The burgeoning obesity and diabetes epidemics threaten health worldwide, yet the molecular mechanisms underlying these phenomena are incompletely understood. Recently, attention has focused on the potential contributions of environmental pollutants that act as endocrine disrupting chemicals (EDCs) in the pathogenesis of metabolic diseases. Because glucocorticoid signaling is central to adipocyte differentiation, the ability of EDCs to stimulate the glucocorticoid receptor (GR) and drive adipogenesis was assessed in the 3T3-L1 cell line. Various EDCs were screened for glucocorticoid-like activity using a luciferase reporter construct, and four (bisphenol A (BPA), dicyclohexyl phthalate (DCHP), endrin, and tolylfluanid (TF)) were shown to significantly stimulate GR without significant activation of the peroxisome proliferator-activated receptor-γ. 3T3-L1 preadipocytes were then treated with EDCs and a weak differentiation cocktail containing dehydrocorticosterone (DHC) in place of the synthetic dexamethasone. The capacity of these compounds to promote adipogenesis was assessed by quantitative oil red O staining and immunoblotting for adipocyte-specific proteins. The four EDCs increased lipid accumulation in the differentiating adipocytes and also upregulated the expression of adipocytic proteins. Interestingly, proadipogenic effects were observed at picomolar concentrations for several of the EDCs. Because there was no detectable adipogenesis when the preadipocytes were treated with compounds alone, the EDCs are likely promoting adipocyte differentiation by synergizing with agents present in the differentiation cocktail. Thus, EDCs are able to promote adipogenesis through the activation of the GR, further implicating these compounds in the rising rates of obesity and diabetes.

The development of the neonatal gastrointestinal tract microbiota remains a poorly understood process. The interplay between neonatal (gestational age, genetic background), maternal (mode of delivery, nutritional status) and environmental factors (antibiotic exposure, available nutrition) are thought to influence microbial colonization, however, the exact mechanisms are unclear. Derangements in this process likely contribute to various gastrointestinal diseases including necrotizing enterocolitis and inflammatory bowel disease. As such, enhanced understanding of microbiota development may hold the key to significantly reduce the burden of gastrointestinal disease in the pediatric population. The most debatable topics during microbial seeding and possible future treatment approaches will be highlighted in this review.

Background: COVID-19 threatens to quickly overwhelm our existing critical care infrastructure in the USA. Systemic tissue plasminogen activator (tPA) has been previously demonstrated to improve PaO 2 /FiO 2 (mmHg) when given to critically ill patients with acute respiratory distress syndrome (ARDS). It is unclear to what extent tPA may impact population-based survival during the current US COVID-19 pandemic. Methods: A decision analytic Markov state transition model was created to simulate the life critically ill COVID-19 patients as they transitioned to either recovery or death. Two patient groups were simulated (50,000 patients in each group); (1) Patients received tPA immediately upon diagnosis of ARDS and (2) patients received standard therapy for ARDS. Base case critically ill COVID-19 patients were defined as having a refractory PaO 2 /FiO 2 of < 60 mmHg (salvage use criteria). Transition from severe to moderate to mild ARDS, recovery, and death were estimated. Markov model parameters were extracted from existing ARDS/COVID-19 literature. Results: The use of tPA was associated with reduced mortality (47.6% [tTPA] vs. 71.0% [no tPA]) for base case patients. When extrapolated to the projected COVID-19 eligible for salvage use tPA in the USA, peak mortality (deaths/100,000 patients) was reduced for both optimal social distancing (70.5 [tPA] vs. 75.0 [no tPA]) and no social distancing (158.7 [tPA] vs. 168.8 [no tPA]) scenarios.Conclusions: Salvage use of tPA may improve recovery of ARDS patients, thereby reducing COVID-19-related mortality and ensuring sufficient resources to manage this pandemic.

Background and objective: No current nationwide consensus exists on pilonidal disease (PD) treatment in Switzerland and Austria. The objective of this study was to assess and compare the spectrum of PD treatment strategies in Switzerland and Austria. Materials and Methods: A survey including 196 certified institutions (Switzerland, N = 99 and Austria, N = 97) was performed. Treatment strategies for both chronic and acute pilonidal disease were investigated, as well as evolution of treatment over the last 20 years. Results: In total, 92 of 196 (47%) hospitals participated in the survey. Recurrence rate (20%) was similar between the two countries. In acute pilonidal disease, a two-stage approach with incision and drainage as the first step was preferred over a one-stage procedure in both countries. In Austria, all patients with chronic pilonidal disease were treated as inpatients, whereas 28% of patients in Switzerland were treated on an outpatient basis (p = 0.0019). Median length of hospital stay was double in Austria (four days) compared to Switzerland (two days; p < 0.001). Primary resection and off-midline closure (p = 0.017) and the use of tissue flaps (p = 0.023) were performed more commonly in Austria than in Switzerland. Minimally invasive techniques were performed more often in Switzerland than in Austria (52% vs. 4%, p < 0.001). Overall, wide excision with secondary wound healing or midline closures declined over the last 20 years. Conclusion: Treatment strategies for chronic PD differ between Austria and Switzerland with more and longer inpatient care in Austria, increasingly minimally invasive approaches in Switzerland, and outdated procedures still being performed in both countries. Overall, heterogeneity of practice dominates in both countries.

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