Myeloid-Specific Deletion of Mcl-1 Yields Severely Neutropenic Mice That Survive and Breed in Homozygous Form

Mouse strains with specific deficiency of given hematopoietic lineages provide invaluable tools for understanding blood cell function in health and disease. Whereas neutrophils are dominant leukocytes in humans and mice, there are no widely useful genetic models of neutrophil deficiency in mice. In this study, we show that myeloid-specific deletion of the Mcl-1 antiapoptotic protein in Lyz2Cre/CreMcl1flox/flox (Mcl1ΔMyelo) mice leads to dramatic reduction of circulating and tissue neutrophil counts without affecting circulating lymphocyte, monocyte, or eosinophil numbers. Surprisingly, Mcl1ΔMyelo mice appeared normally, and their survival was mostly normal both under specific pathogen-free and conventional housing conditions. Mcl1ΔMyelo mice were also able to breed in homozygous form, making them highly useful for in vivo experimental studies. The functional relevance of neutropenia was confirmed by the complete protection of Mcl1ΔMyelo mice from arthritis development in the K/B×N serum-transfer model and from skin inflammation in an autoantibody-induced mouse model of epidermolysis bullosa acquisita. Mcl1ΔMyelo mice were also highly susceptible to systemic Staphylococcus aureus or Candida albicans infection, due to defective clearance of the invading pathogens. Although neutrophil-specific deletion of Mcl-1 in MRP8-CreMcl1flox/flox (Mcl1ΔPMN) mice also led to severe neutropenia, those mice showed an overt wasting phenotype and strongly reduced survival and breeding, limiting their use as an experimental model of neutrophil deficiency. Taken together, our results with the Mcl1ΔMyelo mice indicate that severe neutropenia does not abrogate the viability and fertility of mice, and they provide a useful genetic mouse model for the analysis of the role of neutrophils in health and disease

Burnout and Occupational Stress Among Hungarian Radiographers Working in Emergency and Non-Emergency Departments During COVID-19 Pandemic

Introduction: The increased workload caused by the coronavirus pandemic may have had a significant impact on the mental health of radiographers. The aim of our study was to investigate burnout and occupational stress in radiographers working in emergency departments (ED) and non-emergency departments (NED). Methods: Quantitative, cross-sectional, descriptive research was carried out among radiographers working in the public health sector in Hungary. Due to the cross-sectional nature of our survey, there was no overlap between the ED and NED groups. For data collection, we used simultaneously the Maslach Burnout Inventory (MBI), the Effort-Reward Imbalance questionnaire (ERI), and our self-designed questionnaire. Results: We excluded incomplete questionnaires from our survey; finally, 439 responses were evaluated. Significantly higher scores for depersonalisation (DP; 8.43 (SD = 6.69) vs. 5.63 (SD = 4.21) and emotional exhaustion (EE; 25.07 (SD = 11.41) vs. 19.72 (SD = 11.72)) were observed in radiographers working in ED (p = 0.001; p = 0.001) when compared to NED. Male radiographers working in ED aged 20–29 and 30–39 years with experience of 1–9 years were more affected by DP (p ≤ 0.05). Worrying about one's own health had a negative effect on DP and EE (p ≤ 0.05). Having close friend with a COVID-19 infection had a negative effect on EE (p ≤ 0.05); not being infected with coronavirus, not being quarantined and relocating within the workplace had a positive effect on personal accomplishment (PA); radiographers who were 50 years or older with 20–29 years of experience were more affected by depersonalisation (DP); and those who worried about their health had significantly higher stress scores (p ≤ 0.05) in both ED and NED settings. Conclusion: Male radiographers at the beginning of their careers were more affected by burnout. Employment in EDs had a negative impact on DP and EE. Implications for practice: Our results support the implementation of interventions to counter the effects of occupational stress and burnout among radiographers working in ED

Update on protein biomarkers in traumatic brain injury with emphasis on clinical use in adults and pediatrics

Purpose This review summarizes protein biomarkers in mild and severe traumatic brain injury in adults and children and presents a strategy for conducting rationally designed clinical studies on biomarkers in head trauma. Methods We performed an electronic search of the National Library of Medicine’s MEDLINE and Biomedical Library of University of Pennsylvania database in March 2008 using a search heading of traumatic head injury and protein biomarkers. The search was focused especially on protein degradation products (spectrin breakdown product, c-tau, amyloid-β1–42) in the last 10 years, but recent data on “classical” markers (S-100B, neuron-specific enolase, etc.) were also examined. Results We identified 85 articles focusing on clinical use of biomarkers; 58 articles were prospective cohort studies with injury and/or outcome assessment. Conclusions We conclude that only S-100B in severe traumatic brain injury has consistently demonstrated the ability to predict injury and outcome in adults. The number of studies with protein degradation products is insufficient especially in the pediatric care. Cohort studies with welldefined end points and further neuroproteomic search for biomarkers in mild injury should be triggered. After critically reviewing the study designs, we found that large homogenous patient populations, consistent injury, and outcome measures prospectively determined cutoff values, and a combined use of different predictors should be considered in future studies