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| 2. |
- Ahlin, Sofie, 1985, et al.
(författare)
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A new sensitive and accurate model to predict moderate to severe obstructive sleep apnea in patients with obesity
- 2019
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Ingår i: Medicine (United States). - : Ovid Technologies (Wolters Kluwer Health). - 0025-7974 .- 1536-5964. ; 98:32
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Tidskriftsartikel (refereegranskat)abstract
- Obstructive sleep apnea (OSA) has a high prevalence in patients with obesity. Only patients with clinical symptoms of OSA are admitted to polysomnography; however, many patients with OSA are asymptomatic. We aimed to create and validate a population-based risk score that predicts the severity of OSA in patients with obesity. We here report the cross-sectional analysis at baseline of an ongoing study investigating the long-term effect of bariatric surgery on OSA. One-hundred sixty-one patients of the Obesity Center of the Catholic University Hospital in Rome, Italy were included in the study. The patients underwent overnight cardiorespiratory monitoring, blood chemistry analyses, hepatic ultrasound, and anthropometric measurements. The patients were divided into 2 groups according OSA severity assessed by the apnea-hypopnea index (AHI): AHI < 15 = no or mild and AHI >= 15 moderate to severe OSA. A statistical prediction model was created and validated. C statistics was used to evaluate the discrimination performance of the model. The prevalence of OSA was 96.3% with 74.5% of the subjects having moderate/severe OSA. Sex, body mass index, diabetes, and age were included in the final prediction model that had excellent discrimination ability (C statistics equals to 83%). An OSA risk chart score for clinical use was created. Patients with severe obesity are at a very high risk for moderate or severe OSA in particular if they are men, older, more obese, and/or with type 2 diabetes. The OSA risk chart can be useful for general practitioners and patients as well as for bariatric surgeons to select patients with high risk of moderate to severe OSA for further polysomnography.
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| 4. |
- Leusen, JHW, et al.
(författare)
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Disturbed interaction of p21-rac with mutated p67-phox causes chronic granulomatous disease
- 1996
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Ingår i: The Journal of experimental medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 184:4, s. 1243-1249
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Tidskriftsartikel (refereegranskat)abstract
- Chronic granulomatous disease (CGD) is characterized by the failure of phagocytic leukocytes to generate superoxide, needed for the intracellular killing of microorganisms. This is caused by mutations in any one of the four subunits of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. In a rare, autosomal recessive form of CGD, a 67-kD cytosolic component of this enzyme (p67-phox) is missing. We here report on a patient with a mutation in the p67-phox gene that leads to expression of a nonfunctional p67-phox protein. The purified granulocytes of this patient failed to produce superoxide and contained about half of the normal amount of p67-phox. Analysis of the cDNA and genomic DNA of this patient showed that the patient is a compound heterozygote for a triplet nucleotide deletion in the p67-phox gene, predicting an in-frame deletion of lysine 58 in the p67-phox protein and a larger deletion of 11-13 kb in the other allele. Interestingly, the 58Lys deletion in p67-phox disrupts the interaction with p21-rac1, a ras-related protein involved in the activation of the NADPH oxidase. In contrast to normal neutrophils, in which p47-phox and p67-phox translocate to the plasma membrane upon cell activation, the cells of the patient did not show this translocation, indicating that an interaction between p67-phox and p21-rac1 is essential for translocation of these cytosolic proteins and activation of the NADPH oxidase. Moreover, this CGD patient represents the first case of disease caused by a disturbed binding of a ras-related protein to its target protein.
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| 5. |
- Ahlin, Sofie, 1985, et al.
(författare)
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Metabolite Changes After Metabolic Surgery – Associations to Parameters Reflecting Glucose Homeostasis and Lipid Levels
- 2021
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To test the hypothesis that adipose tissue gene expression patterns would be affected by metabolic surgery and we aimed to identify genes and metabolic pathways as well as metabolites correlating with metabolic changes following metabolic surgery. Materials and Methods: This observational study was conducted at the Obesity Unit at the Catholic University Hospital of the Sacred Heart in Rome, Italy. Fifteen patients, of which six patients underwent Roux-en-Y gastric bypass and nine patients underwent biliopancreatic diversion, were included. The participants underwent an oral glucose tolerance test and a hyperinsulinemic euglycemic clamp. Small polar metabolites were analyzed with a two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC-TOFMS). Gene expression analysis of genes related to metabolism of amino acids and fatty acids were analyzed in subcutaneous adipose tissue. All procedures were performed at study start and at follow-up (after 185.3 ± 72.9 days). Results: Twelve metabolites were significantly changed after metabolic surgery. Six metabolites were identified as 3-indoleacetic acid, 2-hydroxybutyric acid, valine, glutamic acid, 4-hydroxybenzeneacetic acid and alpha-tocopherol. The branched chain amino acids displayed a significant decrease together with a decrease in BCAT1 adipose tissue mRNA levels. Changes in the identified metabolites were associated to changes in lipid, insulin and glucose levels. Conclusions: Our study has identified metabolites and metabolic pathways that are altered by metabolic surgery and may be used as biomarkers for metabolic improvement. Copyright © 2021 Ahlin, Cefalo, Bondia-Pons, Trošt, Capristo, Marini, Romero, Zorzano, Gastaldelli, Mingrone and Nolan.
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| 6. |
- Klintman, Marie, et al.
(författare)
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The Prognostic Value of Mitotic Activity Index (MAI), Phosphohistone H3 (PPH3), Cyclin B1, Cyclin A, and Ki67, Alone and in Combinations, in Node-Negative Premenopausal Breast Cancer
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12
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Tidskriftsartikel (refereegranskat)abstract
- Proliferation, either as the main common denominator in genetic profiles, or in the form of single factors such as Ki67, is recommended for clinical use especially in estrogen receptor-positive (ER) patients. However, due to high costs of genetic profiles and lack of reproducibility for Ki67, studies on other proliferation factors are warranted. The aim of the present study was to evaluate the prognostic value of the proliferation factors mitotic activity index (MAI), phosphohistone H3 (PPH3), cyclin B1, cyclin A and Ki67, alone and in combinations. In 222 consecutive premenopausal node-negative breast cancer patients (87% without adjuvant medical treatment), MAI was assessed on whole tissue sections (predefined cut-off >= 10 mitoses), and PPH3, cyclin B1, cyclin A, and Ki67 on tissue microarray (predefined cut-offs 7th decile). In univariable analysis (high versus low) the strongest prognostic proliferation factor for 10-year distant disease-free survival was MAI (Hazard Ratio (HR)=3.3, 95% Confidence Interval (CI): 1.8-6.1), followed by PPH3, cyclin A, Ki67, and cyclin B1. A combination variable, with patients with MAI and/or cyclin A high defined as high-risk, had even stronger prognostic value (HR=4.2, 95% CI: 2.2-7). When stratifying for ER-status, MAI was a significant prognostic factor in ER-positive patients only (HR=7.0, 95% CI: 3.1-16). Stratified for histological grade, MAI added prognostic value in grade 2 (HR=7.2, 95% CI: 3.1-38) and grade 1 patients. In multivariable analysis including HER2, age, adjuvant medical treatment, ER, and one proliferation factor at a time, only MAI (HR=2.7, 95% CI: 1.1-6.7), and cyclin A (HR=2.7, 95% CI: 1.2-6.0) remained independently prognostic. In conclusion this study confirms the strong prognostic value of all proliferation factors, especially MAI and cyclin A, in all patients, and more specifically in ER-positive patients, and patients with histological grade 2 and 1. Additionally, by combining two proliferation factors, an even stronger prognostic value may be found.
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| 7. |
- Mingrone, G., et al.
(författare)
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Insulin sensitivity depends on the route of glucose administration
- 2020
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 63, s. 1382-1395
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis The small intestine plays an important role in hepatic and whole-body insulin sensitivity, as shown by bariatric surgery. Our goal was to study whether routes and dose of glucose administration have an acute impact on insulin sensitivity. The primary endpoint of this proof-of-concept study was the difference in insulin-mediated metabolic clearance rate (MCR/I) of glucose between the oral and intravenous routes of glucose administration. Secondary endpoints were differences in insulin effect on proteolysis, ketogenesis, lipolysis and glucagon levels. Methods In this parallel cohort study, we administered multiple oral glucose loads to 23 participants (aged between 18 and 65 years) with morbid obesity and with normal or impaired glucose tolerance or type 2 diabetes. In a different session, we administered isoglycaemic intravenous glucose infusions (IGIVI) to match the plasma glucose levels observed during the oral challenges. Glucose rate of appearance (R-a) and disappearance (R-d) and endogenous glucose production (EGP) were calculated by infusing [6,6-H-2(2)]glucose with or without oral [U-C-13(6)]glucose. Plasma small polar metabolites were measured by gas chromatography and time-of-flight mass spectrometry. Lipids were measured by ultra-HPLC and quadrupole mass spectrometry. Glucagon-like peptide-1, insulin, C-peptide and glucagon were also measured. Participants, caregivers, people doing measurements or examinations, and people assessing the outcomes were unblinded to group assignment. Results Glucose MCR/I was significantly higher during IGIVI than during oral glucose administration, independently of glycaemic status (12 +/- 6 for IGIVI vs 7.4 +/- 3 ml min(-1) kg(-1) per nmol/l for oral, p< 0.001 from paired t test). Insulin secretion was higher during oral administration than during IGIVI (p< 0.001). The disposition index was significantly lower during the oral procedure: 4260 +/- 1820 vs 5000 +/- 2360 (ml min(-1) kg(-1) (nmol/l)(-1) pmol/min; p = 0.005). Insulin clearance was significantly higher when glucose was infused rather than ingested (2.53 +/- 0.82 vs 2.16 +/- 0.49 l/min in intravenous and oral procedure, respectively, p = 0.006). The efficacy of insulin in inhibiting lipolysis and proteolysis was decreased after oral glucose loads. A heat map diagram showed a different pattern for the metabolites between the two routes of glucose administration. Conclusions/interpretation Our study shows that insulin sensitivity depends on the route of glucose administration, the oral route leading to increased insulin secretion and compensatory insulin resistance compared with the intravenous route. The efficacy of insulin in blocking lipolysis and protein breakdown is lower after oral glucose loads vs the intravenous route. Our findings suggest that, while the glucose-mediated incretin release is followed by an increase in insulin release, the effect of the released insulin is limited by an increase in insulin resistance.
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| 11. |
- van Schaarenburg, Rosanne A., et al.
(författare)
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Marked variability in clinical presentation and outcome of patients with C1q immunodeficiency
- 2015
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Ingår i: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411 .- 1095-9157. ; 62, s. 39-44
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Globally approximately 60 cases of C1q deficiency have been described with a high prevalence of Systemic Lupus Erythematosus (SLE). So far treatment has been guided by the clinical presentation rather than the underlying C1q deficiency. Recently, it was shown that C1q production can be restored by allogeneic hematopoietic stem cell transplantation. Current literature lacks information on disease progression and quality of life of C1q deficient persons which is of major importance to guide clinicians taking care of patients with this rare disease.Methods: We performed an international survey, of clinicians treating C1q deficient patients. A high response rate of >70% of the contacted clinicians yielded information on 45 patients with C1q deficiency of which 25 are published.Results: Follow-up data of 45 patients from 31 families was obtained for a median of 11 years after diagnosis. Of these patients 36 (80%) suffer from SLE, of which 16 suffer from SLE and infections, 5 (11%) suffer from infections only and 4 (9%) have no symptoms. In total 9 (20%) of the C1q deficient individuals had died. All except for one died before the age of 20 years. Estimated survival times suggest 20% case-fatality before the age of 20, and at least 50% of patients are expected to reach their middle ages.Conclusion: Here we report the largest phenotypic data set on C1q deficiency to date, revealing high variance; with high mortality but also a subset of patients with an excellent prognosis. Management of C1q deficiency requires a personalized approach.
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| 18. |
- Ahlin, Gustav, et al.
(författare)
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Structural requirements for drug inhibition of the liver specific human organic cation transport protein 1
- 2008
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 51:19, s. 5932-5942
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Tidskriftsartikel (refereegranskat)abstract
- The liver-specific organic cation transport protein (OCT1; SLC22A1) transports several cationic drugs including the antidiabetic drug metformin and the anticancer agents oxaliplatin and imatinib. In this study, we explored the chemical space of registered oral drugs with the aim of studying the inhibition pattern of OCT1 and of developing predictive computational models of OCT1 inhibition. In total, 191 structurally diverse compounds were examined in HEK293-OCT1 cells. The assay identified 47 novel inhibitors and confirmed 15 previously known inhibitors. The enrichment of OCT1 inhibitors was seen in several drug classes including antidepressants. High lipophilicity and a positive net charge were found to be the key physicochemical properties for OCT1 inhibition, whereas a high molecular dipole moment and many hydrogen bonds were negatively correlated to OCT1 inhibition. The data were used to generate OPLS-DA models for OCT1 inhibitors; the final model correctly predicted 82% of the inhibitors and 88% of the noninhibitors of the test set.
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| 19. |
- Ahlin, Karin, 1963-
(författare)
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Benefits of Digital Technical Information
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In our daily work life, we use a wealth of information, including a category of information produced as a part of products and their life-cycle phases, named digital technical information (DTI). Manufacturing organizations focus more often on the product than on DTI, because DTI’s impact seems almost invisible, despite its crucial role to the product and its life-cycle phases, development, production, maintenance, and destruction. Hence, the aim of this thesis is to describe DTI’s benefits and the research questions: “What are the benefits of the DTI?” and “What are the perceptions of how to measure benefits of DTI?” The thesis contains five studies related to identifying and measuring DTI’s benefits. The empirical material is based on semi-structured interviews and group interviews within five organizations and a survey among manufacturing organizations in Sweden.I used three characteristics of the DTI and two pairs of previously known benefit categories to analyse the benefits. The analysis shows that the benefits are recognized in the particular product’s life cycle phase where the DTI is published. However, the DTI continues to offer benefits in the product’s other life cycle phases. In relationship to the product, the benefits evolve from supporting an individual product to supporting more general product lines or all products and a more complex product is said to increase DTI’s benefits. DTI’s structure adds benefits as synthesized or aggregated DTI, where the DTI is synthesized or aggregated automatically or manually. The categorization predetermined benefits related to the change are less numerous than the emerging benefits. The predetermined benefits are strategic by nature, and the emerging ones are mainly used to achieve operational goals. Measuring DTI’s benefits is of importance for a formal comparison of its development and is of special interest for managers. Perceptions from the initial stages on how to measure show that to establish common interpretations among the stakeholders of the measurement process is of importance, especially when it comes to what is viewed as a benefit. The benefits are viewed as intangible by the respondents, which creates difficulties when one is evaluating, using conventional measurement methods. The only perceived way to measure is when DTI reduces co-worker’s workload and efficiency is achieved. The thesis’s contribution to academia consists of the analysis of DTI’s benefits, showing details of the relationships between the DTI and its benefits. For practice, the contributions focus on the systematic evaluation process, which can be used for further development of the DTI and comparison of the evolvement of the DTI itself and relating to other resources. One proposal for future research is to use the analysed benefits and compare various approaches to digitizing DTI, e.g. Industry 4.0. Another proposal is to list, in detail, various ways on how to measure DTI’s benefits and their usefulness. The latter can positively impact on any intangible benefits due to the general approach we have established of how to measure those benefits.
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| 20. |
- Ahlin, Sofie, 1985, et al.
(författare)
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Bile acid changes after metabolic surgery are linked to improvement in insulin sensitivity
- 2019
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 106:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Metabolic surgery is associated with a prompt improvement in insulin resistance, although the mechanism of action remains unknown. The literature on bile acid changes after metabolic surgery is conflicting, and insulin sensitivity is generally assessed by indirect methods. The aim of this study was to investigate the relationship between improvement in insulin sensitivity and concentration of circulating bile acids after biliopancreatic diversion (BPD) and Roux-en-Y gastric bypass (RYGB). Methods: This was a prospective observational study of nine patients who underwent BPD and six who had RYGB. Inclusion criteria for participation were a BMI in excess of 40 kg/m(2), no previous diagnosis of type 2 diabetes and willingness to participate. Exclusion criteria were major endocrine diseases, malignancies and liver cirrhosis. Follow-up visits were carried out after a mean(s.d.) of 185.3(72.9) days. Fasting plasma bile acids were assessed by ultra-high-performance liquid chromatography coupled with a triple quadrupole mass spectrometer, and insulin sensitivity was measured by means of a hyperinsulinaemic-euglycaemic clamp. Results: A significant increase in all bile acids, as well as an amelioration of insulin sensitivity, was observed after metabolic surgery. An increase in conjugated secondary bile acids was significantly associated with an increase in insulin sensitivity. Only the increase in glycodeoxycholic acid was significantly associated with an increase in insulin sensitivity in analysis of individual conjugated secondary bile acids. Conclusion: Glycodeoxycholic acid might drive the improved insulin sensitivity after metabolic surgery.
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| 21. |
- Ahlin, Sofie, 1985, et al.
(författare)
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Macrophage Gene Expression in Adipose Tissue is Associated with Insulin Sensitivity and Serum Lipid Levels Independent of Obesity.
- 2013
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Ingår i: Obesity (Silver Spring, Md.). - : Wiley. - 1930-739X .- 1930-7381. ; 21:12
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Obesity is linked to both increased metabolic disturbances and increased adipose tissue macrophage infiltration. However, whether macrophage infiltration directly influences human metabolism is unclear. The aim of this study was to investigate if there are obesity-independent links between adipose tissue macrophages and metabolic disturbances. Design and Methods: Expression of macrophage markers in adipose tissue was analyzed by DNA microarrays in the SOS Sib Pair study and in patients with type 2 diabetes and a BMI-matched healthy control group. Results: The expression of macrophage markers in adipose tissue was increased in obesity and associated with several metabolic and anthropometric measurements. After adjustment for BMI, the expression remained associated with insulin sensitivity, serum levels of insulin, C-peptide, high density lipoprotein cholesterol (HDL-cholesterol) and triglycerides. In addition, the expression of most macrophage markers was significantly increased in patients with type 2 diabetes compared to the control group. Conclusion: Our study shows that infiltration of macrophages in human adipose tissue, estimated by the expression of macrophage markers, is increased in subjects with obesity and diabetes and associated with insulin sensitivity and serum lipid levels independent of BMI. This indicates that adipose tissue macrophages may contribute to the development of insulin resistance and dyslipidemia.
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| 24. |
- Carson, Dean B., et al.
(författare)
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Decline, Adaptation or Transformation : New Perspectives on Demographic Change in Resource Peripheries in Australia and Sweden
- 2016
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Ingår i: Comparative Population Studies. - 1869-8980 .- 1869-8999. ; 41:3-4, s. 1-29
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Tidskriftsartikel (refereegranskat)abstract
- Many sparsely populated resource peripheries in developed countries are perceived to suffer from periods of demographic decline due to loss of employment opportunities and services, youth out-migration and population ageing. While these trends tend to apply at broad regional scales and for particular time periods, diverse patterns of demographic change may be apparent if different spatial, temporal and social scales of analysis are taken into consideration. Comparing the experiences of two case study regions in northern Sweden and inland South Australia, this paper proposes an alternative conceptual framework to the ‘discourse of decline’, which could be used to examine the nuances of demographic change within resource peripheries. The framework includes spatial scale considerations that contrast broader regional demographic patterns with the experiences of sub-regions and individual settlements. It also includes temporal scale aspects, examining demographic change over different time periods to understand the pace, duration and frequency of population growth and decline. The framework finally includes social unit considerations, emphasising that demographic change affects different social groups in different ways. The results of the case studies suggest that considering demographic change as adaptation or transformation rather than decline may be more useful for identifying new – and qualitatively different – demographic pathways that emerge over time.
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