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Background: Sierra 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.Methods: This 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.Results: Rural 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.Conclusions: This 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Antiretroviral therapy (ART) is the primary mode of treatment for Human Immunodeficiency Virus (HIV). It slows disease progression and reduces the spread of infection. HIV treatment is also known to require a high level of adherence of over 90% to achieve good treatment outcomes and viral load suppression. In Sierra Leone, about 70% of People Living with HIV (PLHIV) are non-adherent in their first year of treatment. Understanding the reasons behind this high rate of non-adherence from the perspectives of both PLHIV and health workers is critical for developing strategies to improve adherence. This qualitative study is rooted in the field of public health services. It identifies the barriers and facilitators influencing adherence to antiretroviral treatment in Sierra Leone.  METHODS: A qualitative study design using in-depth interviews of four healthcare workers and 16 PLHIV in two districts in Sierra Leone- Freetown and Bo. The interviews were analyzed using a grounded theory approach to identify emerging themes from the data.Results: The study identified several facilitators and barriers to ART adherence at the personal, community, and health system levels. The facilitators included perceived benefits of ART, family support, having an informal caregiver, receiving free ART medicines, and belonging to peer support groups. The identified barriers were stigma and discrimination, frequency of medication, use of traditional medicine, lack of money for food and transport, work barriers, inadequate medicines and test kits, limited health workers, and long distances to clinics.Conclusions: Our study emphasized the need for implementing behavioural change communication programmes and activities to reduce stigma and discrimination in the community. Knowledge of the facilitators and barriers to antiretroviral therapy could provide relevant information for more responsive and equitable programmes supporting adherence implementation in low- and middle-income countries. This study also identifies the vital need for community integration of HIV treatment services. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Clinical Trials Registration: ClinicalTrials.gov [NCT02378753] and Pan African Clinical Trials Registry [PACTR201502001037220]. [ABSTRACT FROM AUTHOR]

Background: Few studies look at policy making in the health sector in the aftermath of a conflict or crisis and even fewer specifically focus on Human Resources for Health, which is a critical domain for health sector performance. The main objective of the article is to shed light on the patterns and drivers of post-conflict policy-making. In particular, we explore whether the post-conflict period offers increased chances for the opening of 'windows for opportunity' for change and reform and the potential to reset health systems. Methods: This article uses a comparative policy analysis framework. It is based on qualitative data, collected using three main tools - stakeholder mapping, key informant interviews and document reviews - in Uganda, Sierra Leone, Cambodia and Zimbabwe. Results: We found that HRH challenges were widely shared across the four cases in the post-conflict period but that the policy trajectories were different - driven by the nature of the conflicts but also the wider context. Our findings suggest that there is no formula for whether or when a 'window of opportunity' will arise which allows health systems to be reset. Problems are well understood in all four cases but core issues - such as adequate pay, effective distribution and HRH management - are to a greater or lesser degree unresolved. These problems are not confined to post-conflict settings, but underlying challenges to addressing them - including fiscal space, political consensus, willingness to pursue public objectives over private, and personal and institutional capacity to manage technical solutions - are liable to be even more acute in these settings. The role of the MoH emerged as weaker than expected, while the shift from donor dependence was clearly not linear and can take a considerable time. Conclusions: Windows of opportunity for change and reform can occur but are by no means guaranteed by a crisis - rather they depend on a constellation of leadership, financing, and capacity. Recognition of urgency is certainly a facilitator but not sufficient alone. Post-conflict environments face particularly severe challenges to evidence-based policy making and policy implementation, which also constrain their ability to effectively use the windows which are presented. [ABSTRACT FROM AUTHOR]