| 1. |
- Clifford, B. L., et al.
(författare)
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FXR activation protects against NAFLD via bile-acid-dependent reductions in lipid absorption
- 2021
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131 .- 1932-7420. ; 33:8
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Tidskriftsartikel (refereegranskat)abstract
- FXR agonists are used to treat non-alcoholic fatty liver disease (NAFLD), in part because they reduce hepatic lipids. Here, we show that FXR activation with the FXR agonist GSK2324 controls hepatic lipids via reduced absorption and selective decreases in fatty acid synthesis. Using comprehensive lipidomic analyses, we show that FXR activation in mice or humans specifically reduces hepatic levels of mono-and polyunsaturated fatty acids (MUFA and PUFA). Decreases in MUFA are due to FXR-dependent repression of Scd1, Dgat2, and Lpin1 expression, which is independent of SHP and SREBP1c. FXR-dependent decreases in PUFAs are mediated by decreases in lipid absorption. Replenishing bile acids in the diet prevented decreased lipid absorption in GSK2324-treated mice, suggesting that FXR reduces absorption via decreased bile acids. We used tissue-specific FXR KO mice to show that hepatic FXR controls lipogenic genes, whereas intestinal FXR controls lipid absorption. Together, our studies establish two distinct pathways by which FXR regulates hepatic lipids.
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| 2. |
- Ovadia, C., et al.
(författare)
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Ursodeoxycholic acid enriches intestinal bile salt hydrolase-expressing Bacteroidetes in cholestatic pregnancy
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Ursodeoxycholic acid (UDCA) treatment can reduce itch and lower endogenous serum bile acids in intrahepatic cholestasis of pregnancy (ICP). We sought to determine how it could influence the gut environment in ICP to alter enterohepatic signalling. The gut microbiota and bile acid content were determined in faeces from 35 pregnant women (14 with uncomplicated pregnancies and 21 with ICP, 17 receiving UDCA). Faecal bile salt hydrolase activity was measured using a precipitation assay. Serum fibroblast growth factor 19 (FGF19) and 7α-hydroxy-4-cholesten-3-one (C4) concentrations were measured following a standardised diet for 21 hours. Women with a high ratio of Bacteroidetes to Firmicutes were more likely to be treated with UDCA (Fisher’s exact test p = 0.0178) than those with a lower ratio. Bile salt hydrolase activity was reduced in women with low Bacteroidetes:Firmicutes. Women taking UDCA had higher faecal lithocholic acid (p < 0.0001), with more unconjugated bile acids than women with untreated ICP or uncomplicated pregnancy. UDCA-treatment increased serum FGF19, and reduced C4 (reflecting lower bile acid synthesis). During ICP, UDCA treatment can be associated with enrichment of the gut microbiota with Bacteroidetes. These demonstrate high bile salt hydrolase activity, which deconjugates bile acids enabling secondary modification to FXR agonists, enhancing enterohepatic feedback via FGF19. © 2020, The Author(s).
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| 3. |
- Schneider, K. M., et al.
(författare)
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Gut microbiota depletion exacerbates cholestatic liver injury via loss of FXR signalling
- 2021
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Ingår i: Nature Metabolism. - : Springer Science and Business Media LLC. - 2522-5812. ; 3:9, s. 1228-1241
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Tidskriftsartikel (refereegranskat)abstract
- Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown aetiology for which there are no approved therapeutic options. Patients with PSC display changes in gut microbiota and in bile acid (BA) composition; however, the contribution of these alterations to disease pathogenesis remains controversial. Here we identify a role for microbiota-dependent changes in BA synthesis that modulates PSC pathophysiology. In a genetic mouse model of PSC, we show that loss of microbiota-mediated negative feedback control of BA synthesis results in increased hepatic BA concentrations, disruption of bile duct barrier function and, consequently, fatal liver injury. We further show that these changes are dependent on decreased BA signalling to the farnesoid X receptor, which modulates the activity of the rate-limiting enzyme in BA synthesis, CYP7A1. Moreover, patients with advanced stages of PSC show suppressed BA synthesis as measured by serum C4 levels, which is associated with poor disease prognosis. Our preclinical data highlight the microbiota-dependent dynamics of BA metabolism in cholestatic liver disease, which could be important for future therapies targeting BA and gut microbiome interactions, and identify C4 as a potential biomarker to functionally stratify patients with PSC and predict disease outcomes. Patients with primary sclerosing cholangitis (PSC), a chronic cholestatic liver disease, display changes in the gut microbiota and in bile acid composition. Schneider, Candels and colleagues identify a role for microbiota-dependent regulation of bile acid synthesis through farnesoid X receptor signalling, which is relevant for PSC disease progression.
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| 4. |
- Stjernbrandt, Albin, et al.
(författare)
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Occupational cold exposure and symptoms of carpal tunnel syndrome : a population-based study
- 2022
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Ingår i: BMC Musculoskeletal Disorders. - : BioMed Central. - 1471-2474. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cold exposure is an underrecognized occupational hazard that may increase the risk of peripheral nerve entrapment. The aim of this study was to determine if self-reported occupational exposure to contact and ambient cooling was associated with symptoms of carpal tunnel syndrome (CTS).METHODS: In this mainly cross-sectional study, surveys were conducted on a population-based sample of men and women between 18 and 70 years of age, living in northern Sweden. Cold exposure and presence of symptoms suggestive of CTS were subjectively reported. Associations between exposure and outcome were evaluated using logistic regression.RESULTS: The study included 2,703 women and 2,314 men, with a median age of 60 years (interquartile range 19). Symptoms of CTS were reported by 453 (9.2%). Being highly occupationally exposed (almost always) to contact cooling of the hands was associated with reporting CTS (OR 3.20; 95% CI 1.62-6.33), as was ambient cooling (OR 2.00; 95% CI 1.03-3.88) and severe ambient cooling (OR 4.02 95% CI 2.09-7.71), after adjusting for age, gender, body mass index, current daily smoking, diabetes mellitus, joint disease, and hand-arm vibration exposure. The point estimates increased with longer daily exposure duration. For workers exposed to severe ambient cooling for more than half of their working hours, in addition to performing heavy manual handling every day, the OR for reporting CTS was 7.25 (95% CI 3.88-13.53), with a positive additive interaction effect (expressed as relative excess risk due to interaction) of 4.67.CONCLUSIONS: Self-reported occupational exposure to contact and ambient cooling was associated with symptoms suggestive of CTS. There were statistically significant positive exposure-response patterns for time spent exposed to contact and ambient cooling at work in relation to reporting symptoms of CTS. Positive additive interaction effects between cold exposure and heavy manual handling were also found. Since there was important potential uncontrolled confounding regarding repetitive wrist movements and forceful gripping, the results need to be confirmed by other studies, preferably with longitudinal design and more detailed exposure assessment.
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| 5. |
- Stjernbrandt, Albin, et al.
(författare)
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Occupational cold exposure is associated with upper extremity pain
- 2023
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Ingår i: Frontiers in Pain Research. - : Frontiers Media S.A.. - 2673-561X. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Occupational cold exposure is common in Sweden but potential impacts on musculoskeletal disorders have not been thoroughly investigated. The primary aim of this study was to determine the associations between occupational contact and ambient cooling in relation to pain in the upper extremity.Methods: In this cross-sectional study, a digital survey was conducted on a population-based sample of women and men between 24 and 76 years of age, living in northern Sweden. Occupational cold exposure, heavy manual handling, work with vibrating tools as well as the presence of upper extremity pain at different sites were subjectively reported. Associations between exposure and outcome were evaluated using multiple binary logistic regression.Results: The final study sample included 2,089 (54.4%) women and 1,754 men, with a mean age of 56 years. Hand pain was reported by 196 (5.2%), lower arm pain by 144 (3.8%), and upper arm pain by 451 (11.9%). Severe ambient cooling for more than half of the working time was statistically significantly associated with hand pain (OR: 2.30; 95% CI: 1.23–4.29) and upper arm pain (OR: 1.57; 95% CI: 1.00–2.47) but not lower arm pain (OR: 1.87; 95% CI: 0.96–3.65) after adjusting for gender, age, body mass index, current daily smoking, heavy manual handling, and work with vibrating tools.Conclusions: Occupational cold exposure was statistically significantly associated with hand pain and upper arm pain. Therefore, occupational cold exposure should be recognized as a potential risk factor for musculoskeletal disorders in the upper extremity.
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| 6. |
- Assmann, R. W., et al.
(författare)
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EuPRAXIA Conceptual Design Report
- 2020
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Ingår i: European Physical Journal: Special Topics. - : Springer Science and Business Media LLC. - 1951-6355 .- 1951-6401. ; 229:24, s. 3675-4284
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Tidskriftsartikel (refereegranskat)abstract
- This report presents the conceptual design of a new European research infrastructure EuPRAXIA. The concept has been established over the last four years in a unique collaboration of 41 laboratories within a Horizon 2020 design study funded by the European Union. EuPRAXIA is the first European project that develops a dedicated particle accelerator research infrastructure based on novel plasma acceleration concepts and laser technology. It focuses on the development of electron accelerators and underlying technologies, their user communities, and the exploitation of existing accelerator infrastructures in Europe. EuPRAXIA has involved, amongst others, the international laser community and industry to build links and bridges with accelerator science — through realising synergies, identifying disruptive ideas, innovating, and fostering knowledge exchange. The Eu-PRAXIA project aims at the construction of an innovative electron accelerator using laser- and electron-beam-driven plasma wakefield acceleration that offers a significant reduction in size and possible savings in cost over current state-of-the-art radiofrequency-based accelerators. The foreseen electron energy range of one to five gigaelectronvolts (GeV) and its performance goals will enable versatile applications in various domains, e.g. as a compact free-electron laser (FEL), compact sources for medical imaging and positron generation, table-top test beams for particle detectors, as well as deeply penetrating X-ray and gamma-ray sources for material testing. EuPRAXIA is designed to be the required stepping stone to possible future plasma-based facilities, such as linear colliders at the high-energy physics (HEP) energy frontier. Consistent with a high-confidence approach, the project includes measures to retire risk by establishing scaled technology demonstrators. This report includes preliminary models for project implementation, cost and schedule that would allow operation of the full Eu-PRAXIA facility within 8—10 years. © 2020, The Author(s).
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| 7. |
- Aurelius, Kristina, et al.
(författare)
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Perceptions of mental health, suicide and working conditions in the construction industry-A qualitative study.
- 2024
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 19:7
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to explore perceptions of mental ill health, suicidal behaviour and working conditions among male construction workers, in order to gain an in-depth understanding of these phenomenon and to identify relevant avenues for workplace interventions.Data were collected in individual and group interviews, and 43 individuals from the Swedish construction industry, workers, union representative and managers, participated in the study. Inductive thematic analysis was used to analyse the data.Five main themes were found: Difficult to talk about mental health, Demanding working environment affects mental health, Substance abuse among construction workers, Importance of management, and Need for routines and social support in the workplace. Many participants reported that there was a stigma related to mental health. Suicides that had occurred among colleagues were perceived to come out of the blue. The working environment in the construction industry was perceived to have a negative effect on mental health, and it was reported that the management played an important role in both the cause and prevention of mental health problems.The results from this Swedish study are in accordance with previous international research regarding a macho culture, stigma of mental health and a demanding working environment in the construction industry. The study adds to existing knowledge by highlighting that suicides were perceived to be very unexpected, that poor physical health affected mental health and that many participants did not know how to deal with mental health issues in the workplace.
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| 8. |
- Hjelm, R., et al.
(författare)
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Gear tolerancing for simultaneous optimization of transmission error and contact pressure
- 2021
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Ingår i: Results in Engineering. - : Elsevier BV. - 2590-1230. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- With electrification of vehicles comes an increasing demand on low noise, which for gears translates to transmission error. In this paper, static transmission error, STE, is found for a large number of manufacturing error combinations belonging to different tolerance classes, with focus on those typically used in the automotive industry. There is a lack of studies found in the scientific literature which investigate the link between STE, contact pressure, and manufacturing error tolerances. Therefore, the aim of the present study is to investigate this link. This is done by utilizing a novel simulation tool, developed by the authors, to compute STE for gear sets with pitch and profile slope errors combinations. The model uses a parametric description of the reference profile, includes tooth modifications, uses a hybrid method for compliance, and finds contact from equilibrium. The model handles contact outside the nominal line of action, including tip contact. A simplified method, with predictions based on simulated values, is shown to be accurate and suitable for estimations. Finally, STE is linked to contact pressure for better understanding of how STE and contact pressure interact as a consequence of manufacturing errors. It is shown how this can be used to optimize the gear set with respect to both STE and contact pressure simultaneously.
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| 9. |
- Johnsson, Jesper, et al.
(författare)
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Functional outcomes associated with varying levels of targeted temperature management after out-of-hospital cardiac arrest — An INTCAR2 registry analysis
- 2020
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 146, s. 229-236
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Targeted temperature management (TTM) after out-of-hospital cardiac arrest (OHCA) has been recommended in international guidelines since 2005. The TTM-trial published in 2013 showed no difference in survival or neurological outcome for patients randomised to 33 °C or 36 °C, and many hospitals have changed practice. The optimal utilization of TTM is still debated. This study aimed to analyse if a difference in temperature goal was associated with outcome in an unselected international registry population. Methods: This is a retrospective observational study based on a prospective registry — the International Cardiac Arrest Registry 2. Patients were categorized as receiving TTM in the lower range at 32–34 °C (TTM-low) or at 35–37 °C (TTM-high). Primary outcome was good functional status defined as cerebral performance category (CPC) of 1–2 at hospital discharge and secondary outcome was adverse events related to TTM. A logistic regression model was created to evaluate the independent effect of temperature by correcting for clinical and demographic factors associated with outcome. Results: Of 1710 patients included, 1242 (72,6%) received TTM-low and 468 (27,4%) TTM-high. In patients receiving TTM-low, 31.3% survived with good outcome compared to 28.8% in the TTM-high group. There was no significant association between temperature and outcome (p = 0.352). In analyses adjusted for baseline differences the OR for a good outcome with TTM-low was 1.27, 95% CI (0.94–1.73). Haemodynamic instability leading to discontinuation of TTM was more common in TTM-low. Conclusions: No significant difference in functional outcome at hospital discharge was found in patients receiving lower- versus higher targeted temperature management.
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| 10. |
- Lewis, Charlotte A., et al.
(författare)
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Surgery for subacromial impingement syndrome and occupational biomechanical risk factors in a 16-year prospective study among male construction workers
- 2023
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Ingår i: Scandinavian Journal of Work, Environment and Health. - Helsinki : NOROSH. - 0355-3140 .- 1795-990X. ; 49:2, s. 156-163
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The aim of this study was to assess the association between occupational biomechanical exposures and the occurrence of surgical treatment for subacromial impingement syndrome (SIS).Methods. A cohort of 220 295 male constructions workers who participated in a national occupational health surveillance program (1971–1993) were examined prospectively over a 16-year follow-up period (2001–2016) for surgically treated SIS. Worker job title, smoking status, height, weight, and age were registered on health examination. Job titles were mapped to 21 occupational groups based on tasks and training. A job exposure matrix (JEM) was developed with exposure estimates for each occupational group. Surgical cases were determined through linkage with the Swedish national in- and outpatient registers. Poisson regression was used to assess the relative risks (RR) for each biomechanical exposure.Results. The total incidence rate of surgically treated SIS over the 16-year observation period was 201.1 cases per 100 000 person-years. Increased risk was evident for workers exposed to upper-extremity loading (push/pull/lift) (RR 1.45–2.30), high hand grip force (RR 1.47–2.23), using handheld tools (RR 1.52–2.09), frequent work with hands above shoulders (RR 1.62–2.11), static work (RR 1.77–2.26), and hand-arm vibration (RR 1.78–2.13). There was an increased risk for SIS surgery for all occupational groups (construction trades) compared with white-collar workers (RR 1.56–2.61).Conclusions. Occupational upper-extremity load and posture exposures were associated with increased risk for surgical treatment of SIS, which underlines the need for reducing workplace exposures and early symptom detection in highly exposed occupational groups.
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