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Rats repeatedly exposed to high airborne concentrations of ethylene develop eosinophilic rhinitis and mucous cell hyperplasia/hypertrophy (MCH) in nasal respiratory epithelium. Mechanisms underlying these lesions are not well understood to inform occupational exposure guidelines. In this study, we determined (1) the nasal histopathology in rats episodically exposed to ethylene, (2) the ethylene-induced nasal histopathology in similarly exposed mice, and (3) how innate lymphoid cells (ILCs) play a role in ethylene-induced MCH. BMS493 price Animals were exposed to 0 or 10,000 ppm ethylene, 6 h/d, 5 d/wk, for 2 weeks and sacrificed 1 day or 2 weeks postexposure. Others received three 2-week exposure blocks separated by 2-week intervals of no exposure. Episodic exposure was chosen to aid in distinguishing irritant from immune responses. Mucous cell hyperplasia/hypertrophy was induced by ethylene in both species. Rats developed a mild, but transient, eosinophilic rhinitis. Mucous cell hyperplasia/hypertrophy was transient in mice, but persistent in rats. Increases in epithelial mucosubstances after 2 weeks of exposure were only present in ILC-sufficient mice, but not in ILC-deficient mice suggesting that ILCs play a role in MCH and overexpression of genes associated with mucus production/secretion. These findings in animals suggest that inhaled ethylene does not act as a sensitizing agent and will not induce allergen-like nasal airway disease.Long-acting delivery platforms for intravitreal therapies are an active area of research in ophthalmic drug development. The aim of these platforms is to decrease the burden of intravitreal therapies for patients, by increasing the period between intravitreal injections. This brief communication describes the in-life, histologic and immunohistochemical findings associated with repeat-dose intravitreal administration of poly D, L sustained lactide-co-glycolide polymeric rods, an intravitreal depot, in the cynomolgus monkey (Macaca fascicularis). These nonclinical investigations illustrate a pattern of foreign body reaction around intravitreal depots at the temporal pars plana and demonstrated the histopathologic and immunohistologic features of retinal degeneration and epiretinal membrane formation in the inferior retina.

Progress in precision medicine relies on the access to, use of, and exchange of genomic and associated clinical data, including from children. The ethical, legal, and social issues (ELSI) of such data access, use, and exchange may be accentuated in the pediatric context due in part to the highly sensitive nature of genomic data, children’s consent-related vulnerabilities, and uncertain risks of reidentification. Systematic analyses of the ELSI and scientific reasons for why and how genomic data may be shared responsibly are, however, limited.

We conducted a modified systematic review of reasons according to Sofaer and Strech to examine the ELSI and scientific reasons for “responsible” sharing of children’s genomic and associated clinical data. Empirical articles, commentaries, and data-sharing policies indexed in Medline, Scopus, Web of Science, and BIOSIS were included in the analysis if they discussed ELSI and were published between 2003 and 2017 in English.

One hundred and fifty-one records met ourue reasons and 8 subreasons for why children’s genomic data should or should not be shared. Enhancing the prospect of direct and indirect benefits and maximizing the utility of children’s data were top reasons why data should be shared. Inadequate data privacy protection was the leading reason why it should not. We furthermore identified 8 reasons and 30 subreasons that support conditional data sharing, in which recontact for the continued use of children’s data once they reach the age of majority was the most frequently endorsed condition. Conclusions The complete list of ELSI reasons and responsible conditions provides an evidentiary basis upon which institutions can develop data-sharing policies. Institutions should encourage the sharing of children’s data to advance genomic research, while heeding special reconsent and data protection mechanisms that may help mitigate uncertain longitudinal risks for children and families.SOX2 is a major transcriptional regulator of stem cell pluripotency and self-renewability. Its expression in cancer stem cells from several different tumor types in humans and rodent models directly implicates SOX2 in tumorigenicity, metastasis, drug resistance, recurrence, and poor survival. Our objective was to investigate the expression of SOX2 in canine neoplasia. Immunohistochemistry for SOX2 was performed in sets of 10 archived formalin-fixed paraffin-embedded tissues from 45 distinct canine neoplasms. Normal expression of SOX2 was evaluated in a canine tissue microarray. Strong and diffuse SOX2 intranuclear immunolabeling was consistently found in the majority of ectodermal (13/15) and endodermal tumors (5/7). Negative, variable, or inconsistent SOX2 intranuclear immunolabeling was detected in the majority of mesodermal tumors (10/16) and in tumors with dual or uncertain origin (5/7). Although further studies are necessary to understand mechanistically how SOX2 contributes to the biology of each tumor type, this study demonstrates the expression of SOX2 in a wide variety of canine cancers. In the future, screening methods based on cellular plasticity and pluripotency biomarkers may provide avenues for the rational design of therapeutic strategies that target vulnerable signals upstream or downstream of SOX2 in different cancers, and possibly offer novel clinical applications for SOX2 as a prognostic indicator.Calf muscle pump (CMP) promotes venous return from the lower extremity and contributes to preload and cardiac output. Impaired CMP function may reflect a measure of frailty or cumulative disease burden or may impede cardiac function. The study objective was to test the hypothesis that impaired CMP negatively impacts survival. Consecutive adult patients who underwent venous strain gauge plethysmography at the Mayo Clinic Gonda Vascular Laboratory (January 1, 1998 – December 31, 2011) were assessed for overall survival. Patients with venous incompetence, venous obstruction or unilateral calf pump dysfunction were excluded. Risk of mortality was assessed with Cox proportional hazard ratios and after adjusting for Charlson Comorbidity Index variables. Over the study period, 2728 patients were included in the analysis. Compared to patients with normal CMP, those with impaired CMP were older (p less then 0.001), predominantly female (p = 0.01) and had higher mean Charlson scores (p less then 0.001). Patients with impaired CMP had a higher mortality rate at 5 (8.