Epilepsy surgery in tuberous sclerosis: The Dutch experience

SummaryIntroductionEpilepsy associated with tuberous sclerosis complex (TSC) is drug resistant in more than half of the patients. Epilepsy surgery may be an alternative treatment option, if the epileptogenic tuber can be identified reliably and if seizure reduction is not at the expense of cognitive or other functions. We report the pre-surgical identification of the epileptogenic tuber and post-surgical outcome of patients with TSC in The Netherlands.MethodsTwenty-five patients underwent the pre-surgical evaluation of the Dutch Comprehensive Epilepsy Surgery Programme, including a detailed seizure history, interictal and ictal video EEG registrations, 3D FLAIR MRI scans and neuropsychological testing. Suitability of the candidates was decided in consensus. Seizure outcome, scored with the Engel classification, and cognition were reassessed at fixed post-surgery intervals.ResultsEpilepsy surgery was performed in six patients. At follow-up, four patients had Engel classification 1, two had classification 4. Improved development and behaviour was perceived by the parents of two patients. Epilepsy surgery was not performed in 19 patients because seizures were not captured, ictal onset zones could not be localised or were multiple, interictal EEG, video EEG and MEG results were not concordant, or seizure burden had diminished during decision making. A higher cognition index was found in the surgical patients compared to the non-surgical candidates.ConclusionsEpilepsy surgery can be performed safely and successfully in patients in whom semiology, interictal EEG, ictal EEG, MEG and the location of tubers are concordant. In other cases the risk of surgery should be weighed against the chance of seizure relief and in case of children subsequent impact on neurodevelopment

The bio in the ink: cartilage regeneration with bioprintable hydrogels and articular cartilage-derived progenitor cells

Cell-laden hydrogels are the primary building blocks for bioprinting, and, also termed bioinks, are the foundations for creating structures that can potentially recapitulate the architecture of articular cartilage. To be functional, hydrogel constructs need to unlock the regenerative capacity of encapsulated cells. The recent identification of multipotent articular cartilage-resident chondroprogenitor cells (ACPCs), which share important traits with adult stem cells, represents a new opportunity for cartilage regeneration. However, little is known about the suitability of ACPCs for tissue engineering, especially in combination with biomaterials. This study aimed to investigate the potential of ACPCs in hydrogels for cartilage regeneration and biofabrication, and to evaluate their ability for zone-specific matrix production. Gelatin methacryloyl (gelMA)-based hydrogels were used to culture ACPCs, bone marrow mesenchymal stromal cells (MSCs) and chondrocytes, and as bioinks for printing. Our data shows ACPCs outperformed chondrocytes in terms of neo-cartilage production and unlike MSCs, ACPCs had the lowest gene expression levels of hypertrophy marker collagen type X, and the highest expression of PRG4, a key factor in joint lubrication. Co-cultures of the cell types in multi-compartment hydrogels allowed generating constructs with a layered distribution of collagens and glycosaminoglycans. By combining ACPC- and MSC-laden bioinks, a bioprinted model of articular cartilage was generated, consisting of defined superficial and deep regions, each with distinct cellular and extracellular matrix composition. Taken together, these results provide important information for the use of ACPC-laden hydrogels in regenerative medicine, and pave the way to the biofabrication of 3D constructs with multiple cell types for cartilage regeneration or in vitro tissue models

Расчет потерь давления воздуха в горных выработках с учетом равномерных и неравномерных утечек

Охарактеризовано метод розрахунку втрат тиску повітря у гірничих виробках за наявності витоків (притоків), який може бути використано під час проектування системи провітрювання шахти з метою вибору засобів місцевого керування повітряних потоків, розрахунку конфігурації ліній витоку у виробленому просторі та при оцінці зміни витоків у аварійній ситуації і розробці методів керування ними.The method of calculation losses of pressure of air in the mining workings at presence of leakages (inflows), which can be used for planning of the ventilation system of mine with the purpose of choice facilities of the local control of air blast, calculation of configuration lines of leakages in the worked out goaf and at estimation change of leakages in an emergency situation and development methods of control by them

Persistence of Livestock Associated MRSA CC398 in Humans Is Dependent on Intensity of Animal Contact

INTRODUCTION: The presence of Livestock Associated MRSA (LA-MRSA) in humans is associated with intensity of animal contact. It is unknown whether the presence of LA-MRSA is a result of carriage or retention of MRSA-contaminated dust. We conducted a longitudinal study among 155 veal farmers in which repeated nasal and throat swabs were taken for MRSA detection. Periods with and without animal exposure were covered. METHODS: Randomly, 51 veal calf farms were visited from June-December 2008. Participants were asked to fill in questionnaires (n = 155) to identify potential risk factors for MRSA colonisation. Nasal and throat swabs were repeatedly taken from each participant for approximately 2 months. Swabs were analysed for MRSA and MSSA by selective bacteriological culturing. Spa-types of the isolates were identified and a ST398 specific PCR was performed. Data were analyzed using generalized estimation equations (GEE) to allow for correlated observations within individuals. RESULTS: Mean MRSA prevalence was 38% in farmers and 16% in family members. Presence of MRSA in farmers was strongly related to duration of animal contact and was strongly reduced in periods with absence of animal contact (-58%). Family members, especially children, were more often carriers when the farmer was a carrier (OR = 2,

Nijmegen. Geschiedenis van de oudste stad van Nederland

Contains fulltext : 42505incompleet.pdf (publisher's version ) (Open Access)Incomplete kopie van alleen het eerste deel1500 p

Oxidative stress and inflammation in a spectrum of epileptogenic cortical malformations: molecular insights into their interdependence

Oxidative stress (OS) occurs in brains of patients with epilepsy and coincides with brain inflammation, and both phenomena contribute to seizure generation in animal models. We investigated whether expression of OS and brain inflammation markers co-occurred also in resected brain tissue of patients with epileptogenic cortical malformations: hemimegalencephaly (HME), focal cortical dysplasia (FCD) and cortical tubers in tuberous sclerosis complex (TSC). Moreover, we studied molecular mechanisms linking OS and inflammation in an in vitro model of neuronal function. Untangling interdependency and underlying molecular mechanisms might pose new therapeutic strategies for treating patients with drug-resistant epilepsy of different etiologies. Immunohistochemistry was performed for specific OS markers xCT and iNOS and brain inflammation markers TLR4, COX-2 and NF-κB in cortical tissue derived from patients with HME, FCD IIa, IIb and TSC. Additionally, we studied gene expression of these markers using the human neuronal cell line SH-SY5Y in which OS was induced using H 2 O 2 . OS markers were higher in dysmorphic neurons and balloon/giant cells in cortex of patients with FCD IIb or TSC. Expression of OS markers was positively correlated to expression of brain inflammation markers. In vitro, 100 µM, but not 50 µM, of H 2 O 2 increased expression of TLR4, IL-1β and COX-2. We found that NF-κB signaling was activated only upon stimulation with 100 µM H 2 O 2 leading to upregulation of TLR4 signaling and IL-1β. The NF-κB inhibitor TPCA-1 completely reversed this effect. Our results show that OS positively correlates with neuroinflammation and is particularly evident in brain tissue of patients with FCD IIb and TSC. In vitro, NF-κB is involved in the switch to an inflammatory state after OS. We propose that the extent of OS can predict the neuroinflammatory state of the brain. Additionally, antioxidant treatments may prevent the switch to inflammation in neurons thus targeting multiple epileptogenic processes at once

Sharon Macdonald – Memorylands: Heritage and Identity in Europe Today

Memorylands: Heritage and Identity in Europe Today é um livro de síntese que assinala o culminar de anos de trabalho da antropóloga britânica Sharon Macdonald sobre os temas relacionados do património, da memória e da identidade em contextos europeus. Em Reimagining Culture: Histories, Identities and the Gaelic Renaissance, de 1997, situava o eixo analítico entre o local e o global, focando o seu olhar na questão dos muitos “renascimentos identitários” de escala local e regional que à época –..