The healing myocardium mobilizes a distinct B-cell subset through a CXCL13-CXCR5-dependent mechanism.

AIMS: Recent studies have revealed that B cells and antibodies can influence inflammation and remodelling following a myocardial infarction (MI) and culminating in heart failure-but the mechanisms underlying these observations remain elusive. We therefore conducted in mice a deep phenotyping of the post-MI B-cell responses in infarcted hearts and mediastinal lymph nodes, which drain the myocardium. Thereby, we sought to dissect the mechanisms controlling B-cell mobilization and activity in situ. METHODS AND RESULTS: Histological, flow cytometry, and single-cell RNA-sequencing (scRNA-seq) analyses revealed a rapid accumulation of diverse B-cell subsets in infarcted murine hearts, paralleled by mild clonal expansion of germinal centre B cells in the mediastinal lymph nodes. The repertoire of cardiac B cells was largely polyclonal and showed no sign of antigen-driven clonal expansion. Instead, it included a distinct subset exclusively found in the heart, herein termed 'heart-associated B cells' (hB) that expressed high levels of Cd69 as an activation marker, C-C-chemokine receptor type 7 (Ccr7), CXC-chemokine receptor type 5 (Cxcr5), and transforming growth factor beta 1 (Tgfb1). This distinct signature was not shared with any other cell population in the healing myocardium. Moreover, we detected a myocardial gradient of CXC-motif chemokine ligand 13 (CXCL13, the ligand of CXCR5) on Days 1 and 5 post-MI. When compared with wild-type controls, mice treated with a neutralizing CXCL13-specific antibody as well as CXCR5-deficient mice showed reduced post-MI infiltration of B cells and reduced local Tgfb1 expression but no differences in contractile function nor myocardial morphology were observed between groups. CONCLUSION: Our study reveals that polyclonal B cells showing no sign of antigen-specificity readily infiltrate the heart after MI via the CXCL13-CXCR5 axis and contribute to local TGF-ß1 production. The local B-cell responses are paralleled by mild antigen-driven germinal centre reactions in the mediastinal lymph nodes that might ultimately lead to the production of specific antibodies.

An observational ergonomic tool for assessing the worn condition of slip-resistant shoes.

Worn shoes are known to contribute to slip-and-fall risk, a common cause of workplace injuries. However, guidelines for replacing shoes are not well developed. Recent experiments and lubrication theory suggest that the size of the worn region is an important contributor to the shoe tread's ability to drain fluid and therefore the under-shoe friction. This study evaluated a simple test for comparing the size of the worn region relative to a common object (AAA and AA battery) as a means of determining shoe replacement. This study consisted of three components involving slip-resistant shoes: Experiment #1: a longitudinal, mechanical, accelerated wear experiment; Experiment #2: a longitudinal experiment where the same shoes were tested after each month of worker use; and Experiment #3: a cross-sectional experiment that exposed participants to a slippery condition, while donning their own worn shoes. The COF (Experiments #1 and #2); under-shoe fluid pressure (all experiments); and slip severity (Experiment #3) were compared across outcomes (fail/pass) of the battery tests. Larger fluid pressures, lower coefficient of friction, and more severe slips were observed for shoes that failed the battery tests compared with those passing the tests. This method offers promise for assessing loss in friction and an increase in slip risk for slip-resistant shoes.

Extravascular lung water and its association with weight, height, age, and gender: a study in intensive care unit patients.

PURPOSE: With regard to large inter-individual variability of height, body weight (BW), and age, several hemodynamic parameters are adjusted for biometric data. This also applies to extravascular lung water (EVLW), which traditionally was indexed to actual BW (BW-act) resulting in EVLW-index (EVLWI; i.e., EVLWI-act). Since indexation to BW-act might inappropriately diminish EVLWI-act in obese patients, the indexation has been changed to predicted BW (BW-pred) resulting in EVLWI-pred. BW-pred is a weight estimation formula calculated from height and gender that has not been derived from population-based data. The aim of the study was to investigate the independent association of biometric data with EVLW. METHODS: We analyzed a hemodynamic monitoring database including 3,691 transpulmonary thermodilution-derived EVLW measurements (234 consecutive patients; intensive care unit of a university hospital). We performed univariate and multivariate analyses regarding the association of biometric data with the first EVLW measurement and the mean EVLW value of each patient. RESULTS: In univariate analysis, the first EVLW significantly correlated with height (r = 0.254; p < 0.001), but neither with age nor BW-act. Similar findings were made in the analysis of the patients' EVLW means of all measurements ("one point per patient"). In multivariate analysis (primary endpoint), including BW-act, height, age, and gender, only height was independently associated with EVLW, with each centimeter of height increasing the first measurement of EVLW by 6.882 mL (p < 0.001) and mean EVLW by 6.727 mL (p < 0.001). CONCLUSIONS: Height is the only biometric parameter independently associated with the first and mean EVLW. In adult patients, EVLW should be indexed to height.