SARS-CoV-2 infects human cardiomyocytes promoted by inflammation and oxidative stress

INTRODUCTION The respiratory illness triggered by severe acute respiratory syndrome virus-2 (SARS-CoV-2) is often particularly serious or fatal amongst patients with pre-existing heart conditions. Although the mechanisms underlying SARS-CoV-2-related cardiac damage remain elusive, inflammation (i.e. 'cytokine storm') and oxidative stress are likely involved. METHODS AND RESULTS Here we sought to determine: 1) if cardiomyocytes are targeted by SARS-CoV-2 and 2) how inflammation and oxidative stress promote the viral entry into cardiac cells. We analysed pro-inflammatory and oxidative stress and its impact on virus entry and virus-associated cardiac damage from SARS-CoV-2 infected patients and compared it to left ventricular myocardial tissues obtained from non-infected transplanted hearts either from end stage heart failure or non-failing hearts (donor group). We found that neuropilin-1 potentiates SARS-CoV-2 entry into human cardiomyocytes, a phenomenon driven by inflammatory and oxidant signals. These changes accounted for increased proteases activity and apoptotic markers thus leading to cell damage and apoptosis. CONCLUSION This study provides new insights into the mechanisms of SARS-CoV-2 entry into the heart and defines promising targets for antiviral interventions for COVID-19 patients with pre-existing heart conditions or patients with co-morbidities

Cooperation of cancer drivers with regulatory germline variants shapes clinical outcomes

Pediatric malignancies including Ewing sarcoma (EwS) feature a paucity of somatic alterations except for pathognomonic driver-mutations that cannot explain overt variations in clinical outcome. Here, we demonstrate in EwS how cooperation of dominant oncogenes and regulatory germline variants determine tumor growth, patient survival and drug response. Binding of the oncogenic EWSR1-FLI1 fusion transcription factor to a polymorphic enhancerlike DNA element controls expression of the transcription factor MYBL2 mediating these phenotypes. Whole-genome and RNA sequencing reveals that variability at this locus is inherited via the germline and is associated with variable inter-tumoral MYBL2 expression. High MYBL2 levels sensitize EwS cells for inhibition of its upstream activating kinase CDK2 in vitro and in vivo, suggesting MYBL2 as a putative biomarker for anti-CDK2-therapy. Collectively, we establish cooperation of somatic mutations and regulatory germline variants as a major determinant of tumor progression and highlight the importance of integrating the regulatory genome in precision medicine

Psychosocial and Sociodemographic Contributors to Breastfeeding Intention in First-Time Mothers

Objective Breastfeeding has multiple benefits for women and babies. Understanding factors contributing to intention to exclusively breastfeed may allow for improving the rates in first-time mothers. The study objective was to examine factors associated with a woman’s intention to breastfeed her first child. Methods A secondary analysis of the prospective “Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be” (nuMoM2b) study of nulliparous women in the U.S. with singleton pregnancies was performed. Sociodemographic and psychosocial factors were analyzed for associations with breastfeeding intention. Results For the 6443 women with complete information about breastfeeding intention and all factors under consideration, women who intended to breastfeed (either exclusively or any breastfeeding) were more likely to be older, not black, have reached a higher level of education, have higher incomes, have a lower body mass index (BMI), and be nonsmokers. Reporting a planned pregnancy and several psychosocial measures were also associated with intention to breastfeed. In the multivariable analysis for exclusive breastfeeding, in addition to age, BMI, race, income, education, and smoking, of the psychosocial measures assessed, only women with higher hassle intensity ratios on the Pregnancy Experience Scale had lower odds of exclusive breastfeeding intention (OR 0.71, 95% CI 0.55–0.92). Other psychosocial measures were not associated with either exclusive breastfeeding or any breastfeeding after controlling for demographic characteristics. Conclusions for Practice Several sociodemographic factors, having a planned pregnancy, and fewer intense pregnancy hassles compared to uplifts are associated with intention to exclusively breastfeed. Identifying these factors may allow providers to identify women for focused, multilevel efforts to enhance breastfeeding rates

Hearing Screening in the Community

Background: Adults typically wait 7–10 yr after noticing hearing problems before seeking help, possibly because they are unaware of the extent of their impairment. Hearing screenings, frequently conducted at health fairs, community events, and retirement centers can increase this awareness. To our knowledge, there are no published studies in which testing conditions and outcomes have been examined for multiple “typical screening events.” Purpose: The purpose of this article is to report hearing screening outcomes for pure tones and self-report screening tests and to examine their relationship with ambient noise levels in various screening environments. Study Sample: One thousand nine hundred fifty-four individuals who completed a hearing screening at one of 191 community-based screening events that took place in the Portland, OR, and Tampa, FL, metro areas. Data Collection and Analysis: The data were collected during the recruitment phase of a large multisite study. All participants received a hearing screening that consisted of otoscopy, pure-tone screening, and completion of the Hearing Handicap Inventory–Screening Version (HHI-S). In addition, ambient sound pressure levels were measured just before pure-tone testing. Results: Many more individuals failed the pure-tone screening (n = 1,238) and then failed the HHI-S (n = 796). The percentage of individuals who failed the pure-tone screening increased linearly with age from \u3c20% for ages \u3c45 yr to almost 100% for individuals aged ≥85 yr. On the other hand, the percentage of individuals who failed the HHI-S remained unchanged at approximately 40% for individuals aged ≥55 yr. Ambient noise levels varied considerably across the hearing screening locations. They impacted the pure-tone screen failure rate but not the HHI-S failure rate. Conclusions: It is important to select screening locations with a quiet space for pure-tone screening, use headphones with good passive attenuation, measure sound levels regularly during hearing screening events, halt testing if ambient noise levels are high, and/or alert individuals to the possibility of a false-positive screening failure. The data substantiate prior findings that the relationship between pure-tone sensitivity and reported hearing loss changes with age. Although it might be possible to develop age-specific HHI-S failure criteria to adjust for this, such an endeavor is not recommended because perceived difficulties are the best predictor of hearing health behaviors. Instead, it is proposed that a public health focus on education about hearing and hearing loss would be more effective

Many babies 3 rule learning - Stage 1 Registered Report - In principle acceptance

The ability to learn and apply rules lies at the heart of cognition. In a seminal study, Marcus, Vijayan, Rao, and Vishton (1999) reported that seven-month-old infants learned abstract rules over syllable sequences and were able to generalize those rules to novel syllable sequences. Dozens of studies have since extended on that research using different rules, modalities, stimuli, participants (human adults and non-human animals) and experimental procedures. Yet questions remain about the robustness of Marcus et al.’s (1999) core findings, as the presence of significant learning effects has been mixed. In the current study, we aimed to address this issue by testing XX infants of a wide age range (5;0-12;0 months) in a multi-laboratory (XX laboratories) replication of the Marcus et al. (1999) study