Effects of Probiotics on Colitis-Induced Exacerbation of Alzheimer's Disease in AppNL-G-F Mice.

Alzheimer's disease (AD) is characterized by progressive cognitive decline and is a leading cause of death in the United States. Neuroinflammation has been implicated in the progression of AD, and several recent studies suggest that peripheral immune dysfunction may influence the disease. Continuing evidence indicates that intestinal dysbiosis is an attribute of AD, and inflammatory bowel disease (IBD) has been shown to aggravate cognitive impairment. Previously, we separately demonstrated that an IBD-like condition exacerbates AD-related changes in the brains of the AppNL-G-F mouse model of AD, while probiotic intervention has an attenuating effect. In this study, we investigated the combination of a dietary probiotic and an IBD-like condition for effects on the brains of mice. Male C57BL/6 wild type (WT) and AppNL-G-F mice were randomly divided into four groups: vehicle control, oral probiotic, dextran sulfate sodium (DSS), and DSS given with probiotics. As anticipated, probiotic treatment attenuated the DSS-induced colitis disease activity index in WT and AppNL-G-F mice. Although probiotic feeding significantly attenuated the DSS-mediated increase in WT colonic lipocalin levels, it was less protective in the AppNL-G-F DSS-treated group. In parallel with the intestinal changes, combined probiotic and DSS treatment increased microglial, neutrophil elastase, and 5hmC immunoreactivity while decreasing c-Fos staining compared to DSS treatment alone in the brains of WT mice. Although less abundant, probiotic combined with DSS treatment demonstrated a few similar changes in AppNL-G-F brains with increased microglial and decreased c-Fos immunoreactivity in addition to a slight increase in Aß plaque staining. Both probiotic and DSS treatment also altered the levels of several cytokines in WT and AppNL-G-F brains, with a unique increase in the levels of TNFα and IL-2 being observed in only AppNL-G-F mice following combined DSS and probiotic treatment. Our data indicate that, while dietary probiotic intervention provides protection against the colitis-like condition, it also influences numerous glial, cytokine, and neuronal changes in the brain that may regulate brain function and the progression of AD.

Incidental prostate cancer diagnosed at radical cystoprostatectomy for bladder cancer: disease-specific outcomes and survival.

BACKGROUND: The current standard of care for men with muscle-invasive bladder cancer is radical cystoprostatectomy (RCP). One-third of RCP specimens demonstrate incidental prostate cancer, primarily reported in small series with limited follow-up. The aim of this study is to report mature outcomes, including patterns of failure and disease-specific recurrence rates, and survival, for a large cohort of men with incidental prostate cancer at RCP performed at a tertiary referral center. METHODS: This retrospective study describes cancer control and survival rates for men who underwent RCP for bladder cancer and were found incidentally to have prostate cancer. Analysis of patient-, tumor-, and treatment-specific factors were analyzed for association with disease control and survival endpoints. RESULTS: Between 2002 and 2010, 94 patients with incidental discovery of prostate cancer postRCP were identified for inclusion in this study. Forty-five patients (45%) underwent RCP for recurrent (rather than initial presentation of) bladder carcinoma. At a median follow-up of 40.3 months (71.2 months for survivors; range, 8.9-155.5 months), 42 patients were alive without recurrence and 52 patients had died (25 associated with disease). The estimated 5-year bladder cancer disease-free, urinary tract malignancy disease-free, and prostate specific antigen (PSA) relapse-free survivals were 76% [95% confidence interval (CI), 65-84%], 64% (52-74%), and 97% (79-100%), respectively. The estimated 5-year urinary tract malignancy-specific and overall survivals were 61% (49-71%) and 52% (41-62%), respectively. Univariate analysis demonstrated associations between pathologic T/N-stage and nodal ratio with bladder cancer disease-free, urinary tract malignancy disease-specific, and overall survivals, with patient age at diagnosis as an additional adverse factor associated with overall survival. Multivariate analysis confirmed pN-stage and age as independently associated with worse survival. CONCLUSION: For men undergoing RCP for bladder cancer, the present study suggests that incidentally discovered prostate cancers, irrespective of pathologic stage, Gleason score, or clinical significance, do not impact 5-year disease control or survival outcomes.