Memorial University of Newfoundland

About: Memorial University of Newfoundland is a education organization based out in St. John's, Newfoundland and Labrador, Canada. It is known for research contribution in the topics: Population & Context (language use). The organization has 13818 authors who have published 27785 publications receiving 743594 citations. The organization is also known as: Memorial University & Memorial University of Newfoundland and Labrador.

The short- and long-term impact of multi-disciplinary clinics in addition to standard nephrology care on patient outcomes

Abstract: Background. This two country case control study of incident dialysis patients evaluates the outcomes of patients exposed to formalized multi-disciplinary clinic (MDC) programmes vs standard nephrologist care. Methods. Patients commencing dialysis in two centres (Vancouver, Canada and Cremona, Italy) were evaluated at and after dialysis start, as a function of MDC exposure vs nephrologist care alone. Only chronic kidney disease patients, with longer than 3 months of exposure to nephrology care, who had not previously received kidney replacement therapy were included. Study outcomes included laboratory parameters and survival. The MDC was similar in both countries and average exposure was 6–8 h per patient-year, as compared to 2–4 h for standard care. All patients had equal access to resources prior to dialysis and with respect to dialysis start, as all had been referred to the same local nephrology practices. Results. During the evaluation period 288 patients commenced dialysis after receiving more than 3 months nephrology care prior to dialysis. There were no major demographic differences between the cohorts. Mean duration of nephrology care prior to dialysis was 42 months, and dialysis was initiated at similar low glomerular filtration rate (GFR), though statistically significantly different (7.0 and 8.4 ml/min/m 2 , P ¼ 0.001). The MDC patients had higher haemoglobin (102 vs 90 g/l, P<0.0001), albumin (37.0 vs 34.8 g/l, P ¼ 0.002) and calcium levels (2.29 vs 2.16 mmol/l, P<0.0001) at dialysis start. Survival was significantly better in the MDC group demonstrated by Kaplan– Meier analysis (P ¼ 0.01). Cox proportional hazards analysis demonstrated standard nephrology clinic vs MDC attendance was a statistically significant independent predictor of death (hazards ratio ¼ 2.17, 95% confidence interval 1.11–4.28) after adjusting for other variables known to impact outcomes. Conclusions. This analysis of outcomes in two different countries suggests that despite equal and long exposure to nephrology care prior to dialysis, there appears to be an association of survival advantage for those patients exposed to formalized clinic care in addition to standard nephrologist follow-up. While other known predictors of survival such as adequacy of dialysis and severity of illness measures were not included in the model, those parameters require time on dialysis to be accumulated. Thus, the data do suggest that knowledge of patient status at the time of dialysis start is important. Further research is needed to determine which specific components of care both prior to dialysis and after its commencement are most important with respect to outcomes.

Meta-analysis of New Genome-wide Association Studies of Colorectal Cancer Risk

Abstract: Colorectal cancer is the second leading cause of cancer death in developed countries. Genome-wide association studies (GWAS) have successfully identified novel susceptibility loci for colorectal cancer. To follow up on these findings, and try to identify novel colorectal cancer susceptibility loci, we present results for GWAS of colorectal cancer (2,906 cases, 3,416 controls) that have not previously published main associations. Specifically, we calculated odds ratios and 95% confidence intervals using log-additive models for each study. In order to improve our power to detect novel colorectal cancer susceptibility loci, we performed a meta-analysis combining the results across studies. We selected the most statistically significant single nucleotide polymorphisms (SNPs) for replication using ten independent studies (8,161 cases and 9,101 controls). We again used a meta-analysis to summarize results for the replication studies alone, and for a combined analysis of GWAS and replication studies. We measured ten SNPs previously identified in colorectal cancer susceptibility loci and found eight to be associated with colorectal cancer (p value range 0.02 to 1.8 × 10(-8)). When we excluded studies that have previously published on these SNPs, five SNPs remained significant at p < 0.05 in the combined analysis. No novel susceptibility loci were significant in the replication study after adjustment for multiple testing, and none reached genome-wide significance from a combined analysis of GWAS and replication. We observed marginally significant evidence for a second independent SNP in the BMP2 region at chromosomal location 20p12 (rs4813802; replication p value 0.03; combined p value 7.3 × 10(-5)). In a region on 5p33.15, which includes the coding regions of the TERT-CLPTM1L genes and has been identified in GWAS to be associated with susceptibility to at least seven other cancers, we observed a marginally significant association with rs2853668 (replication p value 0.03; combined p value 1.9 × 10(-4)). Our study suggests a complex nature of the contribution of common genetic variants to risk for colorectal cancer.

Rare Deletions at the Neurexin 3 Locus in Autism Spectrum Disorder

Abstract: The three members of the human neurexin gene family, neurexin 1 (NRXN1), neurexin 2 (NRXN2), and neurexin 3 (NRXN3), encode neuronal adhesion proteins that have important roles in synapse development and function. In autism spectrum disorder (ASD), as well as in other neurodevelopmental conditions, rare exonic copy-number variants and/or point mutations have been identified in the NRXN1 and NRXN2 loci. We present clinical characterization of four index cases who have been diagnosed with ASD and who possess rare inherited or de novo microdeletions at 14q24.3–31.1, a region that overlaps exons of the alpha and/or beta isoforms of NRXN3. NRXN3 deletions were found in one father with subclinical autism and in a carrier mother and father without formal ASD diagnoses, indicating issues of penetrance and expressivity at this locus. Notwithstanding these clinical complexities, this report on ASD-affected individuals who harbor NRXN3 exonic deletions advances the understanding of the genetic etiology of autism, further enabling molecular diagnoses.

Glutamate: a truly functional amino acid

Abstract: Glutamate is one of the most abundant of the amino acids. In addition to its role in protein structure, it plays critical roles in nutrition, metabolism and signaling. Post-translational carboxylation of glutamyl residues increases their affinity for calcium and plays a major role in hemostasis. Glutamate is of fundamental importance to amino acid metabolism, yet the great bulk of dietary glutamate is catabolyzed within the intestine. It is necessary for the synthesis of key molecules, such as glutathione and the polyglutamated folate cofactors. It plays a major role in signaling. Within the central nervous system, glutamate is the major excitatory neurotransmitter and its product, GABA, the major inhibitory neurotransmitter. Glutamate interaction with specific taste cells in the tongue is a major component of umami taste. The finding of glutamate receptors throughout the gastrointestinal tract has opened up a new vista in glutamate function. Glutamate is truly a functional amino acid.