Traumatic axonal injury in the spinal cord evoked by traumatic brain injury

Although it is well known that traumatic brain injury (TBI) evokes traumatic axonal injury (TAI) within the brain, TBI-induced axonal damage in the spinal cord (SC) has been less extensively investigated. Detection of such axonal injury in the spinal cord would further the complexity of TBI while also challenging some functional neurobehavioral endpoints frequently used to assess recovery in various models of TBI. To assess TAI in the spinal cord associated with TBI, we analyzed the craniocervical junction (CCJ), cervico-thoracic (CT), and thoraco-lumber (ThL) spinal cord in a rodent model of impact acceleration of TBI of varying severities. Rats were transcardially fixed with aldehydes at 2, 6, and 24 h post-injury (n � 36); each group included on sham-injured rodent. Semi-serial vibratome sections were reacted with antibodies targeting TAI via alteration in cytoskeletal integrity or impaired axonal transport. Consistent with previous observations in this model, the CCJ contained numerous injured axons. Immunoreactive, damaged axonal profiles were also detected as caudal, as the ThL spinal cord displayed morphological characteristics entirely consistent with those described in the brainstem and the CCJ. Quantitative analyses demonstrated that the occurrence and extent of TAI is positively associated with the impact/energy of injury and negatively with the distance from the brainstem. These observations show that TBI can evoke TAI in regions remote from the injury site, including the spinal cord itself. This finding is relevant to shaken baby syndrome as well as during the analysis of data in functional recovery in various models of TBI

Lateral–torsional buckling resistance of corrugated web girders based on deterministic and stochastic nonlinear analysis

There is no commonly accepted and reliable design method to determine the lateral–torsional buckling (LTB) resistance of steel trapezoidally corrugated web girders. Therefore, the focus of the current paper is on the investigation of this failure mode, detailed evaluation of the structural behavior and determination of the accurate LTB resistance. An advanced finite element (FE) model is developed and validated using the results of laboratory test performed at the Budapest University of Technology and Economics in 2018. Based on the experimental background virtual tests are performed on a simply supported beam subjected by pure bending moment. The effect of the different flange sizes, corrugation layouts, boundary conditions and steel grade including high-strength steel as well, are investigated. Two kinds of parametric studies are performed using (i) deterministic and (ii) stochastic nonlinear analysis. In both cases the imperfections have a key role in the FEM-based resistance calculation. Therefore, the imperfections are considered as initial geometric imperfections and residual stress, and also as equivalent geometric imperfections and their results are compared. The required equivalent geometric imperfection magnitude is determined and proposed in such a way to achieve the same impact as the initial geometric imperfection and residual stresses have. By both the deterministic and stochastic analysis results the required buckling curve of the Eurocode is determined by reliability assessment. The results of the two different analyses are compared and design recommendation is given for reduction factor determination for trapezoidally corrugated web girders

Applicable Equivalent Bow Imperfections in GMNIA for Eurocode Buckling Curves – in Case of Box Sections

The flexural buckling resistance of compressed columns is typically determined using the flexural buckling curves of EN1993-1-1. With advances in computing capabilities, it has become possible to obtain the flexural buckling resistance as a result of a geometrically and materially nonlinear analysis (GMNIA) using imperfections. In design practice, equivalent geometric imperfections are usually used, but their values are calibrated against GNIA analysis. In the present research work, welded box-section columns are investigated and a proposal for relative slenderness and yield strength dependent equivalent geometric imperfection magnitudes is developed. The required equivalent bow imperfection magnitude is determined to achieve the same resistance level as the calculation according to Eurocode-based buckling curves. GMNIA analysis are conducted on simply supported columns subjected to concentrated force. The steel grade varied between S235 and S960. Several different section geometries are studied, the relative slenderness ratio is varied between 0.3 and 2.2. Design curve is fitted to the results and recommendation is given for applicable equivalent geometric imperfection magnitudes for steel welded box-section columns

A nagyobb méretű géndeletiók jelentősége a sclerosis tuberosa diagnosztikájában: az első magyar esetek bemutatása | Importance of gross deletions in the diagnosis of tuberous sclerosis complex: the first Hungarian cases

Absztrakt: A sclerosis tuberosa nagyfokú fenotípusos heterogenitást mutató ritka betegség, jellemző tünete a multiplex hamartomák megjelenése különböző szervekben. Autoszomális domináns öröklődésmenetet mutat, hátterében két génnek, a TSC1-nek, illetve a TSC2-nek a mutációi állnak. Jelen közleményünkben két fiú, illetve két középkorú nőbeteg esetét mutatjuk be, akiknél a TSC1/TSC2 génben Sanger-szekvenálással kóroki eltérést nem tudtunk igazolni, azonban a multiplex ligatiofüggő próba amplifikációjával különböző méretű deletiókat igazoltunk a TSC2 különböző régióiban. Valamennyi beteg hordozza a betegség jellegzetes vezető klinikai tüneteit, azonban az egyéni fenotípusos variabilitásuk rendkívüli módon különbözik. Közleményünkkel a nagyobb méretű géndeletiók relatív gyakori előfordulására hívjuk fel a figyelmet. Orv Hetil. 2017; 158(30): 1188–1194. | Abstract: Tuberous sclerosis complex is a rare disease with high phenotypic heterogeneity, characterized by the appearance of multiplex hamartomas in the different organs. The disease is inherited by autosomal dominant manner, due to the mutations of two genes: the TSC1 or the TSC2. In this publication we present the cases of two young male and two middle-aged female patients, where pathogenetic differences of TSC1/TSC2 could not be verified by Sanger sequencing. However, multiplex ligation-dependent probe amplification confirmed different sizes of deletions in different regions of the TSC2 gene. All patients carry the typical clinical signs of the disease. However, the individual phenotypic variability is very different. With this manuscript, we would like to draw attention to the relative frequent rate of gross gene deletions. Orv Hetil. 2017; 158(30): 1188–1194

De novo SCN1A géndeletio terápiarezisztens Dravet-szindrómában

A Dravet-szindróma vagy régebbi nevén súlyos csecsemőkori myoclonusos epilepszia igen ritka formája az epilepsziának. Az autoszomális domináns öröklésmenetet mutató kórkép leggyakoribb oka a feszültségfüggő nátriumcsatorna alfa-1 alegységet kódoló SCN1A gén mutációja. Az esetek többségének hátterében de novo pontmutáció áll, azonban néhány betegben a gén kópiaszám-változása figyelhető meg. Az SCN1A gén által kódolt fehérje a neuronalis ingerület kiváltásában és vezetésében játszik szerepet. A génmutációk többsége következtében kialakuló funkcióvesztés a neuronalis hálózat fokozott ingerelhetőségéhez vezet, ami az epilepsziás görcsök kialakulását eredményezi. A szerzők intézetében 2013 óta elérhető az SCN1A gén kópiaszám-változásának (deletio/duplikáció) vizsgálata is a gén teljes szekvenálása mellett. Jelen közleményben egy 7 éves beteg esetét mutatják be, aki 2 éves betegút után került intézetükbe. A molekuláris genetikai vizsgálat, amely de novo SCN1A géndeletiót detektált heterozigóta formában, fényt derített a rendkívül terápiarezisztens görcsök hátterében az SCN1A gén asszociálta monogénes epilepszia szindrómára

Generalizált epilepszia hátterében azonosított ioncsatorna-génmutáció ritka formája = A rare form of ion channel gene mutation identified as underlying cause of generalized epilepsy

Absztrakt: A molekuláris genetikai technológiák fejlődése következtében egyre több, korábban idiopátiásnak tartott betegség hátterében ismerjük meg a genetikai eltérést. A generalizált epilepsziában szenvedő, a betegség lefolyása során epilepsziaszindrómát váltó, jó intellektusú, kiterjedt hipopigmentált folttal rendelkező fiúgyermek célzott genetikai vizsgálata neurocutan szindróma irányába nem hozott eredményt. Teljesexom-szekvenálás során egy kálium-klorid-kotranszporter génjének heterozigóta misszensz mutációja igazolódott, ami a fenotípussal összevetve, az irodalomban az idiopátiás generalizált epilepszia 14-es típusaként ismert epilepsziaszindróma diagnózisát támasztja alá. Orv Hetil. 2019; 160(21): 835–838. | Abstract: The advances in molecular genetic methods has lead to the discovery of the genetic alterations that underlie the etiology of most diseases previously held to be idiopathic. Targeted genetic examination of a pediatric male patient showing a normal intellect, an extended area of skin hypopigmentation, and suffering from generalized epilepsy displaying a switch in epilepsy syndrome during the course of the disease towards a neurocutaneous syndrome was unsuccessful. Whole-exome sequencing identified a heterozygous missense mutation in a potassium chloride cotransporter gene, which together with the phenotype underscores the diagnosis of an epilepsy syndrome known in the literature as idiopathic generalized epilepsy type 14. Orv Hetil. 2019; 160(21): 835–838