| 61. |
- Edlund, Anna, et al.
(författare)
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CFTR is involved in the regulation of glucagon secretion in human and rodent alpha cells
- 2017
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1, s. 90-
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Tidskriftsartikel (refereegranskat)abstract
- Glucagon is the main counterregulatory hormone in the body. Still, the mechanism involved in the regulation of glucagon secretion from pancreatic alpha cells remains elusive. Dysregulated glucagon secretion is common in patients with Cystic Fibrosis (CF) that develop CF related diabetes (CFRD). CF is caused by a mutation in the Cl− channel Cystic fibrosis transmembrane conductance regulator (CFTR), but whether CFTR is present in human alpha cells and regulate glucagon secretion has not been investigated in detail. Here, both human and mouse alpha cells showed CFTR protein expression, whereas CFTR was absent in somatostatin secreting delta cells. CFTR-current activity induced by cAMP was measured in single alpha cells. Glucagon secretion at different glucose levels and in the presence of forskolin was increased by CFTR-inhibition in human islets, whereas depolarization-induced glucagon secretion was unaffected. CFTR is suggested to mainly regulate the membrane potential through an intrinsic alpha cell effect, as supported by a mathematical model of alpha cell electrophysiology. In conclusion, CFTR channels are present in alpha cells and act as important negative regulators of cAMP-enhanced glucagon secretion through effects on alpha cell membrane potential. Our data support that loss-of-function mutations in CFTR contributes to dysregulated glucagon secretion in CFRD.
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| 62. |
- Edlund, Anna, et al.
(författare)
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Defective exocytosis and processing of insulin in a cystic fibrosis mouse model
- 2019
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Ingår i: Journal of Endocrinology. - 1479-6805. ; 241:1, s. 45-57
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Tidskriftsartikel (refereegranskat)abstract
- Cystic fibrosis-related diabetes (CFRD) is a common complication for patients with cystic fibrosis (CF), a disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). The cause of CFRD is unclear, but a commonly observed reduction in first-phase insulin secretion suggests defects at the beta cell level. Here we aimed to examine beta- and alpha-cell function in the Cftrtm1EUR/F508del mouse model (C57BL/6J), which carries the most common human mutation in CFTR, the F508del mutation. CFTR expression, beta cell mass, insulin granule distribution, hormone secretion and single cell capacitance changes were evaluated using islets (or beta cells) from F508del mice and age-matched wild-type mice aged 7-10 weeks. Granular pH was measured with DND-189 fluorescence. Serum glucose, insulin and glucagon levels were measured in vivo, and glucose tolerance was assessed using IPGTT. We show increased secretion of proinsulin and concomitant reduced secretion of C-peptide in islets from F508del mice compared to WT mice. Exocytosis and number of docked granules was reduced. We confirmed reduced granular pH by CFTR stimulation. We detected decreased pancreatic beta cell area, but unchanged beta cell number. Moreover, the F508del mutation caused failure to suppress glucagon secretion leading to hyperglucagonemia. In conclusion, F508del mice have beta cell defects resulting in 1) reduced number of docked insulin granules and reduced exocytosis, and 2) potential defective proinsulin cleavage and secretion of immature insulin. These observations provide insight into the functional role of CFTR in pancreatic islets and contribute to increased understanding of the pathogenesis of CFRD.
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| 63. |
- Eliasson, Ann-Christin, et al.
(författare)
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Efficacy of the small step program in a randomised controlled trial for infants below age 12 months with clinical signs of CP; a study protocol
- 2016
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Ingår i: BMC Pediatrics. - London : Springer Science and Business Media LLC. - 1471-2431. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Children with cerebral palsy (CP) have life-long motor disorders, and they are typically subjected to extensive treatment throughout their childhood. Despite this, there is a lack of evidence supporting the effectiveness of early interventions aiming at improving motor function, activity, and participation in daily life. The study will evaluate the effectiveness of the newly developed Small Step Program, which is introduced to children at risk of developing CP during their first year of life. The intervention is based upon theories of early learning-induced brain plasticity and comprises important components of evidence-based intervention approaches used with older children with CP.Method and design: A two-group randomised control trial will be conducted. Invited infants at risk of developing CP due to a neonatal event affecting the brain will be randomised to either the Small Step Program or to usual care. They will be recruited from Astrid Lindgren Children's Hospital at regular check-up and included at age 3-8 months. The Small Step Program was designed to provide individualized, goal directed, and intensive intervention focusing on hand use, mobility, and communication in the child's own home environment and carried out by their parents who have been trained and coached by therapists. The primary endpoint will be approximately 35 weeks after the start of the intervention, and the secondary endpoint will be at 2 years of age. The primary outcome measure will be the Peabody Developmental Motor Scale (second edition). Secondary assessments will measure and describe the children's general and specific development and brain pathology. In addition, the parents' perspective of the program will be evaluated. General linear models will be used to compare outcomes between groups.Discussion: This paper presents the background and rationale for developing the Small-Step Program and the design and protocol of a randomized controlled trial. The aim of the Small Step Program is to influence development by enabling children to function on a higher level than if not treated by the program and to evaluate whether the program will affect parent's ability to cope with stress and anxiety related to having a child at risk of developing CP.
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| 64. |
- Eliasson, Ann-Christin, 1950-, et al.
(författare)
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Guidelines for future research in constraint-induced movement therapy for children with unilateral cerebral palsy : an expert consensus
- 2014
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Ingår i: Developmental Medicine & Child Neurology. - : Mac Keith Press. - 0012-1622 .- 1469-8749. ; 56:2, s. 125-137
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The aim of this study was to provide an overview of what is known about constraintinduced movement therapy (CIMT) in children with unilateral cerebral palsy (CP), to identify current knowledge gaps, and to provide suggestions for future research.METHOD: Nine experts participated in a consensus meeting. A comprehensive literature search was conducted and data were summarized before the meeting. The core model produced by the European network for Health Technology Assessment was used as a framework for discussion and to identify critical issues for future research.RESULTS: All models of CIMT have demonstrated improvements in the upper limb abilities of children with unilateral CP. A consensus was reached on 11 important questions to be further explored in future studies. The areas of highest priority included the effect of dosage, the effect of repeated CIMT, and the impact of predictive factors, such as age, on the response to CIMT. Consensus suggestions for future study designs and the use of validated outcome measures were also provided.INTERPRETATION: The CIMT construct is complex, and much remains unknown. It is unclear whether a specific model of CIMT demonstrates superiority over others and whether dosage of training matters. Future research should build upon existing knowledge and aim to provide information that will help implement CIMT in various countries with different healthcare resources and organizational structures.
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| 65. |
- Eliasson, Ann-Christin, 1950-, et al.
(författare)
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Mini-MACS : development of the Manual Ability Classification System for children younger than 4 years of age with signs of cerebral palsy
- 2017
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Ingår i: Developmental Medicine & Child Neurology. - : Mac Keith Press. - 0012-1622 .- 1469-8749. ; 59:1, s. 72-78
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To develop the Mini-Manual Ability Classification System (Mini-MACS) and to evaluate the extent to which its ratings are valid and reliable when children younger than 4 years are rated by their parents and therapists.METHOD: The Mini-MACS was created by making adjustments to the MACS. The development involved a pilot project, consensus discussions within an expert group, and the creation of a test version of the Mini-MACS that was evaluated for content validity and interrater reliability. A convenience sample of 61 children with signs of cerebral palsy aged 12 to 51 months (mean age 30.2mo [SD 10.1]) were classified by one parent and two occupational therapists across a total of 64 assessments. Agreement between the parents' and therapists' ratings was evaluated using the intraclass correlation coefficient (ICC) and the percentage of agreement.RESULTS: The first sentence of the five levels in the MACS was kept, but other descriptions within the Mini-MACS were adjusted to be more relevant for the younger age group. The ICC between parents and therapists was 0.90 (95% confidence interval [CI] 0.79-0.92), and for the two therapists it was 0.97 (95% CI 0.78-0.92). Most parents and therapists found the descriptions in the Mini-MACS suitable and easy to understand.INTERPRETATION: The Mini-MACS seems applicable for children from 1 to 4 years of age.
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| 66. |
- Eliasson, A. C., et al.
(författare)
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The Manual Ability Classification System (MACS) for children with cerebral palsy: scale development and evidence of validity and reliability
- 2006
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Ingår i: Dev Med Child Neurol. - 0012-1622 .- 1469-8749. ; 48:7, s. 549-54
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Tidskriftsartikel (refereegranskat)abstract
- The Manual Ability Classification System (MACS) has been developed to classify how children with cerebral palsy (CP) use their hands when handling objects in daily activities. The classification is designed to reflect the child's typical manual performance, not the child's maximal capacity. It classifies the collaborative use of both hands together. Validation was based on the experience within an expert group, a review of the literature, and thorough analysis of children across a spectrum of function. Discussions continued until consensus was reached, first about the constructs, then about the content of the five levels. Parents and therapists were interviewed about the content and the description of levels. Reliability was tested between pairs of therapists for 168 children (70 females, 98 males; with hemiplegia [n=52], diplegia [n=70], tetraplegia [n=19], ataxia [n=6], dyskinesia [n=19], and unspecified CP [n=2]) between 4 and 18 years and between 25 parents and their children's therapists. The results demonstrated that MACS has good validity and reliability. The intraclass correlation coefficient between therapists was 0.97 (95% confidence interval 0.96-0.98), and between parents and therapist was 0.96 (0.89-0.98), indicating excellent agreement.
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| 67. |
- Eliasson, Ann-Christin, et al.
(författare)
-
The Manual Ability Classification System (MACS) for children with cerebral palsy: scale development and evidence of validity and reliability
- 2006
-
Ingår i: Developmental Medicine & Child Neurology. - : Wiley. - 0012-1622 .- 1469-8749. ; 48:7, s. 549-554
-
Tidskriftsartikel (refereegranskat)abstract
- The Manual Ability Classification System (MACS) has been developed to classify how children with cerebral palsy (CP) use their hands when handling objects in daily activities. The classification is designed to reflect the child's typical manual performance, not the child's maximal capacity. It classifies the collaborative use of both hands together. Validation was based on the experience within an expert group, a review of the literature, and thorough analysis of children across a spectrum of function. Discussions continued until consensus was reached, first about the constructs, then about the content of the five levels. Parents and therapists were interviewed about the content and the description of levels. Reliability was tested between pairs of therapists for 168 children (70 females, 98 males; with hemiplegia [n=52], diplegia [n=70], tetraplegia [n=19], ataxia [n=6], dyskinesia [n=19], and unspecified CP [n=2]) between 4 and 18 years and between 25 parents and their children's therapists. The results demonstrated that MACS has good validity and reliability. The intraclass correlation coefficient between therapists was 0.97 (95% confidence interval 0.96-0.98), and between parents and therapist was 0.96 (0.89-0.98), indicating excellent agreement.
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| 68. |
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| 69. |
- Eliasson, G, et al.
(författare)
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Bättre kontakt mellan primär-och sjukhusvård. Dansk praksiskonsulentordning i nordiskt perspektiv
- 1998
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Ingår i: Nordisk medicin. - 0029-1420. ; 113:8, s. 272-274
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Tidskriftsartikel (refereegranskat)abstract
- A successful model of liaison between the primary and secondary (hospital) levels of health care entails improved co-operation between hospital doctors and general practitioners (GPs). Since its introduction in Denmark in 1991, this approach has been adopted in Sweden and, to a lesser extent, in Norway. Important principles of the model include: 1) both at the primary and secondary level, responsibility for cooperation rests with the physicians themselves; 2) all physicians at both levels are involved; 3) liaison is maintained by selected GPs serving as liaison officers acting in concert under the guidance of a coordinator; 4) liaison officers are responsible for cultivating personal contacts and good relations at hospitals, and promoting interest in and commitment to the system. Evaluation of the model requires both quantitative and qualitative studies. Although few evaluations have been completed, and no definite conclusions can be drawn, the preliminary results of current evaluations in progress in Sweden and Norway are promising, as are the reported experiences of those who use the system. A Nordic ad hoc group has been actively engaged in promoting the quality of primary-secondary health care liaison since 1997.
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| 70. |
- Eliasson, Jonas, et al.
(författare)
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Introduction : Editorial
- 2009
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Ingår i: Transportation Research Part A. - Amsterdam : Elsevier. - 0965-8564 .- 1879-2375. ; 43:3, s. 237-239
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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