Assessment of Functioning of Village Health and Sanitation Committees (VHSCs) of Indore District

Background: The NRHM framework of implementation mentions provision of Village Health and Sanitation Committee (VHSC) in each revenue village that has to be formed within the overall framework of Panchayati Raj Institution (PRI). Objective: To review the current status of formation, training and functioning of VHSCs in Indore district and mechanism of utilization of united funds in these VHSCs. Materials and Methods: A cross sectional study was carried out in 32 villages, of four blocks of Indore district. Different stakeholders of VHSCs of these 32 villages were included purposively as study subjects. Data was collected using predesigned, pretested semi structured questionnaires and checklist. Total of 133 interviews of different stakeholders and 32 record reviews were carried out. The quantitative data collected by interviews and record reviews was analyzed by SPSS software and qualitative data was analyzed manually using qualifier. Results: Significant association between knowledge and awareness about any aspect of VHSC and type of stakeholder has been observed. PRI members and Self Help Group (SHG) members have been found to be totally ignorant about many aspects of VHSC. No formal training has ever been imparted to the members of VHSCs regarding functioning of VHSC at village level. None of the functionaries were found to be aware of village health plan. Conclusion: The efficiency and impact of VHSCs have been found to be very limited

Nepal's Response to Earthquake 2015: Experience of Emergency Responders and Humanitarian Assistance providers in Inclusive and Accessible Humanitarian Assistance Delivery

The earthquake that hit Nepal in 2015 received worldwide attention for the devastation it caused to lives and infrastructures. Yet, the impact of it on people with disabilities (PWDs) and experiences of emergency responders and humanitarian assistance providers have remained under researched. This study aims to explore first hand experiences faced by emergency responders and humanitarian assistance providers to evaluate the effectiveness in implementation of disability inclusive and accessible emergency response during disaster; and to identify good practices and barriers faced by them in facilitating inclusive and accessible recovery and rehabilitation post disaster. Lessons learnt from barriers and challenges faced by the service providers, when addressed, will promote improved policies, processes and programmes around inclusive and accessible emergency and humanitarian response, recovery and rehabilitation. This study is based on semi-structured interviews with 20 key informants/stakeholders, and thematic analysis of the data generated. Findings suggest that most stakeholders were engaged in disability inclusive disaster risk management (DiDRM), capacity building and resilience developing awareness campaigns. However, there are significant gaps in policies, training and practices. These gaps include, a dire lack of inclusive and accessible equipment and resources; lack of and failure to implement and utilise knowledge and resources available; lack of data and guidelines on disability inclusive emergency response (DIER); and lack of communication and coordination between emergency responders and DPOs. These challenges hindered search and rescue (SAR) and relief efforts resulting in inappropriate and slow recovery and rehabilitation for PWDs. This study recommends for including PWDs in planning, designing and building inclusive and accessible emergency preparedness, response, SAR toolkit and emergency shelters. Nepal now has opportunities to integrate accessible infrastructures, DiDRM and implementation at community level. One way of achieving DiDRM at community level could be building a bank of desegregated data, skilled volunteers and accessible equipment to meet the emergency needs of PWDs

Comparison of multiplex meta analysis techniques for understanding the acute rejection of solid organ transplants

<p>Abstract</p> <p>Background</p> <p>Combining the results of studies using highly parallelized measurements of gene expression such as microarrays and RNAseq offer unique challenges in meta analysis. Motivated by a need for a deeper understanding of organ transplant rejection, we combine the data from five separate studies to compare acute rejection versus stability after solid organ transplantation, and use this data to examine approaches to multiplex meta analysis.</p> <p>Results</p> <p>We demonstrate that a commonly used parametric effect size estimate approach and a commonly used non-parametric method give very different results in prioritizing genes. The parametric method providing a meta effect estimate was superior at ranking genes based on our gold-standard of identifying immune response genes in the transplant rejection datasets.</p> <p>Conclusion</p> <p>Different methods of multiplex analysis can give substantially different results. The method which is best for any given application will likely depend on the particular domain, and it remains for future work to see if any one method is consistently better at identifying important biological signal across gene expression experiments.</p

Ten Years of Pathway Analysis: Current Approaches and Outstanding Challenges

Pathway analysis has become the first choice for gaining insight into the underlying biology of differentially expressed genes and proteins, as it reduces complexity and has increased explanatory power. We discuss the evolution of knowledge base–driven pathway analysis over its first decade, distinctly divided into three generations. We also discuss the limitations that are specific to each generation, and how they are addressed by successive generations of methods. We identify a number of annotation challenges that must be addressed to enable development of the next generation of pathway analysis methods. Furthermore, we identify a number of methodological challenges that the next generation of methods must tackle to take advantage of the technological advances in genomics and proteomics in order to improve specificity, sensitivity, and relevance of pathway analysis

Non-invasive measurements of exhaled NO and CO associated with methacholine responses in mice

<p>Abstract</p> <p>Background</p> <p>Nitric oxide (NO) and carbon monoxide (CO) in exhaled breath are considered obtainable biomarkers of physiologic mechanisms. Therefore, obtaining their measures simply, non-invasively, and repeatedly, is of interest, and was the purpose of the current study.</p> <p>Methods</p> <p>Expired NO (E_NO) and CO (E_CO) were measured non-invasively using a gas micro-analyzer on several strains of mice (C57Bl6, IL-10^-/-, A/J, MKK3^-/-, JNK1^-/-, NOS-2^-/-and NOS-3^-/-) with and without allergic airway inflammation (AI) induced by ovalbumin systemic sensitization and aerosol challenge, compared using independent-sample t-tests between groups, and repeated measures analysis of variance (ANOVA) within groups over time of inflammation induction. E_NOand E_COwere also measured in C57Bl6 and IL-10-/- mice, ages 8–58 weeks old, the relationship of which was determined by regression analysis. S-methionyl-L-thiocitrulline (SMTC), and tin protoporphyrin (SnPP) were used to inhibit neuronal/constitutive NOS-1 and heme-oxygenase, respectively, and alter NO and CO production, respectively, as assessed by paired t-tests. Methacholine-associated airway responses (AR) were measured by the enhanced pause method, with comparisons by repeated measures ANOVA and post-hoc testing.</p> <p>Results</p> <p>E_NOwas significantly elevated in naïve IL-10^-/-(9–14 ppb) and NOS-2^-/-(16 ppb) mice as compared to others (average: 5–8 ppb), whereas E_COwas significantly higher in naïve A/J, NOS-3^-/-(3–4 ppm), and MKK3^-/-(4–5 ppm) mice, as compared to others (average: 2.5 ppm). As compared to C57Bl6 mice, AR of IL-10^-/-, JNK1^-/-, NOS-2^-/-, and NOS-3^-/-mice were decreased, whereas they were greater for A/J and MKK3^-/-mice. SMTC significantly decreased E_NOby ~30%, but did not change AR in NOS-2^-/-mice. SnPP reduced E_COin C57Bl6 and IL-10^-/-mice, and increased AR in NOS-2^-/-mice. E_NOdecreased as a function of age in IL-10^-/-mice, remaining unchanged in C57Bl6 mice.</p> <p>Conclusion</p> <p>These results are consistent with the ideas that: 1) E_NOis associated with mouse strain and knockout differences in NO production and AR, 2) alterations of E_NOand E_COcan be measured non-invasively with induction of allergic AI or inhibition of key gas-producing enzymes, and 3) alterations in AR may be dependent on the relative balance of NO and CO in the airway.</p

Exhaled carbon monoxide in asthmatics: a meta-analysis

<p>Abstract</p> <p>Background</p> <p>The non-invasive assessment of airway inflammation is potentially advantageous in asthma management. Exhaled carbon monoxide (eCO) measurement is cheap and has been proposed to reflect airway inflammation and oxidative stress but current data are conflicting. The purpose of this meta-analysis is to determine whether eCO is elevated in asthmatics, is regulated by steroid treatment and reflects disease severity and control.</p> <p>Methods</p> <p>A systematic search for English language articles published between 1997 and 2009 was performed using Medline, Embase and Cochrane databases. Observational studies comparing eCO in non-smoking asthmatics and healthy subjects or asthmatics before and after steroid treatment were included. Data were independently extracted by two investigators and analyzed to generate weighted mean differences using either a fixed or random effects meta-analysis depending upon the degree of heterogeneity.</p> <p>Results</p> <p>18 studies were included in the meta-analysis. The eCO level was significantly higher in asthmatics as compared to healthy subjects and in intermittent asthma as compared to persistent asthma. However, eCO could not distinguish between steroid-treated asthmatics and steroid-free patients nor separate controlled and partly-controlled asthma from uncontrolled asthma in cross-sectional studies. In contrast, eCO was significantly reduced following a course of corticosteroid treatment.</p> <p>Conclusions</p> <p>eCO is elevated in asthmatics but levels only partially reflect disease severity and control. eCO might be a potentially useful non-invasive biomarker of airway inflammation and oxidative stress in nonsmoking asthmatics.</p

Purine Nucleoside Phosphorylase mediated molecular chemotherapy and conventional chemotherapy: A tangible union against chemoresistant cancer

Background Late stage Ovarian Cancer is essentially incurable primarily due to late diagnosis and its inherent heterogeneity. Single agent treatments are inadequate and generally lead to severe side effects at therapeutic doses. It is crucial to develop clinically relevant novel combination regimens involving synergistic modalities that target a wider repertoire of cells and lead to lowered individual doses. Stemming from this premise, this is the first report of two- and three-way synergies between Adenovirus-mediated Purine Nucleoside Phosphorylase based gene directed enzyme prodrug therapy (PNP-GDEPT), docetaxel and/or carboplatin in multidrug-resistant ovarian cancer cells. Methods The effects of PNP-GDEPT on different cellular processes were determined using Shotgun Proteomics analyses. The in vitro cell growth inhibition in differentially treated drug resistant human ovarian cancer cell lines was established using a cell-viability assay. The extent of synergy, additivity, or antagonism between treatments was evaluated using CalcuSyn statistical analyses. The involvement of apoptosis and implicated proteins in effects of different treatments was established using flow cytometry based detection of M30 (an early marker of apoptosis), cell cycle analyses and finally western blot based analyses. Results Efficacy of the trimodal treatment was significantly greater than that achieved with bimodal- or individual treatments with potential for 10-50 fold dose reduction compared to that required for individual treatments. Of note was the marked enhancement in apoptosis that specifically accompanied the combinations that included PNP-GDEPT and accordingly correlated with a shift in the expression of anti- and pro-apoptotic proteins. PNP-GDEPT mediated enhancement of apoptosis was reinforced by cell cycle analyses. Proteomic analyses of PNP-GDEPT treated cells indicated a dowregulation of proteins involved in oncogenesis or cancer drug resistance in treated cells with accompanying upregulation of apoptotic- and tumour- suppressor proteins. Conclusion Inclusion of PNP-GDEPT in regular chemotherapy regimens can lead to significant enhancement of the cancer cell susceptibility to the combined treatment. Overall, these data will underpin the development of regimens that can benefit patients with late stage ovarian cancer leading to significantly improved efficacy and increased quality of life

Improving local health through community health workers in Cambodia: challenges and solutions

Volunteer community health workers (CHWs) are an important link between the public health system and the community. The ‘Community Participation Policy for Health’ in Cambodia identifies CHWs as key to local health promotion and as a critical link between district health centres and the community. However, research on the challenges CHWs face and identifying what is required to optimise their performance is limited in the Cambodian context. This research explores the views of CHWs in rural Cambodia, on the challenges they face when implementing health initiatives