Transtorno disforico interictal: uma comorbidade psiquiatrica frequente entre pacientes com epilepsia acompanhados em dois servicos terciarios

Psychiatric disorders are frequent among patients with epilepsy. Data in the literature have shown a heterogeneous clinical presentation of psychiatric disorders in patients with epilepsy. Interictal dysphoric disorder could be a specific psychiatric comorbidity associated with epilepsy, primarily in patients treated in tertiary centers.Objective The present study aimed to determine the prevalence of interictal dysphoric disorder among patients with epilepsy who were followed in two tertiary epilepsy services in Brazil. Method Sixty-five patients with epilepsy completed the Portuguese version of the Interictal Dysphoric Disorder Inventory. Results Thirty-three (50.7%) patients fulfilled the diagnostic criteria for interictal dysphoric disorder, although all participants answered positively to having at least one key symptom. Conclusion The high rate of patients with epilepsy who fulfilled the diagnosis of interictal dysphoric disorder confirms an association between epilepsy and psychiatric disorders. However, there is clearly a need to improve diagnostic tools to allow better differentiation between interictal dysphoric disorder and other psychiatric disorders.Transtornos psiquiátricos são frequentes entre pacientes com epilepsia. Estudos evidenciam apresentações clínicas heterogêneas neste grupo. O transtorno disfórico interictal pode um transtorno específico destes pacientes, particularmente naqueles acompanhados em centros terciários.Objetivo Determinar a prevalência de transtorno disfórico interictal entre pacientes com epilepsia atendidos em dois serviços terciários de epilepsia do Brasil. Método Sessenta e cinco pacientes foram convidados a responder a versão brasileira do Interictal Dysphoric Disorder Inventory adaptado e validado para o Português. Resultados Trinta e três pacientes (50,7%) preencheram critérios para transtorno disfórico interictal, embora todos os entrevistados tenham afirmado que são acometidos por ao menos um dos sintomas-chave. Conclusão A alta prevalência de transtorno disfórico interictal em pacientes com epilepsia pode ser um indício da associação entre epilepsia e transtornos psiquiátricos. No entanto, é necessário melhorar a acurácia dos instrumentos de diagnóstico para poder diferenciar casos de transtorno disfórico interictal de outros transtornos psiquiátricos.Universidade Federal de São Paulo (UNIFESP) Department of Neurology and NeurosurgeryUniversidade Federal de Pernambuco Department of Neurology and NeurosurgeryUniversidade Federal de São Paulo (UNIFESP) Department of PsychiatryUNIFESP, Department of Neurology and NeurosurgeryUNIFESP, Department of PsychiatrySciEL

O sincretismo de culturas sob a ótica da arquitetura vernácula do imigrante japonês na cidade de Registro, São Paulo

O presente artigo aborda os métodos construtivos empregados pelos imigrantes japoneses que vieram, em 1918, para a cidade de Registro, na região do Vale do Ribeira do Iguape, no estado de São Paulo. A vinda dessa nova frente de imigração foi incentivada pelo Governo do Estado, com o propósito de promover o processo de colonização, bem como de estimular o desenvolvimento econômico do Vale do Ribeira do Iguape por meio da expansão da cultura do café para a região. As características dessa frente de imigração são muito diferenciadas em relação às demais, tendo em vista que os que dela faziam parte chegaram ao Brasil como proprietários de terras e com apoio financeiro e logístico oferecido por uma empresa particular japonesa, responsável por gerenciar o empreendimento. Esses imigrantes, portanto, contaram com auxílio de uma complexa infra-estrutura, cujo objetivo era viabilizar a sua missão de desenvolvimento da região. Mesmo tendo essa particularidade lhes proporcionado a liberdade de recriar sua cultura em solo brasileiro, a realidade do novo habitat forçou-os a reinterpretar seus hábitos culturais ante as novas circunstâncias físicas, econômicas e sociais encontradas. A fim de entender esse processo de adaptação, foi realizado um estudo dos métodos construtivos empregados em suas edificações, baseado nos conhecimentos desses imigrantes sobre sua arquitetura tradicional. Essa análise permitiu examinar o longo processo de sincretismo entre a cultura oriental e o conhecimento construtivo vernáculo dos habitantes do Vale do Ribeira do Iguape.The present article addresses the methods of construction employed by Japanese immigrants, who settled the city of Registro, in the region of the Ribeira valley of Iguape, located in the State of Sao Paulo, in the year of 1918. This settlement received incentives from the State Government of Sao Paulo, in order to promote the colonization of the Ribeira valley of Iguape, as well as to boost local economical development, by means of expanding the agricultural production of coffee to this region. The characteristics of this group of immigrants were notably different from others, due to fact that they arrived in Brazil already as landholders, sponsored financially and logistically by a Japanese private company, which was responsible for the management of this enterprise. These immigrants could count on a complex infrastructure, which aided them in their mission to advance the development of this region. Even though the particularities of this group of immigrants gave them a certain amount of freedom to recreate their own culture in Brazilian land, the reality of this new environment, its new physical, economical and social contingencies forced them to reinterpret their cultural traditions and customs. In order to understand this adaptation process, a study of the construction methods employed by this group of immigrants in their buildings was undertaken, based on their knowledge of traditional Japanese architecture. This study rendered possible the analysis of a long process of cultural syncretism between oriental culture and the vernacular architecture of the inhabitants of the Ribeira valley of Iguape

The General Transcriptional Repressor Tup1 Is Required for Dimorphism and Virulence in a Fungal Plant Pathogen

A critical step in the life cycle of many fungal pathogens is the transition between yeast-like growth and the formation of filamentous structures, a process known as dimorphism. This morphological shift, typically triggered by multiple environmental signals, is tightly controlled by complex genetic pathways to ensure successful pathogenic development. In animal pathogenic fungi, one of the best known regulators of dimorphism is the general transcriptional repressor, Tup1. However, the role of Tup1 in fungal dimorphism is completely unknown in plant pathogens. Here we show that Tup1 plays a key role in orchestrating the yeast to hypha transition in the maize pathogen Ustilago maydis. Deletion of the tup1 gene causes a drastic reduction in the mating and filamentation capacity of the fungus, in turn leading to a reduced virulence phenotype. In U. maydis, these processes are controlled by the a and b mating-type loci, whose expression depends on the Prf1 transcription factor. Interestingly, Δtup1 strains show a critical reduction in the expression of prf1 and that of Prf1 target genes at both loci. Moreover, we observed that Tup1 appears to regulate Prf1 activity by controlling the expression of the prf1 transcriptional activators, rop1 and hap2. Additionally, we describe a putative novel prf1 repressor, named Pac2, which seems to be an important target of Tup1 in the control of dimorphism and virulence. Furthermore, we show that Tup1 is required for full pathogenic development since tup1 deletion mutants are unable to complete the sexual cycle. Our findings establish Tup1 as a key factor coordinating dimorphism in the phytopathogen U. maydis and support a conserved role for Tup1 in the control of hypha-specific genes among animal and plant fungal pathogens

A roupa nova do presidente: a politização da imagem pública de Jânio Quadros (1947-1961)

Jânio Quadros public image is often considered deprived of any political meaning either by historians or by collective memory. In most cases he is treated as a demagogue who promoted himself only through his personalism, which could be seen in his public appearances unkempt and with open-necked shirts. Such perspective is deeply related to the way his opponents and enemies represented him in the political debates, and its core has been successful in penetrating the historiography. However in this text I intend to suggest that Jânio's images conveyed an array of political senses during the 1950s and early 1960s, since the beginning of his career till when he disputed presidential elections and ruled Brazil as president. Through his gestures and clothes, among which his Indian slacks deserve more attention, he tried to express his project related to the Christian Democracy and the Independent Foreign Policy. To deal with such hypothesis, the main sources will be the magazines O Cruzeiro and Manchete and others photos and drawings that were considerably widespread at that time.A imagem pública de Jânio Quadros é frequentemente considerada como desprovida de quaisquer significados políticos, seja por historiadores ou pela memória coletiva. Na maioria dos casos, ele é tratado como um demagogo que se promovia apenas através de seu personalismo, exibindo-se em suas aparições públicas despenteado e com camisas abertas no colarinho. Tal perspectiva está profundamente relacionada com a forma pela qual seus oponentes e inimigos o representavam nos debates políticos, e em seu cerne foi bem-sucedida, tendo penetrado na historiografia. Neste texto, porém, pretendo sugerir que, perpassando a década de 1950 e o início da de 1960, desde o início de sua carreira até o momento em que disputou eleições presidenciais e foi o presidente do Brasil, as imagens de Jânio veiculavam um amplo leque de sentidos políticos. Por meio de gestos e roupas, destacando-se aí seus slacks indianos, ele procurou expressar seus projetos relacionados à Democracia Cristã e à Política Externa Independente. Para lidar com essa hipótese, as principais fontes fotográficas e textuais elencadas são as revistas O Cruzeiro e Manchete da época, e outras fotos e ilustrações que então foram bastante difundidas

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

A case study of an integrative genomic and experimental therapeutic approach for rare tumors: identification of vulnerabilities in a pediatric poorly differentiated carcinoma

Abstract Background Precision medicine approaches are ideally suited for rare tumors where comprehensive characterization may have diagnostic, prognostic, and therapeutic value. We describe the clinical case and molecular characterization of an adolescent with metastatic poorly differentiated carcinoma (PDC). Given the rarity and poor prognosis associated with PDC in children, we utilized genomic analysis and preclinical models to validate oncogenic drivers and identify molecular vulnerabilities. Methods We utilized whole exome sequencing (WES) and transcriptome analysis to identify germline and somatic alterations in the patient’s tumor. In silico and in vitro studies were used to determine the functional consequences of genomic alterations. Primary tumor was used to generate a patient-derived xenograft (PDX) model, which was used for in vivo assessment of predicted therapeutic options. Results WES revealed a novel germline frameshift variant (p.E1554fs) in APC, establishing a diagnosis of Gardner syndrome, along with a somatic nonsense (p.R790*) APC mutation in the tumor. Somatic mutations in TP53, MAX, BRAF, ROS1, and RPTOR were also identified and transcriptome and immunohistochemical analyses suggested hyperactivation of the Wnt/ß-catenin and AKT/mTOR pathways. In silico and biochemical assays demonstrated that the MAX p.R60Q and BRAF p.K483E mutations were activating mutations, whereas the ROS1 and RPTOR mutations were of lower utility for therapeutic targeting. Utilizing a patient-specific PDX model, we demonstrated in vivo activity of mTOR inhibition with temsirolimus and partial response to inhibition of MEK. Conclusions This clinical case illustrates the depth of investigation necessary to fully characterize the functional significance of the breadth of alterations identified through genomic analysis