Myocardial SERCA2 Protects Against Cardiac Damage and Dysfunction Caused by Inhaled Bromine.

Myocardial sarcoendoplasmic reticulum calcium ATPase 2 (SERCA2) activity is critical for heart function. We have demonstrated that inhaled halogen (chlorine or bromine) gases inactivate SERCA2, impair calcium homeostasis, increase proteolysis, and damage the myocardium ultimately leading to cardiac dysfunction. To further elucidate the mechanistic role of SERCA2 in halogen-induced myocardial damage, we used bromine-exposed cardiac-specific SERCA2 knockout (KO) mice [tamoxifen-administered SERCA2 (flox/flox) Tg (αMHC-MerCreMer) mice] and compared them to the oil-administered controls. We performed echocardiography and hemodynamic analysis to investigate cardiac function 24 hours after bromine (600 ppm for 30 minutes) exposure and measured cardiac injury markers in plasma and proteolytic activity in cardiac tissue and performed electron microscopy of the left ventricle (LV). Cardiac-specific SERCA2 knockout mice demonstrated enhanced toxicity to bromine. Bromine exposure increased ultrastructural damage, perturbed LV shape geometry, and demonstrated acutely increased phosphorylation of phospholamban in the KO mice. Bromine-exposed KO mice revealed significantly enhanced mean arterial pressure and sphericity index and decreased LV end diastolic diameter and LV end systolic pressure when compared with the bromine-exposed control FF mice. Strain analysis showed loss of synchronicity, evidenced by an irregular endocardial shape in systole and irregular vector orientation of contractile motion across different segments of the LV in KO mice, both at baseline and after bromine exposure. These studies underscore the critical role of myocardial SERCA2 in preserving cardiac ultrastructure and function during toxic halogen gas exposures. SIGNIFICANCE STATEMENT: Due to their increased industrial production and transportation, halogens such as chlorine and bromine pose an enhanced risk of exposure to the public. Our studies have demonstrated that inhalation of these halogens leads to the inactivation of cardiopulmonary SERCA2 and results in calcium overload. Using cardiac-specific SERCA2 KO mice, these studies further validated the role of SERCA2 in bromine-induced myocardial injury. These studies highlight the increased susceptibility of individuals with pathological loss of cardiac SERCA2 to the effects of bromine.

Obesity does not impact complications and conversion to total knee arthroplasty after high tibial osteotomy: A systematic review.

PURPOSE: The purpose of this systematic review is to consolidate outcomes of obese patients undergoing high tibial osteotomy and to investigate the effect of obesity on postoperative outcomes, including symptomatic relief and time to conversion to arthroplasty. METHODS: Medline, Embase and Cochrane Library were searched from database inception up to April 2023 according to PRISMA guidelines by two reviewers. Search terms including 'obesity', 'BMI', 'osteotomy' and 'high tibial osteotomy (HTO)' were included to identify all relevant articles. Only studies that explicitly reported outcomes for obese patients were included. Disagreements in study inclusion or quality assessment were resolved by a senior third reviewer. Metrics compared include time to arthroplasty, preoperative and postoperative mechanical tibiofemoral angle (mTFA), patient-reported satisfaction scores and postoperative complications. RESULTS: Nine studies comparing 973 patients were included. The mean age was 52.7 ± 4.2 years old and 38.4% were male. Six studies performed the medial opening-wedge HTO, and three utilized the medial wedge closing technique. Most studies indicated significant improvement following surgical intervention with satisfactory outcomes in obese and nonobese patients. In addition, differences in complication rates were minimal between obese and nonobese patients (n.s.), while functional scores did not vary significantly. Conversion to total knee arthroplasty was not found to increase in obese patients (n.s.). CONCLUSION: Obesity does not appear to carry a greater complication risk or worse outcomes following high tibial osteotomies, and surgeons should consider HTO a viable option for young obese patients with symptomatic unicompartmental chondral wear with coronal limb malalignment. LEVEL OF EVIDENCE: Level IV.

Depression, Anxiety, and Stress Among Nurses During the COVID-19 Wave III: Results of a Cross-Sectional Assessment.

PURPOSE: The current study was aimed to evaluate depression, anxiety, and stress among nurses during the COVID-19 (wave III) at a public hospital in Quetta city, Pakistan. PARTICIPANTS AND METHODS: By using the validated Depression, Anxiety and Stress Scale - 21, three hundred and twenty-five nurses practicing at the Sandeman Provincial Hospital, Quetta were approached for data collection. Through SPSS, both descriptive and inferential statistics were used during data analysis. Chi-square test was used to assess the goodness-of-fit between observed values and demographic variables. The factors that were significantly associated with depression, anxiety, and stress were further assessed by binary logistic regression analysis. The statistical significance was set at 0.05. RESULTS: Out of the 325 nurses, 297 participated in the study with a response rate of 91.3%. Mild depression and stress were reported in the current cohort of nurses (6.00 ± 5.30 and 8.01 ± 4.47), respectively. The mean anxiety score was 6.68 ± 4.86 indicating moderate anxiety among the study respondents. Marital status, working department, and job experience were significantly associated with depression, anxiety, and stress with moderate effect size (>0.3). The logistic regression reported department in which nurses were stationed (adjusted OR = 2.54, 95% CI = 1.118-1.415, p < 0.001) and job experience (adjusted OR = 1.004, 95% CI = 1.001-1.215, p = 0.002) as significant predictors of depression, anxiety and stress. Nurses working in the corona ward were more likely to develop depression, anxiety and stress by a factor of 2.54 and married nurses with a factor of 1.004 provided controlling other confounding factors. CONCLUSION: Moderate depression, anxiety, and stress were observed among nurses and it calls for hospital management to consider interventions for all nurses irrespective of their present working departments. Facilitating continuous and comprehensive support mechanisms aimed at protecting nurses' mental health is of great importance during pandemics. The findings of the study have some clear suggestions for mental health advocacy among nurses that are essential for improving the quality of services and patients' safety.