in presenilin 1 (PSEN1) (S169del) or (A246E). We characterized the AD-iPSCs characteristic properties of human pluripotent stem cells and differentiate them into functional neurons. Results: We found abnormally enhanced neuronal differentiation in AD iPSC-derived neural progenitor cells (AD-NPCs), and a reduction in the number of NPCs in AD-NPCs during differentiation. Consistently, we detected a decreased proliferation and an increased apoptosis in differentiating AD-NPCs. In addition, we identified the same phenotypes when PSEN1 with the mutation of A246E was introduced into control iPSCs. Furthermore, knockdown of mutated PSEN1 in AD-NPCs significantly attenuated the premature neuronal differentiation. Our results suggest that PSEN1 mutation causes reduction in the NPC pool, which might be relevant to the neuronal loss in the brain of AD patients. Additionally, our genome-wide transcript analyses identified differentially expressed genes relevant to neuronal differentiation and cell cycle in differentiating AD-NPCs. Conclusion: Collectively, our study uncovers previously unappreciated early NPC dysfunctions in FAD-NPCs and provides new cues to elucidate molecular mechanisms underlying AD development.

Materials and methods: Analysis of the numbers of MNB hospitalizations and death rate through Unified Health System (UHS), from 2008 to 2013 in Brazil. The Hospital Information System (HIS) -Unified Health System Informatics Department (UHSID) provided data. Results: MNB corresponded to 1.89% (17th cause) of the hospitalizations by neoplasms in Brazil, which had been rising since 2008, but decreased 8.3% in 2013. São Paulo was the state with the highest absolute values, responsible for 27.15% of national hospitalizations. However, stratified data evidenced Rio Grande do Sul with the highest rates for all years analyzed, with an average rate of 483.83, and a peak in 2012 (512.49), which was higher than national average (315.55), while São Paulo had an average of 351.00. Regarding death rates, although there was a slight decrease in 2013, MNB remained the 7th cause (13.65%). Conclusion: MNB are the 17th in hospitalizations in Brazil, corresponds to approximately 2% of the malignant neoplasms, befitting the literature, as well as the distribution pattern, presenting more cases in regions with higher HDI. They were also the 7th cause of deaths in the country, evidencing their high lethality.

Objetivo. Propomos verificar as relações entre desequilíbrios, déficits cognitivos e dependência funcional de pacientes com diagnóstico provável de Doença de Alzheimer. Método. Utilizamos a Escala de Equilíbrio Funcional de Berg, o teste Timed Up and Go na forma clássica e duas variações, o Mini-Exame do Estado Mental, a Bateria Breve de Rastreio Cognitivo e o questionário de Atividades Funcionais de Pfeffer. Participaram 16 indivíduos (75,2±1,6 anos), em fase moderada da doença. Resultados. O teste de correlação de Pearson constatoucorrelação de moderada magnitude entre as comparações (0,3<r<0,7; p<0,05), refletindo interferência cognitiva e motora no equilíbrio, além de déficits funcionais secundários. Conclusão. Nos pacientes estudados, há alterações motoras tônicas e cognitivas, que geram alterações de equilíbrio e de atividades funcionais e instrumentais de vida diária, e que estas variáveis se correlacionam entre si positivamente, gerando impacto sobre a independência do paciente.

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