Caveolin-1 deficiency induces a MEK-ERK1/2-Snail-1-dependent epithelial-mesenchymal transition and fibrosis during peritoneal dialysis

Peritoneal dialysis (PD) is a form of renal replacement therapy whose repeated use can alter dialytic function through induction of epithelial-mesenchymal transition (EMT) and fibrosis, eventually leading to PD discontinuation. The peritoneum from Cav1-/- mice showed increased EMT, thickness and fibrosis. Exposure of Cav1-/- mice to PD fluids further increased peritoneal membrane thickness, altered permeability and increased the number of FSP-1/cytokeratin-positive cells invading the sub-mesothelial stroma. High-throughput quantitative proteomics revealed increased abundance of collagens, FN and laminin, as well as proteins related to TGF- activity in matrices derived from Cav1-/- cells. Lack of Cav1 was associated with hyperactivation of a MEK-ERK1/2-Snail-1 pathway that regulated the Smad2-3/Smad1-5-8 balance. Pharmacological blockade of MEK rescued E-cadherin and ZO-1 inter-cellular junction localization, reduced fibrosis and restored peritoneal function in Cav1-/- mice. Moreover, treatment of human PD-patient-derived MCs with drugs increasing Cav1 levels, as well as ectopic Cav1 expression, induced reacquisition of epithelial features. This study demonstrates a pivotal role of Cav1 in the balance of epithelial versus mesenchymal state and suggests targets for the prevention of fibrosis during PD

Percutaneous mitral repair: current and future devices

Mitral regurgitation (MR) is the second most common valvular heart disease and its prevalence is increasing with population ageing. In the recent years we have witnessed the development of several transcatheter devices to correct MR in patients at high-risk for surgery. The majority of evidence regarding safety and efficacy of this new therapy comes from MitraClip studies. However, new alternatives on the field of valve repair have emerged with promising results. The aim of this review is to portrait the landscape of transcatheter mitral repair alternatives, from currently used devices to those that will have a role in the near future

A rightward shift in the visuospatial attention vector with healthy aging

The study of lateralised visuospatial attention bias in non-clinical samples has revealed a systematic group-level leftward bias (pseudoneglect), possibly as a consequence of right hemisphere dominance for visuospatial attention. Pseudoneglect appears to be modulated by age, with a reduced or even reversed bias typically present in elderly participants. It has been suggested that this shift in bias may arise due to disproportionate aging of the right hemisphere and/or an increase in complementary functional recruitment of the left hemisphere for visuospatial processing. In this study, we report rightward shifts in subjective midpoint judgement relative to healthy young participants whilst elderly participants performed a computerized version of the landmark task (in which they had to judge whether a transection mark appeared closer to the right or left end of a line) on three different line lengths. This manipulation of stimulus properties led to a similar behavioural pattern in both the young and the elderly: a rightward shift in subjective midpoint with decreasing line length, which even resulted in a systematic rightward bias in elderly participants for the shortest line length (1.98° of visual angle). Overall performance precision for the task was lower in the elderly participants regardless of line length, suggesting reduced landmark task discrimination sensitivity with healthy aging. This rightward shift in the attentional vector with healthy aging is likely to result from a reduction in right hemisphere resources/dominance for attentional processing in elderly participants. The significant rightward bias in the elderly for short lines may even suggest a reversal of hemisphere dominance in favour of the left hemisphere/right visual field under specific conditions

Caveolin-1 deficiency induces a MEK-ERK1/2-Snail-1-dependent epithelial-mesenchymal transition and fibrosis during peritoneal dialysis

Peer reviewe

Transmission of malaria and genotypic variability of Plasmodium falciparum on the Island of Annobon (Equatorial Guinea)

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Tuberculosis in seals caused by a novel member of the Mycobacterium tuberculosis complex: Mycobacterium pinnipedii sp. nov.

A comparison of Mycobacterium tuberculosis complex isolates from seals (pinnipeds) in Australia, Argentina, Uruguay, Great Britain and New Zealand was undertaken to determine their relationships to each other and their taxonomic position within the complex. Isolates from 30 cases of tuberculosis in six species of pinniped and seven related isolates were compared to representative and standard strains of the M. tuberculosis complex. The seal isolates could be distinguished from other members of the M. tuberculosis complex, including the recently defined ‘Mycobacterium canettii’ and ‘Mycobacterium caprae’, on the basis of host preference and phenotypic and genetic tests. Pinnipeds appear to be the natural host for this ‘seal bacillus’, although the organism is also pathogenic in guinea pigs, rabbits, humans, Brazilian tapir (Tapirus terrestris) and, possibly, cattle. Infection caused by the seal bacillus is predominantly associated with granulomatous lesions in the peripheral lymph nodes, lungs, pleura, spleen and peritoneum. Cases of disseminated disease have been found. As with other members of the M. tuberculosis complex, aerosols are the most likely route of transmission. The name Mycobacterium pinnipedii sp. nov. is proposed for this novel member of the M. tuberculosis ..

The EUropean Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EU-GEI): Incidence and First-Episode Case–Control Programme

Funder: FP7 Ideas: European Research Council; doi: http://dx.doi.org/10.13039/100011199; Grant(s): HEALTH-F2-2010-241909Abstract: Purpose: The EUropean Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EU-GEI) study contains an unparalleled wealth of comprehensive data that allows for testing hypotheses about (1) variations in incidence within and between countries, including by urbanicity and minority ethnic groups; and (2) the role of multiple environmental and genetic risk factors, and their interactions, in the development of psychotic disorders. Methods: Between 2010 and 2015, we identified 2774 incident cases of psychotic disorders during 12.9 million person-years at risk, across 17 sites in 6 countries (UK, The Netherlands, France, Spain, Italy, and Brazil). Of the 2774 incident cases, 1130 cases were assessed in detail and form the case sample for case–control analyses. Across all sites, 1497 controls were recruited and assessed. We collected data on an extensive range of exposures and outcomes, including demographic, clinical (e.g. premorbid adjustment), social (e.g. childhood and adult adversity, cannabis use, migration, discrimination), cognitive (e.g. IQ, facial affect processing, attributional biases), and biological (DNA via blood sample/cheek swab). We describe the methodology of the study and some descriptive results, including representativeness of the cohort. Conclusions: This resource constitutes the largest and most extensive incidence and case–control study of psychosis ever conducted