A prospective study of methylenetetrahydrofolate reductase and methionine synthase gene polymorphisms, and risk of colorectal adenoma

We examined the relationship between a functional polymorphism (667C-- >T, ala-->val) of the methylenetetrahydrofolate reductase gene (MTHFR) and the risk of colorectal adenomas in the prospective Nurses' Health Study. Among 257 incident polyp cases and 713 controls, the MTHFR val/val polymorphism [relative risk (RR) = 1.35, 95% confidence interval (CI) 0.84-2.17] was not significantly associated with risk of adenomas. This lack of association was observed for both small (RR = 1.36, 95% CI 0.76-2.45) and large (RR = 1.32, 95% CI 0.66-2.66) adenomas. Furthermore, there was no significant interaction between this polymorphism and consumption of either folate, methionine or alcohol. We also examined the relationship of a newly identified polymorphism (asp919gly) of the methionine synthase gene (MS) with the risk of colorectal adenomas in the same population. The MS gly/gly polymorphism was also not significantly associated with risk of colorectal adenomas (RR = 0.66, 95% CI 0.26-1.70). These results, which need to be confirmed in other studies, suggest that the MTHFR val/val polymorphism, which has been previously inversely associated with risk of colorectal cancer, plays a role only in a late stage (adenoma-- >carcinoma) of colorectal tumorigenesis, and/or may protect against malignant transformation in the subset of benign adenomas, which may progress to malignancy.      

Headless compression screw fixation prevents symptomatic metalwork in arthroscopic ankle arthrodesis

BackgroundArthroscopic ankle arthrodesis (AAA) is a recognised salvage procedure for end-stage arthritis. Its reported disadvantages include a high rate of re-operation for symptomatic prominence of metalwork. We propose that the use of a headless screw would reduce this re-operation rate.MethodsWe reviewed 32 AAAs, using the Acutrak?6/7 mm headless screw fixation system, to determine peri-operative parameters and complication rates.ResultsAt an average of 22 months follow-up, 28 (88%) had united radiologically. There were 2 stable fibrous non-unions not requiring further intervention. Of the other 2, one was successfully revised using an open technique, and the other patient died of unrelated causes.There were no other complications in this series, with no cases of metalwork removal for prominence or pain.ConclusionsUsing a headless screw fixation for arthroscopic ankle arthrodesis prevents symptomatic metalwork prominence and the requirement for removal.     

Ventricular measurements in computed tomography of responders and non-responders to donepezil in the treatment of Alzheimer's disease

INTRODUCTION: We attempt to see whether the ventricular measurements in routine CT scans performed prior to commencing donepezil differed in patients who duly responded well and those who did not, and to explore the potential application of the findings in clinical practice. METHOD: The study included all patients who were prescribed donepezil during a 2-year period in Warrington ( n =59). Two groups of patients were compared in respect of their baseline CT scan ventricular measurements: those who improved or remained stable cognitively on donepezil ( n =43) and those who declined while on donepezil (MMSE < 10) during the study period ( n =16). RESULTS: Significant differences in means between the two groups were found in relation to the bicaudate span and bicaudate ratio. Of ventricular measurements, only the bicaudate parameters were significantly correlated with the baseline Mini Mental State Examination (MMSE) score as well as the rate of decline in cognitive function during the study period ( P < 0.05). CONCLUSION: Baseline bicaudate diameter and ratio may be of some value if included in the initial assessment of patients on donepezil. These measurements, in conjunction with other cognitive and functional assessments, may prove helpful in deciding whether to commence treatment, and give a rough guide to the outcome. Future studies, with sufficient statistical power, are necessary to explore the use of ventricular parameters in predicting and monitoring patients' response to current and future pharmacological treatment in Alzheimer's disease.     

Research with youth of color in low-income communities: Strategies for recruiting and retaining participants

BackgroundYouth of color from low-income urban communities are crucial participants in research, as their involvement can shape effective, culturally responsive interventions and policy to promote youth health and well-being. These young people, however, are an often-neglected research population, due in part to perceived challenges associated with their inclusion as well as marginalized communities’ justifiable mistrust of research.ObjectivesBased on our experience conducting a school-based randomized intervention trial in Baltimore, Maryland, we present strategies for conducting research with low-income, urban youth of color. We discuss strategies in three domains: university-community partnership development, participant recruitment, and participant retention.MethodsWe reviewed partnership building and recruitment strategies employed by our team across four years of trial implementation and evaluated success of participant retention at our final survey timepoint.ResultsPartnership building was facilitated by selection of a study design that maximized benefits for all participants, promotion of capacity building at partner institutions, and attention to research staff hiring and training practices. Effective study recruitment strategies included personal contact with parents and close cooperation between school personnel and study staff. Providing incentives and collecting multiple types of participant contact information contributed to increased retention rates. On average, those who participated in the final survey timepoint were less likely to be male and Latinx and exhibited more favorable baseline mental health than those who did not, suggesting differential attrition based on youth characteristics.ConclusionsLessons learned from this school-based trial can be applied more broadly to research with low-income urban youth of color. Researchers should strive to maximize scientific rigor, minimize harm to vulnerable adolescents and their communities, promote positive research experiences for young people, and provide concrete benefits to those who participate.     

Angiographic estimates of myocardium at risk during acute myocardial infarction: validation study using cardiac magnetic resonance imaging.

AIMS: Global angiographic scores have been developed to determine the extent of myocardium jeopardized by significant coronary stenosis. We adapted these scores to quantify the anatomic area at risk during acute myocardial infarction. We used contrast-enhanced magnetic resonance (CMR) infarct imaging to measure the portion of myocardium that developed necrosis within the so defined angiographic area at risk. METHODS AND RESULTS: In 83 subjects presenting for primary percutaneous intervention, the myocardium at risk was estimated angiographically using the Myocardial Jeopardy Index (BARI) and a modified version of the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) scores. CMR was performed within a week to measure infarct size, infarct endocardial surface area (infarct-ESA), and infarct transmurality. As infarct transmurality increased, the infarct size closely approximated the myocardium at risk by angiography. In 35 subjects with transmural infarcts, the area at risk by BARI and APPROACH scores matched the infarct size (r = 0.90 and r = 0.92, P < 0.001). Additionally, BARI and APPROACH scores matched the infarct-ESA in all subjects independently of collateral flow and time to reperfusion (r = 0.90 and r = 0.87, P < 0.001). The presence of early reperfusion, collaterals, or both was associated with a progressive decrease in infarct transmurality (P < 0.001 for trend) with no difference in the infarct-ESA. CONCLUSION: The myocardium at risk of infarction can be determined angiographically as validated in subjects with transmural myocardial infarcts. Salvage provided by early reperfusion or collaterals occurs by limiting infarct transmurality, thereby the extent of endocardial infarct involved also allows estimation of the myocardium at risk in patients presenting with STEMI.