Burden of rotavirus gastroenteritis in the Middle Eastern and North African pediatric population

Background

The primary strategy to interrupt transmission of wild poliovirus in India is to improve supplemental immunization activities and routine immunization coverage in priority districts with a focus on 107 high-risk blocks of western Uttar Pradesh and central Bihar. Villages or urban areas with a history of wild poliovirus transmission, or hard-to-reach or resistant populations are categorized as high-risk areas within blocks. The Social Mobilization Network (SM Net) was formed in Uttar Pradesh in 2003 to support polio eradication efforts through improved planning, implementation and monitoring of social mobilization activities in those high-risk areas. In this paper, we examine the vaccination outcomes in districts of SM Net where the CORE Group works.

Methods

We carried out a secondary data analysis of routine monitoring information collected by the SM Net and the Government of India. These data include information about vaccination outcomes in SM Net areas and non-SM Net areas within the districts where the CORE Group operates. Statistical analysis was used to compare, between SM Net and non-SM Net areas, vaccination outcomes considered sensitive to social mobilization efforts of the SM Net. We employed Generalized Estimating Equations (GEE) statistical method to account for Intra-cluster Correlation (ICC), and used 'Quasi-likelihood under the independence model criterion (QIC)' as the model selection method.

Results

Vaccination outcomes in SM Net areas were as high as or higher than in non-SM Net areas. There was considerable variation in vaccination outcomes between districts.

Conclusions

While not conclusive, the results suggest that the social mobilization efforts of the SM Net and the CORE Group are helping to increase vaccination levels in high-risk areas of Uttar Pradesh. Vaccination outcomes in CORE Group areas were equal or higher than in non-CORE, non-SM Net areas. This occurred even though SM Net areas are those with more community resistance to polio vaccination and/or are have harder-to-reach populations than non-SM Net areas. Other likely explanations for the relatively good vaccination performance in SM Net areas are not apparent.     

The use of ultrasound to assess aortic biomechanics: Implications for aneurysm and dissection

Arterial stiffening, which occurs when conduit arteries thicken and lose elasticity, has been associated with cardiovascular disease and increased risk for future cardiovascular events. Specifically, aortic stiffening plays a large role in the pathogenesis of vascular diseases, such as aneurysm formation and dissection. Current parameters used to assess risk of aortic rupture include absolute diameter and growth rate. However, these properties lack the reliability required to accurately risk-stratify patients. As with any elastic conduit, it is important to assess the biomechanical properties of the aorta in order to assess cardiovascular risk and prevent disease progression. There are several invasive and noninvasive methods by which stiffness of the large arteries can be assessed. Of particular interest are ultrasound-based methods, such as tissue Doppler imaging and speckle-tracking echocardiography, due to their noninvasive and feasible nature. In this review, we summarize studies demonstrating utility of noninvasive ultrasound imaging methods for measuring aortic biomechanics for the assessment and management of aortic aneurysms.     

The PRC1 Polycomb group complex interacts with PLZF/RARA to mediate leukemic transformation

Ectopic repression of retinoic acid (RA) receptor target genes by PML/RARA and PLZF/RARA fusion proteins through aberrant recruitment of nuclear corepressor complexes drives cellular transformation and acute promyelocytic leukemia (APL) development. In the case of PML/RARA, this repression can be reversed through treatment with all-trans RA (ATRA), leading to leukemic remission. However, PLZF/RARA ectopic repression is insensitive to ATRA, resulting in persistence of the leukemic diseased state after treatment, a phenomenon that is still poorly understood. Here we show that, like PML/RARA, PLZF/RARA expression leads to recruitment of the Polycomb-repressive complex 2 (PRC2) Polycomb group (PcG) complex to RA response elements. However, unlike PML/RARA, PLZF/RARA directly interacts with the PcG protein Bmi-1 and forms a stable component of the PRC1 PcG complex, resulting in PLZF/RARA-dependent ectopic recruitment of PRC1 to RA response elements. Upon treatment with ATRA, ectopic recruitment of PRC2 by either PML/RARA or PLZF/RARA is lost, whereas PRC1 recruited by PLZF/RARA remains, resulting in persistent RA-insensitive gene repression. We further show that Bmi-1 is essential for the PLZF/RARA cellular transformation property and implicates a central role for PRC1 in PLZF/RARA-mediated myeloid leukemic development.     

Identifying Patients Eligible for a Short Hospital Stay After Stoma Closure

Introduction: The implementation of enhanced recovery programmes after elective colorectal surgery has dramatically reduced the length of stay. The objective of this study was to assess the selection of good candidates for short post-operative stay (GCSS) in the context of stoma closure. Methods: Between January 2011 and December 2014, 222 patients were included in the present retrospective, single-center study. The primary endpoint was the proportion of GCSS. We also identified factors associated with GCSS status and built a predictive score. Results: The study population was predominantly male (n = 122, 55%). 60% of the patients had undergone ileostomy and 85% had undergone hand-sewn anastomosis. The postoperative ileus rate was 5% and the readmission rate was 3.5%. 41% (n = 92) of the study population were considered to be GCSS. In a multivariate analysis, age under 50 (odds ratio (OR) [95% confidence interval (CI)] = 2.8 [1.2-5.6], p = 0.008), the absence of vascular comorbidities (OR [95%CI] = 3.2 [1.3-12.3]; p = 0.006) and stapled anastomosis (OR: 4.2, 95%CI: 1.1-17.3, p = 0.03) were associated with GCSS status. Predictive scores of 0, 1, 2, and 3 were associated with GCSS rates of 20%, 18%, 44%, and 62%, respectively (p < 0.001). Conclusion: In the context of stoma closure, 41% of patients were GCSS.     

Fisetin disposition and metabolism in mice: Identification of geraldol as an active metabolite

Although the natural flavonoid fisetin (3,3′,4′,7-tetrahydroxyflavone) has been recently identified as an anticancer agent with antiangiogenic properties in mice, its in vivo pharmacokinetics and metabolism are presently not characterized. Our purpose was to determine the pharmacokinetics and metabolism of fisetin in mice and determine the biological activity of a detected fisetin metabolite. After fisetin administration of an efficacious dose of 223 mg/kg i.p. in mice, the maximum fisetin concentration reached 2.5 μg/ml at 15 min and the plasma concentration declined biphasically with a rapid half-life of 0.09 h and a terminal half-life of 3.1 h. Three metabolites were detected, one of which was a glucuronide of fisetin (M1), whereas another glucuronide (M2) was a glucuronide of a previously unknown fisetin metabolite (M3). HPLC–MS/MS analysis indicated that M3 was a methoxylated metabolite of fisetin (MW = 300 Da). The UV spectrum of M3 was identical to that of fisetin and standard 3,4′,7-trihydroxy-3′-methoxyflavone (geraldol). In addition, because M3 co-eluted with standard geraldol in 4 different chromatographic ternary gradient conditions, M3 was therefore assigned to geraldol. Of interest, this metabolite was shown to achieve higher concentrations than fisetin in Lewis lung tumors. We also compared the cytotoxic and antiangiogenic activities of fisetin and geraldol in vitro and it was found that the latter was more cytotoxic than the parent compound toward tumor cells, and that it could also inhibit endothelial cells migration and proliferation. In conclusion, these results suggest that fisetin metabolism plays an important role in its in vivo anticancer activities.     

Involvement of Nrf2 activation in resistance to 5-fluorouracil in human colon cancer HT-29 cells

Acquisition of drug resistance by cancer cells is attributed to various factors including alterations in apoptotic pathways, enhanced expression of multidrug resistance-associated proteins, altered drug metabolism or uptake and/or overexpression of cytoprotective genes. Thus, potential induction of defence pathways by anticancer drugs might have a marked incidence on cancer cell resistance. 5-Fluorouracil (5-FU) remains the most commonly used anticancer drug for the treatment of colorectal cancer, although objective response rates are as low as 20%. The aim of our study was to investigate the effects of 5-FU on cytoprotective systems in human colon HT-29 cells. Our results demonstrate that 5-FU induced the expression of mRNAs encoding glutathione transferases and antioxidant enzymes. To further determine the mechanisms involved in 5-FU effects, we investigated whether it activates the Nrf2/antioxidant response element pathway which is implicated in the regulation of several genes involved in cytoprotection. Translocation of Nrf2 into the nucleus after 5-FU exposure was demonstrated by immunocytochemistry and western blotting. Using an ARE-driven reporter gene assay, activation of the luciferase activity by 5-FU was also evidenced. Moreover, transfection of HT-29 cells with siRNA directed against Nrf2 inhibited induction of Nrf2 target genes and increased 5-FU cytotoxicity. In conclusion, we demonstrate for the first time that 5-FU activates the Nrf2/ARE pathway which in turn induces cytoprotective genes and modulates chemosensitivity of HT-29 colon cancer cells. Therefore, we postulate that Nrf2 might represent a potential therapeutic target in 5-FU treatment of colon cancer.