Risk factors for Nipah virus encephalitis in Bangladesh

Nipah virus (NiV) is a paramyxovirus that causes severe encephalitis in humans. During January 2004, twelve patients with NiV encephalitis (NiVE) were identified in west-central Bangladesh. A case-control study was conducted to identify factors associated with NiV infection. NiVE patients from the outbreak were enrolled in a matched case-control study. Exact odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by using a matched analysis. Climbing trees (83% of cases vs. 51% of controls, OR 8.2, 95% CI 1.25-infinity) and contact with another NiVE patient (67% of cases vs. 9% of controls, OR 21.4, 95% CI 2.78-966.1) were associated with infection. We did not identify an increased risk for NiV infection among persons who had contact with a potential intermediate host. Although we cannot rule out person-to-person transmission, case-patients were likely infected from contact with fruit bats or their secretions.     

Pharmacologic synergy between dual phosphoinositide-3-kinase and mammalian target of rapamycin inhibition and 5-fluorouracil in PIK3CA mutant gastric cancer cells

Phosphoinositide-3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitors are an emerging class of anti-cancer agents. Here, we tested the hypothesis that the dual PI3K/mTOR inhibitor, PI103, could synergize with the chemotherapeutic agent, 5-fluorouracil (5-FU) by inhibiting E2F1, thymidylate synthase (TS) and enhancing DNA damage. Drug combination effects were assessed in gastric cancer cells using the median-effect equation. The specific effects of inhibition of E2F1 and PIK3CA were examined by siRNA, and mTOR by rapamycin exposure. Protein expression and apoptosis pre- and post-treatment was measured using standard methods. PI103 and 5-FU was synergistic in 3/5 gastric cancer cell lines tested. Synergy was associated with PI3KCA mutation, reduced TS and E2F1 protein levels, increased H2AX phosphorylation and apoptosis. E2F1 siRNA enhanced sensitivity to 5-FU only in cells displaying synergy. Excess thymidine exposure converted synergism to antagonism in all cells. Inhibition of PI3K and mTOR alone enhanced 5-FU cytotoxicity in only 2/3 cell lines that displayed synergy each. In AGS cells, PI3K inhibition alone enhanced 5-FU sensitivity as much as dual PI3K/mTOR inhibition. In HGC27 cells, dual inhibition increased 5-FU sensitivity more than single PI3K or mTOR inhibition. Combined PI103 and 5-FU treatment reduced in vivo tumor growth more than treatment with single agents. PI3K/mTOR inhibitors can enhance 5-FU cytotoxicity in vitro and in vivo, especially in PIK3CA mutant tumor cells. Dual, rather than single, PI3K/mTOR inhibitors may combine better with 5-FU due to cellular heterogeneity in sensitivity to PI3K and mTOR inhibition.     

Pilot Survey of Subway and Bus Stop Noise Levels

Excessive noise exposure is a serious global urban health problem, adversely affecting millions of people. One often cited source of urban noise is mass transit, particularly subway systems. As a first step in determining risk within this context, we recently conducted an environmental survey of noise levels of the New York City transit system. Over 90 noise measurements were made using a sound level meter. Average and maximum noise levels were measured on subway platforms, and maximum levels were measured inside subway cars and at several bus stops for comparison purposes. The average noise level measured on the subway platforms was 86 ± 4 dBA (decibel-A weighting). Maximum levels of 106, 112, and 89 dBA were measured on subway platforms, inside subway cars, and at bus stops, respectively. These results indicate that noise levels in subway and bus stop environments have the potential to exceed recommended exposure guidelines from the World Health Organization (WHO) and U.S. Environmental Protection Agency (EPA), given sufficient exposure duration. Risk reduction strategies following the standard hierarchy of control measures should be applied, where feasible, to reduce subway noise exposure.Gershon and Barrera are with the Department of Sociomedical Sciences, Columbia University, Mailman School of Public Health, 600 West 168th Street, 4th Floor, New York, NY 10032, USA; Neitzel is with the Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98105, USA; Akram is with the Department of Environmental Health Sciences, Columbia University, Mailman School of Public Health, New York, NY 10032, USA.     

Treatment of chronic myeloid leukemia in the imatinib era: perspective from a developing country

BACKGROUND: There is paucity of data from developing countries on the efficacy and safety of imatinib mesylate in chronic myeloid leukemia (CML). The primary objective of this study was to document complete and partial cytogenetic responses to imatinib in all phases of CML. Secondary objectives included evaluations of complete hematologic response, safety, time to progression, and survival. METHODS: Two hundred seventy-five patients in all phases of CML who received treatment with imatinib from January 2001 to December 2005 were included in the study. All patients had on bone marrow or BCR-ABL positive in peripheral blood by polymerase chain reaction. RESULTS: After a median follow-up of 18 months, major cytogenetic responses (Ph <35%) in chronic phase (CP), accelerated phase (AP), and blastic phase (BP) were documented in 61%, 57%, and 28% of patients, respectively. A complete cytogenetic response was observed in 39.4%, 35.7%, and 14.3% of patients in CP, AP, and BP, respectively; and a complete hematologic response was observed in 90%, 86%, and 30%, respectively. The median time to progression at 18 months was 91% in CP and 68% in AP. The overall survivals in CP, AP, and BP at 18 months was 92%, 74%, and 38%, respectively. CONCLUSIONS: Impressive hematologic, cytogenetic, and molecular responses to imatinib were observed, similar to the responses reported in patients from Western countries. Patients had good compliance, toxicity was limited, and overall quality of life was improved markedly. The results indicated that the biology of CML is not different in patients from developing countries.     

From Molecular Pathology of COVID-19 to Nigella Sativum as a Treatment Option:Scientific Based Evidence of Its Myth or Reality

COVID-19 virus is a causative agent of viral pandemic in human beings which specifically targets respiratory system of humans and causes viral pneumonia.This un...     

Intracardiac versus transesophageal echocardiography to guide transcatheter closure of interatrial communications: Nationwide trend and comparative analysis

Objectives

This study aimed to assess current temporal trends in utilization of ICE versus TEE guided closure of interatrial communications, and to compare periprocedural complications and resource utilization between the two imaging modalities.

Background

While transesophageal echocardiography (TEE) has historically been used to guide percutaneous structural heart interventions, intracardiac echocardiography (ICE) is being increasingly utilized to guide many of these procedures such as closure of interatrial communications.

Methods

Using the Nationwide Inpatient Sample, all patients aged >18 years, who underwent ASD or PFO closure with either ICE or TEE guidance between 2003 and 2014 were included. Comparative analysis of outcomes and resource utilization was performed using a propensity score‐matching model.

Results

ICE guidance for interatrial communication closure increased from 9.7% in 2003 to 50.6% in 2014. In the matched model, the primary endpoint of major adverse cardiovascular events occurred less frequently in the ICE group versus the TEE group (11.1% vs 14.3%, respectively, P = 0.008), mainly driven by less vascular complications in the ICE group (0.5% vs 1.3%, P = 0.045). Length of stay was shorter in the ICE group (3 ± 4 vs 4 ± 4 days, P < 0.0001). Cost was similar in the two groups 18 454 ± 17 035$ in the TEE group vs 18 278 ± 15 780$ in the ICE group (P = 0.75).

Conclusions

Intracardiac echocardiogram utilization to guide closure of interatrial communications has plateaued after a rapid rise throughout the 2000s. When utilized to guide interatrial communication closure procedure, ICE is as safe as TEE and does not increase cost or prolonged hospitalizations.

     

Naringina e Trimetazidina Melhoram a Sensibilidade Barorreflexa e a Atividade Elétrica do Trato Solitário do Núcleo na Lesão de Isquemia-Reperfusão Renal

Background:Nucleus tractus solitarius (NTS) is a brain area that plays a key role in kidney and cardiovascular regulation via baroreceptors impulses.Objectives:The aim of this study was to evaluate the effect of naringin (NAR) and trimetazidine (TMZ) alone and their combination on NTS electrical activity and baroreceptor sensitivity (BRS) in renal ischemia- reperfusion (I/R) injury.Methods:Forty male Sprague-Dawley rats (200- 250 g) were allocated into 5 groups with 8 in each. 1) Sham; 2) I/R; 3) TMZ 5 mg/kg; 4) NAR 100 mg/kg; and 5) TMZ5+ NAR100. The left femoral vein was cannulated to infuse saline solution or drug and the BRS was evaluated. I/R was induced by occlusion of renal pedicles for 45 min, followed by 4 hours of reperfusion. The NTS local electroencephalogram (EEG) was recorded before, during ischemia and throughout the reperfusion. Phenylephrine was injected intravenously to evaluate BRS at the end of reperfusion time. The data were analyzed by two-way repeated measurement ANOVA followed by Tukey''s post hoc test. A p-value <0.05 was considered significant.Results:NTS electrical waves did not change during ischemia time, while they significantly decreased during the entire reperfusion time. NTS electrical activity and BRS dramatically reduced in rats with I/R injury; however, administration of NAR, TMZ alone or their combination significantly improved these changes in rats with I/R injury.Conclusions:The results showed that I/R injury leads to reduced BRS and NTS electrical activity and there may be an association between I/R and decreased BRS. In addition, NAR and TMZ are promising agents to treat I/R complications.