Evidence for the role of EPHX2 gene variants in anorexia nervosa.

Anorexia nervosa (AN) and related eating disorders are complex, multifactorial neuropsychiatric conditions with likely rare and common genetic and environmental determinants. To identify genetic variants associated with AN, we pursued a series of sequencing and genotyping studies focusing on the coding regions and upstream sequence of 152 candidate genes in a total of 1205 AN cases and 1948 controls. We identified individual variant associations in the Estrogen Receptor-ß (ESR2) gene, as well as a set of rare and common variants in the Epoxide Hydrolase 2 (EPHX2) gene, in an initial sequencing study of 261 early-onset severe AN cases and 73 controls (P=0.0004). The association of EPHX2 variants was further delineated in: (1) a pooling-based replication study involving an additional 500 AN patients and 500 controls (replication set P=0.00000016); (2) single-locus studies in a cohort of 386 previously genotyped broadly defined AN cases and 295 female population controls from the Bogalusa Heart Study (BHS) and a cohort of 58 individuals with self-reported eating disturbances and 851 controls (combined smallest single locus P<0.01). As EPHX2 is known to influence cholesterol metabolism, and AN is often associated with elevated cholesterol levels, we also investigated the association of EPHX2 variants and longitudinal body mass index (BMI) and cholesterol in BHS female and male subjects (N=229) and found evidence for a modifying effect of a subset of variants on the relationship between cholesterol and BMI (P<0.01). These findings suggest a novel association of gene variants within EPHX2 to susceptibility to AN and provide a foundation for future study of this important yet poorly understood condition

Species Differentiation on a Dynamic Landscape: Shifts in Metapopulation Genetic Structure Using the Chronology of the Hawaiian Archipelago

Species formation during adaptive radiation often occurs in the context of a changing environment. The establishment and arrangement of populations, in space and time, sets up ecological and genetic processes that dictate the rate and pattern of differentiation. Here, we focus on how a dynamic habitat can affect genetic structure, and ultimately, differentiation among populations. We make use of the chronology and geographical history provided by the Hawaiian archipelago to examine the initial stages of population establishment and genetic divergence. We use data from a set of 6 spider lineages that differ in habitat affinities, some preferring low elevation habitats with a longer history of connection, others being more specialized for high elevation and/or wet forest, some with more general habitat affinities. We show that habitat preferences associated with lineages are important in ecological and genetic structuring. Lineages that have more restricted habitat preferences are subject to repeated episodes of isolation and fragmentation as a result of lava flows and vegetation succession. The initial dynamic set up by the landscape translates over time into discrete lineages. Further work is needed to understand how genetic changes interact with a changing set of ecological interactions amongst a shifting mosaic of landscapes to achieve species formation

Image-Derived Input Function for Human Brain Using High Resolution PET Imaging with [11C](R)-rolipram and [11C]PBR28

The aim of this study was to test seven previously published image-input methods in state-of-the-art high resolution PET brain images. Images were obtained with a High Resolution Research Tomograph plus a resolution-recovery reconstruction algorithm using two different radioligands with different radiometabolite fractions. Three of the methods required arterial blood samples to scale the image-input, and four were blood-free methods. values was quantified using a scoring system. Using the image input methods that gave the most accurate results with Logan analysis, we also performed kinetic modelling with a two-tissue compartment model.)-rolipram, which has a lower metabolite fraction. Compartment modeling gave less reliable results, especially for the estimation of individual rate constants.C]PBR28), the more difficult it is to obtain a reliable image-derived input function; and 4) in association with image inputs, graphical analyses should be preferred over compartmental modelling

WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear Β-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer cells express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector Β-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the self-renewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.Peer reviewe

Social marketing and healthy eating : Findings from young people in Greece

This document is the Accepted Manuscript version. The final publication is available at Springer via http://dx.doi.org/10.1007/s12208-013-0112-xGreece has high rates of obesity and non-communicable diseases owing to poor dietary choices. This research provides lessons for social marketing to tackle the severe nutrition-related problems in this country by obtaining insight into the eating behaviour of young adults aged 18–23. Also, the main behavioural theories used to inform the research are critically discussed. The research was conducted in Athens. Nine focus groups with young adults from eight educational institutions were conducted and fifty-nine participants’ views towards eating habits, healthy eating and the factors that affect their food choices were explored. The study found that the participants adopted unhealthier nutritional habits after enrolment. Motivations for healthy eating were good health, appearance and psychological consequences, while barriers included lack of time, fast-food availability and taste, peer pressure, lack of knowledge and lack of family support. Participants reported lack of supportive environments when deciding on food choices. Based on the findings, recommendations about the development of the basic 4Ps of the marketing mix, as well as of a fifth P, for Policy are proposedPeer reviewe

The significance of measuring monocyte tissue factor activity in patients with breast and colorectal cancer

Monocytes express tissue factor (mTF) in several conditions including cancer where levels may be valuable in assessing tumour presence and progression. Using a two-stage kinetic chromogenic assay (KCA), mTF levels were measured in controls [normal subjects (n = 60) and patients undergoing hernia repair or cholecystectomy (n = 60)], in patients with benign and malignant disease of the breast (n = 83) and of the large bowel (n = 62). This was performed under fresh (resting) conditions and after incubation for 6 h without (unstimulated) and with (stimulated) Escherichia coli endotoxin. The malignant groups showed higher mTF levels than each of the three controls for resting (P < 0.05 breast, P < 0.05 colorectal) unstimulated (P < 0.05 breast, P < 0.05 colorectal) and stimulated cells (P < 0.001 breast, P < 0.01 colorectal). Similarly, the benign inflammatory groups had higher mTF levels than controls for resting (P < 0.05 colorectal), unstimulated (P < 0.05 colorectal) and stimulated cells (P < 0.01 breast, P < 0.01 colorectal). There was no significant difference between malignant and benign inflammatory groups in each organ. mTF levels showed an increase corresponding to that of histological tumour progression and were higher in non-surviving patients. In conclusion, mTF levels are raised in malignant and inflammatory disease compared to controls and patients with non-inflammatory conditions. Stimulated cells give better discrimination between the groups and may be of value in identifying high risk individuals. mTF levels showed an association with tumour grade or stage and the patients' survival time

Independent and combined influence of healthy lifestyle factors on academic performance in adolescents: DADOS Study

BACKGROUND. Few studies have analyzed the combined effect of lifestyle factors on academic performance (AP) in adolescents. The aim of this study was to analyze the independent and combined effects of weight status, screen time, sleep quality, daily meal frequency, cardiorespiratory fitness and physical activity (PA) on AP in adolescents. METHODS. A total of 262 adolescents (13.9±0.3 years) from the DADOS study were included in the analysis. Weight status was assessed through body mass index (kg/m 2 ). Participants completed questionnaires to evaluate screen time, sleep quality and daily meal frequency. Cardiorespiratory fitness was assessed by the 20-m shuttle run test. PA was evaluated by a wrist-worn GENEActiv accelerometer. AP was assessed through the final academic grades and a validated questionnaire. RESULTS. Non-overweight status, low screen time, good sleep quality and proper meal frequency showed independent, positive influence on AP. Moreover, adolescents achieving at least 3 healthy lifestyles were more likely to be in the high-performance group for academic grades than those achieving ≤ 1 (math OR: 3.02-9.51, language OR: 3.51-6.76 and grade point average OR: 4.22-9.36). CONCLUSIONS. Although individual healthy lifestyles are independently and positively associated with AP, the cumulative effect of multiple healthy lifestyles have a stronger impact

Association between neighborhood socioeconomic status and screen time among pre-school children: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Sedentary behavior is considered a separate construct from physical activity and engaging in sedentary behaviors results in health effects independent of physical activity levels. A major source of sedentary behavior in children is time spent viewing TV or movies, playing video games, and using computers. To date no study has examined the impact of neighborhood socioeconomic status (SES) on pre-school children's screen time behavior.</p> <p>Methods</p> <p>Proxy reports of weekday and weekend screen time (TV/movies, video games, and computer use) were completed by 1633 parents on their 4-5 year-old children in Edmonton, Alberta between November, 2005 and August, 2007. Postal codes were used to classified neighborhoods into low, medium or high SES. Multiple linear and logistic regression models were conducted to examine relationships between screen time and neighborhood SES.</p> <p>Results</p> <p>Girls living in low SES neighborhoods engaged in significantly more weekly overall screen time and TV/movie minutes compared to girls living in high SES neighborhoods. The same relationship was not observed in boys. Children living in low SES neighborhoods were significantly more likely to be video game users and less likely to be computer users compared to children living in high SES neighborhoods. Also, children living in medium SES neighborhoods were significantly less likely to be computer users compared to children living in high SES neighborhoods.</p> <p>Conclusions</p> <p>Some consideration should be given to providing alternative activity opportunities for children, especially girls who live in lower SES neighborhoods. Also, future research should continue to investigate the independent effects of neighborhood SES on screen time as well as the potential mediating variables for this relationship.</p