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1.
  • Patterson, Brooke E., et al. (author)
  • Evaluation of an injury prevention programme (Prep-to-Play) in women and girls playing Australian Football : design of a pragmatic, type III, hybrid implementation-effectiveness, stepped-wedge, cluster randomised controlled trial
  • 2022
  • In: BMJ Open. - : BMJ Publishing Group. - 2044-6055. ; 12:9
  • Journal article (peer-reviewed)abstract
    • Introduction Due to the increase in participation and risk of anterior cruciate ligament (ACL) injuries and concussion in womens Australian Football, an injury prevention programme (Prep-to-Play) was codesigned with consumers (eg, coaches, players) and stakeholders (eg, the Australian Football League). The impact of supported and unsupported interventions on the use of Prep-to-Play (primary aim) and injury rates (secondary aim) will be evaluated in women and girls playing community Australian Football. Methods and analysis This stepped-wedge, cluster randomised controlled trial will include >= 140 teams from U16, U18 or senior womens competitions. All 10 geographically separated clusters (each containing >= 14 teams) will start in the control (unsupported) phase and be randomised to one of five dates (or wedges) during the 2021 or 2022 season to sequentially transition to the intervention (supported Prep-to-Play), until all teams receive the intervention. Prep-to-Play includes four elements: a neuromuscular training warm-up, contact-focussed football skills (eg, tackling), strength exercises and education (eg, technique cues). When transitioning to supported interventions, study physiotherapists will deliver a workshop to coaches and player leaders on how to use Prep-to-Play, attend team training at least two times and provide ongoing support. In the unsupported phase, team will continue usual routines and may freely access available Prep-to-Play resources online (eg, posters and videos about the four elements), but without additional face-to-face support. Outcomes will be evaluated throughout the 2021 and 2022 seasons (similar to 14 weeks per season). Primary outcome: use of Prep-to-Play will be reported via a team designate (weekly) and an independent observer (five visits over the two seasons) and defined as the team completing 75% of the programme, two-thirds (67%) of the time. Secondary outcomes: injuries will be reported by the team sports trainer and/or players. Injury definition: any injury occurring during a football match or training that results in: (1) being unable to return to the field of play for that match or (2) missing >= one match. Outcomes in the supported and unsupported phases will be compared using a generalised linear mixed model adjusting for clustering and time. Due to the type III hybrid implementation-effectiveness design, the study is powered to detect a improvement in use of Prep-to-Play and a reduction in ACL injuries. Ethics and dissemination La Trobe University Ethics Committee (HREC 20488) approved. Coaches provided informed consent to receive the supported intervention and players provided consent to be contacted if they sustained a head or knee injury. Results will be disseminated through partner organisations, peer-reviewed publications and scientific conferences.
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2.
  • Hägglund, H, et al. (author)
  • Treatment of hepatic venoocclusive disease with recombinant human tissue plasminogen activator or orthotopic liver transplantation after allogeneic bone marrow transplantation
  • 1996
  • In: Transplantation. - : Ovid Technologies (Wolters Kluwer Health). - 0041-1337 .- 1534-6080. ; 62:8, s. 1076-1080
  • Journal article (peer-reviewed)abstract
    • Ten allogeneic bone marrow transplant (BMT) recipients with hepatic venoocclusive disease (VOD) were treated with recombinant human tissue plasminogen activator (rt-PA). Two of them subsequently underwent orthotopic liver transplantation (OLT). One additional patient with VOD underwent OLT without prior rt-PA treatment. Treatment with rt-PA was started a median of 14 (1--35) days after BMT. The dose of rt-PA given to adults was 10-50 mg i.v. and that given to children was 3-10 mg i.v. Treatment was given for 2-4 days. In three patients, the dose was administered over a longer period or it was repeated. Four patients responded to rt-PA therapy and six did not. Eight patients suffered from hemorrhages, one intracranial and three gastrointestinal. Four patients required blood transfusions. Four had minor subcutaneous hemorrhages and/or epistaxis. One patient died of intracranial hemorrhage and five from hepatic and/or multiorgan failure. Two patients treated with rt-PA, 10 mg/day for 4 days, are alive; one is alive and well 3 months after BMT, the other has relapsed after 7 months. The three patients undergoing OLT died of chronic hepatic failure, cerebral edema, and pneumonia. Our experience suggests that rt-PA should not be administered in high doses and that the treatment should not be given over a longer period, because of the risk of severe hemorrhages.
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3.
  • Nordmark, E., et al. (author)
  • The American paediatric evaluation of disability inventory (PEDI). Applicability of PEDI in Sweden for children aged 2.0-6.9 years
  • 1999
  • In: Scandinavian Journal of Rehabilitation Medicine. - : Informa UK Limited. - 0036-5505. ; 31:2, s. 95-100
  • Journal article (peer-reviewed)abstract
    • The American Paediatric Evaluation of Disability Inventory (PEDI) is a new instrument for evaluating functional performance in disabled children aged 6 months to 7.5 years. It was developed to determine a child's functional capacity and performance in three domains, self-care, mobility and social function, as reflected in scores on three scales: (i) functional skills (current capability in specific tasks), (ii) caregiver assistance (i.e. provided to facilitate the child's performance), and (iii) modifications (i.e. environmental or technical modifications needed to facilitate the child's function). The present study was designed to compare results obtained using the PEDI in a Swedish sample with the American normative data, and to analyse the content and relevance of PEDI items for use in Sweden. The PEDI was administered as a questionnaire in structured interview form to the parents of 52 non-disabled Swedish children aged 2.0- 6.9 years, divided into ten age groups. Correlation analysis (Pearson's r) showed scores for the Swedish sample to manifest strong correlation with the respective American normative data, both for the functional skills (r = 0.90- 0.98) and caregiver assistance (r = 0.93-0.99) scales, respectively. Scores for the modification scale were not compared. Thus, the results suggest the American normative data to be appropriate for reference purposes in Sweden.
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  • Bahar Gogani, Jalil, 1967-, et al. (author)
  • Assessment of correlated dose and sensitivity profiles on a multi-slice CT scanner
  • 2005
  • In: Radiation Protection Dosimetry. - : Oxford University Press (OUP). - 0144-8420 .- 1742-3406. ; 114:1-3, s. 332-336
  • Journal article (peer-reviewed)abstract
    • In the case of computed tomography (CT) scanners as well as other imaging techniques utilising ionising radiation, it is imperative that radiation is confined to the sensitive part of the image detector. Assuring this for a CT scanner requires detailed information about the scanner dose and sensitivity profiles and their spatial correlation. The profiles should ideally be co-centric and tightly fit to each other. Ensuring this inherent performance of the scanner can be seen as one of the fundamental steps in optimising diagnostic examinations with CT. A measurement device using a dedicated liquid ionisation chamber is employed to investigate the performance of a Toshiba Aquilion 16 scanner in this aspect. Dose profile and sensitivity profile pairs for four collimations are presented where each pair of profiles are spatially correlated to each other. The measurement device can be applied to any scanner for fast and accurate assessment of dose and sensitivity profiles and their spatial correlation. © The Author 2005. Published by Oxford University Press. All rights reserved.
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8.
  • Broesby-Olsen, Sigurd, et al. (author)
  • Multidisciplinary Management of Mastocytosis : Nordic Expert Group Consensus
  • 2016
  • In: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 96:5
  • Journal article (peer-reviewed)abstract
    • Mastocytosis is a heterogeneous group of diseases defined by an increased number and accumulation of mast cells, and often also by signs and symptoms of mast cell activation. Disease subtypes range from indolent to rare aggressive forms. Mastocytosis affects people of all ages and has been considered rare; however, it is probably underdiagnosed with potential severe implications. Diagnosis can be challenging and symptoms may be complex and involve multiple organ-systems. In general it is advised that patients should be referred to centres with experience in the disease offering an individualized, multidisciplinary approach. We present here consensus recommendations from a Nordic expert group for the diagnosis and general management of patients with mastocytosis.
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9.
  • Bruder, Andrea M., et al. (author)
  • If we build it together, will they use it? A mixed-methods study evaluating the implementation of Prep-to-Play PRO: an injury prevention programme for women's elite Australian Football
  • 2024
  • In: British Journal of Sports Medicine. - : BMJ PUBLISHING GROUP. - 0306-3674 .- 1473-0480.
  • Journal article (peer-reviewed)abstract
    • Objectives We evaluated the implementation of Prep-to-Play PRO, an injury prevention programme for women's elite Australian Football League (AFLW).Methods The Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) of Prep-to-Play PRO were assessed based on the proportion of AFLW players and/or staff who: were aware of the programme (R), believed it may reduce anterior cruciate ligament injury (E), attempted to implement any/all programme components (A), implemented all intended components as practically as possible (I) and intended future programme implementation (M). Quantitative and qualitative data were triangulated to assess 58 RE-AIM items (evidence of yes/no/unsure/no evidence) and the 5 RE-AIM dimensions (fully achieved=evidence of yes on >50% dimension items, partially achieved=50% of items evidence of yes and 50% unsure or 50% mix of unsure and unanswered, or not met=evidence of yes on <50% dimension items).Results Multiple sources including AFLW training observations (n=7 total), post-implementation surveys (141 players, 25 staff), semistructured interviews (19 players, 13 staff) and internal programme records (9 staff) contributed to the RE-AIM assessment. After the 2019 season, 8 of 10 (80%) AFLW clubs fully met all five RE-AIM dimensions. All 10 clubs participating in the AFLW fully achieved the reach (R) dimension. One club partially achieved the implementation (I) dimension, and one club partially achieved the effectiveness (E) and adoption (A) dimensions.Conclusion The Prep-to-Play PRO injury prevention programme for the AFLW achieved high implementation, possibly due to the programme's deliberately flexible approach coupled with our pragmatic definition of implementation. Engaging key stakeholders at multiple ecological levels (organisation, coaches, athletes) throughout programme development and implementation likely enhanced programme implementation.
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10.
  • Carlsson, G, et al. (author)
  • Hematopoietic stem cell transplantation in severe congenital neutropenia
  • 2011
  • In: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 56:3, s. 444-451
  • Journal article (peer-reviewed)abstract
    • BACKGROUND:Severe congenital neutropenia (SCN) is an immunodeficiency characterized by disturbed myelopoiesis and an absolute neutrophil count (ANC) <0.5 × 10(9)/L. SCN is also a premalignant condition; a significant proportion of patients develop myelodysplastic syndrome or leukemia (MDS/L). Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for SCN.PROCEDURE:Since 2004, eight HSCT have been performed in seven patients at our center. The indications were transformation to MDS/L (n = 2), granulocyte colony-stimulating factor receptor (CSF3R) mutation(s) (n = 2), granulocyte colony-stimulating factor (G-CSF) resistance (n = 2), and at the patient's own request (n = 1).RESULTS:The mean age at transplantation was 13 years (2.8-28 years) (mean follow-up 32 months, range 21-60). Three patients harbored ELANE mutations, three HAX1 mutations, and in one patient no causative mutation was identified. Two of the ELANE mutations were novel mutations. Three patients initially received myeloablative conditioning and four had reduced intensity conditioning (RIC). Three grafts were from HLA-identical siblings, three from matched unrelated donors and two were cord blood units. Engraftment occurred in all patients. Two of seven (29%) patients died; both had MDS/L and both were among the three that underwent myeloablative conditioning. One patient has chronic GVHD 2 years post-transplant.CONCLUSIONS:The role of HSCT should be explored further in patients with SCN. In particular, the influence of the conditioning regime needs to be evaluated in a larger cohort of patients.
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  • Caruso, Vanni, et al. (author)
  • The G protein-coupled receptor GPR162 is widely distributed in the CNS and highly expressed in the hypothalamus and in hedonic feeding areas
  • 2014
  • In: Gene. - : Elsevier BV. - 0378-1119 .- 1879-0038. ; 553:1, s. 1-6
  • Journal article (peer-reviewed)abstract
    • The Rhodopsin family is a class of integral membrane proteins belonging to G protein-coupled receptors (GPCRs). To date, several orphan GPCRs are still uncharacterized and in this study we present an anatomical characterization of the GPR162 protein and an attempt to describe its functional role. Our results show that GPR162 is widely expressed in GABAergic as well as other neurons within the mouse hippocampus, whereas extensive expression is observed in areas related to energy homeostasis and hedonic feeding such as hypothalamus, amygdala and ventral tegmental area, regions known to be involved in the regulation of palatable food consumption.
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  • Finlayson, L., et al. (author)
  • The head shaft angle is associated with hip displacement in children at GMFCS levels III-V - A population based study
  • 2018
  • In: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 19:1
  • Journal article (peer-reviewed)abstract
    • Background: An increased Head Shaft Angle (HSA) has been reported as a risk factor for hip displacement in children with cerebral palsy (CP) but opinions differ in the literature. The purpose of this study was to re-evaluate the relationship between HSA and hip displacement in a different population of children with CP. Methods: The Cerebral Palsy Integrated Pathway Scotland surveillance programme includes 95% of all children with CP in Scotland. The pelvic radiographs from 640 children in GMFCS levels III-V were chosen. The most displaced hip was analysed and the radiographs used were those taken at the child's first registration in the database to avoid the potential effects of surveillance on subsequent hip centration. A logistic regression model was used with hip displacement (migration percentage [MP] ≥40%) as outcome and HSA, GMFCS, age and sex as covariates. Results: The MP was ≥40% in 118 hips with a mean HSA of 164° (range 121-180°) and < 40% in 522 hips with a mean HSA of 160° (range 111-180°). The logistic regression analysis showed no significant influence of age and sex on MP in this population but a high GMFCS level was strongly associated with hip displacement. An increased HSA was also associated with hip displacement, a 10° difference in HSA for children adjusted for age, sex, and GMFCS gave an odds ratio of 1.26 for hip displacement equal or above 40% (p = 0.009) and hips with HSA above 164.5 degrees had an odds ratio of 1.96 compared with hips with HSA below 164.5 degrees (p = 0.002). Conclusion: These findings confirm that HSA is associated with hip displacement in children in GMFCS levels III-V.
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  • Fredriksson, Robert, et al. (author)
  • The polyamine transporter Slc18b1(VPAT) is important for both short and long time memory and for regulation of polyamine content in the brain.
  • 2019
  • In: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 15:12
  • Journal article (peer-reviewed)abstract
    • SLC18B1 is a sister gene to the vesicular monoamine and acetylcholine transporters, and the only known polyamine transporter, with unknown physiological role. We reveal that Slc18b1 knock out mice has significantly reduced polyamine content in the brain providing the first evidence that Slc18b1 is functionally required for regulating polyamine levels. We found that this mouse has impaired short and long term memory in novel object recognition, radial arm maze and self-administration paradigms. We also show that Slc18b1 KO mice have altered expression of genes involved in Long Term Potentiation, plasticity, calcium signalling and synaptic functions and that expression of components of GABA and glutamate signalling are changed. We further observe a partial resistance to diazepam, manifested as significantly lowered reduction in locomotion after diazepam treatment. We suggest that removal of Slc18b1 leads to reduction of polyamine contents in neurons, resulting in reduced GABA signalling due to long-term reduction in glutamatergic signalling.
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  • Fredriksson, Robert, et al. (author)
  • The solute carrier (SLC) complement of the human genome : phylogenetic classification reveals four major families
  • 2008
  • In: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 582:27, s. 3811-3816
  • Journal article (peer-reviewed)abstract
    • Solute carriers (SLCs) is the largest group of transporters, embracing transporters for inorganic ions, amino acids, neurotransmitters, sugars, purines and fatty acids among other substrates. We mined the finished assembly of the human genome using Hidden Markov Models (HMMs) obtaining a total of 384 unique SLC sequences. Detailed clustering and phylogenetic analysis of the entire SLC family showed that 15 of the families place into four large phylogenetic clusters with the largest containing eight SLC families, suggesting that many of the distinct families of SLCs have a common evolutionary origin. This study represents the first overall genomic roadmap of the SLCs providing large sequence sets and clarifies the phylogenetic relationships among the families of the second largest group of membrane proteins.
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  • Gülen, T, et al. (author)
  • High prevalence of anaphylaxis in patients with systemic mastocytosis : a single-centre experience
  • 2014
  • In: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 44:1, s. 121-129
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Systemic mastocytosis (SM) is a clonal mast cells disorder characterized by the proliferation, accumulation and activation of mast cells in extracutaneous tissues. The clinical picture is heterogeneous and may range from asymptomatic to potentially fatal anaphylactic reactions due to excessive mast cell mediator release.OBJECTIVE: The aim of this study was to investigate the prevalence and trigger factors of anaphylactic reactions among adult SM patients. We also explored the clinical spectrum of mast cell mediator-related symptoms in patients with SM.METHODS: This descriptive study was performed among 84 consecutive adult (≥ 18 years) patients those were diagnosed with SM according to WHO criteria. Sixty-six of the patients also underwent a comprehensive allergy work-up.RESULTS: Sixty of 84 patients with SM (71%) had bone marrow mast cell aggregates and fulfilled the major criteria for SM and 76 patients (91%) had indolent disease. Simultaneous occurrence of cutaneous mastocytosis was observed in 59 patients (70%). Thirty-six patients (43%) had had at least one episode of an anaphylactic reaction. The clinical courses of the reactions were usually severe and patients often presented with syncope attacks (72%). Most patients reacted after hymenoptera venom stings (19/36; 53%). In 39% (14/36), a clear aetiology could not be determined. While males and females were equally frequent among the patients with SM, anaphylaxis patients showed a male predominance (61%). Anaphylactic reactions occurred more frequently in patients without cutaneous engagement. The rate of allergy sensitization was significantly higher in SM patients with anaphylaxis as compared with non-anaphylaxis SM patients, 70% vs. 23%, respectively (P = 0.0002).CONCLUSIONS AND CLINICAL RELEVANCE: Anaphylaxis is more prevalent in patients with SM, predominantly in patients with atopic SM. Hymenoptera venom-induced and idiopathic anaphylaxis were the most frequent elicitors. Our findings implicate that all mastocytosis patients with anaphylaxis should undergo detailed allergological assessment before considering treatment and preventive measures.
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  • Gülen, T, et al. (author)
  • Systemic mastocytosis : progressive evolution of an occult disease into fatal mast cell leukemia
  • 2012
  • In: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 29:5, s. 3540-3546
  • Journal article (peer-reviewed)abstract
    • Systemic mastocytosis (SM) may be associated with a clonal hematopoietic non-mast cell-lineage disease (AHNMD). SM and AHNMD even may be clonally related. This report contributes to a better understanding of the different morphological aspects of SM by demonstrating that various AHNMDs can be detected in one patient during the course of disease. Routinely processed biopsy specimens of bone marrow and spleen removed from a 63-year-old man were investigated including a broad panel of immunohistochemical stainings. KIT codon 816 mutation analysis was carried out by melting point analysis of nested PCR products amplified from DNA of pooled microdissected mast cells. The histomorphological features of the initial bone marrow showed diffuse infiltration by hairy cell leukemia (HCL). Occult SM was only detected retrospectively by demonstration of a slight diffuse increase in loosely scattered, spindle-shaped mast cells carrying the activating point mutation KIT ( D816V ). In the second bone marrow, core biopsy removed about two years later HCL had been completely eradicated, while a diagnosis of SM-AHNMD with multifocal compact mast cell infiltrates associated with a myeloproliferative neoplasm (MPN) and significant increase in eosinophilic granulocytes was established. The third and last bone marrow biopsy specimen lacked the features of both MPN and HCL but showed progression into a secondary mast cell leukemia (MCL) with a focal sarcomatous component. To the best of the authors' knowledge, this is the first description of a case of SM-AHNMD with coexisting hematological neoplasms of lymphatic and myeloid origin initially presenting as occult disease and terminating as secondary MCL.
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  • Hartmann, Karin, et al. (author)
  • Cutaneous manifestations in patients with mastocytosis : Consensus report of the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology
  • 2016
  • In: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 137:1, s. 35-45
  • Journal article (peer-reviewed)abstract
    • Cutaneous lesions in patients with mastocytosis are highly heterogeneous and encompass localized and disseminated forms. Although a classification and criteria for cutaneous mastocytosis (CM) have been proposed, there remains a need to better define subforms of cutaneous manifestations in patients with mastocytosis. To address this unmet need, an international task force involving experts from different organizations (including the European Competence Network on Mastocytosis; the American Academy of Allergy, Asthma & Immunology; and the European Academy of Allergology and Clinical Immunology) met several times between 2010 and 2014 to discuss the classification and criteria for diagnosis of cutaneous manifestations in patients with mastocytosis. This article provides the major outcomes of these meetings and a proposal for a revised definition and criteria. In particular, we recommend that the typical maculopapular cutaneous lesions (urticaria pigmentosa) should be subdivided into 2 variants, namely a monomorphic variant with small maculopapular lesions, which is typically seen in adult patients, and a polymorphic variant with larger lesions of variable size and shape, which is typically seen in pediatric patients. Clinical observations suggest that the monomorphic variant, if it develops in children, often persists into adulthood, whereas the polymorphic variant may resolve around puberty. This delineation might have important prognostic implications, and its implementation in diagnostic algorithms and future mastocytosis classifications is recommended. Refinements are also suggested for the diagnostic criteria of CM, removal of telangiectasia macularis eruptiva perstans from the current classification of CM, and removal of the adjunct solitary from the term solitary mastocytoma.
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  • Hermanson, M., et al. (author)
  • Inter- and intra-rater reliability of the head-shaft angle in children with cerebral palsy
  • 2017
  • In: Journal of Children's Orthopaedics. - : SAGE Publications. - 1863-2521 .- 1863-2548. ; 11:4, s. 256-262
  • Journal article (peer-reviewed)abstract
    • Purpose. Children with cerebral palsy (CP) are at increased risk for hip dislocation. This can be prevented in most cases using surveillance programmes that include radiographic examinations. Known risk factors for hip dislocation include young age, high Gross Motor Function Classification System (GMFCS) level and high migration percentage (MP). The head-shaft angle (HSA) has recently been described as an additional risk factor. The study aim was to determine inter- and intra-rater reliability of the HSA in a surveillance programme for children with CP. Methods. We included hip radiographs from the CP surveillance programme CPUP in southern Sweden during the first half of 2016. Fifty radiographs were included from children at GMFCS levels II-V, with a mean age of 6.6 (SD 3.2) years. Three raters measured the HSA of one hip (left or right) at baseline and four weeks later; intraclass correlation coefficient (ICC) was used to estimate interand intra-rater reliability. Results. Interand intra-rater reliability were excellent for the HSA, with ICC 0.92 (95% CI 0.87-0.96) and ICC 0.99 (95% CI 0.98-0.99), respectively. Conclusion. The HSA showed excellent interand intra-rater reliability for children with CP, providing further evidence for use of the HSA as an additional factor for identifying risk for further hip displacement or dislocation.
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  • Hägglund, A C, et al. (author)
  • Regulation and localization of matrix metalloproteinases and tissue inhibitors of metalloproteinases in the mouse ovary during gonadotropin-induced ovulation.
  • 1999
  • In: Endocrinology. - 0013-7227 .- 1945-7170. ; 140:9, s. 4351-8
  • Journal article (peer-reviewed)abstract
    • At the time of ovulation, proteolytic degradation of the follicular wall is required to release the mature oocyte. Extracellular proteases, such as serine proteases and matrix metalloproteinases (MMPs), are thought to play important roles in this process. In this study we have examined the regulation of 11 MMPs and 3 tissue inhibitors of metalloproteinases (TIMPs) during gonadotropin-induced ovulation in the mouse. Northern blot hybridization showed that messenger RNA for several MMPs and TIMPs, including gelatinase A, MT1-MMP, stromelysin-3, MMP-19, TIMP-1, TIMP-2, and TIMP-3, were present at detectable levels in the mouse ovary. In addition, ovarian extracts contained gelatinolytic activities corresponding to the inactive proforms of gelatinase A and gelatinase B. Most of the MMPs and TIMPs were expressed at a constitutive level throughout the periovulatory period. However, MMP-19 and TIMP-1 revealed a different expression pattern; they were both induced 5-10 times by hCG and reached their maximum levels at 12 h after hCG treatment, corresponding to the time of ovulation. At this time point, MMP-19 and TIMP-1 messenger RNA were localized to the granulosa and thecal-interstitial cells of large preovulatory and ovulating follicles. This temporal and spatial regulation pattern suggests that MMP-19 might be involved in the tissue degradation that occurs during follicular rupture and that TIMP-1 could have a role in terminating MMP activity after ovulation.
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  • Hägglund, G. (author)
  • Pinning the slipped and contralateral hips in the treatment of slipped capital femoral epiphysis
  • 2017
  • In: Journal of Children's Orthopaedics. - : SAGE Publications. - 1863-2521 .- 1863-2548. ; 11:2 Special Issue, s. 110-113
  • Research review (peer-reviewed)abstract
    • Purpose To describe and comment on the treatment of the slipped capital femoral epiphysis (SCFE) with pinning and to present the pros and cons of prophylactic pinning of the contralateral hip. Summary Pinning the SCFE aims to fix the epiphysis and prevent further slipping. Some devices allow for further growth and remodeling of the femoral neck post-operatively. This results in maintained femoral offset and probably reduced risk of femoroacetabular impingement. There are currently no long-term follow-up studies showing less complications or better function than after in situ fixation. The contralateral hip can be managed by prophylactic pinning or close follow-up with repeated radiographic examinations. Which of the methods is best is still controversial due to different opinions on the risk of bilateral SCFE, the consequences of a later contralateral slip and the risks of prophylactic pinning. Although research supports prophylactic pinning the child and the family’s preference is crucial.
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  • Hägglund, Maria G A, et al. (author)
  • B(0)AT2 (SLC6A15) is localized to neurons and astrocytes, and is involved in mediating the effect of leucine in the brain
  • 2013
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:3, s. e58651-
  • Journal article (peer-reviewed)abstract
    • The B(0)AT2 protein is a product of the SLC6A15 gene belonging to the SLC6 subfamily and has been shown to be a transporter of essential branched-chain amino acids. We aimed to further characterize the B(0)AT2 transporter in CNS, and to use Slc6a15 knock out (KO) mice to investigate whether B(0)AT2 is important for mediating the anorexigenic effect of leucine. We used the Slc6a15 KO mice to investigate the role of B(0)AT2 in brain in response to leucine and in particular the effect on food intake. Slc6a15 KO mice show lower reduction of food intake as well as lower neuronal activation in the ventromedial hypothalamic nucleus (VMH) in response to leucine injections compared to wild type mice. We also used RT-PCR on rat tissues, in situ hybridization and immunohistochemistry on mouse CNS tissues to document in detail the distribution of SLC6A15 on gene and protein levels. We showed that B(0)AT2 immunoreactivity is mainly neuronal, including localization in many GABAergic neurons and spinal cord motor neurons. B(0)AT2 immunoreactivity was also found in astrocytes close to ventricles, and co-localized with cytokeratin and diazepam binding inhibitor (DBI) in epithelial cells of the choroid plexus. The data suggest that B(0)AT2 play a role in leucine homeostasis in the brain.
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  • Hägglund, Maria G. A., et al. (author)
  • Characterization of the transporterB0AT3 (Slc6a17) in the rodent central nervous system
  • 2013
  • In: BMC Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 14, s. 54-
  • Journal article (peer-reviewed)abstract
    • Background: The vesicular B(0)AT3 transporter (SLC6A17), one of the members of the SLC6 family, is a transporter for neutral amino acids and is exclusively expressed in brain. Here we provide a comprehensive expression profile of B(0)AT3 in mouse brain using in situ hybridization and immunohistochemistry. Results: We confirmed previous expression data from rat brain and used a novel custom made antibody to obtain detailed co-labelling with several cell type specific markers. B(0)AT3 was highly expressed in both inhibitory and excitatory neurons. The B(0)AT3 expression was highly overlapping with those of vesicular glutamate transporter 2 (VGLUT2) and vesicular glutamate transporter 1 (VGLUT1). We also show here that Slc6a17mRNA is up-regulated in animals subjected to short term food deprivation as well as animals treated with the serotonin reuptake inhibitor fluoxetine and the dopamine/noradrenaline reuptake inhibitor bupropion. Conclusions: This suggests that the B(0)AT3 transporter have a role in regulation of monoaminergic as well as glutamatergic synapses.
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  • Hägglund, Maria G. A., et al. (author)
  • Identification of SLC38A7 (SNAT7) Protein as a Glutamine Transporter Expressed in Neurons
  • 2011
  • In: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 286:23, s. 20500-20511
  • Journal article (peer-reviewed)abstract
    • The SLC38 family of transporters has in total 11 members in humans and they encode amino acid transporters called sodium-coupled amino acid transporters (SNAT). To date, five SNATs have been characterized and functionally subdivided into systems A (SLC38A1, SLC38A2, and SLC38A4) and N (SLC38A3 and SLC38A5) showing the highest transport for glutamine and alanine. Here we present identification of a novel glutamine transporter encoded by the Slc38a7 gene, which we propose should be named SNAT7. This transporter has L-glutamine as the preferred substrate but also transports other amino acids with polar side chains, as well as L-histidine and L-alanine. The expression pattern and substrate profile for SLC38A7 shows highest similarity to the known system N transporters. Therefore, we propose that SLC38A7 is a novel member of this system. We used in situ hybridization and immunohistochemistry with a custom-made antibody to show that SLC38A7 is expressed in all neurons, but not in astrocytes, in the mouse brain. SLC38A7 is unique in being the first system N transporter expressed in GABAergic and also other neurons. The preferred substrate and axonal localization of SLC38A7 close to the synaptic cleft indicates that SLC38A7 could have an important function for the reuptake and recycling of glutamate.
  •  
30.
  • Hägglund, Maria G A, et al. (author)
  • Transport of L-glutamine, L-alanine, L-arginine and L-histidine by the neuron-specific Slc38a8 (SNAT8) in CNS
  • 2015
  • In: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 427:6, s. 1495-1512
  • Journal article (peer-reviewed)abstract
    • Glutamine transporters are important for regulating levels of glutamate and GABA in the brain. To date, six members of the SLC38 family (SNATs) have been characterized and functionally subdivided into System A (SNAT1, SNAT2 and SNAT4) and System N (SNAT3, SNAT5 and SNAT7). Here we present a first functional characterization of SLC38A8, one of the previous orphan transporters from the family and we suggest that the encoded protein should be named SNAT8 to adhere with the SNAT nomenclature. We show that SLC38A8 have preference for transporting L-glutamine, L-alanine, L-arginine, L-histidine, and L-aspartate using a Na(+)-dependent transport mechanism and that the functional characteristics of SNAT8 has highest similarity to the known System A transporters. We also provide a comprehensive CNS expression profile in mouse brain for the Slc38a8 gene and the SNAT8 protein. We show that Slc38a8 (SNAT8) is expressed in all neurons, both excitatory and inhibitory, in mouse brain using in situ hybridization and immunohistochemistry. Furthermore, proximity ligation assay show highly similar subcellular expression of SNAT7 and SNAT8. In conclusion, the neuronal SLC38A8 have a broad amino acid transport profile and is the first identified neuronal System A transporter. This suggests a key role of SNAT8 in the glutamine/glutamate(GABA) cycle in the brain.
  •  
31.
  • Hägglund, Maria, Lektor, 1975-, et al. (author)
  • Världsbäst på eHälsa kräver internationellt samarbete
  • 2017
  • In: Svenska dagbladet. - Stockholm, Sweden : Svenska Dagbladet AB & Co.. - 1101-2412.
  • Journal article (pop. science, debate, etc.)abstract
    • Det är glädjande att myndigheter nu äntligen tittar mer på internationellt delade detaljerade dokumentationsmodeller för innehåll i journaler. Vi hoppas att de ger tillräckligt kraftfulla och tydliga budskap så att de upphandlande vårdgivarna också ser vikten av detta. Om vi ska bli världsbäst på eHälsa krävs internationellt samarbete, skriver flera forskare i medicinsk informatik.
  •  
32.
  • Hägglund, Robert, 1975- (author)
  • An optimization-based approach to efficient design of analog circuits
  • 2006
  • Doctoral thesis (other academic/artistic)abstract
    • Traditional design methods for analog circuits are based on rules-of-thumbs, experience, and trial-and-error approaches involving the use of circuit simulators. It is an unstructured process, which is time-consuming, error prone, and requires the attention of a skilled analog designer. This situation calls for design methodologies that are more efficient.We have developed an efficient approach and corresponding tools that address these issues. A computer-aided design tool for design of large analog circuits with low level of human intervention has been developed. The tool combines efficient performance measure evaluation and optimization methods to determine the device sizes and generate layouts for analog circuits. Large analog circuits with about 200 devices have been designed. The circuits are optimized with respect to, e.g., power consumption, and subject to a large number of performance requirements. All performance measures are automatically derived, which reduces the probability of introducing errors.Experimental results indicate that our approach can be used to design robust highperformance analog circuits with improved performance compared to manual approaches. Furthermore, the computer-aided tool decreases both the overall design time and the time required of a skilled designer.We have developed a technique that derives the performance equations directly from the circuit schematics as well as techniques for efficient evaluation of the equations. This approach reduces the risk of introducing errors and enables the use of accurate device models, i.e., high-accuracy equations without approximations are obtained.In fully differential circuits, common-mode stabilization is required. Even though a multitude of common-mode feedback circuits have been presented in the literature, the performance requirements for these circuits are rarely fully explained. Here, the common-mode feedback design problem is addressed to gain design insights. A Volterra series model is used to analyze the distortion terms caused by the use of a common-mode feedback. From this analysis, the DC gain, bandwidth, and stability requirements of the common-mode loop are discussed.
  •  
33.
  • Ingvarsson, T, et al. (author)
  • Assessment of primary hip osteoarthritis: comparison of radiographic methods using colon radiographs : comparison of radiographic methods using colon radiographs
  • 2000
  • In: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 59:8, s. 650-653
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To compare the reliability of quantitative measurement of minimum hip joint space with a qualitative global assessment of radiological features for estimating the prevalence of primary osteoarthritis (OA) of the hip in colon radiographs.METHODS: All colon radiographs from patients aged 35 or older, taken at three different radiographic departments in Iceland during the years 1990-96, were examined. A total of 3002 hips in 638 men and 863 women were analysed. Intraobserver and interobserver reliability was assessed by measuring 147 randomly selected radiographs (294 hips) twice by the same observer, and 87 and 98 randomly selected radiographs (174 and 196 hips) by two additional independent observers. Minimum hip joint space was measured with a millimetre ruler, and global assessment of radiological features by a published atlas.RESULTS: With a minimum joint space of 2.5 mm or less as definition for OA, 212 hips were defined as having OA. When the global Kellgren and Lawrence assessment with grade 2 (definite narrowing in the presence of definite osteophytes) or higher as definition for OA was used, 202 hips showed OA. However, only 166 hips were diagnosed as OA with both systems. With 2.0 or 3.0 mm minimum joint space as cut off point, the difference between the two methods increased. Both intrarater and interrater reliability was significantly higher with joint space measurement than with global assessment.CONCLUSIONS: Overall prevalence of radiological OA was similar with the two methods. However, the quantitative measurement of minimum hip joint space had a better within-observer and between-observer reliability than qualitative global assessment of radiographic features of hip OA. It is thus suggested that minimum joint space measurement is a preferable method in epidemiological studies of radiological hip OA.
  •  
34.
  • Ingvarsson, T, et al. (author)
  • Long-term results after adolescent Blount's disease
  • 1997
  • In: Journal of Pediatric Orthopaedics Part B. - 1060-152X. ; 6:2, s. 6-153
  • Journal article (peer-reviewed)abstract
    • A long-term follow-up study was made of 23 patients with an average age of 47 years (range 38-68 years) who had adolescent Blount's disease. Four patients had bilateral disease (27 affected knees). Nine knees had no treatment during childhood, 11 were treated by physiodesis, and seven were treated by osteotomy of the proximal tibia. At follow-up, most of the patients had no pain or mild pain from their knee. Nine knees showed arthrosis. We conclude that most children with adolescent Blount's disease will have a straight leg at middle age without arthrosis and that this result can be obtained in one of four patients without treatment.
  •  
35.
  • Ingvarsson, T, et al. (author)
  • Long-term results after infantile Blount's disease
  • 1998
  • In: Journal of Pediatric Orthopaedics Part B. - 1060-152X. ; 7:3, s. 9-226
  • Journal article (peer-reviewed)abstract
    • A long-term follow-up of 49 patients with an average age of 38 years (range: 25-67 years) who had experienced infantile Blount's disease was done. Thirty-seven patients had bilateral disease, giving a total of 86 affected knees. Thirty-eight knees had conservative or no treatment during childhood; 13 were treated by epiphysiodesis, and 35 by osteotomy. At follow-up, 11 knees showed arthrosis, and 9 were graded as mild. Ten knees had been surgically treated by medial meniscectomy at an average age of 29 years (range: 19-45 years), after the diagnosis of Blount's disease. Four of the knees showed arthrosis. Most of the patients had a straight leg and mild or no pain from their knee. It is concluded that most children with infantile Blount's disease will, at the age of 40 years, have a straight leg without arthrosis and that one third can reach this result without any treatment.
  •  
36.
  • Kennedy, Vanessa E., et al. (author)
  • Mast cell leukemia : clinical and molecular features and survival outcomes of patients in the ECNM Registry
  • 2023
  • In: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 7:9, s. 1713-1724
  • Journal article (peer-reviewed)abstract
    • Mast cell leukemia (MCL) is a rare subtype of systemic mastocytosis defined by >= 20% mast cells (MC) on a bone marrow aspirate. We evaluated 92 patients with MCL from the European Competence Network on Mastocytosis registry. Thirty-one (34%) patients had a diagnosis of MCL with an associated hematologic neoplasm (MCL-AHN). Chronic MCL (lack of C-findings) comprised 14% of patients, and only 4.5% had "leukemic MCL" (>= 10% circulating MCs). KIT D816V was found in 62/85 (73%) evaluable patients; 9 (11%) individuals exhibited alternative KIT mutations, and no KIT variants were detected in 14 (17%) subjects. Ten evaluable patients (17%) had an abnormal karyotype and the poor-risk SRSF2, ASXL1, and RUNX1 (S/A/R) mutations were identified in 16/36 (44%) patients who underwent next-generation sequencing. Midostaurin was the most common therapy administered to 65% of patients and 45% as first-line therapy. The median overall survival (OS) was 1.6 years. In multivariate analysis (S/A/R mutations excluded owing to low event rates), a diagnosis of MCL-AHN (hazard ratio [HR], 4.7; 95% confidence interval [CI], 1.7-13.0; P = .001) and abnormal karyotype (HR, 5.6; 95% CI, 1.4-13.3; P = .02) were associated with inferior OS; KIT D816V positivity (HR, 0.33; 95% CI, 0.11-0.98; P = .04) and midostaurin treatment (HR, 0.32; 95% CI, 0.08-0.72; P = .008) were associated with superior OS. These data provide the most comprehensive snapshot of the clinicopathologic, molecular, and treatment landscape of MCL to date, and should help further inform subtyping and prognostication of MCL.
  •  
37.
  •  
38.
  • Kilic, O., et al. (author)
  • Severe musculoskeletal time-loss injuries and symptoms of common mental disorders in professional soccer: a longitudinal analysis of 12-month follow-up data
  • 2018
  • In: Knee Surgery, Sports Traumatology, Arthroscopy. - : SPRINGER. - 0942-2056 .- 1433-7347. ; 26:3, s. 946-954
  • Journal article (peer-reviewed)abstract
    • Psychological factors have shown to be predictors of injury in professional football. However, it seems that this is a two-way relationship, as severe musculoskeletal time-loss injuries have shown to be associated with the onset of symptoms of common mental disorders (CMD). There is no longitudinal study performed exploring this interaction between symptoms of CMD and injuries. The purpose of this study was to explore the interaction between severe musculoskeletal time-loss injuries and symptoms of CMD in professional football players over a 12-month period. Players were recruited by their national players unions in five European countries. Symptoms of CMD included in the study were related to distress, anxiety/depression, sleep disturbance and adverse alcohol use. A total of 384 professional football players were enrolled in the study, of whom 262 (68%) completed the 12-month follow-up period. The mean age of the participants at baseline was 27 +/- 5 years, and they had played professional football for 8 +/- 5 years on average. Symptoms of CMD at baseline were not associated with the onset of severe musculoskeletal time-loss injuries during the follow-up period with relative risks (and 95% CI) ranging from 0.6 (0.3-1.0) to 1.0 (0.5-2.2). In contrast, severe musculoskeletal time-loss injuries reported at baseline were associated with the onset of symptoms of CMD during the follow-up period with relative risks ranging from 1.8 (0.8-3.7) to 6.9 (4.0-11.9). No relationship was found between symptoms of CMD and the onset of severe musculoskeletal time-loss injuries. However, professional football players who suffered from severe musculoskeletal time-loss injuries are likely to develop subsequent symptoms of CMD. This study emphasizes the need for an interdisciplinary medical approach, which not only focuses on the physical but also on the mental health of professional football players. An early identification of players at risk of symptoms of CMD, such as those suffering from severe musculoskeletal injuries, creates the opportunity for an interdisciplinary clinical medical team to treat the players timely and adequately. Prospective cohort study, Level II.
  •  
39.
  • Kluin-Nelemans, Hanneke C., et al. (author)
  • Cytogenetic and molecular aberrations and worse outcome for male patients in systemic mastocytosis
  • 2021
  • In: Theranostics. - : Ivyspring International Publisher. - 1838-7640. ; 11:1, s. 292-303
  • Journal article (peer-reviewed)abstract
    • In systemic mastocytosis (SM), the clinical features and survival vary greatly. Patient-related factors determining the outcome in SM are largely unknown. Methods: We examined the impact of sex on the clinical features, progression-free survival (PFS), and overall survival (OS) in 3403 patients with mastocytosis collected in the registry of the European Competence Network on Mastocytosis (ECNM). The impact of cytogenetic and molecular genetic aberrations on sex differences was analyzed in a subset of patients. Results: Of all patients enrolled, 55.3% were females. However, a male predominance was found in a subset of advanced SM (AdvSM) patients, namely SM with an associated hematologic neoplasm (SM-AHN, 70%; p < 0.001). Correspondingly, organomegaly (male: 23% vs. female: 13%, p = 0.007) was more, whereas skin involvement (male: 71% vs. female: 86%, p = 0.001) was less frequent in males. In all patients together, OS (p < 0.0001) was significantly inferior in males, and also within the WHO sub-categories indolent SM, aggressive SM (ASM) and SM-AHN. PFS was significantly (p = 0.0002) worse in males when all patients were grouped together; due to low numbers of events, this significance persisted only in the subcategory smoldering SM. Finally, prognostically relevant cytogenetic abnormalities (10% vs. 5%, p = 0.006) or molecular aberrations (SRSF2/ASXLI/RUNXI profile; 63% vs. 40%, p = 0.003) were more frequently present in males. Conclusions: Male sex has a major impact on clinical features, disease progression, and survival in mastocytosis. Male patients have an inferior survival, which seems related to the fact that they more frequently develop a multi-mutated AdvSM associated with a high-risk molecular background.
  •  
40.
  • Lübke, Johannes, et al. (author)
  • Serum chemistry profiling and prognostication in systemic mastocytosis : a registry-based study of the ECNM and GREM
  • 2024
  • In: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 8:11, s. 2890-2900
  • Journal article (peer-reviewed)abstract
    • Certain laboratory abnormalities correlate with subvariants of systemic mastocytosis (SM) and are often prognostically relevant. To assess the diagnostic and prognostic value of individual serum chemistry parameters in SM, 2607 patients enrolled within the European Competence Network on Mastocytosis and 575 patients enrolled within the German Registry on Eosinophils and Mast Cells were analyzed. For screening and diagnosis of SM, tryptase was identified as the most speci fic serum parameter. For differentiation between indolent and advanced SM (AdvSM), the following serum parameters were most relevant: tryptase, alkaline phosphatase, beta 2-microglobulin, lactate dehydrogenase (LDH), albumin, vitamin B12, and C-reactive protein (P < .001). With regard to subvariants of AdvSM, an elevated LDH of ≥ 260 U/L was associated with multilineage expansion (leukocytosis, r = 0.37, P < .001; monocytosis, r = 0.26, P < .001) and the presence of an associated myeloid neoplasm (P < .001), whereas tryptase levels were highest in mast cell leukemia (MCL) vs non-MCL (308 μg/L vs 146 μg/L, P = .003). Based on multivariable analysis, the hazard-risk weighted assignment of 1 point to LDH (hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.1-4.0; P = .018) and 1.5 points each to β2-microglobulin (HR, 2.7; 95% CI, 1.4-5.4; P = .004) and albumin (HR, 3.3; 95% CI, 1.7-6.5; P = .001) delineated a highly predictive 3-tier risk classification system (0 points, 8.1 years vs 1 point, 2.5 years; ≥1.5 points, 1.7 years; P < .001). Moreover, serum chemistry parameters enabled further stratification of patients classified as having an International Prognostic Scoring System for Mastocytosis-AdvSM1/2 risk score (P = .027). In conclusion, serum chemistry pro filing is a crucial tool in the clinical practice supporting diagnosis and prognostication of SM and its subvariants.
  •  
41.
  •  
42.
  • Nordmark, E., et al. (author)
  • Cerebral palsy in southern Sweden II. Gross motor function and disabilities
  • 2001
  • In: Acta Paediatrica, International Journal of Paediatrics. - 0803-5253. ; 90:11, s. 1277-1282
  • Journal article (peer-reviewed)abstract
    • The gross motor function and disabilities in children with cerebral palsy in southern Sweden were investigated and related to clinical features. The study covered the birth year period 1990-1993 and comprised 167 children, 145 of them born in Sweden and 22 born abroad. The clinical features and gross motor function were analysed at a mean age of 6.8 y. Clinical features were obtained from a continuing healthcare follow-up programme. Gross motor function was classified according to the Gross Motor Function Classification System (GMFCS). Walking independently was possible for 86% of the hemiplegic, 63% of the pure ataxic, 61% of the diplegic and 21% of the dyskinetic children. None of the tetraplegic children was able to walk. The classification of gross motor function revealed that 59% of the children were categorized into levels I and II (mildly disabled), 14% into level III (moderately disabled) and 27% into levels IV and V (severely disabled). Children born abroad were more severely disabled. Conclusion: The standardized age-related classification system GMFCS enabled a specific description of gross motor function in relation to clinical features. Significant differences between GMFCS levels and subgroups of diagnosis, aetiology, intellectual capacity, epilepsy and visual impairment were found.
  •  
43.
  • Ny, A, et al. (author)
  • Ovulation in plasminogen-deficient mice.
  • 1999
  • In: Endocrinology. - 0013-7227 .- 1945-7170. ; 140:11, s. 5030-5
  • Journal article (peer-reviewed)abstract
    • Many different studies suggest that plasmin generated from plasminogen plays a crucial role in the degradation of the follicular wall at the time of ovulation. We have assessed the physiological relevance of plasmin on ovulation by studying plasminogen-deficient mice. Ovulation efficiency (mean number of ova released per mouse) was determined both in a standardized ovulation model in which 25-day-old immature mice were injected with finite amounts of gonadotropins to induce ovulation and during physiological ovulation using adult normally cycling mice. Our results revealed that the temporal onset of follicular wall rupture (first ova observed in bursa or oviduct) was not delayed in plasminogen-deficient mice during gonadotropin-induced ovulation. However, there was a trend toward slightly reduced ovulation efficiency in the plasminogen-deficient mice. This reduction was only 13% and not statistically significant (P = 0.084) and may be connected to a delayed maturation of these mice manifested in reduced body and ovary weights. During physiological ovulation adult plasminogen-deficient mice had normal ovulation efficiency compared with plasminogen wild-type mice. Taken together our results indicate that under the conditions used in this study plasmin is not required for efficient follicular rupture or for activation of other proteases involved in this process. Alternatively, the role of plasmin may be effectively compensated for by other mechanisms in the absence of plasmin.
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44.
  •  
45.
  • Odelgard, Anna, et al. (author)
  • Phylogeny and Expansion of Serine/Threonine Kinases in Phagocytotic Bacteria in the Phylum Planctomycetota
  • 2024
  • In: Genome Biology and Evolution. - : Oxford University Press. - 1759-6653. ; 16:4
  • Journal article (peer-reviewed)abstract
    • The recently isolated bacterium "Candidatus Uabimicrobium amorphum" is the only known prokaryote that can engulf other bacterial cells. Its proteome contains a high fraction of proteins involved in signal transduction systems, which is a feature normally associated with multicellularity in eukaryotes. Here, we present a protein-based phylogeny which shows that "Ca. Uabimicrobium amorphum" represents an early diverging lineage that clusters with the Saltatorellus clade within the phylum Planctomycetota. A gene flux analysis indicated a gain of 126 protein families for signal transduction functions in "Ca. Uabimicrobium amorphum", of which 66 families contained eukaryotic-like Serine/Threonine kinases with Pkinase domains. In total, we predicted 525 functional Serine/Threonine kinases in "Ca. Uabimicrobium amorphum", which represent 8% of the proteome and is the highest fraction of Serine/Threonine kinases in a bacterial proteome. The majority of Serine/Threonine kinases in this species are membrane proteins and 30% contain long, tandem arrays of WD40 or TPR domains. The pKinase domain was predicted to be located in the cytoplasm, while the WD40 and TPR domains were predicted to be located in the periplasm. Such domain combinations were also identified in the Serine/Threonine kinases of other species in the Planctomycetota, although in much lower abundances. A phylogenetic analysis of the Serine/Threonine kinases in the Planctomycetota inferred from the Pkinase domain alone provided support for lineage-specific expansions of the Serine/Threonine kinases in "Ca. Uabimicrobium amorphum". The results imply that expansions of eukaryotic-like signal transduction systems are not restricted to multicellular organisms, but have occurred in parallel in prokaryotes with predatory lifestyles and phagocytotic-like behaviors.
  •  
46.
  • Rodas, G., et al. (author)
  • Male field hockey prospective injury study. Comparison with soccer [Estudio lesional prospectivo en hockey hierba. Comparaci�n con el f�tbol]
  • 2009
  • In: Archivos de Medicina del Deporte. - 0212-8799. ; 26:129, s. 22-30
  • Journal article (peer-reviewed)abstract
    • The next work describes the injuries incidence, severity, type and anatomical distribution of a male field hockey team from the honour division and one Spanish first division soccer team. Field hockey is a sport that, up to date, has had a limited scientific follow-up and we just have few investigation studies from a methodological point of view. Most of the existing works had a retrospective methodology and are just for a concrete competitions or championships. Our study provides, in addition, a comparison between the most frequent injuries in each of the sports and between the risks factors that can produce them according with the diagnosis and classification of the UEFA model for the study of injuries in professional football. The results show us a major lesional incidence in field hockey in spite of having fewer exposition hours than football along the season. This fact, as it is commented in the discussion, can be made clear by the semiprofessional character of this sport. There is also targeted that the distribution of the most frequent injuries is in certain relation comparing both sports. It is also the first comparative study in our country of injury incidence between these sports, and the first prospective study in field hockey, waiting to serve as a starting point for more studies about it.
  •  
47.
  • Schiöth, Helgi B, et al. (author)
  • Evolutionary origin of amino acid transporter families SLC32, SLC36 and SLC38 and physiological, pathological and therapeutic aspects
  • 2013
  • In: Molecular Aspects of Medicine. - : Elsevier BV. - 0098-2997 .- 1872-9452. ; 34:2-3, s. 571-585
  • Research review (peer-reviewed)abstract
    • About 25% of all solute carriers (SLCs) are likely to transport amino acids as their primary substrate. One of the major phylogenetic clusters of amino acid transporters from the SLC family is the β-family, which is part of the PFAM APC clan. The β-family includes three SLC families, SLC32, SLC36 and SLC38 with one, four and eleven members in humans, respectively. The most well characterized genes within these families are the vesicular inhibitory amino acid transporter (VIAAT, SLC32A1), PAT1 (SLC36A1), PAT2 (SLC36A2), PAT4 (SLC36A4), SNAT1 (SLC38A1), SNAT2 (SLC38A2), SNAT3 (SLC38A3), and SNAT4 (SLC38A4). Here we review the structural characteristics and functional role of these transporters. We also mined the complete protein sequence datasets for nine different genomes to clarify the evolutionary history of the β-family of transporters. We show that all three main branches of the this family are found as far back as green algae suggesting that genes from these families existed in the early eukaryote before the split of animals and plants and that they are present in most animal species. We also address the potential of further drug development within this field highlighting the important role of these transporters in neurotransmission and transport of amino acids as nutrients.
  •  
48.
  • Sperr, Wolfgang R., et al. (author)
  • International prognostic scoring system for mastocytosis (IPSM) : a retrospective cohort study
  • 2019
  • In: The Lancet Haematology. - : ELSEVIER SCI LTD. - 2352-3026. ; 6:12, s. E638-E649
  • Journal article (peer-reviewed)abstract
    • Background The WHO classification separates mastocytosis into distinct variants, but prognostication remains a clinical challenge. The aim of this study was to improve prognostication for patients with mastocytosis. Methods We analysed data of the registry of the European Competence Network on Mastocytosis including 1639 patients (age 17-90 years) diagnosed with mastocytosis according to WHO criteria between Jan 12, 1978, and March 16, 2017. Univariate and multivariate analyses with Cox regression were applied to identify prognostic variables predicting survival outcomes and to establish a prognostic score. We validated this International Prognostic Scoring System in Mastocytosis (IPSM) with data of 462 patients (age 17-79 years) from the Spanish network Red Espanola de Mastocitosis diagnosed between Jan 22, 1998, and Nov 2, 2017. Findings The prognostic value of the WHO classification was confirmed in our study (p<0.0001). For patients with non-advanced mastocytosis (n=1380), we identified age 60 years or older (HR 10.75, 95% CI 5.68-20.32) and a concentration of alkaline phosphatase 100 U/L or higher (2.91, 1.60-5.30) as additional independent prognostic variables for overall survival. The resulting scoring system divided patients with non-advanced mastocytosis into three groups: low (no risk factors), intermediate 1 (one risk factor), and intermediate 2 (two risk factors). Overall survival and progression-free survival differed significantly among these groups (p<0.0001). In patients with advanced mastocytosis (n=259), age 60 years or older (HR 2.14, 95% CI 1.42-3.22), a concentration of tryptase 125 ng/mL or higher (1.81, 1.20-2.75), a leukocyte count of 16 x 10(9) per L or higher (1.88, 1.27-2.79), haemoglobin of 11 g/dL or lower (1.71, 1.13-2.57), a platelet count of 100 x 10(9) per L or lower (1.63, 1.13-2.34), and skin involvement (0.46, 0.30-0.69) were prognostic variables. Based on these variables, a separate score for advanced mastocytosis with four risk categories was established, with significantly different outcomes for overall survival and progression-free survival (p<0.0001). The prognostic value of both scores was confirmed in 413 patients with non-advanced disease and 49 with advanced mastocytosis from the validation cohort. Interpretation The IPSM scores for patients with non-advanced and advanced mastocytosis can be used to predict survival outcomes and guide treatment decisions. However, the predictive value of the IPSM needs to be confirmed in forthcoming trials. Copyright (C) 2019 Elsevier Ltd. All rights reserved.
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49.
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50.
  • Taloyan, Marina, et al. (author)
  • Remote digital monitoring for selected chronic diseases in primary health care
  • 2023
  • In: The Cochrane Library. - : John Wiley & Sons. - 1465-1858. ; :3
  • Journal article (peer-reviewed)abstract
    • Abstract - Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the benefits and harms of remote digital monitoring for adults with selected chronic diseases (hypertension, type 2 diabetes, chronic obstructive pulmonary disease, congestive heart failure, and asthma) in primary healthcare settings.
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