| 1. |
- Ek, Linda, et al.
(författare)
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Hand Assessment for Infants : normative reference values
- 2019
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Ingår i: Developmental Medicine & Child Neurology. - : Mac Keith Press. - 0012-1622 .- 1469-8749. ; 61:9, s. 1087-1092
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To create normative reference values for unilateral and bilateral use of the hands, using the Hand Assessment for Infants (HAI), a newly developed criterion-referenced assessment measuring hand use in infants aged 3 months to 12 months at risk of cerebral palsy (CP).METHOD: In total, 489 HAI assessments of typically developing infants (243 females, 246 males), aged 3 months to 10 months (mean 6mo 14d [SD 2mo 5d]), were collected in Italy and Sweden. Normative growth curves based on mean and SDs were created, as well as skill acquisition curves for each test item. Correlation to age and differences between groups based on sex and nationality, as well as differences between the right and the left hand, were investigated.RESULTS: The growth curves showed a steady increase in mean value and a decrease in SD over age. There were no differences between groups based on sex or nationality. There was a negligible mean difference (0.1 raw score) between the right and left hands.INTERPRETATION: HAI normative reference values are now available, which can assist in identifying deviating hand use for each month of age, as well as a side difference between hands in infants at risk of CP.WHAT THIS PAPER ADDS: A Hand Assessment for Infants (HAI) result greater than 2SD below the mean indicates atypical hand use. Skill acquisition curves describe the age at which typically developing infants master the HAI items. Most typically developing infants do not demonstrate asymmetry in hand use.
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| 2. |
- Eliasson, Ann-Christin, 1950-, et al.
(författare)
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Efficacy of baby-CIMT : study protocol for a randomised controlled trial on infants below age 12 months, with clinical signs of unilateral CP
- 2014
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Ingår i: BMC Pediatrics. - : BioMed Central. - 1471-2431. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Infants with unilateral brain lesions are at high risk of developing unilateral cerebral palsy (CP). Given the great plasticity of the young brain, possible interventions for infants at risk of unilateral CP deserve exploration. Constraint-induced movement therapy (CIMT) is known to be effective for older children with unilateral CP but is not systematically used for infants. The development of CIMT for infants (baby-CIMT) is described here, as is the methodology of an RCT comparing the effects on manual ability development of baby-CIMT versus baby-massage. The main hypothesis is that infants receiving baby-CIMT will develop manual ability in the involved hand faster than will infants receiving baby-massage in the first year of life.METHOD AND DESIGN: The study will be a randomised, controlled, prospective parallel-group trial. Invited infants will be to be randomised to either the baby-CIMT or the baby-massage group if they: 1) are at risk of developing unilateral CP due to a known neonatal event affecting the brain or 2) have been referred to Astrid Lindgren Children's Hospital due to asymmetric hand function. The inclusion criteria are age 3-8 months and established asymmetric hand use. Infants in both groups will receive two 6-weeks training periods separated by a 6-week pause, for 12 weeks in total of treatment. The primary outcome measure will be the new Hand Assessment for Infants (HAI) for evaluating manual ability. In addition, the Parenting Sense of Competence scale and Alberta Infant Motor Scale will be used. Clinical neuroimaging will be utilized to characterise the brain lesion type. To compare outcomes between treatment groups generalised linear models will be used.DISCUSSION: The model of early intensive intervention for hand function, baby-CIMT evaluated by the Hand Assessment for Infants (HAI) will have the potential to significantly increase our understanding of how early intervention of upper limb function in infants at risk of developing unilateral CP can be performed and measured.TRIAL REGISTRATION: SFO-V4072/2012, 05/22/2013.
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| 3. |
- Eliasson, Ann-Christin, 1950-, et al.
(författare)
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The effectiveness of Baby-CIMT in infants younger than 12 months with clinical signs of unilateral-cerebral palsy : an explorative study with randomized design
- 2018
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Ingår i: Research in Developmental Disabilities. - : Elsevier. - 0891-4222 .- 1873-3379. ; 72, s. 191-201
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To explore the effectiveness of baby-CIMT (constraint-induced movement therapy) and baby-massage for improving the manual ability of infants younger than 12 months with unilateral cerebral palsy (CP).METHOD: Infants eligible for inclusion were 3-8 months old with asymmetric hand function and at high risk of developing unilateral CP. Thirty-seven infants were assigned randomly to receive baby-CIMT or baby-massage. At one year of age 31 children were diagnosed with unilateral CP, 18 (8 boys, 6.1±1.7months) of these had received baby-CIMT and 13 (8 boys, 5.0±1.6months) baby-massage. There were two 6-week training periods separated by a 6-week pause. The Hand Assessment for Infants (HAI), Assisting Hand Assessment (AHA), the Parenting Sense of Competence Scale (PSCS) and a questionnaire concerning feasibility were applied.RESULTS: There was improvement in the "Affected hand score" of HAI from median 10 (6;13 IQR) to 13 (7;17 IQR) raw score in the baby-CIMT group and from 5 (4;11 IQR) to 6 (3;12 IQR) for baby-massage with a significant between group difference (p=0.041). At 18-month of age, the median AHA score were 51 (38;72 IQR) after baby-CIMT (n=18) compared to 24 (19;43 IQR) baby-massage (n=9). The PSCS revealed an enhanced sense of competence of being a parent among fathers in the baby-CIMT group compared to fathers in the baby-massage (p=0.002). Parents considered both interventions to be feasible.CONCLUSION: Baby-CIMT appears to improve the unimanual ability of young children with unilateral CP more than massage.
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| 4. |
- Eliasson, Jonas, et al.
(författare)
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The Stockholm Congestion-Charging Trial 2006 : Overview of the effects
- 2009
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Ingår i: Transportation Research Part A. - Amsterdam : Elsevier BV. - 0965-8564 .- 1879-2375. ; 43:3, s. 240-250
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Tidskriftsartikel (refereegranskat)abstract
- The Stockholm congestion charging trial in 2006 demonstrated the effects of a full-scale time-differentiated urban road toll scheme. Improvements in travel times were large enough to be perceived by the general public. This was pivotal to the radical change of public attitudes that occurred during the trial and that resulted in a positive outcome of a subsequent referendum on a proposal for making the system permanent. This paper summarises the effects of the trial and analyses to what extent targets were met. Effects on congestion reduction were larger than anticipated, which also resulted in favourable economic and environmental effects. The trial showed that a single-cordon toll could affect traffic within a large area, i.e., not just close to the zone limits.
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| 5. |
- Jones, Helena, et al.
(författare)
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beta-cell PDE3B regulates Ca(2+)-stimulated exocytosis of insulin.
- 2007
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Ingår i: Cellular Signalling. - : Elsevier BV. - 1873-3913 .- 0898-6568. ; 19:Feb 12, s. 1505-1513
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Tidskriftsartikel (refereegranskat)abstract
- cAMP signaling is important for the regulation of insulin secretion in pancreatic beta-cells. The level of intracellular cAMP is controlled through its production by adenylyl cyclases and its breakdown by cyclic nucleotide phosphodiesterases (PDEs). We have previously shown that PDE3B is involved in the regulation of nutrient-stimulated insulin secretion. Here, aiming at getting deeper functional insights, we have examined the role of PDE3B in the two phases of insulin secretion as well as its localization in the beta-cell. Depolarization-induced insulin secretion was assessed and in models where PDE3B was overexpressed [islets from transgenic RIP-PDE3B/7 mice and adenovirally (AdPDE3B) infected INS-I (832/13) cells], the first phase of insulin secretion, occurring in response to stimulation with high K+ for 5 min, was significantly reduced (similar to 25% compared to controls). In contrast, in islets from PDE3B(-/-) mice the response to high K+ was increased. Further, stimulation of isolated beta-cells from RIP-PDE3B/7 islets, using successive trains of voltage-clamped depolarizations, resulted in reduced Ca2+-triggered first phase exocytotic response as well as reduced granule mobilization-dependent second phase, compared to wild-type beta-cells. Using sub-cellular fractionation, confocal microscopy and transmission electron microscopy of isolated mouse islets and INS-1 (832/13) cells, we show that endogenous and overexpressed PDE3B is localized to insulin granules and plasma membrane. We conclude that PDE3B, through hydrolysis of cAMP in pools regulated by Ca2+, plays a regulatory role in depolarization-induced insulin secretion and that the enzyme is associated with the exocytotic machinery in beta-cells. (c) 2007 Elsevier Inc. All rights reserved.
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| 6. |
- Krumlinde-Sundholm, Lena, et al.
(författare)
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Development of the Hand Assessment for Infants : evidence of internal scale validity
- 2017
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Ingår i: Developmental Medicine & Child Neurology. - : Mac Keith Press. - 0012-1622 .- 1469-8749. ; 59:12, s. 1276-1283
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Tidskriftsartikel (refereegranskat)abstract
- AIM: The aim of this study was to develop a descriptive and evaluative assessment of upper limb function for infants aged 3 to 12 months and to investigate its internal scale validity for use with infants at risk of unilateral cerebral palsy.METHOD: The concepts of the test items and scoring criteria were developed. Internal scale validity and aspects of reliability were investigated on the basis of 156 assessments of infants at 3 to 12 months corrected age (mean 7.2mo, SD 2.5) with signs of asymmetric hand use. Rasch measurement model analysis and non-parametric statistics were used.RESULTS: The new test, the Hand Assessment for Infants (HAI), consists of 12 unimanual and five bimanual items, each scored on a 3-point rating scale. It demonstrated a unidimensional construct and good fit to the Rasch model requirements. The excellent person reliability enabled person separation to six significant ability strata. The HAI produced an interval-level measure of bilateral hand use as well as unimanual scores of each hand, allowing a quantification of possible asymmetry expressed as an asymmetry index.INTERPRETATION: The HAI can be considered a valid assessment tool for measuring bilateral hand use and quantifying side difference between hands among infants at risk of developing unilateral cerebral palsy.WHAT THIS PAPER ADDS: The Hand Assessment for Infants (HAI) measures the use of both hands and quantifies a possible asymmetry of hand use. HAI is valid for infants at 3 to 12 months corrected age at risk of unilateral cerebral palsy.
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| 7. |
- Alonso, Lorena, et al.
(författare)
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TIGER : The gene expression regulatory variation landscape of human pancreatic islets
- 2021
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 37:2
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWASs) identified hundreds of signals associated with type 2 diabetes (T2D). To gain insight into their underlying molecular mechanisms, we have created the translational human pancreatic islet genotype tissue-expression resource (TIGER), aggregating >500 human islet genomic datasets from five cohorts in the Horizon 2020 consortium T2DSystems. We impute genotypes using four reference panels and meta-analyze cohorts to improve the coverage of expression quantitative trait loci (eQTL) and develop a method to combine allele-specific expression across samples (cASE). We identify >1 million islet eQTLs, 53 of which colocalize with T2D signals. Among them, a low-frequency allele that reduces T2D risk by half increases CCND2 expression. We identify eight cASE colocalizations, among which we found a T2D-associated SLC30A8 variant. We make all data available through the TIGER portal (http://tiger.bsc.es), which represents a comprehensive human islet genomic data resource to elucidate how genetic variation affects islet function and translates into therapeutic insight and precision medicine for T2D.
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| 8. |
- Andersson, Sofia A, et al.
(författare)
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Glucose-dependent docking and SNARE protein-mediated exocytosis in mouse pancreatic alpha-cell
- 2011
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Ingår i: Pflügers Archiv. - : Springer. - 0031-6768 .- 1432-2013. ; 462:3, s. 443-454
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Tidskriftsartikel (refereegranskat)abstract
- The function of alpha-cells in patients with type 2 diabetes is often disturbed; glucagon secretion is increased at hyperglycaemia, yet fails to respond to hypoglycaemia. A crucial mechanism behind the fine-tuned release of glucagon relies in the exocytotic machinery including SNARE proteins. Here, we aimed to investigate the temporal role of syntaxin 1A and SNAP-25 in mouse alpha-cell exocytosis. First, we used confocal imaging to investigate glucose dependency in the localisation of SNAP-25 and syntaxin 1A. SNAP-25 was mainly distributed in the plasma membrane at 2.8 mM glucose, whereas the syntaxin 1A distribution in the plasma membrane, as compared to the cytosolic fraction, was highest at 8.3 mM glucose. Furthermore, following inclusion of an antibody against SNAP-25 or syntaxin 1A, exocytosis evoked by a train of ten depolarisations and measured as an increase in membrane capacitance was reduced by ~50%. Closer inspection revealed a reduction in the refilling of granules from the reserve pool (RP), but also showed a decreased size of the readily releasable pool (RRP) by ~45%. Disparate from the situation in pancreatic beta-cells, the voltage-dependent Ca²⁺ current was not reduced, but the Ca²⁺ sensitivity of exocytosis decreased by the antibody against syntaxin 1A. Finally, ultrastructural analysis revealed that the number of docked granules was >2-fold higher at 16.7 mM than at 1 mM glucose. We conclude that syntaxin 1A and SNAP-25 are necessary for alpha-cell exocytosis and regulate fusion of granules belonging to both the RRP and RP without affecting the Ca²⁺ current.
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| 9. |
- Andersson, Sofia A, et al.
(författare)
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Reduced insulin secretion correlates with decreased expression of exocytotic genes in pancreatic islets from patients with type 2 diabetes.
- 2012
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Ingår i: Molecular and Cellular Endocrinology. - : Elsevier BV. - 1872-8057 .- 0303-7207. ; 364:1-2, s. 36-45
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Tidskriftsartikel (refereegranskat)abstract
- Reduced insulin release has been linked to defect exocytosis in β-cells. However, whether expression of genes suggested to be involved in the exocytotic process (exocytotic genes) is altered in pancreatic islets from patients with type 2 diabetes (T2D), and correlate to insulin secretion, needs to be further investigated. Analysing expression levels of 23 exocytotic genes using microarray revealed reduced expression of five genes in human T2D islets (χ(2)=13.25; p<0.001). Gene expression of STX1A, SYT4, SYT7, SYT11, SYT13, SNAP25 and STXBP1 correlated negatively to in vivo measurements of HbA1c levels and positively to glucose stimulated insulin secretion (GSIS) in vitro in human islets. STX1A, SYT4 and SYT11 protein levels correspondingly decreased in human T2D islets. Moreover, silencing of SYT4 and SYT13 reduced GSIS in INS1-832/13 cells. Our data support that reduced expression of exocytotic genes contributes to impaired insulin secretion, and suggest decreased expression of these genes as part of T2D pathogenesis.
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| 10. |
- Armour, Sarah L., et al.
(författare)
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Glucose Controls Glucagon Secretion by Regulating Fatty Acid Oxidation in Pancreatic α-Cells
- 2023
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Ingår i: DIABETES. - 0012-1797 .- 1939-327X. ; 72:10, s. 1446-1459
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Tidskriftsartikel (refereegranskat)abstract
- Whole-body glucose homeostasis is coordinated through secretion of glucagon and insulin from pancreatic islets. When glucose is low, glucagon is released from alpha-cells to stimulate hepatic glucose production. However, the mechanisms that regulate glucagon secretion from pancreatic alpha-cells remain unclear. Here we show that in alpha-cells, the interaction between fatty acid oxidation and glucose metabolism controls glucagon secretion. The glucose-dependent inhibition of glucagon secretion relies on pyruvate dehydrogenase and carnitine palmitoyl transferase 1a activity and lowering of mitochondrial fatty acid oxidation by increases in glucose. This results in reduced intracellular ATP and leads to membrane repolarization and inhibition of glucagon secretion. These findings provide a new framework for the metabolic regulation of the alpha-cell, where regulation of fatty acid oxidation by glucose accounts for the stimulation and inhibition of glucagon secretion.Article Highlights It has become clear that dysregulation of glucagon secretion and alpha-cell function plays an important role in the development of diabetes, but we do not know how glucagon secretion is regulated. Here we asked whether glucose inhibits fatty acid oxidation in alpha-cells to regulate glucagon secretion. We found that fatty acid oxidation is required for the inhibitory effects of glucose on glucagon secretion through reductions in ATP. These findings provide a new framework for the regulation of glucagon secretion by glucose.
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