| 1. |
- Azzu, V., et al.
(författare)
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Suppression of insulin-induced gene 1 (INSIG1) function promotes hepatic lipid remodelling and restrains NASH progression
- 2021
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Ingår i: Molecular Metabolism. - : Elsevier BV. - 2212-8778. ; 48
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Non-alcoholic fatty liver disease (NAFLD) is a silent pandemic associated with obesity and the metabolic syndrome, and also increases cardiovascular- and cirrhosis-related morbidity and mortality. A complete understanding of adaptive compensatory metabolic programmes that modulate non-alcoholic steatohepatitis (NASH) progression is lacking. Methods and results: Transcriptomic analysis of liver biopsies in patients with NASH revealed that NASH progression is associated with rewiring of metabolic pathways, including upregulation of de novo lipid/cholesterol synthesis and fatty acid remodelling. The modulation of these metabolic programmes was achieved by activating sterol regulatory element-binding protein (SREBP) transcriptional networks; however, it is still debated whether, in the context of NASH, activation of SREBPs acts as a pathogenic driver of lipotoxicity, or rather promotes the biosynthesis of protective lipids that buffer excessive lipid accumulation, preventing inflammation and fibrosis. To elucidate the pathophysiological role of SCAP/SREBP in NASH and wound-healing response, we used an Insig1 deficient (with hyper-efficient SREBPs) murine model challenged with a NASH-inducing diet. Despite enhanced lipid and cholesterol biosynthesis, Insig1 KO mice had similar systemic metabolism and insulin sensitivity to Het/WT littermates. Moreover, activating SREBPs resulted in remodelling the lipidome, decreased hepatocellular damage, and improved wound-healing responses. Conclusions: Our study provides actionable knowledge about the pathways and mechanisms involved in NAFLD pathogenesis, which may prove useful for developing new therapeutic strategies. Our results also suggest that the SCAP/SREBP/INSIG1 trio governs transcriptional programmes aimed at protecting the liver from lipotoxic insults in NASH. (C) 2021 Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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| 2. |
- Friedman, James M., et al.
(författare)
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Distance to hospital and utilization of surgical services in Haiti: do children, delivering mothers, and patients with emergent surgical conditions experience greater geographical barriers to surgical care?
- 2013
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Ingår i: International Journal of Health Planning and Management. - : Wiley. - 1099-1751 .- 0749-6753. ; 28:3, s. 248-256
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Tidskriftsartikel (refereegranskat)abstract
- Background An inverse relationship between healthcare utilization and distance to care has been previously described. The purpose of this study was to evaluate this effect related to emergency and essential surgical care in central Haiti. Methods We conducted a retrospective review of operative logbooks from the Clinique Bon Sauveur in Cange, Haiti, from 2008 to 2010. We used Geographic Information Systems to map the home locations of all patients. Spearman's correlation was used to determine the relationship between surgical utilization and distance, and a multivariate linear regression model identified characteristics associated with differences in distances traveled to care. Results The highest annual surgical utilization rate was 184 operations/100 000 inhabitants. We found a significant inverse correlation between surgical utilization rate and distance from residence to hospital (r(s) = -0.68, p = 0.02). The median distance from residence to hospital was 55.9 km. Pediatric patients lived 10.1% closer to the hospital than adults (p<0.01), and distance from residence to hospital was not significantly different between men and women (p = 0.25). Patients who received obstetric or gynecologic surgery originated 7.8% closer to the hospital than patients seeking other operations (p<0.01), and patients who received emergent surgical care originated 24.8% closer to the hospital than patients who received elective surgery (p<0.01). Copyright (C) 2012 John Wiley & Sons, Ltd. Conclusions Utilization of surgical services was low and inversely related to distance from residence to hospital in rural areas of central Haiti. Children and patients receiving obstetric, gynecologic or emergent surgery lived significantly closer to the hospital, and these groups may need special attention to ensure adequate access to surgical care. Copyright (C) 2012 John Wiley & Sons, Ltd.
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| 3. |
- Hagander, Lars, et al.
(författare)
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Surgeon Migration Between Developing Countries and the United States: Train, Retain, and Gain from Brain Drain
- 2013
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Ingår i: World Journal of Surgery. - : Springer Science and Business Media LLC. - 1432-2323 .- 0364-2313. ; 37:1, s. 14-23
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Tidskriftsartikel (refereegranskat)abstract
- The critical shortage of surgeons in many low- and middle-income countries (LMICs) prevents adequate responses to surgical needs, but the factors that affect surgeon migration have remained incompletely understood. The goal of this study was to examine the importance of personal, professional, and infrastructural factors on surgeon migration from LMICs to the United States. We hypothesized that the main drivers of surgeon migration can be addressed by providing adequate domestic surgical infrastructure, surgical training programs, and viable surgical career paths. We conducted an internet-based nationwide survey of surgeons living in the US who originated from LMICs. 66 surgeons completed the survey. The most influential factors for primary migration were related to professional reasons (p a parts per thousand currency sign 0.001). Nonprofessional factors, such as concern for remuneration, family, and security were significantly less important for the initial migration decisions, but adopted a more substantial role in deciding whether or not to return after training in the United States. Migration to the United States was initially considered temporary (44 %), and a majority of the surveyed surgeons have returned to their source countries in some capacity (56 %), often on multiple occasions (80 %), to contribute to clinical work, research, and education. This study suggests that surgically oriented medical graduates from LMICs migrate primarily for professional reasons. Initiatives to improve specialist education and surgical infrastructure in LMICs have the potential to promote retention of the surgical workforce. There may be formal ways for LMICs to gain from the international pool of relocated surgeons.
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| 4. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 5. |
- Naepflin, Kathrin, et al.
(författare)
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Genomics of host-pathogen interactions: challenges and opportunities across ecological and spatiotemporal scales
- 2019
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Ingår i: PeerJ. - 2167-8359. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Evolutionary genomics has recently entered a new era in the study of host-pathogen interactions. A variety of novel genomic techniques has transformed the identification, detection and classification of both hosts and pathogens, allowing a greater resolution that helps decipher their underlying dynamics and provides novel insights into their environmental context. Nevertheless, many challenges to a general understanding of host-pathogen interactions remain, in particular in the synthesis and integration of concepts and findings across a variety of systems and different spatiotemporal and ecological scales. In this perspective we aim to highlight some of the commonalities and complexities across diverse studies of host-pathogen interactions, with a focus on ecological, spatiotemporal variation, and the choice of genomic methods used. We performed a quantitative review of recent literature to investigate links, patterns and potential tradeoffs between the complexity of genomic, ecological and spatiotemporal scales undertaken in individual host-pathogen studies. We found that the majority of studies used whole genome resolution to address their research objectives across a broad range of ecological scales, especially when focusing on the pathogen side of the interaction. Nevertheless, genomic studies conducted in a complex spatiotemporal context are currently rare in the literature. Because processes of host-pathogen interactions can be understood at multiple scales, from molecular-, cellular-, and physiological-scales to the levels of populations and ecosystems, we conclude that a major obstacle for synthesis across diverse host-pathogen systems is that data are collected on widely diverging scales with different degrees of resolution. This disparity not only hampers effective infrastructural organization of the data but also data granularity and accessibility. Comprehensive metadata deposited in association with genomic data in easily accessible databases will allow greater inference across systems in the future, especially when combined with open data standards and practices. The standardization and comparability of such data will facilitate early detection of emerging infectious diseases as well as studies of the impact of anthropogenic stressors, such as climate change, on disease dynamics in humans and wildlife.
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