AMPA receptor GluA2 subunit defects are a cause of neurodevelopmental disorders.

AMPA receptors (AMPARs) are tetrameric ligand-gated channels made up of combinations of GluA1-4 subunits encoded by GRIA1-4 genes. GluA2 has an especially important role because, following post-transcriptional editing at the Q607 site, it renders heteromultimeric AMPARs Ca2+-impermeable, with a linear relationship between current and trans-membrane voltage. Here, we report heterozygous de novo GRIA2 mutations in 28 unrelated patients with intellectual disability (ID) and neurodevelopmental abnormalities including autism spectrum disorder (ASD), Rett syndrome-like features, and seizures or developmental epileptic encephalopathy (DEE). In functional expression studies, mutations lead to a decrease in agonist-evoked current mediated by mutant subunits compared to wild-type channels. When GluA2 subunits are co-expressed with GluA1, most GRIA2 mutations cause a decreased current amplitude and some also affect voltage rectification. Our results show that de-novo variants in GRIA2 can cause neurodevelopmental disorders, complementing evidence that other genetic causes of ID, ASD and DEE also disrupt glutamatergic synaptic transmission

Gender Differences in Work-Life Integration, Career Satisfaction, and Burnout in Pediatric Emergency Medicine Physicians: A Cross-Sectional Analysis.

OBJECTIVE: Women physicians report worse work-life integration, career satisfaction, and burnout than men. No studies have evaluated work-life integration and career satisfaction in pediatric emergency medicine (PEM) or explored gender differences for these outcomes. This study aims to (1) compare work-life integration, career satisfaction, and burnout in women and men PEM physicians and (2) compare associated individual and occupational factors to distinguish modifiable factors. METHODS: We distributed an electronic survey to assess well-being parameters in PEM physicians. We assessed career satisfaction and work-life integration with single-item measures. We used a 2-item screen to measure burnout. We performed descriptive analyses, univariate analysis to compare gender differences, and multivariate logistic regression analysis for each outcome. RESULTS: Two hundred thirty-nine PEM physicians participated, yielding a response rate of 50% (57% women; age range, 30-80 years). Overall satisfaction with work-life integration was 42.9%, with 34.3% of women reporting appropriate work-life integration, compared with 55.4% of men (P = 0.001). Career satisfaction rate was 77.8%, with 71.6% of women reporting career satisfaction, compared with 86.1% of men (P = 0.008). Burnout rate was 44.5%, with 53.7% of women reporting burnout compared with 33.7% of men (P = 0.002). Modifiable factors identified include perception of unfair compensation, inadequate physical and mental health support provided by organization, feeling unappreciated, inadequate provider staffing, inadequate resources for patient care, lack of advance notice or control of work schedule, and inadequate sleep. CONCLUSIONS: Of PEM physicians, women have worse work-life integration, less career satisfaction, and more burnout than men. The PEM community should devote resources to modifiable occupational factors to improve gender disparities in well-being parameters

Mild-to-moderate severity of psoriasis may be assessed remotely based on photographs and self-reported extent of skin involvementCapsule Summary

Background: Remote monitoring was used to assess and manage skin diseases. Objective: To investigate to what extent smartphone photographs along with a self-reported body region (BR) score can be used to evaluate psoriasis severity. Methods: Psoriasis severity was assessed in the clinic using the psoriasis area and severity index and the physician’s global assessment. On the same day, the patients took a photograph of a representative lesion from 4 BR (head/neck, upper limbs, trunk, and lower limbs) and completed a questionnaire about BR score. The photographs were rated by 5 dermatologists. Intraclass correlation coefficients with 95% CIs were calculated. Results: Overall, 32 were included, of which 6% had almost clear, 69% had mild, and 25% had moderate psoriasis. Perfect agreement between the self-reported and the doctors’ BR score was observed for 59%, and near-perfect agreement (deviation of maximum 1 score) was 92%. The intraclass correlation coefficient between clinical and photographic psoriasis area and severity index was 0.78 (95% CI, 0.55-0.90), and for physician’s global assessment, perfect agreement was 53%. Conclusions: The agreement between psoriasis severity assessed clinically and by photographs was good in a study setting. This gives the opportunity to remotely assess psoriasis severity by combining photographs with self-reported BR scores

Continued breathing followed by gasping or apnea in a swine model of ventricular fibrillation cardiac arrest

Continued breathing following ventricular fibrillation has here-to-fore not been described