Prevention of age-associated dementia.

The advancement of medical sciences during the last century has resulted in a considerable increase in life expectancy. As more people live to old age, one of the most fundamental questions of the 21st century is whether the number of individuals suffering from dementia will also continue to increase. Alzheimer's disease (AD) accounts for the majority of cases of dementia in the elderly, but there is currently no curative treatment available. Several strategies have been introduced for treatment, the most recent strategy of which was the immunization of patients using antibodies against Abeta, which is a naturally occurring, even though misfolded peptide in the AD brain. Both active and passive immunization routes have been shown to reduce the pathology associated with Abeta accumulation in brains of genetically designed animal models. However, despite tremendous efforts, no unequivocal proof of therapeutic efficacy could be shown in AD patients. Particularly, the persistence of the neurofibrillary tangles in immunized brains and the issue of inducing cerebral amyloid angiopathy are major limiting factors of antibody therapy. Furthermore, physical activity, a healthy immune system and nutritional habits are suggested to protect against the onset of age-associated dementia. Thus, accumulative evidence suggests that an early integrated strategy, combining pharmacological, immunological, nutritional and life-style factors, is the most pragmatic approach to delay the onset and progression of age-associated dementia.

Association of nuclear matrix proteins with granular and threaded nuclear bodies in cell lines undergoing apoptosis.

The granules which appear in the nucleolar area in apoptotic HL-60 cells after camptothecin administration (Zweyer et al., Exp. Cell Res. 221,27-40, 1995) were detected also in several other cell lines induced to undergo apoptosis by different stimuli, such as MOLT-4 treated with staurosporine, K-562 incubated with actinomycin D, P-815 exposed to temperature causing heat shock, Jurkat cells treated with EGTA, U-937 growing in the presence of cycloheximide and tumor necrosis factor-alpha, and HeLa cells treated with etoposide. Using immunoelectron microscopy techniques, we demonstrate that, besides the already described nuclear matrix proteins p125 and p160, these granules contain other nucleoskeletal polypeptides such as proliferating cell nuclear antigen, a component of ribonucleoprotein particles, a 105-kDa constituent of nuclear spliceosomes, and the 240-kDa nuclear mitotic apparatus-associated protein referred to as NuMA. Moreover, we also found in the granules SAF-A/hn-RNP-U and SATB1 proteins, two polypeptides that have been reported to bind scaffold-associated regions DNA sequences in vitro, thus mediating the formation of looped DNA structures in vivo. Fibrillarin and coilin are not present in these granules or the PML protein. Thus, the granules seen during the apoptotic process apparently are different from coiled bodies or other types of nuclear bodies. Furthermore, these granules do not contain chromatin components such as histones and DNA. Last, Western blotting analysis revealed that nuclear matrix proteins present in the granules are not proteolytically degraded except for the NuMA polypeptide. We propose that these granules might represent aggregates of nuclear matrix proteins forming during the apoptotic process. Moreover, since the granules are present in several cell lines undergoing apoptosis, they could be considered a previously unrecognized morphological hallmark of the apoptotic process.

Planeamento Estratégico e Desenvolvimento do Município de Tarrafal de Santiago

O presente trabalho intitulado” Planeamento Estratégico e Desenvolvimento do Município de Tarrafal de Santiago ”, enquadra-se no âmbito do curso de licenciatura em Administração Pública e Autárquica, ministrada pela Universidade Jean Piaget de Cabo Verde. Esta monografia tem como objectivo analisar a qualidade do planeamento local desenvolvido no município de Tarrafal de Santiago, objectivando a criação de instrumento de organização e hierarquização das demandas locais e, também como instrumento de promoção de desenvolvimento, através da busca de soluções locais para os problemas enfrentados. Para conhecer a actividade de planeamento municipal foi estudado, neste trabalho, o plano Estratégico de desenvolvimento do município de Tarrafal de Santiago. Para alcançar os objectivos traçados e comprovar as hipóteses de trabalho foram analisadas as etapas de elaboração do plano estratégico, compreender o processo de planeamento no seu processo de desenvolvimento do Município de Tarrafal de Santiago e a correlação entre os problemas e as propostas do plano. A pesquisa é de natureza qualitativa, sendo a recolha dos dados e das informações é feita por meio do estudo documental. Das análises documentais elaborados no quadro teórico chegou a conclusão de que o desenvolvimento do Município do Tarrafal depende da existência e implementação adequada do plano estratégico.

Condiciones oceanográficas en verano 2005: Crucero demersal BIC Olaya 0501- 02

El crucero de verano BIC Olaya 0501-02 se desarrolló del 18 de enero al 16 de febrero entre Punta Lobos (9º50'S) y el dominio marítimo norte del litoral peruano (3º25'S) hasta las 70 mn de la costa. Se realizaron dos perfiles oceanográficos de 150 mn (Paita y Punta Falsa) y de 100 mn (Chicama) a fin de conocer las características superficiales y subsuperficia, relacionar las variables ambientales con el compor tamiento de los recursos demersales. Las condiciones marinas fueron algo frías al norte de los 6ºS y cálidas al frente de Chicama (7º30'S), debido a la incursión de las Aguas Subtropicales Superficiales (ASS). Se observó la presencia de tres masas de agua: (a) aguas ecuatoriales superficiales (AES) al norte de Punta Sal; (b) aguas sub- tropicales superficiales (ASS) con anomalías positivas de +2ºC al frente de Mórrope y Chicama hasta las 40 mn de la costa; (c) predominancia de las aguas costeras frías (ACF) entre Paita y Casma, hasta las 30 mn de la costa. Ligeros procesos de mezcla (ASS y ACF) entre Punta La Negra y Mórrope, restringieron el afloramiento costero.

Distal and proximal colon cancers differ in terms of molecular, pathological, and clinical features.

BACKGROUND: Differences exist between the proximal and distal colon in terms of developmental origin, exposure to patterning genes, environmental mutagens, and gut flora. Little is known on how these differences may affect mechanisms of tumorigenesis, side-specific therapy response or prognosis. We explored systematic differences in pathway activation and their clinical implications. MATERIALS AND METHODS: Detailed clinicopathological data for 3045 colon carcinoma patients enrolled in the PETACC3 adjuvant chemotherapy trial were available for analysis. A subset of 1404 samples had molecular data, including gene expression and DNA copy number profiles for 589 and 199 samples, respectively. In addition, 413 colon adenocarcinoma from TCGA collection were also analyzed. Tumor side-effect on anti-epidermal growth factor receptor (EGFR) therapy was assessed in a cohort of 325 metastatic patients. Outcome variables considered were relapse-free survival and survival after relapse (SAR). RESULTS: Proximal carcinomas were more often mucinous, microsatellite instable (MSI)-high, mutated in key tumorigenic pathways, expressed a B-Raf proto-oncogene, serine/threonine kinase (BRAF)-like and a serrated pathway signature, regardless of histological type. Distal carcinomas were more often chromosome instable and EGFR or human epidermal growth factor receptor 2 (HER2) amplified, and more frequently overexpressed epiregulin. While risk of relapse was not different per side, SAR was much poorer for proximal than for distal stage III carcinomas in a multivariable model including BRAF mutation status [N = 285; HR 1.95, 95% CI (1.6-2.4), P < 0.001]. Only patients with metastases from a distal carcinoma responded to anti-EGFR therapy, in line with the predictions of our pathway enrichment analysis. CONCLUSIONS: Colorectal carcinoma side is associated with differences in key molecular features, some immediately druggable, with important prognostic effects which are maintained in metastatic lesions. Although within side significant molecular heterogeneity remains, our findings justify stratification of patients by side for retrospective and prospective analyses of drug efficacy and prognosis.

Stage of change of cigarette smoking in drug dependent patients.

Nicotine cessation programmes in Switzerland, which are commonly based on the stage of change model of Prochaska and DiClemente (1983), are rarely offered to patients with illicit drug dependence. This stands in contrast to the high smoking rates and the heavy burden of tobacco-related problems in these patients. The stage of change was therefore assessed by self-administered questionnaire in 100 inpatients attending an illegal drug withdrawal programme. Only 15% of the patients were in the contemplation or decision stage. 93% considered smoking cessation to be difficult or very difficult. These data show a discrepancy between the motivation to change illegal drug consumption habits and the motivation for smoking cessation. The high proportion of patients remaining in the precontemplation stage for smoking cessation, in spite of their motivation for illicit drug detoxification, may be due to the perception that cessation of smoking is more difficult than illicit drug abuse cessation.

Notes et pièces relatives à la généalogie et aux possessions de la famille de Grignan.

On y remarque des lettres autographes du marquis de Vence, 4 février 1688 (fol. 64), — du marquis de Châteauneuf, 1785-1786 (fol. 67-74 et 79), — de M. de Trans de Tourrettes, 10 déc. 1699 (fol. 75) ; — des notes relatives à la baronnie de La Garde (fol. 88) ; — un « Inventaire des papiers concernant Les Granges Gontardes lez La Garde » (fol. 113) ; — et une copie des preuves de noblesse faites, en juin 1716, par Mlle Marguerite de Villeneuve de Trans, pour être reçue à Saint-Cyr (fol. 147).

« Coustumes du païs et duché de Bourbonnois.)) (1500).

Original. — En tête (fol. 1-7), procès-verbal de rédaction, signé par Thibault Baillet et Guillaume de Besançon. On y a inséré des lettres de Louis XII, datées de Lyon, 11 avril 1499, par lesquelles sont vidimées des lettres de Charles VIII, données à Moulins, le 2 septembre 1497.