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Background: Heart failure with reduced ejection fraction is associated with potentially deleterious imbalance of the cardiac autonomic nervous system. Sacubitril/valsartan (angiotensin receptor-neprilysin inhibitor [ARNI]) reduces cardiovascular mortality and hospitalization for heart failure with reduced ejection fraction. Whether ARNI affects the cardiac autonomic nervous system has not been studied., Methods and Results: This investigator-initiated, prospective, single-center cohort study compared heart rate (HR) variability, HR, deceleration capacity, and periodic repolarization dynamics as noninvasive measures of the cardiac autonomic nervous system before and after initiation of ARNI therapy. Patients underwent standardized 12-lead Holter-ECG, echocardiography and laboratory testing before and 3 months after start of therapy. End points were changes in HR variability (SD of normal-to-normal intervals, mean square of differences between consecutive R-R intervals), HR, deceleration capacity, and periodic repolarization dynamics as well as ventricular function and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Of 63 patients with heart failure with reduced ejection fraction enrolled, 48 (76.2%) patients were still on ARNI at follow-up. SD of normal-to-normal intervals increased from 25 to 36 milliseconds ( P <0.001), mean square of differences between consecutive R-R intervals increased from 12 to 19 milliseconds ( P <0.001), HR decreased from 73±9 bpm to 67±4 bpm, ( P <0.001), and deceleration capacity increased from 2.1 to 4.4 milliseconds ( P <0.001). A trend for periodic repolarization dynamics reduction was observed (5.6 deg 2 versus 4.7 deg 2 , P =0.09). Autonomic changes were accompanied by increased left ventricular ejection fraction (29±6% versus 40±8%, P <0.001) and reduced NT-proBNP (3548 versus 685 ng/L, P <0.001). Correlation analysis showed a significant relationship between volume-unloading (as evidenced by NT-proBNP reduction) and autonomic improvement., Conclusions: Three months of ARNI therapy resulted in a significant increase in cardiac parasympathetic tone. The improvement in autonomic properties may be mediated by "volume unloading" and likely contributes to the beneficial effects of ARNI in heart failure with reduced ejection fraction., Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04587947.

Background: The onset of mental illness such as depression and anxiety disorders in pregnancy and postpartum period is common. The coronavirus induced disease 2019 (COVID-19) pandemic and the resulting public policy responses represent an exceptional situation worldwide and there are hints for adverse psychosocial impact, hence, the study of psychological effects of the pandemic in women during hospitalization for delivery and in the postpartum period is highly relevant., Methods: Patients who gave birth during the first wave of the COVID-19 pandemic in Germany (March to June 2020) at the Department of Obstetrics and Gynecology, University of Würzburg, Germany, were recruited at hospital admission for delivery. Biosamples were collected for analysis of SARS-CoV-2 infection and various stress hormones and interleukin-6 (IL-6). In addition to sociodemographic and medical obstetric data, survey questionnaires in relation to concerns about and fear of COVID-19, depression, stress, anxiety, loneliness, maternal self-efficacy and the mother-child bonding were administered at T1 (delivery stay) and T2 (3-6 months postpartum)., Results: In total, all 94 recruited patients had a moderate concern of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at T1 with a significant rise at T2. This concern correlated with low to low-medium general psychosocial stress levels and stress symptoms, and the women showed a significant increase of active coping from T1 to T2. Anxiety levels were low and the Edinburgh Postnatal Depression Scale showed a medium score of 5 with a significant (T1), but only week correlation with the concerns about SARS-CoV-2. In contrast to the overall good maternal bonding without correlation to SARS-CoV-2 concern, the maternal self-efficiency correlated negatively with the obstetric impairment caused by the COVID-19 pandemic., Conclusion: Obstetric patients` concerns regarding SARS-CoV-2 and the accompanying pandemic increased during the course of the pandemic correlating positively with stress and depression. Of note is the increase in active coping over time and the overall good mother-child-bonding. Maternal self-efficacy was affected in part by the restrictions of the pandemic. Clinical trial registration DRKS00022506., (© 2022. The Author(s).)

Four groups of 16 age-matched female Crl:SKH1-hrBR hairless mice were exposed to either control soil or polychlorinated biphenyl (PCB)-contaminated soil (retrieved from an electrical waste landfill in Southern Illinois) for 11 weeks. The mice were exposed in a study to determine interactions between environmental PCBs and ultraviolet radiation (UVR), but the UVR group did not differ and provided a replicate for the residue study. Ear biopsies were performed immediately after the termination of soil exposure. The mice were maintained in regular bedding for 37 weeks thereafter. The ear-skin, trunk-skin, fat-pad, and liver samples were collected and weighed at the end of the study (week 48) and analyzed for PCB residues. A total of 141 PCB congeners were target analytes. There were significant differences in body weights and food consumption from week 2 to 28. The liver weights of mice treated with PCB only were significantly greater than those of UVR-treated mice. The fat-pad weight did not differ among treated groups. PCB residues in the ear biopsies specimens of mice exposed to contaminated soil were 342.3 and 317.2 ppm in the PCB- and PCB + UVR-treated groups, respectively, and contained both persistent and episodic congeners. After 37 weeks of isolation from soil, the ear PCB residues decreased to 21.5 ppm (PCB group) and 14.5 ppm (PCB + UVR group), and only persistent congeners contributed to the total PCB residues. The accumulation of PCB residues was highest in the fat pad (fat pad > ear skin > trunk skin > liver) in both PCB +/- UVR groups at the end of the study. However, the percentage of individual congeners contributing to total PCBs in these different tissues did not differ.