A Prominent Role for DC-SIGN+ Dendritic Cells in Initiation and Dissemination of Measles Virus Infection in Non-Human Primates

Measles virus (MV) is a highly contagious virus that is transmitted by aerosols. During systemic infection, CD150+T and B lymphocytes in blood and lymphoid tissues are the main cells infected by pathogenic MV. However, it is unclear which cell types are the primary targets for MV in the lungs and how the virus reaches the lymphoid tissues. In vitro studies have shown that dendritic cell (DC) C-type lectin DC-SIGN captures MV, leading to infection of DCs as well as transmission to lymphocytes. However, evidence of DC-SIGN-mediated transmission in vivo has not been established. Here we identified DC-SIGNhiDCs as first target cells in vivo and demonstrate that macaque DC-SIGN functions as an attachment receptor for MV. Notably, DC-SIGNhicells from macaque broncho-alveolar lavage and lymph nodes transmit MV to B lymphocytes, providing in vivo support for an important role for DCs in both initiation and dissemination of MV infection

Factors associated with disease evolution in Greek patients with inflammatory bowel disease

BACKGROUND: The majority of Crohn's disease patients with B1 phenotype at diagnosis (i.e. non-stricturing non-penetrating disease) will develop over time a stricturing or a penetrating pattern. Conflicting data exist on the rate of proximal disease extension in ulcerative colitis patients with proctitis or left-sided colitis at diagnosis. We aimed to study disease evolution in Crohn's disease B1 patients and ulcerative colitis patients with proctitis and left-sided colitis at diagnosis. METHODS: 116 Crohn's disease and 256 ulcerative colitis patients were followed-up for at least 5 years after diagnosis. Crohn's disease patients were classified according to the Vienna criteria. Data were analysed actuarially. RESULTS: B1 phenotype accounted for 68.9% of Crohn's disease patients at diagnosis. The cumulative probability of change in disease behaviour in B1 patients was 43.6% at 10 years after diagnosis. Active smoking (Hazard Ratio: 3.01) and non-colonic disease (non-L2) (Hazard Ratio: 3.01) were associated with behavioural change in B1 patients. Proctitis and left-sided colitis accounted for 24.2%, and 48.4% of ulcerative colitis patients at diagnosis. The 10 year cumulative probability of proximal disease extension in patients with proctitis and left-sided colitis was 36.8%, and 17.1%, respectively (p: 0.003). Among proctitis patients, proximal extension was more common in non-smokers (Hazard Ratio: 4.39). CONCLUSION: Classification of Crohn's disease patients in B1 phenotype should be considered as temporary. Smoking and non-colonic disease are risk factors for behavioural change in B1 Crohn's disease patients. Proximal extension is more common in ulcerative colitis patients with proctitis than in those with left-sided colitis. Among proctitis patients, proximal extension is more common in non-smokers

A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

Acetylcholine contributes through muscarinic receptors to attentional modulation in V1

Attention exerts a strong influence over neuronal processing in cortical areas. It selectively increases firing rates and affects tuning properties, including changing receptive field locations and sizes. Although these effects are well studied, their cellular mechanisms are poorly understood. To study the cellular mechanisms, we combined iontophoretic pharmacological analysis of cholinergic receptors with single cell recordings in V1 while rhesus macaque monkeys (Macaca mulatta) performed a task that demanded top-down spatial attention. Attending to the receptive field of the V1 neuron under study caused an increase in firing rates. Here we show that this attentional modulation was enhanced by low doses of acetylcholine. Furthermore, applying the muscarinic antagonist scopolamine reduced attentional modulation, whereas the nicotinic antagonist mecamylamine had no systematic effect. These results demonstrate that muscarinic cholinergic mechanisms play a central part in mediating the effects of attention in V1

Consensus guidelines for the definition of time-to-event end points in image-guided tumor ablation: Results of the sio and datecan initiative

There is currently no consensus regarding preferred clinical outcome measures following image-guided tumor ablation or clear definitions of oncologic end points. This consensus document proposes standardized definitions for a broad range of oncologic outcome measures with recommendations on how to uniformly document, analyze, and report outcomes. The initiative was coordinated by the Society of Interventional Oncology in collaboration with the Definition for the Assessment of Time-to-Event End Points in Cancer Trials, or DATECAN, group. According to predefined criteria, based on experience with clinical trials, an international panel of 62 experts convened. Recommendations were developed using the validated three-step modified Delphi consensus method. Consensus was reached on when to assess outcomes per patient, per session, or per tumor; on starting and ending time and survival time definitions; and on time-to-event end points. Although no consensus was reached on the preferred classification system to report complications, quality of life, and health economics issues, the panel did agree on using the most recent version of a validated patient-reported outcome questionnaire. This article provides a framework of key opinion leader recommendations with the intent to facilitate a clear interpretation of results and standardize worldwide communication. Widespread adoption will improve reproducibility, allow for accurate comparisons, and avoid misinterpretations in the field of interventional oncology research