Computational analysis to predict functional role of hsa-miR-3065-3p as an antiviral therapeutic agent for treatment of triple infections: HCV, HIV-1, and HBV

Background: Triple infection (TI) with HIV-1, HCV, and HBV (TI) is highly prevalent in intravenous drug users (IDUs). These TI patients have a faster progression to AIDS, and even after antiretroviral therapy (ART) the prognosis of their disease is poor. The use of microRNA (miRNA) to silence genes holds potential applications for anti-HCV therapy. Methods: We analyzed the role of human miRNAs (hsa-miRs) in TI by computational analyses for HCV, HIV-1, and HBV showing identity to these three viral genomes. Results: We identified one unique miRNA, hsa-miR-3065-3p, that shares significant mutual identity to these three viral genomes (6183%). In addition, hsa-miR-99, hsa-miR-548, and hsa-miR-122 also showed mutual identity with these three viral genomes, albeit at a lower degree (5288%). Conclusion: Here, we present evidence using essential components of bioinformatics tools, and hypothesize that utility of hsa-miR-3065-3p and perhaps miR-548 would be potential antiviral therapeutic agents in the treatment of TI patients because it shows near perfect alignment in the seed region for all three viruses. We also make an argument that current proposed therapy with hsa-miR-122 may not be the optimal choice for HCV patients since it lacks essential gene alignment and may be harmful for the patients.Keywords: HBV; HCV; HIV-1; homology; identity; inhibition; microRNA-based therapy; RNAi; triple infectio

Silencing of PTK7 in Colon Cancer Cells: Caspase-10-Dependent Apoptosis via Mitochondrial Pathway

Protein tyrosine kinase-7 (PTK7) is a catalytically inactive receptor tyrosine kinase (RTK). PTK7 is upregulated in many common human cancers, including colon cancer, lung cancer, gastric cancer and acute myeloid leukemia. The reason for this up-regulation is not yet known. To explore the functional role of PTK7, the expression of PTK7 in HCT 116 cells was examined using small interference (siRNA)-mediated gene silencing. Following transfection, the siRNA successfully suppressed PTK7 mRNA and protein expression. Knocking down of PTK7 in HCT 116 cells inhibited cell proliferation compared to control groups and induced apoptosis. Furthermore, this apoptosis was characterized by decreased mitochondrial membrane potential and activation of caspase-9 and -10. Addition of a caspase-10 inhibitor totally blocked this apoptosis, suggesting that caspase-10 may play a critical role in PTK7-knockdown-induced apoptosis, downstream of mitochondria. These observations may indicate a role for PTK7 in cell proliferation and cell apoptosis and may provide a potential therapeutic pathway for the treatment of a variety of cancers

Health and survival of young children in southern Tanzania

With a view to developing health systems strategies to improve reach to high-risk groups, we present information on health and survival from household and health facility perspectives in five districts of southern Tanzania. We documented availability of health workers, vaccines, drugs, supplies and services essential for child health through a survey of all health facilities in the area. We did a representative cluster sample survey of 21,600 households using a modular questionnaire including household assets, birth histories, and antenatal care in currently pregnant women. In a subsample of households we asked about health of all children under two years, including breastfeeding, mosquito net use, vaccination, vitamin A, and care-seeking for recent illness, and measured haemoglobin and malaria parasitaemia. In the health facility survey, a prescriber or nurse was present on the day of the survey in about 40% of 114 dispensaries. Less than half of health facilities had all seven 'essential oral treatments', and water was available in only 22%. In the household survey, antenatal attendance (88%) and DPT-HepB3 vaccine coverage in children (81%) were high. Neonatal and infant mortality were 43.2 and 76.4 per 1000 live births respectively. Infant mortality was 40% higher for teenage mothers than older women (RR 1.4, 95% confidence interval (CI) 1.1 - 1.7), and 20% higher for mothers with no formal education than those who had been to school (RR 1.2, CI 1.0 - 1.4). The benefits of education on survival were apparently restricted to post-neonatal infants. There was no evidence of inequality in infant mortality by socio-economic status. Vaccine coverage, net use, anaemia and parasitaemia were inequitable: the least poor had a consistent advantage over children from the poorest families. Infant mortality was higher in families living over 5 km from their nearest health facility compared to those living closer (RR 1.25, CI 1.0 - 1.5): 75% of households live within this distance. Relatively short distances to health facilities, high antenatal and vaccine coverage show that peripheral health facilities have huge potential to make a difference to health and survival at household level in rural Tanzania, even with current human resources

The XMM Cluster Survey analysis of the SDSS DR8 redMaPPer catalogue: implications for scatter, selection bias, and isotropy in cluster scaling relations

In this paper, we present the X-ray analysis of Sloan Digital Sky Survey DR8 redMaPPer (SDSSRM) clusters using data products from the XMM Cluster Survey (XCS). In total, 1189 SDSSRM clusters fall within the XMM-Newton footprint. This has yielded 456 confirmed detections accompanied by X-ray luminosity (LX) measurements. Of these clusters, 381 have an associated X-ray temperature measurement (TX). This represents one of the largest samples of coherently derived cluster TX values to date. Our analysis of the X-ray observable to richness scaling relations has demonstrated that scatter in the TX-λ relation is roughly a third of that in the LX-λ relation, and that the LX-λ scatter is intrinsic, i.e. will not be significantly reduced with larger sample sizes. Analysis of the scaling relation between LX and TX has shown that the fits are sensitive to the selection method of the sample, i.e. whether the sample is made up of clusters detected 'serendipitously' compared to those deliberately targeted by XMM. These differences are also seen in the LX-λ relation and, to a lesser extent, in the TX-λ relation. Exclusion of the emission from the cluster core does not make a significant impact on the findings. A combination of selection biases is a likely, but yet unproven, reason for these differences. Finally, we have also used our data to probe recent claims of anisotropy in the LX-TX relation across the sky. We find no evidence of anistropy, but stress this may be masked in our analysis by the incomplete declination coverage of the SDSS

The XMM Cluster Survey analysis of the SDSS DR8 redMaPPer Catalogue:mplications for scatter, selection bias, and isotropy in cluster scaling relations

In this paper, we present the X-ray analysis of SDSS DR8 redMaPPer (SDSSRM) clusters using data products from the XMM Cluster Survey (XCS). In total, 1189 SDSSRM clusters fall within the XMM-Newton footprint. This has yielded 456 confirmed detections accompanied by X-ray luminosity (LX) measurements. Of these clusters, 381 have an associated X-ray temperature measurement (TX). This represents one of the largest samples of coherently derived cluster TX values to date. Our analysis of the X-ray observable to richness scaling relations has demonstrated that scatter in the TX − λ relation is roughly a third of that in the LX − λ relation, and that the LX − λ scatter is intrinsic, i.e. will not be significantly reduced with larger sample sizes. Analysis of the scaling relation between LX and TX has shown that the fits are sensitive to the selection method of the sample, i.e. whether the sample is made up of clusters detected “serendipitously” compared to those deliberately targeted by XMM. These differences are also seen in the LX − λ relation and, to a lesser extent, in the TX − λ relation. Exclusion of the emission from the cluster core does not make a significant impact on the findings. A combination of selection biases is a likely, but yet unproven, reason for these differences. Finally, we have also used our data to probe recent claims of anisotropy in the LX − TX relation across the sky. We find no evidence of anistropy, but stress this may be masked in our analysis by the incomplete declination coverage of the SDSS

Does use of a government service depend on distance from the health facility?

To reduce mortality from common childhood illnesses such as diarrhoea and upper respiratory infections, it is important that health services are available and used appropriately. Physical accessibility to a health facility may influence its use, particularly in rural areas. We assessed whether use of government services for treatment of the three most common acute childhood illnesses (fever, diarrhoea and upper respiratory infections) was influenced by the physical accessibility of the government primary health care centres. We analyzed data from a household survey which was collected between November 1992 and January 1993, from 139 randomly selected villages located around 14 government facilities in Thatta, a rural district of Pakistan. There were 691 children under 5 years of age who suffered from the three acute illnesses; 85% of these children used either a government or a private service. Children living at less than 4 km from a government facility made 22% less use of that facility than those living 4 km or more away. After controlling for the effects of distance from a private facility and treatment cost in a multiple logistic regression model, children living less than 4 km from a government facility were no more likely to use the facility than those living 4 km or more away (Adjusted Odds Ratio: 1.01, 95% Confidence Interval: 0.68-1.50). These results suggest that factors other than distance are the primary determinants of use of government services for treating children in the Thatta district. To increase the use of government health services, policymakers should assess carefully the factors determining the use of existing facilities, before they plan the building of more health facilities. Further studies are needed to examine the management of health facilities and the clients\u27 perception of health-care providers

Patterns of Maxillofacial Injures Caused by Motorcycle Accidents

Introduction Motorcycles are used as a common means of transportation, and motorcycle accidents are responsible for a major portion of trauma injuries. Objectives The purpose of this study was to analyze the patterns of facial injuries in motorcyclists, to evaluate the types of injuries, and to investigate if the accident-related factors had any impact on the characteristics of the injuries. Methods This retrospective observational study included 74 patients with maxillofacial injuries following motorcycle-related accidents. Investigated data were divided into four main categories: sociodemographic, accident-related, injury-related, and treatment-related. Results All the patients were males with a mean age (±SD) of 25.03 (±9.986) years. Most accidents (n = 44, 59.4%) occurred in the evening. Most of the patients (n = 40, 54%) were traveling on motorcycle models that had maximum speed of over 120 km/h. Furthermore, 15 patients (18.9%) were under the influence of alcohol during the crashes and only one patient was wearing a helmet. Fractures of the maxillofacial bones were observed in 50 (67.5%) crash victims; 24 of them (48%) had middle third fractures, 11 (22%) had mandibular fractures, and 15 patients (30%) presented with a combination of lower, middle, and upper third fractures. Conclusion Almost all patients were not wearing helmets at the moment of the crash. The most common fractured site was the maxilla. The majority of the patients received surgical treatment. Increased enforcement of safety measures for riders and raising awareness about the dangers of motorcycle crashes are required measures to improve traffic safety and, ultimately, population health

Assessment of the uptake of neonatal and young infant referrals by community health workers to public health facilities in an urban informal settlement, KwaZulu-Natal, South Africa.

BACKGROUND: Globally, 40% of the 7.6 million deaths of children under five every year occur in the neonatal period (first 28 days after birth). Increased and earlier recognition of illness facilitated by community health workers (CHWs), coupled with effective referral systems can result in better child health outcomes. This model has not been tested in a peri-urban poor setting in Africa, or in a high HIV context. METHODS: The Good Start Saving Newborn Lives (SNL) study (ISRCTN41046462) conducted in Umlazi, KwaZulu-Natal, was a community randomized trial to assess the effect of an integrated home visit package delivered to mothers by CHWs during pregnancy and post-delivery on uptake of PMTCT interventions and appropriate newborn care practices. CHWs were trained to refer babies with illnesses or identified danger signs. The aim of this sub-study was to assess the effectiveness of this referral system by describing CHW referral completion rates as well as mothers' health-care seeking practices. Interviews were conducted using a structured questionnaire with all mothers whose babies had been referred by a CHW since the start of the SNL trial. Descriptive analysis was conducted to describe referral completion and health seeking behaviour of mothers. RESULTS: Of the 2423 women enrolled in the SNL study, 148 sick infants were referred between June 2008 and June 2010. 62% of referrals occurred during the first 4 weeks of life and 22% between birth and 2 weeks of age. Almost all mothers (95%) completed the referral as advised by CHWs. Difficulty breathing, rash and redness/discharge around the cord accounted for the highest number of referrals (26%, 19% and 17% respectively). Only16% of health workers gave written feedback on the outcome of the referral to the referring CHW. CONCLUSIONS: We found high compliance with CHW referral of sick babies in an urban South African township. This suggests that CHWs can play a significant role, within community outreach teams, to improve newborn health and reduce child mortality. This supports the current primary health care re-engineering process being undertaken by the South African National Department of Health which involves the establishment of family health worker teams including CHWs. TRIAL REGISTRATION NUMBER: ISRCTN41046462