The purpose of this project was to compare the Attention to Memory (AtoM) and the Episodic Buffer (EB) Models. The AtoM model proposes that the ventral parietal cortex (VPC) and dorsal parietal cortex (DPC) are responsive to bottom-up and top- down attention to memory, respectively, (Cabeza, 2008; Cabeza et al., 2008; Ciaramelli et al., 2008). The EB model, on the other hand, proposes that the VPC is involved in the episodic buffer component of Baddeley's working memory model (Vilberg & Rugg, 2008). Using objective (source) and subjective (Remember/Know) retrieval tasks, specific patterns of PPC activity were posited based on the propositions of the AtoM model. These expectations included greater VPC activity for Remember and False Alarms compared to Correct Rejections and Subjective Know, greater DPC activity for Know and Objective Remember compared to Subjective Remember and correct rejections, and no difference in VPC activity for remembering both font and color compared to remembering only one contextual detail. During encoding participants saw words in one of two colors, red or yellow, and in one of two fonts, curvy or straight, and were required to indicate the color the word was presented in. Following each encoding scan participants performed either an Objective or Subjective retrieval task. During Objective retrieval task, participants performed a forced-choice source memory test choosing the word with the correct fontand color or the "new" option. During Subjective retrieval participants were presented with the word in a neutral font and white color and performed a Remember/Know test. On the Subjective retrieval task both VPC and DPC were active for recollection compared to familiar items and Correct Rejections. On the Objective retrieval task the DPC was active for all correct old responses. Neither the VPC nor the DPC were significantly active for False Alarms on both the Subjective and Objective tasks. Both VPC and DPC were more active for Subjective Remember compared to Objective Remember response. Neither PPC region was more active for remembering font and color compared to remembering only font or color. Memory load effects for retrieval of information from long-term memory were only seen in the hippocampus on the Subjective retrieval task. These patterns of activity support the role of the VPC in recollection, as seen on the Subjective task, and the role of the DPC in familiarity, as shown in both the Subjective and Objective tasks. The role of the VPC and DPC during recollection and familiarity processing supports both the AtoM and the EB model. The key predictor of the Episodic Buffer model, memory load effects, was not supported and provides the only evidence against one of the two proposed models. Future work should examine the role of the posterior parietal cortex in spontaneous episodic retrieval to assess the validity of the AtoM model. Advanced imaging analysis techniques should be used to determine functional connectivity between the PPC and frontal and temporal memory regions.

Posterior reversible encephalopathy syndrome (PRES) is a clinical-radiographic syndrome that presents with neurological manifestations, including seizures, headache, or confusion, and is associated with posterior cerebral white matter edema on imaging. PRES is typically a benign and reversible condition. However, PRES can be fatal or associated with permanent deficits. Numerous conditions are associated with PRES, including hypertensive encephalopathy, renal diseases, and cytotoxic or immunosuppressant drugs. Recently, many case reports described the association between PRES and chemotherapeutic agents. However, trastuzumab-associated PRES is rarely reported. Herein, we report a case of a 51-year-old female with a history of metastatic gastric cancer who developed seizures while being treated with trastuzumab, and neuroimaging confirmed the diagnosis of PRES.

Im Jahre 2011 wurden erstmals neuronale Stammzellen (NSCs) im Nucleus Cochlearis (N.C.) der Ratte beschrieben (Rak et al. 2011). Um diese Zellen besser zu charakterisieren, war das Ziel der vorliegenden Arbeit, die NSCs des N.C. im Hinblick auf ihre Maturation und Interaktion in neuronalen Netzwerken sowie auf die Möglichkeiten nichtinvasiver Beeinflussung dieser Zellen zu untersuchen und diese mit primären Neuronen des N.C. zu vergleichen. Für die Untersuchungen waren intrazelluläre Calcium-Ionen (Ca2+) von besonderem Interesse, da diese über spannungsgesteuerte Ca2+-Kanäle (VGCCs) und deren Spontanoszillationen indirekt die Aktivität und Differenzierung der Neurone widerspiegeln könnten. Für die Analyse wurden N.C.s von P6 Ratten mikroskopisch präpariert und nach Dissoziation in Einzelzellen die NSCs für 8 Wochen in Stammzellmedium kultiviert oder direkt als primäre Neurone im Stammzellmedium ausplattiert. Zur Vorbereitung der Untersuchungen fand eine Kultivierung der jeweiligen Zellen für 4 Tage in Differenzierungsmedium statt. Anschließend wurden sie für Calcium-Imaging-Messungen mit dem Ca2+-sensitiven Fluorophor Oregon Green BAPTA-1 beladen. Zum einen wurde eine Analyse der Grundaktivitäten innerhalb der Zellareale und im neuronalen Netzwerk im Verlauf der Maturation durchgeführt. Zum anderen fand am Tag 4 der Zelldifferenzierung (DIF d4) eine Untersuchung der qualitativen und quantitativen Verteilung von VGCCs über die Zugabe der Ca2+-Kanalinhibitoren Nifedipin, ω-Conotoxin MVIIC, Kurtoxin und SNX-482 statt. In jedem Fall wurden die Zellen anschließend mit PFA fixiert und immunzytologisch untersucht. Zudem wurde eine Markierung der VGCCs mit dem Antikörper anti-Ca2+-Channel-(1 Subunit)-Pan vorgenommen. Innerhalb der Ergebnisse konnte eine Abhängigkeit der neuronalen Reifung von der Zellaktivität in Form von Ca2+-Strömen nachgewiesen werden. Hierfür zeigte sich ursächlich eine Variation im qualitativen und quantitativen Vorkommen von VGCCs und in ihrer Spontanaktivität innerhalb der Zellareale im Verlauf der neuronalen Maturation. NSCs zeigten ein ähnliches Verhalten wie primär kultivierte Neurone - sowohl bezüglich ihres Aktivitätsmusters während der Differenzierung als auch bezüglich ihrer Möglichkeit der Inhibierung, was auf eine ähnliche Expression von VGCCs hinweisen könnte. Die höchste Aktivität zeigte sich in beiden Fällen bei DIF d4. Die neurogene Nische, welche in der Literatur sowohl bei Ratten (Rak et al. 2011) als auch bei Mäusen (Volkenstein et al. 2013) im N.C. nachweisbar war, könnte somit zur Analysierung pathologischer Prozesse sowie auch zu deren Behandlung in Betracht gezogen werden. Zusammenfassend konnte in der vorliegenden Dissertation eine Charakterisierung des N.C. der Hörbahn in elektrophysiologischer und biochemischer Hinsicht erreicht werden. Die Ansätze dieser Arbeit könnten in Zukunft zu Therapieoptionen der Hörrehabilitation auf dieser Ebene beitragen. / Neural stem cells (NSCs) have been described in the cochlear nucleus (C.N.) of rats. The objective of this thesis was further characterize these cells with regard to their maturation and interaction in neural networks in comparison with primary neurons of the C.N. and the possibility of non-invasive influence by soluble factors. In this context, particular attention should be paid to the intracellular calcium ions as these could indirectly reflect the activity and differentiation of the neurons via voltage gated calcium channels (VGCCs) and their spontaneous oscillations. For analysis the C.N.s from p6 rats were microscopically prepared and after dissociation in single cells the NSCs were cultured in a neurosphere assay or plated directly as primary neurons. For calcium imaging measurements cells were loaded with the calcium sensitive fluorophore Oregon Green BAPTA-1. Spontaneous activities were analyzed within the cell areas and in neural networks during course of maturation. In addition, the qualitative and quantitative distribution of VGCCs was investigated by blocking the cells with the calcium channel inhibitors Nifedipine, ω-Conotoxin MVIIC, Kurtoxin and SNX-482. After calcium imaging analysis cells were fixed with paraformaldehyde and examined immunocytologically regarding to their status of differentiation. In addition, the VGCCs were marked by the antibody anti-calcium-channel-(1 subunit)-pan. A dependence of neural maturation on cell activity by calcium currents could be demonstrated. The reason for this was a variation in qualitative and quantitative occurrence of VGCCs and in their spontaneous activity within the cell areas in the course of neural maturation. Interestingly NSCs behaved similar to primary cultured neurons - both in their activity pattern and in their possibility of inhibition during differentiation, which indicates a similar expression of VGCCs. The highest activity in both cell types was found on day 4 of cell differentiation. In the presented thesis NSCs of the C.N. were further characterized by electrophysiological and biochemical investigations. The results could contribute to the development of new therapeutic strategies for hearing rehabilitation in the future.

22q11.2 deletion syndrome (22q), also known as Velocardiofacial Syndrome or DiGeorge Syndrome, is one of the most common genetic syndromes with an incidence of 1 in 2500 to 1 in 4000 (Wang et al., 2009). It is the most identified human chromosomal microdeletion syndrome to date (Wang et al., 2009). 22q is associated with a wide spectrum of clinical features including various palate, cardiac, and immunological abnormalities (Lynch et al., 1995; Wang et al., 2009). 22q is also the most common genetic cause of velopharyngeal dysfunction (VPD). Posterior cranial fossa (PCF) and cervical spine variations may influence velopharyngeal (VP) port closure. Although some studies have analyzed PCF size in individuals with 22q, there has not been extensive analysis of skull base anomalies and their correlation to velopharyngeal depth. The purpose of this study was to examine PCF measures and their effects on VP dimensions in children with 22q using a non-sedated imaging protocol. 34 participants, 17 with 22q and 17 with normal VP anatomy (age range: 4-12 years) completed the study. Participants were imaged using a 3D anatomical scan. MRIs were transferred into Amira 6.4 Visualization Volume Modeling software. Linear and angular measures were obtained in the sagittal image plane on the 3D MRI scans. Measures included: distance from the palatal plane to C1, pharyngeal depth, anterior cranial base angle, posterior cranial base angle, length of the clivus, McRae line and supraocciput of the PCF, angle of clivus, and the PCF angle formed by the McRae line and the supraocciput. It is hypothesized that shorter clivus length and smaller PCF angle between McRae line and supraocciput noted in individuals with 22q DS could be related to larger pharyngeal depth, which contributes to hypernasality typically seen in 22q. Results from this study indicate that children with 22q demonstrate larger pharyngeal depth, a more obtuse anterior cranial base angle (NSB angle), a more acute posterior cranial base angle (SBO angle), shorter length of the clivus, longer supraocciput length, and a more obtuse angle of clivus. The NSB angle was positively correlated with pharyngeal depth while the SBO angle was negatively correlated with pharyngeal depth. The angle of clivus was positively correlated with both pharyngeal depth and resonance severity.

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The development of postural stability in children with and without visual impairments (VI) was compared. Thirty eight subjects (4- 12 years old) without VI and 12 subjects with VI (5- 12 years) took part. Stability was measured in 4 quiet standing tasks (normal or foam surface, eyes open (EO) or eyes closed (EC)) and by measuring stability limits (SL) in the anterio-posterior (a-p) and lateral (lat) planes. Results for control subjects were compared using Pearson correlation coefficients, analysis of variance, and analysis of covariance (height as the covariate). For quiet standing tasks, outcome parameters were the standard deviation (SO) of the centre of pressure (CP) in the a-p and lat planes, and mean velocity (vel) of CP movements. For the leaning tasks, SL was measured (normalized to the base of support) in the a-p and lat planes, and SL was compared to CP. Individual results for subjects with VI were compared qualitatively to control subjects. For control subjects, stability increased with age. Subjects with VI were less _stable than controls on all outcome parameters. Differences between groups were more apparent as age increased, particularly for EO conditions. This could indicate a slower pattern of development for subjects with VI compared to controls. The groups were different both in the EO and EC conditions, indicating that postural control with EC is not the same as postural control with a VI, and that vision is important to the development of postural control in children. / Thesis / Master of Science (MSc)

O objetivo do presente estudo foi avaliar a atividade eletromiográfica dos músculos masseter e temporal e o comportamento esquelético e dental de crianças submetidas à expansão maxilar com o aparelho quadri-hélice. A amostra foi composta por doze crianças (10 meninas e 2 meninos), com idade média de 7 anos e 4 meses, portadoras de mordida cruzada posterior unilateral. Foram realizados traçados cefalométricos laterais antes do início do tratamento (T1) e após a remoção do aparelho (T2). A atividade eletromiográfica dos músculos masseter e temporal foi analisada nas situações clínicas de repouso muscular, apertamento dental máximo e mastigação não habitual e habitual, antes do início do tratamento (T1) e um mês após a remoção do aparelho quadri-hélice (T2). As medidas cefalométricas e eletromiográficas foram submetidas à análise estatística utilizando os programas GraphPad Prism e SPSS for Windows, respectivamente. A diferença das médias T1 e T2 foi avaliada pelo teste-t para medidas repetidas. Os resultados da análise cefalométrica mostraram que a expansão maxilar com o aparelho quadri-hélice não promoveu alterações esqueléticas ântero-posteriores e verticais significantes. Apenas a medida 1-PP apresentou aumento significante dentre as avaliadas no padrão dental. Na condição clínica de repouso, a análise eletromiográfica indicou uma diminuição na atividade do músculo masseter e um aumento significante na atividade do temporal. Durante o apertamento dental, a atividade eletromiográfica dos músculos masseteres apresentou uma leve diminuição e dos temporais manteve-se constante ao final do tratamento. Todos os músculos apresentaram aumento na atividade eletromiográfica durante a mastigação não habitual, sendo estatisticamente significante apenas para o músculo temporal direito. A atividade eletromiográfica diminuiu significantemente em todos os músculos avaliados na condição clínica de mastigação habitual após a remoção do aparelho quadri-hélice. / The aim of the present study was to analyze the electromyographic activity of masseter and temporal muscles and the skeletal and dental effects of maxillary expansion realized in children with the quad-helix appliance. The sample consisted of twelve children (10 girls and 2 boys), mean age 7 years and 4 months, with unilateral posterior crossbite. Lateral cephalograms were taken before treatment (T1) and after the quad-helix appliance was removed (T2). The electromyographic activity of masseter and temporal muscles was analyzed before treatment (T1) and after the appliance was removed (T2). The muscular activity was electromyographic analyzed during the clinical situation of rest, maximal voluntary dental clench, non-habitual and habitual chewing. The cephalometric and electromyographic measurements were analyzed statiscally using GraphPad Prism and SPSS 10.0 for Windows, respectively. The differences between T1 and T2 data were evaluated using the paired t- test. The results of the cephalometric analyze showed that the maxillary expansion realized in children with the quad-helix appliance didn?t promote vertical and sagittal skeletal significant change. Only the linear measure 1-PP showed a significant raise considering the dental pattern. During the clinical situation of rest, the electromyographic analyze indicated a diminution on the activity of the masseter muscle and a significant increase on the temporal activity. During maximal voluntary clench, the electromyographic activity of masseter muscle presented a slight diminution and the temporal activity stayed the same at the end of the treatment. Every muscle showed a raise on the electromyographic activity during non-habitual chewing, being statistically significant only for right temporal muscle. The electromyographic activity diminished significantly for every muscle evaluated during the clinical situation of habitual chewing after removal of the quad-helix appliance.

INTRODUÇÃO: A disfunção do tendão tibial posterior (DTTP), principal causa de pé plano adquirido no adulto, é mais frequente em indivíduos do gênero feminino e apresenta pico de incidência na sexta década de vida. Diversos fatores de risco - intrínsecos e extrínsecos - e condições sistêmicas associadas são descritas na literatura. A predisposição genética resultante da maior expressão de genes relacionados ao metabolismo hormonal, principalmente do estrogênio, pode desempenhar influência na fisiopatogenia dessa lesão em associação aos fatores comportamentais e endógenos. OBJETIVO: Analisar a frequência de polimorfismos nos genes dos receptores de estrogênio (RE) dos tipos alfa (RE1) e beta (RE2), em pacientes na pós-menopausa com diagnóstico de tendinopatia do tendão do músculo tibial posterior e em pacientes assintomáticas. CASUÍSTICAS e MÉTODOS: Foram incluídas 202 pacientes do gênero feminino (N=202), com idade superior a 40 anos, divididas em 2 grupos (n=101), de casos e controles. Foram definidos como casos pacientes na pós-menopausa com diagnóstico de DTTP, realizado por meio dos exames clínico e de imagem (RM), e, como controles, pacientes com as mesmas características epidemiológicas, assintomáticas, que apresentavam exames clínico e de imagem normais para a avaliação do tendão tibial posterior. Células epiteliais da mucosa bucal das pacientes incluídas no estudo foram coletadas por meio de bochecho com solução glicosada para extração e análise do RESULTADOS: Pacientes portadoras do genótipo xx do SNP XbaI apresentaram risco estimado 2,38 vezes maior (p = 0,029) de desenvolver a DTTP quando comparadas às portadoras dos genótipos selvagem ou heterozigoto. Já a distribuição dos genótipos dos SNP PvuII e AluI não apresentou associação com o desenvolvimento da doença. ADN genômico. Os SNP dos genes dos RE1 (XbaI e PvuII) e RE2 (AluI) foram avaliados com base em PCR-RFLP. CONCLUSÃO: O presente estudo demonstra que pacientes com polimorfismo XbaI do RE1 apresentam maior risco de desenvolvimento da disfunção do tendão tibial posterior / INTRODUCTION: Posterior tibial tendon dysfunction (PTTD), the most common cause of flatfoot deformity in adults, is more frequent in the female gender with peak incidence in the sixth decade of life. Multiple risk factors - intrinsic and extrinsic - and associated systemic conditions have been described in the literature. Genetic predisposition secondary to hyperexpression of genes related to hormonal metabolism, particularly the estrogens, may play a role in the pathogenesis of this disease acting in association with behavioral and endogenous risk factors. OBJECTIVE: The aim of this study was to analyze the frequency of polymorphisms of the estrogen receptors (ER) alpha (ER1) and beta (ER2) in postmenopausal women with PTTD when compared to asymptomatic control patients. METHODS: 202 female patients over the age of 40 were included in the study (N = 202). They were then divided into 2 different groups (n = 101): cases and controls. We defined as cases postmenopausal women with symptomatic PTTD, diagnosed by clinical and MRI examinations. Females with similar epidemiology, but clinically asymptomatic and with normal MRI evaluation for the posterior tibial tendon were defined as controls. Oral mucosa epithelial cells were collected from the patients and genomic DNA was extracted from the samples. The SNPs for the ER1 (XbaI and PvuII) and ER2 (AluI) genes were assessed by PCR-RFLP. RESULTS: Patients with SNP Xbal genotype xx had 2.38 higher estimated risk (p = 0,029) in developing PTTD, when compared to patients with the other genotypes. No associations were found for the SNP PvuII and AluI. CONCLUSION: The present study demonstrates that patients with the Xbal single nucleotide polymorphism of estrogen receptor 1 gene have higher risk of developing posterior tibial tendon dysfunction