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Background: The Better Health Outcomes through Mentoring and Assessment (BHOMA) project is a cluster randomized controlled trial aimed at reducing age-standardized mortality rates in three rural districts through involvement of Community Health Workers (CHWs), Traditional Birth Attendants (TBAs), and Neighborhood Health Committees (NHCs). CHWs conduct quarterly surveys on all households using a questionnaire that captures key health events occurring within their catchment population. In order to validate contact with households, we utilize the Lot Quality Assurance Sampling (LQAS) methodology. In this study, we report experiences of applying the LQAS approach to monitor performance of CHWs in Luangwa District.Methods: Between April 2011 and December 2013, seven health facilities in Luangwa district were enrolled into the BHOMA project. The health facility catchment areas were divided into 33 geographic zones. Quality assurance was performed each quarter by randomly selecting zones representing about 90% of enrolled catchment areas from which 19 households per zone where also randomly identified. The surveys were conducted by CHW supervisors who had been trained on using the LQAS questionnaire. Information collected included household identity number (ID), whether the CHW visited the household, duration of the most recent visit, and what health information was discussed during the CHW visit. The threshold for success was set at 75% household outreach by CHWs in each zone.Results: There are 4,616 total households in the 33 zones. This yielded a target of 32,212 household visits by community health workers during the 7 survey rounds. Based on the set cutoff point for passing the surveys (at least 75% households confirmed as visited), only one team of CHWs at Luangwa high school failed to reach the target during round 1 of the surveys; all the teams otherwise registered successful visits in all the surveys.Conclusions: We have employed the LQAS methodology for assurance that quarterly surveys were successfully done. This methodology proved helpful in identifying poorly performing CHWs and could be useful for evaluating CHW performance in other areas.Trial Registration: Identifier: NCT01942278 . Date of Registration: September 2013. [ABSTRACT FROM AUTHOR]

Skeletal muscles have a fundamental role in locomotion and whole body metabolism, with muscle mass and quality being linked to improved health and even lifespan. Optimizing nutrition in combination with exercise is considered an established, effective ergogenic practice for athletic performance. Importantly, exercise and nutritional approaches also remain arguably the most effective countermeasure for muscle dysfunction associated with aging and numerous clinical conditions, e.g., cancer cachexia, COPD, and organ failure, via engendering favorable adaptations such as increased muscle mass and oxidative capacity. Therefore, it is important to consider the effects of established and novel effectors of muscle mass, function, and metabolism in relation to nutrition and exercise. To address this gap, in this review, we detail existing evidence surrounding the efficacy of a nonexhaustive list of macronutrient, micronutrient, and "nutraceutical" compounds alone and in combination with exercise in relation to skeletal muscle mass, metabolism (protein and fuel), and exercise performance (i.e., strength and endurance capacity). It has long been established that macronutrients have specific roles and impact upon protein metabolism and exercise performance, (i.e., protein positively influences muscle mass and protein metabolism), whereas carbohydrate and fat intakes can influence fuel metabolism and exercise performance. Regarding novel nutraceuticals, we show that the following ones in particular may have effects in relation to 1) muscle mass/protein metabolism: leucine, hydroxyl β-methylbutyrate, creatine, vitamin-D, ursolic acid, and phosphatidic acid; and 2) exercise performance: (i.e., strength or endurance capacity): hydroxyl β-methylbutyrate, carnitine, creatine, nitrates, and β-alanine. [ABSTRACT FROM AUTHOR]

Background: Primary health care (PHC) outreach teams are part of a policy of PHC re-engineering in South Africa. It attempts to move the deployment of community health workers (CHWs) from vertical programmes into an integrated generalised team-based approach to care for defined populations in municipal wards. There has little evaluation of PHC outreach teams. Managers' insights are anecdotal.Methods: This is descriptive qualitative study with focus group discussions with health district managers of Johannesburg, the largest city in South Africa. This was conducted in a sequence of three meetings with questions around implementation, human resources, and integrated PHC teamwork. There was a thematic content analysis of validated transcripts using the framework method.Results: There were two major themes: leadership-management challenges and human resource challenges. Whilst there was some positive sentiment, leadership-management challenges loomed large: poor leadership and planning with an under-resourced centralised approach, poor communications both within the service and with community, concerns with its impact on current services and resistance to change, and poor integration, both with other streams of PHC re-engineering and current district programmes. Discussion by managers on human resources was mostly on the plight of CHWs and calls for formalisation of CHWs functioning and training and nurse challenges with inappropriate planning and deployment of the team structure, with brief mention of the extended team.Conclusions: Whilst there is positive sentiment towards intent of the PHC outreach team, programme managers in Johannesburg were critical of management of the programme in their health district. Whilst the objective of PHC reform is people-centred health care, its implementation struggles with a centralising tendency amongst managers in the health service in South Africa. Managers in Johannesburg advocated for decentralisation. The implementation of PHC outreach teams is also limited by difficulties with formalisation and training of CHWs and appropriate task shifting to nurses. Change management is required to create true integrate PHC teamwork. Policy review requires addressing these issues. [ABSTRACT FROM AUTHOR]

Saliva is easily obtainable for medical research and requires little effort or training for collection. Because saliva contains a variety of biological compounds, including vitamin C, malondialdehyde, amylase, and proteomes, it has been successfully used as a biospecimen for the reflection of health status. A popular topic of discussion in medical research is the potential association between oxidative stress and negative outcomes. Systemic biomarkers that represent oxidative stress can be found in saliva. It is unclear, however, if saliva is an accurate biospecimen as is blood and/or plasma. Exercise can induce oxidative stress, resulting in a trend of antioxidant supplementation to combat its assumed detriments. Vitamin C is a popular antioxidant supplement in the realm of sports and exercise. One potential avenue for evaluating exercise induced oxidative stress is through assessment of biomarkers like vitamin C and malondialdehyde in saliva. At present, limited research has been done in this area. The current state of research involving exercise-induced oxidative stress, salivary biomarkers, and vitamin C supplementation is reviewed in this article. [ABSTRACT FROM AUTHOR]

Suicidal behavior (SB) has a complex etiology involving genes and environment. One of the genetic components in SB could be copy number variations (CNVs), as CNVs are implicated in neurodevelopmental disorders. However, a recently published genome-wide and case-control study did not observe any significant role of CNVs in SB. Here we complemented these initial observations by instead using a family-based trio-sample that is robust to control biases, having severe suicide attempt (SA) in offspring as main outcome (n = 660 trios). We first tested for CNV associations on the genome-wide Illumina 1M SNP-array by using FBAT-CNV methodology, which allows for evaluating CNVs without reliance on CNV calling algorithms, analogous to a common SNP-based GWAS. We observed association of certain T-cell receptor markers, but this likely reflected inter-individual variation in somatic rearrangements rather than association with SA outcome. Next, we used the PennCNV software to call 385 putative rare (<1%) and large (>100 kb) CNVs, observed in n = 225 SA offspring. Nine SA offspring had rare CNV calls in a set of previously schizophrenia-associated loci, indicating the importance of such CNVs in certain SA subjects. Several additional, very large (>1MB) sized CNV calls in 15 other SA offspring also spanned pathogenic regions or other neural genes of interest. Overall, 45 SA had CNVs enriched for 65 medically relevant genes previously shown to be affected by CNVs, which were characterized by a neurodevelopmental biology. A neurodevelopmental implication was partly congruent with our previous SNP-based GWAS, but follow-up analysis here indicated that carriers of rare CNVs had a decreased burden of common SNP risk-alleles compared to non-carriers. In conclusion, while CNVs did not show genome-wide association by the FBAT-CNV methodology, our preliminary observations indicate rare pathogenic CNVs affecting neurodevelopmental functions in a subset of SA, who were distinct from SA having increased SNP risk-allele burden. These observations may open up new avenues in the genetic etiology of SB. [ABSTRACT FROM AUTHOR]

Integrins are heterodimeric cell surface receptors that bind to different extracellular ligands depending on their composition and regulate all processes which enable multicellular life. In cancer, integrins trigger and play key roles in all the features that were once described as the Hallmarks of Cancer. In this review, we will discuss the contribution of integrins to these hallmarks, including uncontrolled and limitless proliferation, invasion of tumor cells, promotion of tumor angiogenesis and evasion of apoptosis and resistance to growth suppressors, by highlighting the latest findings. Further on, given the paramount role of integrins in cancer, we will present novel strategies for integrin inhibition that are starting to emerge, promising a hopeful future regarding cancer treatment. [ABSTRACT FROM AUTHOR]

Afghanistan is one of the most fragile and conflict-affected countries in the world. It has experienced almost uninterrupted conflict for the last thirty years, with the present conflict now lasting over a decade. With no history of a functioning healthcare system, the creation of the Basic Package of Health Services (BPHS) in 2003 was a response to Afghanistan's dire health needs following decades of war. Its objective was to provide a bare minimum of essential health services, which could be scaled up rapidly through contracting mechanisms with Non- Governmental Organisations (NGOs). The central thesis of this article is that, despite the good intentions of the BPHS, not enough has been done to overcome the barriers to accessing its services. This analysis, enabled through a review of the existing literature, identifies and categorises these barriers into the three access dimensions of: acceptability, affordability and availability. As each of these is explored individually, analysis will show the extent to which these barriers to access are a critical issue, consider the underlying reasons for their existence and evaluate the efforts to overcome these barriers. Understanding these barriers and the policies that have been implemented to address them is critical to the future of health system strengthening in Afghanistan. [ABSTRACT FROM AUTHOR]

Background: There has been a substantial increase in publications and interest in community health workers (CHWs) in low- and middle-income countries (LMIC) over the last years. This paper examines the growth, geographical distribution and programmatic orientations of the indexed literature on CHWs in LMIC over a 10-year period. Methods: A scoping review of publications on CHWs from 2005 to 2014 was conducted. Using an inclusive list of terms, we searched seven databases (including MEDLINE, CINAHL, Cochrane) for all English-language publications on CHWs in LMIC. Two authors independently screened titles/abstracts, downloading full-text publications meeting inclusion criteria. These were coded in an Excel spreadsheet by year, type of publication (e.g. review, empirical), country, region, programmatic orientation (e.g. maternal-child health, HIV/AIDS, comprehensive) and CHW roles (e.g. prevention, treatment) and further analysed in Stata14. Drawing principally on the subset of review articles, specific roles within programme areas were identified and grouped. Findings: Six hundred seventy-eight publications from 46 countries on CHWs were inventoried over the 10-year period. There was a sevenfold increase in annual number of publications from 23 in 2005 to 156 in 2014. Half the publications were reporting on initiatives in Africa, a third from Asia and 11% from the Americas (mostly Brazil). The largest single focus and driver of the growth in publications was on CHW roles in meeting the Millennium Development Goals of maternal, child and neonatal survival (35% of total), followed by HIV/AIDS (16%), reproductive health (6%), non-communicable diseases (4%) and mental health (4%). Only 17% of the publications approached CHW roles in an integrated fashion. There were also distinct regional (and sometimes country) profiles, reflecting different histories and programme traditions. Conclusions: The growth in literature on CHWs provides empirical evidence of ever-increasing expectations for addressing health burdens through community-based action. This literature has a strong disease- or programme-specific orientation, raising important questions for the design and sustainable delivery of integrated national programmes. [ABSTRACT FROM AUTHOR]

A popular belief is that reactive oxygen species (ROS) and reactive nitrogen species (RNS) produced during exercise by the mitochondria and other subcellular compartments ubiquitously cause skeletal muscle damage, fatigue and impair recovery. However, the importance of ROS and RNS as signals in the cellular adaptation process to stress is now evident. In an effort to combat the perceived deleterious effects of ROS and RNS it has become common practice for active individuals to ingest supplements with antioxidant properties, but interfering with ROS/RNS signalling in skeletal muscle during acute exercise may blunt favourable adaptation. There is building evidence that antioxidant supplementation can attenuate endurance training-induced and ROS/RNS-mediated enhancements in antioxidant capacity, mitochondrial biogenesis, cellular defence mechanisms and insulin sensitivity. However, this is not a universal finding, potentially indicating that there is redundancy in the mechanisms controlling skeletal muscle adaptation to exercise, meaning that in some circumstances the negative impact of antioxidants on acute exercise response can be overcome by training. Antioxidant supplementation has been more consistently reported to have deleterious effects on the response to overload stress and high-intensity training, suggesting that remodelling of skeletal muscle following resistance and high-intensity exercise is more dependent on ROS/RNS signalling. Importantly there is no convincing evidence to suggest that antioxidant supplementation enhances exercise-training adaptions. Overall, ROS/RNS are likely to exhibit a non-linear (hormetic) pattern on exercise adaptations, where physiological doses are beneficial and high exposure (which would seldom be achieved during normal exercise training) may be detrimental. [ABSTRACT FROM AUTHOR]

Background: Primary health care services are fundamental to improving health and health equity, particularly in the context of low and middle-income settings where resources are scarce. During the past decade, Ethiopia undertook an ambitious investment in primary health care known as the Ethiopian Health Extension Program that recorded impressive gains in several health outcomes. Despite this progress, substantial disparities in health outcomes persist across the country. The objective of this study was to understand how variation in the implementation of the primary health care efforts may explain differences in key health outcomes. Methods and Findings: We conducted a qualitative study of higher-performing and lower-performing woredas using site visits and in-depth interviews undertaken in 7 woredas. We classified woredas as higher-performing or lower-performing based on data on 5 indicators. We conducted a total of 94 open-ended interviews; 12–15 from each woreda. The data were analyzed using the constant comparative method of qualitative data analysis. Substantial contrasts were apparent between higher-performing and lower-performing woredas in use of data for problem solving and performance improvement; collaboration and respectful relationships among health extension workers, community members, and health center staff; and coordination between the woreda health office and higher-level regulatory and financing bodies at the zonal and regional levels. We found similarities in what was reported to motivate or demotivate health extension workers and other staff. Additionally, higher-performing and lower-performing woredas shared concerns about hospitals being isolated from health centers and health posts. Participants from both woredas also highlighted a mismatch between the urban health extension program design and the urban-dwelling communities’ expectations for primary health care. Conclusions: Data-informed problem solving, respectful and supportive relationships with the community, and strong support from zonal and regional health bureaus contributed to woreda performance, suggesting avenues for achieving higher performance in primary health care. [ABSTRACT FROM AUTHOR]

Methyl CpG binding protein 2 (MeCP2) is a highly abundant chromosomal protein within the brain. It is hence not surprising that perturbations in its genome-wide distribution, and at particular loci within this tissue, can result in widespread neurological disorders that transcend the early implications of this protein in Rett syndrome (RTT). Yet, the details of its role and involvement in chromatin organization are still poorly understood. This paper focuses on what is known to date about all of this with special emphasis on the relation to different epigenetic modifications (DNA methylation, histone acetylation/ubiquitination, MeCP2 phosphorylation and miRNA). We showcase all of the above in two particular important neurological functional alterations in the brain: depression (major depressive disorder [MDD]) and cocaine addiction, both of which affect the MeCP2 homeostasis and result in significant changes in the overall levels of these epigenetic marks. [ABSTRACT FROM AUTHOR]

Background: The low transcriptionally efficient short-allele of the 5HTTLPR serotonin transporter polymorphism has been implicated to moderate the relationship between the experience of stressful life events (SLEs) and depression. Despite numerous attempts at replicating this observation, results remain inconclusive. Methods: We examined this relationship in young-adult Non-Hispanic white males and females between the ages of 22 and 26 (n = 4724) participating in the National Longitudinal Study of Adolescent to Adult Health (Add Health) with follow-up information every six years since 1995. Results: Linear and logistic regression models, corrected for multiple testing, indicated that carriers of one or more of the S-alleles were more sensitive to stress than those with two L-alleles and at a higher risk for depression. This relationship behaved in a dose-response manner such that the risk for depression was greatest among those who reported experiencing higher numbers of SLEs. In post-hoc analyses we were not able to replicate an interaction effect for suicide ideation but did find suggestive evidence that the effects of SLEs and 5HTTLPR on suicide ideation differed for males and females. There were no effects of childhood maltreatment. Discussion: Our results provide partial support for the original hypothesis that 5-HTTLPR genotype interacts with the experience of stressful life events in the etiology of depression during young adulthood. However, even with this large sample, and a carefully constructed a priori analysis plan, the results were still not definitive. For the purposes of replication, characterizing the 5HTTLPR in other large data sets with extensive environmental and depression measures is needed. [ABSTRACT FROM AUTHOR]

Background: Engagement of communities and civil society organizations is a critical part of the Post-2015 End TB Strategy. Since 2007, many models of community referral have been implemented to boost TB case detection in Nigeria. Yet clear insights into the comparative TB yield from particular approaches have been limited.Methods: We compared four models of active case finding in three Nigerian states. Data on presumptive TB case referral by community workers (CWs), TB diagnoses among referred clients, active case finding model characteristics, and CWs compensation details for 2012 were obtained from implementers and CWs via interviews and log book review. Self-reported performance data were triangulated against routine surveillance data to assess concordance. Analysis focused on assessing the predictors of presumptive TB referral.Results: CWs referred 4-22% of presumptive TB clients tested, and 4-24% of the total TB cases detected. The annual median referral per CW ranged widely among the models from 1 to 48 clients, with an overall average of 13.4 referrals per CW. The highest median referrals (48 per CW/yr) and mean TB diagnoses (7.1/yr) per CW (H =70.850, p < 0.001) was obtained by the model with training supervision, and $80/quarterly payments (Comprehensive Quotas-Oriented model). The model with irregularly supervised, trained, and compensated CWs contributed the least to TB case detection with a median of 13 referrals per CW/yr and mean of 0.53 TB diagnoses per CW/yr. Hours spent weekly on presumptive TB referral made the strongest unique contribution (Beta = 0.514, p < 0.001) to explaining presumptive TB referral after controlling for other variables.Conclusion: All community based TB case-finding projects studied referred a relative low number of symptomatic individuals. The study shows that incentivized referral, appropriate selection of CWs, supportive supervision, leveraged treatment support roles, and a responsive TB program to receive clients for testing were the key drivers of community TB case finding. [ABSTRACT FROM AUTHOR]

Objective: This paper examines whether Australian regional primary health care organisations - in this case, Medicare Locals (MLs) and Primary Health Networks (PHNs) - have engaged with migrant and refugee health, and what factors encourage work in this area., Methods: The study used mixed methods with surveys of ML (N=210) and PHN staff (N=66), interviews with ML (N=50) and PHN (N=55) staff, national consultations with migrant and refugee organisations (N=8 groups with 62 participants), and analysis of ML and PHN documents., Results: Needs assessment documents identified migrant and refugee health issues in 46% of MLs and 74% of PHNs. However, 48% of MLs and 55% of PHNs did not report any activities on migrant health, and 78% and 62% did not report any activities for refugees, respectively. Key factors identified by participants as associated with whether ML and PHN focus on migrant and refugee health were the determination of local priority areas, policy context and funding, collaboration with migrant and refugee organisations and communities, and mechanisms for engagement., Conclusions: Despite the importance of primary health care for migrants and refugees, there was relatively little attention paid to these population groups in MLs and PHNs, with a small number of notable exceptions. Implications for public health: The paper concludes with a range of recommendations for improving regional primary health care organisation engagement with migrant and refugee health., (© 2020 The Authors.)

Background: In Mozambique, integrated community case management (iCCM) of diarrhoea, malaria and pneumonia is embedded in the national community health worker (CHW) programme, mainstreaming it into government policy and service delivery. Since its inception in 1978, the CHW programme has functioned unevenly, was suspended in 1989, but relaunched in 2010. To assess the long-term success of iCCM in Mozambique, this article addresses whether the current CHW programme exhibits characteristics that facilitate or impede its sustainability.Methodology: We undertook a qualitative case study based on document review (n = 54) and key informant interviews (n = 21) with respondents from the Ministry of Health (MOH), multilateral and bilateral agencies and non-governmental organizations (NGOs) in Maputo in 2012. Interviews were mostly undertaken in Portuguese and all were coded using NVivo. A sustainability framework guided thematic analysis according to nine domains: strategic planning, organizational capacity, programme adaptation, programme monitoring and evaluation, communications, funding stability, political support, partnerships and public health impact.Results: Government commitment was high, with the MOH leading a consultative process in Maputo and facilitating successful technical coordination. The MOH made strategic decisions to pay CHWs, authorize their prescribing abilities, foster guidance development, support operational planning and incorporate previously excluded 'old' CHWs. Nonetheless, policy negotiations excluded certain key actors and uncertainty remains about CHW integration into the civil service and their long-term retention. In addition, reliance on NGOs and donor funding has led to geographic distortions in scaling up, alongside challenges in harmonization. Finally, dependence on external funding, when both external and government funding are declining, may hamper sustainability.Conclusions: Our analysis represents a nuanced assessment of the various domains that influence CHW programme sustainability, highlighting strategic areas such as CHW payment and programme financing. These organizational and contextual determinants of sustainability are central to CHW programme strengthening and iCCM policy support. [ABSTRACT FROM AUTHOR]

Research in humans and animals has shown that negative childhood experiences (NCE) can have long-term effects on the structure and function of the brain. Alterations have been noted in grey and white matter, in the brain's resting state, on the glutamatergic system, and on neural and behavioural responses to aversive stimuli. These effects can be linked to psychiatric disorder such as depression and anxiety disorders that are influenced by excessive exposure to early life stressors. The aim of the current study was to investigate the effect of NCEs on these systems. Resting state functional MRI (rsfMRI), aversion task fMRI, glutamate magnetic resonance spectroscopy (MRS), and diffusion magnetic resonance imaging (dMRI) were combined with the Childhood Trauma Questionnaire (CTQ) in healthy subjects to examine the impact of NCEs on the brain. Low CTQ scores, a measure of NCEs, were related to higher resting state glutamate levels and higher resting state entropy in the medial prefrontal cortex (mPFC). CTQ scores, mPFC glutamate and entropy, correlated with neural BOLD responses to the anticipation of aversive stimuli in regions throughout the aversion-related network, with strong correlations between all measures in the motor cortex and left insula. Structural connectivity strength, measured using mean fractional anisotropy, between the mPFC and left insula correlated to aversion-related signal changes in the motor cortex. These findings highlight the impact of NCEs on multiple inter-related brain systems. In particular, they highlight the role of a prefrontal-insular-motor cortical network in the processing and responsivity to aversive stimuli and its potential adaptability by NCEs. Hum Brain Mapp 36:4622-4637, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background: In 2012, the Ministry of Health and Social Welfare (MOHSW), Tanzania, approved national guidelines and training materials for community health workers (CHWs) in integrated maternal, newborn and child health (Integrated MNCH), with CHWs trained and deployed across five districts of Morogoro Region soon after. To inform future scale up, this study assessed motivation and satisfaction among these CHWs. Methods: A survey of all CHWs trained by the Integrated MNCH Programme was conducted in the last quarter of 2013. Motivation and satisfaction were assessed using a five-point Likert scale with 29 and 27 items based on a literature review and discussions with CHW programme stakeholders. Exploratory factor analysis was conducted to identify motivation and satisfaction determinants. Results: Out of 238 eligible CHWs, 96 % were included in the study. Findings showed that respondents were motivated to become CHWs due to altruism (work on MNCH, desire to serve God, work hard) and intrinsic needs (help community, improve health, pride) than due to external stimuli (monetary incentives, skill utilization, community respect or hope for employment). CHWs were satisfied by relationships with health workers and communities, job aids and the capacity to provide services. CHWs were dissatisfied with the lack of transportation, communication devices and financial incentives for carrying out their tasks. Factors influencing motivation and satisfaction did not differ across CHW socio-demographic characteristics. Nonetheless, older and less educated CHWs were more likely to be motivated by altruism, intrinsic needs and skill utilization, community respect and hope for employment. Less educated CHWs were more satisfied with service and quality factors and more wealthy CHWs satisfied with job aids. Conclusion and recommendations: A combination of financial and non-financial incentives is required to support motivation and satisfaction among CHWs. Although CHWs joined mainly due to their altruistic nature, they became discontented with the lack of monetary compensation, transportation and communication support received. With the planned rollout of the national CHW cadre, improved understanding of CHWs as a heterogeneous group with nuanced needs and varied ambitions is vital for ensuring sustainability. [ABSTRACT FROM AUTHOR]

Background: Several broad lines of evidence support the involvement of epigenetic processes in neurodevelopment and psychiatric disorders. Epigenetic disruption also provides a potential mechanism to account for the numerous gene-environment interactions that have been reported in association with neuropsychiatric phenotypes.Methods: A review of the literature was performed with keywords 'depression', 'depressive disorder' or 'antidepressants' and 'DNA methylation', or 'epigenetics' in humans. Citations were limited to those written in English and published prior to July 2014.Results: We present a summary of results to date. Most studies have focused on DNA methylation in various CNS or peripheral tissue, with almost universally small sample sizes. Although seven epigenome-wide association studies have now been reported, the majority of studies have used a candidate-gene approach. Three genes (SLC6A4, BDNF, NR3C1) have been investigated in more than one study, but replication of findings is generally lacking.Conclusions: Recent evidence provides insights to epigenetic processes in psychiatric disorders; however, replication is lacking and care must be taken in the interpretation of current findings. This applies to epigenetic epidemiology generally, which is subject to various limitations that no single approach can address in isolation. Due to limited focus of most depression studies to date, placing the findings within the broader context of mood disorder pathophysiology may prove challenging. However, identifying peripheral biomarkers for depressive disorder remains a tantalising possibility, especially given the potential for carefully-designed longitudinal studies with multiple biospecimens and ongoing advances in epigenetic technologies. [ABSTRACT FROM AUTHOR]

Hormesis encompasses the notion that low levels of stress stimulate or upregulate existing cellular and molecular pathways that improve the capacity of cells and organisms to withstand greater stress. This notion underlies much of what we know about how exercise conditions the body and induces long-term adaptations. During exercise, the body is exposed to various forms of stress, including thermal, metabolic, hypoxic, oxidative, and mechanical stress. These stressors activate biochemical messengers, which in turn activate various signaling pathways that regulate gene expression and adaptive responses. Historically, antioxidant supplements, nonsteroidal anti-inflammatory drugs, and cryotherapy have been favored to attenuate or counteract exercise-induced oxidative stress and inflammation. However, reactive oxygen species and inflammatory mediators are key signaling molecules in muscle, and such strategies may mitigate adaptations to exercise. Conversely, withholding dietary carbohydrate and restricting muscle blood flow during exercise may augment adaptations to exercise. In this review article, we combine, integrate, and apply knowledge about the fundamental mechanisms of exercise adaptation. We also critically evaluate the rationale for using interventions that target these mechanisms under the overarching concept of hormesis. There is currently insufficient evidence to establish whether these treatments exert dose-dependent effects on muscle adaptation. However, there appears to be some dissociation between the biochemical/molecular effects and functional/performance outcomes of some of these treatments. Although several of these treatments influence common kinases, transcription factors, and proteins, it remains to be determined if these interventions complement or negate each other, and whether such effects are strong enough to influence adaptations to exercise. [ABSTRACT FROM AUTHOR]

Introduction: Community health workers (CHWs) have been proposed as a means for bridging gaps in healthcare delivery in rural communities. Recent CHW programmes have been shown to improve child and neonatal health outcomes, and it is increasingly being suggested that paid CHWs become an integral part of health systems. Remuneration of CHWs can potentially effect their motivation and focus. Broadly, programmes follow a social, monetary or mixed market approach to remuneration. Conscious understanding of the differences, and of what each has to offer, is important in selecting the most appropriate approach according to the context. Case descriptions: The objective of this review is to identify and examine different remuneration models of CHWs that have been utilized in large-scale sustained programmes to gain insight into the effect that remuneration has on the motivation and focus of CHWs. A MEDLINE search using Ovid SP was undertaken and data collected from secondary sources about CHW programmes in Iran, Ethiopia, India, Bangladesh and Nepal. Five main approaches were identified: part-time volunteer CHWs without regular financial incentives, volunteers that sell health-related merchandise, volunteers with financial incentives, paid full-time CHWs and a mixed model of paid and volunteer CHWs. Discussion and evaluation: Both volunteer and remunerated CHWs are potentially effective and can bring something to the health arena that the other may not. For example, well-trained, supervised volunteers and full-time CHWs who receive regular payment, or a combination of both, are more likely to engage the community in grass-roots health-related empowerment. Programmes that utilize minimal economic incentives to part-time CHWs tend to limit their focus, with financially incentivized activities becoming central. They can, however, improve outcomes in well-circumscribed areas. In order to maintain benefits from different approaches, there is a need to distinguish between CHWs that are trained and remunerated to be a part of an existing health system and those who, with little training, take on roles and are motivated by a range of contextual factors. Governments and planners can benefit from understanding the programme that can best be supported in their communities, thereby maximizing motivation and effectiveness. [ABSTRACT FROM AUTHOR]

Suicide and suicide attempts are complex behaviors that result from the interaction of different factors, including genetic variants that increase the predisposition to suicidal behaviors. Copy number variations (CNVs) are deletions or duplications of a segment of DNA usually larger than one kilobase. These structural genetic changes, although quite rare, have been associated with genetic liability to mental disorders, such as autism, schizophrenia, and bipolar disorder. No genome-wide level studies have been published investigating the potential role of CNVs in suicidal behaviors. Based on single-nucleotide polymorphism array data, we followed the Penn-CNV standards to detect CNVs in 1,608 subjects, comprising 475 suicide and suicide attempt cases and 1,133 controls. Although the initial algorithms determined the presence of CNVs on chromosomes 6 and 12 in seven and eight cases, respectively, compared with none of the controls, visual inspection of the raw data did not support this finding. Furthermore we were unable to validate these findings by CNV-specific real-time polymerase chain reaction. Additionally, rare CNV burden analysis did not find an association between the frequency or length of rare CNVs and suicidal behavior in our sample population. Although our findings suggest CNVs do not play an important role in the etiology of suicidal behaviors, they are not inconsistent with the strong evidence from the literature suggesting that other genetic variants account for a portion of the total phenotypic variability in suicidal behavior. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer (GC) is the world’s fifth most common cancer, and the third leading cause of cancer-related death. Over 70% of incident cases and deaths occur in developing countries. We explored whether disparities in access to improved drinking water sources were associated with GC risk in the Golestan Gastric Cancer Case Control Study. Methods and Findings: 306 cases and 605 controls were matched on age, gender, and place of residence. We conducted unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CI), adjusted for age, gender, ethnicity, marital status, education, head of household education, place of birth and residence, homeownership, home size, wealth score, vegetable consumption, and H. pylori seropositivity. Fully-adjusted ORs were 0.23 (95% CI: 0.05–1.04) for chlorinated well water, 4.58 (95% CI: 2.07–10.16) for unchlorinated well water, 4.26 (95% CI: 1.81–10.04) for surface water, 1.11 (95% CI: 0.61–2.03) for water from cisterns, and 1.79 (95% CI: 1.20–2.69) for all unpiped sources, compared to in-home piped water. Comparing unchlorinated water to chlorinated water, we found over a two-fold increased GC risk (OR 2.37, 95% CI: 1.56–3.61). Conclusions: Unpiped and unchlorinated drinking water sources, particularly wells and surface water, were significantly associated with the risk of GC. [ABSTRACT FROM AUTHOR]

Introduction: Close-to-community (CTC) providers, including community health workers or volunteers or health extension workers, can be effective in promoting access to and utilization of health services. Tasks are often shifted to these providers with limited resources and support from CTC programmes or communities. The Community Health System Strengthening (CHSS) model is part of an improvement approach which draws on existing formal and informal networks within a community, such as agricultural or women's groups, to support CTC providers and address gaps in community-based health services. The model offers a framework for bringing representatives from existing community networks, CTC providers, and health facility staff together to form a community team charged with identifying challenges in service delivery, testing solutions, and monitoring changes. CTC providers draw upon fellow community team members to disseminate health messages and refer community members in need of services. Cases: Two cases are presented. In Ethiopia, the CHSS model was applied in 18 communities to increase HIV testing among pregnant women and antenatal care service utilization and improve sanitation. Prior to implementation, representatives from community groups were unaware of health extension workers or were uncomfortable making referrals. By participating on the community team, representatives became familiar with and comfortable referring people to health extension workers and spreading health messages. During implementation, more pregnant women registered for antenatal care and tested for HIV; health extension workers conducted more postnatal visits; and more households had functioning latrines and proper latrine use increased. In Tanzania, the CHSS model was applied in five communities to improve HIV testing and retention into care. Community team members talked to their families and social networks about HIV testing and, when they identified someone who had dropped out of treatment, they referred those individuals to the home-based care volunteer. Increases in HIV testing and a reduction in patients lost to follow-up were observed. Discussion and conclusion: The CHSS model brings together existing networks within communities to support and lend legitimacy to CTC providers. This approach may result in sustainable community-based programmes, especially in HIV where the continuum of care extends beyond the facility and into the community. [ABSTRACT FROM AUTHOR]

Background Antisocial personality disorder (ASPD) is characterised by elevated impulsive aggression and increased risk for criminal behaviour and incarceration. Deficient activity of the monoamine oxidase A (MAOA) gene is suggested to contribute to serotonergic system dysregulation strongly associated with impulsive aggression and antisocial criminality. Aims To elucidate the role of epigenetic processes in altered MAOA expression and serotonin regulation in a population of incarcerated offenders with ASPD compared with a healthy non-incarcerated control population. Method Participants were 86 incarcerated participants with ASPD and 73 healthy controls. MAOA promoter methylation was compared between case and control groups. We explored the functional impact of MAOA promoter methylation on gene expression in vitro and blood 5-HT levels in a subset of the case group. Results Results suggest that MAOA promoter hypermethylation is associated with ASPD and may contribute to downregulation of MAOA gene expression, as indicated by functional assays in vitro, and regression analysis with whole-blood serotonin levels in offenders with ASPD. Conclusions These results are consistent with prior literature suggesting MAOA and serotonergic dysregulation in antisocial populations. Our results offer the first evidence suggesting epigenetic mechanisms may contribute to MAOA dysregulation in antisocial offenders. [ABSTRACT FROM AUTHOR]

Background: Community health workers (CHWs) are increasingly recognized as an integral component of the health workforce needed to achieve public health goals in low- and middle-income countries (LMICs). Many factors intersect to influence CHW performance. A systematic review with a narrative analysis was conducted to identify contextual factors influencing performance of CHWs. Methods: We searched six databases for quantitative, qualitative, and mixed-methods studies that included CHWs working in promotional, preventive or curative primary health care services in LMICs. We differentiated CHW performance outcome measures at two levels: CHW level and end-user level. Ninety-four studies met the inclusion criteria and were double read to extract data relevant to the context of CHW programmes. Thematic coding was conducted and evidence on five main categories of contextual factors influencing CHW performance was synthesized. Results: Few studies had the influence of contextual factors on CHW performance as their primary research focus. Contextual factors related to community (most prominently), economy, environment, and health system policy and practice were found to influence CHW performance. Socio-cultural factors (including gender norms and values and disease related stigma), safety and security and education and knowledge level of the target group were community factors that influenced CHW performance. Existence of a CHW policy, human resource policy legislation related to CHWs and political commitment were found to be influencing factors within the health system policy context. Health system practice factors included health service functionality, human resources provisions, level of decision-making, costs of health services, and the governance and coordination structure. All contextual factors can interact to shape CHW performance and affect the performance of CHW interventions or programmes. Conclusions: Research on CHW programmes often does not capture or explicitly discuss the context in which CHW interventions take place. This synthesis situates and discusses the influence of context on CHW and programme performance. Future health policy and systems research should better address the complexity of contextual influences on programmes. This insight can help policy makers and programme managers to develop CHW interventions that adequately address and respond to context to optimise performance. [ABSTRACT FROM AUTHOR]

Sex hormones have been implicated in neurite outgrowth, synaptogenesis, dendritic branching, myelination and other important mechanisms of neural plasticity. Here we review the evidence from animal experiments and human studies reporting interactions between sex hormones and the dominant neurotransmitters, such as serotonin, dopamine, GABA and glutamate. We provide an overview of accumulating data during physiological and pathological conditions and discuss currently conceptualized theories on how sex hormones potentially trigger neuroplasticity changes through these four neurochemical systems. Many brain regions have been demonstrated to express high densities for estrogen- and progesterone receptors, such as the amygdala, the hypothalamus, and the hippocampus. As the hippocampus is of particular relevance in the context of mediating structural plasticity in the adult brain, we put particular emphasis on what evidence could be gathered thus far that links differences in behavior, neurochemical patterns and hippocampal structure to a changing hormonal environment. Finally, we discuss how physiologically occurring hormonal transition periods in humans can be used to model how changes in sex hormones influence functional connectivity, neurotransmission and brain structure in vivo. [ABSTRACT FROM AUTHOR]

Background: Subpopulations and Intermediate Outcomes in COPD Study (SPIROMICS) is a multi-center longitudinal, observational study to identify novel phenotypes and biomarkers of chronic obstructive pulmonary disease (COPD). In a subset of 300 subjects enrolled at six clinical centers, we are performing flow cytometric analyses of leukocytes from induced sputum, bronchoalveolar lavage (BAL) and peripheral blood. To minimize several sources of variability, we use a "just-in-time" design that permits immediate staining without pre-fixation of samples, followed by centralized analysis on a single instrument. Methods: The Immunophenotyping Core prepares 12-color antibody panels, which are shipped to the six Clinical Centers shortly before study visits. Sputum induction occurs at least two weeks before a bronchoscopy visit, at which time peripheral blood and bronchoalveolar lavage are collected. Immunostaining is performed at each clinical site on the day that the samples are collected. Samples are fixed and express shipped to the Immunophenotyping Core for data acquisition on a single modified LSR II flow cytometer. Results are analyzed using FACS Diva and FloJo software and cross-checked by Core scientists who are blinded to subject data. Results: Thus far, a total of 152 sputum samples and 117 samples of blood and BAL have been returned to the Immunophenotyping Core. Initial quality checks indicate useable data from 126 sputum samples (83%), 106 blood samples (91%) and 91 BAL samples (78%). In all three sample types, we are able to identify and characterize the activation state or subset of multiple leukocyte cell populations (including CD4+ and CD8+ T cells, B cells, monocytes, macrophages, neutrophils and eosinophils), thereby demonstrating the validity of the antibody panel. Conclusions: Our study design, which relies on bi-directional communication between clinical centers and the Core according to a pre-specified protocol, appears to reduce several sources of variability often seen in flow cytometric studies involving multiple clinical sites. Because leukocytes contribute to lung pathology in COPD, these analyses will help achieve SPIROMICS aims of identifying subgroups of patients with specific COPD phenotypes. Future analyses will correlate cell-surface markers on a given cell type with smoking history, spirometry, airway measurements, and other parameters. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a devastating neuropsychiatric disorder encompassing a wide range of cognitive and emotional dysfunctions. The prevalence of MDD is expected to continue its growth to become the second leading cause of disease burden (after HIV) by 2030. Despite an extensive research effort, the exact etiology of MDD remains elusive and the diagnostics uncertain. Moreover, a marked inter-individual variability is observed in the vulnerability to develop depression, as well as in response to antidepressant treatment, for nearly 50% of patients. Although a genetic component accounts for some cases of MDD, it is now clearly established that MDD results from strong gene and environment interactions. Such interactions could be mediated by epigenetic mechanisms, defined as chromatin and DNA modifications that alter gene expression without changing the DNA structure itself. Some epigenetic mechanisms have recently emerged as particularly relevant molecular substrates, promoting vulnerability or resilience to the development of depressive-like symptoms. Although the role of brainderived neurotrophic factor (BDNF) in the pathophysiology of MDD remains unclear, its modulation of the efficacy of antidepressants is clearly established. Therefore, in this review, we focus on the epigenetic mechanisms regulating the expression of BDNF in humans and in animal models of depression, and discuss their role in individual differences in vulnerability to depression and response to antidepressant drugs. [ABSTRACT FROM AUTHOR]

Suicidal behaviors (SB) may be regarded as the outmost consequence of mental illnesses, or as a distinct entity per se. Regardless, the consequences of SB are very large to both society and affected individuals. The path leading to SB is clearly a complex one involving interactions between the subject's biology and environmental influences throughout life. With the aim to generate a representative and diversified overview of the different neurobiological components hypothesized or shown implicated across the entire SB field up to date by any approach, we selected and compiled a list of 212 gene symbols from the literature. An increasing number of novel gene (products) have been introduced as candidates, with half being implicated in SB in only the last 4 years. These candidates represent different neurosystems and functions and might therefore be regarded as competing or redundant explanations. We then adopted a unifying approach by treating them all as parts of the same meta-system, using bioinformatic tools. We present a network of all components connected by physical protein-protein interactions (the SB interactome). We proceeded by exploring the differences between the highly connected core (~30% of the candidate genes) and its peripheral parts, observing more functional homogeneity at the core, with multiple signal transduction pathways and actin-interacting proteins connecting a subset of receptors in nerve cell compartments as well as development/morphology phenotypes and the stress-sensitive synaptic plasticity processes of long term potentiation/depression. We suggest that SB neurobiology might also be viewed as one meta-system and perhaps be explained as intrinsic unbalances acting within the core or as imbalances arising between core and specific peripheral components. [ABSTRACT FROM AUTHOR]

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Key points Although antioxidant supplements are generally believed to give health benefits, recent experiments show that they may adversely affect adaptations to endurance exercise., This study is the first to investigate the effects of high dosages of vitamins C and E on the cellular and physiological adaptations to strength training in humans., Here we report that vitamin C and E supplementation interfered with exercise-induced signalling in muscle cells after a session of strength training, by reducing the phosphorylation of p70S6 kinase and mitogen-activated protein kinases p38 and ERK1/2., The vitamin C and E supplement did not significantly blunt muscle hypertrophy during 10 weeks of training; however, some measurements of muscle strength revealed lower increases in the supplemented group than the placebo group., Even though the cellular events are not clearly reflected in physiological and performance measurements, this study implies that redox signalling is important for inducing skeletal muscle adaptations to strength training and that vitamin C and E supplements in high dosages should be avoided by healthy, young individuals engaged in strength training., Abstract This study investigated the effects of vitamin C and E supplementation on acute responses and adaptations to strength training. Thirty-two recreationally strength-trained men and women were randomly allocated to receive a vitamin C and E supplement (1000 mg day−1 and 235 mg day−1, respectively), or a placebo, for 10 weeks. During this period the participants' training involved heavy-load resistance exercise four times per week. Muscle biopsies from m. vastus lateralis were collected, and 1 repetition maximum (1RM) and maximal isometric voluntary contraction force, body composition (dual-energy X-ray absorptiometry), and muscle cross-sectional area (magnetic resonance imaging) were measured before and after the intervention. Furthermore, the cellular responses to a single exercise session were assessed midway in the training period by measurements of muscle protein fractional synthetic rate and phosphorylation of several hypertrophic signalling proteins. Muscle biopsies were obtained from m. vastus lateralis twice before, and 100 and 150 min after, the exercise session (4 × 8RM, leg press and knee-extension). The supplementation did not affect the increase in muscle mass or the acute change in protein synthesis, but it hampered certain strength increases (biceps curl). Moreover, increased phosphorylation of p38 mitogen-activated protein kinase, Extracellular signal-regulated protein kinases 1 and 2 and p70S6 kinase after the exercise session was blunted by vitamin C and E supplementation. The total ubiquitination levels after the exercise session, however, were lower with vitamin C and E than placebo. We concluded that vitamin C and E supplementation interfered with the acute cellular response to heavy-load resistance exercise and demonstrated tentative long-term negative effects on adaptation to strength training. [ABSTRACT FROM AUTHOR]

Background: StemSport (SS; StemTech International, Inc. San Clemente, CA) contains a proprietary blend of the botanical Aphanizomenon flos-aquae and several herbal antioxidant and anti-inflammatory substances. SS has been purported to accelerate tissue repair and restore muscle function following resistance exercise. Here, we examine the effects of SS supplementation on strength adaptations resulting from a 12-week resistance training program in healthy young adults. Methods: Twenty-four young adults (16 males, 8 females, mean age = 20.5 ± 1.9 years, mass = 70.9 ± 11.9 kg, stature = 176.6 ± 9.9 cm) completed the twelve week training program. The study design was a double-blind, placebo controlled parallel group trial. Subjects either received placebo or StemSport supplement (SS; mg/day) during the training. 1-RM bench press, 1-RM leg press, vertical jump height, balance (star excursion and center of mass excursion), isokinetic strength (elbow and knee flexion/extension) and perception of recovery were measured at baseline and following the 12-week training intervention. Results: Resistance training increased 1-RM strength (p < 0.008), vertical jump height (p < 0.03), and isokinetic strength (p < 0.05) in both SS and placebo groups. No significant group-by-time interactions were observed (all p-values >0.10). Conclusions: These data suggest that compared to placebo, the SS herbal/botanical supplement did not enhance training induced adaptations to strength, balance, and muscle function above strength training alone. [ABSTRACT FROM AUTHOR]

Background Afghanistan is a country that has been in conflict for decades, resulting in the destruction of much of its social infrastructure including the health system. In 2003, after the intervention of US-led NATO forces, the new government with support from its international partners designed a Basic Package of Health Services to provide services to the majority rural population; its specific focus is on women and children. The workforce to deliver these services consists of Community Health Workers (CHWs). In this paper we aim to 1) describe the CHW program, 2) explore the gender dynamics of the workforce, and 3) identify facilitators and challenges to the program. Method Our descriptive, qualitative study involved an analysis of policy and administrative documents, in-depth interviews and focus groups, and non-participant observation. Ethical approval for the fieldwork was obtained from the University of Ottawa, and the Afghanistan National Public Health Institute. Results There are more than 20,000 CHWs across the country serving as village primary care providers, functioning as a liaison between the community and health-care facilities, and working as community developers; more than half are women. Noteworthy is a gender hierarchy: as one moves up the hierarchy of supervision and training, management and decision-making, the ratio of women to men diminishes. We found that female CHWs accomplished their tasks vis-à-vis maternal child health with greater ease than their male counterparts, as societal gender dynamics influences task allocation. Volunteerism helps to deploy a larger number of CHWs, but also makes their retention difficult. Community participation facilitates tasks of CHWs, but also poses challenges to the program, such as traditional leaders influencing the recruitment of CHWs that may not be the best choice for the community. Drug supply and support for CHWs is vital to the effectiveness of the program. Conclusions This case study of the decade-long, rural health workforce CHW program in Afghanistan suggests that CHWs play an important role in post-conflict, developing countries, potentially contributing to health system strengthening. [ABSTRACT FROM AUTHOR]

OBJECTIVES To identify factors affecting the implementation of large-scale programmes to optimise the health workforce in low- and middle-income countries. METHODS We conducted a multicountry case study synthesis. Eligible programmes were identified through consultation with experts and using Internet searches. Programmes were selected purposively to match the inclusion criteria. Programme documents were gathered via Google Scholar and PubMed and from key informants. The SURE Framework - a comprehensive list of factors that may influence the implementation of health system interventions - was used to organise the data. Thematic analysis was used to identify the key issues that emerged from the case studies. RESULTS Programmes from Brazil, Ethiopia, India, Iran, Malawi, Venezuela and Zimbabwe were selected. Key system-level factors affecting the implementation of the programmes were related to health worker training and continuing education, management and programme support structures, the organisation and delivery of services, community participation, and the sociopolitical environment. CONCLUSIONS Existing weaknesses in health systems may undermine the implementation of largescale programmes to optimise the health workforce. Changes in the roles and responsibilities of cadres may also, in turn, impact the health system throughout. [ABSTRACT FROM AUTHOR]

Suicide ranks among the leading causes of death around the world and takes a heavy emotional and public health toll on most societies. Both distal and proximal factors contribute to suicidal behaviour. Distal factors - such as familial and genetic predisposition, as well as early-life adversity - increase the lifetime risk of suicide. They alter responses to stress and other processes through epigenetic modification of genes and associated changes in gene expression, and through the regulation of emotional and behavioural traits. Proximal factors are associated with the precipitation of a suicidal event and include alterations in key neurotransmitter systems, inflammatory changes and glial dysfunction in the brain. This Review explores the key molecular changes that are associated with suicidality and discusses some promising avenues for future research. [ABSTRACT FROM AUTHOR]

Background: Rural family physician program as the new reform in the Iranian health system has been implemented since 2005. Its success depends much on physicians' retention. The present study aimed to identify influential factors on physicians' willingness to leave out this program in Kerman province. Methods: The present cross-sectional study was performed in Kerman province in 2011. All family physicians working in this program (n = 271) were studied using a questionnaire. Data analysis was carried out using descriptive statistics and logistic regression through SPSS version 18.0. Results: Twenty-six percent (70) of the physicians had left out the program in the past. In addition, 77.3% (208) intended to leave out in the near future. Opportunity for continuing education, inappropriate and long working hours, unsuitable requirements of salary, irregular payments, lack of job security and high working responsibility were regarded as the most important reasons for leaving out the program in the past and intention to leave out in future orderly. According to univariate logistic regression, younger physicians (odds ratio [OR] =2.479; 95% confidence interval [CI]: 1.261-4.872) and physicians who had older children (OR = 4.743; 95% CI: 1.441-15.607) were more willing to leave out the plan in the near future, however it was not significant in multivariate logistic regression. Conclusions: Physician retention in family physician program is faced with serious doubts due to different reasons. The success of the program is endangered because of the pivotal role of human resources. Hence, the revision of human resources policies of the program seems necessary in order to reduce physicians leave out and improving its effectiveness. [ABSTRACT FROM AUTHOR]

Background Suicidal behavior is a leading cause of injury and death worldwide. Several studies have provided a possible relationship between genetic factors and suicidal behavior. Also, these studies have shown evidence for altered serotonergic neural transmission in the pathogenesis of suicidal behavior. In addition, genes pertaining to the serotonergic system have been proposed as candidates to establish biological correlates between suicidal behavior and the serotonergic system. The most studied genes are SCL6A4, HTR2A, HTR2C, HTR1A, HTR1B, TPH-1, and TPH-2. To get a comprehensive understanding of the association with suicidal behavior we will conduct genotype assays studies in a Mexican population. Methods/Design We will conduct a case-control study. The population sample will comprise adolescent and adult patients admitted for attempted of suicide and diagnosed by a psychiatrist. A peripheral blood sample will be taken from all the subjects (cases and controls). Genomic DNA from the leukocytes blood sample will be extracted. The genotypes of interest are distributed in the following genes: SCL6A4, HTR2A, HTR1A, HTR1B, HTR2C, TPH-2 and TPH-1. All the samples will be analyzed using a polymerase chain reaction (PCR) end-point method. We will evaluate the Hardy-Weinberg Equilibrium. The chi-squared test or Fisher's exact test will be used to compare genotype and allele frequencies between control and case groups. The Quanto 1.2 software will measure the sample size of the association. For all the association analyses the level of significance will be set at p = 0.05 and the confidence interval at 95%. Discussion Suicidal behavior has been increase in Mexico, principally in young population. Our study will demonstrate the association between serotoninergic genes and suicide behavior in Mexican population. [ABSTRACT FROM AUTHOR]

Background: The 4-year (20072011) Revitalizing Health for All international research program (http://www. globalhealthequity.ca/projects/proj_revitalizing/index.shtml) supported 20 research teams located in 15 lowand middle-income countries to explore the strengths and weaknesses of comprehensive primary health care (CPHC) initiatives at their local or national levels. Teams were organized in a triad comprised of a senior researcher, a new researcher, and a ‘research user’ from government, health services, or other organizations with the authority or capacity to apply the research findings. Multiple regional and global team capacityenhancement meetings were organized to refine methods and to discuss and assess cross-case findings. Objective: Most research projects used mixed methods, incorporating analyses of qualitative data (interviews and focus groups), secondary data, and key policy and program documents. Some incorporated historical case study analyses, and a few undertook new surveys. The synthesis of findings in this report was derived through qualitative analysis of final project reports undertaken by three different reviewers. Results: Evidence of comprehensiveness (defined in this research program as efforts to improve equity in access, community empowerment and participation, social and environmental health determinants, and intersectoral action) was found in many of the cases. Conclusions: Despite the important contextual differences amongst the different country studies, the similarity of many of their findings, often generated using mixed methods, attests to certain transferable health systems characteristics to create and sustain CPHC practices. These include: 1. Well-trained and supported community health workers (CHWs) able to work effectively with marginalized communities 2. Effective mechanisms for community participation, both informal (through participation in projects and programs, and meaningful consultation) and formal (though program management structures) 3. Co-partnership models in program and policy development (in which financial and knowledge supports from governments or institutions are provided to communities, which retain decision-making powers in program design and implementation) 4. Support for community advocacy and engagement in health and social systems decision making These characteristics, in turn, require a political context that supports state responsibilities for redistributive health and social protection measures. [ABSTRACT FROM AUTHOR]

Background: There is no consensus about the prognostic role of HER2 expression and that of other members of the EGFR family in gastric cancer patients. The aim of this study was to evaluate the prognostic value of the EGFR family in gastric cancer. Methods: This retrospective study included 201 patients with gastric and esophagogastric junction adenocarcinoma stages 0-IV (AJCC 6th edition) who underwent primary tumor resection. Tissues from primary tumors were analyzed by tissue microarray technology and immunohistochemistry. Correlations between receptor expression and clinicopathological characteristics were performed according to the chi-square test. Survival analysis was calculated according to the Weibull model with a mixture model incorporating long-term survivors. Multivariate analysis of prognostic factors was performed by a regression model incorporating long-term survivors with the Weibull distribution. Results: Membrane expression of HER1, HER2, and HER4 were 9, 17, and 15 %, respectively. No membrane expression of HER3 was observed. Cytoplasmic expression of HER1, HER3, and HER4 were 45, 62, and 24 %, respectively. HER2 and HER3 expression were correlated ( p < 0.001) and associated with intestinal-type histology ( p = 0.001 and p < 0.001, respectively) and advanced age ( p = 0.011 and p = 0.008, respectively). According to a regression model adjusted for age, surgical radicality, surgical modality, Laurén histology, adjuvant therapy, TNM stage, and receptor expressions, only TNM stage showed prognostic influence. Conclusions: According to analysis by a parametric model, the EGFR family did not have prognostic influence in the gastric cancer population studied. The data presented showed a correlation between HER2 and HER3 expression, which might suggest a potential role for HER2-HER3 heterodimerization inhibitors. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small, non-coding RNA molecules that play an important role in the post-transcriptional regulation of mRNA. These molecules have been the subject of growing interest as they are believed to control the regulation of a large number of genes, including those expressed in the brain. Evidence suggests that miRNAs could be involved in the pathogenesis of neuropsychiatric disorders. Alterations in metabolic enzymes of the polyamine system have been reported to play a role in predisposition to suicidal behaviour. We have previously shown the expression of the polyamine genes SAT1 and SMOX to be down-regulated in the brains of suicide completers. In this study, we hypothesized that the dysregulation of these genes in depressed suicide completers could be influenced by miRNA post-transcriptional regulation. Using a stringent target prediction analysis, we identified several miRNAs that target the 3'UTR of SAT1 and SMOX. We profiled the expression of 10 miRNAs in the prefrontal cortex (BA44) of suicide completers (N = 15) and controls (N = 16) using qRT-PCR. We found that several miRNAs showed significant up-regulation in the prefrontal cortex of suicide completers compared to psychiatric healthy controls. Furthermore, we demonstrated a significant correlation between these miRNAs and the expression levels of both SAT1 and SMOX. Our results suggest a relationship between miRNAs and polyamine gene expression in the suicide brain, and postulate a mechanism for SAT1 and SMOX down-regulation by post-transcriptional activity of miRNAs. [ABSTRACT FROM AUTHOR]

Background There is a renewed interest in community health workers (CHWs) in Tanzania, but also a concern that low motivation of CHWs may decrease the benefits of investments in CHW programs. This study aimed to explore sources of CHW motivation to inform programs in Tanzania and similar contexts. Methods We conducted semi-structured interviews with 20 CHWs in Morogoro Region, Tanzania. Interviews were digitally recorded, transcribed, and coded prior to translation and thematic analysis. The authors then conducted a literature review on CHW motivation and a framework that aligned with our findings was modified to guide the presentation of results. Results Sources of CHW motivation were identified at the individual, family, community, and organizational levels. At the individual level, CHWs are predisposed to volunteer work and apply knowledge gained to their own problems and those of their families and communities. Families and communities supplement other sources of motivation by providing moral, financial, and material support, including service fees, supplies, money for transportation, and help with farm work and CHW tasks. Resistance to CHW work exhibited by families and community members is limited. The organizational level (the government and its development partners) provides motivation in the form of stipends, potential employment, materials, training, and supervision, but inadequate remuneration and supplies discourage CHWs. Supervision can also be dis-incentivizing if perceived as a sign of poor performance. Conclusions Tanzanian CHWs who work despite not receiving a salary have an intrinsic desire to volunteer, and their motivation often derives from support received from their families when other sources of motivation are insufficient. Policy-makers and program managers should consider the burden that a lack of remuneration imposes on the families of CHWs. In addition, CHWs' intrinsic desire to volunteer does not preclude a desire for external rewards. Rather, adequate and formal financial incentives and in-kind alternatives would allow already-motivated CHWs to increase their commitment to their work. [ABSTRACT FROM AUTHOR]

Background We investigated the association of early life social factors—maternal age, single motherhood, socioeconomic position, birth order and family size—with future risk of suicide in Taiwan.Methods Using a nested case-control design, we used linked data from Taiwan’s Birth Registry (1978–93) and Taiwan’s Death Registry (1993–2008) and identified 3984 suicides aged 15–30 years. For each suicide, 30 controls matched by age and sex were randomly selected, using incidence density sampling. Conditional logistic regression models were estimated to assess the association of early life risk factors with suicide.Results Younger maternal age (<25 years), single motherhood, lower paternal educational level and higher birth order were independently associated with increased risk of suicide. Stratified analyses suggest that lower paternal educational level was associated with male, but not female suicide risk (Pinteraction = 0.02). Single motherhood was a stronger risk factor for suicide in female than in male offspring [odds ratios (95% confidence interval) = 2.30 (1.47, 3.58) vs. 1.50 (1.01, 2.20), Pinteraction = 0.12]. There was a suggestion that in families with large sibship size (&geq;4 siblings), the excess in suicide risk was greater among later born daughters compared with later born sons (Pinteraction = 0.05).Conclusions Our findings provide support for the results of European studies, suggesting that early life social circumstances influence future risk of suicide. Factors specific to Taiwanese culture, such as a preference for male offspring, may have influenced gender-specific patterns of risk. [ABSTRACT FROM AUTHOR]

Background: At the 1994 International Conference on Population and Development (ICPD), held in Cairo, the global community agreed to the goal of achieving universal access to sexual and reproductive health (SRH) and rights by 2015. This research explores the accelerators and decelerators of achieving universal access to the sexual and reproductive health targets and accordingly makes some suggestions.Method: We have critically reviewed the latest national reports and extracted the background data on each SRH indicator. The key stakeholders, both national and international, were visited and interviewed at two sites. A total of 55 in-depth interviews were conducted with religious leaders, policy-makers, senior managers, senior academics, and health care managers. Six focus-group discussions were also held among health care providers. The study was qualitative in nature.Results: Obstacles on the road to achieving universal access to SRH can be viewed from two perspectives. One gap exists between current achievements and the targets. The other gap arises due to age, marital status, and residency status. The most recently observed trends in the indicators of the universal access to SRH shows that the achievements in the "unmet need for family planning" have been poor. Unmet need for family planning could directly be translated to unwanted pregnancies and unwanted childbirths; the former calls for sexual education to underserved people, including adolescents; and the latter calls for access to safe abortion. Local religious leaders have not actively attended international goal-setting programs. Therefore, they usually do not presume a positive attitude towards these goals. Such negative attitudes seem to be the most important factors hindering the progress towards universal access to SRH. Lack of international donors to fund for SRH programs is also another barrier. In national levels both state and the society are interactively playing their roles. We have used a cascade model for presenting the barriers at the state levels from the strategic planning to implementation. Social factors are to be considered as a background for other factors at all stages.Conclusion: Accelerating universal access to SRH requires adequate funding, firm political commitment, creative programming, and the involvement of diverse actors, including faith-based, civil society, and private sector partners. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF) plays an important role in dopaminergic and serotonergic neurotransmission by modulating dopaminergic neuron differentiation and establishment. Multiple studies have analyzed the functional BDNF Val66Met variant in relation to antipsychotic response in schizophrenia (SCZ) patients, yielding mixed results. A meta-analysis was thus performed to examine the relationship between this variant and symptom improvement during antipsychotic treatment. Searches using PubMed, Web of Science, and PsycInfo until October 2017 yielded 11 studies that met inclusion criteria (total n = 3774). These studies investigated the BDNF Val66Met variant and antipsychotic response in patients with SCZ or schizoaffective disorder. Responders to antipsychotics were defined using the original criteria applied in each study. Effect sizes were computed using odds ratios, which were pooled according to the Mantel-Haenszel method. The BDNF Val66Met variant was not associated with the total number of responders and non-responders (p > 0.05) under dominant, recessive, or allelic models. Secondary analyses stratifying for individuals of each ethnicity and drug type also revealed no significant associations. Our findings suggest that the BDNF Val66Met variant is not associated with response to antipsychotics in individuals with SCZ. However, considering the current sample size, small effects cannot be ruled out. Moreover, recent studies have suggested that Val66Met forms haplotypes with other BDNF variants. Future studies should examine the Val66Met variant in conjunction with these other variants in relation to antipsychotic response. Moreover, since illness duration appears to influence BDNF levels in SCZ patients, future studies should aim to control for this potential confounding factor in response analyses.

Background: Both exercise and vitamin E supplementation have been shown to reduce oxidative stress and cardiovascular disease risk in older adults, and when combined there is evidence suggesting that they act synergistically. The currently recommended amount of exercise for older adults is 150 min/week of moderate-intensity exercise; however, the minimum amount of exercise necessary to achieve health benefits is not known. The purpose of this study was to investigate the effects of 12 weeks of participation in a low-volume walking exercise programme (i.e. 90 min/week) combined with daily vitamin E supplementation on thiobarbituric acid reactive substances (TBARS) and oxidised low-density lipoprotein (LDL) concentrations in older adults. Methods: The participants were recruited from the following four groups separately: 1) control (CG, n = 14), 2) vitamin E supplementation (SG, n = 10), 3) walking (WG, n = 7), or 4) walking + supplementation (WSG, n = 7). In the CG, participants were advised to maintain their normal lifestyle during the study. Participants in both the SG and WSG received 450 IU (300 mg) /day of α-tocopherol for 12 weeks. The exercise programme for the WG and WSG consisted of two 30-60 minute sessions weekly for 12 weeks (average walking time was 44.5 ± 1.6 min/ session). Blood samples were collected at baseline and at 12 weeks. Results: Delta plasma oxidised LDL concentrations did not differ among four groups (One-factor ANOVA, P = 0.116). However, negative delta plasma TBARS, a marker of oxidative damage, concentrations were observed in the WG, WSG and SG relative to the CG at the end of the study period (One-factor ANOVA, P = 0.001; post hoc tests; CG compared with WG, WSG and SG, P = 0.005; P = 0.021; P = 0.024, respectively). Conclusion: These findings suggest that a low-volume of physical activity and/or vitamin E supplementation may be an effective intervention strategy for reducing TBARS concentrations of older adults. Trial registration: UMIN000008304. [ABSTRACT FROM AUTHOR]

Stream programming model has been productively applied to a number of important application domains. Software pipelining is an important code scheduling technique for stream programs. However, the multicore evolution has presented a new dimension of challenges: that is how to orchestrate the best software pipelining schedule in the face of resource constrained architectures (e.g., number of cores, available memory, and bandwidth)? In this paper, we proposed a new solution methodology to address the problem above. Our main contributions include the following. A unified Integer Linear Programming (ILP) formulation has been proposed that combines the requirement of both rate-optimal software pipelining and the minimization of intercore communication overhead. Next, an extended formulation has been proposed to formulate the schedule under memory size constrained systems. It orchestrates the rate-optimal software pipelining execution for stream programs with strict memory, processor cores, and communication constraints. A solution testbed has been implemented for the proposed problem formulations. This has been realized by extending the Brook programming environment with our software pipelining support—named DFBrook. An experimental study has been conducted to verify the effectiveness of the proposed solutions. [ABSTRACT FROM PUBLISHER]