Coordinated induction of cell survival signaling in the inflamed microenvironment of the prostate

PURPOSE: Both prostate cancer and benign prostatic hyperplasia are associated with inflammatory microenvironments. Inflammation is damaging to tissues, but it is unclear how the inflammatory microenvironment protects specialized epithelial cells that function to proliferate and repair the tissue. The objective of this study is to characterize the cell death and cell survival response of the prostatic epithelium in response to inflammation. METHODS: We assessed induction of cell death (TNF, TRAIL, TWEAK, FasL) and cell survival factors (IGFs, hedgehogs, IL-6, FGFs, and TGFs) in inflamed and control mouse prostates by ELISA. Cell death mechanisms were determined by immunoblotting and immunofluorescence for cleavage of caspases and TUNEL. Survival pathway activation was assessed by immunoblotting and immunofluorescence for Mcl-1, Bcl-2, Bcl-XL, and survivin. Autophagy was determined by immunoblotting and immunofluorescence for free and membrane associated light chain 3 (LC-3). RESULTS: Cleavage of all four caspases was significantly increased during the first 2 days of inflammation, and survival protein expression was substantially increased subsequently, maximizing at 3 days. By 5 days of inflammation, 50% of prostatic epithelial cells expressed survivin. Autophagy was also evident during the recovery phase (3 days). Finally, immunofluorescent staining of human specimens indicates strong activation of survival proteins juxtaposed to inflammation in inflamed prostate specimens. CONCLUSIONS: The prostate responds to deleterious inflammation with induction of cell survival mechanisms, most notably survivin and autophagy, demonstrating a coordinated induction of survival factors that protects and expands a specialized set of prostatic epithelial cells as part of the repair and recovery process during inflammation

Anorectic and aversive effects of GLP-1 receptor agonism are mediated by brainstem cholecystokinin neurons, and modulated by GIP receptor activation

This work was funded by an MRC Career Development Award (MR/ P009824/1 and MR/P009824/2) to GD’A, as well as an MRC grant to SML/GD’A (MR/T032669/1), a BBSRC grant to SML (BB/M001067/1), and an additional direct contribution from Eli Lilly. D.J.H. was sup- ported by MRC (MR/N00275X/1 and MR/S025618/1), Diabetes UK (17/ 0005681), and the European Research Council (ERC) under the Eu- ropean Union’s Horizon 2020 research and innovation programme (Starting Grant 715884 to D.J.H.). AC was supported for part of this project by a travel grant from the Italian Society of Pharmacology and a fellowship from the Veronesi Foundation (Italy).Peer reviewedPublisher PD

Increasing human papillomavirus vaccination in a federally qualified health center organization using a systems‑based intervention integrating EHR and statewide immunization information system

Public acceptance of the HPV vaccine has not matched that of other common adolescent vaccines, and HPV vaccination rates remain below the Healthy People 2020 target of 80% compliance. The purpose of this study was to evaluate the capacity of nine pediatric clinics in a Federally Qualified Health Center organization to implement a systems-based intervention targeting office staff and providers using EHRs and a statewide immunization information system to increase HPV vaccination rates in girls and boys, ages 11 to 16 over a 16-month period. System changes included automated HPV prompts to staff, postcard reminders to parents when youths turned 11 or 12 years old, and monthly assessment of provider vaccination rates. During the intervention, 8960 patients (11–16 yo) were followed, with 48.8% girls (n=4370) and 51.2% boys (n=4590). For this study period, 80.5% of total patients received the first dose of the HPV vaccine and 47% received the second dose. For the first dose, 55.5% of 11 year old girls and 54.3% of 11 year old boys were vaccinated. For ages 12 to 16, first dose vaccination rates ranged from the lowest rate of 84.5% for 14 yo girls up to the highest rate of 90.5% for 13 yo boys. Logistic regression showed age was highly significantly associated with first dose completion (OR 1.565, 95% CI 1.501, 1.631) while males did not have a significant association with first dose completion compared to females. The intervention increased overall counts of first and second HPV vaccination rates.Journal ArticleFinal article publishe