Community based system dynamic as an approach for understanding and acting on messy problems: a case study for global mental health intervention in Afghanistan

BACKGROUND: Afghanistan lacks suitable specialized mental healthcare services despite high prevalence of severe mental health disorders which are aggravated by the conflict and numerous daily stressors. Recent studies have shown that Afghans with mental illness are not only deprived of care but are vulnerable in many other ways. Innovative participatory approaches to the design of mental healthcare policies and programs are needed in such challenging context. METHODS: We employed community based system dynamics to examine interactions between multiple factors and actors to examine the problem of persistently low service utilization for people with mental illness. Group model building sessions, designed based on a series of scripts and led by three facilitators, took place with NGO staff members in Mazar-I-Sharif in July 2014 and in Kabul in February 2015. RESULTS: We identified major feedback loops that constitute a hypothesis of how system components interact to generate a persistently low rate of service utilization by people with mental illness. In particular, we found that the interaction of the combined burdens of poverty and cost of treatment interact with cultural and social stigmatizing beliefs, in the context of limited clinical or other treatment support, to perpetuate low access to care for people with mental disorders. These findings indicate that the introduction of mental healthcare services alone will not be sufficient to meaningfully improve the condition of individuals with mental illness if community stigma and poverty are not addressed concurrently. CONCLUSIONS: Our model highlights important factors that prevent persons with mental illness from accessing services. Our study demonstrates that group model building methods using community based system dynamics can provide an effective tool to elicit a common vision on a complex problem and identify shared potential strategies for intervention in a development and global health context. Its strength and originality is the leadership role played by the actors embedded within the system in describing the complex problem and suggesting interventions

Integrated transcriptomic and proteomic analysis of the global response of Wolbachia to doxycycline-induced stress

The bacterium Wolbachia (order Rickettsiales), representing perhaps the most abundant vertically transmitted microbe worldwide, infects arthropods and filarial nematodes. In arthropods, Wolbachia can induce reproductive alterations and interfere with the transmission of several arthropod-borne pathogens. In addition, Wolbachia is an obligate mutualist of the filarial parasites that cause lymphatic filariasis and onchocerciasis in the tropics. Targeting Wolbachia with tetracycline antibiotics leads to sterilisation and ultimately death of adult filariae. However, several weeks of treatment are required, restricting the implementation of this control strategy. To date, the response of Wolbachia to stress has not been investigated, and almost nothing is known about global regulation of gene expression in this organism. We exposed an arthropod Wolbachia strain to doxycycline in vitro, and analysed differential expression by directional RNA-seq and label-free, quantitative proteomics. We found that Wolbachia responded not only by modulating expression of the translation machinery, but also by upregulating nucleotide synthesis and energy metabolism, while downregulating outer membrane proteins. Moreover, Wolbachia increased the expression of a key component of the twin-arginine translocase (tatA) and a phosphate ABC transporter ATPase (PstB); the latter is associated with decreased susceptibility to antimicrobials in free-living bacteria. Finally, the downregulation of 6S RNA during translational inhibition suggests that this small RNA is involved in growth rate control. Despite its highly reduced genome, Wolbachia shows a surprising ability to regulate gene expression during exposure to a potent stressor. Our findings have general relevance for the chemotherapy of obligate intracellular bacteria and the mechanistic basis of persistence in the Rickettsiales

Phylotranscriptomic insights into the diversification of endothermic Thunnus tunas

Birds, mammals, and certain fishes, including tunas, opahs and lamnid sharks, are endothermic, conserving internally generated, metabolic heat to maintain body or tissue temperatures above that of the environment. Bluefin tunas are commercially important fishes worldwide, and some populations are threatened. They are renowned for their endothermy, maintaining elevated temperatures of the oxidative locomotor muscle, viscera, brain and eyes, and occupying cold, productive high-latitude waters. Less cold-tolerant tunas, such as yellowfin tuna, by contrast, remain in warm-temperate to tropical waters year-round, reproducing more rapidly than most temperate bluefin tuna populations, providing resiliency in the face of large-scale industrial fisheries. Despite the importance of these traits to not only fisheries but also habitat utilization and responses to climate change, little is known of the genetic processes underlying the diversification of tunas. In collecting and analyzing sequence data across 29,556 genes, we found that parallel selection on standing genetic variation is associated with the evolution of endothermy in bluefin tunas. This includes two shared substitutions in genes encoding glycerol-3 phosphate dehydrogenase, an enzyme that contributes to thermogenesis in bumblebees and mammals, as well as four genes involved in the Krebs cycle, oxidative phosphorylation, β-oxidation, and superoxide removal. Using phylogenetic techniques, we further illustrate that the eight Thunnus species are genetically distinct, but found evidence of mitochondrial genome introgression across two species. Phylogeny-based metrics highlight conservation needs for some of these species