Ischemia Induces P-Selectin-Mediated Selective Progenitor Cell Engraftment in the Isolated-Perfused Heart

Clinical trials infusing Bone Marrow Cells (BMCs) into injured hearts have produced measureable improvements in cardiac performance, but were insufficient to improve patient outcomes. Low engraftment rates are cited as probable contributor to limited improvements. To understand the mechanisms that control myocardial engraftment of BMCs following ischemia-reperfusion injury, in isolated–perfused mouse hearts, stop-flow ischemia was followed by variable-duration reperfusion (0–60 min) before addition of labeled syngenic BMCs to the perfusate. After a buffer-only wash, the heart was disaggregated. Retained BMCs (digest) and infused BMCs (aliquot) were compared by flow cytometry for c-kit and CD45 expression to determine the proportion of cell subtypes engrafted versus delivered (selectivity ratio). In these studies, a time-dependent selective retention of c-kit+ cells was apparent starting at 30 min of reperfusion, at which time c-kit+/CD45+ BMCs showed a selectivity ratio of 18 ± 2 (versus 2 ± 1 in sham-ischemic controls). To study the underlying mechanism for this selective retention, neutralizing antibodies for P-selectin or L-selectin were infused into the heart preparation and incubated with BMCs prior to BMC infusion. Blocking P-selectin in ischemic hearts ablated selectivity for c-kit+/CD45+ BMCs at 30 min reperfusion (selectivity ratio of 3 ± 1) while selectivity persisted in the presence of L-selectin neutralization (selectivity ratio of 17 ± 2). To corroborate this finding, a parallel plate flow chamber was used to study capture and rolling dynamics of purified c-kit+ versus c-kit- BMCs on various selectin molecules. C-kit+ BMCs interacted weakly with L-selectin substrates (0.03 ± 0.01% adhered) but adhered strongly to P-selectin (0.28 ± 0.04% adhered). C-kit- BMCs showed intermediate binding regardless of substrate (0.18 ± 0.04% adhered on L-selectin versus 0.17 ± 0.04% adhered on P-selectin). Myocardial ischemia–reperfusion stress induces selective engraftment of c-kit+ bone marrow progenitor cells via P-selectin activation

The impact of COVID-19 on the psychological well-being of surgeons in Pakistan: A multicenter cross-sectional study

Introduction The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic left a profound and pervasive impact on the healthcare infrastructure on a global scale. Since its onset, the pattern of reported cases and its associated mortality had shown variability with intermittent peaks causing a significant effect on the psychological well-being of the surgeons of Pakistan. The aim of this study was to assess the effects of the COVID-19 pandemic on the mental well-being of surgeons in Pakistan. Methods This multicenter cross-sectional study was carried out to assess the impact of COVID-19 on the psychological well-being of surgeons in Pakistan. The validated Self-Reporting Questionnaire-20 (SRQ-20) tool was circulated electronically via Google Forms (Google, Inc., Mountain View, CA, USA) in the practicing surgical fraternity across all five regions of Pakistan, i.e., Sindh, Punjab, Baluchistan, Khyber Pakhtunkhwa (KPK), and Azad Jammu and Kashmir (AJK). Results This study showed that the female gender, having fewer years of working experience, non-satisfaction with the available personal protective equipment (PPE), and working in the public sector were the factors affecting the psychological well-being of surgeons during the pandemic. Conclusion Considering the continuous rise in new cases during the ongoing pandemic, the mental health of surgeons working in low- and middle-income countries (LMIC) such as Pakistan has been significantly affected. There is an undeniable need to pay close attention to their psychological well-being. Measures need to be undertaken to ensure their physical and mental health and wellness