Citations

Multinucleated epithelial giant cells mimicking viropathic effect or dysplasia have been documented in the gastrointestinal tract, specifically in the esophagus and colorectal polyps. This finding has been associated with either inflammation or hyperplasia in prior case series. The authors report the first occurrence in the small intestine involving a 30-year-old woman without a coexisting inflammatory or hyperplastic process. The multinucleated epithelial giant cells featured numerous homogenous nulei (mean 9 nuclei, range 5-18) limited to duodenal villi. Immunohistochemistry revealed strong positivity for cytokeratin AE1/AE3 and negativity for herpes simplex virus 1 and 2, varicella simplex virus, and cytomegalovirus. In situ hybridizations for adenovirus and Epstein–Barr virus were also negative. Despite a lack of a specific etiologic agent, evidence suggests multinucleated epithelial giant cells are the consequence of inflammation, chronic injury, or cellular degeneration.

Obesity and depression are often comorbid conditions. There appears to be a bidirectional relationship between these. Obesity at baseline has been shown to increase the risk of onset of depression and depression at baseline increased the odds for developing obesity. Less is understood about the impact of obesity on depression treatment outcomes. The authors’ hypothesis was that obesity (body mass index [BMI] ≥30 kg/m 2 ) and morbid obesity (BMI ≥ 40 kg/m 2 ) would each have negative effects on depression remission rates after 6 months of enrollment into collaborative care management for depression. In a retrospective analysis of 1111 depressed patients with a PHQ-9 (Patient Health Questionnaire) score of 10 or greater, multivariate analysis for the odds ratio of achieving remission at 6 months demonstrated that the patient’s BMI at baseline was not an independent risk factor for depression outcome at 6 months. Collaborative care management for depression has been shown to be effective for improving depression outcomes, yet minimal prior research has focused on other clinical comorbidities that might affect outcomes. Although obesity was common in the study population, it was reassuring, based on this study that 6-month depression treatment outcomes do not appear to be significantly affected by the patient’s baseline BMI.

The transition between puberty and adulthood is accompanied by a slowing in linear growth. Although GH is a key factor that drives somatic development into adulthood, early adulthood coincides with a reduction in circulating levels of GH. To this extent, a pathological decline in postpubertal GH secretion is detrimental to attainment of peak lean muscle mass and bone mass and promotes adiposity and increases susceptibility to the development of obesity in adulthood. Here we characterized pulsatile GH secretion in C57BL/6J mice at 12 and 16 wk of age. Deconvolution analysis of these measures reveals a reduction in pulsatile GH secretion between 12 and 16 wk of age. Dietary intervention with high-fat feeding at 8 wk of age results in a significant increase in adiposity, the development of glucose intolerance, and hyperinsulinemia. We show the exacerbation of the age-associated decline in pulsatile GH secretion in high-fat-fed mice after 4 wk of dietary intervention (at 12 wk of age), and a further suppression of pulsatile GH secretion by 8 wk of dietary intervention (at 16 wk of age). Suppressed pulsatile secretion of GH did not coincide with an elevation in circulating free fatty acids. Rather, we observed increased hepatic triglyceride content and an eventual decrease in circulating levels of IGF-I. Given the established role of GH in maintaining healthy aging, we anticipate that an advancing of the age-associated decline in pulsatile GH secretion as a consequence of dietary-induced weight gain may have long-term ramifications on adult health.

Abstract After a primary immune response, T cell memory occurs when a subset of Ag-specific T cells resists peripheral selection by acquiring resistance to TCR-induced death. Recent data have implicated Bcl-2 interacting mediator of death (Bim) as an essential mediator of the contraction phase of T cell immunity. In this article, we describe that stromal-derived factor-1α (SDF-1α) ligation of CXCR4 on activated T cells promotes two parallel processes that favor survival, phospho-inactivation of Foxo3A, as well as Bim extralong isoform (BimEL) degradation, both in an Akt- and Erk-dependent manner. Activated primary CD4 T cells treated with SDF-1α therefore become resistant to the proapoptotic effects of TCR ligation or IL-2 deprivation and accumulate cells of a memory phenotype. Unlike SDF-1α, gp120 ligation of CXCR4 has the opposite effect because it causes p38-dependent BimEL upregulation. However, when activated CD4 T cells are treated with both gp120 and SDF-1α, the SDF-1α–driven effects of BimEL degradation and acquired resistance to TCR-induced death predominate. These results provide a novel causal link between SDF-1α–induced chemotaxis, degradation of BimEL, and the development of CD4 T cell memory.

Background— Spontaneous coronary artery dissection (SCAD) is an acute coronary event of uncertain origin. Clinical features and prognosis remain insufficiently characterized. Methods and Results— A retrospective single-center cohort study identified 87 patients with angiographically confirmed SCAD. Incidence, clinical characteristics, treatment modalities, in-hospital outcomes, and long-term risk of SCAD recurrence or major adverse cardiac events were evaluated. Mean age was 42.6 years; 82% were female. Extreme exertion at SCAD onset was more frequent in men (7 of 16 versus 2 of 71; P <0.001), and postpartum status was observed in 13 of 71 women (18%). Presentation was ST-elevation myocardial infarction in 49%. Multivessel SCAD was found in 23%. Initial conservative management (31 of 87) and coronary artery bypass grafting (7 of 87) were associated with an uncomplicated in-hospital course, whereas percutaneous coronary intervention was complicated by technical failure in 15 of 43 patients (35%) and 1 death. During a median follow-up of 47 months (interquartile range, 18–106 months), SCAD recurred in 15 patients, all female. Estimated 10-year rate of major adverse cardiac events (death, heart failure, myocardial infarction, and SCAD recurrence) was 47%. Fibromuscular dysplasia of the iliac artery was identified incidentally in 8 of 16 femoral angiograms (50%) undertaken before closure device placement and in the carotid arteries of 2 others with carotid dissection. Conclusions— SCAD affects a young, predominantly female population, frequently presenting as ST-elevation myocardial infarction. Although in-hospital mortality is low regardless of initial treatment, percutaneous coronary intervention is associated with high rates of complication. Risks of SCAD recurrence and major adverse cardiac events in the long term emphasize the need for close follow-up. Fibromuscular dysplasia is a novel association and potentially causative factor.