UBXN proteins likely participate in the global regulation of protein turnover, and we have shown that UBXN1 interferes with RIG-I-like receptor (RLR) signaling by interacting with MAVS and impeding its downstream effector functions. Here we demonstrate that over-expression of multiple UBXN family members decreased lentivirus and retrovirus production by several orders-of-magnitude in single cycle assays, at the level of long terminal repeat-driven transcription, and three family members, UBXN1, N9, and N11 blocked the canonical NFκB pathway by binding to Cullin1 (Cul1), inhibiting IκBα degradation. Multiple regions of UBXN1, including its UBA domain, were critical for its activity. Elimination of UBXN1 resulted in early murine embryonic lethality. shRNA-mediated knockdown of UBXN1 enhanced human immunodeficiency virus type 1 (HIV) production up to 10-fold in single cycle assays. In primary human fibroblasts, knockdown of UBXN1 caused prolonged degradation of IκBα and enhanced NFκB signaling, which was also observed after CRISPR-mediated knockout of UBXN1 in mouse embryo fibroblasts. Knockout of UBXN1 significantly up- and down-regulated hundreds of genes, notably those of several cell adhesion and immune signaling pathways. Reduction in UBXN1 gene expression in Jurkat T cells latently infected with HIV resulted in enhanced HIV gene expression, consistent with the role of UBXN1 in modulating the NFκB pathway. Based upon co-immunoprecipitation studies with host factors known to bind Cul1, models are presented as to how UBXN1 could be inhibiting Cul1 activity. The ability of UBXN1 and other family members to negatively regulate the NFκB pathway may be important for dampening the host immune response in disease processes and also re-activating quiescent HIV from latent viral reservoirs in chronically infected individuals.
Stevens johnson syndrome is an acute, self-limited disease, presenting as severe mucosal erosions with widespread erythematous, cutaneous macules or atypical targets. Even though sulfadiazine has been mainly associated with haematological-related adverse effects, sulfadiazine induced skin necrosis has received less attention or went unrecognized. Here is a 29-year- old Indian male received T. Sulfadiazine 500mg 1-1-1-1 and experienced a severe skin reaction which was diagnosed as stevens johnson syndrome (SJS). The above drug will be implicated in cases of stevens johnson syndrome (SJS)/toxic epidermal necrosis (TEN). There are few case reports of that have been associated with stevens johnson syndrome (SJS)/toxic epidermal necrosis (TEN). We hope that this case report creates awareness to the health care professionals. Clinicians must be aware of these adverse reactions and advise their patients to contact them as soon as they observe any unexpected clinical response. Early diagnosis helps the clinician to elude secondary infection and subsequent complications. The offending drug should be discontinued and never be rechallenged.
Since continuous glucose monitors (CGMs) first became commercially available in 2000, numerous studies have shown that their use improves the management of diabetes for both pediatric and adult patients and both type 1 and type 2 diabetes. 1-5 However, there remain little data on their efficacy in certain subpopulations such as patients with significant medical comorbidities, mental health conditions, or substantial social barriers, who were largely excluded from the studies of CGM's efficacy. 6 Commonwealth Care Alliance (CCA) is a not-for-profit, community-based healthcare organization that offers comprehensive health plans to patients dually eligible for Medicare and Medicaid, a medically and socially complex patient population. In April 2017, CCA launched a pilot program to implement professional CGMs in patients with diabetes who had poorly controlled hyperglycemia or suspicion of asymptomatic hypoglycemia. The device used in this pilot was the Freestyle Libre Pro System, a professional CGM that does not provide patients with real-time access to glucose readings. Patients continued their prior methods of glucose monitoring and control while using the device. The CGM was placed for a minimum of one week (range: 8-18 days). The data collected were reviewed by CCA clinicians and used to guide clinical decision making. Surveys were conducted with the patients and clinicians to determine the user and provider experience with the device. Thirteen patients were enrolled in the study (Table 1). The cohort had a high burden of chronic disease (average of 14.5 chronic conditions), behavioral health conditions (100% carried a mental health diagnosis), functional needs (100% required assistance with activities of daily living or instrumental activities of daily living), and recent hospitalizations (62% were hospitalized in the last year). The average pre-CGM hemoglobin A1c (HbA1c) was 9.4% with a range of 6.2% to 14.5%. The average change in HbA1c was −0.5% (P = .38). Among the nine subjects with starting HbA1c values above 8% (enrolled for uncontrolled hyperglycemia), the average HbA1c change was −0.9% (P = .23).
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