Complex SCN8A DNA-abnormalities in an individual with therapy resistant absence epilepsy

Background De novo SCN8A missense mutations have been identified as a rare dominant cause of epileptic encephalopathy. We described a person with epileptic encephalopathy associated with a mosaic deletion of the SCN8A gene. Methods Array comparative genome hybridization was used to identify chromosomal abnormalities. Next Generation Sequencing was used to screen for variants in known and candidate epilepsy genes. A single nucleotide polymorphism array was used to test whether the SCN8A variants were in cis or in trans. Results We identified a de novo mosaic deletion of exons 2–14 of SCN8A, and a rare maternally inherited missense variant on the other allele in a woman presenting with absence seizures, challenging behavior, intellectual disability and QRS-fragmentation on the ECG. We also found a variant in SCN5A. Conclusions The combination of a rare missense variant with a de novo mosaic deletion of a large part of the SCN8A gene suggests that other possible mechanisms for SCN8A mutations may cause epilepsy; loss of function, genetic modifiers and cellular interference may play a role. This case expands the phenotype associated with SCN8A mutations, with absence epilepsy and regression in language and memory skills

Symptomatology of carbamazepine- and oxcarbazepine-induced hyponatremia in people with epilepsy

OBJECTIVE: To ascertain whether adverse effects experienced by people taking carbamazepine or oxcarbazepine could be attributed to carbamazepine- or oxcarbazepine-induced hyponatremia (COIH). METHODS: We performed an observational study, collecting data between 2017 and 2019 on serum sodium levels and adverse effects retrospectively in people with epilepsy while receiving treatment with either carbamazepine (CBZ) or oxcarbazepine (OXC). We defined hyponatremia as sodium level ≤134 mEq/L and severe hyponatremia as sodium level ≤128 mEq/L. Adverse effects experienced were compared between groups of individuals with and without hyponatremia. RESULTS: A total of 1370 people using CBZ or OXC were identified, of whom 410 had at least one episode of hyponatremia. We checked for symptoms related to the use of CBZ and OXC in 710 people (410 with and 300 without hyponatremia) and found relevant information in 688. Adverse effects occurred in 65% of people with hyponatremia compared to 21% with normal sodium levels (odds ratio [OR] 7.5, P ≤ .001) and in 83% of people with severe hyponatremia compared to 55% in those with mild hyponatremia (P ≤ .001). Significant predictors of adverse effects were the drug (OXC vs CBZ), and the number of concomitant anti-seizure medications. Dizziness (28% vs 6%), tiredness (22% vs 7%), instability (19% vs 3%), and diplopia (16% vs 4%) were reported more often in the hyponatremia group than in patients with normal levels. SIGNIFICANCE: People with COIH had a 7-fold increased risk of developing adverse effects during treatment. Clinicians should consider ascertainment of sodium levels in patients taking CBZ and OXC and act upon findings

Transverse and secondary voltages in BSCCO single crystals

Multicontact configuration is one of the most powerful arrangements for electrical transport measurements applied to study vortex phase transition and vortex phase dimensionality in strongly anisotropic high-Tc superconducting materials. In this paper we present electrical transport measurements using a multiterminal configuration, which prove both the existence of guided vortex motion in BSCCO single crystals near the transition temperature and that secondary voltage in zero external magnetic field is induced by thermally activated vortex loop unbinding. The phase transition between the bound and unbound states of the vortex loops was found to be below the temperature where the phase coherence of the superconducting order parameter extends over the whole volume of the sample. We show experimentally that 3D/2D phase transition in vortex dimensionality is a length-scale-dependent layer decoupling process and takes place simultaneously with the 3D/2D phase transition in superconductivity at the same temperature.Comment: 8 pages, 5 figures, to be published in Physica

Absence of the Transition into Abrikosov Vortex State of Two-Dimensional Type-II Superconductor with Weak Pinning

The resistive properties of thin amorphous NbO_{x} films with weak pinning were investigated experimentally above and below the second critical field H_{c2}. As opposed to bulk type II superconductors with weak pinning where a sharp change of resistive properties at the transition into the Abrikosov state is observed at H_{c4}, some percent below H_{c2} (V.A.Marchenko and A.V.Nikulov, 1981), no qualitative change of resistive properties is observed down to a very low magnetic field, H_{c4} < 0.006 H_{c2}, in thin films with weak pinning. The smooth dependencies of the resistivity observed in these films can be described by paraconductivity theory both above and below H_{c2}. This means that the fluctuation superconducting state without phase coherence remains appreciably below H_{c2} in the two-dimensional superconductor with weak pinning. The difference the H_{c4}/H_{c2} values, i.e. position of the transition into the Abrikosov state, in three- and two-dimensional superconductors conforms to the Maki-Takayama result 1971 year according to which the Abrikosov solution 1957 year is valid only for a superconductor with finite dimensions. Because of the fluctuation this solution obtained in the mean field approximation is not valid in a relatively narrow region below H_{c2} for bulk superconductors with real dimensions and much below H_{c2} for thin films with real dimensions. The superconducting state without phase coherence should not be identified with the mythical vortex liquid because the vortex, as a singularity in superconducting state with phase coherence, can not exist without phase coherence.Comment: 4 pages, 4 figure

Melting of two dimensional solids on disordered substrate

We study 2D solids with weak substrate disorder, using Coulomb gas renormalisation. The melting transition is found to be replaced by a sharp crossover between a high $T$ liquid with thermally induced dislocations, and a low $T$ glassy regime with disorder induced dislocations at scales larger than $\xi_{d}$ which we compute ($\xi_{d}\gg R_{c}\sim R_{a}$, the Larkin and translational correlation lengths). We discuss experimental consequences, reminiscent of melting, such as size effects in vortex flow and AC response in superconducting films.Comment: 4 pages, uses RevTeX, Amssymb, multicol,eps

Urinary concentrations of bisphenols and parabens and their association with attention, hyperactivity and impulsivity at adolescence

Background: Neurobehavioural disorder diagnoses have been increasing over the last decades, leading to heightened interest in the aetiological factors involved. Endocrine disrupting chemicals, such as parabens and bisphenols, have been suggested as one of those factors. It is unknown whether exposure during adolescence may affect neurobehavioural development. Objective: To determine whether urinary concentrations of parabens and bisphenols are associated with attention and concentration in adolescents, in general and sex-specific. Methods: We invited 188 adolescents (13–15 years old) for the follow-up birth cohort-study. Concentrations of five parabens and three bisphenols (BPA; BPF; BPS) were measured in morning urine after overnight fasting, using a validated LC-MS/MS method. Attention and concentration were assessed at the clinic with subtests of the Test of Everyday Attention in Children and the Dutch Attention Deficit Hyperactivity Disorder questionnaire (AVL), the latter being filled in by parents. Linear regression analyses were performed, adjusting for urine creatinine concentrations and potential confounding factors.Results: 101 (54%) adolescents participated (46 girls; 55 boys). Urinary paraben concentrations were higher in girls than in boys. Methylparaben was positively associated with attention in girls (p ≤ .05; B= −2.836; 95%CI= −5.175;−.497), ethylparaben negatively with hyperactivity (p ≤ .05; B= −1.864; 95%CI= −3.587;−.141). Butylparaben was associated with more optimal scores on parent reported attention. Propylparaben was negatively associated with scores on sustained auditory attention in girls (p ≤ .10; B=.444; 95%CI= −.009;.896). Bisphenol concentrations were not associated with scores on attention and concentration after adjusting for confounders.Conclusion: In 13–15-year-old Dutch adolescents, urinary concentrations of methylparaben and ethylparaben were associated with better attention and less hyperactivity, whereas a trend toward significance was found between higher urinary propylparaben concentrations and poorer attention. Bisphenol concentrations were not associated with attention and concentration after adjusting for confounders.</p

Vortices in a Thin Film Superconductor with a Spherical Geometry

We report results from Monte Carlo simulations of a thin film superconductor in a spherical geometry within the lowest Landau level approximation. We observe the absence of a phase transition to a low temperature vortex solid phase with these boundary conditions; the system remains in the vortex liquid phase for all accessible temperatures. The correlation lengths are measured for phase coherence and density modulation. Both lengths display identical temperature dependences, with an asymptotic scaling form consistent with a continuous zero temperature transition. This contrasts with the first order freezing transition which is seen in the alternative quasi-periodic boundary conditions. The high temperature perturbation theory and the ground states of the spherical system suggest that the thermodynamic limit of the spherical geometry is the same as that on the flat plane. We discuss the advantages and drawbacks of simulations with different geometries, and compare with current experimental conclusions. The effect of having a large scale inhomogeneity in the applied field is also considered.Comment: This replacment contains substantial revisions: the new article is twice as long with new and different results on the thermodynamic limit on the sphere plus a full discussion on the alternative boundary conditions used in simulations in the LLL approximation. 19 pages, 12 encapsulated PostScript figures, 1 JPEG figure, uses RevTeX (with epsf

Genome-wide mega-analysis identifies 16 loci and highlights diverse biological mechanisms in the common epilepsies

sem informaçãoThe epilepsies affect around 65 million people worldwide and have a substantial missing heritability component. We report a genome-wide mega-analysis involving 15,212 individuals with epilepsy and 29,677 controls, which reveals 16 genome-wide significant91sem informaçãosem informaçãosem informaçã