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Oncolytic herpes simplex viruses (oHSVs) have demonstrated efficient lytic replication in human glioblastoma tumors using immunodeficient mouse models, but early-phase clinical trials have reported few complete responses. Potential reasons for the lack of efficacy are limited vector potency and the suppressive glioma tumor microenvironment (TME). Here we compare the oncolytic activity of two HSV-1 vectors, a KOS-strain derivative KG4:T124 and an F-strain derivative rQNestin34.5v.1, in the CT2A and GL261N4 murine syngeneic glioma models. rQNestin34.5v1 generally demonstrated a greater in vivo viral burden compared to KG4:T124. However, both vectors were rapidly cleared from CT2A tumors, while virus remained ensconced in GL261N4 tumors. Immunological evaluation revealed that the two vectors induced similar changes in immune cell recruitment to either tumor type at 2 days after infection. However, at 7 days after infection, the CT2A microenvironment displayed the phenotype of an untreated tumor, while GL261N4 tumors exhibited macrophage and CD4+/CD8+ T cell accumulation. Furthermore, the CT2A model was completely resistant to virus therapy, while in the GL261N4 model rQNestin34.5v1 treatment resulted in enhanced macrophage recruitment, impaired tumor progression, and long-term survival of a few animals. We conclude that prolonged intratumoral viral presence correlates with immune cell recruitment, and both are needed to enhance anti-tumor immunity.

Although end-stage renal disease (ESRD) and surrogate markers for renal dysfunction are frequently used as outcome markers for IgA nephropathy, the clinical course after reaching ESRD is not well documented. This study examined outcomes of progression to ESRD and age at death in a cohort of adults with IgA nephropathy with a long duration of follow-up. Methods: Patient and kidney survival of 251 adult patients with IgA nephropathy from the southeastern United States diagnosed between January 1, 1976 and December 31, 2005 were analyzed. Results: Median age at diagnosis was 36.9 years. Most patients were men (69%) and Caucasian (95%). Only 46% had an estimated glomerular filtration rate >60 ml/min per 1.73 m2 at diagnosis. Mean follow-up time from time of diagnostic biopsy to death or end of study was 19.3 years. Of 251 patients, 132 (53%) progressed to ESRD and 97 (39%) died. Life expectancy was reduced by 10.1 years, with a median observed age of death at 65.7 years and a median expected age at death of 75.8 years. Eighty-three percent of the deaths occurred after progression to ESRD. Conclusion: Life expectancy is substantially reduced for patients diagnosed with IgA nephropathy in the southeastern United States.

Understanding contextual influences on obesity requires comparison of heterogeneous communities and concurrent assessment of multiple contextual domains. We used a theoretically-based measurement model to assess multidimensional socioeconomic and built environment factors theorized to influence childhood obesity across a diverse geography ranging from rural to urban. Confirmatory factor analysis specified four factors—community socioeconomic deprivation (CSED), food outlet abundance (FOOD), fitness and recreational assets (FIT), and utilitarian physical activity favorability (UTIL)—which were assigned to communities (townships, boroughs, city census tracts) in 37 Pennsylvania counties. Using electronic health records from 2001 to 2012 from 163,820 youth aged 3–18 years from 1288 communities, we conducted multilevel linear regression analyses with factor quartiles and their cross products with age, age2, and age3 to test whether community factors impacted body mass index (BMI) growth trajectories. Models controlled for sex, age, race/ethnicity, and Medical Assistance. Factor scores were lowest in townships, indicating less deprivation, fewer food and physical activity outlets, and lower utilitarian physical activity favorability. BMI at average age was lower in townships versus boroughs (beta [SE]) (0.217 [0.027], P