| 1. |
- Zhang, C., et al.
(författare)
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The acute effect of metabolic cofactor supplementation: a potential therapeutic strategy against non-alcoholic fatty liver disease
- 2020
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Ingår i: Molecular Systems Biology. - : EMBO. - 1744-4292. ; 16:4
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of non-alcoholic fatty liver disease (NAFLD) continues to increase dramatically, and there is no approved medication for its treatment. Recently, we predicted the underlying molecular mechanisms involved in the progression of NAFLD using network analysis and identified metabolic cofactors that might be beneficial as supplements to decrease human liver fat. Here, we first assessed the tolerability of the combined metabolic cofactors including l-serine, N-acetyl-l-cysteine (NAC), nicotinamide riboside (NR), and l-carnitine by performing a 7-day rat toxicology study. Second, we performed a human calibration study by supplementing combined metabolic cofactors and a control study to study the kinetics of these metabolites in the plasma of healthy subjects with and without supplementation. We measured clinical parameters and observed no immediate side effects. Next, we generated plasma metabolomics and inflammatory protein markers data to reveal the acute changes associated with the supplementation of the metabolic cofactors. We also integrated metabolomics data using personalized genome-scale metabolic modeling and observed that such supplementation significantly affects the global human lipid, amino acid, and antioxidant metabolism. Finally, we predicted blood concentrations of these compounds during daily long-term supplementation by generating an ordinary differential equation model and liver concentrations of serine by generating a pharmacokinetic model and finally adjusted the doses of individual metabolic cofactors for future human clinical trials.
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| 2. |
- Abdellah, Tebani, et al.
(författare)
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Integration of molecular profiles in a longitudinal wellness profiling cohort.
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies andimmune cell profiling, complementedwith gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.
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| 3. |
- Hugelius, Karin, et al.
(författare)
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Katastrofmedicin måste bli obligatorisk utbildning
- 2020
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Ingår i: Dagens Nyheter. - 1101-2447. ; 2020:13 JULI
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Experter inom svensk katastrof- och försvarsmedicin: Svenska läkare och sjuksköterskor får otillräcklig utbildning för att kunna ge vård i kris och krig. Ämnesområdet måste bli en obligatorisk del i grundutbildningen så att vi står rustade även inför nästa kris, oavsett om det är en pandemi, naturkatastrof eller ett terrordåd.
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| 4. |
- Molinaro, Antonio, et al.
(författare)
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Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism.
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| 5. |
- Nilsen, M. S., et al.
(författare)
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3-Hydroxyisobutyrate, A Strong Marker of Insulin Resistance in Type 2 Diabetes and Obesity That Modulates White and Brown Adipocyte Metabolism
- 2020
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 69:9, s. 1903-1916
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Tidskriftsartikel (refereegranskat)abstract
- Circulating branched-chain amino acids (BCAAs) associate with insulin resistance and type 2 diabetes. 3-Hydroxyisobutyrate (3-HIB) is a catabolic intermediate of the BCAA valine. In this study, we show that in a cohort of 4,942 men and women, circulating 3-HIB is elevated according to levels of hyperglycemia and established type 2 diabetes. In complementary cohorts with measures of insulin resistance, we found positive correlates for circulating 3-HIB concentrations with HOMA2 of insulin resistance, as well as a transient increase in 3-HIB followed by a marked decrease after bariatric surgery and weight loss. During differentiation, both white and brown adipocytes upregulate BCAA utilization and release increasing amounts of 3-HIB. Knockdown of the 3-HIB-forming enzyme 3-hydroxyisobutyryl-CoA hydrolase decreases release of 3-HIB and lipid accumulation in both cell types. Conversely, addition of 3-HIB to white and brown adipocyte cultures increases fatty acid uptake and modulated insulin-stimulated glucose uptake in a time-dependent manner. Finally, 3-HIB treatment decreases mitochondrial oxygen consumption and generation of reactive oxygen species in white adipocytes, while increasing these measures in brown adipocytes. Our data establish 3-HIB as a novel adipocyte-derived regulator of adipocyte subtype-specific functions strongly linked to obesity, insulin resistance, and type 2 diabetes.
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| 6. |
- Rosén, Anders, 1970, et al.
(författare)
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Biomarkers of neuronal damage in saturation diving—a controlled observational study
- 2020
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Ingår i: European Journal of Applied Physiology. - : Springer Nature. - 1439-6319 .- 1439-6327.
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: A prospective and controlled observational study was performed to determine if the central nervous system injury markers glial fibrillary acidic protein (GFAp), neurofilament light (NfL) and tau concentrations changed in response to a saturation dive. Methods: The intervention group consisted of 14 submariners compressed to 401 kPa in a dry hyperbaric chamber. They remained pressurized for 36 h and were then decompressed over 70 h. A control group of 12 individuals was used. Blood samples were obtained from both groups before, during and after hyperbaric exposure, and from the intervention group after a further 25–26 h. Results: There were no statistically significant changes in the concentrations of GFAp, NfL and tau in the intervention group. During hyperbaric exposure, GFAp decreased in the control group (mean/median − 15.1/ − 8.9 pg·mL−1, p < 0.01) and there was a significant difference in absolute change of GFAp and NfL between the groups (17.7 pg·mL−1, p = 0.02 and 2.34 pg·mL−1, p = 0.02, respectively). Albumin decreased in the control group (mean/median − 2.74 g/L/ − 0.95 g/L, p = 0.02), but there was no statistically significant difference in albumin levels between the groups. In the intervention group, haematocrit and mean haemoglobin values were slightly increased after hyperbaric exposure (mean/median 2.3%/1.5%, p = 0.02 and 4.9 g/L, p = 0.06, respectively). Conclusion: Hyperbaric exposure to 401 kPa for 36 h was not associated with significant increases in GFAp, NfL or tau concentrations. Albumin levels, changes in hydration or diurnal variation were unlikely to have confounded the results. Saturation exposure to 401 kPa seems to be a procedure not harmful to the central nervous system. Trial registration: ClinicalTrials.gov NCT03192930.
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| 7. |
- Eriksson, Anna-Lena, 1971, et al.
(författare)
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[Prescribing knowledge in final-year medical students attending a curriculum without a summative prescribing exam]. : Läkarstudenter anser sig behöva utbildning i läkemedelsbehandling.
- 2020
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Ingår i: Lakartidningen. - 1652-7518. ; 117:43
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Tidskriftsartikel (refereegranskat)abstract
- In Sweden, unlike some other European countries, there is no prescribing exam at the end of the final year of medical school. To investigate the level of knowledge achieved without such an exam, we developed an anonymous test consisting of 48 multiple choice questions which was completed by 80 final-year medical students at the University of Gothenburg (median age: 26 years; 56% female). Median percentage of correct answers was 51%. The test included 31 questions from the prescribing exam in the Netherlands. Using the pass mark from the examination in the Netherlands for these questions (85% correct answers), 7.5% of the Swedish students reached a sufficient level of knowledge. Only 12% of the students agreed that medical school had prepared them well for prescribing. In free text answers, more focus on pharmacotherapy education and training as well as undergraduate exams were frequent suggestions to increase junior physicians' professional competence in prescribing. To direct learning activities and student engagement as well as to ensure sufficient prescribing skills, we suggest the introduction of a prescribing exam in Sweden.
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| 8. |
- Gremyr, Andreas, et al.
(författare)
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Using Complexity Assessment to Inform the Development and Deployment of a Digital Dashboard for Schizophrenia Care: Case Study
- 2020
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Ingår i: Journal of Medical Internet Research. - : JMIR Publications Inc.. - 1438-8871. ; 22:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Health care is becoming more complex. For an increasing number of individuals, interacting with health care means addressing more than just one illness or disorder, engaging in more than one treatment, and interacting with more than one care provider. Individuals with severe mental illnesses such as schizophrenia are disproportionately affected by this complexity. Characteristic symptoms can make it harder to establish and maintain relationships. Treatment failure is common even where there is access to effective treatments, increasing suicide risk. Knowledge of complex adaptive systems has been increasingly recognized as useful in understanding and developing health care. A complex adaptive system is a collection of interconnected agents with the freedom to act based on their own internalized rules, affecting each other. In a complex health care system, relevant feedback is crucial in enabling continuous learning and improvement on all levels. New technology has potential, but the failure rate of technology projects in health care is high, arguably due to complexity. The Nonadoption, Abandonment, and challenges to Scale-up, Spread, and Sustainability (NASSS) framework and complexity assessment tool (NASSS-CAT) have been developed specifically to help identify and manage complexity in technology-related development projects in health care. Objective: This study aimed to use a pilot version of the NASSS-CAT instrument to inform the development and deployment of a point-of-care dashboard supporting schizophrenia care in west Sweden. Specifically, we report on the complexity profile of the project, stakeholders' experiences with using NASSS-CAT, and practical implications. Methods: We used complexity assessment to structure data collection and feedback sessions with stakeholders, thereby informing an emergent approach to the development and deployment of the point-of-care dashboard. We also performed a thematic analysis, drawing on observations and documents related to stakeholders' use of the NASSS-CAT to describe their views on its usefulness. Results: Application of the NASSS framework revealed different types of complexity across multiple domains, including the condition, technology, value proposition, organizational tasks and pathways, and wider system. Stakeholders perceived the NASSS-CAT tool as useful in gaining perspective and new insights, covering areas that might otherwise have been neglected. Practical implications derived from feedback sessions with managers and developers are described. Conclusions: This case study shows how stakeholders can identify and plan to address complexities during the introduction of a technological solution. Our findings suggest that NASSS-CAT can bring participants a greater understanding of complexities in digitalization projects in general.
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| 9. |
- Hörberg, Ulrica, 1968-, et al.
(författare)
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Women's lived experience of well-being in everyday life when living with a stress-related illness
- 2020
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Ingår i: International Journal of Qualitative Studies on Health and Well-being. - : Informa UK Limited. - 1748-2623 .- 1748-2631. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The aim of the study was to describe how women with stress-related illness experience well-being in everyday life. Methods: The study was based on a reflective lifeworld research (RLR) approach and the methodological principles of openness, flexibility and bridling. Twelve women, aged 27-54 years, diagnosed with stress-related illness were included. Data were collected with lifeworld interviews based on photographs taken by the women relating to well-being in everyday life. The data were analysed for meaning. Results: Well-being emerged in situations where women could feel an unconditional beingness. This entails not having demands on oneself and includes some form of freedom from having to perform. The surroundings and supportive environments are important for this unconditional beingness to be present. In order to feel well-being in everyday life, the women need to balance their energy and find helpful tools that can achieve a balance in everyday life. Conclusions: Healthcare staff need to understand the importance of unconditional beingness in supportive environments for patients living with stress-related illness in order to support their health and well-being. It is also important to support patients in finding helpful tools that can aid them to achieve a balance in everyday life.
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| 10. |
- Johanson, Suzanne, et al.
(författare)
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Implementation of a novel return-to-work approach for persons with affective disorders in a traditional vocational rehabilitation context: a case study
- 2020
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Ingår i: International Journal of Mental Health Systems. - : Springer Science and Business Media LLC. - 1752-4458. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The person-centred Individual Enabling and Support (IES) model is a novel return-to-work (RTW) intervention for people with affective disorders that was developed from evidence-based supported employment for persons with severe mental illness. Typically, supported employment is integrated into mental healthcare and provides a network around the service user and close collaboration with employment and insurance services and employers. Introducing integrated models into a highly sectored welfare system that includes traditional mental healthcare and vocational rehabilitation is challenging. Greater knowledge is needed to understand how facilitating or hindering factors influence this introduction. The aim of this study was to investigate essential components in implementation of the IES model. Methods A case-study was conducted and included four mental healthcare services. Data collection was comprised of semi-structured interviews with 19 key informants, documentation from meetings, and reflection notes. Analyses were performed according to directed content analysis, using the components of the Consolidated Framework of Implementation Research (CFIR) as a guiding tool. Fidelity assessments were performed at 6 and 12 months. Results Anticipating RTW support for the target group, and building collaborative relationships and a network with employment specialists that engaged staff in every organization were components that resulted in the greatest facilitation if IES implementation. Barriers consisted of difficulty in integrating employment specialists into the mental healthcare teams, insufficient engagement of first line managers, reorganization and differing perceptions of the IES model fit into a traditional vocational context. Delivery of the IES model had good fidelity. Conclusions The IES model can be implemented with good fidelity, several model advantages, and context adaptation. Team integration difficulties and negative perceptions of model fit in a traditional vocational rehabilitation context can be overcome to a certain degree, but this is insufficient for sustainable implementation on a larger scale. Policy and guidelines need to promote integrative and person-centred RTW approaches rather than a segregated stepwise approach. Further implementation studies in the traditional vocational rehabilitation context are needed.
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