Thesis (Ph. D.)--University of Washington, 2005. / Vita. Includes bibliographical references (leaves 137-167).

Multiple sclerosis (MS) is a chronic neurological disease characterized by the destruction of central nervous system (CNS) myelin. Although the neurotrophin, brain derived neurotrophic factor (BDNF) has a beneficial role in re-myelination and/or myelin repair, these effects are hampered by the over-expression of a transcriptional repressor isoform of methyl CpG binding protein 2 (MeCP2) called MeCP2E1. We hypothesize that following experimental autoimmune encephalomyelitis (EAE) -induced myelin damage, the immune system induction of the pathogenic MeCP2E1 isoform hampers the re-myelination and/or myelin repair process by repressing BDNF expression. Our research identified the temporal gene and protein expression changes of MeCP2E1, MeCP2E2 and BDNF in an EAE mouse model of MS, and correlated them with the changes in the neurological disability scores (NDS). Our results indicated MeCP2E1 mRNA levels are elevated in EAE animals which is responsible for the repressed BDNF production in the spinal cord that prevents re-myelination and/or myelin repair. / February 2016

Contexto: As oscilações hormonais ao longo da vida estão associadas às variações de humor em mulheres normais. O estrógeno (E) parece estar associado aos níveis de fator neurotrófico derivado do cérebro (BDNF) em voluntárias saudáveis. No entanto, essa associação não foi investigada em pacientes com transtorno bipolar (TB). Sabe-se que os episódios de humor do TB estão associados a alterações dos níveis de BDNF; entretanto, não está claro o papel dos hormônios femininos. Objetivo: investigar a existência de uma possível associação entre os níveis de BDNF e os níveis de hormônios do eixo hipotálamo-hipófise-gonadal em mulheres com TB, incluindo pacientes durante o período reprodutivo e também na pós-menopausa. Métodos: Mulheres eutímicas (HAM-D e YMRS com escores menores que 8) com transtorno bipolar I(TB I), II (TB II) ou transtorno bipolar sem outra especificação (TB SOE) foram incluídas. As pacientes em idade reprodutiva tinham ciclos menstruais regulares (CMR) e não faziam uso de nenhum tipo de contracepção hormonal (CH); e as na pós-menopausa não estavam em uso de terapia de reposição hormonal (TRH). Condições endócrinas instáveis foram consideradas um fator de exclusão. Todas as pacientes estavam em tratamento farmacológico, associado ou não a intervenções psicossociais. Amostras de sangue foram retiradas para as medidas de BDNF, estrogênio (E), progesterona (P), LH e FSH, sendo coletadas nas fases folicular (FF) e lútea (FL) do ciclo menstrual, e uma única vez nas mulheres na pós-menopausa. Os diagnósticos foram confirmados através de entrevista clínica estruturada para o DSM-IV Transtornos do Eixo I (SCID-I), administrado por investigadores treinados. Resultados: Foram avaliadas 96 pacientes com TB. Destas, 64 não preenchiam critérios de inclusão ou apresentavam fatores de exclusão. Foram estudadas 32 mulheres com idades entre 22 e 69 anos (média = 52,78 anos). Considerando toda a amostra, o BDNF apresentou uma correlação positiva com os níveis de estradiol (r = 0,36, p = 0,043). Nas pacientes em período reprodutivo, na fase lútea(FL), houve uma correlação negativa entre o BDNF e o FSH (r = 0,831, p = 0,040). Um resultado semelhante foi encontrado com os níveis de LH (r = 0,908, p= 0,012) nessa mesma fase do ciclo menstrual. Conclusão: Os resultados encontrados na amostra de mulheres com TB foram semelhantes aos descritos na literatura em indivíduos saudáveis, que também apresentam correlação entre E e BDNF (Begliuomini et al., 2007). Estes achados indicam que o estímulo estrogênico pode ser importante na manutenção de s níveis fisiológicos de BDNF. A partir desses resultados novas vias devem ser incluídas na investigação na fisiopatologia das alterações de humor relacionadas a variações hormonais, bem como ao tratamento do TB. Além disso, ressalta a importância de incluir as variações hormonais femininas na equação diagnóstica e prognóstica do TB. / Background: Background: Hormonal oscilations across lifetime have been associated with mood variations in healthy women. Oestrogen (E) seems to be associated with Brain Derived Neurotrophic Factor (BDNF) levels in healthy volunteers. This assictaion was not studied in women with Bipolar Disorder (BD). Mood episodes of BD are associated with reductions in BDNF levels, although the role of feminine hormones in pathophysiology of BD hás not been completely studied. Objective: To investigate the association between BDNF levels and hormones involved in hypothalamus-pituitary-gonadal axis in women with BD, comparing a group during reproductive years with a menopausal group. In addition, differences across the two phases of menstrual cycle were also evaluated in the group during reproductive years. Methods: Women euthymic (HAM-D and YMRS scoring less than 8) with bipolar I, II or bipolar disorder not otherwise specified were included. Patients of reproductive age had regular menstrual cycles (RMC) and did not use any type of hormonal contraception (CH) and postmenopausal were not using hormone replacement therapy (HRT). Endocrine instable conditions were considered an exclusion factor. All patients were on pharmacotherapy, associed or not with psychosocial interventions. Blood samples withdrawn for measures of BDNF, oestrogen (E), progesterone (P), LH and FSH levels, being collected in the follicular phase (FP) and luteal (FL) of the menstrual cycle, menopausal women were held only one blood sample. Diagnoses were assessed using structured clinical interview for DSM-IV Axis I Disorders (SCID-I), administered by certified investigators. Results: Ninety six patients with BD were evaluated, of these, 64 did not meet inclusion criteria or met exclusion factors. The sample was constituted by 32 women with BD aged 22 to 69 years (mean = 52.78 years). Considering the whole sample, the BDNF was significantly correlated with estradiol levels (r = 0.36, p = 0.043). In patients in reproductive period, in the luteal phase, there was a negative correlation with FSH (r = 0.831, p = 0.040). A similar result was found with levels o LH (r = 0.908, p = 0.012) in the same menstrual cycle phase. Conclusion: The results found in the sample of women with TB were similar to those previously reported in healthy subjects, which also show a correlation between E and BDNF (Begliuomini et al., 2007). These findings indicate that estrogenic stimulation may be important in maintaining physiological BDNF levels. From these results, new avenues should be included in research on the pathophysiology of mood swings related to hormonal changes as well as the treatment of TB. Furthermore, the importance of including female hormonal changes in the equation of TB diagnostic and.

Fundamentação: O acidente vascular cerebral (AVC) é uma das principais causas de morte em todo o mundo e a maioria dos sobreviventes permanece com alguma sequela neurológica após o evento agudo. O presente estudo objetiva investigar a associação de alguns biomarcadores sanguíneos com as escalas de AVC, bem como avaliar a capacidade dos biomarcadores selecionados na predição de desfechos neurológicos durante o tempo de acompanhamento. Material e Métodos: Incluímos nesse estudo 60 pacientes com AVC agudo admitidos na unidade neurovascular da emergência ou na unidade de medicina intensiva do Hospital de Clínicas de Porto Alegre, nas primeiras 24 horas do início dos sintomas. Foram coletas amostras sanguíneas nas primeiras 24 horas, no terceiro e no quinto dias após o AVC para dosagem de enolase neurônio específica (ENS), proteína S100ß (S100ß), interleucina 6 (IL-6), proteína C reativa (PCR) e fator neurotrófico derivado do cérebro (BDNF). A gravidade do AVC e o grau de dependência funcional dos pacientes após o AVC foram mensurados através das escalas do National Institutes of Health Stroke Scale (NIHSS) e modified Rankin Scale (mRS) nos três momentos das coletas sanguíneas e na alta hospitalar. Resultados: Os níveis séricos de S100ß, IL-6 e PCR mostraram-se o melhor painel de biomarcadores após o AVC nesse estudo. Quando os pacientes foram subdivididos em dois grupos para a avaliação de desfechos neurológicos, usando as escalas do NIHSS (NIHSS ≤ 6 e NHISS > 6) e mRS (mRS ≤ 3 e mRS > 3), ambas as escalas apresentaram boa associação entre as concentrações de S100ß e de IL-6 em todas as medidas e as escalas de AVC para bom prognóstico (NIHSS ≤ 6 e mRS ≤ 3) na alta hospitalar. Dentre os biomarcadores selecionados para o estudo, foram os três citados acima que apresentaram as melhores correlações com as escalas de AVC e com o prognóstico pós AVC durante o tempo de acompanhamento. Conclusão: Os biomarcadores séricos podem ser úteis na avaliação da gravidade e do prognóstico após o AVC. A associação de S100ß, IL-6 e PCR parece acrescentar pouco às escalas validadas de AVC na capacidade de predizer desfechos após o evento agudo. / Background and Purpose: Stroke is an important cause of death worldwide, and the majority of stroke survivors suffer from some form of residual disability. This study aimed to investigate the association of blood biomarkers with stroke scales and their predictive value after acute stroke at the time of admission until hospital discharge. Design and Methods: We investigated 60 patients with acute stroke who were admitted within 24 h of event onset at the intensive care unit or neurovascular emergency unit of Clínicas Hospital. All patients provided venous blood samples for the measurement of neuron-specific enolase (NSE), S100ß protein (S100ß), interleukin-6 (IL-6), C-reactive protein (CRP) and brain-derived neurotrophic factor (BDNF) within 24 h of the acute event, on the third day and on the fifth day after the stroke. Neurological stroke severity and global disability were determined with the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) at the same three times of blood collection and at the time of hospital discharge. Results: The serum levels of the S100ß protein, IL-6 and CRP seem to constitute the best panel of biomarkers after acute stroke in this study. When patients were subdivided into two groups according to the NIHSS (NIHSS ≤ 6 and NIHSS > 6) and mRS (mRS ≤ 3 and mRS > 3) scores, which were used as neurological outcome measures, both neurologic scores for good outcome (NIHSS ≤ 6 and mRS ≤ 3) at hospital discharge were significantly related to the S100ß protein and IL-6 levels at all of the measured time points. Among the analyzed blood markers, S100ß, IL-6 and PCR levels significanttly correlated with the stroke scales and prognostic value. Conclusion: Blood biomarkers may be useful in acute stroke either by suggesting stroke severity or providing a prognostic value. The addition of the S100ß protein, IL-6 and CRP to previously validated stroke scales slightly improves the ability of these scales to predict outcome.

During my thesis work I studied the expression and potential function of brain expressed microRNAs (miRNAs) in human prefrontal cortex (PFC). Initially, I used combinatorial computational analysis and microarray data to identify miRNAs that are predicted with high probability to target the human Brain Derived Neurotrophic Factor (BDNF) 3’ Untranslated Region (3’UTR) and are expressed in moderate to high levels in adult human prefrontal cortex. A subset of 10 miRNAs segregating into 5 different miRNA families (miR-30a-d, miR-103/107, miR-16/195, miR-191 and miR-495) met the above criteria. I then designed a protocol to detect these miRNAs with Locked Nucleic Acid (LNA) in situ hybridization in human prefrontal cortex and determine their layer and cellular expression patterns. LNA in situ revealed differential lamina and cellular enrichment of BDNF-related miRNAs. As an example, miR-30a-5p was found to be enriched in large pyramidal neurons of layer 3, which was verified using laser capture microdissection of layer 3 pyramidal neurons and quantitative Real Time Polymerase Chain Reaction (qRT-PCR) following dissection of upper and deeper layers of human PFC. Parallel to this, I used miRNA qRT-PCR to determine the developmental expression of miRNAs using postmortem PFC tissues ranging from embryonic age to old adulthood and compared miRNA to BDNF protein levels. My results revealed a robust inverse correlation between BDNF-related miRNAs and BDNF protein during late maturation and aging of human prefrontal cortex. In vitro luciferase assays and/or lentivirus mediated neuronal miRNA overexpression experiments validated that at least two miRNAs, miR-30a-5p and miR-195, target human BDNF 3’UTR and mediate its translational repression. In the second part of my thesis work I measured levels of miR-30a and miR-195 in the prefrontal cortex of patients with schizophrenia and compared them with levels of BDNF protein and BDNF-related GABAergic mRNAs. According to my results differences in miR-195 levels in a subset of subjects diagnosed with schizophrenia were found to be associated with disease related changes in BDNF protein levels and deficits in BDNF dependent GABAergic gene expression. In the last part of my work I focused on miR-30b, another member of the miR-30 family, which I found to be reduced in the prefrontal cortex of female but not male subjects with schizophrenia. More importantly, disease related changes in miR-30b levels were strongly associated with the age of onset of the disease. Additional experiments in mouse cortex and hippocampus revealed a gender dimorphic expression pattern of this miRNA with higher expression in female brain. Collectively, my results suggest that miRNAs could participate in novel molecular pathways that play an important role during cortical development and maturation and are potentially linked to the pathophysiology of neuropsychiatric disease.

Base Teórica: A prevalência de dor crônica na infância é bem documentada e estima-se que atinja entre 20 a 35% da população pediátrica, podendo causar enorme sofrimento em seus portadores, inaptidões pessoais e ser acompanhada de sintomas emocionais importantes. O manejo dessas criancas inclui a compreensão dos fatores biomecânicos, psicológicos e socioculturais associados ao seu contexto. Dentre os fatores psíquicos o pensamento catastrófico sobre a dor, definido como uma resposta negativa exagerada a mesma, tem sido identificado como uma estratégia adaptativa às circunstâncias. A escala de avaliação do pensamento catastrófico em crianças - Pain Catastrophizing Scale – child version (PCS-C), adaptada da escala para adultos, já está validada em diferentes línguas, no entanto, pouco se sabe sobre o catastrofismo em crianças brasileiras. Objetivos: O objetivo desse estudo é validar e adaptar a PCS-C para o português do Brasil, examinar as propriedades psicométricas, bem como a estrutura fatorial da escala, e sua correlação com a dor e suas consequências em crianças com e sem dor crônica. Métodos: A versão em português do Brasil foi modificada por um grupo de especialistas a fim de torná-la apropriada para aplicação em crianças entre 7-12 anos. Para avaliar as propriedades psicométricas, 100 crianças (44 com dor crônica e 56 saudáveis) responderam a versão brasileira da PCS-C (BPCS-C). Também foram questionadas quanto aos níveis de dor e quanto à capacidade funcional durante atividades da prática de educação física na escola. Ainda, amostras de saliva foram passivamente coletadas a fim de se medir o fator neurotrófico derivado do cérebro (BDNF). O subgrupo de crianças com dor crônica foi recrutado dos ambulatórios de gastro pediatria, oncologia e reumatologia do Hospital de Clínicas de Porto Alegre e o subgrupo de crianças saudáveis foi recrutado de uma escola pública. Resultados: O estudo mostrou uma boa consistência interna do instrumento (alfa de Crombach: 0,81 para o escore total da BPCS-C). Tanto a análise paralela, quanto a análise fatorial exploratória identificaram 2 dimensões (fatores) no instrumento. A análise fatorial confirmatória apresentou os melhores valores de ajustamento (CFI, confirmatory fit-index) quando comparada a outros modelos já existentes. Os escores totais da BPCS-C não diferiram entre as crianças com dor crônica e as saudáveis. No entanto, a dificuldade progressiva de realizar as atividades da Educação Física na escola foi associada com o catastrofismo (p=0,019) nos pacientes com dor crônica. BDNF salivar apresentou fraca associação (r=0,27 p=0,012) com o catastrofismo. Conclusão: Os resultados suportam a validade e confiabilidade da BPCS-C. A estrutura de 2 fatores apresentou adequado ajustamento podendo ser usada, mesmo que diferindo do número de fatores da escala original, pois escore total é o valor mais utilizado para composição do diagnóstico. A ausência de diferença entre os escores nas crianças doentes e saudáveis sugere a necessidade de estudos mais profundos sobre a catastrofização em crianças e a necessidade de instrumentos específicos, e não apenas adaptação daqueles utilizados em adultos. / Introduction: The prevalence of chronic pain in childhood is well documented and is estimated to reach 20 and 35% of the pediatric population. Chronica pain can cause enormous suffering, personal miscarriages and it can be accompanied by important emotional symptoms. The management of these children includes understanding the biomechanical, psychological and sociocultural factors associated in this context. Among the psychic factors, catastrophic thinking about pain is identified as an adaptive strategy to the circumstances. The instrument for catastrophic thinking evaluation in children - Pain Catastrophizing Scale - child version (PCS-C), adapted from the scale for adults, is already validated in different languages, however little is known about catastrophism in Brazilian children. Objectives:. With this cross-sectional study, we aim to adapt the Brazilian version of the PCS-C (BPCS-C) and to examine the psychometric properties and factorial structure of the scale for children with and without chronic pain. Methods: The Brazilian version of the PCS-C was modified by a group of experts to appropriate it for children between 7-12 years. To asses the psychometric properties of the version, 100 children (44 with chronic pain and 56 healthy children) answered the BPCS-C, the visual analog scale and one functional school activity question. It was also collected a passive salivary sample to measure BDNF. The chronic pain children sample was recruited from the gastropediatric, oncologic, and reumatologic ambulatories at a tertiary hospital and the healthy children from a fifth grade public school. Results: We observed good internal consistency (Cronbach’s value of 0.81 for the total BPCS-C). Both parallel analysis and exploratory factorial analysis retained 2 factors for instrument dimensions. The confirmatory factorial analysis presented the best adjustment values (CFI, confirmatory fit-index) when compared to other existing pre-existing models. BPCS-C total scores were not diferente between chronic pain and healthy children. However, the progressive difficulty of performing physical education activities at school was associated with catastrophism (p = 0.019) in patients with chronic pain. 6 Salivary BDNF presented a weak association (r = 0.27 p = 0.012) with catastrophism. Discussion: The results support the validity and reliability of BPCS-C. The 2-factors structure presented an adequate adjustment and can be used for brazilian children population. Although different from the number of factors of the original scale, the instrument measured the most used value for diagnosis, total score. The lack of difference between scores in chronic pain and healthy children suggests the necessity of further studies on catastrophizing in children, as well as for specific instruments, instead of simple adaptation of those used in adults.

Contexto: As oscilações hormonais ao longo da vida estão associadas às variações de humor em mulheres normais. O estrógeno (E) parece estar associado aos níveis de fator neurotrófico derivado do cérebro (BDNF) em voluntárias saudáveis. No entanto, essa associação não foi investigada em pacientes com transtorno bipolar (TB). Sabe-se que os episódios de humor do TB estão associados a alterações dos níveis de BDNF; entretanto, não está claro o papel dos hormônios femininos. Objetivo: investigar a existência de uma possível associação entre os níveis de BDNF e os níveis de hormônios do eixo hipotálamo-hipófise-gonadal em mulheres com TB, incluindo pacientes durante o período reprodutivo e também na pós-menopausa. Métodos: Mulheres eutímicas (HAM-D e YMRS com escores menores que 8) com transtorno bipolar I(TB I), II (TB II) ou transtorno bipolar sem outra especificação (TB SOE) foram incluídas. As pacientes em idade reprodutiva tinham ciclos menstruais regulares (CMR) e não faziam uso de nenhum tipo de contracepção hormonal (CH); e as na pós-menopausa não estavam em uso de terapia de reposição hormonal (TRH). Condições endócrinas instáveis foram consideradas um fator de exclusão. Todas as pacientes estavam em tratamento farmacológico, associado ou não a intervenções psicossociais. Amostras de sangue foram retiradas para as medidas de BDNF, estrogênio (E), progesterona (P), LH e FSH, sendo coletadas nas fases folicular (FF) e lútea (FL) do ciclo menstrual, e uma única vez nas mulheres na pós-menopausa. Os diagnósticos foram confirmados através de entrevista clínica estruturada para o DSM-IV Transtornos do Eixo I (SCID-I), administrado por investigadores treinados. Resultados: Foram avaliadas 96 pacientes com TB. Destas, 64 não preenchiam critérios de inclusão ou apresentavam fatores de exclusão. Foram estudadas 32 mulheres com idades entre 22 e 69 anos (média = 52,78 anos). Considerando toda a amostra, o BDNF apresentou uma correlação positiva com os níveis de estradiol (r = 0,36, p = 0,043). Nas pacientes em período reprodutivo, na fase lútea(FL), houve uma correlação negativa entre o BDNF e o FSH (r = 0,831, p = 0,040). Um resultado semelhante foi encontrado com os níveis de LH (r = 0,908, p= 0,012) nessa mesma fase do ciclo menstrual. Conclusão: Os resultados encontrados na amostra de mulheres com TB foram semelhantes aos descritos na literatura em indivíduos saudáveis, que também apresentam correlação entre E e BDNF (Begliuomini et al., 2007). Estes achados indicam que o estímulo estrogênico pode ser importante na manutenção de s níveis fisiológicos de BDNF. A partir desses resultados novas vias devem ser incluídas na investigação na fisiopatologia das alterações de humor relacionadas a variações hormonais, bem como ao tratamento do TB. Além disso, ressalta a importância de incluir as variações hormonais femininas na equação diagnóstica e prognóstica do TB. / Background: Background: Hormonal oscilations across lifetime have been associated with mood variations in healthy women. Oestrogen (E) seems to be associated with Brain Derived Neurotrophic Factor (BDNF) levels in healthy volunteers. This assictaion was not studied in women with Bipolar Disorder (BD). Mood episodes of BD are associated with reductions in BDNF levels, although the role of feminine hormones in pathophysiology of BD hás not been completely studied. Objective: To investigate the association between BDNF levels and hormones involved in hypothalamus-pituitary-gonadal axis in women with BD, comparing a group during reproductive years with a menopausal group. In addition, differences across the two phases of menstrual cycle were also evaluated in the group during reproductive years. Methods: Women euthymic (HAM-D and YMRS scoring less than 8) with bipolar I, II or bipolar disorder not otherwise specified were included. Patients of reproductive age had regular menstrual cycles (RMC) and did not use any type of hormonal contraception (CH) and postmenopausal were not using hormone replacement therapy (HRT). Endocrine instable conditions were considered an exclusion factor. All patients were on pharmacotherapy, associed or not with psychosocial interventions. Blood samples withdrawn for measures of BDNF, oestrogen (E), progesterone (P), LH and FSH levels, being collected in the follicular phase (FP) and luteal (FL) of the menstrual cycle, menopausal women were held only one blood sample. Diagnoses were assessed using structured clinical interview for DSM-IV Axis I Disorders (SCID-I), administered by certified investigators. Results: Ninety six patients with BD were evaluated, of these, 64 did not meet inclusion criteria or met exclusion factors. The sample was constituted by 32 women with BD aged 22 to 69 years (mean = 52.78 years). Considering the whole sample, the BDNF was significantly correlated with estradiol levels (r = 0.36, p = 0.043). In patients in reproductive period, in the luteal phase, there was a negative correlation with FSH (r = 0.831, p = 0.040). A similar result was found with levels o LH (r = 0.908, p = 0.012) in the same menstrual cycle phase. Conclusion: The results found in the sample of women with TB were similar to those previously reported in healthy subjects, which also show a correlation between E and BDNF (Begliuomini et al., 2007). These findings indicate that estrogenic stimulation may be important in maintaining physiological BDNF levels. From these results, new avenues should be included in research on the pathophysiology of mood swings related to hormonal changes as well as the treatment of TB. Furthermore, the importance of including female hormonal changes in the equation of TB diagnostic and.

Affect and cognition have traditionally been considered mutually exclusive domains and their study has evolved into two separate research fields. In recent years, however, there is increasing evidence of affective modulations of cognitive processes and interest in the study of affective cognition has grown. This thesis presents analyses of data collected in four mixed-design experiments between 2009 and 2011, which were designed to investigate affective memory and its electrophysiological correlates, individual differences in said affective memory and electrophysiological correlates, the time-course of affective memory and attentional disengagement from affective stimuli respectively. The first aim of the research presented here was to further understanding of how affective content influences picture processing and memory. Event-related potentials (ERPs) provide a valuable tool for the investigation of modulations of cognitive processes, as their excellent temporal resolution allows for the dissociation between different processes contributing to behavioural outcomes. Several important results for the study of affective cognition are reported: The late positive potential (LPP) was shown to be modulated differentially by affective content when compared to a behavioural attentional disengagement task. While the behavioural measure of attention replicated findings from participants’ self-report of arousal, LPP enhancement did not. This novel finding demonstrates that the affective modulation of the LPP cannot be used as an electrophysiological marker of slowed attentional disengagement as is common in the literature. In the domain of recognition memory, affective modulation of performance was shown to be time-sensitive, with effects developing faster for negative than for positive picture content. Affective pictures were associated with a less conservative response bias than neutral pictures but only negative pictures elicited better discrimination performance, driven by an increased in the rate of “remembered” as compared to merely familiar pictures. This was reflected in an increase of the ERP old/new effect for negative pictures in the 500 to 800ms time window, the purported correlate of recollection. The late right-frontal old/new effect between 800 and 1500 ms post stimulus onset was shown to be attenuated by affective content, supporting the interpretation of the late right-frontal effect as a correlate of relevance detection over a retrieval success interpretation. In combination, the findings add weight to the conclusion that affective content enhances memory through selective memory sparing for affective stimuli. Novel evidence for gender differences in affective cognition was found. Comparisons between female and male participants revealed that the affective modulation of the late right-frontal effect differs between the genders, underlining the importance of assessing and understanding gender differences as part of the study of affective cognition. Brain-derived neurotrophic factor (BDNF) gene val66met single nucleotide polymorphism (SNP), a small genetic change that affects the functioning of BDNF, a protein that plays an important role in neuron growth, differentiation and survival, is shown here to also affect the interaction of affect and cognition. BDNF val66met genotype modulated the early “familiarity” old/new effect selectively in response to positive pictures. The present study clearly demonstrates the value of the ERP technique in the investigation of individual differences in affective and cognitive processing and the need to take such individual differences into account as part of the endeavour to fully understand the mechanisms of affective processing, cognition and affective cognition. A better understanding of the role of gender and genetic differences in the affective modulation of affective processing and memory will have important practical implications in fields where affect and cognition interact.

Base Teórica: A prevalência de dor crônica na infância é bem documentada e estima-se que atinja entre 20 a 35% da população pediátrica, podendo causar enorme sofrimento em seus portadores, inaptidões pessoais e ser acompanhada de sintomas emocionais importantes. O manejo dessas criancas inclui a compreensão dos fatores biomecânicos, psicológicos e socioculturais associados ao seu contexto. Dentre os fatores psíquicos o pensamento catastrófico sobre a dor, definido como uma resposta negativa exagerada a mesma, tem sido identificado como uma estratégia adaptativa às circunstâncias. A escala de avaliação do pensamento catastrófico em crianças - Pain Catastrophizing Scale – child version (PCS-C), adaptada da escala para adultos, já está validada em diferentes línguas, no entanto, pouco se sabe sobre o catastrofismo em crianças brasileiras. Objetivos: O objetivo desse estudo é validar e adaptar a PCS-C para o português do Brasil, examinar as propriedades psicométricas, bem como a estrutura fatorial da escala, e sua correlação com a dor e suas consequências em crianças com e sem dor crônica. Métodos: A versão em português do Brasil foi modificada por um grupo de especialistas a fim de torná-la apropriada para aplicação em crianças entre 7-12 anos. Para avaliar as propriedades psicométricas, 100 crianças (44 com dor crônica e 56 saudáveis) responderam a versão brasileira da PCS-C (BPCS-C). Também foram questionadas quanto aos níveis de dor e quanto à capacidade funcional durante atividades da prática de educação física na escola. Ainda, amostras de saliva foram passivamente coletadas a fim de se medir o fator neurotrófico derivado do cérebro (BDNF). O subgrupo de crianças com dor crônica foi recrutado dos ambulatórios de gastro pediatria, oncologia e reumatologia do Hospital de Clínicas de Porto Alegre e o subgrupo de crianças saudáveis foi recrutado de uma escola pública. Resultados: O estudo mostrou uma boa consistência interna do instrumento (alfa de Crombach: 0,81 para o escore total da BPCS-C). Tanto a análise paralela, quanto a análise fatorial exploratória identificaram 2 dimensões (fatores) no instrumento. A análise fatorial confirmatória apresentou os melhores valores de ajustamento (CFI, confirmatory fit-index) quando comparada a outros modelos já existentes. Os escores totais da BPCS-C não diferiram entre as crianças com dor crônica e as saudáveis. No entanto, a dificuldade progressiva de realizar as atividades da Educação Física na escola foi associada com o catastrofismo (p=0,019) nos pacientes com dor crônica. BDNF salivar apresentou fraca associação (r=0,27 p=0,012) com o catastrofismo. Conclusão: Os resultados suportam a validade e confiabilidade da BPCS-C. A estrutura de 2 fatores apresentou adequado ajustamento podendo ser usada, mesmo que diferindo do número de fatores da escala original, pois escore total é o valor mais utilizado para composição do diagnóstico. A ausência de diferença entre os escores nas crianças doentes e saudáveis sugere a necessidade de estudos mais profundos sobre a catastrofização em crianças e a necessidade de instrumentos específicos, e não apenas adaptação daqueles utilizados em adultos. / Introduction: The prevalence of chronic pain in childhood is well documented and is estimated to reach 20 and 35% of the pediatric population. Chronica pain can cause enormous suffering, personal miscarriages and it can be accompanied by important emotional symptoms. The management of these children includes understanding the biomechanical, psychological and sociocultural factors associated in this context. Among the psychic factors, catastrophic thinking about pain is identified as an adaptive strategy to the circumstances. The instrument for catastrophic thinking evaluation in children - Pain Catastrophizing Scale - child version (PCS-C), adapted from the scale for adults, is already validated in different languages, however little is known about catastrophism in Brazilian children. Objectives:. With this cross-sectional study, we aim to adapt the Brazilian version of the PCS-C (BPCS-C) and to examine the psychometric properties and factorial structure of the scale for children with and without chronic pain. Methods: The Brazilian version of the PCS-C was modified by a group of experts to appropriate it for children between 7-12 years. To asses the psychometric properties of the version, 100 children (44 with chronic pain and 56 healthy children) answered the BPCS-C, the visual analog scale and one functional school activity question. It was also collected a passive salivary sample to measure BDNF. The chronic pain children sample was recruited from the gastropediatric, oncologic, and reumatologic ambulatories at a tertiary hospital and the healthy children from a fifth grade public school. Results: We observed good internal consistency (Cronbach’s value of 0.81 for the total BPCS-C). Both parallel analysis and exploratory factorial analysis retained 2 factors for instrument dimensions. The confirmatory factorial analysis presented the best adjustment values (CFI, confirmatory fit-index) when compared to other existing pre-existing models. BPCS-C total scores were not diferente between chronic pain and healthy children. However, the progressive difficulty of performing physical education activities at school was associated with catastrophism (p = 0.019) in patients with chronic pain. 6 Salivary BDNF presented a weak association (r = 0.27 p = 0.012) with catastrophism. Discussion: The results support the validity and reliability of BPCS-C. The 2-factors structure presented an adequate adjustment and can be used for brazilian children population. Although different from the number of factors of the original scale, the instrument measured the most used value for diagnosis, total score. The lack of difference between scores in chronic pain and healthy children suggests the necessity of further studies on catastrophizing in children, as well as for specific instruments, instead of simple adaptation of those used in adults.

Fundamentação: O acidente vascular cerebral (AVC) é uma das principais causas de morte em todo o mundo e a maioria dos sobreviventes permanece com alguma sequela neurológica após o evento agudo. O presente estudo objetiva investigar a associação de alguns biomarcadores sanguíneos com as escalas de AVC, bem como avaliar a capacidade dos biomarcadores selecionados na predição de desfechos neurológicos durante o tempo de acompanhamento. Material e Métodos: Incluímos nesse estudo 60 pacientes com AVC agudo admitidos na unidade neurovascular da emergência ou na unidade de medicina intensiva do Hospital de Clínicas de Porto Alegre, nas primeiras 24 horas do início dos sintomas. Foram coletas amostras sanguíneas nas primeiras 24 horas, no terceiro e no quinto dias após o AVC para dosagem de enolase neurônio específica (ENS), proteína S100ß (S100ß), interleucina 6 (IL-6), proteína C reativa (PCR) e fator neurotrófico derivado do cérebro (BDNF). A gravidade do AVC e o grau de dependência funcional dos pacientes após o AVC foram mensurados através das escalas do National Institutes of Health Stroke Scale (NIHSS) e modified Rankin Scale (mRS) nos três momentos das coletas sanguíneas e na alta hospitalar. Resultados: Os níveis séricos de S100ß, IL-6 e PCR mostraram-se o melhor painel de biomarcadores após o AVC nesse estudo. Quando os pacientes foram subdivididos em dois grupos para a avaliação de desfechos neurológicos, usando as escalas do NIHSS (NIHSS ≤ 6 e NHISS > 6) e mRS (mRS ≤ 3 e mRS > 3), ambas as escalas apresentaram boa associação entre as concentrações de S100ß e de IL-6 em todas as medidas e as escalas de AVC para bom prognóstico (NIHSS ≤ 6 e mRS ≤ 3) na alta hospitalar. Dentre os biomarcadores selecionados para o estudo, foram os três citados acima que apresentaram as melhores correlações com as escalas de AVC e com o prognóstico pós AVC durante o tempo de acompanhamento. Conclusão: Os biomarcadores séricos podem ser úteis na avaliação da gravidade e do prognóstico após o AVC. A associação de S100ß, IL-6 e PCR parece acrescentar pouco às escalas validadas de AVC na capacidade de predizer desfechos após o evento agudo. / Background and Purpose: Stroke is an important cause of death worldwide, and the majority of stroke survivors suffer from some form of residual disability. This study aimed to investigate the association of blood biomarkers with stroke scales and their predictive value after acute stroke at the time of admission until hospital discharge. Design and Methods: We investigated 60 patients with acute stroke who were admitted within 24 h of event onset at the intensive care unit or neurovascular emergency unit of Clínicas Hospital. All patients provided venous blood samples for the measurement of neuron-specific enolase (NSE), S100ß protein (S100ß), interleukin-6 (IL-6), C-reactive protein (CRP) and brain-derived neurotrophic factor (BDNF) within 24 h of the acute event, on the third day and on the fifth day after the stroke. Neurological stroke severity and global disability were determined with the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) at the same three times of blood collection and at the time of hospital discharge. Results: The serum levels of the S100ß protein, IL-6 and CRP seem to constitute the best panel of biomarkers after acute stroke in this study. When patients were subdivided into two groups according to the NIHSS (NIHSS ≤ 6 and NIHSS > 6) and mRS (mRS ≤ 3 and mRS > 3) scores, which were used as neurological outcome measures, both neurologic scores for good outcome (NIHSS ≤ 6 and mRS ≤ 3) at hospital discharge were significantly related to the S100ß protein and IL-6 levels at all of the measured time points. Among the analyzed blood markers, S100ß, IL-6 and PCR levels significanttly correlated with the stroke scales and prognostic value. Conclusion: Blood biomarkers may be useful in acute stroke either by suggesting stroke severity or providing a prognostic value. The addition of the S100ß protein, IL-6 and CRP to previously validated stroke scales slightly improves the ability of these scales to predict outcome.