The mental health toll of COVID-19 on healthcare workers (HCW) is not yet fully described. We characterized distress, coping, and preferences for support among NYC HCWs during the COVID-19 pandemic. Methods: This was a cross-sectional web survey of physicians, advanced practice providers, residents/fellows, and nurses, conducted during a peak of inpatient admissions for COVID-19 in NYC (April 9th-April 24th 2020) at a large medical center in NYC (n = 657). Results: Positive screens for psychological symptoms were common; 57% for acute stress, 48% for depressive, and 33% for anxiety symptoms. For each, a higher percent of nurses/advanced practice providers screened positive vs. attending physicians, though housestaff's rates for acute stress and depression did not differ from either. Sixty-one percent of participants reported increased sense of meaning/purpose since the COVID-19 outbreak. Physical activity/exercise was the most common coping behavior (59%), and access to an individual therapist with online self-guided counseling (33%) garnered the most interest. Conclusions: NYC HCWs, especially nurses and advanced practice providers, are experiencing COVID-19-related psychological distress. Participants reported using empirically-supported coping behaviors, and endorsed indicators of resilience, but they also reported interest in additional wellness resources. Programs developed to mitigate stress among HCWs during the COVID-19 pandemic should integrate HCW preferences.

Ceramide is among a number of potential lipotoxic molecules that are thought to modulate cellular energy metabolism. The heart is one of the tissues thought to become dysfunctional due to excess lipid accumulation. Dilated lipotoxic cardiomyopathy, thought to be the result of diabetes and severe obesity, has been modeled in several genetically altered mice, including animals with cardiac-specific overexpression of glycosylphosphatidylinositol (GPI)-anchored human lipoprotein lipase (LpL GPI ). To test whether excess ceramide was implicated in cardiac lipotoxicity, de novo ceramide biosynthesis was inhibited pharmacologically by myriocin and genetically by heterozygous deletion of LCB1, a subunit of serine palmitoyltransferase (SPT). Inhibition of SPT, a rate-limiting enzyme in ceramide biosynthesis, reduced fatty acid and increased glucose oxidation in isolated perfused LpL GPI hearts, improved systolic function, and prolonged survival rates. Our results suggest a critical role for ceramide accumulation in the pathogenesis of lipotoxic cardiomyopathy.-Park, T

Three forms of PPARs are expressed in the heart. In animal models, PPARγ agonist treatment improves lipotoxic cardiomyopathy; however, PPARγ agonist treatment of humans is associated with peripheral edema and increased heart failure. To directly assess effects of increased PPARγ on heart function, we created transgenic mice expressing PPARγ1 in the heart via the cardiac α-myosin heavy chain (α-MHC) promoter. PPARγ1-transgenic mice had increased cardiac expression of fatty acid oxidation genes and increased lipoprotein triglyceride (TG) uptake. Unlike in cardiac PPARα-transgenic mice, heart glucose transporter 4 (GLUT4) mRNA expression and glucose uptake were not decreased. PPARγ1-transgenic mice developed a dilated cardiomyopathy associated with increased lipid and glycogen stores, distorted architecture of the mitochondrial inner matrix, and disrupted cristae. Thus, while PPARγ agonists appear to have multiple beneficial effects, their direct actions on the myocardium have the potential to lead to deterioration in heart function.

Objectives To assess the independent effect of increased body size on left ventricular (LV) diastolic function. Background Obese and overweight individuals are at increased risk of heart failure. LV diastolic dysfunction is an asymptomatic condition associated with future heart failure. It is unclear whether obesity and overweight are independently associated with LV diastolic dysfunction. Methods LV diastolic function was evaluated in 950 participants from the Cardiovascular Abnormalities and Brain Lesions (CABL) study by traditional and tissue-Doppler imaging. Peak early and late trans-mitral diastolic flow velocities (E, A) and early diastolic mitral annulus velocity (E′) were measured, and E/A and E/E′ were calculated. The study sample was divided into three groups: normal weight [body mass index (BMI)<25.0], overweight (BMI 25.0–29.9) and obese (BMI≥30). Results In multivariate analyses, BMI was independently associated with higher E, A, and E/E′, an indicator of LV filling pressure (all p≤0.01). Overweight and obese had lower E′ (both p<0.01) and higher E/E′ (both p<0.01) than normal weight participants. E/A was lower in obese than normal weight subjects (p<0.01). The risk of diastolic dysfunction was significantly higher in overweight (adjusted odds ratio: 1.52, 95% confidence intervals 1.04–2.22) and obese (adjusted odds ratio: 1.60, 95% confidence intervals 1.06–2.41) compared to normal weight individuals. Conclusions Increased BMI was associated with worse LV diastolic function independent of LV mass and associated risk factors. The increased risk of LV diastolic dysfunction in both overweight and obese individuals may partially account for the increased risk of heart failure associated with both conditions.

Rationale Efficient clearance of apoptotic cells (efferocytosis) is a prerequisite for inflammation resolution and tissue repair. Following myocardial infarction (MI), phagocytes are recruited to the heart and promote clearance of dying cardiomyocytes (CMs). The molecular mechanisms of efferocytosis of CMs and in the myocardium are unknown. The injured heart provides a unique model to examine relationships between efferocytosis and subsequent inflammation resolution, tissue remodeling, and organ function. Objective We set out to identify mechanisms of dying cardiomyocyte (CM) engulfment by phagocytes and to for the first time assess the causal significance of disrupting efferocytosis during MI. Methods and Results In contrast to other apoptotic cell receptors, macrophage MER tyrosine kinase (MER-TK) was necessary and sufficient for efferocytosis of CMs ex vivo. In mice, Mertk was specifically induced in Ly6cLO myocardial phagocytes after experimental coronary occlusion. Mertk deficiency led to an accumulation of apoptotic CMs, independent of changes in non-CMs, and a reduced index of in vivo efferocytosis. Importantly, suppressed efferocytosis preceded increases in myocardial infarct size and led to delayed inflammation resolution and reduced systolic performance. Reduced cardiac function was reproduced in chimeric mice deficient in bone marrow Mertk; reciprocal transplantation of Mertk+/+ marrow into Mertk-/- mice corrected systolic dysfunction. Interestingly, an inactivated form of MERTK, known as solMER, was identified in infarcted myocardium, implicating a natural mechanism of MERTK inactivation post MI. Conclusions These data collectively and directly link efferocytosis to wound healing in the heart and identify Mertk as a significant link between acute inflammation resolution and organ function.

Methods GPI-LpL construct.A PCR-based strategy was used to ligate the DNA sequence encoding the last 37 amino acids of membrane decay accelerating factor (DAF) (9, 10) containing the GPI-anchoring sequence to a human LpL (hLpL) minigene (11) (see Figure 1a). This strategy required the elimination of the LpL termination codon

Background and Purpose-Although the cause of stroke among patients with patent foramen ovale (PFO) may be due to paradoxical cerebral embolism (PCE), this mechanism is often difficult to prove. The aim of our study was to evaluate the association between brain imaging findings suggestive of embolism and PFO among ischemic stroke patients.

Ethnic associations with PAD remained significant even after adjustment for traditional and novel risk factors. This suggests that unknown factors may account for the residual ethnic differences in PAD.