TheamnGene Product Is Required in Extraembryonic Tissues for the Generation of Middle Primitive Streak Derivatives

AbstractThe primitive streak is the defining feature of the gastrulating mouse embryo. Currently, little is known in the mouse about the mechanisms that mediate the assembly of the primitive streak or about the signaling pathways that specify the different types of mesoderm and endoderm generated from the streak. To gain insight into primitive streak assembly and function, we have conducted a detailed phenotypic characterization ofamnionless,a transgene-induced insertional mouse mutation that arrests embryonic development during gastrulation. Our histological and molecular analyses, when examined in the context of the mouse gastrula fate map, lead to the model that middle streak formation is specifically impaired in theamnionlessmutant. Significantly, these observations argue that the formation of the middle streak is mediated by a pathway that is genetically separable from those that direct the specification of the distal and proximal streak regions. Intriguingly, our findings from wt ES cell ↔amnionless−/−blastocyst chimeras indicate that this proposed separate pathway for middle streak formation is dependent onamnionlessgene functions in the visceral endoderm

Long-term outcome of vertebral artery origin stenosis in patients with acute ischemic stroke

BACKGROUND: Vertebral artery origin (VAO) stenosis is occasionally observed in patients who have acute ischemic stroke. We investigated the long-term outcomes and clinical significance of VAO stenosis in patients with acute ischemic stroke. METHODS: We performed a prospective observational study using a single stroke center registry to investigate the risk of recurrent stroke and vascular outcomes in patients with acute ischemic stroke and VAO stenosis. To relate the clinical significance of VAO stenosis to the vascular territory of the index stroke, patients were classified into an asymptomatic VAO stenosis group and a symptomatic VAO stenosis group. RESULTS: Of the 774 patients who had acute ischemic stroke, 149 (19.3%) of them had more than 50% stenosis of the VAO. During 309 patient-years of follow-up (mean, 2.3 years), there were 7 ischemic strokes, 6 hemorrhagic strokes, and 2 unknown strokes. The annual event rates were 0.97% for posterior circulation ischemic stroke, 4.86% for all stroke, and 6.80% for the composite cardiovascular outcome. The annual event rate for ischemic stroke in the posterior circulation was significantly higher in patients who had symptomatic VAO stenosis than in patients who had asymptomatic stenosis (1.88% vs. 0%, p = 0.046). In a multivariate analysis, the hazard ratio, per one point increase of the Essen Stroke Risk Score (ESRS) for the composite cardiovascular outcome, was 1.46 (95% CI, 1.02-2.08, p = 0.036). CONCLUSIONS: Long-term outcomes of more than 50% stenosis of the VAO in patients with acute ischemic stroke were generally favorable. Additionally, ESRS was a predictor for the composite cardiovascular outcome. Asymptomatic VAO stenosis may not be a specific risk factor for recurrent ischemic stroke in the posterior circulation. However, VAO stenosis may require more clinical attention as a potential source of recurrent stroke when VAO stenosis is observed in patients who have concurrent ischemic stroke in the posterior circulation

Single-virion sequencing of lamivudine-treated HBV populations reveal population evolution dynamics and demographic history.

BACKGROUND: Viral populations are complex, dynamic, and fast evolving. The evolution of groups of closely related viruses in a competitive environment is termed quasispecies. To fully understand the role that quasispecies play in viral evolution, characterizing the trajectories of viral genotypes in an evolving population is the key. In particular, long-range haplotype information for thousands of individual viruses is critical; yet generating this information is non-trivial. Popular deep sequencing methods generate relatively short reads that do not preserve linkage information, while third generation sequencing methods have higher error rates that make detection of low frequency mutations a bioinformatics challenge. Here we applied BAsE-Seq, an Illumina-based single-virion sequencing technology, to eight samples from four chronic hepatitis B (CHB) patients - once before antiviral treatment and once after viral rebound due to resistance. RESULTS: With single-virion sequencing, we obtained 248-8796 single-virion sequences per sample, which allowed us to find evidence for both hard and soft selective sweeps. We were able to reconstruct population demographic history that was independently verified by clinically collected data. We further verified four of the samples independently through PacBio SMRT and Illumina Pooled deep sequencing. CONCLUSIONS: Overall, we showed that single-virion sequencing yields insight into viral evolution and population dynamics in an efficient and high throughput manner. We believe that single-virion sequencing is widely applicable to the study of viral evolution in the context of drug resistance and host adaptation, allows differentiation between soft or hard selective sweeps, and may be useful in the reconstruction of intra-host viral population demographic history

Renal Cell Carcinoma in Young Patients is Associated with Poorer Prognosis

Abstract Introduction: Renal cell carcinoma (RCC) in young patients is uncommon but thought to represent a distinctive clinical entity from older patients with different clinico-pathologic features and outcomes. We evaluated the association of age at the time of diagnosis with pathological staging, histological parameters, disease recurrence and overall survival (OS) following radical or partial nephrectomy for non-metastatic RCC in native kidneys. Materials and Methods: A retrospective review of 316 patients with RCC after nephrectomy at a single institution between January 2001 and June 2008 was performed. Eligible patients included all histologically proven primary non-metastatic RCC treated by radical or partial nephrectomy. They were categorised into group A (≤40 years at diagnosis) and B (>40 years). Differences in clinical parameters were analysed using the Mann Whitney U test. The prognostic potential of age at diagnosis was evaluated using Cox proportional hazards regression. Survival was estimated using the Kaplan Meier method. Results: There were 33 patients in group A and 283 patients in group B. There were more non-clear cell tumours in the younger group (30% vs 14%, P <0.05). No statistical differences were found in the stage and grade of both groups. At a median follow-up time of 41 months, the younger group had a higher metastatic rate (18% vs 10.5%, P <0.05), lower 5-year cancer-specifi c survival (82% vs 98%, P <0.05) and lower 5-year OS (82 % vs 95%, P <0.05). Conclusion: Younger patients were more likely to have non-clear cell RCC with higher disease recurrence and lower OS. They should not be assumed to have similar features and outcomes as screen-detected early RCC in older patients

Review of the Current Status of Intra-Arterial Thrombolysis for Treating Acute Cerebral Infarction: a Retrospective Analysis of the Data from Multiple Centers in Korea

Objective The purpose of the study was to review the current status of intra-arterial (IA) thrombolysis in Korea by conducting a retrospective analysis of the data from multiple domestic centers. Materials and Methods The radiologists at each participating institution were asked to fill out case report forms on all patients who had undergone IA recanalization due to acute anterior circulation ischemia. These forms included clinical, imaging and procedure-related information. A central reader analyzed the CT/MR and angiographic results. The rates of successful recanalization, hemorrhagic transformation and functional outcome were obtained. The univariate analyses were performed together with the multivariate analysis. Results We analyzed the data from 163 patients, and they had been treated at seven institutes. The initial imaging modalities were CT for 46 patients (28%), MR for 63 (39%), and both for 54 (33%). Various mechanical treatment methods were applied together in 50% of the patients. Radiologically significant hemorrhage was noted in 20/155 patients (13%). We found various factors that influenced the recanalization rate and the occurrence of significant hemorrhagic transformations. The favorable outcome rate, reported as modified Rankin Scale ≤ 2, was 40%, and the mortality rate was 11%. The factors that predicted a poor functional outcome were old age (p = 0.01), initially severe neurological symptoms (p < 0.0001), MR findings of a wide distribution of lesions (p = 0.001), involvement of the basal ganglia (p = 0.01), performance of procedures after working hours (p = 0.01), failure of recanalization (p = 0.003), contrast extravasation after the procedure (p = 0.007) and significant hemorrhagic transformation (p = 0.002). The subsequent multivariate analysis failed to show any statistically significant variable. Conclusion There was a trend toward increased dependency on MR imaging during the initial evaluation and increased usage of combined pharmacologic/mechanical thrombolysis. The imaging and clinical outcome results of this study were comparable to those of the previous major thrombolytic trials.ope