The COVID-19 pandemic has drastically affected the traditional methods residency programs use to train their residents. Chief residents serve a unique role as part of the residency leadership to foster the education and development of the residents. Given the rapid shift in demands on physicians in the face of the pandemic, the responsibilities of the chief residents have also shifted to help prepare the residents to meet these demands as frontline providers. There is not a precedent for how residency programs respond to this crisis while maintaining their primary role to develop and train physicians. The authors have identified 5 questions chief residents can ask to guide their program’s response to the demands of COVID-19 during this uncertain time in health care.

Social interactions in rodents are rewarding and motivating and social isolation is aversive. Accumulating evidence suggests that disruption of the social environment in adolescence has long-term effects on social interactions, on anxiety-like behavior and on stress reactivity. In previous work we showed that adolescent isolation produced increased reactivity to acute and to repeated stress in female rats, whereas lower corticosterone responses to acute stress and decreased anxiety-related behavior were noted in isolated males. These results indicate a sex specific impact on the effects of social stress in adolescence. However, little is known about whether social isolation impacts behaviors related to affect and whether it does so differently in male and female rats. The present study investigated the impact of adolescent social isolation from day 30-50 of age in male and female Sprague Dawley rats on behavior in the forced swim test at the end of adolescence and in adulthood and on behavior in the sucrose preference test in adulthood. Adult female rats that were isolated in adolescence exhibited increased climbing on the first and second day of the forced swim test and showed an increased preference for sucrose compared to adult females that were group-housed in adolescence. There were no effects in male rats. The results indicate that social isolation in adolescence produces a stable and active behavioral phenotype in adult female rats.

Autism is a complex neurodevelopmental disorder that has significant phenotypic overlap with several diseases, many of which fall within the broader category of autism spectrum disorders (ASDs). The etiology of the disorder is unclear and seems to involve a complex interplay of polygenic as well as environmental factors. We discuss evidence that suggests that epigenetic dysregulation is highly implicated as a contributing cause of ASDs and autism. Specifically, we examine neurodevelopmental disorders that share significant phenotypic overlap with ASDs and feature the dysregulation of epigenetically modified genes including UBE3A, GABA receptor genes, and RELN. We then look at the dysregulated expression of implicated epigenetic modifiers, namely MeCP2, that yield complex and varied downstream pleiotropic effects. Finally, we examine epigenetically mediated parent-of-origin effects through which paternal gene expression dominates that of maternal contributing to contrasting phenotypes implicated in ASDs. Such preliminary evidence suggests that elucidating the complex role of epigenetic regulations involved in ASDs could prove vital in furthering our understanding of the complex etiology of autism and ASDs.

Ewing sarcoma (ES) is an aggressive bone and soft tissue malignancy that predominantly affects children and adolescents. CD99 is a cell surface protein that is highly expressed on ES cells and is required to maintain their malignancy. We screened small molecule libraries for binding to extracellular domain of recombinant CD99 and subsequent inhibition of ES cell growth. We identified two structurally similar FDA-approved compounds, clofarabine and cladribine that selectively inhibited the growth of ES cells in a panel of 14 ES vs. 28 non-ES cell lines. Both drugs inhibited CD99 dimerization and its interaction with downstream signaling components. A membrane-impermeable analog of clofarabine showed similar cytotoxicity in culture, suggesting that it can function through inhibiting CD99 independent of DNA metabolism. Both drugs drastically inhibited anchorage-independent growth of ES cells, but clofarabine was more effective in inhibiting growth of three different ES xenografts. Our findings provide a novel molecular mechanism for clofarabine that involves direct binding to a cell surface receptor CD99 and inhibiting its biological activities.

Fractional exhaled nitric oxide (FeNO) is a marker of airway inflammation that is well‐characterized in allergic disease states. However, FeNO is also involved in nonallergic inflammatory and pulmonary vascular mechanisms or responses to environmental stimuli. We sought to determine the extent to which obesity or sedentary lifestyle is associated with FeNO in adolescents not selected on the basis of allergic disease. In Project Viva, a prebirth cohort study, we measured body mass index (BMI), skinfold thicknesses, waist circumference, body fat, hours watching television, hours of physical activity, and heart rate after exercise among 929 adolescents (median age, 12.9). We measured FeNO twice and averaged these as a continuous, log‐transformed outcome. We performed linear regression models, adjusted for child age, sex, height, and race/ethnicity, maternal education and smoking during pregnancy, household income and smoking, and neighbourhood characteristics. In secondary analysis, we additionally adjusted for asthma. More than 2 hours spent watching TV was associated with 10% lower FeNO (95% confidence interval [CI]: −20, 0%). Higher body fat percentage was also associated with lower FeNO. After additional adjustment for asthma, teens who are underweight (BMI <5th %tile, 3%) had 22% lower FeNO (95%CI: −40, 2%) and teens who are overweight (BMI ≥85th %ile, 28%) had 13% lower FeNO (95%CI: −23, −2%). Each of these associations of lifestyle and body weight with lower FeNO were greater in magnitude after adjusting for asthma. In summary, sedentary lifestyle, high and low BMI were all associated with lower FeNO in this adolescent cohort.

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Fractional exhaled nitric oxide (FeNO) is an indicator of allergic airway inflammation. However, it is unknown how asthma, allergic rhinitis (AR) and allergic sensitisation relate to FeNO, particularly among adolescents and in overlapping conditions. We sought to determine the associations between asthma, AR, and aeroallergen IgE and FeNO in adolescents.We measured FeNO among 929 adolescents (11–16 years) in Project Viva, an unselected prebirth cohort in Massachusetts. We defined asthma as ever asthma physician diagnosis plus wheezing in the past year or taking asthma medications in the past month; AR as a physician diagnosis of hay fever or AR; and aeroallergen IgE as any IgE>0.35 IU·mL−1 among 592 participants who provided blood samples. We examined associations of asthma, AR, and IgE with percent difference in FeNO in linear regression models adjusted for sex, race/ethnicity, age and height; maternal education and smoking during pregnancy; and household/neighborhood demographics.Asthma (14%) was associated with 97% higher FeNO (95%CI 70, 128%), AR (21%) with 45% higher FeNO (95%CI 28, 65%), and aeroallergen IgE (58%) with 102% higher FeNO (95%CI 80, 126%) compared to those without each condition, respectively. In the absence of asthma or AR, aeroallergen IgE was associated with 75% higher FeNO (95%CI 52, 101), while asthma and AR were not associated with FeNO in the absence of IgE.The link between asthma and AR with FeNO is limited to those with IgE-mediated phenotypes. FeNO may be elevated in those with allergic sensitisation alone, even in the absence of asthma or AR.

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