| 1. |
- Pauli Bock, Emelie, et al.
(författare)
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Literature Review : Evidence-Based Health Outcomes and Perceptions of the Built Environment in Pediatric Hospital Facilities.
- 2021
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Ingår i: Journal of Pediatric Nursing. - : Elsevier. - 0882-5963 .- 1532-8449. ; 61, s. e42-e50
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Tidskriftsartikel (refereegranskat)abstract
- PROBLEM: The current knowledge of evidence-based design for adults is not always implemented when hospital buildings are designed. Scientific data are sparse on the effects of hospital design in pediatric settings on health outcomes in children, parents, and staff. The objective of this review is to determine the evidence-based impact of the built environment in pediatric hospital facilities on health outcomes in children, parents, and staff.ELIGIBILITY CRITERIA: A systematic literature review was carried out on the electronic databases Cochrane Library, Embase, Medline and CINAHL from the period of 2008 to 2019. The review considered studies using either quantitative, qualitative, or mixed methodologies.SAMPLE: Out of 1414 reviewed articles the result is based on eight included articles.RESULTS: Two of these eight articles included health outcomes. The other six articles presented results on measures of perceptions and/or satisfaction for children, parents or staff with the built environment when transitioning to a new or renovated facility. These were generally higher for the new compared to the old facility.CONCLUSIONS: Given the small number of studies addressing the question posed in this review, no firm conclusions can be drawn.IMPLICATIONS: The review illustrates the need for more research in the pediatric setting assessing the evidence-based health outcomes of aspects of physical environmental design in pediatric hospitals or units in children, parents and staff.
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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. |
- Chantzichristos, Dimitrios, 1976, et al.
(författare)
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Identification of human glucocorticoid response markers using integrated multi-omic analysis from a randomized crossover trial.
- 2021
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Ingår i: eLife. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Glucocorticoids are among the most commonly prescribed drugs, but there is no biomarker that can quantify their action. The aim of the study was to identify and validate circulating biomarkers of glucocorticoid action.In a randomized, crossover, single-blind, discovery study, 10 subjects with primary adrenal insufficiency (and no other endocrinopathies) were admitted at the in-patient clinic and studied during physiological glucocorticoid exposure and withdrawal. A randomization plan before the first intervention was used. Besides mild physical and/or mental fatigue and salt craving, no serious adverse events were observed. The transcriptome in peripheral blood mononuclear cells and adipose tissue, plasma miRNAomic, and serum metabolomics were compared between the interventions using integrated multi-omic analysis.We identified a transcriptomic profile derived from two tissues and a multi-omic cluster, both predictive of glucocorticoid exposure. A microRNA (miR-122-5p) that was correlated with genes and metabolites regulated by glucocorticoid exposure was identified (p=0.009) and replicated in independent studies with varying glucocorticoid exposure (0.01 ≤ p≤0.05).We have generated results that construct the basis for successful discovery of biomarker(s) to measure effects of glucocorticoids, allowing strategies to individualize and optimize glucocorticoid therapy, and shedding light on disease etiology related to unphysiological glucocorticoid exposure, such as in cardiovascular disease and obesity.The Swedish Research Council (Grant 2015-02561 and 2019-01112); The Swedish federal government under the LUA/ALF agreement (Grant ALFGBG-719531); The Swedish Endocrinology Association; The Gothenburg Medical Society; Wellcome Trust; The Medical Research Council, UK; The Chief Scientist Office, UK; The Eva Madura's Foundation; The Research Foundation of Copenhagen University Hospital; and The Danish Rheumatism Association.NCT02152553.
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| 4. |
- Drake, Isabel, et al.
(författare)
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The role of circulating galectin-1 in type 2 diabetes and chronic kidney disease: evidence from cross-sectional, longitudinal and Mendelian randomisation analyses
- 2022
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 65, s. 128-139
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis Galectin-1 modulates inflammation and angiogenesis, and cross-sectional studies indicate that galectin-1 may be a uniting factor between obesity, type 2 diabetes and kidney function. We examined whether circulating galectin-1 can predict incidence of chronic kidney disease (CKD) and type 2 diabetes in a middle-aged population, and if Mendelian randomisation (MR) can provide evidence for causal direction of effects. Methods Participants (n = 4022; 58.6% women) in the Malmo Diet and Cancer Study-Cardiovascular Cohort enrolled between 1991 and 1994 (mean age 57.6 years) were examined. eGFR was calculated at baseline and after a mean follow-up of 16.6 +/- 1.5 years. Diabetes status was ascertained through registry linkage (mean follow-up of 18.4 +/- 6.1 years). The associations of baseline galectin-1 with incident CKD and type 2 diabetes were assessed with Cox regression, adjusting for established risk factors. In addition, a genome-wide association study on galectin-1 was performed to identify genetic instruments for two-sample MR analyses utilising the genetic associations obtained from the Chronic Kidney Disease Genetics (CKDGen) Consortium (41,395 cases and 439,303 controls) and the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium (74,124 cases and 824,006 controls). One genome-wide significant locus in the galectin-1 gene region was identified (sentinel SNP rs7285699; p = 2.4 x 10(-11)). The association between galectin-1 and eGFR was also examined in individuals with newly diagnosed diabetes from the All New Diabetics In Scania (ANDIS) cohort. Results Galectin-1 was strongly associated with lower eGFR at baseline (p = 2.3 x 10(-89)) but not with incident CKD. However, galectin-1 was associated with increased risk of type 2 diabetes (per SD increase, HR 1.12; 95% CI 1.02, 1.24). Two-sample MR analyses could not ascertain a causal effect of galectin-1 on CKD (OR 0.92; 95% CI 0.82, 1.02) or type 2 diabetes (OR 1.05; 95% CI 0.98, 1.14) in a general population. However, in individuals with type 2 diabetes from ANDIS who belonged to the severe insulin-resistant diabetes subgroup and were at high risk of diabetic nephropathy, genetically elevated galectin-1 was significantly associated with higher eGFR (p = 5.7 x 10(-3)). Conclusions/interpretation Galectin-1 is strongly associated with lower kidney function in cross-sectional analyses, and two-sample MR analyses suggest a causal protective effect on kidney function among individuals with type 2 diabetes at high risk of diabetic nephropathy. Future studies are needed to explore the mechanisms by which galectin-1 affects kidney function and whether it could be a useful target among individuals with type 2 diabetes for renal improvement.
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| 5. |
- Gummesson, Anders, 1973, et al.
(författare)
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Longitudinal plasma protein profiling of newly diagnosed type 2 diabetes
- 2021
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Ingår i: EBioMedicine. - : Elsevier B.V.. - 2352-3964. ; 63
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Tidskriftsartikel (refereegranskat)abstract
- Background: Comprehensive proteomics profiling may offer new insights into the dysregulated metabolic milieu of type 2 diabetes, and in the future, serve as a useful tool for personalized medicine. This calls for a better understanding of circulating protein patterns at the early stage of type 2 diabetes as well as the dynamics of protein patterns during changes in metabolic status. Methods: To elucidate the systemic alterations in early-stage diabetes and to investigate the effects on the proteome during metabolic improvement, we measured 974 circulating proteins in 52 newly diagnosed, treatment-naïve type 2 diabetes subjects at baseline and after 1 and 3 months of guideline-based diabetes treatment, while comparing their protein profiles to that of 94 subjects without diabetes. Findings: Early stage type 2 diabetes was associated with distinct protein patterns, reflecting key metabolic syndrome features including insulin resistance, adiposity, hyperglycemia and liver steatosis. The protein profiles at baseline were attenuated during guideline-based diabetes treatment and several plasma proteins associated with metformin medication independently of metabolic variables, such as circulating EPCAM. Interpretation: The results advance our knowledge about the biochemical manifestations of type 2 diabetes and suggest that comprehensive protein profiling may serve as a useful tool for metabolic phenotyping and for elucidating the biological effects of diabetes treatments. Funding: This work was supported by the Swedish Heart and Lung Foundation, the Swedish Research Council, the Erling Persson Foundation, the Knut and Alice Wallenberg Foundation, and the Swedish state under the agreement between the Swedish government and the county councils (ALF-agreement).
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| 6. |
- Hägg, Daniel, 1974, et al.
(författare)
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Osteoblast-lineage cells regulate metabolism and fat mass
- 2023
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Ingår i: Current Opinion in Endocrine and Metabolic Research. - 2451-9650. ; 31
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Forskningsöversikt (refereegranskat)abstract
- As energy depots in many circumstances have been limited during evolution, it is necessary to prioritize how to manage energy resources. In this review we summarize data from the last 15 years indicating that osteoblast-lineage cells are regulators of whole-body energy metabolism and fat mass. We focus mainly on three factors, osteocalcin, lipocalin-2 and sclerostin, that are released by osteoblast-lineage cells and proposed to exert endocrine effects on metabolism. In addition, we present a hypothesis on why osteoblast-lineage cells during evolution have developed a function to regulate metabolism and fat mass. We propose that osteoblast-lineage cells through the osteocyte network in bone are sensors of gravitational forces induced by body mass and gravity on land-living species. By sensing the body weight, the osteoblastlineage cells may then feed-back this information on the whole-body nutritional status via osteoblast-derived endocrine factors or via the nervous system to regulate energy metabolism and fat mass.
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| 7. |
- Jansson, John-Olov, 1954, et al.
(författare)
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The dual hypothesis of homeostatic body weight regulation, including gravity-dependent and leptin-dependent actions.
- 2023
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Ingår i: Philosophical transactions of the Royal Society of London. Series B, Biological sciences. - 1471-2970. ; 378:1888
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Forskningsöversikt (refereegranskat)abstract
- Body weight is tightly regulated when outside the normal range. It has been proposed that there are individual-specific lower and upper intervention points for when the homeostatic regulation of body weight is initiated. The nature of the homeostatic mechanisms regulating body weight at the lower and upper ends of the body weight spectrum might differ. Previous studies demonstrate that leptin is the main regulator of body weight at the lower end of the body weight spectrum. We have proposed that land-living animals use gravity to regulate their body weight. We named this homeostatic system the gravitostat and proposed that there are two components of the gravitostat. First, an obvious mechanism involves increased energy consumption in relation to body weight when working against gravity on land. In addition, we propose that there exists a component, involving sensing of the body weight by osteocytes in the weight-bearing bones, resulting in a feedback regulation of energy metabolism and body weight. The gravity-dependent homeostatic regulation is mainly active in obese mice. We, herein, propose the dual hypothesis of body weight regulation, including gravity-dependent actions (= gravitostat) at the upper end and leptin-dependent actions at the lower end of the body weight spectrum. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part II)'.
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| 8. |
- Ohlsson, Claes, 1965, et al.
(författare)
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Increased weight loading reduces body weight and body fat in obese subjects – A proof of concept randomized clinical trial
- 2020
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Ingår i: EClinicalMedicine. - : Elsevier BV. - 2589-5370. ; 22
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recently we provided evidence for a leptin-independent homeostatic regulation, the gravitostat, of body weight in rodents. The aim of the present translational proof of concept study was to test the gravitostat hypothesis in humans. Methods: We conducted a randomized controlled single center trial (ClinicalTrial.gov number, NCT03672903), to evaluate the efficacy of artificially increased weight loading on body weight in subjects with mild obesity (BMI 30–35 kg/m2). Subjects were either treated with a heavy (=high load; 11% of body weight) or light (=low load; 1% of body weight) weight vest for eight hours per day for three weeks. The primary outcome was change in body weight. Secondary outcomes included change in body fat mass and fat-free mass as measured using bioelectrical impedance analysis. Findings: In total 72 participants underwent randomization and 69 (36 high load and 33 low load) completed the study for the primary outcome. High load treatment resulted in a more pronounced relative body weight loss compared to low load treatment (mean difference -1.37%, 95% confidence interval (CI), -1.96 to -0.79; p = 1.5 × 10−5). High load treatment reduced fat mass (-4.04%, 95% CI, -6,53 to -1.55; p = 1.9 × 10−3) but not fat free mass (0.43%, 95% CI, -1.47 to 2.34; p = 0.65) compared to low load treatment. Interpretation: Increased weight loading reduces body weight and fat mass in obese subjects in a similar way as previously shown in obese rodents. These findings demonstrate that there is weight loading dependent homeostatic regulation of body weight, the gravitostat, also in humans. Funding: Funded by Jane and Dan Olsson (JADO) Foundation, the Torsten Söderberg Foundation, The Knut and Alice Wallenberg's Foundation and the Novo Nordisk Foundation. © 2020 The Author(s)
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| 9. |
- Pournaras, N., et al.
(författare)
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Glucose Homeostasis in Relation to Neutrophil Mobilization in Smokers with COPD
- 2022
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Ingår i: International Journal of Chronic Obstructive Pulmonary Disease. - 1178-2005. ; 17, s. 1179-1194
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) are common comorbidities in chronic obstructive pulmonary disease (COPD), but the underlying pathogenic mechanisms are poorly understood. Given that these morbidities all display increased neutrophil mobilization, the current study aimed to address whether glucose homeostasis relates to signs of neutrophil mobilization in COPD. Methods: The study population included healthy non-smokers (HNS) and long-term smokers without (LTS) and with COPD (LTS +COPD). No subject had T2DM or MetS. Serum cotinine was quantified to evaluate current smoking. Capillary blood glucose was measured after overnight fasting and during an oral glucose tolerance test (OGTT). Neutrophils were quantified in blood and bronchoalveolar lavage samples (BAL). The neutrophil-related cytokines IL-36 alpha, -beta and -gamma were quantified (ELISA) along with IL-6, IL-8, INF-gamma and CXCL10 (U-Plex (R)) in plasma and cell-free BAL fluid (BALF). In addition, we quantified neutrophil elastase (ELISA) and net proteinase activity (substrate assay) in BALF. Results: The LTS+COPD group had lower fasting glucose, greater change in glucose during OGTT and higher neutrophil concentrations in BAL and blood compared with HNS. Fasting glucose correlated in a positive manner with blood neutrophil concentration, forced expiratory volume in 1 second/forced vital capacity ratio (FEV1/FVC) and FEV1 (% of predicted) in LTS+COPD. In this group, the concentration of IL-36 alpha in BALF correlated in a negative manner with fasting glucose, blood neutrophil concentration and FEV1, while the CXCL10 concentration in BALF correlated in a negative manner with glucose at the end of OGTT (120 min). We observed no corresponding correlations for neutrophil elastase, net proteinase or gelatinase activity. Conclusion: In smokers with COPD, altered glucose homeostasis is associated with local and systemic signs of increased neutrophil mobilization, but not with local proteinases. This suggests that other specific aspects of neutrophil mobilization constitute pathogenic factors that affect glucose homeostasis in COPD.
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| 10. |
- Fryk, Emanuel, et al.
(författare)
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Feasibility of high-dose tadalafil and effects on insulin resistance in well-controlled patients with type 2 diabetes (MAKROTAD): a single-centre, double-blind, randomised, placebo-controlled, cross-over phase 2 trial
- 2023
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Ingår i: Eclinicalmedicine. ; 59
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Tidskriftsartikel (refereegranskat)abstract
- Background Phosphodiesterase-5 inhibitors exert positive vascular and metabolic effects in type 2 diabetes (T2D), but the effect on insulin resistance in T2D is unclear. Methods This randomised, double blind, placebo-controlled, two-period crossover trial was conducted at Sahlgrenska University Hospital (Gothenburg, Sweden). Men without apparent erectile dysfunction (age 40-70 years) and women (age 55-70 years, post-menopause) diagnosed with T2D between 3 months and 10 years, haemoglobin A1c (HbA1c) < 60 mmol/mol and a body mass index (BMI) 27-40 kg/m2 were enrolled. Participants were randomly assigned to one period of oral tadalafil 20 mg once a day and one period of placebo for 6 weeks, separated by an 8-week wash-out period. Placebo and tadalafil tablets were made visually indistinguishable and delivered randomized in two separate boxes for each participant. Both treatment periods ended with a glucose clamp, and measurements of body composition and metabolic markers in blood, subcutaneous and muscular interstitial fluid. The primary aim was to assess difference in whole-body insulin resistance after 6-weeks of treatment, determined after completion of the two study arms, and secondary aims were to study effects of tadalafil on pathophysiology of T2D as well as tolerability of high-dose tadalafil in T2D. Primary analysis was performed in participants with full analysis set (FAS) and safety analysis in all participants who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov (NCT02601989), and EudraCT (2015-000573). Findings Between January 22nd, 2016, and January 31st, 2019, 23 participants with T2D were enrolled, of whom 18 were included in the full analysis set. The effect of tadalafil on insulin resistance was neutral compared with placebo. However, tadalafil decreased glycaemia measured as HbA1c (mean difference -2.50 mmol/mol, 95% confidence interval (CI), -4.20; -0.78, p = 0.005), and, further, we observed amelioration of endothelial function and markers of liver steatosis and glycolysis, whereas no statistically significant differences of other clinical phenotyping were shown. Muscle pain, dyspepsia, and headache were more frequent in participants on high-dose tadalafil compared with placebo (p < 0.05) but no difference between treatments appeared for serious adverse events. Interpretation High-dose tadalafil does not decrease whole-body insulin resistance, but increases microcirculation, induces positive effects in the liver and in intermediate metabolites, in parallel with an improved metabolic control measured as HbA1c. High-dose tadalafil is moderately well tolerated, warranting larger trials to define the optimal treatment regimen in T2D.
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