The sporadic nature of Alzheimer's disease argues for an environmental link that may drive AD pathogenesis; however, the triggering factors and the period of their action are unknown. Recent studies in rodents have shown that exposure to lead during brain development predetermined the expression and regulation of the amyloid precursor protein and its amyloidogenic beta-amyloid product in old age. Here, we report that the expression of AD-related genes [APP, BACE1 ] as well as their transcriptional regulator were elevated in aged (...) monkeys exposed to Pb as infants. Furthermore, developmental exposure to Pb altered the levels, characteristics, and intracellular distribution of Abeta staining and amyloid plaques in the frontal association cortex. These latent effects were accompanied by a decrease in DNA methyltransferase activity and higher levels of oxidative damage to DNA, indicating that epigenetic imprinting in early life influenced the expression of AD-related genes and promoted DNA damage and pathogenesis. These data suggest that AD pathogenesis is influenced by early life exposures and argue for both an environmental trigger and a developmental origin of AD. (shrink)

PURPOSE: To evaluate the effects of social support on comprehension and recall of consent form information in a study of Parkinson disease patients and their caregivers.DESIGN and METHODS: Comparison of comprehension and recall outcomes among participants who read and signed the consent form accompanied by a family member/friend versus those of participants who read and signed the consent form unaccompanied. Comprehension and recall of consent form information were measured at one week and one month respectively, using Part A of the (...) Quality of Informed Consent Questionnaire .RESULTS: The mean age of the sample of 143 participants was 71 years . Analysis of covariance was used to compare QuIC scores between the intervention group and control group . In the 1-week model, no statistically significant intervention effect was found . However, the intervention status by patient status interaction was statistically significant . In the 1-month model, no statistically significant intervention effect was found . Again, however, the intervention status by patient status interaction was statistically significant . At both time periods, intervention group patients scored higher on the QuIC than did intervention group caregivers, and control group patients scored lower on the QuIC than did control group caregivers.IMPLICATIONS: Social support played a significant role in enhancing comprehension and recall of consent form information among patients. (shrink)

Oxidative damage to DNA has been associated with neurodegenerative diseases. Developmental exposure to lead has been shown to elevate the Alzheimer's disease related beta-amyloid peptide , which is known to generate reactive oxygen species in the aging brain. This study measures the lifetime cerebral 8-hydroxy-2'-deoxyguanosine levels and the activity of the DNA repair enzyme 8-oxoguanine DNA glycosylase in rats developmentally exposed to Pb. Oxo8dG was transiently modulated early in life , but was later elevated 20 months after exposure to Pb (...) had ceased, while Ogg1 activity was not altered. Furthermore, an age-dependent loss in the inverse correlation between Ogg1 activity and oxo8dG accumulation was observed. The effect of Pb on oxo8dG levels did not occur if animals were exposed to Pb in old age. These increases in DNA damage occurred in the absence of any Pb-induced changes in copper/zinc-superoxide dismutase , manganese-SOD , and reduced-form glutathion . These data suggest that oxidative damage and neurodegeneration in the aging brain could be impacted by the developmental disturbances. (shrink)

In the modal literature various notions of completeness have been studied for normal modal logics. Four of these are defined here, viz. (plain) completeness, first-order completeness, canonicity and possession of the finite model property — and their connections are studied. Up to one important exception, all possible inclusion relations are either proved or disproved. Hopefully, this helps to establish some order in the jungle of concepts concerning modal logics. In the course of the exposition, the interesting properties of first-order definability (...) and preservation under ultrafilter extensions are introduced and studied as well. (shrink)

Avez-vous remarqué que dans le monde tout ce qui compte va par quatre? La musique : timbre, harmonie, rythme et mélodie. Le repérage : altitude, latitude, longitude et datation. Les quatre aspects de la cause: pour quoi, avec quoi, par quoi et selon quoi? Les forces de la nature : interactions faible, forte, électromagnétique et gravitationnelle... Les vingt-quatre particules élémentaires qui constituent la matière une famille de six leptons associée à trois familles de quarks. Et aussi la logique d'un discours (...) nuancé : oui, non, oui et non, ni oui ni non. Pourquoi quatre est-il partout? La notion de quaternité apporte une réponse à la fois simple et surprenante à cette question. A partir d'exemples tirés de l'expérience humaine, les auteurs en dégagent les aspects structurels et s'en servent pour approfondir le sens des mathématiques et de divers autres domaines liés à la genèse de la connaissance. Il s'agit d'une nouvelle épistémologie, fondée sur un modèle logique qui complète celui d'Aristote. (shrink)

Roman Catholic moral theology follows a centuries-old tradition of moral reflection. Contemporary Roman Catholic moral theory applies these traditional arguments to the realm of medical ethics, including the issues of active euthanasia and physician-assisted suicide. Unavoidable moral limits on licit medical intervention sometimes require that the moral duty to treat, cede to the duty to cease treatment when measures become more harmful than beneficial to the patient. This does not reduce the need for the compassionate use of palliative care in (...) response to suffering. However, it does mean that rather than being excessively committed to maintaining mere biological human life, or actively seeking death, that we learn a sober realism about the limits of human life. Catholic moral analysis examines an act objectively, both in its relation to the agent and as a material event in the world. This allows both the virtuous or vicious intentions of the agent and the effects of the action to be included in its moral evaluation. Thus, Catholic moral analysis is both quasi-deontological and quasi-consequentialist. Objectively, active euthanasia and physician-assisted suicide, as acts of deliberate killing, are seen as repugnant, in that they fail to incarnate a benign inner intention or to form an agent in virtue. Catholic moral theology is extremely skeptical that an act of intending death directly can be consonant with a sincere compassion for the dying, suffering person and views it as a direct negation of the precious gift of human life. (shrink)