IKK phosphorylates Huntingtin and targets it for degradation by the proteasome and lysosome

Expansion of the polyglutamine repeat within the protein Huntingtin (Htt) causes Huntington's disease, a neurodegenerative disease associated with aging and the accumulation of mutant Htt in diseased neurons. Understanding the mechanisms that influence Htt cellular degradation may target treatments designed to activate mutant Htt clearance pathways. We find that Htt is phosphorylated by the inflammatory kinase IKK, enhancing its normal clearance by the proteasome and lysosome. Phosphorylation of Htt regulates additional post-translational modifications, including Htt ubiquitination, SUMOylation, and acetylation, and increases Htt nuclear localization, cleavage, and clearance mediated by lysosomal-associated membrane protein 2A and Hsc70. We propose that IKK activates mutant Htt clearance until an age-related loss of proteasome/lysosome function promotes accumulation of toxic post-translationally modified mutant Htt. Thus, IKK activation may modulate mutant Htt neurotoxicity depending on the cell's ability to degrade the modified species

Pain Control in Breast Surgery: Survey of Current Practice and Recommendations for Optimizing Management—American Society of Breast Surgeons Opioid/Pain Control Workgroup

Introduction: The opioid epidemic in the United States is a public health crisis. Breast surgeons are obligated to provide good pain control for their patients after surgery but also must minimize administration of narcotics to prevent a surgical episode of care from becoming a patient's gateway into opioid dependence. Methods: A survey to ascertain pain management practice patterns after breast surgery was performed. A review of currently available literature that was specific to breast surgery was performed to create recommendations regarding pain management strategies. Results: A total of 609 surgeons completed the survey and demonstrated significant variations in pain management practices, specifically within regards to utilization of regional anesthesia (e.g., nerve blocks), and quantity of prescribed narcotics. There is excellent data to guide the use of local and regional anesthesia. There are, however, fewer studies to guide narcotic recommendations; thus, these recommendations were guided by prevailing practice patterns. Conclusions: Pain management practices after breast surgery have significant variation and represent an opportunity to improve patient safety and quality of care. Multimodality approaches in conjunction with standardized quantities of narcotics are recommended

Introduction to the societal violence scale : Physical integrity rights violations and nonstate actors

Measures of physical integrity rights violations typically focus on abuses by state actors. However, nonstate actors also represent a grave threat to personal security. This article introduces the Societal Violence Scale (SVS) which uses the US State Department Human Rights reports as a basis for developing a new scale of physical integrity rights abuses by nonstate actors to gain a more comprehensive, but at the same time disaggregated, picture of human security threats across the globe

VITT following Ad26.COV2.S vaccination presenting without radiographically demonstrable thrombosis

We report a case of vaccine-induced immune thrombotic thrombocytopenia (VITT) in a young man diagnosed 13 days after Ad26.COV2.S COVID-19 (Johnson & Johnson/Janssen) vaccination. He presented to us with 5 days of progressive left leg pain, thrombocytopenia, hypofibrinogenemia, and markedly elevated d-dimers, but without radiographically demonstrable thrombosis. Despite negative imaging, we initiated treatment of presumptive VITT given the striking clinical picture that included the timing of his recent adenovirus-based COVID-19 vaccine, leg symptoms, marked thrombocytopenia, and consumptive coagulopathy. He received intravenous immune globulin, prednisone, and argatroban and was discharged 7 days later much improved. His positive platelet factor 4 enzyme-linked immunosorbent assay antibody test returned after treatment was initiated. To our knowledge, this is the first reported case of VITT following Ad26.COV2.S vaccination presenting without radiographically demonstrable thrombosis. Our patient highlights the importance of knowing vaccine status and initiating treatment as soon as possible in the right clinical setting, even in the absence of radiographic evidence of thrombus. Early VITT recognition and treatment provide an opportunity to prevent serious thrombotic complications

Pain Control in Breast Surgery: Survey of Current Practice and Recommendations for Optimizing Management—American Society of Breast Surgeons Opioid/Pain Control Workgroup

IntroductionThe opioid epidemic in the United States is a public health crisis. Breast surgeons are obligated to provide good pain control for their patients after surgery but also must minimize administration of narcotics to prevent a surgical episode of care from becoming a patient's gateway into opioid dependence.MethodsA survey to ascertain pain management practice patterns after breast surgery was performed. A review of currently available literature that was specific to breast surgery was performed to create recommendations regarding pain management strategies.ResultsA total of 609 surgeons completed the survey and demonstrated significant variations in pain management practices, specifically within regards to utilization of regional anesthesia (e.g., nerve blocks), and quantity of prescribed narcotics. There is excellent data to guide the use of local and regional anesthesia. There are, however, fewer studies to guide narcotic recommendations; thus, these recommendations were guided by prevailing practice patterns.ConclusionsPain management practices after breast surgery have significant variation and represent an opportunity to improve patient safety and quality of care. Multimodality approaches in conjunction with standardized quantities of narcotics are recommended