A cross-sectional survey of stigma towards people with a mental illness in the general public:The role of employment, domestic noise disturbance and age

INTRODUCTION: Stigmatization impedes the social integration of persons recovering from mental illnesses. Little is known about characteristics of the stigmatized person that lessen or aggravate public stigma. PURPOSE: This study investigates which characteristics of persons with mental illnesses (i.e. with a depression or a psychotic disorder) might increase or decrease the likelihood of public stigma. METHODS: Over 2,000 adults read one of sixteen vignettes describing a person with a depressive disorder or a psychotic disorder and answered a set of items measuring social distance. RESULTS: The person who was employed (vs. unemployed), or whose neighbors did not experience domestic noise disturbance (vs. disturbance) elicited significantly less social distance. Also persons with a depressive disorder elicited less social distance, vs. persons with a psychotic disorder. CONCLUSION: Employment and good housing circumstances may destigmatize persons coping with mental illnesses. Mental health and social services should encourage paid employment, quality housing and other paths to community integration

Gain of 20q11.21 in human pluripotent stem cells impairs TGF-β-dependent neuroectodermal commitment

Gain of 20q11.21 is one of the most common recurrent genomic aberrations in human pluripotent stem cells. Although it is known that overexpression of the antiapoptotic gene Bcl-xL confers a survival advantage to the abnormal cells, their differentiation capacity has not been fully investigated. RNA sequencing of mutant and control hESC lines, and a line transgenically overexpressing Bcl-xL, shows that overexpression of Bcl-xL is sufficient to cause most transcriptional changes induced by the gain of 20q11.21. Moreover, the differentially expressed genes in mutant and Bcl-xL overexpressing lines are enriched for genes involved in TGF-beta- and SMAD-mediated signaling, and neuron differentiation. Finally, we show that this altered signaling has a dramatic negative effect on neuroectodermal differentiation, while the cells maintain their ability to differentiate to mesendoderm derivatives. These findings stress the importance of thorough genetic testing of the lines before their use in research or the clinic

What is the evidence base of used aggregated antibiotic resistance percentages to change empirical antibiotic treatment? A scoping review

Contains fulltext : 251404.pdf (Publisher’s version ) (Open Access)OBJECTIVES: Antibiotic resistance requires continuous monitoring by experts to decide whether empirical antibiotic therapies (EATs) should be replaced by alternative antibiotics. The exact moment and criteria for this change are unclear and generally based on consensus between experts. This scoping review aims to identify from the literature the resistance thresholds used for a change in EAT and the criteria on which they are based. METHODS: Scoping review for which a comprehensive structured literature search was conducted. Rayyan, software for systematic reviews, was used for the screening of abstracts and titles. Data sources were Pubmed and a hand-search of reference lists and grey literature. Papers were eligible if they concerned any type of bacterial infectious disease and mentioned or defined antibiotic resistance thresholds for decision-making purposes for EAT. The inclusion and analysis of articles was done by two researchers; any conflicts were resolved through discussion or by consulting a third reviewer. RESULTS: We identified 3146 unique papers. Following title/abstract screening, 125 papers were comprehensively read, and 16 papers were included. The included papers gave thresholds for urinary tract infections, respiratory tract infections, meningitis, skin and soft tissue infections, gonorrhoea, and bone and joint infections. Six criteria were found that were commonly used to base the thresholds on. These were: disease severity, efficacy of treatment, adverse drug events, risk of Clostridioides difficile infection, costs, and increased resistance. The number of criteria used to define each threshold varied from one to six between papers. CONCLUSIONS: The thresholds used for EATs are few, commonly based on expert opinion estimates, and can therefore have broad ranges. Used criteria underlying reported thresholds are heterogenous and require standardization. Considering the rising trend in resistance, there is a clear need for rigid tools to determine thresholds in order to support guideline development with the best and timely evidence

GATA2 haploinsufficient patients lack innate lymphoid cells that arise after hematopoietic cell transplantation.

Innate lymphoid cells (ILC) are important barrier tissue immune regulators. They play a pivotal role in early non-specific protection against infiltrating pathogens, regulation of epithelial integrity, suppression of pro-inflammatory immune responses and shaping the intestinal microbiota. GATA2 haploinsufficiency causes an immune disorder that is characterized by bone marrow failure and (near) absence of monocytes, dendritic cells, B cells and natural killer (NK) cells. T cells develop normally, albeit at lower numbers. Here, we describe the absence of ILCs and their progenitors in blood and bone marrow of two patients with GATA2 haploinsufficiency and show that all subsets of ILCs appear after allogeneic hematopoietic stem cell transplantation, irrespective of the preparative conditioning regimen. Our data indicate that GATA2 is involved in the development of hematopoietic precursor cells (HPC) towards the ILC lineage

Blockade of T-cell activation by dithiocarbamates involves novel mechanisms of inhibition of nuclear factor of activated T cells.

Dithiocarbamates (DTCs) have recently been reported as powerful inhibitors of NF-kappaB activation in a number of cell types. Given the role of this transcription factor in the regulation of gene expression in the inflammatory response, NF-kappaB inhibitors have been suggested as potential therapeutic drugs for inflammatory diseases. We show here that DTCs inhibited both interleukin 2 (IL-2) synthesis and membrane expression of antigens which are induced during T-cell activation. This inhibition, which occurred with a parallel activation of c-Jun transactivating functions and expression, was reflected by transfection experiments at the IL-2 promoter level, and involved not only the inhibition of NF-kappaB-driven reporter activation but also that of nuclear factor of activated T cells (NFAT). Accordingly, electrophoretic mobility shift assays (EMSAs) indicated that pyrrolidine DTC (PDTC) prevented NF-kappaB, and NFAT DNA-binding activity in T cells stimulated with either phorbol myristate acetate plus ionophore or antibodies against the CD3-T-cell receptor complex and simultaneously activated the binding of AP-1. Furthermore, PDTC differentially targeted both NFATp and NFATc family members, inhibiting the transactivation functions of NFATp and mRNA induction of NFATc. Strikingly, Western blotting and immunocytochemical experiments indicated that PDTC promoted a transient and rapid shuttling of NFATp and NFATc, leading to their accelerated export from the nucleus of activated T cells. We propose that the activation of an NFAT kinase by PDTC could be responsible for the rapid shuttling of the NFAT, therefore transiently converting the sustained transactivation of this transcription factor that occurs during lymphocyte activation, and show that c-Jun NH2-terminal kinase (JNK) can act by directly phosphorylating NFATp. In addition, the combined inhibitory effects on NFAT and NF-KB support a potential use of DTCs as immunosuppressants

Generation of lung epithelial-like tissue from human embryonic stem cells

<p>Abstract</p> <p>Background</p> <p>Human embryonic stem cells (hESC) have the capacity to differentiate <it>in vivo </it>and <it>in vitro </it>into cells from all three germ lineages. The aim of the present study was to investigate the effect of specific culture conditions on the differentiation of hESC into lung epithelial cells.</p> <p>Methods</p> <p>Undifferentiated hESC, grown on a porous membrane in hESC medium for four days, were switched to a differentiation medium for four days; this was followed by culture in air-liquid interface conditions during another 20 days. Expression of several lung markers was measured by immunohistochemistry and by quantitative real-time RT-PCR at four different time points throughout the differentiation and compared to appropriate controls.</p> <p>Results</p> <p>Expression of <it>CC16 </it>and <it>NKX2.1 </it>showed a 1,000- and 10,000- fold increase at day 10 of differentiation. Other lung markers such as <it>SP-C </it>and <it>Aquaporin 5 </it>had the highest expression after twenty days of culture, as well as two markers for ciliated cells, <it>FOXJ1 </it>and <it>β-tubulin IV</it>. The results from qRT-PCR were confirmed by immunohistochemistry on paraffin-embedded samples. Antibodies against CC16, SP-A and SP-C were chosen as specific markers for Clara Cells and alveolar type II cells. The functionality was tested by measuring the secretion of CC16 in the medium using an enzyme immunoassay.</p> <p>Conclusion</p> <p>These results suggest that by using our novel culture protocol hESC can be differentiated into the major cell types of lung epithelial tissue.</p