend the use of these drugs in patients with chronic lung disease and PH. This recommendation, however, is not always in agreement with medical ethics as physicians feel sometimes inclined to treat other form of pulmonary hypertension which may affect quality of life and survival of these patients in a similar manner. In June 2010, a group of German experts met in Cologne, Germany, to discuss open and controversial issues surrounding the practical implementation of the European Guidelines. The conference was sponsored by the German Society of Cardiology, the German Society of Respiratory Medicine and the German Society of Pediatric Cardiology. One of the working groups was dedicated to the diagnosis and treatment of PH in patients with chronic lung disease. The recommendations of this working group are summarized in the present paper., (© Georg Thieme Verlag KG Stuttgart · New York.)