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Treating neuropathic pain is a critical clinical issue. Although numerous therapies have been proposed, effective treatments have not been established. Therefore, safe and feasible treatment methods are urgently needed. In this study, we investigated the therapeutic effects of autologous intrathecal administration of bone-marrow-derived mononuclear cells (MNCs) on neuropathic pain. We generated a mouse model of neuropathic pain by transecting the spinal nerve and evaluated neuropathic pain by measuring the mechanical threshold in the following 14 days. Mice in the MNC injection group had a higher mechanical threshold than those in the buffer group. We assessed the effect of MNC treatment on the dorsal root ganglia and spinal cord by immunohistochemistry, mRNA expression, and cytokine assay. The migration and accumulation of microglia were significantly suppressed in the MNC group, and the mRNA expression of inflammatory cytokines such as interleukin (IL)-6, IL-1β, and tumor necrosis factor alpha (TNF-α) was markedly downregulated. Furthermore, MNC administration tended to suppress various cytokines in the cerebrospinal fluid of the model mice. In conclusion, our results suggest that intrathecal injection of MNCs relieves neuropathic pain and might be a promising cell therapy for the treatment of this condition. © 2020 The Author(s).Background The objective of this study was to investigate whether 100% antiretroviral therapy (ART) adherence in men with HIV (MWH) is associated with normalization of concentrations of biomarkers of inflammation and immune activation compared with HIV-uninfected men. Methods We analyzed person-visits with available biomarker data from the Multicenter AIDS Cohort Study (MACS) among MWH receiving ART with HIV RNA  less then 50 copies/mL and among HIV-uninfected men. Self-reported adherence was classified as 100% if no missed ART doses in the past 4 days were reported. We evaluated associations between ART adherence and concentrations of 24 serum biomarkers compared with HIV-uninfected visits using a generalized gamma model, adjusting for potential confounders. Results Person-visits (2565 from MWH reporting 100% ART adherence and 1588 from HIV-uninfected men) from a total of 1469 men were included in the analysis. Serum concentrations of interleukin-6 (IL-6), soluble interleukin-6 receptor (sIL-6R), IL-1β, interferon-γ (IFN-γ), chemokine C-C motif ligand 2 (CCL2), and CCL14 from person-visits among MWH who reported 100% adherence were similar to HIV-uninfected person-visits. Comparatively higher concentrations of 11 biomarkers and lower concentrations of 7 biomarkers were observed in person-visits from MWH who reported 100% ART adherence, compared with HIV-uninfected person-visits. Conclusions Although MWH with virologic suppression who reported 100% ART adherence exhibited overall higher concentrations of biomarkers of inflammation and immune activation compared with HIV-uninfected men, some biomarker concentrations were similar in both groups. These findings suggest that optimal ART adherence could have clinical implications beyond achieving and sustaining viral suppression. © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.Background Procalcitonin testing has been adopted by antimicrobial stewardship programs as a means of reducing inappropriate antibiotic use, including within intensive care units (ICUs). However, concerns regarding procalcitonin's sensitivity exist. The purpose of this study is to calculate the sensitivity of procalcitonin for bacteremia among hospitalized patients. Methods This was a retrospective cohort study of adult patients admitted to an academic medical center between July 1, 2018, and June 30, 2019, with ≥1 positive blood culture within 24 hours of admission and procalcitonin testing within 48 hours. Low procalcitonin was defined as 24-hour delayed receipt of antibiotic therapy (3% vs 8%; P = .04), including among patients admitted to the ICU (1% vs 18%; P = .02). Conclusions The sensitivity of procalcitonin for bacteremia is unacceptably low for a rule-out test. Antimicrobial stewardship programs should use caution before promoting the withholding of antibiotic therapy for patients with low initial procalcitonin values. © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.Background Sharing needles and ancillary injecting equipment is a primary risk exposure for hepatitis C virus (HCV) infection among people who inject drugs (PWID); however, infectivity of these exposures is not well quantified. We aimed to estimate per-event HCV infectivity associated with receptive needle sharing (RNS) among susceptible PWID. Methods Participants in a prospective cohort study of young adult PWID who were anti-HCV and HCV RNA negative at baseline and attended at least 2 follow-up study visits between 2003 and 2014 were eligible. Data were selected from the first HCV-negative through the first HCV-positive visit (or last HCV-negative among those uninfected). Anti-HCV and HCV-RNA tests were used to determine infection status. A probabilistic exposure model linking observed HCV infection outcomes to self-reported exposure events was applied to estimate infectivity. Results Among 344 participants, a maximum likelihood estimate considering RNS yielded a pooled population per RNS event HCV probability of 0.25% (95% confidence interval [CI], 0.10%-0.43%), and 1.12% (95% CI, 0.48%-2.35%) among those who acquired any HCV infection (primary or reinfection). Conclusions HCV is highly infectious in association with RNS, a primary injection-related risk exposure. Dinaciclib concentration Our infectivity estimate among participants who acquired any HCV infection is 1.7 times higher than that estimated for HIV infection in PWID and 2.24 times higher than that estimated among health care workers exposed through needle sticks. The strengths of this study include the assessment of receptive needle sharing events, the prospective design, and relatively short recall and testing periods. These results can inform transmission models and research to prevent HCV infection. © The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
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