372 research outputs found
Assessing the Quality of Care for Pneumonia in Integrated Community Case Management: A Cross-Sectional Mixed Methods Study
Background Pneumonia is the leading infectious cause of mortality in children under five worldwide. Community-level interventions, such as integrated community case management, have great potential to reduce the burden of pneumonia, as well as other diseases, especially in remote populations. However, there are still questions as to whether community health workers (CHW) are able to accurately assess symptoms of pneumonia and prescribe appropriate treatment. This research addresses limitations of previous studies using innovative methodology to assess the accuracy of respiratory rate measurement by CHWs and provides new evidence on the quality of care given for children with symptoms of pneumonia. It is one of few that assesses CHW performance in their usual setting, with independent re-examination by experts, following a considerable period of time post-training of CHWs. Methods In this cross-sectional mixed methods study, 1,497 CHW consultations, conducted by 90 CHWs in two districts of Luapula province, Zambia, were directly observed, with measurement of respiratory rate for children with suspected pneumonia recorded by video. Using the video footage, a retrospective reference standard assessment of respiratory rate was conducted by experts. Counts taken by CHWs were compared against the reference standard and appropriateness of the treatment prescribed by CHWs was assessed. To supplement observational findings, three focus group discussions and nine in depth interviews with CHWs were conducted. Results and Conclusion The findings support existing literature that CHWs are capable of measuring respiratory rates and providing appropriate treatment, with 81% and 78% agreement, respectively, between CHWs and experts. Accuracy in diagnosis could be strengthened through further training and the development of improved diagnostic tools appropriate for resource-poor settings
A single residue substitution in the receptor-binding domain of H5N1 hemagglutinin is critical for packaging into pseudotyped lentiviral particles
© 2012 Tang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Serological studies for influenza infection and vaccine response often involve microneutralization and hemagglutination inhibition assays to evaluate neutralizing antibodies against human and avian influenza viruses, including H5N1. We have previously characterized lentiviral particles pseudotyped with H5-HA (H5pp) and validated an H5pp-based assay as a safe alternative for high-throughput serological studies in BSL-2 facilities. Here we show that H5-HAs from different clades do not always give rise to efficient production of H5pp and the underlying mechanisms are addressed.
Methodology/Findings: We have carried out mutational analysis to delineate the molecular determinants responsible for efficient packaging of HA from A/Cambodia/40808/2005 (H5Cam) and A/Anhui/1/2005 (H5Anh) into H5pp. Our results demonstrate that a single A134V mutation in the 130-loop of the receptor binding domain is sufficient to render H5Anh the ability to generate H5Anh-pp efficiently, whereas the reverse V134A mutation greatly hampers production of H5Cam-pp. Although protein expression in total cell lysates is similar for H5Anh and H5Cam, cell surface expression of H5Cam is detected at a significantly higher level than that of H5Anh. We further demonstrate by several independent lines of evidence that the behaviour of H5Anh can be explained by a stronger binding to sialic acid receptors implicating residue 134.
Conclusions: We have identified a single A134V mutation as the molecular determinant in H5-HA for efficient incorporation into H5pp envelope and delineated the underlying mechanism. The reduced binding to sialic acid receptors as a result of the A134V mutation not only exerts a critical influence in pseudotyping efficiency of H5-HA, but has also an impact at the whole virus level. Because A134V substitution has been reported as a naturally occurring mutation in human host, our results may have implications for the understanding of human host adaptation of avian influenza H5N1 virusesThis work was supported by grants from the Research Fund for the Control of Infectious Diseases of Hong Kong (RFCID#08070972), the Area of
Excellence Scheme of the University Grants Committee (grant AoE/M-12/-06 of the Hong Kong Special Administrative Region, China), the French Ministry of Health, and the RESPARI project of the Institut Pasteur International Network
What constitutes responsiveness of physicians: A qualitative study in rural Bangladesh
Responsiveness entails the social actions by health providers to meet the legitimate expectations
of patients. It plays a critical role in ensuring continuity and effectiveness of care
within people centered health systems. Given the lack of contextualized research on
responsiveness, we qualitatively explored the perceptions of outpatient users and providers
regarding what constitute responsiveness in rural Bangladesh. An exploratory study was
undertaken in Chuadanga, a southwestern Bangladeshi District, involving in-depth interviews
of physicians (n = 17) and users (n = 7), focus group discussions with users (n = 4),
and observations of patient provider interactions (three weeks). Analysis was guided by a
conceptual framework of responsiveness, which includes friendliness, respecting, informing
and guiding, gaining trust and optimizing benefits. In terms of friendliness, patients expected
physicians to greet them before starting consultations; even though physicians considered
this unusual. Patients also expected physicians to hold social talks during consultations,
which was uncommon. With regards to respect patients expected physicians to refrain from
disrespecting them in various ways; but also by showing respect explicitly. Patients also had
expectations related to informing and guiding: they desired explanation on at least the diagnosis,
seriousness of illness, treatment and preventive steps. In gaining trust, patients
expected that physicians would refrain from illegal or unethical activities related to patients,
e.g., demanding money against free services, bringing patients in own private clinics by brokers
(dalals), colluding with diagnostic centers, accepting gifts from pharmaceutical representatives.
In terms of optimizing benefits: patients expected that physicians should be
financially sensitive and consider individual need of patients. There were multiple dimensions
of responsiveness- for some, stakeholders had a consensus; context was an important
factor to understand them. This being an exploratory study, further research is
recommended to validate the nuances of the findings. It can be a guideline for responsiveness
practices, and a tipping point for future research
Open data and digital morphology
Over the past two decades, the development of methods for visualizing and analysing specimens digitally, in three and even four dimensions, has transformed the study of living and fossil organisms. However, the initial promise, that the widespread application of such methods would facilitate access to the underlying digital data, has not been fully achieved. The underlying datasets for many published studies are not readily or freely available, introducing a barrier to verification and reproducibility, and the reuse of data. There is no current agreement or policy on the amount and type of data that should be made available alongside studies that use, and in some cases are wholly reliant on, digital morphology. Here, we propose a set of recommendations for minimum standards and additional best practice for 3D digital data publication, and review the issues around data storage, management and accessibility
Identifying the determinants of premature mortality in Russia: overcoming a methodological challenge
<p>Abstract</p> <p>Background</p> <p>It is thought that excessive alcohol consumption is related to the high mortality among working age men in Russia. Moreover it has been suggested that alcohol is a key proximate driver of the very sharp fluctuations in mortality seen in this group since the mid-1980s. Designing an individual-level study suitable to address the potential acute effects of alcohol consumption on mortality in Russia has posed a challenge to epidemiologists, especially because of the need to identify factors that could underlie the rapid changes up and down in mortality rates that have been such a distinctive feature of the Russian mortality crisis. In order to address this study question which focuses on exposures acting shortly before sudden death, a cohort would be unfeasibly large and would suffer from recruitment bias.</p> <p>Methods</p> <p>Although the situation in Russia is unusual, with a very high death rate characterised by many sudden and apparently unexpected deaths in young men, the methodological problem is common to research on any cause of death where many deaths are sudden.</p> <p>Results</p> <p>We describe the development of an innovative approach that has overcome some of these challenges: a case-control study employing proxy informants and external data sources to collect information about proximate determinants of mortality.</p> <p>Conclusion</p> <p>This offers a set of principles that can be adopted by epidemiologists studying sudden and unexpected deaths in other settings.</p
Expression of EBV Encoded viral RNA 1, 2 and anti-inflammatory Cytokine (interleukin-10) in FFPE lymphoma specimens: a preliminary study for diagnostic implication in Pakistan
<p>Abstract</p> <p>Background</p> <p>Epstein Barr Virus (EBV) plays a significant role as a cofactor in the process of tumorigenesis and has consistently been associated with a variety of malignancies. EBV encoded RNAs (EBER1 and EBER2) are the most abundant viral transcripts in latently EBV-infected cells and their role in viral infection is still unclear. Formalin Fixed Paraffin Embedded (FFPE) tissues of surgically removed carcinoma biopsies are widely available form but have never been exploited for expressional studies previously in Pakistan. Immunohistochemistry (IHC) and <it>in situ </it>hybridization (ISH) in FFPE biopsy tissues remains the gold standard for proving EBV relationship in a histopathological lesion but their reagents associated limitations confines their reliability in some applications. Recently introduced targeted drug delivery systems induce viral lytic gene expression and therefore require more sensitive method to quantify viral as well as cellular gene expression.</p> <p>Methods</p> <p>Eight (8) lymphoma samples were screened to detect the EBV genome. Qualitative and quantitative expression of EBV Encoded RNAs (EBER1, EBER2) and anti-inflammatory cytokine (interleukin-10) in FFPE EBV positive lymphoma tissue samples were then analysed by using Reverse transcriptase Polymerase Chain Reaction (RT-PCR) and Real Time Polymerase Chain Reaction (qRT-PCR), respectively.</p> <p>Results</p> <p>In this study we have successfully quantified elevated expressional levels of both cellular and viral transcripts, namely EBER1, EBER2 and anti-inflammatory cytokine (IL-10) in the FFPE Burkitt's lymphoma (BL) specimens of Pakistani origin.</p> <p>Conclusions</p> <p>These results indicate that FFPE samples may retain viral as well as cellular RNA expression information at detectable level. To our knowledge, this is first study which represents elevated expressional levels of EBER1, EBER2 and IL-10 in FFPE tissue samples of Burkitt's lymphoma in Pakistan. These observations will potentially improve current lacunas in clinical as well as diagnostic practices in Pakistan and can be further exploited to develop new strategies for studying cellular and/or viral gene expression.</p
Exosomes released by EBV-infected nasopharyngeal carcinoma cells convey the viral Latent Membrane Protein 1 and the immunomodulatory protein galectin 9
BACKGROUND: Nasopharyngeal carcinomas (NPC) are consistently associated with the Epstein-Barr virus (EBV). Their malignant epithelial cells contain the viral genome and express several antigenic viral proteins. However, the mechanisms of immune escape in NPCs are still poorly understood. EBV-transformed B-cells have been reported to release exosomes carrying the EBV-encoded latent membrane protein 1 (LMP1) which has T-cell inhibitory activity. Although this report suggested that NPC cells could also produce exosomes carrying immunosuppressive proteins, this hypothesis has remained so far untested. METHODS: Malignant epithelial cells derived from NPC xenografts – LMP1-positive (C15) or negative (C17) – were used to prepare conditioned culture medium. Various microparticles and vesicles released in the culture medium were collected and fractionated by differential centrifugation. Exosomes collected in the last centrifugation step were further purified by immunomagnetic capture on beads carrying antibody directed to HLA class II molecules. Purified exosomes were visualized by electron microscopy and analysed by western blotting. The T-cell inhibitory activities of recombinant LMP1 and galectin 9 were assessed on peripheral blood mononuclear cells activated by CD3/CD28 cross-linking. RESULTS: HLA-class II-positive exosomes purified from C15 and C17 cell supernatants were containing either LMP1 and galectin 9 (C15) or galectin 9 only (C17). Recombinant LMP1 induced a strong inhibition of T-cell proliferation (IC50 = 0.17 nM). In contrast recombinant galectin 9 had a weaker inhibitory effect (IC50 = 46 nM) with no synergy with LMP1. CONCLUSION: This study provides the proof of concept that NPC cells can release HLA class-II positive exosomes containing galectin 9 and/or LMP1. It confirms that the LMP1 molecule has intrinsic T-cell inhibitory activity. These findings will encourage investigations of tumor exosomes in the blood of NPC patients and assessment of their effects on various types of target cells
A survey on knowledge and self-reported formula handling practices of parents and child care workers in Palermo, Italy
Powdered infant formula (PIF) is not a sterile product, but this information appears to be poorly diffused among child caregivers. Parents and child care workers may behave in an unsafe manner when handling PIF. Methods: This study involved parents and child care workers in the 24 municipal child care centres of Palermo. Knowledge and self-reported practices about PIF handling were investigated by a structured questionnaire. A Likert scale was used to measure the strength of the respondent's feelings. Association of knowledge and self-reported practices with demographic variables was also evaluated. Results: 42.4% of parents and 71.0% of child care workers filled in the questionnaire. Significant differences were found between parents and child care workers for age and education. 73.2% of parents and 84.4% of child care workers were confident in sterility of PIF. Generally, adherence to safe procedures when reconstituting and handling PIF was more frequently reported by child care workers who, according to the existing legislation, are regularly subjected to a periodic training on food safety principles and practices. Age and education significantly influenced the answers to the questionnaire of both parents and child care workers. Conclusion: The results of the study reveal that parents and child care workers are generally unaware that powdered formulas may contain viable microorganisms. However, child care workers consistently chose safer options than parents when answering the questions about adherence to hygienic practices. At present it seems unfeasible to produce sterile PIF, but the risk of growth of hazardous organisms in formula at the time of administration should be minimized by promoting safer behaviours among caregivers to infants in both institutional settings and home. \ua9 2009 Calamusa et al; licensee BioMed Central Ltd
Designing Adverse Event Forms for Real-World Reporting: Participatory Research in Uganda
The wide-scale roll-out of artemisinin combination therapies (ACTs) for the treatment of malaria should be accompanied by continued surveillance of their safety. Post-marketing pharmacovigilance (PV) relies on adverse event (AE) reporting by clinicians, but as a large proportion of treatments are provided by non-clinicians in low-resource settings, the effectiveness of such PV systems is limited. To facilitate reporting, AE forms should be easily completed; however, most are challenging for lower-level health workers and non-clinicians to complete. Through participatory research, we sought to develop user-friendly AE report forms to capture information on events associated with ACTs
Disability, Home Physical Environment and Non-Fatal Injuries among Young Children in China
We compared the patterns of medically attended injuries between children with and without disabilities and explored the residential environment risks in five counties of Hubei Province in the People's Republic of China by a 1:1 matched case-control study based on the biopsychosocial model of the International Classification of Functioning, Disability and Health--ICF.1201 children aged 1-14 with disabilities and 1201 their healthy counterparts matched as having the same gender, same age, and lived in the same neighborhood were recruited in our study. Characteristics of injuries in the past 12 months were compared between children with and without disabilities. The associations among disability status, home environment factors and injuries were examined in logistic regression analysis taking into account sociodemographic factors.Children with disabilities had a significantly higher prevalence of injury than children without disabilities (10.2% vs. 4.4%; P<.001). The two groups differed significantly in terms of number of injury episodes, injury place and activity at time of injury. Falls were the leading mechanism of injury regardless of disability status. Most of the injury events happened inside the home and leisure activities were the most reported activity when injured for both groups. The univariate OR for injury was 4.46 (2.57-7.74) for the disabled children compared with the non-disabled children. Disabled children whose family raised cat/dog(s) were 76% more likely to be injured during the last 12 months (OR = 1.76; 95% CI = 1.02, 3.02), comparing with those whose family did not have any cat/dog. And for children without disabilities, those whose family had cat/dog(s) were over 3 times more likely to having injuries comparing with those whose family did not have any cat/dog.Children with disabilities had a significantly increased risk for injury. Interventions to prevent residential injury are an important public health priority in children with disabilities
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