Improving mental health among intensive care unit staff with communication skills training.

Purpose: Intensive Care Unit (ICU) staff report that a large part of the work-related distress they experience is related to communication situations with colleagues, patients, and relatives. Based on these findings, the aim of the present study was to preliminary evaluate the effects of a novel Communication Skills Training (CST) program on mental health among ICU staff.

Methods: The CST program was delivered to the entire work force of an ICU at a Swedish hospital and was evaluated as an uncontrolled clinical trial with three repeated measures.

Myocardin related transcription factor and galectin-3 drive lipid accumulation in human blood vessels.

Objective: Diabetes and hypertension are important risk factors for vascular disease, including atherosclerosis. A driving factor in this process is lipid accumulation in smooth muscle cells of the vascular wall. The glucose- and mechano-sensitive transcriptional coactivator, myocardin-related transcription factor A (MRTF-A/MKL1) can promote lipid accumulation in cultured human smooth muscle cells and contribute to the formation of smooth muscle-derived foam cells.

Itga8-Cre-mediated deletion of YAP and TAZ impairs bladder contractility with minimal inflammation and chondrogenic differentiation.

A role of Yes1-associated transcriptional regulator (YAP) and WW domain-containing transcription regulator 1 (TAZ) in vascular and gastrointestinal contractility due to control of myocardin (Myocd) expression, which in turn activates contractile genes, has been demonstrated. Whether this transcriptional hierarchy applies to the urinary bladder is unclear. We found that YAP/TAZ are expressed in human detrusor myocytes and therefore exploited the model for the deletion of YAP/TAZ.

Vascular smooth muscle-specific YAP/TAZ deletion triggers aneurysm development in mouse aorta.

Inadequate adaption to mechanical forces, including blood pressure, contributes to development of arterial aneurysms. Recent studies have pointed to a mechanoprotective role of YAP and TAZ in vascular smooth muscle cells (SMCs). Here, we identified reduced expression of YAP1 in human aortic aneurysms.

Introducing Braining-physical exercise as adjunctive therapy in psychiatric care: a retrospective cohort study of a new method.

Background: Patients with severe mental disorders suffer from higher rates of poor somatic health and have shorter life expectancy than the average population. Physical activity can treat and prevent several diseases, e.g.

Transcription factor GATA6 promotes migration of human coronary artery smooth muscle cells .

Vascular smooth muscle cell plasticity plays a pivotal role in the pathophysiology of vascular diseases. Despite compelling evidence demonstrating the importance of transcription factor GATA6 in vascular smooth muscle, the functional role of GATA6 remains poorly understood. The aim of this study was to elucidate the role of GATA6 on cell migration and to gain insight into GATA6-sensitive genes in smooth muscle.

Role of smooth muscle YAP and TAZ in protection against phenotypic modulation, inflammation, and aneurysm development.

A ruptured arterial aneurysm, especially in the aorta, represents one of the most acute and mortal conditions encountered in clinical medicine. Population-based screening in elderly men, treatment of risk factors, such as hypertension, and endovascular or open repair of rupture-prone lesions, represent cornerstones in management. Surgical repair has a sizeable effect on life-expectancy, but medical therapy that retards aneurysm growth still represents a considerable and unmet clinical need.

HIF-1 stabilization in T cells hampers the control of Mycobacterium tuberculosis infection.

The hypoxia-inducible factors (HIFs) regulate the main transcriptional pathway of response to hypoxia in T cells and are negatively regulated by von Hippel-Lindau factor (VHL). But the role of HIFs in the regulation of CD4 T cell responses during infection with M. tuberculosis isn't well understood.

PRC2-mediated repression is essential to maintain identity and function of differentiated dopaminergic and serotonergic neurons.

How neurons can maintain cellular identity over an entire life span remains largely unknown. Here, we show that maintenance of identity in differentiated dopaminergic and serotonergic neurons is critically reliant on the Polycomb repressive complex 2 (PRC2). Deletion of the obligate PRC2 component, , in these neurons resulted in global loss of H3K27me3, followed by a gradual activation of genes harboring both H3K27me3 and H3K9me3 modifications.

Impaired oxygen-sensitive regulation of mitochondrial biogenesis within the von Hippel-Lindau syndrome.

Mitochondria are the main consumers of oxygen within the cell. How mitochondria sense oxygen levels remains unknown. Here we show an oxygen-sensitive regulation of TFAM, an activator of mitochondrial transcription and replication, whose alteration is linked to tumours arising in the von Hippel-Lindau syndrome.

YAP and TAZ in Vascular Smooth Muscle Confer Protection Against Hypertensive Vasculopathy.

Background: Hypertension remains a major risk factor for cardiovascular diseases, but the underlying mechanisms are not well understood. We hypothesize that appropriate mechanotransduction and contractile function in vascular smooth muscle cells are crucial to maintain vascular wall integrity. The Hippo pathway effectors YAP (yes-associated protein 1) and TAZ (WW domain containing transcription regulator 1) have been identified as mechanosensitive transcriptional coactivators.

The Rapid Implementation of a Psychological Support Model for Frontline Healthcare Workers During the COVID-19 Pandemic: A Case Study and Process Evaluation.

The COVID-19 pandemic highlighted the need for psychological support initiatives directed toward frontline healthcare workers, which can be rapidly and sustainably implemented during an infectious disease outbreak. The current case study presents a comprehensive model of psychological support that was implemented at an intensive care unit (ICU) during the first wave of the COVID-19 pandemic. The psychological support model aimed at promoting a resilient stress reaction among frontline staff by protecting physical, social, and psychological resources.

Activation of endogenous retroviruses during brain development causes an inflammatory response.

Endogenous retroviruses (ERVs) make up a large fraction of mammalian genomes and are thought to contribute to human disease, including brain disorders. In the brain, aberrant activation of ERVs is a potential trigger for an inflammatory response, but mechanistic insight into this phenomenon remains lacking. Using CRISPR/Cas9-based gene disruption of the epigenetic co-repressor protein Trim28, we found a dynamic H3K9me3-dependent regulation of ERVs in proliferating neural progenitor cells (NPCs), but not in adult neurons.

Aberrant splicing in neuroblastoma generates RNA-fusion transcripts and provides vulnerability to spliceosome inhibitors.

The paucity of recurrent mutations has hampered efforts to understand and treat neuroblastoma. Alternative splicing and splicing-dependent RNA-fusions represent mechanisms able to increase the gene product repertoire but their role in neuroblastoma remains largely unexplored. Here we investigate the presence and possible roles of aberrant splicing and splicing-dependent RNA-fusion transcripts in neuroblastoma.

MRTFA overexpression promotes conversion of human coronary artery smooth muscle cells into lipid-laden foam cells.

Objective: Smooth muscle cells contribute significantly to lipid-laden foam cells in atherosclerotic plaques. However, the underlying mechanisms transforming smooth muscle cells into foam cells are poorly understood. The purpose of this study was to gain insight into the molecular mechanisms regulating smooth muscle foam cell formation.

Psychological Flexibility and Its Relationship to Distress and Work Engagement Among Intensive Care Medical Staff.

Intensive care settings place specific work-related demands on health care professionals that may elicit stress and negatively influence occupational health and work engagement. Psychological flexibility has emerged as a promising construct that could help explain variation in reported health. Understanding the role of psychological flexibility in occupational psychological health among intensive care medical staff may potentially guide the development of effective interventions.

Inducible Deletion of YAP and TAZ in Adult Mouse Smooth Muscle Causes Rapid and Lethal Colonic Pseudo-Obstruction.

Background & Aims: YAP (Yap1) and TAZ (Wwtr1) are transcriptional co-activators and downstream effectors of the Hippo pathway, which play crucial roles in organ size control and cancer pathogenesis. Genetic deletion of YAP/TAZ has shown their critical importance for embryonic development of the heart, vasculature, and gastrointestinal mesenchyme. The aim of this study was to determine the functional role of YAP/TAZ in adult smooth muscle cells in vivo.

Dizziness and localized pain are often concurrent in patients with balance or psychological disorders.

Background and aims Symptoms of dizziness and pain are both common complaints and the two symptoms often seem to coincide. When symptoms appear concomitant for sustained periods of time the symptoms might maintain and even exacerbate each other, sometimes leading to psychological distress. In order to evaluate such comorbidity we studied patients referred to a vestibular unit and to a psychiatric outpatient clinic with respectively balance disorders and psychological issues.

Identification of the intermediate filament protein synemin/SYNM as a target of myocardin family coactivators.

Myocardin (MYOCD) is a critical regulator of smooth muscle cell (SMC) differentiation, but its transcriptional targets remain to be exhaustively characterized, especially at the protein level. Here we leveraged human RNA and protein expression data to identify novel potential MYOCD targets. Using correlation analyses we found several targets that we could confirm at the protein level, including SORBS1, SLMAP, SYNM, and MCAM.

EglN3 hydroxylase stabilizes BIM-EL linking VHL type 2C mutations to pheochromocytoma pathogenesis and chemotherapy resistance.

Despite the discovery of the oxygen-sensitive regulation of HIFα by the von Hippel-Lindau (VHL) protein, the mechanisms underlying the complex genotype/phenotype correlations in VHL disease remain unknown. Some germline mutations cause familial pheochromocytoma and encode proteins that preserve their ability to down-regulate HIFα. While type 1, 2A, and 2B mutants are defective in regulating HIFα, type 2C mutants encode proteins that preserve their ability to down-regulate HIFα.

EPAS1/HIF2α correlates with features of low-risk neuroblastoma and with adrenal chromaffin cell differentiation during sympathoadrenal development.

The hypoxia inducible transcription factor EPAS1/HIF2α has been described as an oncogene and a potential therapeutic target in neuroblastoma. Our analysis of several neuroblastoma tumour expression datasets does not support an oncogenic role, instead EPAS1 expression is associated with better patient outcome and characteristics of low-risk tumours. Treatment with HIF2α inhibitors did not block in vitro neuroblastoma cell proliferation nor xenograft growth.

Exploratory Profiling of Urine MicroRNAs in the Mouse Model of LAMA2-CMD: Relation to Disease Progression.

Circulating microRNAs (miRNAs) are being considered as non-invasive biomarkers for disease progression and clinical trials. Congenital muscular dystrophy with deficiency of laminin α2 chain (LAMA2-CMD) is a very severe form of muscular dystrophy, for which no treatment is available. In order to identify LAMA2-CMD biomarkers we have profiled miRNAs in urine from the / mouse model of LAMA2-CMD at three distinct time points (representing asymptomatic, initial and established disease).