COX-derived prostanoid pathways in gastrointestinal cancer development and progression : novel targets for prevention and intervention

Arachidonic acid metabolism through cyclooxygenase (COX) pathways leads to the generation of biologically active eicosanoids. Eicosanoid expression levels vary during development and progression of gastrointestinal (GI) malignancies. COX-2 is the major COX-isoform responsible for G.I. cancer development/progression. COX-2 expression increases during progression from a normal to cancerous state. Evidence from observational studies has demonstrated that chronic NSAID use reduces the risk of cancer development, while both incidence and risk of death due to G.I. cancers were significantly reduced by daily aspirin intake. A number of randomized controlled trials (APC trial, Prevention of Sporadic Adenomatous Polyps trial, APPROVe trial) have also shown a significant protective effect in patients receiving selective COX-2 inhibitors. However, chronic use of selective COX-2 inhibitors at high doses was associated with increased cardiovascular risk, while NSAIDs have also been associated with increased risk. More recently, downstream effectors of COX-signaling have been investigated in cancer development/progression. PGE 2, which binds to both EP and PPAR receptors, is the major prostanoid implicated in the carcinogenesis of G.I. cancers. The role of TXA 2 in G.I. cancers has also been examined, although further studies are required to uncover its role in carcinogenesis. Other prostanoids investigated include PGD 2 and its metabolite 15d-PGJ2, PGF 1α and PGI 2. Targeting these prostanoids in G.I. cancers has the promise of avoiding cardiovascular toxicity associated with chronic selective COX-2 inhibition, while maintaining anti-tumor reactivity.A progressive sequence from normal to pre-malignant to a malignant state has been identified in G.I. cancers. In this review, we will discuss the role of the COX-derived prostanoids in G.I. cancer development and progression. Targeting these downstream prostanoids for chemoprevention and/or treatment of G.I. cancers will also be discussed. Finally, we will highlight the latest pre-clinical technologies as well as avenues for future investigation in this highly topical research field. © 2011 Elsevier B.V.

The effects and interactions of GABAergic and dopaminergic agents in the prevention of form deprivation myopia by brief periods of normal vision

Intravitreal injections of GABA antagonists, dopamine agonists and brief periods of normal vision have been shown separately to inhibit form-deprivation myopia (FDM). Our study had three aims: (i) establish whether GABAergic agents modify the myopia protective effect of normal vision, (ii) investigate the receptor sub-type specificity of any observed effect, and (iii) consider an interaction with the dopamine (DA) system. Prior to the period of normal vision GABAergic agents were applied either (i) individually, (ii) in combination with other GABAergic agents (an agonist with an antagonist), or (iii) in combination with DA agonists and antagonists. Water injections were given to groups not receiving drug treatments so that all experimental eyes received intravitreal injections. As shown previously, constant form-deprivation resulted in high myopia and when diffusers were removed for 2 h per day the period of normal vision greatly reduced the FDM that developed. GABA agonists inhibited the protective effect of normal vision whereas antagonists had the opposite effect. GABAA/C agonists and D2 DA antagonists when used in combination were additive in suppressing the protective effect of normal vision. A D2 DA agonist restored some of the protective effect of normal vision that was inhibited by a GABA agonist (muscimol). The protective effect of normal vision against form-deprivation is modifiable by both the GABAergic and DAergic pathways.

Flapless dental implant surgery : a retrospective study of 1,241 consecutive implants

Purpose: The purpose of this study was to identify retrospectively the predictors of implant survival when the flapless protocol was used in two private dental practices. Materials and Methods: The collected data were initially computer searched to identify the patients; later, a hand search of patient records was carried out to identify all flapless implants consecutively inserted over the last 10 years. The demographic information gathered on statistical predictors included age, sex, periodontal and peri-implantitis status, smoking, details of implants inserted, implant locations, placement time after extraction, use of simultaneous guided hard and soft tissue regeneration procedures, loading protocols, type of prosthesis, and treatment outcomes (implant survival and complications). Excluded were any implants that required flaps or simultaneous guided hard and soft tissue regeneration procedures, and implants narrower than 3.25 mm. Results: A total of 1,241 implants had been placed in 472 patients. Life table analysis indicated cumulative 5-year and 10-year implant survival rates of 97.9% and 96.5%, respectively. Most of the failed implants occurred in the posterior maxilla (54%) in type 4 bone (74.0%), and 55.0% of failed implants had been placed in smokers. Conclusion: Flapless dental implant surgery can yield an implant survival rate comparable to that reported in other studies using traditional flap techniques.

Comparing outcomes of a school based injury prevention intervention for low-medium risk adolescents with high-risk adoelscents

High-risk adolescents are shown to jeopardise their future social and health functioning as well as placing themselves and others at immediate risk of harm. The challenge of “reaching” high-risk adolescents, who are often marginalised, is considerable. There is a positive relationship between age and risk taking behaviors during adolescence. This study examines outcomes (alcohol use, transport risk behaviors, violence) of a school based intervention (SPIY) by comparing low-medium risk adolescents with high-risk adolescents over a six month period.

Skin cancer prevention and fashion – frontier bedfellows

Problem Queensland has the highest rates of skin cancer in the world, even after wide-ranging public programs promoting sun safety awareness. To-date, public awareness campaigns on the dangers of excessive sun exposure have been highly successful. For adolescents, however, where a significant amount of lifetime sun exposure occurs, perilous exposure still ensues, despite awareness of the risks. New frontier approaches are required to target this key audience cluster, for this significant national problem. Approach For the majority of adolescents, being part of a collective norm defines their visual, attitudinal and behavioural actions and fashion has been validated as one of the most powerful forces that can form, shape and bolster these norms. Considering clothing is the easiest method to limit the amount of skin exposed to UV, fashion (in its many subtle, yet influential guises) is proposed as an avenue to advance positive sun safe practices for adolescents. Through an action-led methodology, this research explores the potential of fashion, as one of the key parts of a complex equation, to be a prime driver to facilitate sun safety for adolescents. Findings This paper advocates that fashion, as distinguishable from clothing, has the potential to positively influence sun protective behaviour. The findings go further and recommend the use of fashion as a stealth driver for sun safety advancement, for adolescents in particular, via shifts in norms of beauty and targeted generational communication strategies. This frontier approach has the potential to significantly reduce risky sun exposure in adolescence.

A proposed approach to monitor private-sector policies and practices related to food environments, obesity and non-communicable disease prevention

Private-sector organizations play a critical role in shaping the food environments of individuals and populations. However, there is currently very limited independent monitoring of private-sector actions related to food environments. This paper reviews previous efforts to monitor the private sector in this area, and outlines a proposed approach to monitor private-sector policies and practices related to food environments, and their influence on obesity and non-communicable disease (NCD) prevention. A step-wise approach to data collection is recommended, in which the first (‘minimal’) step is the collation of publicly available food and nutrition-related policies of selected private-sector organizations. The second (‘expanded’) step assesses the nutritional composition of each organization's products, their promotions to children, their labelling practices, and the accessibility, availability and affordability of their products. The third (‘optimal’) step includes data on other commercial activities that may influence food environments, such as political lobbying and corporate philanthropy. The proposed approach will be further developed and piloted in countries of varying size and income levels. There is potential for this approach to enable national and international benchmarking of private-sector policies and practices, and to inform efforts to hold the private sector to account for their role in obesity and NCD prevention.

Making prevention matter : a survey of child sexual abuse prevention programs in Australia

Throughout Australia, there is considerable concern about the prevalence of child sexual abuse. Sexual abuse is experienced by over 3,500 Australian children each year, causing long-term psychological, health and social problems to children, their families and communities, and significant economic costs to society as a whole. In many countries, the provision of school-based programs has been a core strategy in efforts to prevent child sexual abuse. However, little is known about the range of programs in use in Australia, the numbers of children who have received programs, and the contents and methods used in program delivery. This presentation reports on a detailed National survey of child sexual abuse prevention programs currently used in Australian primary schools. An online survey was conducted over a six-month period from November 2011 to April 2012 yielding detailed data from 38 programs. The presentation will provide an overview of: the scope and reach of programs; program content, teaching strategies and resources; barriers and facilitators to program adoption by schools; and program evaluation strategies.

Development of an evidence-based framework to guide injury prevention interventions for off-road motorcyclists

There is little research on off-road motorcycle and all-terrain vehicle riders though injury levels are high. This thesis identified formal responsibility for monitoring injuries, targeting young male and recreational riders, promotion of family members as models, and controlled and accessible riding locations as ways to increase safety. These recommendations were based on analysis of Queensland hospitalisation records, rider personal reports and survey responses.

The potential role of lycopene for the prevention and therapy of prostate cancer : from molecular mechanisms to clinical evidence

Lycopene is a phytochemical that belongs to a group of pigments known as carotenoids. It is red, lipophilic and naturally occurring in many fruits and vegetables, with tomatoes and tomato-based products containing the highest concentrations of bioavailable lycopene. Several epidemiological studies have linked increased lycopene consumption with decreased prostate cancer risk. These findings are supported by in vitro and in vivo experiments showing that lycopene not only enhances the antioxidant response of prostate cells, but that it is even able to inhibit proliferation, induce apoptosis and decrease the metastatic capacity of prostate cancer cells. However, there is still no clearly proven clinical evidence supporting the use of lycopene in the prevention or treatment of prostate cancer, due to the only limited number of published randomized clinical trials and the varying quality of existing studies. The scope of this article is to discuss the potential impact of lycopene on prostate cancer by giving an overview about its molecular mechanisms and clinical effects. © 2013 by the authors; licensee MDPI, Basel, Switzerland.

Prevention and treatment of acute radiation-induced skin reactions : a systematic review and meta-analysis of randomized controlled trials

Background Radiation-induced skin reaction (RISR) is a common side effect that affects the majority of cancer patients receiving radiation treatment. RISR is often characterised by swelling,redness, pigmentation, fibrosis, and ulceration, pain, warmth, burning, and itching of the skin. The aim of this systematic review was to assess the effects of interventions which aim to prevent or manage RISR in people with cancer. Methods We searched the following databases up to November 2012: Cochrane Skin Group Specialised Register, CENTRAL (2012, Issue 11), MEDLINE (from 1946), EMBASE (from 1974), PsycINFO (from 1806), CINAHL (from 1981) and LILACS (from 1982). Randomized controlled trials evaluating interventions for preventing or managing RISR in cancer patients were included. The primary outcomes were development of RISR, and levels of RISR and symptom severity. Secondary outcomes were time taken to develop erythema or dry desquamation; quality of life; time taken to heal, a number of skin reaction and symptom severity measures; cost, participant satisfaction; ease of use and adverse effects. Where appropriate, we pooled results of randomized controlled trials using mean differences (MD) or odd ratios (OR) with 95% confidence intervals (CI). Results Forty-seven studies were included in this review. These evaluated six types of interventions (oral systemic medications; skin care practices; steroidal topical therapies; non-steroidal topical therapies; dressings and other). Findings from two meta-analyses demonstrated significant benefits of oral Wobe-Mugos E for preventing RISR (OR 0.13 (95% CI 0.05 to 0.38)) and limiting the maximal level of RISR (MD −0.92 (95% CI −1.36 to −0.48)). Another meta-analysis reported that wearing deodorant does not influence the development of RISR (OR 0.80 (95% CI 0.47 to 1.37)). Conclusions Despite the high number of trials in this area, there is limited good, comparative research that provides definitive results suggesting the effectiveness of any single intervention for reducing RISR. More research is required to demonstrate the usefulness of a wide range of products that are being used for reducing RISR. Future efforts for reducing RISR severity should focus on promising interventions, such as Wobe-Mugos E and oral zinc.

The CLIMATE schools combined study : a cluster randomised controlled trial of a universal Internet-based prevention program for youth substance misuse, depression and anxiety

Background Anxiety, depressive and substance use disorders account for three quarters of the disability attributed to mental disorders and frequently co-occur. While programs for the prevention and reduction of symptoms associated with (i) substance use and (ii) mental health disorders exist, research is yet to determine if a combined approach is more effective. This paper describes the study protocol of a cluster randomised controlled trial to evaluate the effectiveness of the CLIMATE Schools Combined intervention, a universal approach to preventing substance use and mental health problems among adolescents. Methods/design Participants will consist of approximately 8400 students aged 13 to 14-years-old from 84 secondary schools in New South Wales, Western Australia and Queensland, Australia. The schools will be cluster randomised to one of four groups; (i) CLIMATE Schools Combined intervention; (ii) CLIMATE Schools - Substance Use; (iii) CLIMATE Schools - Mental Health, or (iv) Control (Health and Physical Education as usual). The primary outcomes of the trial will be the uptake and harmful use of alcohol and other drugs, mental health symptomatology and anxiety, depression and substance use knowledge. Secondary outcomes include substance use related harms, self-efficacy to resist peer pressure, general disability, and truancy. The link between personality and substance use will also be examined. Discussion Compared to students who receive the universal CLIMATE Schools - Substance Use, or CLIMATE Schools - Mental Health or the Control condition (who received usual Health and Physical Education), we expect students who receive the CLIMATE Schools Combined intervention to show greater delays to the initiation of substance use, reductions in substance use and mental health symptoms, and increased substance use and mental health knowledge

Improving dental and medical students’ psychological health using a self-development coaching program : a pilot study

Introduction: Dental and medical students worldwide, including in Saudi Arabia, have been reported to have a high incidence of poor psychological health, such as depression, stress, anxiety, and lowlife satisfaction. Self-development coaching programs have become an increasingly popular way to improve individuals’ lives. However, few studies have evaluated the psychological effects of such programs among dental and medical students. Moreover, no studies have been conducted on self-development coaching programs in Saudi Arabia. Aims: The aim of this study was to assess the feasibility of a larger study via a pilot study and to acquire preliminary findings about the effectiveness of a self-development coaching program on psychological health among dental and medical students in Saudi Arabia. Methods: A pre-post interventional study design was used to test a self-development coaching program (How to be an Ultra-Super Student) with a sample of medical students (n=17) at Umm Al-Qura University at Saudi Arabia. The outcome measures were students’ psychological distress (depression, anxiety, and stress), life satisfaction, self-efficacy, the coach, and coaching program characteristics. Results: The study showed that there was a significant improvement in depression (p=0.04), self-efficacy (p=0.02), and satisfaction with life (p=0.04), which supported the feasibility of a large study in the future. Conclusions: The study’s findings encourage the implementation of a randomized, controlled trial study with a larger sample to further test the effectiveness of using self-development coaching programs with medical and dental students in Saudi Arabia to improve their psychological health.

Prevention of Alcohol-Related Crime and Trauma (PACT) : brief interventions in routine care pathway – a study protocol

Background Globally, alcohol-related injuries cause millions of deaths and huge economic loss each year . The incidence of facial (jawbone) fractures in the Northern Territory of Australia is second only to Greenland, due to a strong involvement of alcohol in its aetiology, and high levels of alcohol consumption. The highest incidences of alcohol-related trauma in the Territory are observed amongst patients in the Maxillofacial Surgery Unit of the Royal Darwin Hospital. Accordingly, this project aims to introduce screening and brief interventions into this unit, with the aims of changing health service provider practice, improving access to care, and improving patient outcomes. Methods Establishment of Project Governance: The project governance team includes a project manager, project leader, an Indigenous Reference Group (IRG) and an Expert Reference Group (ERG). Development of a best practice pathway: PACT project researchers collaborate with clinical staff to develop a best practice pathway suited to the setting of the surgical unit. The pathway provides clear guidelines for screening, assessment, intervention and referral. Implementation: The developed pathway is introduced to the unit through staff training workshops and associate resources and adapted in response to staff feedback. Evaluation: File audits, post workshop questionnaires and semi-structured interviews are administered. Discussion This project allows direct transfer of research findings into clinical practice and can inform future hospital-based injury prevention strategies.