SummaryEmerging evidence suggests a significant role for inflammation and oxidative stress as main contributors to the neuroprogression that is observed in major depressive disorder (MDD), where patients show increased inflammatory and oxidative stress biomarkers. The process of neuroprogression includes stage-related neurodegeneration, cell death, reduced neurogenesis, reduced neuronal plasticity and increased autoimmune responses. Oxidative stress is a consequence of the biological imbalance between reactive oxygen species (ROS) and antioxidants, leading to the alteration of biomolecules and the loss of control of the intracellular redox-related signalling pathways. ROS serve as crucial secondary messengers in signal transduction and significantly affect inflammatory pathways by activating nuclear factor-jB and mitogen-activated protein kinase family stress kinases. When present in excess, ROS inflict damage, affecting cellular constituents with the formation of pro-inflammatory molecules, such as malondialdehyde, 4-hydroxynonenal, neoepitopes and damageassociated molecular patterns promoting immune response, and ultimately leading to cell death. The failure of cells to adapt to the changes in redox homeostasis and the subsequent cell death, together with the damage caused by inflammatory mediators, have been considered as major causes of neuroprogression and hence MDD. Both an activated immune-inflammatory system and increased oxidative stress act synergistically, complicating our understanding of the pathogenesis of depression. The cascade of antioxidative and inflammatory events is orchestrated by several transcription factors, with nuclear factor (erythroid-derived 2)-like 2 and nuclear factor-jB having particular relevance to MDD. This review focuses on potential molecular mechanisms through which impaired redox homeostasis and neuroinflammation can affect the neuronal environment and contribute to depression.

Increased pro-inflammatory cytokines and an overactive hypothalamic-pituitary-adrenal (HPA) axis have both been implicated in the pathogenesis of depression. However, these explanations appear contradictory because glucocorticoids are well recognised for their antiinflammatory effects. Two hypotheses exist to resolve this paradox: the mediating presence of glucocorticoid receptor resistance, or the possibility that glucocorticoids can be proinflammatory in some circumstances. We sought to investigate these hypotheses in a cell model with significant relevance to depression: human hippocampal progenitor cells. We demonstrated that dexamethasone in vitro given for 24 hours and followed by a 24-hour rest interval before an immune challenge produces pro-inflammatory effects in these neural cells, that is, potentiates the IL-6 protein secretion induced by stimulation with IL-1β (10ng/mL for 24 hours) by +49% (P<0.05) at a concentration of 100nM and by +70% (P<0.01) for 1µM.These effects are time-and dose-dependent and require activation of the glucocorticoid receptor. Gene expression microarray assays using Human Gene 2.1st Array Strips demonstrated that glucocorticoid treatment up-regulated several innate immune genes, including chemokines and Nod-like receptor, NLRP6; using transcription factor binding motifs we found limited evidence that glucocorticoid resistance was induced in the cells. Our data suggests a mechanism by which stress may prime the immune system for increased inflammation and suggests that stress and inflammation may be synergistic in the pathogenesis of depression.

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Background Sexual well-being is fundamental to physical and emotional health, and the ability to achieve it depends on access to comprehensive sexuality information and high-quality sexual health care from evidence-informed, nonjudgmental providers. Adequate and timely delivery of these components to individuals who are at high risk for sexually transmitted infections (STIs), including HIV, and unintended pregnancies promotes sexual health and mitigates consequences arising from risky sexual behavior. Brief interventions that allow health care providers to improve the information available to clients and motivate and help them to develop risk-reduction skills are seen as efficient ways to improve knowledge, change client behavior, and reduce provider stigma regarding sexual health. Objective The aim of the study is to evaluate five aspects of feasibility (acceptability, willingness, safety, satisfaction, and process) of a brief sexuality-related communication (BSC) intervention based on motivational interviewing and behavior change techniques in primary health care settings in low- and middle-income countries (LMICs). Methods This protocol outlines a multisite, multiphase study of feasibility of a BSC intervention in primary health care settings in LMICs that will be examined across four phases of the study. Phases I through III involve the collection of formative, qualitative data to examine provider and client perceptions of the feasibility of the intervention, adaptation of the intervention guide, and training providers on how to implement the final version of the BSC intervention. During phase IV, the feasibility of the intervention will be tested in a nonrandomized pre-post test trial where providers and clients will be followed for 6 months and participate in multiphase data collection. Results Phase I is currently underway in Moldova, and phases I and II were completed in Peru in late 2019. Results are expected for the feasibility study in 2021. Conclusions This feasibility study will determine whether the implementation of brief intervention programs aimed at improving sexual health outcomes is possible in the constraints of LMIC health systems and will add to our understanding of factors shaping clinical practice among primary care providers. International Registered Report Identifier (IRRID) DERR1-10.2196/15569

This narrative review was conducted to synthesize and summarize available up-to-date evidence on current health status, including both non-communicable diseases and infectious diseases, of migrants and refugees from the former Soviet Union countries in the Russian Federation. Epidemiological and sociological studies with one or more determinants of the health, as well as relevant qualitative studies characterizing risk factors, well-being indicators, and lifestyles of migrants and refugees from the former Soviet Union countries in Russia published from 2004 to 2019 in Russian and English languages were included in the review. Despite significant limitations of the available research literature in the field, some patterns in migrants’ health in Russia and issues that need to be addressed were identified. In particular, the syndemic epidemics of communicable and non-communicable diseases, additively increasing negative health consequences, including cardiovascular diseases and chronic digestive system diseases, high rates of sexually transmitted infections and HIV, respiratory diseases and a growing percentage of new tuberculosis cases among migrants from the former Soviet Union countries are all of great concern. Possibly, the burden of these co-occurring morbidities is linked to commonly reported issues among this population group, such as poor nutrition and living conditions, high prevalence of unskilled manual labour, non-compliance with sanitary norms, lack of basic vaccinations, lack of basic knowledge about safe sexual practices and risky sexual behaviour, low healthcare seeking behaviour and limited access to health care. Importantly, these findings may urge the government to increase efforts and promote international collaboration in combating the threat of infectious diseases. Additionally, it was found that migrants had higher levels of anxiety and post-traumatic stress disorder, and those who stayed in the receiving country 5 years or more had a higher level of somatic pathology than those whose stay was less than 5 years. In order to ensure an adequate health system response and fulfil the main Universal Health Coverage principle of “leaving no one behind”, a robust monitoring system of the health status of refugees and migrants and an integrated legal framework for the standardized and more inclusive routine care for this population in Russia is urgently needed.

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Background Brief interventions have proven to be valuable instruments for the treatment and care of clients with diverse health needs, due to their potential to impact both the individual and the population. In this regard, the Brief Sexuality-Related Communication (BSC) is presented as a viable and effective alternative for addressing sexual and reproductive health problems, assessing risk behaviors and motivating clients to generate behavioral change. Since health providers are key actors in treatment and prevention, it is essential to know their perceptions about the BSC intervention, as well as its acceptability in different contexts, with diverse client populations. Thus, the following paper reflects the findings of the perceptions and experiences of health providers in Peru from the first phase of the Feasibility study of a BSC intervention to prevent STIs and unintended pregnancies. Methods This is the first phase of a multisite and multiphase study of the feasibility of a BSC intervention. We conducted twenty in-depth interviews (IDI) with health care providers (physicians, obstetricians, psychologists, nurses and peer counselors) recruited from three health care institutions in Peru: The Tahuantinsuyo Bajo Maternal and Child Center (CMI) and the San José Maternal and Child Center, both located in the capital city, Lima; and La Caleta Hospital located in Chimbote, northern coast of Peru. Participating health providers included those working at the HIV/STI Reference service and the family planning/reproductive health service. The IDI addressed three domains: 1) Acceptability of the BSC intervention; 2) Perceived willingness to implement the BSC intervention; and 3) Considerations for the Implementation of the BSC intervention. Results Health providers expressed high acceptance of the BSC intervention, considering it as a useful and effective instrument to address sexual and reproductive health problems with all clients; however, some providers had some concerns about the real impact of the intervention to achieve significant behavior change. On the other hand, health providers showed high willingness to learn and implement the BSC intervention, affirming their commitment to learn new techniques and strategies that could allow them to improve their knowledge and the quality of their care. Health care providers consider it necessary to take into account the barriers that arise in the implementation of the BSC intervention, such as the structural limitations to access, the providers’ abilities to deliver the intervention effectively, and the participants’ reception of the intervention. Finally, providers consider it essential to establish the BSC intervention in a normative framework that allows it to receive the support of the health departments and eventually enforces implementation. Conclusions Health providers consider the BSC intervention as an interesting and exciting behavioral intervention to deal with the sexual and reproductive health issues existing in different populations, and seemed highly willing to adapt and implement it, hoping that it become beneficial to all client populations to prevent HIV/STIs and unintended pregnancies.

Background Brief behavioral interventions are seen as an efficient way to improve knowledge, change behavior, and reduce provider stigma regarding sexual health. When grounded in evidence-based behavioral change techniques and delivered using Brief Sexuality-related Communication (BSC) tools, brief behavioral interventions can address client-driven sexual health goals in a single session with their provider. Evidence for the efficacy of brief interventions for creating gains in sexual health comes largely from resource rich settings, and there is a lack of knowledge of how brief interventions can be implemented in the more resource constrained environments of low- and middle-income countries. As a first step in developing a brief intervention to address sexual health issues in Moldova, this paper reports on qualitative data collected from Moldovan providers to understand their attitudes, willingness and perceived barriers to the brief intervention and its implementation. Methods Thirty-nine in-depth interviews (IDI) were conducted between February and March 2020, with health providers recruited from three primary health care institutions, two Youth Friendly Health Centers and counselors from three NGOs who work with key populations in Moldova, including health centers selected from two cites - the capital city, Chisinau and from the Comrat Region. The IDI addressed four domains of provider attitudes: 1) attitudes towards the intervention; 2) willingness and motivation to implement the intervention; 3) logistics of providing the intervention and 4) ability to implement the intervention. A coding analysis approach was applied to all interview transcripts. Results Providers largely reported being willing to be trained in and implement the brief intervention. Willingness to implement the intervention stemmed from two perceptions: that it would improve the ability of providers to talk with their clients about sex, and that vulnerable groups would benefit from these conversations. However, while there were generally positive attitudes towards the intervention, providers consistently reported structural barriers to their perceived ability to implement the intervention. Conclusions While providers reported high levels of initial acceptance of a brief behavioral intervention, care is needed to ensure that brief interventions, and the training of providers on brief interventions, incorporate cultural attitudes and norms around sex, particularly in highly patriarchal settings, and provide opportunities for providers to practice the intervention in ways that address their assumptions and implicit biases.