Association of the IL1 gene cluster with susceptibility to ankylosing spondylitis: an analysis of three Canadian populations.
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OBJECTIVE: To examine the association between the IL1 gene cluster and susceptibility to ankylosing spondylitis (AS) in 3 independent case-control cohorts. METHODS: We analyzed 394 patients and 446 controls from Alberta, Newfoundland, and Toronto, Canada. Samples were genotyped using a panel of 38 single-nucleotide polymorphism (SNP) markers within the IL1 gene cluster. Data from 20 informative and nonredundant SNP markers were analyzed using several association test strategies. First, we used the program WHAP to identify single-marker associations. Second, we used WHAP to analyze "sliding windows" of 3 contiguous markers along the entire extent of the IL1 gene cluster in order to identify haplotypic associations. Third, we used the linkage disequilibrium mapping program DMLE to estimate the posterior probability distribution of a disease locus. RESULTS: A total of 14 SNP markers showed significant single-locus disease associations, the most significant being rs3783526 (IL1A) (P = 0.0009 in the Alberta cohort, P = 0.04 in the Newfoundland cohort) and rs1143627 (IL1B) (P = 0.0005 in the Alberta cohort, P = 0.02 in the Newfoundland cohort). Analysis of 3-marker sliding windows revealed significant and consistent associations with all of the haplotypes in the IL1A and IL1B loci in the Alberta cohort and with IL1B in the Newfoundland cohort, especially haplotypes rs1143634/rs1143630/rs3917356 and rs1143630/rs3917356/rs3917354 (P = 0.006-0.0001). With DMLE, a strong peak in the probability distribution was estimated near IL1A in both the Alberta and the Newfoundland populations. CONCLUSION: These results indicate that the IL1 locus, or a locus close to IL1, is associated with susceptibility to AS. (+info)
Glycerol production in rainbow smelt (Osmerus mordax) may be triggered by low temperature alone and is associated with the activation of glycerol-3-phosphate dehydrogenase and glycerol-3-phosphatase.
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Rainbow smelt (Osmerus mordax) accumulate high levels of glycerol in winter that serves as an antifreeze. Fish were subjected to controlled decreases in water temperature and levels of plasma glycerol, liver metabolites and liver enzymes were determined in order to identify control mechanisms for the initiation of glycerol synthesis. In two separate experiments, decreases in temperature from 8 degrees C to 0 degrees C over a period of 10-11 days resulted in increases in plasma glycerol from levels of less than 4 mmol l(-1) to approximate mean levels of 40 (first experiment) and 150 mmol l(-1) (second experiment). In a third experiment, decreases in temperature to -1 degrees C resulted in plasma glycerol levels approaching 500 mmol l(-1). The accumulation of glycerol could be driven in either December or March, thus eliminating decreasing photoperiod as a necessary cue for glycerol accumulation. Glycerol accumulation in plasma was associated with changes in metabolites in liver leading to increases in the mass action ratio across the reactions catalyzed by glycerol-3-phosphate dehydrogenase (GPDH) and glycerol-3-phosphatase (G3Pase). The maximal, in vitro activity of GPDH, increased twofold in association with a sharp increase in plasma glycerol level. The metabolite levels and enzyme activities provide complementary evidence that GPDH is a regulatory site in the low temperature triggered synthesis of glycerol. Indirect evidence, based on calculated rates of in vivo glycerol production by liver, suggests that G3Pase is a potential rate-limiting step. As well, transient increases in glyceraldehyde-3-phosphate dehydrogenase and alanine aminotransferase suggest that these sites are components of a suite of responses, in rainbow smelt liver, induced by low temperature. (+info)
Hospitalization due to pneumonia among Innu, Inuit and non-Aboriginal communities, Newfoundland and Labrador, Canada.
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OBJECTIVES: The objective of this study was to compare hospitalization rates due to pneumonia between Innu/Inuit communities in Labrador and non-Aboriginal communities on the Northern Peninsula of Newfoundland, Canada. METHODS: This is a comparative study using data on hospitalization due to pneumonia for the period from April 1, 1995 to March 31, 2001, for the Innu/Inuit communities in Labrador and a sample of non-Aboriginal communities on the Northern Peninsula of Newfoundland. Data were obtained from the provincial hospital database. Hospitalization rates among the study groups were compared by age, gender, and type of pneumonia. RESULTS: The hospitalization rate due to pneumonia for the Innu/Inuit communities was 11.6 compared to 3.0 per 1000 population for non-Aboriginal communities (p<0.01x10(-4)). Among the Innu/Inuit communities, infants had the highest rate of hospitalization due to pneumonia (93.4 per 1000 population), while the elderly (10.2 per 1000 population) were found to have the highest rate among the non-Aboriginal sample. Overall hospitalization rate for the Innu communities (16.9 per 1000 population) was higher than that for Inuit communities (8.4 per 1000 population) (p<0.01x10(-4)). CONCLUSIONS: Aboriginal communities, particularly the Innu communities, had higher rates of hospitalization due to pneumonia compared to the non-Aboriginal sample. Findings of this study will be used as a foundation for more specific studies in an effort to increase our understanding of pneumonia and associated risk factors. (+info)
National and provincial retention of medical graduates of Memorial University of Newfoundland.
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BACKGROUND: Memorial University of Newfoundland (MUN) established its medical school in 1967 to meet the growing demand for physicians and alleviate the reliance on other Canadian and international medical schools for physicians. However, it is unclear how many of the graduates remained to practise in Canada and in Newfoundland and Labrador (NL). We conducted this study to identify the characteristics and predictors of MUN medical graduates working in Canada and NL after residency training. METHODS: We linked data from class lists, and alumni and postgraduate databases with data from the Southam Medical Database to determine 2004 practice locations for MUN graduates from 1973 to 1998. Multiple logistic regression analysis was used to identify predictors for working in Canada and in NL. RESULTS: Of the 1322 MUN graduates in our study, 1147 (86.8%) were working in Canada and 406 (30.7%) in NL in 2004. Predictors of physicians working in Canada included female sex (odds ratio [OR] 1.44, 95% confidence interval [CI] 1.01-2.04), being from Canada (OR 3.71, 95% CI 1.15-2.21), graduating in the 1980s (OR 1.52, 95% CI 1.02-2.24) and 1990s (OR 2.01, 95% CI 1.31-3.09) and having done some or all residency training at MUN (OR 1.59, 95% CI 1.53-9.01). Predictors of physicians working in NL included having a rural background (OR 1.37, 95% CI 1.04-1.81), being from NL (OR 9.23, 95% CI 5.52-15.44) and having done some or all residency training at MUN (OR 5.28, 95% CI 3.80-7.34). INTERPRETATION: The MUN medical school has made a substantial contribution to the local physician supply, producing over half the physicians working in the province in 2004. Initiatives to increase national and provincial retention of medical graduates include attracting rural students to medical careers, increasing admission of local students and providing incentives for graduates to complete their residency training in the province. (+info)
Spousal perspectives on factors influencing recruitment and retention of rural family physicians.
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INTRODUCTION: Recruiting and retaining medical personnel to rural communities is a human resource challenge. Studies suggest that the spouse's experiences and perceptions of a rural community are among the most influential factors in a physician's decision to remain in or leave a rural practice. This study describes the factors that both directly and indirectly influence spousal contentment and explores how these factors contribute toward recruitment and retention of physicians to rural practice locations. METHODS: In this explorative study, 13 interviews were conducted with spouses of rural physicians to gain a better understanding of spousal concerns and experience regarding rural living. Participants in the present study included the spouses of general practitioners and family physicians practising and living in rural communities (population+info)
Late-Neoproterozoic deep-ocean oxygenation and the rise of animal life.
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Because animals require oxygen, an increase in late-Neoproterozoic oxygen concentrations has been suggested as a stimulus for their evolution. The iron content of deep-sea sediments shows that the deep ocean was anoxic and ferruginous before and during the Gaskiers glaciation 580 million years ago and that it became oxic afterward. The first known members of the Ediacara biota arose shortly after the Gaskiers glaciation, suggesting a causal link between their evolution and this oxygenation event. A prolonged stable oxic environment may have permitted the emergence of bilateral motile animals some 25 million years later. (+info)
Borrelia garinii in seabird ticks (Ixodes uriae), Atlantic Coast, North America.
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Borrelia garinii is the most neurotropic of the genospecies of B. burgdorferi sensu lato that cause Lyme disease in Europe, where it is transmitted to avian and mammalian reservoir hosts and to humans by Ixodes ricinus. B. garinii is also maintained in an enzootic cycle in seabirds by I. uriae, a tick found at high latitudes in both the Northern and Southern Hemispheres. To determine whether B. garinii is present in seabird ticks on the Atlantic Coast of North America, we examined 261 I. uriae ticks by polyclonal antiborrelial fluorescent antibody. Ten of 61 ticks from Gull Island, Newfoundland, were positive for borreliae by this screen. Amplicons of DNA obtained by PCR that targeted the B. garinii rrs-rrla intergenic spacer were sequenced and matched to GenBank sequences for B. garinii. The potential for introduction of this agent into the North American Lyme disease enzootic is unknown. (+info)
MLH1 -93G>A promoter polymorphism and the risk of microsatellite-unstable colorectal cancer.
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BACKGROUND: Although up to 30% of patients with colorectal cancer have a positive family history of colorectal neoplasia, few colorectal cancers can be explained by mutations in high-penetrance genes. We investigated whether polymorphisms in DNA mismatch repair genes are associated with the risk of colorectal cancer. METHODS: We genotyped 929 case patients and 1098 control subjects from Ontario and 430 case patients and 275 control subjects from Newfoundland and Labrador for five polymorphisms in the mismatch repair genes MLH1 and MSH2 with the fluorogenic 5' nuclease assay. Tumor microsatellite instability (MSI) was determined with a polymerase chain reaction-based method; MSI status was assigned as high (MSI-H, > or = 30% unstable markers among all markers tested), low (MSI-L, <30% markers unstable), or stable (MSS, no unstable markers). We used unconditional logistic regression to evaluate the association between each polymorphism and colorectal cancer after adjusting for age and sex. The associations between polymorphisms and tumor clinicopathologic features were evaluated with a Pearson's chi-square or Fisher's exact test. All statistical tests were two-sided. RESULTS: We observed strong associations between the MLH1 -93G>A polymorphism and MSI-H tumors among case patients from Ontario (P = .001) and Newfoundland (P = .003). When compared with the control populations, homozygosity for the MLH1 -93G>A variant allele was associated with MSI-H tumors among case patients in Ontario (adjusted odds ratio [OR] = 3.23, 95% confidence interval [CI] = 1.65 to 6.30) and in Newfoundland (OR = 8.88, 95% CI = 2.33 to 33.9), as was heterozygosity among case patients in Ontario (OR = 1.84, 95% CI = 1.20 to 2.83) and in Newfoundland (OR = 2.56, 95% CI = 1.14 to 5.75). Genotype frequencies were similar among case patients with MSS and MSI-L tumors and control subjects, and the majority of homozygous variant carriers had MSS tumors. Among case patients from Ontario, an association between the MLH1 -93G>A polymorphism and a strong family history of colorectal cancer (for Amsterdam criteria I and II, P = .004 and P = .02, respectively) was observed. CONCLUSION: In two patient populations, the MLH1 -93G>A polymorphism was associated with an increased risk of MSI-H colorectal cancer. (+info)