BackgroundThe 2014 Ebola Virus Disease epidemic evolved in alarming ways in Sierra Leone spreading to all districts. The country struggled to control it against a backdrop of a health system that was already over-burdened. Health workers play an important role during epidemics but there is limited research on how they cope during health epidemics in fragile states. This paper explores the challenges faced by health workers and their coping strategies during the Ebola outbreak in four districts – Bonthe, Kenema, Koinadugu and Western Area - of Sierra Leone.MethodsWe used a qualitative study design: key informant interviews (n = 19) with members of the District Health Management Teams and local councils, health facility managers and international partners; and in depth interviews with health workers (n = 25) working in public health facilities and international health workers involved with the treatment of Ebola patients.ResultsThere were several important coping strategies including those that drew upon existing mechanisms: being sustained by religion, a sense of serving their country and community, and peer and family support. Externally derived strategies included: training which built health worker confidence in providing care; provision of equipment to do their job safely; a social media platform which helped health workers deal with challenges; workshops that provided ways to deal with the stigma associated with being a health worker; and the risk allowance, which motivated staff to work in facilities and provided an additional income source.ConclusionsSupportive supervision, peer support networks and better use of communication technology should be pursued, alongside a programme for rebuilding trusting relations with community structures. The challenge is building these mechanisms into routine systems, pre-empting shocks, rather than waiting to respond belatedly to crises.

ContributorsKH and AR led conceptualisation and drafting of the paper. AD led the study on nurses in Uttar Pradesh, ND the study on accredited social health activists in Uttar Pradesh, HW and JR the study on community health workers and community health worker policy in Sierra Leone, LM, JK, and AR the study on gender parity in the global physician workforce, and KH, YA, and NS the study on selfhelp groups in India. FS and RF-M led development of the case on the nurse from eSwatini. VP, RH, and EBa did the systematic literature review on health systems models. JGS and AR led the systematic review on gender transformative clinical interventions. KH, LM, JK, FS, RF-M, AD, YA, JY, EBl, NB, JGS, and AR did the critical reviews of the literature on gender inequalities and gender norms affecting health and helped draft pieces of those reviews, with consideration of diverse geographic contexts. All authors offered critical inputs and reviews of this work, contributed intellectual and substantive revisions to the writing, and provided final approval of the submitted version.

BackgroundSierra Leone has faced a shortage and maldistribution of staff in its post-conflict period. This long-standing challenge is now exacerbated by the systemic shock and damage wrought by Ebola. This study aimed to investigate the importance of different motivation factors in rural areas in Sierra Leone and thus to contribute to better decisions on financial and non-financial incentive packages, here and in similar contexts.MethodsThis article is based on participatory life histories, conducted in 2013 with 23 health workers (doctors, nurses, midwives and Community Health Officers) in four regions of Sierra Leone who had worked in the sector since 2000. Although the interviews covered a wide range of themes, here we present findings on motivating and demotivating factors for staff, especially those in rural areas, based on thematic analysis of transcripts.ResultsRural health workers face particular challenges, some of which stem from the difficult terrain, which add to common disadvantages of rural living (poor social amenities, etc.). Poor working conditions, emotional and financial costs of separation from families, limited access to training, longer working hours (due to staff shortages) and the inability to earn from other sources make working in rural areas less attractive. Moreover, rules on rotation which should protect staff from being left too long in rural areas are not reported to be respected.By contrast, poor management had more resonance in urban areas, with reports of poor delegation, favouritism and a lack of autonomy for staff. Tensions within the team over unclear roles and absenteeism are also significant demotivating factors in general.ConclusionsThis study provides important policy-focused insights into motivation of health workers and can contribute towards building a resilient and responsive health system, incorporating the priorities and needs of health workers. Their voices and experiences should be taken into account as the post-Ebola landscape is shaped.

It is well known that the health workforce composition is influenced by gender relations. However, little research has been done which examines the experiences of health workers through a gender lens, especially in fragile and post-conflict states. In these contexts, there may not only be opportunities to (re)shape occupational norms and responsibilities in the light of challenges in the health workforce, but also threats that put pressure on resources and undermine gender balance, diversity and gender responsive human resources for health (HRH). We present mixed method research on HRH in four fragile and post-conflict contexts (Sierra Leone, Zimbabwe, northern Uganda and Cambodia) with different histories to understand how gender influences the health workforce. We apply a gender analysis framework to explore access to resources, occupations, values, decision-making and power. We draw largely on life histories with male and female health workers to explore their lived experiences, but complement the analysis with evidence from surveys, document reviews, key informant interviews, human resource data and stakeholder mapping. Our findings shed light on patterns of employment: in all contexts women predominate in nursing and midwifery cadres, are under-represented in management positions and are clustered in lower paying positions. Gendered power relations shaped by caring responsibilities at the household level, affect attitudes to rural deployment and women in all contexts face challenges in accessing both pre- and in-service training. Coping strategies within conflict emerged as a key theme, with experiences here shaped by gender, poverty and household structure. Most HRH regulatory frameworks did not sufficiently address gender concerns. Unless these are proactively addressed post-crisis, health workforces will remain too few, poorly distributed and unable to meet the health needs of vulnerable populations. Practical steps need to be taken to identify gender barriers proactively and engage staff and communities on best approaches for change.

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The two diacylglycerol acyltransferases, DGAT1 and DGAT2, are known to have non-redundant functions, in spite of catalysing the same reaction and being present in the same cell types. The basis for this distinctiveness, which is reflected in the very different phenotypes of Dgat1 ) ⁄ ) and Dgat2) ⁄ ) mice, has not been resolved. Using selective inhibitors of human DGAT1 and DGAT2 on HepG2 cells and gene silencing, we show that, although DGAT2 activity accounts for a modest fraction (< 20%) of overall cellular DGAT activity, inhibition of DGAT2 activity specifically inhibits (and is rate-limiting for) the incorporation of de novo synthesized fatty acids and of glycerol into cellular and secreted triglyceride to a much greater extent than it affects the incorporation of exogenously added oleate. By contrast, inhibition of DGAT1 affects equally the incorporation of glycerol and exogenous (preformed) oleate into cellular and secreted triacylglycerol (TAG). These data indicate that DGAT2 acts upstream of DGAT1, largely determines the rate of de novo synthesis of triglyceride, and uses nascent diacylglycerol and de novo synthesized fatty acids as substrates. By contrast, the data suggest that DGAT1 functions in the re-esterification of partial glycerides generated by intracellular lipolysis, using preformed (exogenous) fatty acids. Therefore, we describe distinct but synergistic roles of the two DGATs in an integrated pathway of TAG synthesis and secretion, with DGAT2 acting upstream of DGAT1.

This article is grounded in a research programme which set out to understand how to rebuild health systems post-conflict. Four countries were studied-Uganda, Sierra Leone, Zimbabwe and Cambodia-which were at different distances from conflict and crisis, as well as having unique conflict stories. During the research process, the Ebola epidemic broke out in West Africa. Zimbabwe has continued to face a profound economic crisis. Within our research on health worker incentives, we captured insights from 128 life histories and in-depth interviews with a variety of staff that had remained in service. This article aims to draw together lessons from these contexts which can provide lessons for enhancing staff and therefore health system resilience in future, especially in similarly fragile and conflict-affected contexts. We examine the reported effects, both personal and professional, of the three different types of shock (conflicts, epidemics and prolonged political-economic crises), and how staff coped. We find that the impact of shocks and coping strategies are similar between conflict/post-conflict and epidemic contexts-particularly in relation to physical threats and psychosocial threats-while all three contexts create challenges and staff responses for working conditions and remuneration. Health staff showed considerable inventiveness and resilience, and also benefited from external assistance of various kinds, but there are important gaps which point to ways in which they should be better protected and supported in the future. Health systems are increasingly fragile and conflict-prone, and shocks are often prolonged or repeated. Resilience should not be taken for granted or used as an excuse for abandoning frontline health staff. Strategies should be in place at local, national and international levels to prepare for predictable crises of various sorts, rather than waiting for them to occur and responding belatedly, or relying on personal sacrifices by staff to keep services functioning.

Triacylglycerol (TAG) synthesis and secretion are important functions of the liver that have major impacts on health, as overaccumulation of TAG within the liver (steatosis) or hypersecretion of TAG within very low density lipoproteins (VLDL) both have deleterious metabolic consequences. Two diacylglycerol acyltransferases (DGATs 1 and 2) can catalyze the final step in the synthesis of TAG from diacylglycerol, which has been suggested to play an important role in the transfer of the glyceride moiety across the endoplasmic reticular membrane for (re)synthesis of TAG on the lumenal aspect of the endoplasmic reticular (ER) membrane (Owen, M., Corstorphine, C. C., and Zammit, V. A. (1997) Biochem. J. 323, 17-21). Recent topographical studies suggested that the oligomeric enzyme DGAT1 is exclusively lumen facing (latent) in the ER membrane. By contrast, in the present study, using two specific inhibitors of human DGAT1, we present evidence that DGAT1 has a dual topology within the ER of HepG2 cells, with approximately equal DGAT1 activities exposed on the cytosolic and lumenal aspects of the ER membrane. This was confirmed by the observation of the loss of both overt (partial) and latent (total) DGAT activity in microsomes prepared from livers of Dgat1 ؊/؊ mice. Conformational differences between DGAT1 molecules having the different topologies were indicated by the markedly disparate sensitivities of the overt DGAT1 to one of the inhibitors. These data suggest that DGAT1 belongs to the family of oligomeric membrane proteins that adopt a dual membrane topology.Hypertriglyceridemia is a key biomarker for the metabolic/ insulin resistance syndrome and for associated morbidities, including type-2 diabetes and cardiovascular disease (1). Similarly, excessive accumulation of triglycerides in cytoplasmic lipid droplets results in hepatic steatosis, now recognized as being associated, possibly causatively, with whole body insulin resistance, and which may progress to nonalcoholic fatty liver or steatohepatitis (2, 3). Fasting hypertriglyceridemia is primarily due to the hypersecretion of triglyceride (TAG) 3 by the liver, within very low density lipoproteins (VLDL). Therefore, an understanding of the enzymology involved in triglyceride synthesis, remodeling, storage, and assembly into secreted VLDL is essential for the design of pharmacological strategies aimed at managing dyslipidaemia without the exacerbation of hepatic steatosis, and vice versa.Diacylglycerol acyltransferases (DGATs) catalyze the final reaction of TAG synthesis. Two distinct gene products, DGAT1 and DGAT2, that catalyze most of tissue TAG synthesis have been described (4, 5) but remain relatively poorly characterized, and their respective, nonredundant functions are still to be elucidated. In the present study, we have used two specific inhibitors (which belong to different chemical classes of compounds) of human DGAT1, in combination with the selective permeabilization of the plasma membrane and the ER membrane of whole hepatocytes, to study the sidednes...