| 1. |
- Aranda-Guillén, Maribel, et al.
(författare)
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A polygenic risk score to help discriminate primary adrenal insufficiency of different etiologies.
- 2023
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Ingår i: Journal of internal medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 294:1, s. 96-109
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune Addison's disease (AAD) is the most common cause of primary adrenal insufficiency (PAI). Despite its exceptionally high heritability, tools to estimate disease susceptibility in individual patients are lacking. We hypothesized that polygenic risk score (PRS) for AAD could help investigate PAI pathogenesis in pediatric patients.We here constructed and evaluated a PRS for AAD in 1223 seropositive cases and 4097 controls. To test its clinical utility, we reevaluated 18 pediatric patients, whose whole genome we also sequenced. We next explored the individual PRS in more than 120 seronegative patients with idiopathic PAI.The genetic susceptibility to AAD-quantified using PRS-was on average 1.5 standard deviations (SD) higher in patients compared with healthy controls (p<2e-16), and 1.2 SD higher in the young patients compared with the old (p=3e-4). Using the novel PRS, we searched for pediatric patients with strikingly low AAD susceptibility and identified cases of monogenic PAI, previously misdiagnosed as AAD. By stratifying seronegative adult patients by autoimmune comorbidities and disease duration we could delineate subgroups of PRS suggesting various disease etiologies.The PRS performed well for case-control differentiation and susceptibility estimation in individual patients. Remarkably, a PRS for AAD holds promise as a means to detect disease etiologies other than autoimmunity.
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| 2. |
- Eriksson, D, et al.
(författare)
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Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease
- 2016
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 595-608
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology.METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls.RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10(-15) , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex.CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.
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| 3. |
- Hallgren, Frida, et al.
(författare)
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Antibiotics in treatment of peritonsillar infection: clindamycin versus penicillin
- 2021
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Ingår i: Journal of Laryngology and Otology. - : Cambridge University Press (CUP). - 0022-2151. ; 135:1, s. 64-69
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Tidskriftsartikel (refereegranskat)abstract
- Objective This study aimed to compare antibiotic treatment with clindamycin versus penicillin V or G in terms of time to recovery and recurrence in patients with peritonsillar infection, including both peritonsillar cellulitis and peritonsillar abscess. Method This retrospective cohort study examined the records of 296 patients diagnosed with peritonsillar infection. Based on the ENT doctor's choice of antibiotics, patients were divided into clindamycin and penicillin groups. Results Mean number of days in follow up was 3.5 days in the clindamycin group and 3.4 days in the penicillin group. The recurrence rate within 2 months was 7 per cent in the clindamycin group and 4 per cent in the penicillin group. Conclusion This study found no significant differences in either recovery or recurrence between the groups. This supports the use of penicillin as a first-line treatment, considering the greater frequency of adverse effects of clindamycin shown in previous studies, as well as its profound collateral damage on the intestinal microbiota, resulting in antibiotic resistance.
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| 4. |
- Nyblom, Anna Maria, 1975, et al.
(författare)
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Exceptional overproduction of a functional human membrane protein
- 2007
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Ingår i: Protein Expression and Purification. - : Elsevier BV. - 1046-5928 .- 1096-0279. ; 56:1, s. 110-120
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Tidskriftsartikel (refereegranskat)abstract
- Eukaryotic-especially human-membrane protein overproduction remains a major challenge in biochemistry. Heterologously overproduced and purified proteins provide a starting point for further biochemical, biophysical and structural studies, and the lack of sufficient quantities of functional membrane proteins is frequently a bottleneck hindering this. Here, we report exceptionally high production levels of a correctly folded and crystallisable recombinant human integral membrane protein in its active form; human aquaporin 1 (hAQP1) has been heterologously produced in the membranes of the methylotrophic yeast Pichia pastoris. After solubilisation and a two step purification procedure, at least 90 mg hAQP1 per liter of culture is obtained. Water channel activity of this purified hAQP was verified by reconstitution into proteoliposomes and performing stopped-flow vesicle shrinkage measurements. Mass spectrometry confirmed the identity of hAQPI in crude membrane preparations, and also from purified protein reconstituted into proteoliposomes. Furthermore, crystallisation screens yielded diffraction quality crystals of untagged recombinant hAQP1. This study illustrates the power of the yeast P. pastoris as a host to produce exceptionally high yields of a functionally active, human integral membrane protein for subsequent functional and structural characterization. (c) 2007 Elsevier Inc. All rights reserved.
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| 7. |
- Sjöström, Lars, et al.
(författare)
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Swedish obese subjects (SOS). Recruitment for an intervention study and a selected description of the obese state
- 1992
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Ingår i: International Journal of Obesity. ; 19, s. 465-479
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Tidskriftsartikel (refereegranskat)abstract
- Department of Medicine, Sahlgren's Hospital, University of Göteborg, Sweden. SOS (Swedish obese subjects) is an on-going intervention trial designed to determine whether the mortality and morbidity rates among obese individuals who lose weight by surgical means (gastric banding, vertical banded gastroplasty and gastric by-pass) differ from the rates associated with conventional treatment. For this purpose, the study is recruiting a sample of obese men and women who constitute a registry of potential subjects from which the participants are drawn. Eligibility criteria for participation in the registry were: age at application 37-57 years and BMI greater than or equal to 34 kg/m2 for men and greater than or equal to 38 kg/m2 for women. Before receiving a health examination, all patients complete extensive questionnaires on current and past health status, utilization of medical care and medications, socio-economic status, psychological profiles, dietary habits, physical activity, weight history, and familial disposition to obesity. Each surgical case is matched to its optimal control in the registry, to ensure that the two groups do not differ systematically with respect to any of 18 matching variables that may affect prognosis. The first 1006 subjects included in the registry have been studied with respect to morbidity and compared with on-going population studies of men and women in Göteborg, Sweden. The relative risks of prevalent disease and symptoms associated with obesity in 50-year-old males and females respectively were 4.3 and 4.7 (dyspnoea), 14.7 and 11.8 (angina), 6.3 (myocardial infarction, males only), 2.1 and 4.5 (hypertension), 5.2 and 6.6 (diabetes), 4.6 and 26.1 (claudication) and 1.7 and 1.8 (gall bladder disease). Correspondingly, obese males and females display elevations of systolic and diastolic blood pressure, fasting glucose, insulin, triglyceride, and uric acid levels. However, total cholesterol was not increased in obese males and was in fact significantly lower in obese compared with reference women. HDL-cholesterol was lower in obese than reference men (data were not available in reference women). The rate of taking sick pensions was over twice as high in SOS obese patients than in population controls. Finally, comparison of measurements with self-reported prevalence estimates revealed a considerable amount of previously undiagnosed hypertension and diabetes in the obese subjects. These data suggest that the excess health risks associated with obesity may not be fully appreciated. PMID: 1322873 [PubMed - indexed for MEDLINE]
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| 8. |
- Stirbys, Simonas, 1993, et al.
(författare)
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Privacy-Preserving Location-Proximity for Mobile Apps
- 2017
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Ingår i: 25th Euromicro International Conference on Parallel, Distributed and Network-Based Processing (PDP). - New York : IEEE. - 1066-6192. - 9781509060580
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Konferensbidrag (refereegranskat)abstract
- Location Based Services (LBS) have seen alarming privacy breaches in recent years. While there has been much recent progress by the research community on developing privacy-enhancing mechanisms for LBS, their evaluation has been often focused on the privacy guarantees, while the question of whether these mechanisms can be adopted by practical LBS applications has received limited attention. This paper studies the applicability of Privacy-Preserving Location Proximity (PPLP) protocols in the setting of mobile apps. We categorize popular location social apps and analyze the tradeoffs of privacy and functionality with respect to PPLP enhancements. To investigate the practical performance trade-offs, we present an in-depth case study of an Android application that implements InnerCircle, a state-of-the-art protocol for privacy-preserving location proximity. This study indicates that the performance of the privacy-preserving application for coarse-grained precision is comparable to real applications with the same feature set.
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