Impact of cognitive performance on the functional capacity of an elderly population in Natal, Brazil Impacto do desempenho cognitivo na capacidade funcional em uma amostra populacional de idosos do nordeste brasileiro

Functional incapacity and cognitive impairment are conditions related to the process of human aging. Cognitive impairment is considered an important predicitve factor for functional impairment in elderly populations. This cross-sectional study analyzes the association between cognitive performance and functional capacity in an elderly population sample in Natal, Brazil. A total of 213 elderly persons were assessed by the BOAS Multidimensional Questionnaire (Brazil Old Age Schedule) and the Mini-Mental State Examination (MMSE). The results of multivariate analysis and linear regression showed that age and schooling level are factors associated with cognitive performance in the elderly of this study. The final explicative model, elaborated by logistic regression, found that cognitive performance was the only predicitve variable of functional incapacity for the activities of daily living even when adjusted for sociodemographic variables.<br>A incapacidade funcional e o déficit cognitivo são condições relacionadas com o processo de envelhecimento humano. O déficit cognitivo é considerado um importante fator preditor de prejuízos funcionais em populações idosas. Este estudo transversal analisa a associação do desempenho cognitivo na capacidade funcional de uma amostra populacional idosa residente em Natal-RN. Foram avaliados 213 idosos pelo Questionário Multidimensional-BOAS e pelo Mini-Exame do Estado Mental (MEEM). Através de analise multivariada mediante regressão linear, os resultados apontam a idade e o nível de escolaridade como fatores associados ao desempenho cognitivo nos idosos do estudo. O modelo explicativo final elaborado através de regressão logística apresentou o desempenho cognitivo como a única variável preditora de incapacidade funcional para as atividades da vida diária mesmo quando ajustado por variáveis sócio-demográficas

Functional interactions of DNA topoisomerases with a human replication origin

The human DNA replication origin, located in the lamin B2 gene, interacts with the DNA topoisomerases I and II in a cell cycle-modulated manner. The topoisomerases interact in vivo and in vitro with precise bonds ahead of the start sites of bidirectional replication, within the pre-replicative complex region; topoisomerase I is bound in M, early G1 and G1/S border and topoisomerase II in M and the middle of G1. The Orc2 protein competes for the same sites of the origin bound by either topoisomerase in different moments of the cell cycle; furthermore, it interacts on the DNA with topoisomerase II during the assembly of the pre-replicative complex and with DNA-bound topoisomerase I at the G1/S border. Inhibition of topoisomerase I activity abolishes origin firing. Thus, the two topoisomerases are closely associated with the replicative complexes, and DNA topology plays an essential functional role in origin activation

Inflammation enhances the risks of stroke and death in chronic chagas disease patients.

Ischemic strokes have been implicated as a cause of death in Chagas disease patients. Inflammation has been recognized as a key component in all ischemic processes, including the intravascular events triggered by vessel interruption, brain damage and repair. In this study, we evaluated the association between inflammatory markers and the death risk (DR) and stroke risk (SR) of patients with different clinical forms of chronic Chagas disease. The mRNA expression levels of cytokines, transcription factors expressed in the adaptive immune response (Th1, Th2, Th9, Th17, Th22 and regulatory T cell), and iNOS were analyzed by realtime PCR in peripheral blood mononuclear cells of chagasic patients who exhibited the indeterminate, cardiac, digestive and cardiodigestive clinical forms of the disease, and the levels of these transcripts were correlated with the DR and SR. Cardiac patients exhibited lowermRNA nexpression levels of GATA-3, FoxP3, AHR, IL-4, IL-9, IL-10 and IL 22 but exhibited higher expression of IFN-γ and TNF-α compared with indeterminate patients. Digestive patients showed similar levels of GATA-3, IL-4 and IL-10 than indeterminate patients. Cardiodigestive patients exhibited higher levels of TNF-α compared with indeterminate and digestive patients. Furthermore, we demonstrated that patients with high DR and SR exhibited lower GATA-3, FoxP3, and IL-10 expression and higher IFN-γ, TNF-α and iNOS mRNA expression than patients with low DR and SR. A negative correlation was observed between Foxp3 and IL-10 mRNA expression and the DR and SR. Moreover, TNF-α and iNOS expression was positively correlated with DR and SR. Our data suggest that an inflammatory imbalance in chronic Chagas disease patients is associated with a high DR and SR. This study provides a better understanding of the stroke pathobiology in the general population and might aid the development of therapeutic strategies for controlling the morbidity and mortality of Chagas disease

Cervical Lymph Nodes as a Selective Niche for Brucella during Oral Infections

International audienceCervical lymph nodes (CLN) are the first lymph nodes encountered by material taking the oral route. To study their role in orally acquired infections, we analyzed 307 patients of up to 14 years treated in the university clinic of Skopje, Macedonia, for brucellosis, a zoonotic bacterial disease frequently acquired by ingestion of contaminated dairy products. From these children, 36% had lymphadenopathy. Among orally infected children, lymphadenopathy with CLN being the only lymph nodes affected was significantly more frequent as compared to those infected by contact with animals (83% vs. 63%), suggesting a possible involvement of CLN during orally acquired human brucellosis. Using a murine model where bacteria are delivered into the oral cavity, we show that Brucella quickly and selectively colonize the CLN where they proliferate and persist over long periods of time for up to 50 days post-infection. A similar efficient though less specific drainage to CLN was found for Brucella, Salmonella typhimurium and fluorescent microspheres delivered by gavage, a pathway likely representing a mixed infection mode of intragastric and oral infection, suggesting a central pathway of drained material. Microspheres as well as bacteria drained to CLN predominately reside in cells expressing CD68 and no or low levels of CD11c. Even though no systemic response could be detected, Brucella induced a locally restricted inflammatory reaction with increased expression levels of interferon., interleukin (IL)-6, IL-12, granzyme B and a delayed induction of Nos2. Inflammation led to pronounced lymphadenopathy, infiltration of macrophages/monocytes expressing high levels of major histocompatibility complex II and to formation of epitheloid granulomas. Together, these results highlight the role of CLN in oral infections as both, an initial and efficient trap for bacterial invaders and as possible reservoir for chronic pathogens. They likewise cast a new light on the significance of oral routes for means of vaccination