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The purpose of the study was to examine whether forgiveness and empathy have a significant correlation with psychological wellbeing among nurses. The present research will enable the theorist to develop measures that will cultivate empathy, forgiveness and psychological wellbeing in nurses. This was a correlational, survey based research. A sample of 151 nurses of age range 20-55 was selected via purposive sampling technique from Karachi, Pakistan. The participants were approached through online medium. The study variables were assessed through Toronto Empathy Questionnaire (Spreng et al., 2009), The Heartland Forgiveness scale (Thompson et al., 2005) and Ryff’s Psychological Well-Being Scales (Ryff, 1989). Statistical Package for Social Sciences (SPSS- Version 22) was used for analyzing the data, the results revealed that empathy and forgiveness are significant predictors of psychological wellbeing. Further findings of the research highlighted significant differences in empathy, forgiveness and psychological wellbeing with respect to nurse’s age, gender, education and family structure. The results of the present study could be useful for enhancing nurse’s psychological.

Background — The mental health of medical students has long been a concern. Symptoms of depression and burnout are common among medical students, but the overlap of symptoms of both diseases with risk factors remains unclear. The goal of this study was to determine the prevalence of burnout and depression symptoms’ overlap in medical students. Methods — This cross-sectional study was conducted among students of the clinical course (3rd, 4th and 5th years). A multistage stratified random sampling design was used to select 284students that were offered a validated and structured questionnaire that included a modified Oldenburg Burnout Inventory and Patient Health Questionnaire-9 to assess their emotional burnout and depression, respectively. Chi-square and multinomial regression analyses were done to identify overlapping symptoms of burnout and depression with association of risk factors with dependent variable. Results — Out of 284 students, 13% had symptoms of severe depression, 24% had high burnout symptoms, and 32% had overlapping symptoms of burnout and depression. In regression analysis, higher academic year more than 2 times (5th year, OR 2.03, 95% CI 1.42-7.96, p-value 0.004) and living at dormitory more than 3 times (OR 3.97, 95% CI 1.97-5.01, p-value 0.003) were more likely associated with more extensive overlap of burnout and depression symptoms. Conclusion — There is a high prevalence of burnout and depression symptoms among medical students, with a strong association between the two disorders. Early burnout detection and psychiatric therapies given to affected students and these disorders management training at medical school, may help reduce negative consequences of these conditions.

Background Accessible and quality care during the perinatal period is critical for optimal maternal and neonatal health. Using the socio-ecological model, the purpose of this study was to explore barriers and facilitators that shape the perinatal care experiences of people with intellectual and/or developmental disabilities (IDD). Methods Semi-structured interviews were conducted with 10 individuals with IDD in Ontario, Canada, who had given birth within the past 5 years. Interviews focused on care experiences before, during, and after pregnancy. Data were analyzed using a directed content analysis approach, and the socio-ecological model guided analysis. Results Barriers at the societal (e.g., cultural norms of motherhood), policy/institutional (e.g., child protection policies and practices), interpersonal (e.g., inadequate formal and informal support), and intrapersonal levels (e.g., internalized stigma) contributed to participants having negative perinatal care experiences. Conversely, we identified facilitators on the interpersonal level (e.g., positive interactions with perinatal care providers and familial and social service supports) as positively shaping participants’ perinatal care experiences. Conclusions Findings reveal that the perinatal care experiences of people with IDD are shaped by several interrelated factors that largely stem from societal-level barriers, such as dominant (stigmatizing) discourses of disability. To improve the perinatal care experiences of people with IDD, there is a need for interventions at multiple levels. These include the development of policies to support perinatal care for diverse populations and training care providers to enact policies at the institutional and interpersonal levels.

Background Emergency Departments (EDs) have served as critical surveillance sites for infectious diseases. We sought to determine the prevalence and temporal trends of acute (by PCR) and convalescent (by antibody [Ab]) SARS-CoV-2 infection during the earliest phase of the pandemic among patients in an urban ED in Baltimore City. Methods We tested remnant blood samples from 3255 unique ED patients, collected between March 16th and May 31st 2020 for SARS-CoV-2 Ab. PCR for acute SARS-CoV-2 infection from nasopharyngeal swabs was obtained on any patients based on clinical suspicion. Hospital records were abstracted and factors associated with SARS-CoV-2 infection were assessed. Results Of 3255 ED patients, 8.2% (95%CI: 7.3%, 9.2%) individuals had evidence of SARS-CoV-2 infection; 155 PCR+, 78 Ab+, and 35 who were both PCR+ and Ab+. Prevalence of disease increased throughout the study period, ranging from 3.2% (95%CI: 1.8%, 5.2%) PCR+ and 0.6% (95%CI: 0.1%, 1.8%) Ab+ in March, to 6.2% (95%CI: 5.1%, 7.4%) PCR+ and 4.2% (95%CI: 3.3%, 5.3%) Ab+ in May. The highest SARS-CoV-2 prevalence was found in Hispanic individuals who made up 8.4% (95%CI: 7.4%, 9.4%) of individuals screened, but 35% (95%CI: 29%, 41%) of infections (PCR and/or Ab+). Demographic and clinical factors independently associated with acute infection included Hispanic ethnicity, loss of smell or taste, subjective fever, cough, muscle ache and fever. Factors independently associated with convalescent infection were Hispanic ethnicity and low oxygen saturation. Conclusions The burden of COVID-19 in Baltimore City increased dramatically over the 11-week study period and was disproportionately higher among Hispanic individuals. ED-based surveillance methods are important for identifying both acute and convalescent SARS-CoV-2 infections and provides important information regarding demographic and clinical correlates of disease in the local community.

Current methods to evaluate gene-by-environment (GxE) interactions on biobank-scale datasets are limited. MonsterLM enables multiple linear regression on genome-wide datasets, does not rely on parameters specification and provides unbiased estimates of variance explained by GxE interaction effects. We applied MonsterLM to the UK Biobank for eight blood biomarkers (N=325,991), identifying significant genome-wide interaction variance with waist-to-hip ratio for five biomarkers, with variance explained by interactions ranging from 0.11 to 0.58. 48% to 94% of GxE interaction variance can be attributed to variants without significant marginal association with the phenotype of interest. Conversely, for most traits, >40% of interaction variance was explained by less than 5% of genetic variants. We observed significant improvements in polygenic score prediction with incorporation of GxE interactions in four biomarkers. Our results imply an important contribution of GxE interaction effects, driven largely by a restricted set of variants distinct from loci with strong marginal effects.

Mitochondrial DNA copy number (mtDNA-CN) is an accessible blood-based measurement believed to capture underlying mitochondrial function. The specific biological processes underpinning its regulation, and whether those processes are causative for disease, is an area of active investigation. We developed a novel method for array-based mtDNA-CN estimation suitable for biobank-scale studies, called “AutoMitoC”. We applied AutoMitoC to 395,781 UKBiobank study participants and performed genome and exome-wide association studies, identifying novel common and rare genetic determinants. Overall, genetic analyses identified 73 loci for mtDNA-CN, which implicated several genes involved in rare mtDNA depletion disorders, dNTP metabolism, and the mitochondrial central dogma. Rare variant analysis identified SAMHD1 mutation carriers as having higher mtDNA-CN (beta=0.23 SDs; 95% CI, 0.18-0.29; P=2.6×10−19), a potential therapeutic target for patients with mtDNA depletion disorders, but at increased risk of breast cancer (OR=1.91; 95% CI, 1.52-2.40; P=2.7×10−8). Finally, Mendelian randomization analyses suggest a causal effect of low mtDNA-CN on dementia risk (OR=1.94 per 1 SD decrease in mtDNA-CN; 95% CI, 1.55-2.32; P=7.5×10−4). Altogether, our genetic findings indicate that mtDNA-CN is a complex biomarker reflecting specific mitochondrial processes related to mtDNA regulation, and that these processes are causally related to human diseases.

We previously demonstrated that altering extracellular sodium (Nao) and calcium (Cao) can modulate a form of electrical communication between cardiomyocytes termed “ephaptic coupling” (EpC), especially during loss of gap junction coupling. We hypothesized that altering Nao and Cao modulates conduction velocity (CV) and arrhythmic burden during ischemia. Electrophysiology was quantified by optically mapping Langendorff-perfused guinea pig ventricles with modified Nao (147 or 155 mM) and Cao (1.25 or 2.0 mM) during 30 min of simulated metabolic ischemia (pH 6.5, anoxia, aglycemia). Gap junction-adjacent perinexal width ( WP), a candidate cardiac ephapse, and connexin (Cx)43 protein expression and Cx43 phosphorylation at S368 were quantified by transmission electron microscopy and Western immunoblot analysis, respectively. Metabolic ischemia slowed CV in hearts perfused with 147 mM Nao and 2.0 mM Cao; however, theoretically increasing EpC with 155 mM Nao was arrhythmogenic, and CV could not be measured. Reducing Cao to 1.25 mM expanded WP, as expected during ischemia, consistent with reduced EpC, but attenuated CV slowing while delaying arrhythmia onset. These results were further supported by osmotically reducing WP with albumin, which exacerbated CV slowing and increased early arrhythmias during ischemia, whereas mannitol expanded WP, permitted conduction, and delayed the onset of arrhythmias. Cx43 expression patterns during the various interventions insufficiently correlated with observed CV changes and arrhythmic burden. In conclusion, decreasing perfusate calcium during metabolic ischemia enhances perinexal expansion, attenuates conduction slowing, and delays arrhythmias. Thus, perinexal expansion may be cardioprotective during metabolic ischemia. NEW & NOTEWORTHY This study demonstrates, for the first time, that modulating perfusate ion composition can alter cardiac electrophysiology during simulated metabolic ischemia.

Chest pain with elevated serum troponin is a common clinical presentation and is normally managed as suspected myocardial infarction or acute coronary syndrome (ACS). We report a 49 year old man who presented with central chest pain sweating and breathlessness. He had a significantly elevated serum troponin I level and a subsequent angiogram showed near normal coronary arteries. He was subsequently investigated for fever and found to have a 3cm right sided adrenal mass consistent with a pheochromocytoma. After confirmation and appropriate blockade laparoscopic adrenalectomy was performed. Pheochromocytoma may present as a mimic of acute coronary syndrome but this is often unrecognized and leaves the patient at risk of future pheo crisis events which may be fatal.

A recently-described extracellular nanodomain, termed the perinexus, has been implicated in ephaptic coupling, which is an alternative mechanism for electrical conduction between cardiomyocytes. The current method for quantifying this space by manual segmentation is slow and has low spatial resolution.We developed an algorithm that uses serial image dilations of a binary outline to count the number of pixels between two opposing 2 dimensional edges.This algorithm requires fewer man hours and has a higher spatial resolution than the manual method while preserving the reproducibility of the manual process.In fact, experienced and novice investigators were able to recapitulate the results of a previous study with this new algorithm.The algorithm is limited by the human input needed to manually outline the perinexus and computational power mainly encumbered by a pre-existing pathfinding algorithm.However, the algorithm's high-throughput capabilities, high spatial resolution and reproducibility make it a versatile and robust measurement tool for use across a variety of applications requiring the measurement of the distance between any 2-dimensional (2D) edges.

Sepsis is characterized by systemic activation of coagulation and inflammation in response to microbial infection. Although cell-free DNA (cfDNA) released from activated neutrophils has antimicrobial properties, it may also exert harmful effects by activating coagulation and inflammation. The authors aimed to determine whether deoxyribonuclease (DNase) administration reduces cfDNA levels, attenuates coagulation and inflammation, suppresses organ damage, and improves outcome in a cecal ligation and puncture (CLP) model of polymicrobial sepsis. Healthy C57Bl/6 mice were subjected to CLP, a surgical procedure involving two punctures of the ligated cecum, or sham surgery (no ligation/puncture). Mice were given DNase or saline by intraperitoneal injection 2, 4, or 6 h after surgery. Two hours after treatment, organs were harvested and plasma levels of cfDNA, interleukin-6 (IL-6), IL-10, thrombin-antithrombin complexes, lung myeloperoxidase, creatinine, alanine transaminase, and bacterial load were quantified. Survival studies were also performed. The CLP-operated mice had rapid time-dependent elevations in cfDNA that correlated with elevations in IL-6, IL-10, and thrombin-antithrombin complexes and had organ damage in the lungs and kidneys. Administration of DNase at 2 h after CLP resulted in increased IL-6 and IL-10 levels and organ damage in the lungs and kidneys. In contrast, DNase administration at 4 or 6 h after CLP resulted in reduced cfDNA and IL-6 levels, increased IL-10, and suppressed organ damage and bacterial dissemination. Deoxyribonuclease administration every 6 h after CLP also rescued mice from death. Our studies are the first to demonstrate that delayed but not early administration of DNase may be protective in experimental sepsis.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) targets lipoprotein receptors for degradation, thereby reducing hepatic lipid clearance. PCSK9 inhibition reduces mortality in septic mice, presumably through increased hepatic clearance of pathogen lipids due to increased lipoprotein receptor concentrations. However, PCSK9 overexpression in vivo has not been studied in sepsis. Therefore, this study aimed to evaluate the effects of differential PCSK9 expression on systemic infection, inflammation, and coagulation in sepsis.Wild-type, PCSK9 knockout (KO), and transgenic (Tg) mice that overexpress PCSK9 were subjected to sham surgery or cecal ligation and puncture (CLP). Bacterial loads were measured in lungs, peritoneal cavity fluid, and blood. Organ pathology was assessed in lungs, liver, and kidneys. Lung myeloperoxidase activity, and plasma concentrations of alanine aminotransferase (ALT), creatinine, cell-free DNA (cfDNA), protein C, thrombin-antithrombin (TAT) complexes, interleukin (IL)-6, and IL-10 were also measured 6 h postoperatively. Morbidity was assessed for 16 h following CLP.Overexpression of PCSK9 in mice increased liver and kidney pathology, plasma IL-6, ALT, and TAT concentrations during sepsis, whereas PCSK9 KO mice exhibited reduced bacterial loads, lung and liver pathology, myeloperoxidase activity, plasma IL-10, and cfDNA during CLP-induced sepsis. All septic mice had reduced plasma levels of protein C, but the protein C ratio relative to normal was significantly decreased in PCSK9 Tg mice. Dyspnea, cyanosis, and overall grimace scores were greatest in septic mice overexpressing PCSK9, whereas PCSK9 KO mice retained core body temperature during sepsis.These findings demonstrate that PCSK9 deficiency confers protection against systemic bacterial dissemination, organ pathology, and tissue inflammation, particularly in the lungs and liver, while PCSK9 overexpression exacerbates multi-organ pathology as well as the hypercoagulable and pro-inflammatory states in early sepsis.

Sepsis, a global health issue, is the most common cause of mortality in the intensive care unit. The aim of this study was to develop a new model of sepsis that investigates the impact of prolonged western diet (WD) induced obesity on the response to early sepsis. Male C57BL/6 mice were fed either a high fat WD or normal chow diet (NCD) for 6, 15, or 27 weeks. Septic obese mice at 15 and 27 weeks had significantly lower levels of lung myeloperoxidase (26.3 ± 3.80 U/mg tissue) compared to age matched ad lib (44.1 ± 2.86 U/mg tissue) and diet restricted (63.2 ± 5.60 U/mg tissue) controls. Low levels of lung inflammation were not associated with changes in hepatic cytokines and oxidative stress levels. Obese mice had significantly (P<0.0001) larger livers compared to controls. Histological examination of the livers demonstrated that WD fed mice had increased inflammation with pronounced fat infiltration, steatosis, and hepatocyte ballooning. Using this model of prolonged exposure to high fat diet we have data that agree with recent clinical observations suggesting obese individuals are protected from sepsis-induced lung injury. This model will allow us to investigate the links between damage to the hepatic microcirculation, immune response, and lung injury.

BACKGROUND: Sepsis is a leading cause of mortality among critically ill patients and is associated with both systemic inflammation and up-regulation of coagulation. In the translational sub-study of the HALO (Heparin AnticoaguLation to improve Outcomes in septic shock) pilot trial, we evaluated the mechanisms by which unfractionated heparin (UFH) may reduce inflammation and coagulation in patients with septic shock. METHODS: In this multicenter pilot randomized trial of 69 patients diagnosed with septic shock, we evaluated the feasibility of administering therapeutic dose intravenous UFH (18 IU/kg/hr) compared to thromboprophylactic subcutaneous dalteparin (5000 IU daily). Blood samples were collected on days 1 (baseline prior to study infusion), 2, 3, 5, and 7. We evaluated coagulation using assays for protein C, activated protein C, thrombin-antithrombin (TAT), thrombin generation, clot lysis, plasminogen activator inhibitor-1 (PAI-1) and cell-free DNA (cf-DNA). Systematic inflammation was evaluated by measuring inflammatory cytokines (interleukin (IL)-6, IL-8, IL-10, and IL-17). RESULTS: The mean age of the study population was 61 years, of whom 43% were male. Thirty two patients (46%) were randomized to receive unfractionated heparin while 37 (54%) received dalteparin. The baseline mean aggregate Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 25 ± 7.8, and Multiple Organ Dysfunction Score (MODS) 5.6 ± 2.38. Baseline laboratory testing (coagulation assays and inflammatory cytokines) was not statistically different between UFH vs. LMWH treated patients. On day 2, the median clot lysis time in UFH-treated patients compared to those receiving dalteparin was significantly decreased [6630 (IQR 0 - 14156) seconds vs. 9615 (IQR 8209 - 11018) seconds; p = 0.008] (Figure 1). UFH administration was associated with increased protein C levels [66.4% of normal (IQR 9.9 - 122.9) vs. 41.1% of normal (IQR 4.8 - 77.4); p = 0.02], and reduced thrombin generation of 0 (IQR 0 - 1725) units/min vs. 3393 (IQR 0 - 8519) units/min; p CONCLUSION: In patients diagnosed with septic shock, IV UFH reduces thrombin generation, shortens clot lysis time and improves endogenous protein C levels compared to dalteparin administered for thromboprophylaxis. Analyses for samples obtained on days 3, 5 and 7 are ongoing. These preliminary data provide a biologic rational for the use of heparin in sepsis. Figure 1. Differences in clot lysis, protein C and thrombin generation in patients treated with UFH vs. LMWH. UFH is associated with reduced thrombin generation, improved Protein C levels, and reduced clot lysis time. Figure 1. Differences in clot lysis, protein C and thrombin generation in patients treated with UFH vs. LMWH. UFH is associated with reduced thrombin generation, improved Protein C levels, and reduced clot lysis time. Disclosures No relevant conflicts of interest to declare.