Population-based study of antiepileptic drug exposure in utero—Influence 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: 1.74–4.78) 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 genomgå en abort

Syfte: Syftet med studien var att studera individens upplevelse av att genomgå en abort. I studien belyses de faktorer och aspekter som påverkar individen under abortprocessen. Metod: Studien är en litteraturstudie med integrerad analys där 9 vetenskapliga artiklar ligger till grund för det framtagna resultatet. Samtliga artiklar som inkluderats i resultatet är kvalitetsgranskade. Resultat: Det framtagna resultatet visar på en rad olika aspekter som påverkar individens upplevelse av att genomgå en abort. De huvudresultat som är framtagna är bemötande, självbestämmande, miljö och information För både den abortsökande kvinnan och hennes eventuelle partner är det bemötande man får en stor del av helhetsupplevelsen under abortprocessen. Självbestämmande är en annan viktig aspekt av helhetsupplevelsen. De män som varit delaktiga under abortprocessen värdesätter delaktighet till hög grad och aborter som avslutas i hemmet har fått dem att känna ett ökat ansvar och delaktighet. Vårdpersonalens bemötande influerade helhetsupplevelsen till hög grad. Slutsats: Individer som genomgått en abort har till hög grad en positiv upplevelse av mötet med vården vid abort. Det som värderas högt och påverkar upplevelsen som mest är vårdpersonalens 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 β-Cells: General Survey and Results from mceph/mceph Mice

BACKGROUND:Voltage-dependent K(+) channels (Kv) mediate repolarisation of β-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 β-cell population and also to α- and δ-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 β-cells. This duration effect on action potential in β-cells from mceph/mceph mice was mimicked by dendrotoxin-K in β-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 β-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 1992–1998 to 15–20% in 2002–2009, 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

26th Annual Computational Neuroscience Meeting (CNS*2017): Part 3 - Meeting Abstracts - Antwerp, Belgium. 15–20 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? : Svensklärares attityder till grammatikundervisning Författare: Malin

Det här är en studie om svensklärares attityd till grammatikundervisning. Jag har undersökt vad några svensklärare på gymnasieskolor i Mellansverige har för uppfattning om grammatik, deras egen grammatikundervisning, och grammatik i styrdokumenten. För att försöka svara på frågeställningarna har sex stycken semistrukturerade intervjuer genomförts med svensklärare på några olika skolor i området. Intervjuerna har visat att det finns skilda åsikter bland de medverkande lärarna kring frågor om deras egen erfarenhet av grammatik, deras undervisning, grammatikens roll i svenskämnet och styrdokumentens behandling av grammatiken. Det upptäcktes även likheter i, till exempel, deras uppfattningar om grammatikens nytta och det faktum att de flesta var missnöjda med styrdokumenten samt att elevernas förkunskaper när de börjar på gymnasiet inte alltid är tillräckliga. Studiens resultat ger en inblick i några svensklärares attityder till grammatikundervisning, men är inte generaliserbar och speglar inte hur alla svensklärares åsikter 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