CD19 + CD21lo/neg cells are increased in systemic sclerosis-associated interstitial lung disease

Interstitial lung disease (ILD) represents a significant cause of morbidity and mortality in systemic sclerosis (SSc). The purpose of this study was to examine recirculating lymphocytes from SSc patients for potential biomarkers of interstitial lung disease (ILD). Peripheral blood mononuclear cells (PBMCs) were isolated from patients with SSc and healthy controls enrolled in the Vanderbilt University Myositis and Scleroderma Treatment Initiative Center cohort between 9/2017–6/2019. Clinical phenotyping was performed by chart abstraction. Immunophenotyping was performed using both mass cytometry and fluorescence cytometry combined with t-distributed stochastic neighbor embedding analysis and traditional biaxial gating. This study included 34 patients with SSc-ILD, 14 patients without SSc-ILD, and 25 healthy controls. CD21^lo/neg cells are significantly increased in SSc-ILD but not in SSc without ILD (15.4 ± 13.3% vs. 5.8 ± 0.9%, p = 0.002) or healthy controls (5.0 ± 0.5%, p < 0.0001). While CD21^lo/neg B cells can be identified from a single biaxial gate, tSNE analysis reveals that the biaxial gate is comprised of multiple distinct subsets, all of which are increased in SSc-ILD. CD21^lo/neg cells in both healthy controls and SSc-ILD are predominantly tBET positive and do not have intracellular CD21. Immunohistochemistry staining demonstrated that CD21^lo/neg B cells diffusely infiltrate the lung parenchyma of an SSc-ILD patient. Additional work is needed to validate this biomarker in larger cohorts and longitudinal studies and to understand the role of these cells in SSc-ILD.

     

Update PONV – Was gibt es Neues bei der Prophylaxe und Therapie von postoperativer Übelkeit und postoperativem Erbrechen?

Die Anaesthesiologie - Auch wenn für Anästhesiologen über Jahrzehnte die Prophylaxe und Therapie postoperativer Schmerzen im Rahmen des postoperativen Patientenkomforts an vorderster...     

Interrelationships between Cellular Density,Mosaic Patterning,and Dendritic Coverage of VGluT3 Amacrine Cells

Amacrine cells of the retina are conspicuously variable in their morphologies, their population demographics, and their ensuing functions. Vesicular glutamate transporter 3 (VGluT3) amacrine cells are a recently characterized type of amacrine cell exhibiting local dendritic autonomy. The present analysis has examined three features of this VGluT3 population, including their density, local distribution, and dendritic spread, to discern the extent to which these are interrelated, using male and female mice. We first demonstrate that Bax-mediated cell death transforms the mosaic of VGluT3 cells from a random distribution into a regular mosaic. We subsequently examine the relationship between cell density and mosaic regularity across recombinant inbred strains of mice, finding that, although both traits vary across the strains, they exhibit minimal covariation. Other genetic determinants must therefore contribute independently to final cell number and to mosaic order. Using a conditional KO approach, we further demonstrate that Bax acts via the bipolar cell population, rather than cell-intrinsically, to control VGluT3 cell number. Finally, we consider the relationship between the dendritic arbors of single VGluT3 cells and the distribution of their homotypic neighbors. Dendritic field area was found to be independent of Voronoi domain area, while dendritic coverage of single cells was not conserved, simply increasing with the size of the dendritic field. Bax-KO retinas exhibited a threefold increase in dendritic coverage. Each cell, however, contributed less dendrites at each depth within the plexus, intermingling their processes with those of neighboring cells to approximate a constant volumetric density, yielding a uniformity in process coverage across the population.SIGNIFICANCE STATEMENT Different types of retinal neuron spread their processes across the surface of the retina to achieve a degree of dendritic coverage that is characteristic of each type. Many of these types achieve a constant coverage by varying their dendritic field area inversely with the local density of like-type neighbors. Here we report a population of retinal amacrine cells that do not develop dendritic arbors in relation to the spatial positioning of such homotypic neighbors; rather, this cell type modulates the extent of its dendritic branching when faced with a variable number of overlapping dendritic fields to approximate a uniformity in dendritic density across the retina.     

Influences of simulated gastrointestinal environment on physicochemical properties of gold nanoparticles and their implications on intestinal epithelial permeability

Gold nanoparticles (Au NPs) hold great promise in food, industrial and biomedical applications due to their unique physicochemical properties. However, influences of the gastrointestinal tract (GIT), a likely route for Au NPs administration, on the physicochemical properties of Au NPs has been rarely evaluated. Here, we investigated the influence of GIT fluids on the physicochemical properties of Au NPs (5, 50, and 100?nm) and their implications on intestinal epithelial permeability in vitro. Au NPs aggregated in fasted gastric fluids and generated hydroxyl radicals in the presence of H₂O₂. Cell studies showed that GIT fluids incubation of Au NPs affected the cellular uptake of Au NPs but did not induce cytotoxicity or disturb the intestinal epithelial permeability.     

‘I believe high blood pressure can kill me:’ using the PEN-3 Cultural Model to understand patients’ perceptions of an intervention to control hypertension in Ghana

Objectives: Currently in Ghana, there is an on-going task-shifting strategy in which nurses are trained in hypertension management. While this study will provide useful information on the viability of this approach, it is not clear how patients in the intervention perceive hypertension, the task-shifting strategy, and its effects on blood pressure management. The objective of this paper is to examine patients’ perceptions of hypertension and hypertension management in the context of an on-going task-shifting intervention to manage blood pressure control in Ghana.

Design: Forty-two patients participating in the Task Shifting Strategy for Hypertension program (23 males, 19 females, and mean age 61. 7 years) completed in-depth, qualitative interviews. Interviews were transcribed, and key words and phrases were extracted and coded using the PEN-3 Cultural Model as a guide through open and axial coding techniques, thus allowing rich exploration of the data.

Results: Emergent themes included patients’ perceptions of hypertension, which encompassed misperceptions of hypertension and blood pressure control. Additional themes included enablers and barriers to hypertension management, and how the intervention nurtured lifestyle change associated with blood pressure control. Primary enabling factors included the supportive nature of TASSH nurses, while notable barriers were financial constraints and difficulty accessing medication. Nurturing factors included the motivational interviewing and patient counseling which instilled confidence in the patients that they could make lasting behavior changes.

Conclusions: This study offers a unique perspective of blood pressure control by examining how patients view an on-going task-shifting initiative for hypertension management. The results of this study shed light on factors that can help and hinder individuals in low-resource settings with long-term blood pressure management.