Integrated Study of Globally Expressed microRNAs in IL-1β-stimulated Human Osteoarthritis Chondrocytes and Osteoarthritis Relevant Genes: A Microarray and Bioinformatics Analysis

This study was undertaken to identify and characterize the globally expressed microRNAs (miRNAs) involved in interleukin-1β (IL-1β)-induced joint damage and to predict whether miRNAs can regulate the catabolic effects in osteoarthritis (OA) chondrocytes. Out of 1347 miRNAs analyzed by microarrays in IL-1β-stimulated OA chondrocytes, 35 miRNAs were down-regulated, 1 miRNA was up-regulated, and the expression of 1311 miRNAs remained unchanged. Bioinformatics analysis showed the key inflammatory mediators and key molecular pathways are targeted by differentially expressed miRNAs. Novel miRNAs identified could have important diagnostic and therapeutic potentials in the development of novel therapeutic strategies for pain managements in OA.     

Economic Benefits of Investing in Women’s Health: A Systematic Review

Background

Globally, the status of women’s health falls short of its potential. In addition to the deleterious ethical and human rights implications of this deficit, the negative economic impact may also be consequential, but these mechanisms are poorly understood. Building on the literature that highlights health as a driver of economic growth and poverty alleviation, we aim to systematically investigate the broader economic benefits of investing in women’s health.

Methods

Using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we systematically reviewed health, gender, and economic literature to identify studies that investigate the impact of women’s health on micro- and macroeconomic outcomes. We developed an extensive search algorithm and conducted searches using 10 unique databases spanning the timeframe 01/01/1970 to 01/04/2013. Articles were included if they reported on economic impacts stemming from changes in women’s health (table of outcome measures included in full review,

Association of Neighbourhood and Individual Social Capital,Neighbourhood Economic Deprivation and Self-Rated Health in South Africa – a Multi-Level Analysis

Introduction

Social capital is said to influence health, mostly in research undertaken in high income countries'' settings. Because social capital may differ from one setting to another, it is suggested that its measurement be context specific. We examine the association of individual and neighbourhood level social capital, and neighbourhood deprivation to self-rated health using a multi-level analysis.

Methods

Data are taken from the 2008 South Africa National Income Dynamic Survey. Health was self-reported on a scale from 1 (excellent) to 5 (poor). Two measures of social capital were used: individual, measured by two variables denoting trust and civic participation; and neighbourhood social capital, denoting support, association, behaviour and safety in a community.

Results

Compared to males, females were less likely to report good health (Odds Ratio 0.82: Confidence Interval 0.73, 0.91). There were variations in association of individual social capital and self-rated health among the provinces. In Western Cape (1.37: 0.98, 1.91) and North West (1.39: 1.13, 1.71), trust was positively associated with reporting good health, while the reverse was true in Limpopo (0.56: 0.38, 0.84) and Free State (0.70: 0.48, 1.02). In Western Cape (0.60: 0.44, 0.82) and Mpumalanga (0.72: 0.55, 0.94), neighbourhood social capital was negatively associated with reporting good health. In North West (1.59: 1.27, 1.99) and Gauteng (1.90: 1.21, 2.97), increased neighbourhood social capital was positively associated with reporting good health.

Conclusion

Our study demonstrated the importance of considering contextual factors when analysing the relationship between social capital and health. Analysis by province showed variations in the way in which social capital affected health in different contexts. Further studies should be undertaken to understand the mechanisms through which social capital impacts on health in South Africa.     

A Perspective on the History and Evolution of an Oceans and Human Health “Metadiscipline” in the USA

We review recent history and evolution of Oceans and Human Health programs and related activities in the USA from a perspective within the Federal government. As a result of about a decade of support by the US Congress and through a few Federal agencies, notably the National Science Foundation, National Institute of Environmental Health Sciences, and National Ocean and Atmospheric Administration, robust Oceans and Human Health (OHH) research and application activities are now relatively widespread, although still small, in a number of agencies and academic institutions. OHH themes and issues have been incorporated into comprehensive federal ocean research plans and are reflected in the new National Ocean Policy enunciated by Executive Order 13547. In just a decade, OHH has matured into a recognized “metadiscipline,” with development of a small, but robust and diverse community of science and practice, incorporation into academic educational programs, regular participation in ocean and coastal science and public health societies, and active engagement with public health decision makers. In addition to substantial increases in scientific information, the OHH community has demonstrated ability to respond rapidly and effectively to emergency situations such as those associated with extreme weather events (e.g., hurricanes, floods) and human-caused disasters (e.g., the Deep Water Horizon oil spill). Among many other things, next steps include development and implementation of agency health strategies and provision of specific services, such as ecological forecasts to provide routine early warnings for ocean health threats and opportunities for prevention and mitigation of these risks.     

Antiretroviral Therapy Program Expansion in Zambézia Province,Mozambique: Geospatial Mapping of Community-Based and Health Facility Data for Integrated Health Planning

Objective

To generate maps reflecting the intersection of community-based Voluntary Counseling and Testing (VCT) delivery points with facility-based HIV program demographic information collected at the district level in three districts (Ile, Maganja da Costa and Chinde) of Zambézia Province, Mozambique; in order to guide planning decisions about antiretroviral therapy (ART) program expansion.

Methods

Program information was harvested from two separate open source databases maintained for community-based VCT and facility-based HIV care and treatment monitoring from October 2011 to September 2012. Maps were created using ArcGIS 10.1. Travel distance by foot within a 10 km radius is generally considered a tolerable distance in Mozambique for purposes of adherence and retention planning.

Results

Community-based VCT activities in each of three districts were clustered within geographic proximity to clinics providing ART, within communities with easier transportation access, and/or near the homes of VCT volunteers. Community HIV testing results yielded HIV seropositivity rates in some regions that were incongruent with the Ministry of Health’s estimates for the entire district (2–13% vs. 2% in Ile, 2–54% vs. 11.5% in Maganja da Costa, and 23–43% vs. 14.4% in Chinde). All 3 districts revealed gaps in regional disbursement of community-based VCT activities as well as access to clinics offering ART.

Conclusions

Use of geospatial mapping in the context of program planning and monitoring allowed for characterizing the location and size of each district’s HIV population. In extremely resource limited and logistically challenging settings, maps are valuable tools for informing evidence-based decisions in planning program expansion, including ART.     

Nodular Worm Infection in Wild Chimpanzees in Western Uganda: A Risk for Human Health?

This study focused on Oeosophagostomum sp., and more especially on O. bifurcum, as a parasite that can be lethal to humans and is widespread among humans and monkeys in endemic regions, but has not yet been documented in apes. Its epidemiology and the role played by non-human primates in its transmission are still poorly understood. O. stephanostomum was the only species diagnosed so far in chimpanzees. Until recently, O. bifurcum was assumed to have a high zoonotic potential, but recent findings tend to demonstrate that O. bifurcum of non-human primates and humans might be genetically distinct. As the closest relative to human beings, and a species living in spatial proximity to humans in the field site studied, Pan troglodytes is thus an interesting host to investigate. Recently, a role for chimpanzees in the emergence of HIV and malaria in humans has been documented. In the framework of our long-term health monitoring of wild chimpanzees from Kibale National Park in Western Uganda, we analysed 311 samples of faeces. Coproscopy revealed that high-ranking males are more infected than other individuals. These chimpanzees are also the more frequent crop-raiders. Results from PCR assays conducted on larvae and dried faeces also revealed that O. stephanostomum as well as O. bifurcum are infecting chimpanzees, both species co-existing in the same individuals. Because contacts between humans and great apes are increasing with ecotourism and forest fragmentation in areas of high population density, this paper emphasizes that the presence of potential zoonotic parasites should be viewed as a major concern for public health. Investigations of the parasite status of people living around the park or working inside as well as sympatric non-human primates should be planned, and further research might reveal this as a promising aspect of efforts to reinforce measures against crop-raiding.     

PKCα-Specific Phosphorylation of the Troponin Complex in Human Myocardium: A Functional and Proteomics Analysis

Aims

Protein kinase Cα (PKCα) is one of the predominant PKC isoforms that phosphorylate cardiac troponin. PKCα is implicated in heart failure and serves as a potential therapeutic target, however, the exact consequences for contractile function in human myocardium are unclear. This study aimed to investigate the effects of PKCα phosphorylation of cardiac troponin (cTn) on myofilament function in human failing cardiomyocytes and to resolve the potential targets involved.

Methods and Results

Endogenous cTn from permeabilized cardiomyocytes from patients with end-stage idiopathic dilated cardiomyopathy was exchanged (∼69%) with PKCα-treated recombinant human cTn (cTn (DD+PKCα)). This complex has Ser23/24 on cTnI mutated into aspartic acids (D) to rule out in vitro cross-phosphorylation of the PKA sites by PKCα. Isometric force was measured at various [Ca²⁺] after exchange. The maximal force (F_max) in the cTn (DD+PKCα) group (17.1±1.9 kN/m²) was significantly reduced compared to the cTn (DD) group (26.1±1.9 kN/m²). Exchange of endogenous cTn with cTn (DD+PKCα) increased Ca²⁺-sensitivity of force (pCa₅₀ = 5.59±0.02) compared to cTn (DD) (pCa₅₀ = 5.51±0.02). In contrast, subsequent PKCα treatment of the cells exchanged with cTn (DD+PKCα) reduced pCa₅₀ to 5.45±0.02. Two PKCα-phosphorylated residues were identified with mass spectrometry: Ser198 on cTnI and Ser179 on cTnT, although phosphorylation of Ser198 is very low. Using mass spectrometry based-multiple reaction monitoring, the extent of phosphorylation of the cTnI sites was quantified before and after treatment with PKCα and showed the highest phosphorylation increase on Thr143.

Conclusion

PKCα-mediated phosphorylation of the cTn complex decreases F_max and increases myofilament Ca²⁺-sensitivity, while subsequent treatment with PKCα in situ decreased myofilament Ca²⁺-sensitivity. The known PKC sites as well as two sites which have not been previously linked to PKCα are phosphorylated in human cTn complex treated with PKCα with a high degree of specificity for Thr143.     

Social Networks,the ‘Work’ and Work Force of Chronic Illness Self-Management: A Survey Analysis of Personal Communities

Self-management support forms a central aspect of chronic Illness management nationally and globally. Evidence for the success of self-management support has mainly focussed on individually-centred outcomes of behavioural change. While it is recognised that social network members play an important role there is currently a gap in knowledge regarding who provides what type of support and under what circumstances. This is relevant for understanding the division of labour and the meeting of needs for those living with a long-term condition. We therefore took a network approach to explore self-management support conceptualising it as types of illness ‘work’ undertaken within peoples’ social networks. 300 people from deprived areas and with chronic illnesses took part in a survey conducted in 2010 in the North West of England. A concentric circles diagram was used as a research tool with which participants identified 2,544 network members who contributed to illness management. The results provide an articulation of how social network members are substantially involved in illness management. Whilst partners and close family make the highest contributions there is evidence of inputs from a wide range of relationships. Network member characteristics (type of relationship, proximity, frequency of contact) impact on the amount of illness work undertaken in peoples’ networks. In networks with ‘no partner’ other people tend to contribute more in the way of illness related work than in networks with a partner. This indicates a degree of substitutability between differently constituted networks, and that the level and type of input by different members of a network might change according to circumstances. A network perspective offers an opportunity to redress the balance of an exclusively individual focus on self-management because it addresses the broader set of contributions and resources available to people in need of chronic illness management and support.     

“Solution-Focused Risk Assessment”: A Proposal for the Fusion of Environmental Analysis and Action

For 30 years, more attention and resources have been expended on dissecting problems (risk assessment) than on evaluating actual solutions that reduce risks. The basic dogma holds that risk assessment must precede risk management. But there is an opposite and perhaps better way: the opening question should not be “How bad is the problem?” but “How good are the solutions we might apply to the problem?” Rethinking risk assessment in this context offers three classes of benefits over the status quo. First, it can help break the endless cycle of analysis: when the goal is to know enough to decide, rather than to know everything, natural stopping points emerge. Second, it can lead to more decisions that actually achieve risk reduction, rather than pronouncements about how much risk reduction would be optimal. Third, it can highlight ways to resolve multiple risks simultaneously, avoid needless and tragic risk-risk tradeoffs, and involve affected stakeholders in debating what should be done. Arguably, the longer the disembodied analysis of risk information is allowed to proceed, the more likely it is that the “problem” will be defined in a way that blunts the free-wheeling discussion of solutions, to the detriment of human health, the environment, and the economy.     

A Literature Review of Economic Evaluations for a Neglected Tropical Disease: Human African Trypanosomiasis (“Sleeping Sickness”)

Human African trypanosomiasis (HAT) is a disease caused by infection with the parasite Trypanosoma brucei gambiense or T. b. rhodesiense. It is transmitted to humans via the tsetse fly. Approximately 70 million people worldwide were at risk of infection in 1995, and approximately 20,000 people across Africa are infected with HAT. The objective of this review was to identify existing economic evaluations in order to summarise cost-effective interventions to reduce, control, or eliminate the burden of HAT. The studies included in the review were compared and critically appraised in order to determine if there were existing standardised methods that could be used for economic evaluation of HAT interventions or if innovative methodological approaches are warranted. A search strategy was developed using keywords and was implemented in January 2014 in several databases. The search returned a total of 2,283 articles. After two levels of screening, a total of seven economic evaluations were included and underwent critical appraisal using the Scottish Intercollegiate Guidelines Network (SIGN) Methodology Checklist 6: Economic Evaluations. Results from the existing studies focused on the cost-effectiveness of interventions for the control and reduction of disease transmission. Modelling was a common method to forecast long-term results, and publications focused on interventions by category, such as case detection, diagnostics, drug treatments, and vector control. Most interventions were considered cost-effective based on the thresholds described; however, the current treatment, nifurtomix-eflornithine combination therapy (NECT), has not been evaluated for cost-effectiveness, and considerations for cost-effective strategies for elimination have yet to be completed. Overall, the current evidence highlights the main components that play a role in control; however, economic evaluations of HAT elimination strategies are needed to assist national decision makers, stakeholders, and key funders. These analyses would be of use, as HAT is currently being prioritized as a neglected tropical disease (NTD) to reach elimination by 2020.     

Human Thromboxane A2 Receptor Genetic Variants: In Silico,In Vitro and “In Platelet” Analysis

Thromboxane and its receptor have emerged as key players in modulating vascular thrombotic events. Thus, a dysfunctional hTP genetic variant may protect against (hypoactivity) or promote (hyperactivity) vascular events, based upon its activity on platelets. After extensive in silico analysis, six hTP-α variants were selected (C⁶⁸S, V⁸⁰E, E⁹⁴V, A¹⁶⁰T, V¹⁷⁶E, and V²¹⁷I) for detailed biochemical studies based on structural proximity to key regions involved in receptor function and in silico predictions. Variant biochemical profiles ranged from severe instability (C⁶⁸S) to normal (V²¹⁷I), with most variants demonstrating functional alteration in binding, expression or activation (V⁸⁰E, E⁹⁴V, A¹⁶⁰T, and V¹⁷⁶E). In the absence of patient platelet samples, we developed and validated a novel megakaryocyte based system to evaluate human platelet function in the presence of detected dysfunctional genetic variants. Interestingly, variant V80E exhibited reduced platelet activation whereas A160T demonstrated platelet hyperactivity. This report provides the most comprehensive in silico, in vitro and “in platelet” evaluation of hTP variants to date and highlightscurrent inherent problems in evaluating genetic variants, with possible solutions. The study additionally provides clinical relevance to characterized dysfunctional hTP variants.     

Quantification Methodology of “Health Human Resources” Related to “Health Technologies” Based on Indicators “RhSan”, “TechSan” and “RhTech”: Application to Senegal

ObjectivesAfter a century of spectacular advances, healthcare systems are facing unprecedented crisis, linked to shortage of health human resources and health technologies. In fact, availability of care depends on both technological and human resources of health. The objective of this study is to develop indicators that can measure qualitatively human resources and technologies of health in healthcare facilities, in order to assess availability of care in sub-Saharan African countries.Materials and MethodsRegarding “health technology” related to “medical devices”, an indicator called “TechSan” for “Technologies de Santé” was previously developed and published (Ndione FB et al. (2019) [6]). To address the deficiencies in usual indicators related to health human resources, a second indicator called “RhSan” for “Ressources humaines de santé” in French is proposed. This indicator assigns a weight to each health worker taking into account his specific “level of medical knowledge” and “experience”. In order to correlate “RhSan” with “TechSan”, a third indicator called “RhTech” is also developed to assess matches between “health technologies” and “health human resources” and establish realistic availability of care. These indicators have the advantage to be consolidated by specialty such as laboratory, imaging, surgery, and “mother and child care”.ResultsThe application of TechSan, RhSan and RhTech to data collected in Senegal in 2016, enabled to assess the distribution of “health technology” and “health human resources” in this country. They also permit the mapping of care availability per specialty in Senegal. The results show a strong oversupply of Dakar in terms of both human resources and technologies of health compared to other Senegalese regions. Oppositely, Sedhiou, Kaffrine, Matam and Kédougou are poorly endowed showing limits of the Senegalese health pyramid system.ConclusionTechSan, RhSan and RhTech can provide reliable decision-making tools in order to elaborate health policies in sub-Saharan African countries on more rigorous basis.     

For the Love of Dog: The Human–Dog Bond in Rural and Remote Australian Indigenous Communities

ABSTRACT

The nature of the human–animal bond in contemporary Australian Indigenous communities is little researched, but it is essential to understand this bond in order to develop much needed appropriate animal health and management practices. A semi-structured interview format was used to elicit information on attitudes to dogs in seven Australian Indigenous communities. This explored the importance of dogs to the community and to the individual, and the balance between the positives and negatives of having dogs in the communities, with particular reference to improving dog and community health and welfare. Theme analysis of the semi-structured interview responses (n = 137) revealed a variety of attitudes to dogs within the communities. A strong theme was the importance of dogs at a community level. Many of the reasons given for the importance of dogs in the community were based on traditional cultural values or beliefs. These included dogs being necessary to guard people at night from spirits, and as part of the kin system. Further, the cultural practice of “pay-back” for wrong-doing included wrong-doing directed at dogs in all communities, even the most westernized. Occurring simultaneously with these positive attitudes, the poor health and overpopulation of dogs in the community was acknowledged and the negative effects on people's lives recognized. However, the value of the dogs to the community meant that shooting dogs without consent or poisoning them were not seen as appropriate solutions to overpopulation. Many people were prepared to euthanize some of their dogs (via an overdose of barbiturate) or have them undergo sterilization surgery. Thus, contrary to appearances from a Western perspective, the traditional Indigenous human–dog bond was found to be strong, and thus must be taken into account in developing appropriate and sustainable animal health and management practices.     

Field Validity and Feasibility of Four Techniques for the Detection of Trichuris in Simians: A Model for Monitoring Drug Efficacy in Public Health?

Background

Soil-transmitted helminths, such as Trichuris trichiura, are of major concern in public health. Current efforts to control these helminth infections involve periodic mass treatment in endemic areas. Since these large-scale interventions are likely to intensify, monitoring the drug efficacy will become indispensible. However, studies comparing detection techniques based on sensitivity, fecal egg counts (FEC), feasibility for mass diagnosis and drug efficacy estimates are scarce.

Methodology/Principal Findings

In the present study, the ether-based concentration, the Parasep Solvent Free (SF), the McMaster and the FLOTAC techniques were compared based on both validity and feasibility for the detection of Trichuris eggs in 100 fecal samples of nonhuman primates. In addition, the drug efficacy estimates of quantitative techniques was examined using a statistical simulation. Trichuris eggs were found in 47% of the samples. FLOTAC was the most sensitive technique (100%), followed by the Parasep SF (83.0% [95% confidence interval (CI): 82.4–83.6%]) and the ether-based concentration technique (76.6% [95% CI: 75.8–77.3%]). McMaster was the least sensitive (61.7% [95% CI: 60.7–62.6%]) and failed to detect low FEC. The quantitative comparison revealed a positive correlation between the four techniques (Rs = 0.85–0.93; p<0.0001). However, the ether-based concentration technique and the Parasep SF detected significantly fewer eggs than both the McMaster and the FLOTAC (p<0.0083). Overall, the McMaster was the most feasible technique (3.9 min/sample for preparing, reading and cleaning of the apparatus), followed by the ether-based concentration technique (7.7 min/sample) and the FLOTAC (9.8 min/sample). Parasep SF was the least feasible (17.7 min/sample). The simulation revealed that the sensitivity is less important for monitoring drug efficacy and that both FLOTAC and McMaster were reliable estimators.

Conclusions/Significance

The results of this study demonstrated that McMaster is a promising technique when making use of FEC to monitor drug efficacy in Trichuris.