Impact and cost-effectiveness of rotavirus vaccination in Bangladesh.

INTRODUCTION: Diarrheal disease is a leading cause of child mortality globally, and rotavirus is responsible for more than a third of those deaths. Despite substantial decreases, the number of rotavirus deaths in children under five was 215,000 per year in 2013. Of these deaths, approximately 41% occurred in Asia and 3% of those in Bangladesh. While Bangladesh has yet to introduce rotavirus vaccination, the country applied for Gavi support and plans to introduce it in 2018. This analysis evaluates the impact and cost-effectiveness of rotavirus vaccination in Bangladesh and provides estimates of the costs of the vaccination program to help inform decision-makers and international partners. METHODS: This analysis used Pan American Health Organization's TRIVAC model (version 2.0) to examine nationwide introduction of two-dose rotavirus vaccination in 2017, compared to no vaccination. Three mortality scenarios (low, high, and midpoint) were assessed. Benefits and costs were examined from the societal perspective over ten successive birth cohorts with a 3% discount rate. Model inputs were locally acquired and complemented by internationally validated estimates. RESULTS: Over ten years, rotavirus vaccination would prevent 4000 deaths, nearly 500,000 hospitalizations and 3 million outpatient visits in the base scenario. With a Gavi subsidy, cost/disability adjusted life year (DALY) ratios ranged from $58/DALY to$142/DALY averted. Without a Gavi subsidy and a vaccine price of $2.19 per dose, cost/DALY ratios ranged from$615/DALY to $1514/DALY averted. CONCLUSION: The discounted cost per DALY averted was less than the GDP per capita for nearly all scenarios considered, indicating that a routine rotavirus vaccination program is highly likely to be cost-effective. Even in a low mortality setting with no Gavi subsidy, rotavirus vaccination would be cost-effective. These estimates exclude the herd immunity benefits of vaccination, so represent a conservative estimate of the cost-effectiveness of rotavirus vaccination in Bangladesh

2D-electrophoresis and multiplex immunoassay proteomic analysis of different body fluids and cellular components reveal known and novel markers for extended fasting

Proteomic technologies applied for profiling human biofluids and blood cells are considered to reveal new biomarkers of exposure or provide insights into novel mechanisms of adaptation

Over-the-Counter Monocyclic Non-Steroidal Anti-Inflammatory Drugs in Environment—Sources, Risks, Biodegradation

Recently, the increased use of monocyclic non-steroidal anti-inflammatory drugs has resulted in their presence in the environment. This may have potential negative effects on living organisms. The biotransformation mechanisms of monocyclic nonsteroidal anti-inflammatory drugs in the human body and in other mammals occur by hydroxylation and conjugation with glycine or glucuronic acid. Biotransformation/biodegradation of monocyclic non-steroidal anti-inflammatory drugs in the environment may be caused by fungal or bacterial microorganisms. Salicylic acid derivatives are degraded by catechol or gentisate as intermediates which are cleaved by dioxygenases. The key intermediate of the paracetamol degradation pathways is hydroquinone. Sometimes, after hydrolysis of this drug, 4- aminophenol is formed, which is a dead-end metabolite. Ibuprofen is metabolized by hydroxylation or activation with CoA, resulting in the formation of isobutylocatechol. The aim of this work is to attempt to summarize the knowledge about environmental risk connected with the presence of over-the-counter antiinflammatory drugs, their sources and the biotransformation and/or biodegradation pathways of these drugs

Synthesis of steroidal imidazolidinthiones as potential apoptotic agents: Investigation by theoretical and experimental studies

New steroidal imidazolidinthione derivatives (4-6) were synthesized from steroidal thiosemicarbazones and dichloroethane. The synthesized compounds were characterized using spectral data analysis. Theoretical DFT involving B3LYP/6-31G** level of theory was employed to gain insights into the molecular structure of the target compounds. MEPS and FMO analysis were carried out. HOMO-LUMO energy gap was determined which helped to evaluate various global descriptors like hardness, chemical potential, electronegativity, nucleophilicity and electrophilicity index, etc. The calculated properties established that the synthesized products are more or less similar in their reactivity behaviour. To explore their biological potential, interaction studies of compounds (4-6) with DNA were carried out using various biophysical techniques. The compounds bind DNA preferentially through electrostatic and hydrophobic interactions with K-b of 3.21 x 10(3) M-1, 2.79 x 10(3) M-1 and 2.26 x 10(3) M-1, respectively indicating the higher binding affinity of compound 4 towards DNA. Gel electrophoresis of compound 4 demonstrated strong interaction during the concentration dependent cleavage activity with pBR322 DNA. It was observed that these steroidal imidazolidinthiones are minor groove binders of DNA which was validated using molecular docking studies. An in vitro cytotoxicity screening using MTT assay revealed that the compounds (4-6) exhibit potential toxicity against different human cancer cells. Highest antiproliferative effect was observed on HeLa cells by compound 4. The results suggested that compounds 4-6 cause apoptotic cell death by cleaving apoptotic protein caspase-3 and suppress anti-apoptotic protein Bcl-2 in HeLa cancer cells

DNA binding, artificial nuclease activity and cytotoxic studies of newly synthesized steroidal pyrimidines

The new steroidal pyrimidine derivatives (4-6) were synthesized by the reaction of steroidal thiosemicarbazones with (2-methyl) diethyl malonate in absolute ethanol. After characterization by spectral and analytical data, the DNA interaction studies of compounds (4-6) were carried out by UV-vis, fluorescence spectroscopy, hydrodynamic measurements, molecular docking and gel electrophoresis. The compounds bind to DNA preferentially through electrostatic and hydrophobic interactions with K-b; 2.31 x 10(3) M-1, 1.93 x 10(3) M-1 and 2.05 x 10(3) M-1, respectively indicating the higher binding affinity of compound 4 towards DNA. Gel electrophoresis demonstrated that compound 4 showed a strong interaction during the concentration dependent cleavage activity with pBR322 DNA. The molecular docking study suggested the intercalation of steroidal pyrimidine moiety in the minor groove of DNA. During in vitro cytotoxicity, compounds (4-6) revealed potential toxicity against the different human cancer cells (MTT assay). During DAPI staining, the nuclear fragmentations on cells occurred after treatment with compounds 4 and 5. Western blotting analysis clearly indicates that compound 4 causes apoptosis in MCF-7 cancer cells. The results revealed that compound 4 has better prospectus to act as a cancer chemotherapeutic candidate, which warrants further in vivo anticancer investigations. (C) 2017 Published by Elsevier B.V