A strategy for the characterization of minute chromosome rearrangements using multiple color fluorescence in situ hybridization with chromosome-specific DNA libraries and YAC clones

The identification of marker chromosomes in clinical and tumor cytogenetics by chromosome banding analysis can create problems. In this study, we present a strategy to define minute chromosomal rearrangements by multicolor fluorescence in situ hybridization (FISH) with whole chromosome painting probes derived from chromosome-specific DNA libraries and Alu-polymerase chain reaction (PCR) products of various region-specific yeast artificial chromosome (YAC) clones. To demonstrate the usefulness of this strategy for the characterization of chromosome rearrangements unidentifiable by banding techniques, an 8p+ marker chromosome with two extra bands present in the karyotype of a child with multiple anomalies, malformations, and severe mental retardation was investigated. A series of seven-color FISH experiments with sets of fluorochrome-labeled DNA library probes from flow-sorted chromosomes demonstrated that the additional segment on 8p+ was derived from chromosome 6. For a more detailed characterization of the marker chromosome, three-color FISH experiments with library probes specific to chromosomes 6 and 8 were performed in combination with newly established telomeric and subtelomeric YAC clones from 6q25, 6p23, and 8p23. These experiments demonstrated a trisomy 6pter6p22 and a monosomy 8pter8p23 in the patient. The present limitations for a broad application of this strategy and its possible improvements are discusse

Characterisation of breast fine-needle aspiration biopsies by centrosome aberrations and genomic instability

Recent studies have suggested that aneuploidy in malignant tumours could be a consequence of centrosome aberrations. Using immunofluorescence analysis with an antibody against γ-tubulin and DNA image cytometry, we measured centrosome aberrations and DNA ploidy patterns in fine-needle aspiration biopsies (FNABs) of 58 breast lesions. Benign lesions did not show any centrosome aberrations. DNA diploid carcinomas showed a mean percentage of cells with centrosomal defects of 2.1%. The aneuploid invasive carcinomas could be divided into two subgroups by their significantly (P=0.0003) different percentage of cells with centrosome aberrations (2.0 and 10.3%, respectively) and their significantly (P=0.0003) different percentage of cells with nonmodal DNA content values determined by the Stemline Scatter Index (SSI), a measure of genomic instability. The percentage of cells with centrosome aberrations demonstrated a positive, linear correlation with the corresponding SSI (r=0.82, P<0.0001) and loss of tissue differentiation (r=0.78, P<0.0001). Our results indicate the percentage of cells with centrosome aberrations as being sufficient to divide the investigated tumours into three significantly different groups: benign lesions with no centrosomal aberrations, and two malignant tumour types with mean values of 2.1 and 9.6% of centrosomal defects, respectively. Together, these results demonstrate that centrosome aberrations correlate with genomic instability and loss of tissue differentiation. Furthermore, this study shows the feasibility of centrosomal analysis in FNAB of the breast and suggests centrosomal aberrations as possessing diagnostic and prognostic value

Development of a healthy biscuit: an alternative approach to biscuit manufacture

OBJECTIVE: Obesity (BMI >30) and related health problems, including coronary heart disease (CHD), is without question a public health concern. The purpose of this study was to modify a traditional biscuit by the addition of vitamin B(6), vitamin B(12), Folic Acid, Vitamin C and Prebiotic fibre, while reducing salt and sugar. DESIGN: Development and commercial manufacture of the functional biscuit was carried out in collaboration with a well known and respected biscuit manufacturer of International reputation. The raw materials traditionally referred to as essential in biscuit manufacture, i.e. sugar and fat, were targeted for removal or reduction. In addition, salt was completely removed from the recipe. PARTICIPANTS: University students of both sexes (n = 25) agreed to act as subjects for the study. Ethical approval for the study was granted by the University ethics committee. The test was conducted as a single blind crossover design, and the modified and traditional biscuits were presented to the subjects under the same experimental conditions in a random fashion. RESULTS: No difference was observed between the original and the modified product for taste and consistency (P > 0.05). The modified biscuit was acceptable to the consumer in terms of eating quality, flavour and colour. Commercial acceptability was therefore established. CONCLUSION: This study has confirmed that traditional high-fat and high-sugar biscuits which are not associated with healthy diets by most consumers can be modified to produce a healthy alternative that can be manufactured under strict commercial conditions

Modelling a response as a function of high frequency count data: the association between physical activity and fat mass

We present a new statistical modelling approach where the response is a function of high frequency count data. Our application is about investigating the relationship between the health outcome fat mass and physical activity (PA) measured by accelerometer. The accelerometer quantifies the intensity of physical activity as counts per epoch over a given period of time. We use data from the Avon longitudinal study of parents and children (ALSPAC) where accelerometer data is available as a time series of accelerometer counts per minute over seven days for a subset of children. In order to compare accelerometer profiles between individuals and to reduce the high dimension a functional summary of the profiles is used. We use the histogram as a functional summary due to its simplicity, suitability and ease of interpretation. Our model is an extension of generalised regression of scalars on functions or signal regression. It allows also multi-dimensional functional predictors and additive non-linear predictors for metric covariates. The additive multidimensional functional predictors allow investigating specific questions about whether the effect of PA varies over its intensity, by gender, by time of day or by day of the week. The key feature of the model is that it utilises the full profile of measured PA without requiring cut-points defining intensity levels for light, moderate and vigorous activity. We show that the (not necessarily causal) effect of PA is not linear and not constant over the activity intensity. Also, there is little evidence to suggest that the effect of PA intensity varies by gender or whether it happens on weekdays or on weekends

Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error : the CREAM consortium

Peer reviewe

A genome-wide association meta-analysis on lipoprotein (a) concentrations adjusted for apolipoprotein (a) isoforms

High lipoprotein (a) [Lp(a)] concentrations are an independent risk factor for cardiovascular outcomes. Concentrations are strongly influenced by apo(a) kringle IV repeat isoforms. We aimed to identify genetic loci associated with Lp(a) concentrations using data from five genome- wide association studies (n = 13,781). We identified 48 independent SNPs in the LPA and 1 SNP in the APOE gene region to be significantly associated with Lp(a) concentrations. We also adjusted for apo(a) isoforms to identify loci affecting Lp(a) levels independently from them, which resulted in 31 SNPs (30 in the LPA, 1 in the APOE gene region). Seve

Array-CGH and breast cancer

The introduction of comparative genomic hybridization (CGH) in 1992 opened new avenues in genomic investigation; in particular, it advanced analysis of solid tumours, including breast cancer, because it obviated the need to culture cells before their chromosomes could be analyzed. The current generation of CGH analysis uses ordered arrays of genomic DNA sequences and is therefore referred to as array-CGH or matrix-CGH. It was introduced in 1998, and further increased the potential of CGH to provide insight into the fundamental processes of chromosomal instability and cancer. This review provides a critical evaluation of the data published on array-CGH and breast cancer, and discusses some of its expected future value and developments

Reducing depression in older home care clients: design of a prospective study of a nurse-led interprofessional mental health promotion intervention

Abstract Background Very little research has been conducted in the area of depression among older home care clients using personal support services. These older adults are particularly vulnerable to depression because of decreased cognition, comorbid chronic conditions, functional limitations, lack of social support, and reduced access to health services. To date, research has focused on collaborative, nurse-led depression care programs among older adults in primary care settings. Optimal management of depression among older home care clients is not currently known. The objective of this study is to evaluate the feasibility, acceptability and effectiveness of a 6-month nurse-led, interprofessional mental health promotion intervention aimed at older home care clients with depressive symptoms using personal support services. Methods/Design This one-group pre-test post-test study aims to recruit a total of 250 long-stay (> 60 days) home care clients, 70 years or older, with depressive symptoms who are receiving personal support services through a home care program in Ontario, Canada. The nurse-led intervention is a multi-faceted 6-month program led by a Registered Nurse that involves regular home visits, monthly case conferences, and evidence-based assessment and management of depression using an interprofessional approach. The primary outcome is the change in severity of depressive symptoms from baseline to 6 months using the Centre for Epidemiological Studies in Depression Scale. Secondary outcomes include changes in the prevalence of depressive symptoms and anxiety, health-related quality of life, cognitive function, and the rate and appropriateness of depression treatment from baseline to 12 months. Changes in the costs of use of health services will be assessed from a societal perspective. Descriptive and qualitative data will be collected to examine the feasibility and acceptability of the intervention and identify barriers and facilitators to implementation. Discussion Data collection began in May 2010 and is expected to be completed by July 2012. A collaborative nurse-led strategy may provide a feasible, acceptable and effective means for improving the health of older home care clients by improving the prevention, recognition, and management of depression in this vulnerable population. The challenges involved in designing a practical, transferable and sustainable nurse-led intervention in home care are also discussed. Trial Registration ClinicalTrials.gov: NCT0140792

Genome-Wide Association Studies of Serum Magnesium, Potassium, and Sodium Concentrations Identify Six Loci Influencing Serum Magnesium Levels

Magnesium, potassium, and sodium, cations commonly measured in serum, are involved in many physiological processes including energy metabolism, nerve and muscle function, signal transduction, and fluid and blood pressure regulation. To evaluate the contribution of common genetic variation to normal physiologic variation in serum concentrations of these cations, we conducted genome-wide association studies of serum magnesium, potassium, and sodium concentrations using ∼2.5 million genotyped and imputed common single nucleotide polymorphisms (SNPs) in 15,366 participants of European descent from the international CHARGE Consortium. Study-specific results were combined using fixed-effects inverse-variance weighted meta-analysis. SNPs demonstrating genome-wide significant (p<5×10−8) or suggestive associations (p<4×10−7) were evaluated for replication in an additional 8,463 subjects of European descent. The association of common variants at six genomic regions (in or near MUC1, ATP2B1, DCDC5, TRPM6, SHROOM3, and MDS1) with serum magnesium levels was genome-wide significant when meta-analyzed with the replication dataset. All initially significant SNPs from the CHARGE Consortium showed nominal association with clinically defined hypomagnesemia, two showed association with kidney function, two with bone mineral density, and one of these also associated with fasting glucose levels. Common variants in CNNM2, a magnesium transporter studied only in model systems to date, as well as in CNNM3 and CNNM4, were also associated with magnesium concentrations in this study. We observed no associations with serum sodium or potassium levels exceeding p<4×10−7. Follow-up studies of newly implicated genomic loci may provide additional insights into the regulation and homeostasis of human serum magnesium levels