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To evaluate safety and impact of particle embolization on pancreatic function in a pig model. Embolization of the dorsal pancreatic artery using 100–300-μm particles was performed on 14 Yorkshire pigs. Baseline and post-embolization glucose tolerance testing results and serum amylase/lipase levels were obtained. Pigs were observed for 2 weeks to assess for behavioral signs of pain/distress, bowel changes, and changes to intake/output. After 2 weeks, euthanasia and necropsy with gross and histopathologic assessment of the pancreas were performed. Embolization was technically successful in all pigs. All animals survived the 2-week follow-up without evidence of pain/distress. There were significant increases in amylase and lipase at 24 and 48 hours (P <.001), which normalized by 2 weeks. There was minimal change in glucose tolerance testing at 2 weeks. Bowel habits were unchanged without diarrhea. At necropsy, all examined pancreases had fibrosis in the distal body and tail, without gross evidence of ongoing inflammation. On histopathologic evaluation, all pancreases demonstrated fibrosis in the embolized portions without evidence of active inflammation in treated or adjacent pancreatic tissue. Particle embolization of the pancreas was feasible and tolerated by all tested pigs with transient amylasemia, lipasemia, and mildly impaired glucose tolerance but without clinical or histopathologic evidence of acute pancreatitis and no evident impact on pancreatic endocrine or exocrine function. [Display omitted] [ABSTRACT FROM AUTHOR]

Summary Induction of broadly neutralizing antibodies (bnAbs) that target HIV-1 envelope (Env) is a goal of HIV-1 vaccine development. A bnAb target is the Env third variable loop (V3)-glycan site. To determine whether immunization could induce antibodies to the V3-glycan bnAb binding site, we repetitively immunized macaques over a 4-year period with an Env expressing V3-high mannose glycans. Env immunizations elicited plasma antibodies that neutralized HIV-1 expressing only high-mannose glycans—a characteristic shared by early bnAb B cell lineage members. A rhesus recombinant monoclonal antibody from a vaccinated macaque bound to the V3-glycan site at the same amino acids as broadly neutralizing antibodies. A structure of the antibody bound to glycan revealed that the three variable heavy-chain complementarity-determining regions formed a cavity into which glycan could insert and neutralized multiple HIV-1 isolates with high-mannose glycans. Thus, HIV-1 Env vaccination induced mannose-dependent antibodies with characteristics of V3-glycan bnAb precursors. [ABSTRACT FROM AUTHOR]

Background Salvage surgical resection for non-small cell lung cancer (NSCLC) patients initially treated with definitive chemotherapy and radiotherapy can be performed safely, but the long-term benefits are not well characterized. Methods Perioperative complications and long-term survival of all patients with NSCLC who received curative-intent definitive radiotherapy, with or without chemotherapy, followed by lobectomy from 1995 to 2012 were evaluated. Results During the study period, 31 patients met the inclusion criteria. Clinical stage distribution was stage I in 2 (6%), stage II in 5 (16%), stage IIIA in 15 (48%), stage IIIB in 5 (16%), stage IV in 3 (10%), and unknown in 1 (3%). The reasons surgical resection was initially not considered were: patients deemed medically inoperable (5 [16%]); extent of disease was considered unresectable (21 [68%]); small cell lung cancer misdiagnosis (1 [3%]), and unknown (4 [13%]). Definitive therapy was irradiation alone in 2 (6%), concurrent chemoradiotherapy in 28 (90%), and sequential chemoradiotherapy in 1 (3%). The median radiation dose was 60 Gy. Patients were subsequently referred for resection because of obvious local relapse, medical tolerance of surgical intervention, or posttherapy imaging suggesting residual disease. The median time from radiation to lobectomy was 17.7 weeks. There were no perioperative deaths, and morbidity occurred in 15 patients (48%). None of the 3 patients with residual pathologic nodal disease survived longer than 37 months, but the 5-year survival of pN0 patients was 36%. Patients who underwent lobectomy for obvious relapse (n = 3) also did poorly, with a median overall survival of 9 months. Conclusions Lobectomy after definitive radiotherapy can be done safely and is associated with reasonable long-term survival, particularly when patients do not have residual nodal disease. [ABSTRACT FROM AUTHOR]

Abstract: The inducible nitric oxide synthase (iNOS) enzyme has long been recognized as a key mediator of innate immune responses to infectious diseases across the phyla. Its role in killing or inactivating bacterial, parasitic, and viral pathogens has been documented in numerous host systems. iNOS, and its innate immune mediator NO has also been described to have negative consequence on host tissues as well; therefore understanding the pathogenesis of any infectious agent which induces iNOS expression requires a better understanding of the role iNOS and NO play in that disease. Previous studies in our laboratory and others have demonstrated evidence for increased levels of iNOS and activity of its innate immune mediator NO in the intestine of turkeys infected with astrovirus. To begin to characterize the role iNOS plays in the innate immune response to astrovirus infection, we identified, characterized, developed tkiNOS specific reagents, and demonstrated that the intestinal epithelial cells induce expression of iNOS following astrovirus infection. These data are the first to our knowledge to describe the tkiNOS gene, and demonstrate that astrovirus infection induces intestinal epithelial cells to express iNOS, suggesting these cells play a key role in the antiviral response to enteric infections. [Copyright &y& Elsevier]

The objective of this study was to evaluate the impact of the video-assisted thoracoscopic (VATS) approach on the outcomes of patients who underwent pneumonectomy. The effect of the surgical approach on perioperative complications and survival in patients who underwent pneumonectomy for nonmetastatic non–small cell lung cancer across 3 institutions (2000-2016) was assessed using multivariable logistic regression, Cox proportional hazards analysis, and propensity-score matching. Completion pneumonectomies were excluded from this study, and an "intent-to-treat" analysis was performed. During the study period, 359 patients met inclusion criteria and underwent pneumonectomy for nonmetastatic non–small cell lung cancer; 124 (35%) underwent pneumonectomy via VATS and 235 (65%) via thoracotomy. Perioperative mortality (VATS, 7% [n = 9] vs open, 8% [n = 19]; P =.75) and morbidity (VATS, 28% [n = 35] vs open, 28% [n = 65]; P =.91) were similar between the groups, even after multivariable adjustment. VATS showed similar 5-year survival when compared with thoracotomy in unadjusted analysis (47% [95% confidence interval (CI), 36-56] vs 33% [95% CI, 27-40]; P =.19), even after multivariable adjustment (hazard ratio, 0.76 [95% CI, 0.50-1.18]; P =.23). In a propensity score–matched analysis that balanced patient characteristics, there were no significant differences found in overall survival between the 2 groups (P =.69). Although the role of VATS pneumonectomy will likely become clearer as more surgeons report results, this multicenter study suggests that the VATS approach for pneumonectomy can be performed safely, with at least equivalent oncologic outcomes when compared with thoracotomy. [ABSTRACT FROM AUTHOR]