Ruane et al. demonstrate a role for the microbiota in modulating protective immunity to intranasal vaccination via the ability of lung dendritic cells to induce B cell IgA class switching.

Intranasal vaccination generates immunity across local, regional and distant sites. However, nasal dendritic cells (DC), pivotal for the induction of intranasal vaccine- induced immune responses, have not been studied in detail. Here, using a variety of parameters, we define nasal DCs in mice and humans. Distinct subsets of “classical” DCs, dependent on the transcription factor zbtb46 were identified in the murine nose. The murine nasal DCs were FLT3 ligand-responsive and displayed unique phenotypic and functional characteristics including the ability to present antigen, induce an allogeneic T cell response and migrate in response to LPS or live bacterial pathogens. Importantly, in a cohort of human volunteers, BDCA-1+ DCs were observed to be the dominant nasal DC population at steady state. During chronic inflammation, the frequency of both BDCA-1+ and BDCA-3hi DCs was reduced in the nasal tissue, associating the loss of these immune sentinels with chronic nasal inflammation. The present study is the first detailed description of the phenotypic, ontogenetic and functional properties of nasal DCs and will inform the design of preventative immunization strategies as well as therapeutic modalities against chronic rhinosinusitis.

Alcohol intake has consistently shown a J- or U-shaped relationship with several cardiovascular diseases. Light to moderate alcohol intake has been associated with lower risk of coronary artery disease, heart failure (HF), as well as CV mortality. On the other hand, heavy consumption has been associated with deleterious CV outcomes including increased mortality. However, the evidence is based from observational and population-based studies where risk of confounding cannot be excluded even after meticulous methodological approaches. This is compounded by conflicting data such as higher risk of certain CV diseases like HF in former drinkers compared to abstainers. Further, Mendelian randomization studies using genetic polymorphisms in enzymes have recently questioned the beneficial association of low-moderate drinking with CV system. There has been substantial and consistent evidence that light to moderate alcohol consumption have beneficial effect on overall cardiovascular profile and mortality. However, there are considerable limitations in the reported literature to determine a strong causality of a protective effect of moderate alcohol consumption by itself. Further robust studies or possibly a well-structured randomized controlled could bring an end to this debate.

Niacin therapy does not lead to significant reductions in total or cause-specific mortality or recurrent cardiovascular events among persons with or at risk of atherosclerotic cardiovascular disease.

Dialysis patients are at high risk for infective endocarditis (IE); however, no large contemporary data exist on this issue. We examined outcomes of 44 816 patients with IE on dialysis and 202 547 patients with IE not on dialysis from the Nationwide Inpatient Sample database from 2006 thorough 2011. Dialysis patients were younger (59 AE 15 years vs 62 AE 18 years) and more likely to be female (47% vs 40%) and African-American (47% vs 40%; all P < 0.001). Hospitalizations for IE in the dialysis group increased from 175 to 222 per 10 000 patients (P trend = 0.04). Staphylococcus aureus was the most common microorganism isolated in both dialysis (61%) and nondialysis (45%) groups. IE due to were less likely (all P < 0.001). Dialysis patients had higher in-hospital mortality (aOR: 2.13, 95% CI: 2.04-2.21), lower likelihood of valve-replacement surgery (aOR: 0.82, 95% CI: 0.76-0.86), and higher incidence of stroke (aOR: 1.08, 95% CI: 1.03-1.12; all P < 0.001). We demonstrate rising incidence of IE-related hospitalizations in dialysis patients, highlight significant differences in baseline comorbidities and microbiology of IE compared with the general population, and validate the association of longterm dialysis with worse in-hospital outcomes. K E Y W O R D SInfective Endocarditis, End-Stage Renal Disease, Outcomes

Early readmissions are frequent after LVAD implantation even in contemporary times. Preimplant identification of high-risk patients, and a protocol-driven follow-up using a multidisciplinary approach will be needed to reduce readmissions and improve outcomes.

Objective Injection drug use (IDU) remains a major risk factor for HIV-1 acquisition. The complex interplay between drug use, non-sterile injection, and Hepatitis C remains poorly understood. We conducted a pilot study to determine the effect of IDU on immune parameters among HIV-uninfected and -infected individuals. We hypothesized that IDU could further augment immunological changes associated with HIV-1 infection, which could in turn affect HIV pathogenesis Methods HIV-uninfected and -infected subjects with IDU, and non-IDU controls were recruited to obtain socio-demographic and drug-related behaviours. Blood (PBMC) and mucosal (MMC) mononuclear cells were analysed for cellular markers of immune activation (CD38 and Ki67). Serum ELISA was performed to determine levels of soluble CD14, a marker of immune activation. Results No significant quantitative differences in CD4+ and CD8+ T cell levels were observed between IDU and non-IDU subjects when accounting for the presence of HIV-1 infection. However, increased levels of cellular and soluble markers of immune activation were documented in cells and plasma of HIV-uninfected IDU subjects compared to non-injectors. Additionally, sharing of injection paraphernalia was related to immune activation among HIV-uninfected IDU subjects. Conclusion IDU, with or without HIV-1 infection, results in a significant increase in immune activation in both the peripheral blood and the GI tract. This may have significant impact on HIV transmission, pathogenesis, and immunologic responses to combination antiviral therapy. This study provides compelling preliminary results which in turn support larger studies to better define the relationship between IDU, infection with HIV-1, co-infection with Hepatitis C and immunity.

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