Search results for "Tos"
showing 10 items of 12217 documents
Standardising clinical outcomes measures for adult clinical trials in Fabry disease: A global Delphi consensus.
2021
International audience; Background: Recent years have witnessed a considerable increase in clinical trials of new investigational agents for Fabry disease (FD). Several trials investigating different agents are currently in progress; however, lack of standardisation results in challenges to interpretation and comparison. To facilitate the standardisation of investigational programs, we have developed a common framework for future clinical trials in FD.Methods and findings: A broad consensus regarding clinical outcomes and ways to measure them was obtained via the Delphi methodology. 35 FD clinical experts from 4 continents, representing 3389 FD patients, participated in 3 rounds of Delphi p…
The effects of acceptance and commitment therapy on eating behavior and diet delivered through face-to-face contact and a mobile app: a randomized co…
2018
Background Internal motivation and good psychological capabilities are important factors in successful eating-related behavior change. Thus, we investigated whether general acceptance and commitment therapy (ACT) affects reported eating behavior and diet quality and whether baseline perceived stress moderates the intervention effects. Methods Secondary analysis of unblinded randomized controlled trial in three Finnish cities. Working-aged adults with psychological distress and overweight or obesity in three parallel groups: (1) ACT-based Face-to-face (n = 70; six group sessions led by a psychologist), (2) ACT-based Mobile (n = 78; one group session and mobile app), and (3) Control (n = 71; …
Blimp1 Prevents Methylation of Foxp3 and Loss of Regulatory T Cell Identity at Sites of Inflammation
2018
Summary Foxp3+ regulatory T (Treg) cells restrict immune pathology in inflamed tissues; however, an inflammatory environment presents a threat to Treg cell identity and function. Here, we establish a transcriptional signature of central nervous system (CNS) Treg cells that accumulate during experimental autoimmune encephalitis (EAE) and identify a pathway that maintains Treg cell function and identity during severe inflammation. This pathway is dependent on the transcriptional regulator Blimp1, which prevents downregulation of Foxp3 expression and “toxic” gain-of-function of Treg cells in the inflamed CNS. Blimp1 negatively regulates IL-6- and STAT3-dependent Dnmt3a expression and function …
Temporal profiling of an acute stress-induced behavioral phenotype in mice and role of hippocampal DRR1.
2018
Abstract Understanding the neurobiological mechanisms underlying the response to an acute stressor may provide novel insights into successful stress-coping strategies. Acute behavioral stress-effects may be restricted to a specific time window early after stress-induction. However, existing behavioral test batteries typically span multiple days or even weeks, limiting the feasibility for a broad behavioral analysis following acute stress. Here, we designed a novel comprehensive behavioral test battery in male mice that assesses multiple behavioral dimensions within a sufficiently brief time window to capture acute stress-effects and its temporal profile. Using this battery, we investigated …
Somatosensory Brain Function and Gray Matter Regional Volumes Differ According to Exercise History : Evidence from Monozygotic Twins
2017
Associations between long-term physical activity and cortical function and brain structure are poorly known. Our aim was to assess whether brain functional and/or structural modulation associated with long-term physical activity is detectable using a discordant monozygotic male twin pair design. Nine monozygotic male twin pairs were carefully selected for an intrapair difference in their leisure-time physical activity of at least three years duration (mean age 34 ± 1 years). We registered somatosensory mismatch response (SMMR) in EEG to electrical stimulation of fingers and whole brain MR images. We obtained exercise history and measured physical fitness and body composition. Equivalent ele…
Retrotransposon insertions can initiate colorectal cancer and are associated with poor survival
2019
Genomic instability pathways in colorectal cancer (CRC) have been extensively studied, but the role of retrotransposition in colorectal carcinogenesis remains poorly understood. Although retrotransposons are usually repressed, they become active in several human cancers, in particular those of the gastrointestinal tract. Here we characterize retrotransposon insertions in 202 colorectal tumor whole genomes and investigate their associations with molecular and clinical characteristics. We find highly variable retrotransposon activity among tumors and identify recurrent insertions in 15 known cancer genes. In approximately 1% of the cases we identify insertions in APC, likely to be tumor-initi…
Clinical and biochemical characteristics of individuals with low cholesterol syndromes: A comparison between familial hypobetalipoproteinemia and fam…
2017
Background The most frequent monogenic causes of low plasma cholesterol are familial hypobetalipoproteinemia (FHBL1) because of truncating mutations in apolipoprotein B coding gene (APOB) and familial combined hypolipidemia (FHBL2) due to loss-of-function mutations in ANGPTL3 gene. Objective A direct comparison of lipid phenotypes of these 2 conditions has never been carried out. In addition, although an increased prevalence of liver steatosis in FHBL1 has been consistently reported, the hepatic consequences of FHBL2 are not well established. Methods We investigated 350 subjects, 67 heterozygous carriers of APOB mutations, 63 carriers of the p.S17* mutation in ANGPTL3 (57 heterozygotes and …
Disease severity in patients with visceral leishmaniasis is not altered by co-infection with intestinal parasites
2017
Visceral leishmaniasis (VL) is a neglected tropical disease that affects the poorest communities and can cause substantial morbidity and mortality. Visceral leishmaniasis is characterized by the presence of Leishmania parasites in the spleen, liver and bone marrow, hepatosplenomegaly, pancytopenia, prolonged fever, systemic inflammation and low body mass index (BMI). The factors impacting on the severity of VL are poorly characterized. Here we performed a cross-sectional study to assess whether co-infection of VL patients with intestinal parasites influences disease severity, assessed with clinical and haematological data, inflammation, cytokine profiles and BMI. Data from VL patients was s…
Plasmacytoid dendritic cells promote systemic sclerosis with a key role for TLR8
2018
Systemic sclerosis (SSc) is a multisystem life-threatening fibrosing disorder that lacks effective treatment. The link between the inflammation observed in organs such as the skin and profibrotic mechanisms is not well understood. The plasmacytoid dendritic cell (pDC) is a key cell type mediating Toll-like receptor (TLR)-induced inflammation in autoimmune disease patients, including lupus and skin diseases with interface dermatitis. However, the role of pDCs in fibrosis is less clear. We show that pDCs infiltrate the skin of SSc patients and are chronically activated, leading to secretion of interferon-α (IFN-α) and CXCL4, which are both hallmarks of the disease. We demonstrate that the s…
No pre-zygotic isolation mechanisms between Schistosoma haematobium and Schistosoma bovis parasites: From mating interactions to differential gene ex…
2021
Species usually develop reproductive isolation mechanisms allowing them to avoid interbreeding. These preventive barriers can act before reproduction, “pre-zygotic barriers”, or after reproduction, “post-zygotic barriers”. Pre-zygotic barriers prevent unfavourable mating, while post-zygotic barriers determine the viability and selective success of the hybrid offspring. Hybridization in parasites and the underlying reproductive isolation mechanisms maintaining their genetic integrity have been overlooked. Using an integrated approach this work aims to quantify the relative importance of pre-zygotic barriers in Schistosoma haematobium x S. bovis crosses. These two co-endemic species cause sch…