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| 7. |
- Astell, A. J., et al.
(författare)
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INLIFE - Independent Living Support Functions for the Elderly: Technology and Pilot Overview
- 2018
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Ingår i: INTELLIGENT ENVIRONMENTS 2018. - 9781614998747 - 9781614998730 ; , s. 526-535
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- In this paper, we present the European H2020 project INLIFE (INdependent LIving support Functions for the Elderly). The project brought together 20 partners from nine countries with the goal of integrating into a common ICT platform a range of technologies intended to assist community-dwelling older people with cognitive impairment. The majority of technologies existed prior to INLIFE and a key goal was to bring them together in one place along with a number of new applications to provide a comprehensive set of services. The range of INLIFE services fell into four broad areas: Independent Living Support, Travel Support, Socialization and Communication Support and Caregiver Support. These included security applications, services to facilitate interactions with formal and informal caregivers, multilingual conversation support, web-based physical exercises, teleconsultations, and support for transport navigation. In total, over 2900 people participated in the project; they included elderly adults with cognitive impairment, informal caregivers, healthcare professionals, and other stakeholders. The aim of the study was to assess whether there was improvement/stabilization of cognitive/emotional/physical functioning, as well as overall well-being and quality of life of those using the INLIFE services, and to assess user acceptance of the platform and individual services. The results confirm there is a huge interest and appetite for technological services to support older adults living with cognitive impairment in the community. Different services attracted different amounts of use and evaluation with some proving extremely popular while others less so. The findings provide useful information on the ways in which older adults and their families, health and social care services and other stakeholders wish to access technological services, what sort of services they are seeking, what sort of support they need to access services, and how these services might be funded.
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| 8. |
- Barosi, G, et al.
(författare)
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Clinical end points for drug treatment trials in BCR-ABL1-negative classic myeloproliferative neoplasms : consensus statements from European LeukemiaNET (ELN) and Internation Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)
- 2015
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 29:1, s. 20-26
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of somatic mutations, primarily JAK2V617F and CALR, in classic BCR-ABL1-negative myeloproliferative neoplasms (MPNs) has generated interest in the development of molecularly targeted therapies, whose accurate assessment requires a standardized framework. A working group, comprised of members from European LeukemiaNet (ELN) and International Working Group for MPN Research and Treatment (IWG-MRT), prepared consensus-based recommendations regarding trial design, patient selection and definition of relevant end points. Accordingly, a response able to capture the long-term effect of the drug should be selected as the end point of phase II trials aimed at developing new drugs for MPNs. A time-to-event, such as overall survival, or progression-free survival or both, as co-primary end points, should measure efficacy in phase III studies. New drugs should be tested for preventing disease progression in myelofibrosis patients with early disease in randomized studies, and a time to event, such as progression-free or event-free survival should be the primary end point. Phase III trials aimed at preventing vascular events in polycythemia vera and essential thrombocythemia should be based on a selection of the target population based on new prognostic factors, including JAK2 mutation. In conclusion, we recommended a format for clinical trials in MPNs that facilitates communication between academic investigators, regulatory agencies and drug companies.
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| 9. |
- Baunsgaard, C. B., et al.
(författare)
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EXOSKELETON GAIT TRAINING AFTER SPINAL CORD INJURY: AN EXPLORATORY STUDY ON SECONDARY HEALTH CONDITIONS
- 2018
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Ingår i: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977 .- 1651-2081. ; 50:9, s. 806-813
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To explore changes in pain, spasticity, range of motion, activities of daily living, bowel and lower urinary tract function and quality of life of individuals with spinal cord injury following robotic exoskeleton gait training. Methods: Three training sessions per week for 8 weeks using an Ekso GT robotic exoskeleton (Ekso Bionics). Included were individuals with recent (<1 year) or chronic (>1 year) injury, paraplegia and tetraplegia, complete and incomplete injury, men and women. Results: Fifty-two participants completed the training protocol. Pain was reported by 52% of participants during the week prior to training and 17% during training, but no change occurred longitudinally. Spasticity decreased after a training session compared with before the training session (p< 0.001), but not longitudinally. Chronically injured participants increased Spinal Cord Independence Measure (SCIM III) from 73 to 74 (p= 0.008) and improved life satisfaction (p= 0.036) over 8 weeks of training. Recently injured participants increased SCIM III from 62 to 70 (p<0.001), but no significant change occurred in life satisfaction. Range of motion, bowel and lower urinary function did not change over time. Conclusion: Training seemed not to provoke new pain. Spasticity decreased after a single training session. SCIM III and quality of life increased longitudinally for subsets of participants.
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| 10. |
- Brundin, L., et al.
(författare)
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An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation
- 2016
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Emerging evidence suggests that inflammation has a key role in depression and suicidal behavior. The kynurenine pathway is involved in neuroinflammation and regulates glutamate neurotransmission. In the cerebrospinal fluid (CSF) of suicidal patients, levels of inflammatory cytokines and the kynurenine metabolite quinolinic acid (QUIN), an N-methyl-D-aspartate receptor agonist, are increased. The enzyme amino-beta-carboxymuconate-semialdehyde-decarboxylase (ACMSD) limits QUIN formation by competitive production of the neuroprotective metabolite picolinic acid (PIC). Therefore, decreased ACMSD activity can lead to excess QUIN. We tested the hypothesis that deficient ACMSD activity underlies suicidal behavior. We measured PIC and QUIN in CSF and plasma samples from 137 patients exhibiting suicidal behavior and 71 healthy controls. We used DSM-IV and the Montgomery-Asberg Depression Rating Scale and Suicide Assessment Scale to assess behavioral changes. Finally, we genotyped ACMSD tag single nucleotide polymorphisms (SNPs) in 77 of the patients and 150 population-based controls. Suicide attempters had reduced PIC and a decreased PIC/QUIN ratio in both CSF (P<0.001) and blood (P=0.001 and P<0.01, respectively). The reductions of PIC in CSF were sustained over 2 years after the suicide attempt based on repeated measures. The minor C allele of the ACMSD SNP rs2121337 was more prevalent in suicide attempters and associated with increased CSF QUIN. Taken together, our data suggest that increased QUIN levels may result from reduced activity of ACMSD in suicidal subjects. We conclude that measures of kynurenine metabolites can be explored as biomarkers of suicide risk, and that ACMSD is a potential therapeutic target in suicidal behavior.
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| 11. |
- Chahla, J., et al.
(författare)
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Posterolateral corner of the knee: an expert consensus statement on diagnosis, classification, treatment, and rehabilitation
- 2019
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Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 27:8, s. 2520-2529
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Tidskriftsartikel (refereegranskat)abstract
- PurposeTo develop a statement on the diagnosis, classification, treatment, and rehabilitation concepts of posterolateral corner (PLC) injuries of the knee using a modified Delphi technique.MethodsA working group of three individuals generated a list of statements relating to the diagnosis, classification, treatment, and rehabilitation of PLC injuries to form the basis of an initial survey for rating by an international group of experts. The PLC expert group (composed of 27 experts throughout the world) was surveyed on three occasions to establish consensus on the inclusion/exclusion of each item. In addition to rating agreement, experts were invited to propose further items for inclusion or to suggest modifications of existing items at each round. Pre-defined criteria were used to refine item lists after each survey. Statements reaching consensus in round three were included within the final consensus document.ResultsTwenty-seven experts (100% response rate) completed three rounds of surveys. After three rounds, 29 items achieved consensus with over 75% agreement and less than 5% disagreement. Consensus was reached in 92% of the statements relating to diagnosis of PLC injuries, 100% relating to classification, 70% relating to treatment and in 88% of items relating to rehabilitation statements, with an overall consensus of 81%.ConclusionsThis study has established a consensus statement relating to the diagnosis, classification, treatment, and rehabilitation of PLC injuries. Further research is needed to develop updated classification systems, and better understand the role of non-invasive and minimally invasive approaches along with standardized rehabilitation protocols.Level of evidenceConsensus of expert opinion, Level V.
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| 12. |
- Geyer, Holly L., et al.
(författare)
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Associations between gender, disease features and symptom burden in patients with myeloproliferative neoplasms : an analysis by the MPN QOL International Working Group
- 2017
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 102:1, s. 85-93
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Tidskriftsartikel (refereegranskat)abstract
- The myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia and myelofibrosis, are distinguished by their debilitating symptom profiles, life-threatening complications and profound impact on quality of life. The role gender plays in the symptomatology of myeloproliferative neoplasms remains under-investigated. In this study we evaluated how gender relates to patients' characteristics, disease complications and overall symptom expression. A total of 2,006 patients (polycythemia vera=711, essential thrombocythemia=830, myelofibrosis=460, unknown=5) were prospectively evaluated, with patients completing the Myeloproliferative Neoplasm-Symptom Assessment Form and Brief Fatigue Inventory Patient Reported Outcome tools. Information on the individual patients' characteristics, disease complications and laboratory data was collected. Consistent with known literature, most female patients were more likely to have essential thrombocythemia (48.6% versus 33.0%; P<0.001) and most male patients were more likely to have polycythemia vera (41.8% versus 30.3%; P<0.001). The rate of thrombocytopenia was higher among males than females (13.9% versus 8.2%; P<0.001) and males also had greater red-blood cell transfusion requirements (7.3% versus 4.9%; P=0.02) with shorter mean disease duration (6.4 versus 7.2 years, P=0.03). Despite there being no statistical differences in risk scores, receipt of most therapies or prior complications (hemorrhage, thrombosis), females had more severe and more frequent symptoms for most individual symptoms, along with overall total symptom score (22.8 versus 20.3; P<0.001). Females had particularly high scores for abdominal-related symptoms (abdominal pain/discomfort) and microvascular symptoms (headache, fatigue, insomnia, concentration difficulties, dizziness; all P<0.01). Despite complaining of more severe symptom burden, females had similar quality of life scores to those of males. The results of this study suggest that gender contributes to the heterogeneity of myeloproliferative neoplasms by influencing phenotypic profiles and symptom expression.
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| 13. |
- Hulet, C., et al.
(författare)
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The use of allograft tendons in primary ACL reconstruction
- 2019
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Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 27:6, s. 1754-1770
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Graft choice in primary anterior cruciate ligament (ACL) reconstruction remains controversial. The use of allograft has risen exponentially in recent years with the attraction of absent donor site morbidity, reduced surgical time and reliable graft size. However, the published evidence examining their clinical effectiveness over autograft tendons has been unclear. The aim of this paper is to provide a current review of the clinical evidence available to help guide surgeons through the decision-making process for the use of allografts in primary ACL reconstruction. Methods The literature in relation to allograft healing, storage, sterilisation, differences in surgical technique and rehabilitation have been reviewed in addition to recent comparative studies and all clinical systematic reviews and meta-analyses. Results Early reviews have indicated a higher risk of failure with allografts due to association with irradiation for sterilisation and where rehabilitation programs and post-operative loading may ignore the slower incorporation of allografts. More recent analysis indicates a similar low failure rate for allograft and autograft methods of reconstruction when using non-irradiated allografts that have not undergone chemically processing and where rehabilitation has been slower. However, inferior outcomes with allografts have been reported in young (<25years) highly active patients, and also when irradiated or chemically processed grafts are used. Conclusion When considering use of allografts in primary ACL reconstruction, use of irradiation, chemical processing and rehabilitation programs suited to autograft are important negative factors. Allografts, when used for primary ACL reconstruction, should be fresh frozen and non-irradiated. Quantification of the risk of use of allograft in the young requires further evaluation.
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| 14. |
- Lazarides, A. L., et al.
(författare)
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Advanced Patellar Tendinopathy Is Associated With Increased Rates of Bone-Patellar Tendon-Bone Autograft Failure at Early Follow-up After Anterior Cruciate Ligament Reconstruction
- 2018
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Ingår i: Orthopaedic Journal of Sports Medicine. - : SAGE Publications. - 2325-9671. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Revision anterior cruciate ligament (ACL) reconstruction can be potentially devastating for a patient. As such, it is important to identify prognostic factors that place patients at an increased risk for graft failure. There are no data on the effects of patellar tendinopathy on failure of ACL reconstruction when using a bone-patellar tendon-bone (BPTB) autograft. Purpose/Hypothesis: The purpose of this study was to investigate the association of patellar tendinopathy with the risk of graft failure in primary ACL reconstruction when using a BPTB autograft. The hypothesis was that patellar tendinopathy would result in higher rates of graft failure when using a BPTB autograft for primary ACL reconstruction. Study Design: Cohort study; Level of evidence, 3. Methods: All patients undergoing ACL reconstruction at a single institution from 2005 to 2015 were examined. A total of 168 patients undergoing primary ACL reconstruction with a BPTB autograft were identified. Patients' magnetic resonance imaging scans were reviewed for the presence and grade of patellar tendinopathy by 2 musculoskeletal fellowship-trained radiologists; both were blinded to the aim of the study, patient demographics, surgical details, and outcomes. Patients were divided into 2 groups: failure (defined as presence of symptomatic laxity or graft insufficiency) and success of the ACL graft. Statistical analyses were run to examine the association of patellar tendinopathy with failure of ACL reconstruction using a BPTB autograft. Results: At a mean follow-up of 18 months, there were 7 (4.2%) patients with graft failure. Moderate or severe patellar tendinopathy was associated with ACL graft failure (P = .011). Age, sex, and side of reconstruction were not associated with the risk of graft failure, although the majority of patients who failed were younger than 20 years. The use of patellar tendons with moderate to severe tendinopathy was associated with a relative risk of ruptures of 6.1 (95% CI, 1.37-27.34) as compared with autograft tendons without tendinopathy. Conclusion: Moderate or severe patellar tendinopathy significantly increases the risk of graft failure when using a BPTB autograft for primary ACL reconstruction. Patellar tendinopathy should be considered when determining the optimal graft choice for patients undergoing primary ACL reconstruction with autograft tendons.
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| 16. |
- Nordén, Rickard, 1977, et al.
(författare)
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Recombinant Glycoprotein E of Varicella Zoster Virus Contains Glycan-Peptide Motifs That Modulate B Cell Epitopes into Discrete Immunological Signatures
- 2019
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067. ; 20:4
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Tidskriftsartikel (refereegranskat)abstract
- A recombinant subunit vaccine (Shingrix((R))) was recently licensed for use against herpes zoster. This vaccine is based on glycoprotein E (gE) of varicella zoster virus (VZV), the most abundantly expressed protein of VZV, harboring sites for N- and O-linked glycosylation. The subunit vaccine elicits stronger virus-specific CD4+ T cell response as well as antibody B cell response to gE, compared to the currently used live attenuated vaccine (Zostavax((R))). This situation is at variance with the current notion since a live vaccine, causing an active virus infection, should be far more efficient than a subunit vaccine based on only one single viral glycoprotein. We previously found gE to be heavily glycosylated, not least by numerous clustered O-linked glycans, when it was produced in human fibroblasts. However, in contrast to Zostavax((R)), which is produced in fibroblasts, the recombinant gE of Shingrix((R)) is expressed in Chinese hamster ovary (CHO) cells. Hence, the glycan occupancy and glycan structures of gE may differ considerably between the two vaccine types. Here, we aimed at (i) defining the glycan structures and positions of recombinant gE and (ii) identifying possible features of the recombinant gE O-glycosylation pattern contributing to the vaccine efficacy of Shingrix((R)). Firstly, recombinant gE produced in CHO cells (Shingrix situation) is more scarcely decorated by O-linked glycans than gE from human fibroblasts (Zostavax situation), with respect to glycan site occupancy. Secondly, screening of immunodominant B cell epitopes of gE, using a synthetic peptide library against serum samples from VZV-seropositive individuals, revealed that the O-linked glycan signature promoted binding of IgG antibodies via a decreased number of interfering O-linked glycans, but also via specific O-linked glycans enhancing antibody binding. These findings may, in part, explain the higher protective efficacy of Shingrix((R)), and can also be of relevance for development of subunit vaccines to other enveloped viruses.
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| 19. |
- Persson, M., et al.
(författare)
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The Better Diabetes Diagnosis (BDD) study – A review of a nationwide prospective cohort study in Sweden
- 2018
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 0168-8227 .- 1872-8227. ; 140, s. 236-244
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Forskningsöversikt (refereegranskat)abstract
- The incidence of type 1 diabetes (T1D) in Sweden is one of the highest in the world. However, the possibility of other types of diabetes must also be considered. In addition, individuals with T1D constitute a heterogeneous group. A precise classification of diabetes is a prerequisite for optimal outcome. For precise classification, knowledge on the distribution of genetic factors, biochemical markers and clinical features in individuals with new onset of diabetes is needed. The Better Diabetes Diagnosis (BDD), is a nationwide study in Sweden with the primary aim to facilitate a more precise classification and diagnosis of diabetes in order to enable the most adequate treatment for each patient. Secondary aims include identification of risk factors for diabetes-related co-morbidities. Since 2005, data on almost all children and adolescents with newly diagnosed diabetes in Sweden are prospectively collected and including heredity of diabetes, clinical symptoms, levels of C peptide, genetic analyses and detection of autoantibodies. Since 2011, analyses of HLA profile, autoantibodies and C peptide levels are part of clinical routine in Sweden for all pediatric patients with suspected diagnosis of diabetes. In this review, we present the methods and main results of the BDD study so far and discuss future aspects.
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| 20. |
- Pramling, Niklas, 1973, et al.
(författare)
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The Letter Thief: From Playing to Teaching to Learning to Playing
- 2019
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Ingår i: Play-Responsive Teaching in Early Childhood Education. - Cham : Springer International Publishing. - 2468-8746.
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- In this chapter, we show how a learning content can be introduced in a child-initiated play frame, without interrupting the play. The chapter therefore gives an example of how what is sometimes referred to as academic content can be promoted through such activity. The analysis clarifies how reading and graphical symbols become structuring resources in children’s play. A real-world problem (as is) is introduced and managed within the fictional realm of play (as if). © 2019, The Author(s).
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| 22. |
- Alentorn-Geli, E., et al.
(författare)
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The Association of Recreational and Competitive Running With Hip and Knee Osteoarthritis: A Systematic Review and Meta-analysis
- 2017
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Ingår i: Journal of Orthopaedic & Sports Physical Therapy. - : Journal of Orthopaedic & Sports Physical Therapy (JOSPT). - 0190-6011 .- 1938-1344. ; 47:6, s. 373-390
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Tidskriftsartikel (refereegranskat)abstract
- STUDY DESIGN: Systematic review and meta-analysis. BACKGROUND: Running is a healthy and popular activity worldwide, but data regarding its association with osteoarthritis (OA) are conflicting. OBJECTIVES: To evaluate the association of hip and knee OA with running and to explore the influence of running intensity on this association. METHODS: PubMed, Embase, and Cochrane Library databases were used to identify studies investigating the occurrence of OA of the hip and/or knee among runners. A meta-analysis of studies comparing this occurrence between runners and controls (sedentary, nonrunning individuals) was conducted. Runners were regarded as "competitive" if they were reported as professional/elite athletes or participated in international competitions. Recreational runners were individuals running in a nonprofessional (amateur) context. The prevalence rate and odds ratio (with 95% confidence interval [CI]) for OA between runners (at competitive and recreational levels) and controls were calculated. Subgroup analyses were conducted for OA location (hip or knee), sex, and years of exposure to running (less or more than 15 years). RESULTS: Twenty-five studies (n = 125 810 individuals) were included and 17 (n = 114 829 individuals) were meta-analyzed. The overall prevalence of hip and knee OA was 13.3% (95% CI: 11.6%, 15.2%) in competitive runners, 3.5% (95% CI: 3.4%, 3.6%) in recreational runners, and 10.2% (95% CI: 9.9%, 10.6%) in controls. The odds ratio for hip and/or knee OA in competitive runners was higher than that in recreational runners (1.34; 95% CI: 0.97, 1.86 and 0.86; 95% CI: 0.69, 1.07, respectively; controls as reference group; for difference, P<.001). Exposure to running of less than 15 years was associated with a lower association with hip and/or knee OA compared with controls (OR = 0.6; 95% CI: 0.49, 0.73). CONCLUSION: Recreational runners had a lower occurrence of OA compared with competitive runners and controls. These results indicated that a more sedentary lifestyle or long exposure to high-volume and/or high-intensity running are both associated with hip and/or knee OA. However, it was not possible to determine whether these associations were causative or confounded by other risk factors, such as previous injury.
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| 23. |
- Alentorn-Geli, E., et al.
(författare)
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The presence of patellar tendinopathy in the bone-patellar tendon-bone autograft may increase the risk of anterior cruciate ligament graft failure
- 2019
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Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 27:3, s. 766-772
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Tidskriftsartikel (refereegranskat)abstract
- PurposeThe purpose of this study was to evaluate the influence of patellar tendinopathy on primary anterior cruciate ligament (ACL) reconstruction graft failure when using bone-patellar tendon-bone (BPTB) autograft.MethodsAll patients undergoing primary ACL reconstruction using ipsilateral BPTB with preoperative magnetic resonance imaging (MRI) available for review were approached for eligibility. The medical charts of included patients were reviewed to obtain demographic information, anatomical characteristics, injury characteristics, treatment characteristics, length of follow-up, and presence of graft failure. A single, fellowship-trained, knee-specialist and blinded researcher performed preoperative MRI interpretation of patellar tendinopathy. The presence/absence of patellar tendinopathy (none, mild, moderate, or severe changes) was compared between patients with (cases) and without (controls) failure of ACL reconstruction. There were 559 cases with a median (range) clinical follow-up was 8 (4-30) months and an average age of 21.5years (82% males).ResultsOf the 559 cases, there were 182 (32.6%) with and 377 (67.4%) without patellar tendinopathy. A total of 32 (5.7%) graft failures occurred. There were a significantly higher failure rate in patients with compared to without patellar tendinopathy (p<0.001), and in patients with compared to without partial tendon tear (p<0.001). The odds ratio (95% confidence interval) for graft failure was 5.9 (2.7-13.1), 20.8 (6.8-63.9) and 54.4 (5.5-539.4) in patients with patellar tendinopathy (compared to absence of patellar tendinopathy), moderate or severe patellar tendinopathy (compared to none or mild patellar tendinopathy), or partial tendon tear (compared to absence of tendon tear), respectively.ConclusionThe presence of patellar tendinopathy increases the risk of BPTB graft failure when used for ACL reconstruction. The use of BPTB autograft is not recommended if patellar tendinopathy is obvious or there are suspicious of partial tendon tear on MRI. In such cases, the surgeon should consider using a different graft.Level of evidenceRetrospective cohort analysis, Level III.
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| 24. |
- Beischer, Susanne, et al.
(författare)
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How Is Psychological Outcome Related to Knee Function and Return to Sport Among Adolescent Athletes After Anterior Cruciate Ligament Reconstruction?
- 2019
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Ingår i: American Journal of Sports Medicine. - : SAGE Publications. - 0363-5465 .- 1552-3365. ; 47:7, s. 1567-1575
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Tidskriftsartikel (refereegranskat)abstract
- Background: Adult patients who succeed in returning to their preinjury levels of sport after anterior cruciate ligament (ACL) reconstruction have been characterized by a more positive psychological response. It is not known whether this relationship is valid for adolescent athletes. Purpose: To investigate psychological readiness to return to sport, knee-related self-efficacy, and motivation among adolescent (15-20 years old) and adult (21-30 years old) athletes after ACL reconstruction. A further aim was to compare athletes (15-30 years old) who had recovered their muscle function and returned to sport with athletes who had not. Study Design: Case-control study; Level of evidence, 3. Methods: Data were extracted from a rehabilitation-specific register 8 and 12 months after ACL reconstruction. Athletes previously involved in knee-strenuous sport who had undergone primary ACL reconstruction were included. Data comprised psychological patient-reported outcomes and results from 5 tests of muscle function. Comparisons were performed between age groups, between athletes who had and had not recovered their muscle function, and between patients who had returned to sport and not. Results: In all, 384 (50% females) and 271 athletes (52% females) were included at the 8- and 12- month follow-ups, respectively. Enhanced self-efficacy was reported at both follow-ups by adolescents and by athletes who had recovered their muscle function. Athletes who had recovered their muscle function reported higher (P = .0007) motivation to achieve their goals. Subgroup analyses on patient sex revealed findings similar to those in the main analyses for females but not for males. Moreover, adolescent and adult athletes who had returned to sport reported significantly higher levels on the Knee Self-Efficacy Scale and the ACL-Return to Sport After Injury scale at both follow-ups. Conclusion: Adolescent athletes, especially females, perceived enhanced self-efficacy, had a higher return-to-sport rate, and were more motivated to reach their goals after ACL reconstruction compared with adults. Regardless of age, athletes who had returned to sport and athletes with more symmetrical muscle function had a stronger psychological profile.
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| 25. |
- Darin, Niklas, 1964, et al.
(författare)
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Mutations in PROSC Disrupt Cellular Pyridoxal Phosphate Homeostasis and Cause Vitamin-B6-Dependent Epilepsy.
- 2016
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Ingår i: American journal of human genetics. - : Elsevier BV. - 1537-6605 .- 0002-9297. ; 99:6, s. 1325-1337
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Tidskriftsartikel (refereegranskat)abstract
- Pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, functions as a cofactor in humans for more than 140 enzymes, many of which are involved in neurotransmitter synthesis and degradation. A deficiency of PLP can present, therefore, as seizures and other symptoms that are treatable with PLP and/or pyridoxine. Deficiency of PLP in the brain can be caused by inborn errors affecting B6 vitamer metabolism or by inactivation of PLP, which can occur when compounds accumulate as a result of inborn errors of other pathways or when small molecules are ingested. Whole-exome sequencing of two children from a consanguineous family with pyridoxine-dependent epilepsy revealed a homozygous nonsense mutation in proline synthetase co-transcribed homolog (bacterial), PROSC, which encodes a PLP-binding protein of hitherto unknown function. Subsequent sequencing of 29 unrelated indivduals with pyridoxine-responsive epilepsy identified four additional children with biallelic PROSC mutations. Pre-treatment cerebrospinal fluid samples showed low PLP concentrations and evidence of reduced activity of PLP-dependent enzymes. However, cultured fibroblasts showed excessive PLP accumulation. An E.coli mutant lacking the PROSC homolog (ΔYggS) is pyridoxine sensitive; complementation with human PROSC restored growth whereas hPROSC encoding p.Leu175Pro, p.Arg241Gln, and p.Ser78Ter did not. PLP, a highly reactive aldehyde, poses a problem for cells, which is how to supply enough PLP for apoenzymes while maintaining free PLP concentrations low enough to avoid unwanted reactions with other important cellular nucleophiles. Although the mechanism involved is not fully understood, our studies suggest that PROSC is involved in intracellular homeostatic regulation of PLP, supplying this cofactor to apoenzymes while minimizing any toxic side reactions.
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| 26. |
- Di Gennaro, A., et al.
(författare)
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Cysteinyl leukotriene receptor 1 antagonism prevents experimental abdominal aortic aneurysm
- 2018
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 115:8, s. 1907-1912
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Tidskriftsartikel (refereegranskat)abstract
- Cysteinyl-leukotrienes (cys-LTs) are 5-lipoxygenase-derived lipid mediators involved in the pathogenesis and progression of inflammatory disorders, in particular asthma. We have previously found evidence linking these mediators to increased levels of proteolytic enzymes in tissue specimens of human abdominal aortic aneurysm (AAA). Here we show that antagonism of the CysLT1 receptor by montelukast, an established antiasthma drug, protects against a strong aorta dilatation (>50% increase = aneurysm) in a mouse model of CaCl2-induced AAA at a dose comparable to human medical practice. Analysis of tissue extracts revealed that montelukast reduces the levels of matrix metalloproteinase-9 (MMP-9) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) in the aortic wall. Furthermore, aneurysm progression was specifically mediated through CysLT1 signaling since a selective CysLT2 antagonist was without effect. A significantly reduced vessel dilatation is also observed when treatment with montelukast is started days after aneurysm induction, suggesting that the drug not only prevents but also stops and possibly reverts an already ongoing degenerative process. Moreover, montelukast reduced the incidence of aortic rupture and attenuated the AAA development in two additional independent models, i.e., angiotensin II- and porcine pancreatic elastase-induced AAA, respectively. Our results indicate that cys-LTs are involved in the pathogenesis of AAA and that antagonism of the CysLT1 receptor is a promising strategy for preventive and therapeutic treatment of this clinically silent and highly lethal disease.
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| 27. |
- Forsander, Gun, 1951, et al.
(författare)
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Preferences for treatment among adolescents with Type 1 diabetes: a national study using a discrete choice experiment model
- 2018
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Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 35:5, s. 621-629
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Tidskriftsartikel (refereegranskat)abstract
- AimTo test the possibility of using a discrete choice experiment model, on a national level in adolescents with Type 1 diabetes, in order to obtain a better understanding of drivers of and barriers to diabetes self-care. MethodsA survey instrument was constructed and tested on a small group of the target population: adolescents aged 15 to <18 years with Type 1 diabetes. All individuals in Sweden belonging to this target group (N=2112) were then identified via the Swedish paediatric diabetes quality registry SWEDIABKIDS, and were sent an invitation to answer an online questionnaire. A valid response for the discrete choice experiment analyses was achieved from 431 individuals. ResultsThe included respondents were not statistically different from non-participants in terms of age and duration of diabetes, but more young women entered the study and the participants had (on average) a significantly lower HbA(1c) value than the non-participants. Participants regarded as undesirable both non-severe hypoglycaemic events (day and night) and hyperglycaemic events. Avoiding weight gain and even achieving weight loss were the most important aspects among female respondents, who were willing to trade off a substantial level of glycaemic control [13 mmol/mol (1.2%)] to avoid a weight gain of 3 kg. Hypothetical equipment improvements were desired. ConclusionsThe responses may provide useful indications of the aspects that the respondents would prioritize given a real-life dilemma. For treatment effects, stratification along gender lines was important, whereas the treatment administration aspects were stratified according to treatment type because these aspects are closely related.
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| 28. |
- Geyer, Holly L., et al.
(författare)
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The role of sexuality symptoms in myeloproliferative neoplasm symptom burden and quality of life : An analysis by the MPN QOL International Study Group
- 2016
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Ingår i: Cancer. - : Wiley. - 0008-543X .- 1097-0142. ; 122:12, s. 1888-1896
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDPatients with myeloproliferative neoplasms (MPNs) including polycythemia vera, essential thrombocythemia, and myelofibrosis, are faced with oppressive symptom profiles that compromise daily functioning and quality of life. Among these symptoms, sexuality-related symptoms have emerged as particularly prominent and largely unaddressed. In the current study, the authors evaluated how sexuality symptoms from MPN relate to other patient characteristics, disease features, treatments, and symptoms. METHODSA total of 1971 patients with MPN (827 with essential thrombocythemia, 682 with polycythemia vera, 456 with myelofibrosis, and 6 classified as other) were prospectively evaluated and patient responses to the Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ C30) were collected, along with information regarding individual disease characteristics and laboratory data. Sexuality scores were compared with an age-matched, healthy control population. RESULTSOverall, patients with MPN were found to have greater sexual dysfunction compared with the healthy population (MPN-SAF score of 3.6 vs 2.0; P<.001), with 64% of patients with MPN describing some degree of sexual dysfunction and 43% experiencing severe symptoms. The presence of sexual symptoms correlated closely with all domains of patient functionality (physical, social, cognitive, emotional, and role functioning) and were associated with a reduced quality of life. Sexual problems also were found to be associated with other MPN symptoms, particularly depression and nocturnal and microvascular-related symptoms. Sexual dysfunction was more severe in patients aged >65 years and in those with cytopenias and transfusion requirements, and those receiving certain therapies such as immunomodulators or steroids. ConclusionsThe results of the current study identify the topic of sexuality as a prominent issue for the MPN population, and this area would appear to benefit from additional investigation and management. Cancer 2016;122:1888-96. (c) 2016 American Cancer Society. Sexuality problems impact all domains of functionality, depression, microvascular symptoms, and overall quality of life among patients with myeloproliferative neoplasms. These problems correlate with patient age, the presence of cytopenias, transfusion requirements, and common therapies for myeloproliferative neoplasms. See also pages 1804-6.
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| 29. |
- Geyer, Holly, et al.
(författare)
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Symptomatic Profiles of Patients With Polycythemia Vera : Implications of Inadequately Controlled Disease
- 2016
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 34:2, s. 151-
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) associated with disabling symptoms and a heightened risk of life-threatening complications. Recent studies have demonstrated the effectiveness of JAK inhibitor therapy in patients with PV patients who have a history of prior hydroxyurea (HU) use (including resistance or intolerance), phlebotomy requirements, and palpable splenomegaly. We aimed to determine how these features contribute alone and in aggregate to the PV symptom burden.PATIENTS AND METHODS: Through prospective evaluation of 1,334 patients with PV who had characterized symptom burden, we assessed patient demographics, laboratory data, and the presence of splenomegaly by disease feature (ie, known HU use, known phlebotomy requirements, splenomegaly).RESULTS: The presence of each feature in itself is associated with a moderately high symptom burden (MPN symptom assessment form [SAF] total symptom score [TSS] range, 27.7 to 29.2) that persists independent of PV risk category. In addition, symptoms incrementally increase in severity with the addition of other features. Patients with PV who had all three features (PV-HUPS) faced the highest total score (MPN-SAF TSS, 32.5) but had similar individual symptom scores to patients with known HU use (PV-HU), known phlebotomy (PV-P), and splenomegaly (PV-S).CONCLUSION: The results of this study suggest that patients with PV who have any one of the features in question (known HU use, known phlebotomy, or splenomegaly) have significant PV-associated symptoms. Furthermore, it demonstrates that many PV symptoms remain severe independent of the number of features present.
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| 30. |
- Grassi, A., et al.
(författare)
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Is Platelet-Rich Plasma (PRP) Effective in the Treatment of Acute Muscle Injuries? A Systematic Review and Meta-Analysis
- 2018
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Ingår i: Sports Medicine. - : Springer Science and Business Media LLC. - 0112-1642 .- 1179-2035. ; 48:4, s. 971-989
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Tidskriftsartikel (refereegranskat)abstract
- Background Muscle lesions account for one-third of sport-related injuries, thus representing a substantial problem for both players and their teams. The use of platelet-rich plasma (PRP) injections is rapidly growing in clinical practice, prompted by an unmet clinical need with a large commercial market. However, after early reports of positive preliminary experience, higher quality studies recently questioned the real benefit provided by PRP injections to promote muscle healing and return to sport. Objective To evaluate the effect of platelet-rich plasma (PRP) injections on outcomes following acute muscle injuries. Data sources PubMed (MEDLINE), Cochrane (CENTRAL), Web of Science, clinicaltrials.gov, who. int, isrctn.com, greylit.org, opengrey.eu. Eligibility criteria RCTs investigating the effect of PRP for the treatment of acute muscle injuries against at least one control group including patients treated with placebo injection or physical therapy. The outcomes evaluated were time to return to sport, re-injuries, complications, pain, muscle strength, range of motion (ROM)/flexibility, muscle function, and imaging. Results Six studies, involving 374 patients, were included in the meta-analysis. The time to return to sport evaluated in all six studies was significantly shorter in patients treated with PRP (mean difference = -7.17 days). However, if only the double-blind studies (n = 2) or studies including only hamstring injuries (n = 3) were considered, non-significant differences were found. Re-injuries (relative risk = -0.03) and complications (relative risk = 0.01) were also similar between the two groups (p > 0.05), nor were any substantial differences found regarding pain, muscle strength, ROM/flexibility, muscle function, and imaging. The performance bias was high risk due to the lack of patient blinding in four studies. The quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) was therefore low or very low. Conclusions The promising biological rationale, the positive preclinical findings, and the successful early clinical experience of PRP injections are not confirmed by the recent high-level RCTs. Therefore any benefit in terms of pain, function, return to sport, and recurrence using PRP injections for the treatment of acute muscle injuries is not supported. Due to the bias in the studies, the heterogeneity of the findings, and the limited sample size, the evidence should be considered to be of low or very low quality.
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| 31. |
- Grassi, A., et al.
(författare)
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Patients With Failed Anterior Cruciate Ligament Reconstruction Have an Increased Posterior Lateral Tibial Plateau Slope: A Case-Controlled Study
- 2019
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Ingår i: Arthroscopy-the Journal of Arthroscopic and Related Surgery. - : Elsevier BV. - 0749-8063. ; 35:4, s. 1172-1182
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To compare knee anatomical parameters of patients with failed anterior cruciate ligament reconstruction (ACL-R) with those of a control group of sex-matched patients with successful ACL-R. Methods: Forty-three patients (34 male, 9 female) who experienced graft failure after ACL-R were enrolled in the failed group. These patients were matched to a control group of 43 patients who underwent primary ACL-R with a minimum follow-up of 24 months. On magnetic resonance imaging, the following parameters were evaluated: transepicondylar distance, lateral and medial femoral condyle widths, tibial plateau width, notch width index, and the ratio of width and height of the femoral notch, ratio between the height and depth of the lateral and medial femoral condyle, lateral and medial posterior tibial slopes, and anterior subluxation of the lateral and medial tibial plateau. Multivariate regression with backward elimination, including only the previously identified significant variables, defined the independent predictors for revision surgery. Results: The anatomical variables that were significantly different between the 2 study groups were lateral and medial posterior tibial slopes, anterior subluxation of the lateral and medial tibial plateau, medial tibial plateau width, lateral tibial plateau width, medial femoral condyle width, and transepicondylar distance; however, the multivariate regression analysis identified the lateral posterior tibial slope (LTPs), the anterior subluxation of the medial tibial plateau, and the medial femoral condyle width as significant independent predictors (P < .05). The LPTs had the highest coefficient and the highest sensitivity (88%) and specificity (84%) to identify failures when considering the optimal cutoff value of 7.4 degrees. Conclusions: Several anatomical parameters have been identified that differ significantly between patients with failed ACL-R and those without a documented failure. The most accurate predictor of ACL failure was an LTPs >7.4 degrees, with a sensitivity of 88% and specificity of 84%. Surgeons should consider measuring LTPs during preoperative assessment of ACL-injured patients, and patients with values >7.4 degrees should be considered at high risk of ACL-R failure.
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| 32. |
- Grassi, A., et al.
(författare)
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Postural stability deficit could predict ankle sprains: a systematic review
- 2018
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Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 26:10, s. 3140-3155
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To perform a systematic review aimed to determine (1) if the postural stability deficit represents a risk factor for ankle sprains; (2) the most effective postural stability evaluation to predict ankle sprains and (3) eventual confounding factors that could influence postural stability and ankle sprain risk. Methods A systematic electronic search was performed in MEDLINE, EMBASE and CINAHL using the search terms (balance) OR (postural stability) matched with (lower limb) OR (ankle) OR (foot) and (sprain) OR (injury) on October 2 2017. All prospective studies that evaluated postural stability as risk factor for ankle sprains were included. The PRISMA Checklist guided the reporting and data abstraction. Methodological quality of all included papers was carefully assessed. Results Fifteen studies were included, evaluating 2860 individuals. Various assessment tools or instruments were used to assess postural stability. The injury incidence ranged from 10 to 34%. Postural stability deficit was recognized as risk factor for ankle sprain (OR = 1.22-10.2) in 9 cases [3 out of 3 with Star Excursion Balance Test (SEBT)]. Among the six studies that measured the center-of-gravity sway, five were able to detect worse postural stability in athletes that sustained an ankle sprain. In nine cases, the measurement of postural stability did not show any statistical relationship with ankle sprains (four out of five with examiner evaluation). In the studies that excluded patients with history of ankle sprain, postural stability was reported to be a significant risk factor in five out of six studies. Conclusions The ultimate role of postural stability as risk factor for ankle sprains was not defined, due to the high heterogeneity of results, patient's populations, sports and methods of postural stability evaluation. Regarding assessment instruments, measurement of center-of-gravity sway could detect athletes at risk, however, standardized tools and protocols are needed to confirm this finding. The SEBT could be considered a promising tool that needs further investigation in wider samples. History of ankle sprains is an important confounding factor, since it was itself a source of postural stability impairment and a risk factor for ankle sprains. These information could guide clinicians in developing screening programs and design further prospective cohort studies comparing different evaluation tools.
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| 33. |
- Hamrin Senorski, Eric, 1989, et al.
(författare)
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No differences in subjective knee function between surgical techniques of anterior cruciate ligament reconstruction at 2-year follow-up: a cohort study from the Swedish National Knee Ligament Register
- 2017
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Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 25:12, s. 3945-3954
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate how different techniques of single-bundle anterior cruciate ligament (ACL) reconstruction affect subjective knee function via the Knee injury and Osteoarthritis Outcome Score (KOOS) evaluation 2 years after surgery. It was hypothesized that the surgical techniques of single-bundle ACL reconstruction would result in equivalent results with respect to subjective knee function 2 years after surgery. This cohort study was based on data from the Swedish National Knee Ligament Register during the 10-year period of 1 January 2005 through 31 December 2014. Patients who underwent primary single-bundle ACL reconstruction with hamstrings tendon autograft were included. Details on surgical technique were collected using a web-based questionnaire comprised of essential AARSC items, including utilization of accessory medial portal drilling, anatomic tunnel placement, and visualization of insertion sites and landmarks. A repeated measures ANOVA and an additional linear mixed model analysis were used to investigate the effect of surgical technique on the KOOS4 from the pre-operative period to 2-year follow-up. A total of 13,636 patients who had undergone single-bundle ACL reconstruction comprised the study group for this analysis. A repeated measures ANOVA determined that mean subjective knee function differed between the pre-operative time period and at 2-year follow-up (p < 0.001). No differences were found with respect to the interaction between KOOS4 and surgical technique or gender. Additionally, the linear mixed model adjusted for age at reconstruction, gender, and concomitant injuries showed no difference between surgical techniques in KOOS4 improvement from baseline to 2-year follow-up. However, KOOS4 improved significantly in patients for all surgical techniques of single-bundle ACL reconstruction (p < 0.001); the largest improvement was seen between the pre-operative time period and at 1-year follow-up. Surgical techniques of primary single-bundle ACL reconstruction did not demonstrate differences in the improvement in baseline subjective knee function as measured with the KOOS4 during the first 2 years after surgery. However, subjective knee function improved from pre-operative baseline to 2-year follow-up independently of surgical technique.
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| 34. |
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| 35. |
- Janelidze, Shorena, et al.
(författare)
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Low IL-8 is associated with anxiety in suicidal patients: genetic variation and decreased protein levels
- 2015
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Ingår i: Acta Psychiatrica Scandinavica. - : Wiley: 12 months. - 0001-690X .- 1600-0447. ; 131:4, s. 269-278
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveRecent studies indicate that inflammation may play a role in the pathophysiology of suicidality. Interleukin-8 (IL-8) is a chemokine that in addition to its function in the immune system also exert neuroprotective properties. The involvement of this chemokine in neuropsychiatric conditions is incompletely known. MethodWe measured plasma and cerebrospinal fluid (CSF) IL-8, as well as the genotype frequency of a single nucleotide polymorphism (-251A/T, rs4073) in the promoter region of the IL8 gene, in suicide attempters (n=206) and healthy controls (n=578). ResultsPlasma and CSF levels of IL-8 were significantly lower in suicide attempters with anxiety than in healthy controls. IL-8 in both plasma and CSF correlated negatively with symptoms of anxiety. Compared with the population-based cohort, the IL-8-251T allele was more prevalent among female suicide attempters. Furthermore, suicide attempters carrying this allele showed more severe anxiety. This correlative study warrants further mechanistic studies on the effects of IL-8 in the central nervous system. ConclusionWe suggest that IL-8 might be involved in the biological mechanisms mediating resilience to anxiety. Thus, our findings highlight the chemokine IL-8 as a potential target for future development of anti-anxiety treatments and suicide prevention.
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| 36. |
- Jemt, Elisabeth, et al.
(författare)
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Regulation of DNA replication at the end of the mitochondrial D-loop involves the helicase TWINKLE and a conserved sequence element
- 2015
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Ingår i: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 43:19, s. 9262-9275
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Tidskriftsartikel (refereegranskat)abstract
- The majority of mitochondrial DNA replication events are terminated prematurely. The nascent DNA remains stably associated with the template, forming a triple-stranded displacement loop (D-loop) structure. However, the function of the D-loop region of the mitochondrial genome remains poorly understood. Using a comparative genomics approach we here identify two closely related 15 nt sequence motifs of the D-loop, strongly conserved among vertebrates. One motif is at the D-loop 5'-end and is part of the conserved sequence block 1 (CSB1). The other motif, here denoted coreTAS, is at the D-loop 3'-end. Both these sequences may prevent transcription across the D-loop region, since light and heavy strand transcription is terminated at CSB1 and coreTAS, respectively. Interestingly, the replication of the nascent D-loop strand, occurring in a direction opposite to that of heavy strand transcription, is also terminated at coreTAS, suggesting that coreTAS is involved in termination of both transcription and replication. Finally, we demonstrate that the loading of the helicase TWINKLE at coreTAS is reversible, implying that this site is a crucial component of a switch between D-loop formation and full-length mitochondrial DNA replication.
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| 37. |
- Judy, R. P., et al.
(författare)
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Level of evidence and authorship trends of clinical studies in knee surgery, sports traumatology, arthroscopy, 1995-2015
- 2018
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Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 26:1, s. 9-14
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Tidskriftsartikel (refereegranskat)abstract
- There is increasing emphasis on publication quality and internationalization of author groups in orthopaedic literature. The purpose of this review was to evaluate the type of studies and the level of evidence (LOE) published in knee surgery, sports traumatology, arthroscopy (KSSTA) from 1995 to 2015. The secondary aim was to analyze trends in authorship characteristics in KSSTA. Two reviewers reviewed the table of contents of KSSTA and identified original papers from 1995, 2000, 2005, 2010, and 2015. The reviewers graded LOE from Levels I to IV using guidelines from the University of Oxford's Centre for Evidence-Based Medicine. For each article, the total number of authors and country of author group were also analyzed. A total of 880 papers were analyzed. The proportions in LOE have stayed consistent throughout the study period (n.s.). There has been a significant increase in the number of published articles and the number of Level I and II studies (P < 0.01). Therapeutic articles were the most common type. The mean number of authors per KSSTA article significantly increased from 3.9 to 5.7 over the 20-year period (P < 0.01). The number of represented countries increased yearly and academic institutions from 40 different nationalities published articles in the Journal. Of the examined years, the percent of articles with international collaboration was 17.6%. The proportion of LOE I and II articles published in KSSTA remains consistently high. Therapeutic studies are the most frequently published articles. There is an increase in international groups publishing in KSSTA.
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| 38. |
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| 39. |
- Lang, Tiange, 1976, et al.
(författare)
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Searching the Evolutionary Origin of Epithelial Mucus Protein Components-Mucins and FCGBP
- 2016
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Ingår i: Molecular Biology and Evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 33:8, s. 1921-1936
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Tidskriftsartikel (refereegranskat)abstract
- The gel-forming mucins are large glycosylated proteins that are essential components of the mucus layers covering epithelial cells. Using novel methods of identifying mucins based on profile hidden Markov models, we have found a large number of such proteins in Metazoa, aiding in their classification and allowing evolutionary studies. Most vertebrates have 5-6 gel-forming mucin genes and the genomic arrangement of these genes is well conserved throughout vertebrates. An exception is the frog Xenopus tropicalis with an expanded repertoire of at least 26 mucins of this type. Furthermore, we found that the ovomucin protein, originally identified in chicken, is characteristic of reptiles, birds, and amphibians. Muc6 is absent in teleost fish, but we now show that it is present in animals such as ghost sharks, demonstrating an early origin in vertebrate evolution. Public RNA-Seq data were analyzed with respect tomucins in zebrafish, frog, and chicken, thus allowing comparison in regard of tissue and developmental specificity. Analyses of invertebrate proteins reveal that gel-forming-mucin type of proteins is widely distributed also in this group. Their presence in Cnidaria, Porifera, and in Ctenophora (comb jellies) shows that these proteins were present early in metazoan evolution. Finally, we examined the evolution of the FCGBP protein, abundant in mucus and related to gel-forming mucins in terms of structure and localization. We demonstrate that FCGBP, ubiquitous in vertebrates, has a conserved N-terminal domain. Interestingly, this domain is also present as an N-terminal sequence in a number of bacterial proteins.
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| 40. |
- Lian, Jayson, et al.
(författare)
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Younger age and greater preoperative function predict compliance with 2-year follow-up visits after ACL reconstruction: an analysis of the PIVOT multicentre trial
- 2018
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Ingår i: Journal of ISAKOS. - : Elsevier BV. - 2059-7754. ; 3:5, s. 251-257
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The purpose of this investigation was to identify clinical and demographic variables that may predict compliance, defined as patient follow-up at 1-year and 2-year postoperative appointments, after anterior cruciate ligament reconstruction (ACLR). Methods A total of 107 patients undergoing primary ACLR across four centres were prospectively followed for 2 years. Demographic and clinical data were recorded preoperatively and postoperatively, including patient-reported outcomes such as the Marx Activity Rating Scale, Cincinnati Occupational Rating Scale (CORS), International Knee Documentation Committee Subjective Knee Evaluation Form and Activities of Daily Living Scale (ADLS). Compliance was retrospectively defined using the presence or lack of outcome measures at 1-year and 2-year postoperative visits. Univariate analysis was done to compare demographic and clinical variables between compliant and non-compliant patients at 1-year and 2-year follow-up. Significant variables were entered into a logistic regression model. Significance was set at p<0.05. Results The overall rate of compliance at 1-year and 2-year postoperative appointments was 83.2% (89/107) and 57.0% (61/107), respectively. Regression analysis showed that residence in Kobe, Japan compared with Pittsburgh, USA (OR 10.28; 95% CI 1.0003 to 105.28), and ‘very strenuous’ (OR 16.74; 95% CI 3.21 to 87.43) and ‘strenuous’ (OR 18.78; 95% CI 2.01 to 175.78) preinjury activity level were independent factors associated with compliance at 1-year follow-up. At 2 years follow-up, younger age (OR 0.95; 95% CI 0.91 to 0.997), and greater preoperative score on CORS (OR 1.03; 95% CI 1.01 to 1.06) and on ADLS (OR 1.04; 95% CI 1.01 to 1.07) were independently associated with compliance. Conclusion While patients with greater level of strenuous activity were more likely to follow-up after ACL surgery at 1 year, patients who were younger and had higher preoperative function measured by CORS and ADLS were more likely to follow-up at 2 years. Differences in follow-up rates among the USA, Italy, Sweden and Japan may highlight important cultural, socioeconomic and infrastructural differences across international healthcare systems. Orthopaedic surgeons may consider the results of this study during preoperative discussion with their patients and design of future ACL clinical research trials. Level of evidence Level III, prospective cohort.
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| 41. |
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| 42. |
- Padra, Médea, 1986, et al.
(författare)
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Helicobacter suis binding to carbohydrates on human and porcine gastric mucins and glycolipids occurs via two modes
- 2018
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Ingår i: Virulence. - : Informa UK Limited. - 2150-5594 .- 2150-5608. ; 9:1, s. 898-918
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter suis colonizes the stomach of most pigs and is the most prevalent non-Helicobacter pylori Helicobacter species found in the human stomach. In the human host, H. suis contributes to the development of chronic gastritis, peptic ulcer disease and MALT lymphoma, whereas in pigs it is associated with gastritis, decreased growth and ulcers. Here, we demonstrate that the level of H. pylori and H. suis binding to human and pig gastric mucins varies between individuals with species dependent specificity. The binding optimum of H. pylori is at neutral pH whereas that of H. suis has an acidic pH optimum, and the mucins that H. pylori bind to are different than those that H. suis bind to. Mass spectrometric analysis of mucin O-glycans from the porcine mucin showed that individual variation in binding is reflected by a difference in glycosylation; of 109 oligosaccharide structures identified, only 14 were present in all examined samples. H. suis binding to mucins correlated with glycans containing sulfate, sialic acid and terminal galactose. Among the glycolipids present in pig stomach, binding to lactotetraosylceramide (Gal beta 3GlcNAc beta 3Gal beta 4Glc beta 1Cer) was identified, and adhesion to Gal beta 3GlcNAc beta 3Gal beta 4Glc at both acidic and neutral pH was confirmed using other glycoconjugates. Together with that H. suis bound to DNA (used as a proxy for acidic charge), we conclude that H. suis has two binding modes: one to glycans terminating with Gal beta 3GlcNAc, and one to negatively charged structures. Identification of the glycan structures H. suis interacts with can contribute to development of therapeutic strategies alternative to antibiotics.
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| 43. |
- Peciulyte, Ausra, 1986, et al.
(författare)
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Redox processes acidify and decarboxylate steam-pretreated lignocellulosic biomass and are modulated by LPMO and catalase
- 2018
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Ingår i: Biotechnology for Biofuels. - : Springer Science and Business Media LLC. - 1754-6834 .- 1754-6834. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The bioconversion of lignocellulosic feedstocks to ethanol is being commercialised, but further process development is required to improve their economic feasibility. Efficient saccharification of lignocellulose to fermentable sugars requires oxidative cleavage of glycosidic linkages by lytic polysaccharide monooxygenases (LPMOs). However, a proper understanding of the catalytic mechanism of this enzyme class and the interaction with other redox processes associated with the saccharification of lignocellulose is still lacking. The in-use stability of LPMO-containing enzyme cocktails is increased by the addition of catalase implying that hydrogen peroxide (H2O2) is generated in the slurry during incubation. Therefore, we sought to characterize the effects of enzymatic and abiotic sources of H2O2on lignocellulose hydrolysis to identify parameters that could improve this process. Moreover, we studied the abiotic redox reactions of steam-pretreated wheat straw as a function of temperature and dry-matter (DM) content. Results: Abiotic reactions in pretreated wheat straw consume oxygen, release carbon dioxide (CO2) to the slurry, and decrease the pH. The magnitude of these reactions increased with temperature and with DM content. The presence of LPMO during saccharification reduced the amount of CO2liberated, while the effect on pH was insignificant. Catalase led to increased decarboxylation through an unknown mechanism. Both in situ-generated and added H2O2caused a decrease in pH. Conclusions: Abiotic redox processes similar to those that occur in natural water-logged environments also affect the saccharification of pretreated lignocellulose. Heating of the lignocellulosic material and adjustment of pH trigger rapid oxygen consumption and acidification of the slurry. In industrial settings, it will be of utmost importance to control these processes. LPMOs interact with the surrounding redox compounds and redirect abiotic electron flow from decarboxylating reactions to fuel the oxidative cleavage of glycosidic bonds in cellulose.
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| 44. |
- Ping Zhao, Lue, et al.
(författare)
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Building and validating a prediction model for paediatric type 1 diabetes risk using next generation targeted sequencing of class II HLA genes
- 2017
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Ingår i: Diabetes/Metabolism Research Reviews. - : WILEY. - 1520-7552 .- 1520-7560. ; 33:8
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Tidskriftsartikel (refereegranskat)abstract
- AimIt is of interest to predict possible lifetime risk of type 1 diabetes (T1D) in young children for recruiting high-risk subjects into longitudinal studies of effective prevention strategies. MethodsUtilizing a case-control study in Sweden, we applied a recently developed next generation targeted sequencing technology to genotype class II genes and applied an object-oriented regression to build and validate a prediction model for T1D. ResultsIn the training set, estimated risk scores were significantly different between patients and controls (P=8.12x10(-92)), and the area under the curve (AUC) from the receiver operating characteristic (ROC) analysis was 0.917. Using the validation data set, we validated the result with AUC of 0.886. Combining both training and validation data resulted in a predictive model with AUC of 0.903. Further, we performed a biological validation by correlating risk scores with 6 islet autoantibodies, and found that the risk score was significantly correlated with IA-2A (Z-score=3.628, Pamp;lt;0.001). When applying this prediction model to the Swedish population, where the lifetime T1D risk ranges from 0.5% to 2%, we anticipate identifying approximately 20 000 high-risk subjects after testing all newborns, and this calculation would identify approximately 80% of all patients expected to develop T1D in their lifetime. ConclusionThrough both empirical and biological validation, we have established a prediction model for estimating lifetime T1D risk, using class II HLA. This prediction model should prove useful for future investigations to identify high-risk subjects for prevention research in high-risk populations.
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| 45. |
- Ping Zhao, Lue, et al.
(författare)
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Next-Generation Sequencing Reveals That HLA-DRB3, -DRB4, and -DRB5 May Be Associated With Islet Autoantibodies and Risk for Childhood Type 1 Diabetes
- 2016
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Ingår i: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 65:3, s. 710-718
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Tidskriftsartikel (refereegranskat)abstract
- The possible contribution of HLA-DRB3, -DRB4, and -DRB5 alleles to type 1 diabetes risk and to insulin autoantibody (IAA), GAD65 (GAD autoantibody [GADA]), IA-2 antigen (IA-2A), or ZnT8 against either of the three amino acid variants R, W, or Q at position 325 (ZnT8RA, ZnT8WA, and ZnT8QA, respectively) at clinical diagnosis is unclear. Next-generation sequencing (NGS) was used to determine all DRB alleles in consecutively diagnosed patients ages 1-18 years with islet autoantibody-positive type 1 diabetes (n = 970) and control subjects (n = 448). DRB3, DRB4, or DRB5 alleles were tested for an association with the risk of DRB1 for autoantibodies, type 1 diabetes, or both. The association between type 1 diabetes and DRB1*03:01:01 was affected by DRB3*01:01:02 and DRB3*02:02:01. These DRB3 alleles were associated positively with GADA but negatively with ZnT8WA, IA-2A, and IAA. The negative association between type 1 diabetes and DRB1*13:01:01 was affected by DRB3*01:01:02 to increase the risk and by DRB3*02:02:01 to maintain a negative association. DRB4*01:03:01 was strongly associated with type 1 diabetes (P = 10(-36)), yet its association was extensively affected by DRB1 alleles from protective (DRB1*04:03:01) to high (DRB1*04:01:01) risk, but its association with DRB1*04:05:01 decreased the risk. HLA-DRB3, -DRB4, and -DRB5 affect type 1 diabetes risk and islet autoantibodies. HLA typing with NGS should prove useful to select participants for prevention or intervention trials.
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| 46. |
- Pramling, Niklas, 1973, et al.
(författare)
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The Magical Fruits: Establishing a Narrative Play Frame for Mutual Problem Solving
- 2019
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Ingår i: Play-Responsive Teaching in Early Childhood Education. - Cham : Springer. - 2468-8746. - 9783030159580 ; , s. 137-151
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Bokkapitel (refereegranskat)abstract
- In this chapter, we analyze a prolonged activity from initiation to conclusion, focusing on (i) how the teacher establishes a narrative, imaginary, frame for the activity, (ii) how children participate and contribute to this activity, (iii) what didaktikal challenges are actualized and what support the children are given in the activity, including what contents are constituted, and (iv) what the implications of the activity are for children’s development. © 2019, The Author(s).
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| 47. |
- Prentice, H. A., et al.
(författare)
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Patient demographic and surgical characteristics in anterior cruciate ligament reconstruction: a description of registries from six countries
- 2018
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Ingår i: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 52:11
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Tidskriftsartikel (refereegranskat)abstract
- Objective Findings from individual anterior cruciate ligament reconstruction (ACLR) registry studies are impactful, but how various registries from different countries compare with different patient populations and surgical techniques has not been described. We sought to describe six ACLR registry cohorts to understand variation across countries. Methods Five European registries and one US registry participated. For each registry, all primary ACLR registered between registry establishment through 31December 2014 were identified. Descriptive statistics included frequencies, proportions, medians and IQRs. Revision incidence rates following primary ACLR were computed. Results 101 125 ACLR were included: 21820 in Denmark, 300 in Luxembourg, 17556 in Norway, 30422 in Sweden, 2972 in the UK and 28055 in the US. In all six cohorts, males (range: 56.8%-72.4%) and soccer injuries (range: 14.1%-42.3%) were most common. European countries mostly used autografts (range: 93.7%-99.7%); allograft was most common in the US (39.9%). Interference screw was the most frequent femoral fixation in Luxembourg and the US (84.8% and 42.9%), and suspensory fixation was more frequent in the other countries (range: 43.9%-75.5%). Interference was the most frequent tibial fixation type in all six cohorts (range: 64.8%-98.2%). Three-year cumulative revision probabilities ranged from 2.8% to 3.7%. Conclusions Similarities in patient demographics and injury activity were observed between all cohorts of ACLR. However, graft and fixation choices differed. Revision rates were low. This work, including >100 000 ACLR, is the most comprehensive international description of contemporary practice to date.
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| 48. |
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| 49. |
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| 50. |
- Schwieler, L., et al.
(författare)
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Electroconvulsive therapy suppresses the neurotoxic branch of the kynurenine pathway in treatment-resistant depressed patients
- 2016
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Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neuroinflammation is increasingly recognized as contributing to the pathogenesis of depression. Key inflammatory markers as well as kynurenic acid (KYNA) and quinolinic acid (QUIN), both tryptophan metabolites, have been associated with depressive symptoms and suicidality. The aim of the present study is to investigate the peripheral concentration of cytokines and tryptophan and kynurenine metabolites in patients with unipolar treatment-resistant depression before and after electroconvulsive therapy (ECT), the most effective treatment for depression. Methods: Cytokines in plasma from patients with major depressive disorder (MDD; n = 19) and healthy volunteers (n = 14) were analyzed with electrochemiluminescence detection. Tryptophan and kynurenine metabolites were detected with high-performance liquid chromatography (HPLC) and LC/MS. KYNA was analyzed in a second healthy control cohort (n = 22). Results: Patients with MDD had increased plasma levels of interleukin (IL)-6 compared to healthy volunteers (P < 0.05). We also found an altered kynurenine metabolism in these patients displayed by decreased plasma levels of KYNA (P < 0.0001) as well as a significantly increased QUIN/KYNA ratio (P < 0.001). Plasma levels of tryptophan, kynurenine, and QUIN did not differ between patients and controls. Treatment with ECT was associated with a significant decrease in the plasma levels of tryptophan (P < 0.05), kynurenine (P < 0.01), and QUIN (P < 0.001), whereas plasma levels of KYNA did not change. The QUIN/KYNA ratio was found to significantly decrease in ECT-treated patients (P < 0.05). There was a significant inverse correlation between symptom severity and kynurenine levels at baseline (r = -0.67, P = 0.002). Conclusions: This study confirms an imbalanced kynurenine pathway in MDD supporting the hypothesis of a netstimulation of N-methyl-D-aspartic acid (NMDA) receptors in the disorder. Treatment with ECT profoundly decreased QUIN, an NMDA-receptor agonist previously suggested to be implicated in the pathogenesis of depression, an effect that might have bearing for the good clinical outcome of ECT.
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