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- Paulussen, Aimee D C, et al.
(författare)
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Rare novel variants in the ZIC3 gene cause X-linked heterotaxy
- 2016
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 24:12, s. 1783-1791
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Tidskriftsartikel (refereegranskat)abstract
- Variants in the ZIC3 gene are rare, but have demonstrated their profound clinical significance in X-linked heterotaxy, affecting in particular male patients with abnormal arrangement of thoracic and visceral organs. Several reports have shown relevance of ZIC3 gene variants in both familial and sporadic cases and with a predominance of mutations detected in zinc-finger domains. No studies so far have assessed the functional consequences of ZIC3 variants in an in vivo model organism. A study population of 348 patients collected over more than 10 years with a large variety of congenital heart disease including heterotaxy was screened for variants in the ZIC3 gene. Functional effects of three variants were assessed both in vitro and in vivo in the zebrafish. We identified six novel pathogenic variants (1,7%), all in either male patients with heterotaxy (n=5) or a female patient with multiple male deaths due to heterotaxy in the family (n=1). All variants were located within the zinc-finger domains or leading to a truncation before these domains. Truncating variants showed abnormal trafficking of mutated ZIC3 proteins, whereas the missense variant showed normal trafficking. Overexpression of wild-type and mutated ZIC protein in zebrafish showed full non-functionality of the two frame-shift variants and partial activity of the missense variant compared with wild-type, further underscoring the pathogenic character of these variants. Concluding, we greatly expanded the number of causative variants in ZIC3 and delineated the functional effects of three variants using in vitro and in vivo model systems.
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- Birchenough, George M. H., et al.
(författare)
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Muc2-dependent microbial colonization of the jejunal mucus layer is diet sensitive and confers local resistance to enteric pathogen infection
- 2023
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Ingår i: Cell Reports. - Cambridge : Elsevier BV. - 2211-1247. ; 42:2
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Tidskriftsartikel (refereegranskat)abstract
- Intestinal mucus barriers normally prevent microbial infections but are sensitive to diet-dependent changes in the luminal environment. Here we demonstrate that mice fed a Western-style diet (WSD) suffer regiospe-cific failure of the mucus barrier in the small intestinal jejunum caused by diet-induced mucus aggregation. Mucus barrier disruption due to either WSD exposure or chromosomal Muc2 deletion results in collapse of the commensal jejunal microbiota, which in turn sensitizes mice to atypical jejunal colonization by the enteric pathogen Citrobacter rodentium. We illustrate the jejunal mucus layer as a microbial habitat, and link the re-giospecific mucus dependency of the microbiota to distinctive properties of the jejunal niche. Together, our data demonstrate a symbiotic mucus-microbiota relationship that normally prevents jejunal pathogen colo-nization, but is highly sensitive to disruption by exposure to a WSD.
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- Colebatch, Alexandra N., et al.
(författare)
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EULAR recommendations for the use of imaging of the joints in the clinical management of rheumatoid arthritis
- 2013
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 72:6, s. 804-814
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Forskningsöversikt (refereegranskat)abstract
- Objective To develop evidence-based recommendations on the use of imaging of the joints in the clinical management of rheumatoid arthritis (RA). Methods The task force comprised an expert group of rheumatologists, radiologists, methodologists and experienced rheumatology practitioners from 13 countries. Thirteen key questions on the role of imaging in RA were generated using a process of discussion and consensus. Imaging modalities included were conventional radiography, ultrasound, MRI, CT, dual-emission x-ray absorptiometry, digital x-ray radiogrammetry, scintigraphy and positron emission tomography. Research evidence was searched systematically for each question using MEDLINE, EMBASE and Cochrane CENTRAL. The experts used the evidence obtained from the relevant studies to develop a set of 10 recommendations. The strength of recommendation was assessed using a visual analogue scale. Results A total of 6888 references was identified from the search process, from which 199 studies were included in the systematic review. Ten recommendations were produced encompassing the role of imaging in making a diagnosis of RA, detecting inflammation and damage, predicting outcome and response to treatment, monitoring disease activity, progression and remission. The strength of recommendation for each proposition varied according to both the research evidence and expert opinion. Conclusions Ten key recommendations for the role of imaging in the management of RA were developed using research-based evidence and expert opinion.
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- Kaarre, Janina, 1996, et al.
(författare)
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Metal interference screw fixation combinations show high revision rates in primary hamstring tendon ACL reconstruction
- 2024
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Ingår i: BMC Musculoskeletal Disorders. - 1471-2474. ; 25:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Different fixation methods in anterior cruciate ligament reconstruction (ACLR) have been associated with different revision rates, specifically in the early postoperative period. However, most previous research has either grouped together different fixation types or evaluated femoral-sided fixation or tibial-sided fixation separately. Therefore, the purpose of this study was to determine ACL revision rates for specific combinations of femoral and tibial fixation methods within 2 years of primary hamstring tendon autograft ACLR based on data from the Swedish National Knee Ligament Registry (SNKLR). Methods: Patients that underwent primary hamstring tendon autograft ACLR between 2005 and 2018 in the SNKLR were included. The collected data included patient characteristics (age, sex, body mass index [BMI]), activity at time of injury, surgical information (concomitant injuries, time from injury to surgery, fixation types at the femur and tibia), and subsequent revision ACLR. Revision rate within 2 years of the index procedure was chosen, as ACLR fixation is most likely to contribute to ACLR revision within the first 2 years, during graft maturation. Results: Of the 23,238 included patients undergoing primary hamstring ACLR, 581 (2.5%) underwent revision ACLR within 2 years of the index procedure. Among the combinations used for > 300 patients, the femoral metal interference screw/tibial metal interference screw fixation combination had the highest revision rate followed by metal interference screw/resorbable screw and Endobutton/AO screw fixation combinations, with respective revision rates of 4.0, 3.0, and 3.0%. The lowest revision rate within 2 years of ACLR was found in the Endobutton/metal interference screw with backup Osteosuture fixation combination, used in 433 cases, with a failure rate of 0.9%. Conclusion: Different early ACL revision rates were found across different combinations of femoral and tibial fixation devices within 2 years of primary hamstring tendon autograft ACLR. Metal interference screw fixation, particularly when performed on both the femoral and tibial sides, most frequently resulted in revision ACLR. These findings may be helpful for surgeons in selecting appropriate fixation devices for hamstring ACLR. Level of evidence: IV.
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- Koens, Lisette H, et al.
(författare)
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A Screening Tool to Quickly Identify Movement Disorders in Patients with Inborn Errors of Metabolism
- 2023
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 38:4, s. 646-653
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Movement disorders are frequent in patients with inborn errors of metabolism (IEMs) but poorly recognized, particularly by nonmovement disorder specialists. We propose an easy-to-use clinical screening tool to help recognize movement disorders.OBJECTIVE: The aim is to develop a user-friendly rapid screening tool for nonmovement disorder specialists to detect moderate and severe movement disorders in patients aged ≥4 years with IEMs.METHODS: Videos of 55 patients with different IEMs were scored by experienced movement disorder specialists (n = 12). Inter-rater agreements were determined on the presence and subtype of the movement disorder. Based on ranking and consensus, items were chosen to be incorporated into the screening tool.RESULTS: A movement disorder was rated as present in 80% of the patients, with a moderate inter-rater agreement (κ =0.420, P < 0.001) on the presence of a movement disorder. When considering only moderate and severe movement disorders, the inter-rater agreement increased to almost perfect (κ = 0.900, P < 0.001). Dystonia was most frequently scored (27.3%) as the dominant phenotype. Treatment was mainly suggested for patients with moderate or severe movement disorders. Walking, observations of the arms, and drawing a spiral were found to be the most informative tasks and were included in the screening tool.CONCLUSIONS: We designed a screening tool to recognize movement disorders in patients with IEMs. We propose that this screening tool can contribute to select patients who should be referred to a movement disorder specialist for further evaluation and, if necessary, treatment of the movement disorder. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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- Leffler, Jonatan, et al.
(författare)
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Decreased Neutrophil Extracellular Trap Degradation in Shiga Toxin-Associated Haemolytic Uraemic Syndrome
- 2017
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Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 9:1, s. 12-21
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neutrophil extracellular traps (NETs) can stimulate thrombosis, and their degradation is decreased in several autoimmune disorders. It was recently reported that some patients with haemolytic uraemic syndrome (HUS) also fail to degrade NETs and that neutrophils from Shiga toxin-associated HUS are primed to form NETs. Method: We used a well-characterized cohort of 74 thrombotic microangiopathy (TMA) patients, with a subset also providing follow-up samples, and 112 age-matched controls to investigate NET degradation and serum nuclease activity in TMA before, during and after treatment. Results: We identified that in the cohort of TMA patients, 50% of patients with Shiga toxin-associated HUS displayed a decreased ability to degrade NETs. NET degradation correlated with serum nuclease activity, but not with autoantibodies against double-stranded DNA, which has been previously observed in some autoimmune disorders. Further, NET degradation negatively correlated with serum creatinine levels, suggesting that kidney function was negatively impacted by the low NET degradation ability. Conclusions: We revealed that decreased NET degradation is a common feature of Shiga toxin-associated HUS and that it is associated with decreased kidney function in these patients. It remains to be clarified whether improving NET degradation would be beneficial for the patient.
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- Nazzal, E. M., et al.
(författare)
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Considerations of the Posterior Tibial Slope in Anterior Cruciate Ligament Reconstruction: a Scoping Review
- 2022
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Ingår i: Current Reviews in Musculoskeletal Medicine. - : Springer Science and Business Media LLC. - 1935-973X .- 1935-9748. ; 15, s. 291-299
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Tidskriftsartikel (refereegranskat)abstract
- Purpose of Review The significance of posterior tibial slope (PTS) in the setting of anterior cruciate ligament (ACL) injury and reconstruction has been increasingly recognized in recent years. The purpose of this article is to review the biomechanical and clinical studies of PTS in conjunction with ACL injuries, providing an evidence-based approach for the evaluation and management of this patient population. Recent Findings Several biomechanical and clinical studies suggest that PTS > 12 degrees may be considered with increased strain on the native ACL fibers (or reconstructed graft) and greater anterior tibial translation, predisposing patients to a recurrent ACL injury. The increased rates of ACL injury and graft failure seen in those with increased PTS have garnered attention to diagnose and surgically address increased PTS in the revision ACL setting; however, the role of a slope-reducing high tibial osteotomy (HTO) in primary ACL reconstruction (ACL-R) has yet to be defined. Various HTO techniques to decrease PTS during revision ACL-R have demonstrated promising outcomes, though conclusions are limited by the multifactorial nature of revision surgery and concomitant procedures performed. Recent evidence suggests that increased PTS is a risk factor for failure following ACL-R, which may be mitigated by a slope-reducing HTO. Further investigation is needed to elucidate abnormal PTS values and to determine appropriate indications for a slope-reducing HTO in primary ACL-R.
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