Comparison of age-specific hospitalization during pandemic and seasonal influenza periods from 2009 to 2012 in Taiwan: a nationwide population-based study

BACKGROUND: Determining the age-specific hospitalization burden associated with seasonal influenza and the (H1N1) 2009 pandemic is important for the development of effective vaccine strategies and clinical management. The aim of this study was to investigate age-specific differences in hospitalization rates during the pandemic and seasonal periods. METHODS: Using the Taiwan National Health Insurance Research Database (NHIRD), we identified hospitalized patients with a principle discharge diagnosis of influenza-related infection (ICD-9-CM 487) between 2009 and 2012. RESULTS: Based on the time distribution of influenza-related hospitalizations and previously reported epidemic periods, the first and second waves of the (H1N1) 2009 pandemic (p1 is known as 2009.07-2010.01, and p2 is known as 2010.12-2011.03) and three seasonal periods (s1 is known as 2010.03-2010.11, s2 is known as 2011.10-2012.03, and s3 is known as 2012.04-2012.10) were found. During these five periods, children younger than 7 years of age consistently had the highest hospitalization rate of the studied age groups. In individuals younger than 50 years of age, the seasonal periods were associated with a significantly lower risk of hospitalization than that of p1 (Relative risk (RR) range = 0.18–0.85); however, they had a significantly higher hospitalization risk for adults over 50 years of age (RR = 1.51–3.22). Individuals over 50 years of age also had a higher intensive care unit admission rate and case fatality ratio than individuals under than 50 years of age during the seasonal periods and especially during the pandemic periods. CONCLUSIONS: In both pandemic and seasonal periods, the highest hospitalization rate was observed for children younger than 7 years of age. Adults over 50 years of age had a higher hospitalization risk during the seasonal periods and a higher clinical severity during the pandemic periods. Those results emphasize that the importance of influenza-related prevention strategies in the younger and older age groups, either seasonal or pandemic periods

Clinical significance of erythropoietin receptor expression in oral squamous cell carcinoma

BACKGROUND: Hypoxic tumors are refractory to radiation and chemotherapy. High expression of biomarkers related to hypoxia in head and neck cancer is associated with a poorer prognosis. The present study aimed to evaluate the clinicopathological significance of erythropoietin receptor (EPOR) expression in oral squamous cell carcinoma (OSCC). METHODS: The study included 256 patients who underwent primary surgical resection between October 1996 and August 2005 for treatment of OSCC without previous radiotherapy and/or chemotherapy. Clinicopathological information including gender, age, T classification, N classification, and TNM stage was obtained from clinical records and pathology reports. The mRNA and protein expression levels of EPOR in OSCC specimens were evaluated by Q-RT-PCR, Western blotting and immunohistochemistry assays. RESULTS: We found that EPOR were overexpressed in OSCC tissues. The study included 17 women and 239 men with an average age of 50.9 years (range, 26–87 years). The mean follow-up period was 67 months (range, 2–171 months). High EPOR expression was significantly correlated with advanced T classification (p < 0.001), advanced TNM stage (p < 0.001), and positive N classification (p = 0.001). Furthermore, the univariate analysis revealed that patients with high tumor EPOR expression had a lower 5-year overall survival rate (p = 0.0011) and 5-year disease-specific survival rate (p = 0.0017) than patients who had low tumor levels of EPOR. However, the multivariate analysis using Cox’s regression model revealed that only the T and N classifications were independent prognostic factors for the 5-year overall survival and 5-year disease-specific survival rates. CONCLUSIONS: High EPOR expression in OSCC is associated with an aggressive tumor behavior and poorer prognosis in the univariate analysis among patients with OSCC. Thus, EPOR expression may serve as a treatment target for OSCC in the future

Pin1 positively affects tumorigenesis of esophageal squamous cell carcinoma and correlates with poor survival of patients

BACKGROUND: Pin1 promotes oncogenesis by regulating multiple oncogenic signaling. In this study, we investigated the involvement of Pin1 in tumor progression and in the prognosis of human esophageal squamous cell carcinoma (ESCC). RESULTS: We observed that proliferation, clonogenicity and tumorigenesis of CE81T cells were inhibited by Pin1 knockdown. We next analyzed Pin1 expression in clinical ESCC specimens. When compared to the corresponding non-tumor part, Pin1 protein and mRNA levels in tumor part were higher in 84% and 62% patients, respectively. By immunohistochemistry, we identified that high Pin1 expression was associated with higher primary tumor stage (p = 0.035), higher overall cancer stage (p = 0.047) and poor overall survival (p < 0.001). Furthermore, the association between expression of Pin1 and levels of β-catenin and cyclin D in cell line and clinical specimens was evaluated. β-catenin and cyclin D1 were decreased in CE81T cells with Pin1 knockdown. Cyclin D1 level correlated with Pin1 expression in clinical ESCC specimens. CONCLUSIONS: Pin1 upregulation was associated with advanced stage and poor prognosis of ESCC. Pin1 knockdown inhibited aggressiveness of ESCC cells. β-catenin and cyclin D1 were positively regulated by Pin1. These results indicated that targeting Pin1 pathway could represent a potential modality for treating ESCC

FF-bond: Multi-bit Flip-flop Bonding at Placement

Clock power contributes a significant portion of chip power in modern IC design. Applying multi-bit flip-flops can effectively reduce clock power. State-of-the-artwork performs multi-bit flipflop clustering at the post-placement stage. However, the solution quality may be limited because the combinational gates are immovable during the clustering process. To overcome the deficiency, in this paper, we propose multi-bit flip-flop bonding at placement. Inspired by ionic bonding in Chemistry, we direct flipflops to merging friendly locations thus facilitating flip-flop merging. Experimental results show that our algorithm, called FF-Bond, can save 27% clock power on average. Compared with state-of-the-art post-placement multi-bit flip-flop clustering, FF-Bond can further reduce 14% clock power. © 2013 ACM

Evidence of d-phenylglycine as delivering tool for improving l-dopa absorption

<p>Abstract</p> <p>Background</p> <p><it>l</it>-Dopa has been used for Parkinson's disease management for a long time. However, its wide variety in the rate and the extent of absorption remained challenge in designing suitable therapeutic regime. We report here a design of using <it>d</it>-phenylglycine to guard <it>l</it>-dopa for better absorption in the intestine via intestinal peptide transporter I (PepT1).</p> <p>Methods</p> <p><it>d</it>-Phenylglycine was chemically attached on <it>l</it>-dopa to form <it>d</it>-phenylglycine-<it>l</it>-dopa as a dipeptide prodrug of <it>l</it>-dopa. The cross-membrane transport of this dipeptide and <it>l</it>-dopa via PepT1 was compared in brush-boarder membrane vesicle (BBMV) prepared from rat intestine. The intestinal absorption was compared by <it>in situ </it>jejunal perfusion in rats. The pharmacokinetics after i.v. and p.o. administration of both compounds were also compared in Wistar rats. The striatal dopamine released after i.v. administration of <it>d</it>-phenylglycine-<it>l</it>-dopa was collected by brain microdialysis and monitored by HPLC. Anti-Parkinsonism effect was determined by counting the rotation of 6-OHDA-treated unilateral striatal lesioned rats elicited rotation with (+)-methamphetamine (MA).</p> <p>Results</p> <p>The BBMV uptake of <it>d</it>-phenylglycine-<it>l</it>-dopa was inhibited by Gly-Pro, Gly-Phe and cephradine, the typical PepT1 substrates, but not by amino acids Phe or <it>l</it>-dopa. The cross-membrane permeability (Pm*) determined in rat jejunal perfusion of <it>d</it>-phenylglycine-<it>l</it>-dopa was higher than that of <it>l</it>-dopa (2.58 ± 0.14 vs. 0.94 ± 0.10). The oral bioavailability of <it>d</it>-phenylglycine-<it>l</it>-dopa was 31.7 times higher than that of <it>l-</it>dopa in rats. A sustained releasing profile of striatal dopamine was demonstrated after i. v. injection of <it>d</it>-phenylglycine-<it>l</it>-dopa (50 mg/kg), indicated that <it>d</it>-phenylglycine-<it>l</it>-dopa might be a prodrug of dopamine. <it>d</it>-Phenylglycine-<it>l</it>-dopa was more efficient than <it>l-</it>dopa in lowering the rotation of unilateral striatal lesioned rats (19.1 ± 1.7% vs. 9.9 ± 1.4%).</p> <p>Conclusion</p> <p>The BBMV uptake studies indicated that <it>d</it>-phenylglycine facilitated the transport of <it>l</it>-dopa through the intestinal PepT1 transporter. The higher jejunal permeability and the improved systemic bioavailability of <it>d-</it>phenylglycine-<it>l</it>-dopa in comparison to that of <it>l</it>-dopa suggested that <it>d-</it>phenylglycine is an effective delivery tool for improving the oral absorption of drugs like <it>l</it>-dopa with unsatisfactory pharmacokinetics. The gradual release of dopamine in brain striatum rendered this dipeptide as a potential dopamine sustained-releasing prodrug.</p