Ursachen und Diagnostik pharmakoresistenter fokaler Epilepsien

In den Originalarbeiten der vorliegenden Habilitationsschrift wurden die Mechanismen und Ursachen von Pharmakoresistenz bei Patient*innen mit fokalen strukturellen und autoimmunassoziierten Epilepsien untersucht. Dabei wurden Biomarker der Pharmakoresistenz von strukturellen Epilepsien und die Beteiligung des Multidrug-Efflux-Transporterproteins P-gp mit Hilfe von (R)-[11C]Verapamil-PET. Bei Patient*innen mit fokalen strukturellen Epilepsien aufgrund einer Hippocampussklerose oder zerebraler Entwicklungsstörungen konnte eine on P-gp im Vergleich zu anfallsfreien Patient*innen und gesunden Kontrollpersonen nachgewiesen werden. In Zukunft könnten Patient*innen hinsichtlich einer Überfunktion von P-gp mit (R)-[11C]Verapamil-PET untersucht und ihre ASM individuell angepasst werden, um die Pharmakoresistenz zu überwinden – beispielsweise mittles neu entwickelter Substanzen, die P-gp hemmen oder die dieses Multidrug-Efflux-Transporterprotein umgehen. In unserer Studie bei Patient*innen mit Autoimmunenzephalitiden konnten wir zeigen, dass sich bei Nachweis von GAD-Antikörpern häufig eine autoimmunassoziierte Epilepsie entwickelt. Oft wird eine Autoimmunenzephalitis aufgrund von GAD-Antikörpern jedoch zu spät erkannt und eine Therapie verzögert begonnen. Zusätzlich sprechen diese Antikörper generell schlecht auf Immunsuppressiva an. Im Vergleich dazu ist die Entstehung autoimmunassoziierter Epilepsien bei Autoimmunenzephalitiden aufgrund von neuronalen Oberflächenantikörpern nur sehr selten. Vielmehr treten hier die Anfälle nur in der Akutphase auf. Bei früher Diagnosestellung und rechtzeitiger Einleitung der immunsuppressiven Therapie kann ein Auftreten von wiederkehrenden, unprovozierten Anfällen vermieden werden. Eine langfristige Gabe von ASM ist daher nicht nötig. In der prächirurgischen Diagnostik findet die [18F]FDG-PET insbesondere bei unauffälligem cMRT ihre Anwendung. Mit unserer multizentrischen Studie an fast 1.000 Epilepsie-Patient*innen konnten wir die hohe Sensitivität von [18F]FDG-PET zur Lokalisation der Anfallsursprungszone gerade bei Patienten mit negativem MRT bestätigen. Andere Radiotracer wie der Perfusionstracer [15O]H2O-PET haben diesbezüglich auch vielversprechende Ergebnisse gezeigt

Methylmercury varies more than one order of magnitude in commercial European rice

P.M. thanks the Royal Thai Government for funding and C.C.B. thanks the School of Natural and Computing Science and PS Analytical for funding.Peer reviewedPostprin

Neonatal visual assessment in congenital heart disease: A pilot study

This study assessed neonatal visual maturity in infants with congenital heart disease (CHD) and its predictive value for neurodevelopmental outcomes. Neonates with CHD underwent a standardized visual assessment before and after cardiopulmonary bypass surgery. Visual maturity was rated as normal versus abnormal by means of normative reference data. Twelve-month neurodevelopment was assessed with the Bayley-III. Twenty-five healthy controls served as the reference group. Neonatal visual assessment was performed in five neonates with CHD preoperatively and in 24 postoperatively. Only postoperative assessments were considered for further analysis. Median [IQR] age at assessment was 27.0 [21.5, 42.0] days of life in postoperative neonates with CHD and 24.0 [15.0, 32.0] in controls. Visual performance was within reference values in 87.5% in postoperative CHD versus 90.5% in healthy controls (p = 1.0). Visual maturity was not predictive of neurodevelopment at 12 months. These results demonstrate the limited feasibility and predictive value of neonatal visual assessments in CHD

Atypical gaze-following behaviour in infants with congenital heart disease

BACKGROUND Neurodevelopmental impairments are the most prevalent non-cardiac long-term sequelae in children with complex congenital heart disease (CHD). Deficits include the social-emotional and social-cognitive domains. Little is known about the predecessors of social-cognitive development in infants with CHD during the first year of life. Gaze-following behaviour can be used to measure early social-cognitive abilities. AIMS To assess gaze-following development in infants with CHD compared to healthy controls. STUDY DESIGN Prospective cohort study. PARTICIPANTS Twenty-three infants who underwent neonatal correction for CHD and 84 healthy controls. OUTCOME MEASURES Gaze-following behaviour was assessed by eye tracking at 6 and 12 months. Difference scores for first fixation, fixation frequency and fixation duration towards the gaze-cued object were calculated across 6 trials and compared between groups at both testing time points while adjusting for known confounders. Linear mixed models were calculated to assess the longitudinal trajectory of gaze-following development while accounting for the nested and dependent data structure. RESULTS At 6 months, no difference in gaze-following behaviour between CHD and healthy controls was found. At 12 months, fixation frequency towards the gaze-cued was lower and looking duration was shorter in CHD compared to controls (p = 0.0077; p = 0.0068). Infants with CHD showed less increase with age in the fixation frequency towards the congruent object (p = 0.041) compared to controls. CONCLUSION During the first year of life, gaze-following development diverges in infants with CHD compared to healthy controls. Further research is needed to investigate the clinical relevance of these findings and the association with later social-cognitive development

Why is NanoSIMS elemental imaging of arsenic in seaweed (Laminaria digitata) important for understanding of arsenic biochemistry in addition of speciation information?

Acknowledgements The work was supported by funding from the French “Agence Nationale de la Recherche” via the project ANR-11-EQPX-0027 MARSS. E. E. thanks the EU Erasmus Programme for financial support.Peer reviewedPostprin

Proceedings of the First Karlsruhe Service Summit Workshop - Advances in Service Research, Karlsruhe, Germany, February 2015 (KIT Scientific Reports ; 7692)

Since April 2008 KSRI fosters interdisciplinary research in order to support and advance the progress in the service domain. KSRI brings together academia and industry while serving as a European research hub with respect to service science. For KSS2015 Research Workshop, we invited submissions of theoretical and empirical research dealing with the relevant topics in the context of services including energy, mobility, health care, social collaboration, and web technologies

A reforma do ensino superior no contexto da reforma do estado brasileiro

A Reforma do Estado brasileiro estabelecida nos anos 90 do século XX durante o governo de Fernando Henrique Cardoso (1995-2002) é o ápice da ascensão das políticas neoliberais no país, representadas pelo forte ajuste fiscal e a implantação de um Estado mínimo, conformando o estabelecimento de diminuição ou corte nos gastos públicos e a progressiva privatização de empresas estatais e de serviços públicos de uma maneira geral.  Esta reforma, configura-se como a primeira geração de reformas neoliberais brasileiras que buscam, especificamente, a redefinição do estado e do que lhe é atividade exclusiva e do que será considerado seu corpo de servidores.A segunda geração de reformas acontece nos anos do governo de Lula da Silva (2003-2010), numa expressiva complementaridade ás reformas iniciadas no governo anterior, ainda que estas se mostrem contrárias às necessidades dos trabalhadores brasileiros em geral e fortemente marcadas pelas diretrizes dos organismos internacionais do capital tais como o Banco Mundial e o Fundo Monetário Internacional, para os chamados países periféricos.  Entre os anos de 2003 e 2007, no contexto da Reforma do Estado, passou então a ser institucionalizada a reforma do ensino superior brasileiro, que ganha corpo com a adoção de um conjunto de medidas, dentre elas, o Programa de Apoio aos Planos de Reestruturação e Expansão das Universidades Federais (REUNI), implantado por Decreto lei em 2007. Propomo-nos a analisar, a partir de uma pesquisa bibliográfica, a política de expansão do ensino superior brasileiro efetivada no contexto da reforma do estado e as transformações educacionais determinadas por essa política, implantadas nas instituições publicas de ensino superior no período de 2007-2012. Buscamos identificar nessa expansão, a configuração de um processo efetivo de democratização  do acesso ao ensino superior no Brasil. Nossos estudos, até o momento, apontam para um aumento significativo de instituições federais criadas no periodo, para o  aumento das matrículas, para a expansão de campi, para o aumento na contratação de docentes. Contudo, identificamos problemas na implantação do REUNI, no que diz respeito principalmente à estrutura física com novas Universidades e Campi de Expansão em processo de construção;  à estrutura pedagógica e curricular, com novos cursos criados cujos Projetos pedagógicos encontravam-se em fase de elaboração; ao trabalho docente precarizado pela sobrecarga de disciplinas e o acúmulo de outras atividades afins ao exercício do magistério superior

Perioperative Course and Socioeconomic Status Predict Long-Term Neurodevelopment Better Than Perioperative Conventional Neuroimaging in Children with Congenital Heart Disease

OBJECTIVE The objective of the study was to compare the use of neonatal conventional brain magnetic resonance imaging (MRI) with that of clinical factors and socioeconomic status (SES) to predict long-term neurodevelopment in children with severe congenital heart disease (CHD). STUDY DESIGN In this prospective cohort study, perioperative MRIs were acquired in 57 term-born infants with CHD undergoing cardiopulmonary bypass surgery during their first year of life. Total brain volume (TBV) was measured using an automated method. Brain injury severity (BIS) was assessed by an established scoring system. The neurodevelopmental outcome was assessed at 6 years using standardized test batteries. A multiple linear regression model was used for cognitive and motor outcomes with postoperative TBV, perioperative BIS, CHD complexity, length of hospital stay, and SES as covariates. RESULTS CHD diagnoses included univentricular heart defect (n = 15), transposition of the great arteries (n = 33), and acyanotic CHD (n = 9). Perioperative moderate-to-severe brain injury was detected in 15 (26%) patients. The total IQ was similar to test norms (P = .11), whereas the total motor score (P < .001) was lower. Neither postoperative TBV nor perioperative BIS predicted the total IQ, but SES (P < .001) and longer hospital stay (P = .004) did. No factor predicted the motor outcome. CONCLUSION Although the predictive value of neonatal conventional MRIs for long-term neurodevelopment is low, duration of hospital stay and SES better predict the outcome in this CHD sample. These findings should be considered in initiating early therapeutic support

Viral hemorrhagic fevers: advancing the level of treatment

The management of viral hemorrhagic fevers (VHFs) has mainly focused on strict infection control measures, while standard clinical interventions that are provided to patients with other life-threatening conditions are rarely offered to patients with VHFs. Despite its complexity, a proper clinical case management of VHFs is neither futile nor is it lacking in scientific rationale. Given that patient outcomes improve when treatment is started as soon as possible, development and implementation of protocols to promptly identify and treat patients in the earliest phases of diseases are urgently needed. Different pharmacological options have been proposed to manage patients and, as for other life-threatening conditions, advanced life support has been proved effective to address multiorgan failure. In addition, high throughput screening of small molecular libraries has emerged as a novel promising way to find new candidates drugs for VHFs therapy and a relevant number of new molecules are currently under investigation. Here we discuss the current knowledge about VHF clinical management to propose a way to step up the approach to VHFs beyond the mere application of infection control measures

FORMAÇÃO E ALFABETIZAÇÃO: PROGRAMA ALFABILÍNGUE PARA OS POVOS DA AMAZÔNIA

Este artigo tem como escopo relatar a prática de formação de alfabetizadores e coordenadores de turmas bilíngues de diversas etnias no estado do Amazonas desenvolvida por uma das autoras, enquanto coordenadora do Programa de Letramento Reescrevendo o Futuro, no período de 2003 a 2010.O tema formação de professores sempre traz infinitas reflexões, independente dos arautos aos quais pertença. Apresentamos, em um primeiro momento, a descrição da proposta de formação dos alfabetizadores e coordenadores. Em um segundo momento, explicitamos o relato de uma experiência de alfabetização em língua materna, vivida com um grupo omágua/kambeba, desaldeado e desracializado1 que reside no bairro Zumbi dos Palmares, na cidade de Manaus. Tanto a metodologia das formações quanto a ação de alfabetização tiveram formato presencial e foram acompanhadas sistematicamente por uma equipe pedagógica disponibilizada pelas instituições envolvidas. Como resultado, foi evidenciado que os sujeitos do projeto adquiriram uma nova maneira de interagir com a cultura oral e escrita, ampliando sua leitura de mundo na perspectiva de sua valorização enquanto resgate da cidadania.1 MEDEIROS, Priscila Martins. O Descentramento e a Desracialização do Nacional: estado e relações étnico-raciais e ações afirmativas no Brasil. 2015. 233 f. Tese (Doutorado em Sociologia) – Programa de Pós-graduação em Sociologia, Universidade de São Carlos (UFSCar), São Carlos, 2015.