43 research outputs found
Population-based study of antiepileptic drug exposure in uteroâInfluence on head circumference in newborns
AbstractPurposeTo study the effect of AED exposure on head circumference in the newborn.MethodsData on all Swedish singletons births between 1995 and 2005, over 900,000 births, were obtained from the Swedish Medical Birth Registry. The effects of AEDs on birth-weight-adjusted mean head circumference (bw-adj-HC) were estimated by comparison with data from all births in an analysis which was adjusted for year of birth, maternal age, parity, maternal smoking, and maternal body mass index.ResultsA significant reduction of mean bw-adj-HC was seen after both carbamazepine (CBZ) (standard deviation scores (SDS)=0.15, p<0.001) and valproic acid (VPA) (SDS=0.10, p=0.04) in monotherapy. No effect on mean bw-adj-HC was seen for phenytoin, clonazepam, lamotrigine and gabapentin. There was a significant increase in the occurrence of microcephaly (bw-adj-HC smaller than 2 SD below the mean) after any AED polytherapy (OR=2.85, 95% CI: 1.74â4.78) but not after AED monotherapy or monotherapy with CBZ or VPA. CBZ or VPA was taken by 71% of the pregnant mothers on AED, and the usage increased over time.ConclusionsCBZ and VPA in monotherapy during pregnancy reduce mean bw-adj-HC. AED polytherapy increases the rate of microcephaly but no significant effect is seen of AED monotherapy. The possible significance for the further development of the child is uncertain but should be explored
Individens upplevelse av att genomgÄ en abort
Syfte: Syftet med studien var att studera individens upplevelse av att genomgÄ en abort. I studien belyses de faktorer och aspekter som pÄverkar individen under abortprocessen. Metod: Studien Àr en litteraturstudie med integrerad analys dÀr 9 vetenskapliga artiklar ligger till grund för det framtagna resultatet. Samtliga artiklar som inkluderats i resultatet Àr kvalitetsgranskade. Resultat: Det framtagna resultatet visar pÄ en rad olika aspekter som pÄverkar individens upplevelse av att genomgÄ en abort. De huvudresultat som Àr framtagna Àr bemötande, sjÀlvbestÀmmande, miljö och information För bÄde den abortsökande kvinnan och hennes eventuelle partner Àr det bemötande man fÄr en stor del av helhetsupplevelsen under abortprocessen. SjÀlvbestÀmmande Àr en annan viktig aspekt av helhetsupplevelsen. De mÀn som varit delaktiga under abortprocessen vÀrdesÀtter delaktighet till hög grad och aborter som avslutas i hemmet har fÄtt dem att kÀnna ett ökat ansvar och delaktighet. VÄrdpersonalens bemötande influerade helhetsupplevelsen till hög grad. Slutsats: Individer som genomgÄtt en abort har till hög grad en positiv upplevelse av mötet med vÄrden vid abort. Det som vÀrderas högt och pÄverkar upplevelsen som mest Àr vÄrdpersonalens bemötande
A truncated Kv1.1 protein in the brain of the megencephaly mouse: expression and interaction
BACKGROUND: The megencephaly mouse, mceph/mceph, is epileptic and displays a dramatically increased brain volume and neuronal count. The responsible mutation was recently revealed to be an eleven base pair deletion, leading to a frame shift, in the gene encoding the potassium channel Kv1.1. The predicted MCEPH protein is truncated at amino acid 230 out of 495. Truncated proteins are usually not expressed since nonsense mRNAs are most often degraded. However, high Kv1.1 mRNA levels in mceph/mceph brain indicated that it escaped this control mechanism. Therefore, we hypothesized that the truncated Kv1.1 would be expressed and dysregulate other Kv1 subunits in the mceph/mceph mice. RESULTS: We found that the MCEPH protein is expressed in the brain of mceph/mceph mice. MCEPH was found to lack mature (Golgi) glycosylation, but to be core glycosylated and trapped in the endoplasmic reticulum (ER). Interactions between MCEPH and other Kv1 subunits were studied in cell culture, Xenopus oocytes and the brain. MCEPH can form tetramers with Kv1.1 in cell culture and has a dominant negative effect on Kv1.2 and Kv1.3 currents in oocytes. However, it does not retain Kv1.2 in the ER of neurons. CONCLUSION: The megencephaly mice express a truncated Kv1.1 in the brain, and constitute a unique tool to study Kv1.1 trafficking relevant for understanding epilepsy, ataxia and pathologic brain overgrowth
Evidence for Presence and Functional Effects of Kv1.1 Channels in ÎČ-Cells: General Survey and Results from mceph/mceph Mice
BACKGROUND:Voltage-dependent K(+) channels (Kv) mediate repolarisation of ÎČ-cell action potentials, and thereby abrogate insulin secretion. The role of the Kv1.1 K(+) channel in this process is however unclear. We tested for presence of Kv1.1 in different species and tested for a functional role of Kv1.1 by assessing pancreatic islet function in BALB/cByJ (wild-type) and megencephaly (mceph/mceph) mice, the latter having a deletion in the Kv1.1 gene. METHODOLOGY/PRINCIPAL FINDINGS:Kv1.1 expression was detected in islets from wild-type mice, SD rats and humans, and expression of truncated Kv1.1 was detected in mceph/mceph islets. Full-length Kv1.1 protein was present in islets from wild-type mice, but, as expected, not in those from mceph/mceph mice. Kv1.1 expression was localized to the ÎČ-cell population and also to α- and ÎŽ-cells, with evidence of over-expression of truncated Kv1.1 in mceph/mceph islets. Blood glucose, insulin content, and islet morphology were normal in mceph/mceph mice, but glucose-induced insulin release from batch-incubated islets was (moderately) higher than that from wild-type islets. Reciprocal blocking of Kv1.1 by dendrotoxin-K increased insulin secretion from wild-type but not mceph/mceph islets. Glucose-induced action potential duration, as well as firing frequency, was increased in mceph/mceph mouse ÎČ-cells. This duration effect on action potential in ÎČ-cells from mceph/mceph mice was mimicked by dendrotoxin-K in ÎČ-cells from wild-type mice. Observations concerning the effects of both the mceph mutation, and of dendrotoxin-K, on glucose-induced insulin release were confirmed in pancreatic islets from Kv1.1 null mice. CONCLUSION/SIGNIFICANCE:Kv1.1 channels are expressed in the ÎČ-cells of several species, and these channels can influence glucose-stimulated insulin release
Adenovirus-36 Is Associated with Obesity in Children and Adults in Sweden as Determined by Rapid ELISA
Background
Experimental and natural human adenovirus-36 (Adv36) infection of multiple animal species results in obesity through increasing adipogenesis and lipid accumulation in adipocytes. Presence of Adv36 antibodies detected by serum neutralization assay has previously been associated with obesity in children and adults living in the USA, South Korea and Italy, whereas no association with adult obesity was detected in Belgium/the Netherlands nor among USA military personnel. Adv36 infection has also been shown to reduce blood lipid levels, increase glucose uptake by adipose tissue and skeletal muscle biopsies, and to associate with improved glycemic control in non-diabetic individuals. Principal Findings
Using a novel ELISA, 1946 clinically well-characterized individuals including 424 children and 1522 non-diabetic adults, and 89 anonymous blood donors, residing in central Sweden representing the population in Stockholm area, were studied for the presence of antibodies against Adv36 in serum. The prevalence of Adv36 positivity in lean individuals increased from ~7% in 1992â1998 to 15â20% in 2002â2009, which paralleled the increase in obesity prevalence. We found that Adv36-positive serology was associated with pediatric obesity and with severe obesity in females compared to lean and overweight/mildly obese individuals, with a 1.5 to 2-fold Adv36 positivity increase in cases. Moreover, Adv36 positivity was less common among females and males on antilipid pharmacological treatment or with high blood triglyceride level. Insulin sensitivity, measured as lower HOMA-IR, showed a higher point estimate in Adv36-positive obese females and males, although it was not statistically significant (p = 0.08). Conclusion
Using a novel ELISA we show that Adv36 infection is associated with pediatric obesity, severe obesity in adult females and lower risk of high blood lipid levels in non-diabetic Swedish individuals
High-specificity bioinformatics framework for epigenomic profiling of discordant twins reveals specific and shared markers for ACPA and ACPA-positive rheumatoid arthritis
26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15â20 July 2017
This work was produced as part of the activities of FAPESP Research,\ud
Disseminations and Innovation Center for Neuromathematics (grant\ud
2013/07699-0, S. Paulo Research Foundation). NLK is supported by a\ud
FAPESP postdoctoral fellowship (grant 2016/03855-5). ACR is partially\ud
supported by a CNPq fellowship (grant 306251/2014-0)
Varför grammatik? : SvensklÀrares attityder till grammatikundervisning Författare: Malin
Det hÀr Àr en studie om svensklÀrares attityd till grammatikundervisning. Jag har undersökt vad nÄgra svensklÀrare pÄ gymnasieskolor i Mellansverige har för uppfattning om grammatik, deras egen grammatikundervisning, och grammatik i styrdokumenten. För att försöka svara pÄ frÄgestÀllningarna har sex stycken semistrukturerade intervjuer genomförts med svensklÀrare pÄ nÄgra olika skolor i omrÄdet. Intervjuerna har visat att det finns skilda Äsikter bland de medverkande lÀrarna kring frÄgor om deras egen erfarenhet av grammatik, deras undervisning, grammatikens roll i svenskÀmnet och styrdokumentens behandling av grammatiken. Det upptÀcktes Àven likheter i, till exempel, deras uppfattningar om grammatikens nytta och det faktum att de flesta var missnöjda med styrdokumenten samt att elevernas förkunskaper nÀr de börjar pÄ gymnasiet inte alltid Àr tillrÀckliga. Studiens resultat ger en inblick i nÄgra svensklÀrares attityder till grammatikundervisning, men Àr inte generaliserbar och speglar inte hur alla svensklÀrares Äsikter ser ut.svenska</p
Benefits of skin-to-skin contact during the neonatal period: Governed by epigenetic mechanisms?
The perinatal period experiences are important for later life physiology. Prematurely born babies have been shown to benefit from close contact with their mothers, and evidence suggests that epigenetic mechanisms are involved in these early imprints. This mini review is summarizing current praxis and discusses the need for more and larger studies
Neural growth : With special emphasis on adult neurogenesis and the effect of antiepileptic drugs
Neurons were for a long time thought to not renew themselves. In the
1960ies the phenomenon of neurogenesis was discovered, but it was not
until 1998 that neurogenesis was demonstrated in humans. In this thesis
neurogenesis was studied using a unique genetic mouse model
(mceph/mceph), with postnatal epilepsy and excessive brain growth, due to
a truncated Kv1.1 subunit. The model was used to learn more about how a
channelopathy can disturb hippocampal neurogenesis, leading to
hyperplasia, and how this can be treated. First, the expression and
trafficking of the truncated potassium ion channel Kv1.1 was described to
reveal its molecular nature. It was shown that the defective Kv1.1 does
not form functional channels and moreover has the potential to render
other potassium channel subunits non ]functional. Even though lack of
Kv1.1 is enough for excessive hippocampal growth, the defect Kv1.1
peptide worsens the epileptic condition by blocking additional Kv1
subunits. Cells have previously been shown to be enlarged in the
hippocampus of this mouse. In this thesis a doubling in number of neurons
and astrocytes was demonstrated by stereology. The increase in number of
neurons was due to increased neurogenesis and altered apoptosis. To
identify transcripts involved in the overgrowth of the mceph/mceph
hippocampus a genome ]wide screen for transcripts expressed at different
levels in mceph/mceph versus wild type was performed. The following
genes, involved in regulation of cell number, were verified as
differentially regulated in mceph/mceph; NPY, Penk, Fjx1 and Vgf.
Previously it was shown that oral treatment with the antiepileptic drug
CBZ protect mceph/mceph mice from developing enlarged hippocampus. This
thesis shows that all hippocampal regions studied were protected from
overgrowth and that the number of both neurons and astrocytes were
normalized despite ongoing severe seizures. Transcripts potentially
involved in the protection against the hippocampal overgrowth and
hyperplasia were identified based on different expression levels in a
microarray analysis. Verified genes include Mlc1, Sstr4, ApoD, Ndn, Aatk
and Rgs2. These transcripts have a proposed function in proliferation,
differentiation and/or apoptosis. Finally, an analysis of the effect of
AEDs in utero, with focus on the head size of the newborn, was conducted
on a large population ]based Swedish cohort. This study revealed that the
use of CBZ and VPA is increasing despite reports of malformations and
growth retardations of the baby. Furthermore, CBZ and VPA monotherapy
significantly reduced the head circumference (HC) and AED polytherapy
increase the rate of small HC (> 2 SD). The implications of a smaller
head on the development of the child is uncertain but should be explored.
CBZ mono ] and polytherapy significantly reduced gestational age (GA) and
there was a tendency for clonazepam and gabapentin monotherapy to reduce
GA. The relevance of the reduced pregnancy duration is not clear but
indicates a need for further studies in order to optimize treatment
regimes for epileptic pregnant women