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Folate is key in one-carbon metabolism, disruption of which can interfere with DNA synthesis, repair, and methylation. Efficient one-carbon metabolism requires other B vitamins and the optimal activity of enzymes including 5,10-methylenetetrahydrofolate reductase (MTHFR). We report a population-based case–control study of folate intake, related dietary factors and MTHFR polymorphisms (C677T, A1298C) and colorectal cancer in a population with relatively high colorectal cancer incidence and relatively low folate intake. A total of 264 cases with histologically confirmed incident colorectal cancer and 408 controls participated. There was no clear trend in risk with reported intakes of total, or dietary, folate, riboflavin, vitamin B12 or vitamin B6, nor were there interactions between folate intake and the other B vitamins or alcohol. For C677T, risk decreased with increasing variant alleles (multivariate OR for CT v. CC = 0·77 (95 % CI 0·52, 1·16); OR for TT v. CC = 0·62 (95 % CI 0·31, 1·24)), which, although not statistically significant, was consistent with previous studies. For A1298C, compared with AA subjects, CC subjects had modest, non-significant, reduced risk (multivariate OR = 0·81 (95 % CI 0·45, 1·49)). There were significant interactions between total folate and C677T (P = 0·029) and A1298C (P = 0·025), and total vitamin B6 and both polymorphisms (C677T, P = 0·016; A1298C, P = 0·033), although the patterns observed differed from previous studies. Seen against the setting of low folate intake, the results suggest that the role of folate metabolism in colorectal cancer aetiology may be more complex than previously thought. Investigation of particular folate vitamers (for example, tetrahydrofolate, 5,10-methylenetetrahydrofolate) may help clarify carcinogenesis pathways.
Objectives: To review the literature on older people with enduring or recurrent severe mental illness with an onset earlier than 65 years (graduates) and, in particular, to look at the specific features and needs of this group.
Method: A Medline literature search produced 41 relevant papers and reports on the subject.
Results: There are a substantial number of older people with severe mental illness and the number will rise in line with increased longevity. As they age these patients' psychiatric disabilities are compounded by medical and social problems. The move to community based care has largely ignored the needs of graduates who were previously cared for in psychiatric institutions.
Conclusion: There is an urgent need to plan and develop adequate services for this vulnerable group.
Objectives: There has been no specific planning for older people with enduring or recurrent severe mental illness in Ireland. This survey aims to identify the number of affected over 65 year olds (graduates) and 55-64 year olds (prospective graduates) in the Health Service Executive, Eastern Region, their diagnoses and their use of psychiatric services.
Method: A comprehensive survey of the ten general adult psychiatry and four old age psychiatry services in the (HSE) Eastern Region was undertaken for the year 2003 to determine the number of patients, their diagnoses and service utilisation.
Results: 649 people over 65 years old were identified within the general adult psychiatry services and a further 279 within the old age psychiatry services giving a total of 928. (This number rose to 1141 after correcting for missing outpatient data.) 1,397 people between the ages of 55-64 were identified. (This number rose to 1,916 after correcting for missing outpatient data.)
Conclusions: There are substantial numbers of ‘graduates’ and ‘prospective graduates’ in the Eastern Region. It is essential that services for this population are specifically planned for and further qualitative research is required to inform this process.
Delivery systems for tumour targeting fall into two basic categories: drug conjugate systems, in which individual drug molecules are chemically modified to target them directly to the tumour; and carrier-based systems, in which the drug or gene is first packaged non-covalently into a synthetic carrier that is then targeted to the tumour. In both cases, the objective is to maximise exposure of the target cells to the drug yet minimise side effects that result from nonspecific toxicity in normal tissues. The creation of such dose differentials is based on phenotypic differences between the tumour and the rest of the body. However, although a wide range of such changes have been linked to the transformation of normal cells to cancer cells, no single common feature exists to allow unambiguous targeting to the tumour. In addition, the tumour microenvironment creates physical barriers that significantly impair transport within the tumour. It is therefore important to match the delivery requirements of the drug to the capabilities of the delivery system. In this review, a brief overview is given of the underlying concepts and principles that help guide the development of such tumour-targeting strategies.
By 8000 B.P., sea-mammal hunting and open-sea voyages were established at Eel Point, San Clemente Island, California. The early inhabitants of Eel Point depended heavily on sea-mammal hunting and shellfish collecting, rather than the intensive fishing that developed during the Late Holocene along the Southern California coast. Eel Point technological capabilities rivaled those of Late Holocene groups such as the Chumash Indians, including the ability to fabricate sophisticated watercraft. These data question traditional models of progressive maritime cultural development in coastal Southern California, and reveal the need for more empirical methods of assessing the seafaring capabilities of ancient maritime populations.
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