Dietary glycaemic index and cognitive function: prospective associations in adults of the 1946 British birth cohort

OBJECTIVE: Evidence suggests that the rate of glucose release following consumption of carbohydrate-containing foods, defined as the glycaemic index (GI), is inversely associated with cognitive function. To date, most of the evidence stems from either single-meal studies or highly heterogeneous cohort studies. We aimed to study the prospective associations of diet GI at age 53 years with outcomes of verbal memory and letter search tests at age 69 years and rate of decline between 53 and 69 years. DESING: Longitudinal population-based birth cohort study. SETTING: MRC National Survey for Health and Development. PARTICIPANTS: Cohort members (n 1252). RESULTS: Using multivariable linear and logistic regression, adjusted for potential confounders, associations of higher-GI diet with lower verbal memory, lower letter search speed and lower number of hits in a letter search test were attenuated after adjustments for cognitive ability at age 15 years, educational attainment, further training and occupational social class. No association was observed between diet GI at 53 years and letter search accuracy or speed–accuracy trade-off at 69 years, or between diet GI at 53 years and rate of decline between 53 and 69 years in any cognitive measure. CONCLUSIONS: Diet GI does not appear to predict cognitive function or decline, which was mainly explained by childhood cognitive ability, education and occupational social class. Our findings confirm the need for further research on the association between diet and cognition from a life-course perspective

Clinical characteristics of cyclodeviation

PURPOSE: To retrospectively evaluate the incidence of cyclodeviation among patients with diplopia and analyse the causative diseases and clinical manifestations of cyclodeviation. METHODS: The medical records of 266 consecutive patients of 15 years of age or older presenting with diplopia, who had undergone the Lancaster red-green test (LRGT) from January 2001 to December 2002, were retrospectively reviewed. The presence of cyclodeviation on LRGT, predisposing conditions, causative diseases, and clinical manifestations of cyclotropia were analysed. Cyclodeviation on the LRGT were compared with those from the Maddox double-rod test (MDRT) and fundus photography. RESULTS: A total of 63 (24%) out of 266 patients exhibited cyclodeviation on LRGT. Eight out of 63 patients with cyclodeviation on the LRGT complained of torsional diplopia. Superior oblique palsy (SOP) was the most common causative disease (42 patients), followed by skew deviation (six) and thyroid orbitopathy (three). Excyclodeviation was found in 57 patients and incyclodeviation in four patients on the LRGT. The spontaneous recovery rate was 83% in patients of vascular origin and 17% of traumatic origin. Cyclodeviation with the MDRT and fundus photography showed good correlation with those obtained from the LRGT. There was no association of the amount of cyclotropia with the presence of torsional diplopia as well as with its recovery. CONCLUSION: In spite of the rare complaint of torsional diplopia, 24% of the patients with diplopia showed cyclodeviation on the LRGT. SOP was the most common causative disease. Most of the patients with cyclodeviation of a vascular origin showed spontaneous improvement

A visual and curatorial approach to clinical variant prioritization and disease gene discovery in genome-wide diagnostics

Background: Genome-wide data are increasingly important in the clinical evaluation of human disease. However, the large number of variants observed in individual patients challenges the efficiency and accuracy of diagnostic review. Recent work has shown that systematic integration of clinical phenotype data with genotype information can improve diagnostic workflows and prioritization of filtered rare variants. We have developed visually interactive, analytically transparent analysis software that leverages existing disease catalogs, such as the Online Mendelian Inheritance in Man database (OMIM) and the Human Phenotype Ontology (HPO), to integrate patient phenotype and variant data into ranked diagnostic alternatives. Methods: Our tool, “OMIM Explorer” (http://www.omimexplorer.com), extends the biomedical application of semantic similarity methods beyond those reported in previous studies. The tool also provides a simple interface for translating free-text clinical notes into HPO terms, enabling clinical providers and geneticists to contribute phenotypes to the diagnostic process. The visual approach uses semantic similarity with multidimensional scaling to collapse high-dimensional phenotype and genotype data from an individual into a graphical format that contextualizes the patient within a low-dimensional disease map. The map proposes a differential diagnosis and algorithmically suggests potential alternatives for phenotype queries—in essence, generating a computationally assisted differential diagnosis informed by the individual’s personal genome. Visual interactivity allows the user to filter and update variant rankings by interacting with intermediate results. The tool also implements an adaptive approach for disease gene discovery based on patient phenotypes. Results: We retrospectively analyzed pilot cohort data from the Baylor Miraca Genetics Laboratory, demonstrating performance of the tool and workflow in the re-analysis of clinical exomes. Our tool assigned to clinically reported variants a median rank of 2, placing causal variants in the top 1 % of filtered candidates across the 47 cohort cases with reported molecular diagnoses of exome variants in OMIM Morbidmap genes. Our tool outperformed Phen-Gen, eXtasy, PhenIX, PHIVE, and hiPHIVE in the prioritization of these clinically reported variants. Conclusions: Our integrative paradigm can improve efficiency and, potentially, the quality of genomic medicine by more effectively utilizing available phenotype information, catalog data, and genomic knowledge

Evaluation of a communication skills program for first-year medical students at the University of Toronto

Abstract Background Effective doctor-patient communication has been linked to numerous benefits for both patient and physician. The purpose of this study was to evaluate the effectiveness of the University of Toronto's Therapeutic Communication Program (TCom) at improving first-year medical students' communication skills. Methods Data were collected during the 1996/97, 1997/98, 1998/99 and 1999/00 academic years. The study used a repeated measures design with a waiting list control group: students were randomly assigned to groups starting the educational intervention in either September (N = 38) or February (N = 41), with the latter being used as a control for the former. Communication skills were assessed at the pre- and post-intervention times and at the end of the academic year from the perspectives of student, standardized patient and external rater. Results Only the external rater, using an instrument designed to assess the students' empathy based on their written responses, showed a time × group interaction effect (p = 0.039), thereby partially supporting the hypothesis that TCom improved the students' communication skills. Students rated themselves less positively after participation in the program (p = 0.038), suggesting that self-evaluation was an ineffective measure of actual performance or that the program helped them learn to more accurately assess their abilities. Conclusion The lack of strong findings may be partly due to the study's small sample sizes. Further research at other medical or professional schools could assess the effectiveness of similar courses on students' communication skills and on other capacities that were not measured in this study, such as their understanding of and comfort with patients, their management of the doctor-patient relationship, and their ability to give and receive feedback

Transition of care: experiences and preferences of patients across the primary/secondary interface – a qualitative study

BACKGROUND: Coordination between care providers of different disciplines is essential to improve the quality of care, in particular for patients with chronic diseases. The way in which general practitioners (GP's) and medical specialists interact has important implications for any healthcare system in which the GP plays the role of gatekeeper to specialist care. Patient experiences and preferences have proven to be increasingly important in discussing healthcare policy. The Dutch government initiated the development of a special website with information for patients on performance indicators of hospitals as well as information on illness or treatment.In the present study we focus on the transition of care at the primary - secondary interface with reference to the impact of patients' ability to make choices about their secondary care providers. The purpose of this study is to (a) explore experiences and preferences of patients regarding the transition between primary and secondary care, (b) study informational resources on illness/treatment desired by patients and (c) determine how information supplied could make it easier for the patient to choose between different options for care (hospital or specialist). METHODS: We conducted a qualitative study using semi-structured focus group interviews among 71 patients referred for various indications in the north and west of The Netherlands. RESULTS: Patients find it important that they do not have to wait, that they are taken seriously, and receive adequate and individually relevant information. A lack of continuity from secondary to primary care was experienced. The patient's desire for free choice of type of care did not arise in any of the focus groups. CONCLUSION: Hospital discharge information needs to be improved. The interval between discharge from specialist care and the report of the specialist to the GP might be a suitable performance indicator in healthcare. Patients want to receive information, tailored to their own situation. The need for information, however, is quite variable. Patients do not feel strongly about self-chosen healthcare, contrary to what administrators presently believe

The Role of Particulate Matter-Associated Zinc in Cardiac Injury in Rats

Background: Exposure to particulate matter (PM) has been associated with increased cardiovascular morbidity; however, causative components are unknown. Zinc is a major element detected at high levels in urban air.Objective We investigated the role of PM-associated zinc in cardiac injury. Methods: We repeatedly exposed 12- to 14-week-old male Wistar Kyoto rats intratracheally (1×/week for 8 or16 weeks) to a) saline (control); b) PM having no soluble zinc (Mount St. Helens ash, MSH); or c) whole-combustion PM suspension containing 14.5 μg/mg of water-soluble zinc at high dose (PM-HD) and d ) low dose (PM-LD), e) the aqueous fraction of this suspension (14.5 μg/mg of soluble zinc) (PM-L), or f ) zinc sulfate (rats exposed for 8 weeks received double the concentration of all PM components of rats exposed for 16 weeks). Results: Pulmonary inflammation was apparent in all exposure groups when compared with saline (8 weeks greater than 16 weeks). PM with or without zinc, or with zinc alone caused small increases in focal subepicardial inflammation, degeneration, and fibrosis. Lesions were not detected in controls at 8 weeks but were noted at 16 weeks. We analyzed mitochondrial DNA damage using quantitative polymerase chain reaction and found that all groups except MSH caused varying degrees of damage relative to control. Total cardiac aconitase activity was inhibited in rats receiving soluble zinc. Expression array analysis of heart tissue revealed modest changes in mRNA for genes involved in signaling, ion channels function, oxidative stress, mitochondrial fatty acid metabolism, and cell cycle regulation in zinc but not in MSH-exposed rats. Conclusion: These results suggest that water-soluble PM-associated zinc may be one of the causal components involved in PM cardiac effects

Laser capture microdissection of gonads from juvenile zebrafish

<p>Abstract</p> <p>Background</p> <p>Investigating gonadal gene expression is important in attempting to elucidate the molecular mechanism of sex determination and differentiation in the model species zebrafish. However, the small size of juvenile zebrafish and correspondingly their gonads complicates this type of investigation. Furthermore, the lack of a genetic sex marker in juvenile zebrafish prevents pooling gonads from several individuals. The aim of this study was to establish a method to isolate the gonads from individual juvenile zebrafish allowing future investigations of gonadal gene expression during sex determination and differentiation.</p> <p>Methods</p> <p>The laser capture microdissection technique enables isolation of specific cells and tissues and thereby removes the noise of gene expression from other cells or tissues in the gene expression profile. A protocol developed for laser microdissection of human gonocytes was adjusted and optimised to isolate juvenile zebrafish gonads.</p> <p>Results</p> <p>The juvenile zebrafish gonad is not morphologically distinguishable when using dehydrated cryosections on membrane slides and a specific staining method is necessary to identify the gonads. The protocol setup in this study allows staining, identification, isolation and subsequent RNA purification and amplification of gonads from individual juvenile zebrafish thereby enabling gonadal gene expression profiling.</p> <p>Conclusion</p> <p>The study presents a protocol for isolation of individual juvenile zebrafish gonads, which will enable future investigations of gonadal gene expression during the critical period of sex differentiation. Furthermore, the presented staining method is applicable to other species as it is directed towards alkaline phosphatase that is expressed in gonocytes and embryonic stem cells, which is conserved among vertebrate species.</p

Socioeconomic inequalities in cancer survival in England after the NHS cancer plan

BACKGROUND: Socioeconomic inequalities in survival were observed for many cancers in England during 1981-1999. The NHS Cancer Plan (2000) aimed to improve survival and reduce these inequalities. This study examines trends in the deprivation gap in cancer survival after implementation of the Plan. MATERIALS AND METHOD: We examined relative survival among adults diagnosed with 1 of 21 common cancers in England during 1996-2006, followed up to 31 December 2007. Three periods were defined: 1996-2000 (before the Cancer Plan), 2001-2003 (initialisation) and 2004-2006 (implementation). We estimated the difference in survival between the most deprived and most affluent groups (deprivation gap) at 1 and 3 years after diagnosis, and the change in the deprivation gap both within and between these periods. RESULTS: Survival improved for most cancers, but inequalities in survival were still wide for many cancers in 2006. Only the deprivation gap in 1-year survival narrowed slightly over time. A majority of the socioeconomic disparities in survival occurred soon after a cancer diagnosis, regardless of the cancer prognosis. CONCLUSION: The recently observed reduction in the deprivation gap was minor and limited to 1-year survival, suggesting that, so far, the Cancer Plan has little effect on those inequalities. Our findings highlight that earlier diagnosis and rapid access to optimal treatment should be ensured for all socioeconomic groups

The use of complementary and alternative medicines among patients with locally advanced breast cancer – a descriptive study

BACKGROUND: Complementary and alternative medicine (CAM) use is common among cancer patients. This paper reviews the use of CAM in a series of patients with locally advanced breast cancer (LABC). METHODS: Women with LABC attending a specialist clinic at a single Canadian cancer centre were identified and approached. Participants completed a self-administered survey regarding CAM usage, beliefs associated with CAM usage, views of their risks of developing recurrent cancer and of dying of breast cancer. Responses were scored and compared between CAM users and non-users. RESULTS: Thirty-six patients were approached, 32 completed the questionnaire (response rate 89%). Forty-seven percent of LABC patients were identified as CAM users. CAM users were more likely to be younger, married, in a higher socioeconomic class and of Asian ethnicity than non-users. CAM users were likely to use multiple modalities simultaneously (median 4) with vitamins being the most popular (60%). Motivation for CAM therapy was described as, "assisting their body to heal" (75%), to 'boost the immune system' (56%) and to "give a feeling of control with respect to their treatment" (56%). CAM therapy was used concurrently with conventional treatment in 88% of cases, however, 12% of patients felt that CAM could replace their conventional therapy. Psychological evaluation suggests CAM users perceived their risk of dying of breast cancer was similar to that of the non-Cam group (33% vs. 35%), however the CAM group had less severe anxiety and depression. CONCLUSION: The motivation, objectives and benefits of CAM therapy in a selected population of women with LABC are similar to those reported for women diagnosed with early stage breast cancer. CAM users display less anxiety and depression and are less likely to believe they will die of their breast cancer. However the actual benefit to overall and disease free survival has yet to be demonstrated, as well as the possible interactions with conventional therapy. Consequently more research is needed in this ever-growing field

Microarray-Based Transcriptomic Analysis of Differences between Long-Term Gregarious and Solitarious Desert Locusts

Desert locusts (Schistocerca gregaria) show an extreme form of phenotypic plasticity and can transform between a cryptic solitarious phase and a swarming gregarious phase. The two phases differ extensively in behavior, morphology and physiology but very little is known about the molecular basis of these differences. We used our recently generated Expressed Sequence Tag (EST) database derived from S. gregaria central nervous system (CNS) to design oligonucleotide microarrays and compare the expression of thousands of genes in the CNS of long-term gregarious and solitarious adult desert locusts. This identified 214 differentially expressed genes, of which 40% have been annotated to date. These include genes encoding proteins that are associated with CNS development and modeling, sensory perception, stress response and resistance, and fundamental cellular processes. Our microarray analysis has identified genes whose altered expression may enable locusts of either phase to deal with the different challenges they face. Genes for heat shock proteins and proteins which confer protection from infection were upregulated in gregarious locusts, which may allow them to respond to acute physiological challenges. By contrast the longer-lived solitarious locusts appear to be more strongly protected from the slowly accumulating effects of ageing by an upregulation of genes related to anti-oxidant systems, detoxification and anabolic renewal. Gregarious locusts also had a greater abundance of transcripts for proteins involved in sensory processing and in nervous system development and plasticity. Gregarious locusts live in a more complex sensory environment than solitarious locusts and may require a greater turnover of proteins involved in sensory transduction, and possibly greater neuronal plasticity