RESUMEN
Mirizzi syndrome (MS) is a rare complication of chronic cholelithiasis. The syndrome describes gallstone obstruction of Hartmann's pouch or the cystic duct that extrinsically compresses the common hepatic duct, causing obstructive jaundice. In advanced cases, the gallstones may erode into the biliary tree creating a fistula, requiring prompt diagnosis and careful surgical management. We present a case of an 82-year-old female who presented with upper abdominal pain and jaundice, later diagnosed with suspected MS type I, and managed surgically. We aim to highlight MS type I because of the potential progression and damage to the bile duct, creating complications that may affect overall patient outcome.
RESUMEN
Interleukin-10 (IL-10) is a critical cytokine used by immune cells to suppress inflammation. Paradoxically, immune cell-derived IL-10 can drive insulin resistance in obesity by suppressing adipocyte energy expenditure and thermogenesis. However, the source of IL-10 necessary for the suppression of adipocyte thermogenesis is unknown. We show here that CD4+Foxp3+ regulatory T cells (Tregs) are a substantial source of IL-10 and that Treg-derived IL-10 can suppress adipocyte beiging. Unexpectedly, Treg-specific loss of IL-10 resulted in increased insulin sensitivity and reduced obesity in high-fat diet-fed male mice. Mechanistically, we determined that Treg-specific loss of the transcription factor Blimp-1, a driver of IL-10 expression by Tregs, phenocopied the Treg-specific IL-10-deficient mice. Loss of Blimp-1 expression in Tregs resulted in reduced ST2+KLRG1+, IL-10-secreting Tregs, particularly in the white adipose tissue. Blimp-1-deficient mice were protected from glucose intolerance, insulin resistance, and diet-induced obesity, through increased white adipose tissue browning. Taken together, our data show that Blimp-1-regulated IL-10 secretion by Tregs represses white adipose tissue beiging to maintain adipose tissue homeostasis.
Asunto(s)
Resistencia a la Insulina/inmunología , Resistencia a la Insulina/fisiología , Interleucina-10/inmunología , Obesidad/etiología , Factor 1 de Unión al Dominio 1 de Regulación Positiva/fisiología , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/fisiología , Tejido Adiposo Beige/inmunología , Tejido Adiposo Beige/metabolismo , Tejido Adiposo Blanco/inmunología , Tejido Adiposo Blanco/metabolismo , Animales , Dieta Alta en Grasa/efectos adversos , Intolerancia a la Glucosa/inmunología , Intolerancia a la Glucosa/metabolismo , Interleucina-10/deficiencia , Interleucina-10/genética , Masculino , Ratones , Ratones Noqueados , Ratones Transgénicos , Obesidad/inmunología , Obesidad/fisiopatología , Factor 1 de Unión al Dominio 1 de Regulación Positiva/deficiencia , Factor 1 de Unión al Dominio 1 de Regulación Positiva/genética , Termogénesis/inmunología , Termogénesis/fisiologíaRESUMEN
OBJECTIVE: To design, implement, and evaluate a molecular imaging elective course that would expose Doctor of Pharmacy (PharmD) students to fundamentals of various imaging modalities and their pre-clinical and clinical applications. METHODS: The "Surveys of Multi-Modality Imaging" course is a two-credit hour elective course offered to third-year PharmD and doctoral students. Experiential learning methods including active learning application-based exercises were used to supplement didactic lectures in the form of field trips (with follow-up debriefings), small group team-based tasks, hands-on demonstrations, visual modelling, gamification with problem sets, concept maps regarding given modalities, and concluding with written summary reports and formal in-class group presentations. In addition to standard course evaluations, a pre- and post-course survey were conducted to assess the students' confidence regarding course content. RESULTS: Since its implementation in 2013, 101 students have completed the course with 72% being PharmD students (nâ¯=â¯73) and the remainder being doctoral students in pharmaceutical science (nâ¯=â¯28). Pre- and post-assessments completed by the students the last two offerings (nâ¯=â¯40 of a possible 43) indicated a shift in students' self-reported confidence in discussing imaging modalities from a total of 2.4% confidence (pre-course) to 97.4% confidence (post-course). Also, post-course survey indicated that 77.5% (nâ¯=â¯31 of 40 participants) students strongly agreed that our immersive and experiential learning activities were beneficial to overall learning for this elective. CONCLUSION: Students who participated in this innovative experiential learning-grounded course gained an appreciation for molecular imaging and its value and role in modern drug therapy.