Background: Aberrant activation of autophagy (proteinopathy) leads to neurodegeneration in various neurological disorders. Results: Compensatory basal autophagy is activated, and genotoxins deregulate autophagy in the ubiquitin pathway-compromised ataxia telangiectasia (A-T) cells. Conclusion: Deregulation of autophagy is due to the elevated expression of ISG15 in A-T cells. Significance: Results highlight a causal contribution of a novel "ISG15 proteinopathy" in A-T neurodegeneration.

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Background: Studies of adult and pediatric patients undergoing appendectomy have reported variable outcomes and operative metrics related to the effect of obesity. The purpose of this study was to investigate the effect of obesity in adult and pediatric patients undergoing appendectomy at our institution. Methods: This single-center retrospective study evaluated the relationship between length of hospital stay for appendectomy and body mass index (BMI). Data obtained from the electronic medical record included age, sex, weight, height, BMI, the number of hours the patient experienced symptoms prior to presentation to the emergency room, the number of hours the patient was admitted prior to surgery, the number of hours of hospital admission after surgery, perforated appendix, preoperative comorbidities, and evidence of preoperative sepsis. Results: During the 3-year study period, 118 adults and 38 children who underwent appendectomy composed the study groups. Patients were stratified by obese and nonobese, with obesity defined as BMI ࣙ30.0 kg/m 2. In adults, we found no significant difference between length of stay in obese (n=45) and nonobese (n=73) patients (79.6 ± 65.5 hours vs 101.6 ± 123.0 hours; P=0.21). In children, we found no significant difference between length of stay in obese (n=9) and nonobese (n=29) patients (92.9 ± 64.6 hours vs 109.0 ± 93.5 hours; P=0.54). Conclusion: Obesity did not affect length of stay in adults and children who underwent appendectomy in the present series.

Benign recurrent intrahepatic cholestasis represents a rare class of autosomal recessive chronic cholestasis disorders, usually presenting with recurrent episodes of intense pruritus and jaundice. We report a 27-year-old woman presenting with benign recurrent intrahepatic cholestasis type 2 due to heterozygosity in ABCB11. Interestingly, she was also found to be heterozygous in cystic fibrosis transmembrane conductance regulator, NPHP4, and A1ATD (SERPINA1), which may explain the severe nature of her disease expression because heterozygosity in each of these genes has been associated with cholestasis. Finally, she exhibited a response to steroids that may have implications for future treatment of bile salt export pump-related diseases.