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- Mingardo, E, et al.
(författare)
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A genome-wide association study with tissue transcriptomics identifies genetic drivers for classic bladder exstrophy
- 2022
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Ingår i: Communications biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1, s. 1203-
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Tidskriftsartikel (refereegranskat)abstract
- Classic bladder exstrophy represents the most severe end of all human congenital anomalies of the kidney and urinary tract and is associated with bladder cancer susceptibility. Previous genetic studies identified one locus to be involved in classic bladder exstrophy, but were limited to a restrict number of cohort. Here we show the largest classic bladder exstrophy genome-wide association analysis to date where we identify eight genome-wide significant loci, seven of which are novel. In these regions reside ten coding and four non-coding genes. Among the coding genes is EFNA1, strongly expressed in mouse embryonic genital tubercle, urethra, and primitive bladder. Re-sequence of EFNA1 in the investigated classic bladder exstrophy cohort of our study displays an enrichment of rare protein altering variants. We show that all coding genes are expressed and/or significantly regulated in both mouse and human embryonic developmental bladder stages. Furthermore, nine of the coding genes residing in the regions of genome-wide significance are differentially expressed in bladder cancers. Our data suggest genetic drivers for classic bladder exstrophy, as well as a possible role for these drivers to relevant bladder cancer susceptibility.
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- Isacsson, G., et al.
(författare)
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Bibloc and Monobloc Oral appliances in the Treatment of Obstructive Sleep apnoea : a Multicenter, Randomized, Blinded, Parallel-Group Trial
- 2017
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Ingår i: Sleep Medicine. - : Elsevier. - 1389-9457 .- 1878-5506. ; 40:Suppl 1, s. E142-E143
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: The clinical benefit of bibloc over monobloc appliances has not been established in randomized trials treating obstructive sleep apnoea (OSA). We hypothesized that the two types of appliances are equally effective in treating moderate to severe OSA. Materials and methods: We performed a blinded, multicenter, randomized, controlled, prospective, parallel-group trial including patients aged 18 years or older who had moderate-to-severe OSA. Patients were randomly assigned to receive either a bibloc or a monobloc appliance with the intention to protrude the mandible 75% of the individual maximal protrusion capacity. At baseline a one-night respiratory polygraphy was done without any respiratory support. The polygraphy was iterated with the appliance in place at a 6-week follow-up. The primary outcome was the absolute change in the apnoea-hypopnea-index (AHI) from baseline to the 6-week follow-up, analysed in the per-protocol population. All patients who received an appliance were included in the safety analysis. This trial is registered with ClinicalTrials.gov, number NCT02148510, and approved by Uppsala Regional Ethical Review Board, Sweden (#2014/021). Results: We recruited patients from three dental specialist clinics in Sweden; enrolment of 302 patients was done between March 2014 and April 2016; 146 randomized to bibloc and 156 to monobloc appliance. Twenty-three patients in the bibloc group and 17 in the monobloc group were withdrawn due to reasons like appliance could not be fitted, lack of compliance, adverse events or non-valid follow-up polygraphy i.e. a per-protocol group of 123 bibloc and 139 monobloc treated patients. The mean change of AHI from baseline to 6 weeks of treatment was -13.8 (95% CI -16.1 to -11.5; p < 0.001) in the bibloc group and -12.5 (95% CI -14.8 to -10.3; p < 0.001) in the monobloc group. The mean difference was not significant between the groups (-1.3 (95% CI -4.5 to 1.9). The most common adverse event in the orofacial region was upper airway infection followed by complains from various parts of the mouth, jaws and teeth. Conclusions: Bibloc and monobloc appliance treatment was equal in their effects in treating OSA as measured by at home polygraphic respiratory measures and the appliances were associated with a similar degree of adverse events. Acknowledgements: Funding from Uppsala-Örebro Regional Research Council and Vastmanland County Council, Sweden.
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- Ayoglu, Burcu, et al.
(författare)
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Anoctamin 2 identified as an autoimmune target in multiple sclerosis
- 2016
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences of the USA. - 0027-8424 .- 1091-6490. ; 113:8, s. 2188-2193
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system and also is regarded as an autoimmune condition. However, the antigenic targets of the autoimmune response in MS have not yet been deciphered. In an effort to mine the autoantibody repertoire within MS, we profiled 2,169 plasma samples from MS cases and population-based controls using bead arrays built with 384 human protein fragments selected from an initial screening with 11,520 antigens. Our data revealed prominently increased autoantibody reactivity against the chloride-channel protein anoctamin 2 (ANO2) in MS cases compared with controls. This finding was corroborated in independent assays with alternative protein constructs and by epitope mapping with peptides covering the identified region of ANO2. Additionally, we found a strong interaction between the presence of ANO2 autoantibodies and the HLA complex MS-associated DRB1*15 allele, reinforcing a potential role for ANO2 autoreactivity in MS etiopathogenesis. Furthermore, immunofluorescence analysis in human MS brain tissue showed ANO2 expression as small cellular aggregates near and inside MS lesions. Thus this study represents one of the largest efforts to characterize the autoantibody repertoire within MS. The findings presented here demonstrate that an ANO2 autoimmune subphenotype may exist in MS and lay the groundwork for further studies focusing on the pathogenic role of ANO2 autoantibodies in MS.
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- Isacsson, Göran, et al.
(författare)
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Use of bibloc and monobloc oral appliances in obstructive sleep apnoea : a multicentre, randomized, blinded, parallel-group equivalence trial
- 2019
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Ingår i: European Journal of Orthodontics. - : Oxford University Press. - 0141-5387 .- 1460-2210. ; 41:1, s. 80-88
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Tidskriftsartikel (refereegranskat)abstract
- Background: The clinical benefit of bibloc over monobloc appliances in treating obstructive sleep apnoea (OSA) has not been evaluated in randomized trials. We hypothesized that the two types of appliances are equally effective in treating OSA.Objective: To compare the efficacy of monobloc versus bibloc appliances in a short-term perspective.Patients and methods: In this multicentre, randomized, blinded, controlled, parallel-group equivalence trial, patients with OSA were randomly assigned to use either a bibloc or a monobloc appliance. One-night respiratory polygraphy without respiratory support was performed at baseline, and participants were re-examined with the appliance in place at short-term follow-up. The primary outcome was the change in the apnoea-hypopnea index (AHI). An independent person prepared a randomization list and sealed envelopes. Evaluating dentist and the biomedical analysts who evaluated the polygraphy were blinded to the choice of therapy.Results: Of 302 patients, 146 were randomly assigned to use the bibloc and 156 the monobloc device; 123 and 139 patients, respectively, were analysed as per protocol. The mean changes in AHI were -13.8 (95% confidence interval -16.1 to -11.5) in the bibloc group and -12.5 (-14.8 to -10.3) in the monobloc group. The difference of -1.3 (-4.5 to 1.9) was significant within the equivalence interval (P = 0.011; the greater of the two P values) and was confirmed by the intention-to-treat analysis (P = 0.001). The adverse events were of mild character and were experienced by similar percentages of patients in both groups (39 and 40 per cent for the bibloc and monobloc group, respectively).Limitations: The study shows short-term results with a median time from commencing treatment to the evaluation visit of 56 days and long-term data on efficacy and harm are needed to be fully conclusive.Conclusion: In a short-term perspective, both appliances were equivalent in terms of their positive effects for treating OSA and caused adverse events of similar magnitude.Trial registration: Registered with ClinicalTrials.gov (#NCT02148510).
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