Despite the prevalence of H5N1 influenza viruses in global avian populations, comparatively few cases have been diagnosed in humans. Although viral factors almost certainly play a role in limiting human infection and disease, host genetics most likely contribute substantially. To model host factors in the context of influenza virus infection, we determined the lethal dose of a highly pathogenic H5N1 virus (A/Hong Kong/213/03) in C57BL/6J and DBA/2J mice and identified genetic elements associated with survival after infection. The lethal dose in these hosts varied by 4 logs and was associated with differences in replication kinetics and increased production of proinflammatory cytokines CCL2 and tumor necrosis factor alpha in susceptible DBA/2J mice. Gene mapping with recombinant inbred BXD strains revealed five loci or Qivr (quantitative trait loci for influenza virus resistance) located on chromosomes 2, 7, 11, 15, and 17 associated with resistance to H5N1 virus. In conjunction with gene expression profiling, we identified a number of candidate susceptibility genes. One of the validated genes, the hemolytic complement gene, affected virus titer 7 days after infection. We conclude that H5N1 influenza virus-induced pathology is affected by a complex and multigenic host component.

BACKGROUND: In considering treatment allocation for patients with early esophageal adenocarcinoma, the incidence of lymph node metastasis is a critical determinant; however, this has not been well defined or stratified by the relevant clinical predictors of lymph node spread. METHODS: Data from the Surveillance, Epidemiology, and End Results database of the National Cancer Institute were abstracted from 2004 to 2010 for patients with early-stage esophageal adenocarcinoma. The incidence of lymph node involvement for patients with Tis, T1a, and T1b tumors was examined and was stratified by predictors of spread. RESULTS: A total of 13,996 patients with esophageal adenocarcinoma were evaluated. Excluding those with advanced, metastatic, and/or invasive (T2-T4) disease, 715 patients with Tis, T1a, and T1b tumors were included. .001]) were found to be independently associated with lymph node metastases. There was no lymph node spread noted with Tis tumors. For patients with low-grade (well or moderately differentiated) tumors measuring <2 cm in size, the risk of lymph node metastasis was 1.7% for T1a (P<.001) and 8.6% for T1b (P 5 .001) tumors. CONCLUSIONS: For patients with low-grade Tis or T1 tumors measuring 2 cm in size, the incidence of lymph node metastasis appears to be comparable to the mortality rate associated with esophagectomy. For highly selected patients with early esophageal adenocarcinomas, the results of the current study support the recommendation that local endoscopic resection can be considered as an alternative to surgical management when followed by rigorous endoscopic and radiographic surveillance. Cancer 2016;122:2150-7.

Intravascular imaging modalities have an imperative role in contemporary cardiovascular research. Currently, there are several invasive imaging modalities available in the cardiac catheterization laboratory and new technologies are under development. In the current review, we aimed to provide an update on the research applications of contemporary intravascular imaging tools in the cardiac catheterization laboratory. For the purpose of this review, we separately discuss imaging tools for assessment of epicardial disease (fractional flow reserve and hyperemic stenosis resistance), microvascular function (coronary flow reserve, hyperemic microvascular resistance, and index of microcirculatory resistance), endothelial function, atherosclerotic plaque and vascular remodeling (intravascular ultrasound, optical coherence tomography, angioscopy, and near-infrared spectroscopy), and finally the emerging modalities (palpography and wall shear stress profiling).

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