Design and feasibility testing of a novel group intervention for young women who binge drink in groups

BackgroundYoung women frequently drink alcohol in groups and binge drinking within these natural drinking groups is common. This study describes the design of a theoretically and empirically based group intervention to reduce binge drinking among young women. It also evaluates their engagement with the intervention and the acceptability of the study methods.MethodsFriendship groups of women aged 18–35 years, who had two or more episodes of binge drinking (>6 UK units on one occasion; 48g of alcohol) in the previous 30 days, were recruited from the community. A face-to-face group intervention, based on the Health Action Process Approach, was delivered over three sessions. Components of the intervention were woven around fun activities, such as making alcohol free cocktails. Women were followed up four months after the intervention was delivered. Results The target of 24 groups (comprising 97 women) was recruited. The common pattern of drinking was infrequent, heavy drinking (mean consumption on the heaviest drinking day was UK 18.1 units). Process evaluation revealed that the intervention was delivered with high fidelity and acceptability of the study methods was high. The women engaged positively with intervention components and made group decisions about cutting down. Twenty two groups set goals to reduce their drinking, and these were translated into action plans. Retention of individuals at follow up was 87%.ConclusionsThis study successfully recruited groups of young women whose patterns of drinking place them at high risk of acute harm. This novel approach to delivering an alcohol intervention has potential to reduce binge drinking among young women. The high levels of engagement with key steps in the behavior change process suggests that the group intervention should be tested in a full randomised controlled trial

Regulating levels of the neuromodulator D-serine in human brain: structural insight into pLG72 and D-amino acid oxidase interaction

The human flavoenzyme D-amino acid oxidase (hDAAO) degrades the NMDA-receptor modulator D-serine in the brain. Whereas hDAAO has been extensively characterized, little is known about its main modulator pLG72, a small protein encoded by the primate-specific gene G72 that has been associated with schizophrenia susceptibility. pLG72 interacts with neosynthesized hDAAO, promoting its inactivation and degradation. In this work we used low-resolution techniques to characterize the surface topology of the hDAAO-pLG72 complex. By using limited proteolysis coupled to mass spectrometry we could map the exposed regions in the two proteins after complex formation and highlighted an increased sensitivity to proteolysis of hDAAO in complex with pLG72. Cross-linking experiments by using bis(sulfosuccinimidyl)suberate identified the single covalent bond between T182 in hDAAO and K62 in pLG72. In order to validate the designed mode of interaction, three pLG72 variants incrementally truncated at the C-terminus, in addition to a form lacking the 71 N-terminal residues, were produced. All variants were dimeric, folded, and interacted with hDAAO. The strongest decrease in affinity for hDAAO (as well as for the hydrophobic drug chlorpromazine) was apparent for the N-terminally deleted pLG7272-153 form, which lacked K62. On the other hand, eliminating the disordered C-terminal tail yielded a more stable pLG72 protein, improved the binding to hDAAO, although giving lower enzyme inhibition. Elucidation of the mode of hDAAO-pLG72 interaction now makes it possible to design novel molecules that, by targeting the protein complex, can be therapeutically advantageous for diseases related to impairment in D-serine metabolism. This article is protected by copyright. All rights reserved

Inside athletes' minds: Preliminary results from a pilot study on mental representation of doping and potential implications for anti-doping

<p>Abstract</p> <p>Background</p> <p>Despite the growing body of literature and putative links between the use of ergogenic nutritional supplements, doping and illicit drugs, it remains unclear whether, in athletes' minds, doping aligns with illicit behaviour or with functional use of chemical or natural preparations. To date, no attempt has been made to quantitatively explore athletes' mental representation of doping in relation to illegality and functionality.</p> <p>Methods</p> <p>A convenience sample of student athletes from a large South-Eastern Australian university responded to an on-line survey. Competitive athletes (n = 46) were grouped based on self-reported use as follows: i) none used (30%), ii) supplement only (22%), iii) illicit only (26%) and iv) both supplements and illicit drug use (22%). Whereas no athlete reported doping, data provided on projected supplement-, doping- and drug use by the four user groups allowed evaluation of doping-related cognition in the context of self-reported supplement- and illicit drug taking behaviour; and comparison between these substances.</p> <p>Results</p> <p>A significantly higher prevalence estimation was found for illicit drug use and a trend towards a biased social projection emerged for supplement use. Doping estimates by user groups showed mixed results, suggesting that doping had more in common with the ergogenic nutritional supplement domain than the illicit drug domain.</p> <p>Conclusions</p> <p>Assessing the behavioural domain to which doping belongs to in athletes' mind would greatly advance doping behaviour research toward prevention and intervention. Further investigation refining the peculiarity of the mental representation of doping with a larger study sample, controlling for knowledge of doping and other factors, is warranted.</p

Impact of Circulating Cholesterol Levels on Growth and Intratumoral Androgen Concentration of Prostate Tumors

Prostate cancer (PCa) is the second most common cancer in men. Androgen deprivation therapy (ADT) leads to tumor involution and reduction of tumor burden. However, tumors eventually reemerge that have overcome the absence of gonadal androgens, termed castration resistant PCa (CRPC). Theories underlying the development of CRPC include androgen receptor (AR) mutation allowing for promiscuous activation by non-androgens, AR amplification and overexpression leading to hypersensitivity to low androgen levels, and/or tumoral uptake and conversion of adrenally derived androgens. More recently it has been proposed that prostate tumor cells synthesize their own androgens through de novo steroidogenesis, which involves the step-wise synthesis of androgens from cholesterol. Using the in vivo LNCaP PCa xenograft model, previous data from our group demonstrated that a hypercholesterolemia diet potentiates prostatic tumor growth via induction of angiogenesis. Using this same model we now demonstrate that circulating cholesterol levels are significantly associated with tumor size (R = 0.3957, p = 0.0049) and intratumoral levels of testosterone (R = 0.41, p = 0.0023) in LNCaP tumors grown in hormonally intact mice. We demonstrate tumoral expression of cholesterol uptake genes as well as the spectrum of steroidogenic enzymes necessary for androgen biosynthesis from cholesterol. Moreover, we show that circulating cholesterol levels are directly correlated with tumoral expression of CYP17A, the critical enzyme required for de novo synthesis of androgens from cholesterol (R = 0.4073, p = 0.025) Since hypercholesterolemia does not raise circulating androgen levels and the adrenal gland of the mouse synthesizes minimal androgens, this study provides evidence that hypercholesterolemia increases intratumoral de novo steroidogenesis. Our results are consistent with the hypothesis that cholesterol-fueled intratumoral androgen synthesis may accelerate the growth of prostate tumors, and suggest that treatment of CRPC may be optimized by inclusion of cholesterol reduction therapies in conjunction with therapies targeting androgen synthesis and the AR

Molecular classification of selective oestrogen receptor modulators on the basis of gene expression profiles of breast cancer cells expressing oestrogen receptor α

The purpose of this study was to classify selective oestrogen receptor modulators based on gene expression profiles produced in breast cancer cells expressing either wtERα or mutant351ERα. In total, 54 microarray experiments were carried out by using a commercially available Atlas cDNA Expression Arrays (Clontech), containing 588 cancer-related genes. Nine sets of data were generated for each cell line following 24 h of treatment: expression data were obtained for cells treated with vehicle EtOH (Control); with 10−9 or 10−8 M oestradiol; with 10−6 M 4-hydroxytamoxifen; with 10−6 M raloxifene; with 10−6 M idoxifene, with 10−6 M EM 652, with 10−6 M GW 7604; with 5×10−5 M resveratrol and with 10−6 M ICI 182,780. We developed a new algorithm ‘Expression Signatures’ to classify compounds on the basis of differential gene expression profiles. We created dendrograms for each cell line, in which branches represent relationships between compounds. Additionally, clustering analysis was performed using different subsets of genes to assess the robustness of the analysis. In general, only small differences between gene expression profiles treated with compounds were observed with correlation coefficients ranged from 0.83 to 0.98. This observation may be explained by the use of the same cell context for treatments with compounds that essentially belong to the same class of drugs with oestrogen receptors related mechanisms. The most surprising observation was that ICI 182,780 clustered together with oestrodiol and raloxifene for cells expressing wtERα and clustered together with EM 652 for cells expressing mutant351ERα. These data provide a rationale for a more precise and elaborate study in which custom made oligonucleotide arrays can be used with comprehensive sets of genes known to have consensus and putative oestrogen response elements in their promoter regions

A critical appraisal of the social norms approach as an interventional strategy for health-related behavior and attitude change

© 2018 Dempsey, McAlaney and Bewick. The Social Norms Approach is a widely used intervention strategy for promoting positive health-related behaviors. The Approach operates on the premise that individuals misperceive their peers' behaviors and attitudes, with evidence of under- and over-estimations of behaviors and peer approval for a range of positive and negative behaviors respectively. The greater these misperceptions, the more likely an individual is to engage in negative behaviors such as consuming heavier amounts of alcohol and other substances and reduce positive behaviors such as eating healthily and using sun protection. However, there are many complexities associated with the use of social norms feedback in interventions and empirical studies. Many social norms interventions do not attempt to change misperceptions of social norms or measure changes in normative perceptions pre- and post-intervention. This has led to a conflation of generic social norms interventions with those that are explicitly testing the Approach's assumptions that it is misperceptions of peer norms which drive behavior. The aim of the present review was to provide a critical appraisal of the use of the Social Norms Approach as an intervention strategy for health-related behaviors, identify the current issues with its evidence base, highlight key opportunities and challenges facing the approach, and make recommendations for good practice when using the approach. There are three core challenges and areas for improved practice when using the Social Norms Approach. Firstly, improvements in the methodological rigor and clarity of reporting of 'social norms' research, ensuring that studies are testing the approach's assumption of the role of misperceptions on behaviors are differentiated from studies investigating other forms of 'social norms.' Secondly, the need for a more explicit, unified and testable theoretical model outlining the development of normative misperceptions which can be translated into interventional studies. Finally, a need for a more robust evaluation of social norms interventions in addition to randomized controlled trials, such as the inclusion of process evaluations, qualitative studies of participant experiences of social norms feedback, and alternative study designs better suited for real-world public health settings. Such improvements are required to ensure that the Social Norms Approach is adequately tested and evaluated

Realism and Religion in Graham Greene.

Aristotle is called a "realistic" philosopher though to a modern mind he might seem "idealistic." To avoid any confusion of terms, I have capitalized "Realism" and usually qualify it by the adjective "empirical." At the outset, I should like to make it clear that I do not refer to "realism" in the Aristotelian connotation but to a specific quality that characterizes much of modern, English and American literature