“Combination-oriented molecular-targeting prevention” of cancer: a model involving the combination of TRAIL and a DR5 inducer

Malignant tumors carry a high risk of death, and the prevention of malignant tumors is a crucial issue in preventive medicine. To this end, many chemopreventive agents have been tested, but the effects of single agents have been found to be insufficient to justify clinical trials. We have therefore hypothesized that combinations of different chemopreventive agents may synergistically enhance the preventive effect of chemopreventive agents used singly. To provide the treating physician with some guideline by which to choose the most effective agents to be combined, we propose a strategy which we have termed the “combination-oriented molecular-targeting prevention” of cancer. As the molecular target of our model, we focused on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which specifically causes apoptosis in malignant tumor cells. Many of these agents were found to up-regulate the expression of death receptor 5, a TRAIL receptor. They were also found to synergistically induce apoptosis in malignant tumor cells when combined with TRAIL. Here, we strongly advocate that the strategy of “combination-oriented molecular-targeting prevention” of cancer will be a practical approach for chemoprevention against human malignant tumors.     

Obesity prevention: co-framing for intersectoral ‘buy-in’

The multi-factorial causes of obesity demand integrated prevention policies with the collaboration of diverse sectors, although to date, there is little evidence of engagement by non-health sectors in developing obesity prevention policies. In this commentary, we develop a three-step argument for improving intersectoral collaboration. We first note that to encourage non-health sectors in developing and implementing integrated preventive policies, obesity should be reframed as a systemic problem rather than its dominant framing as a matter of individual behavioural change. We then propose a co-framing of obesity, such that it aligns with the policy goals of diverse non-health sectors. Finally, drawing on the network governance literature, we argue that a network-based governance approach with an independent network administrative organization will best facilitate multisectoral collaboration through a successful co-framing strategy.     

Is there a role for carbohydrate restriction in the treatment and prevention of cancer?

Background

Aflatoxin B1 (AFB1) is potent hepatotoxic and hepatocarcinogenic agent. In aflatoxicosis, oxidative stress is a common mechanism contributing to initiation and progression of hepatic damage. The aim of this work was to evaluate the hepatoprotective effect of cactus cladode extract (CCE) on aflatoxin B1-induced liver damage in mice by measuring malondialdehyde (MDA) level, the protein carbonyls generation and the heat shock proteins Hsp 70 and Hsp 27 expressions in liver. We also looked for an eventual protective effect against AFB1-induced genotoxicity as determined by chromosome aberrations test, SOS Chromotest and DNA fragmentation assay. We further evaluated the modulation of p53, bax and bcl2 protein expressions in liver.

Methods

Adult, healthy balbC (20-25 g) male mice were pre-treated by intraperitonial administration of CCE (50 mg/Kg.b.w) for 2 weeks. Control animals were treated 3 days a week for 4 weeks by intraperitonial administration of 250 μg/Kg.b.w AFB1. Animals treated by AFB1 and CCE were divided into two groups: the first group was administrated CCE 2 hours before each treatment with AFB1 3 days a week for 4 weeks. The second group was administrated without pre-treatment with CCE but this extract was administrated 24 hours after each treatment with AFB1 3 days a week for 4 weeks.

Results

Our results clearly showed that AFB1 induced significant alterations in oxidative stress markers. In addition, it has a genotoxic potential and it increased the expression of pro apoptotic proteins p53 and bax and decreased the expression of bcl2. The treatment of CCE before or after treatment with AFB1, showed (i) a total reduction of AFB1 induced oxidative damage markers, (ii) an anti-genotoxic effect resulting in an efficient prevention of chromosomal aberrations and DNA fragmentation compared to the group treated with AFB1 alone (iii) restriction of the effect of AFB1 by differential modulation of the expression of p53 which decreased as well as its associated genes such as bax and bcl2.

Conclusion

We concluded that CCE might have a hepatoprotective effect against aflatoxicosis in mice, probably acting by promoting the antioxidant defence systems.     

Alzheimer’s disease — The ways of prevention

Several vascular and lifestyle related factors have been suggested to influence the development of dementia and Alzheimer's disease (AD), creating new prevention opportunities. This paper discusses current epidemiological evidence and new findings from the Finnish population based CAIDE study linking some of these factors to dementia/AD. Such findings provide an optimistic outlook especially for persons with genetic susceptibility; it may be possible to reduce the risk or postpone the onset of dementia by adopting healthy lifestyle options. The interplay of genes and environment in the aetiology of AD needs to be further investigated as well as the role of lifestyle and pharmacological interventions for the prevention of dementia.     

Parents’ perceptions of the role of schools in tobacco use prevention and cessation for youth

The purpose of this study was to examine Ohio parents’ perceptions of the role of schools in smoking prevention, cessation, and anti-tobacco policy for their children. A 46-item questionnaire was based on the CDC Guidelines for School Health Programs to Prevent Tobacco Use and Addiction. Surveys (n = 800) were sent to a stratified random sample of parents of junior high and high school aged students and 57% responded. Parents were supportive of smoking prevention activities, but almost two-thirds believed their child’s school should get parents’ input. Furthermore, mothers/step-mothers were more likely than fathers/step-fathers to agree that the school had a role in smoking prevention activities. The majority of parents were also supportive of smoking cessation activities. However, only 8% of parent respondents supported schools providing nicotine gum or patches to students trying to quit smoking. Overall, the majority of parents were supportive of the seven recommendations developed by the CDC as guidelines for school health programs to prevent tobacco use and addiction. Schools have the opportunity to impact student smoking through prevention and cessation activities. Schools need to know that parents are supportive of these activities and want to be included in the process of implementing effective prevention or cessation programs.Jodi Wyman is a Research Assistant, James H. Price, Professor of Public Health, Timothy R. Jordan, Assistant Professor of Public Health, and Susan K. Telljohann, Professor of Health Education, all are affiliated to University of Toledo, Toledo, OH, USA; Joseph A. Dake is Assistant Professor of Health Education, Wayne State University, Detroit, MI, USA.     

‘Pure’ drug users,commercial sex workers and ‘ordinary girls’: gendered narratives of HIV risk and prevention in post-Soviet Ukraine

Abstract

International best practices call for a gender-responsive approach to HIV prevention for women, including those who use drugs and those who engage in sex work. This paper draws on multiple qualitative data sources collected over five years in Ukraine to explore the notions of gender, women and family that buttress HIV-related programmes for women. Our analysis reveals that service providers often cast women as hapless victims of unfortunate family circumstances and troubled personal relationships that produce sudden poverty, or social strivers who seek access to wealth and privilege at the expense of their health. Women are portrayed as most vulnerable to HIV when they lack a male ‘protector’. We argue that the programmes constituted around these stereotypes of women and their vulnerabilities reflect new forms of institutional power that deflect attention away from gendered socio-economic processes that contribute to women’s HIV vulnerability, including job insecurity and unemployment, workplace discrimination, unreliable social benefits and power imbalances within their relationships. We explore how to transform HIV prevention efforts to better address the causes of women’s increased vulnerability to HIV in Ukraine and in Eastern Europe more generally.     

Translating ‘distress’ and screening for emotional distress in multicultural cancer patients in Israel

Background  

The adaptability of the distress thermometer (DT) to multicultural groups has rarely been assessed.     

Oncologists’ and family physicians’ views on value for money of cancer and congestive heart failure care

Background

Previous studies suggest that cancer-related interventions are valued by policy makers more favorably than interventions for other medical conditions, but the views of practicing physicians have not yet been assessed in Israel. Attitudes and judgments of practicing physicians may assist decision-makers in their deliberations on coverage of new technologies. We conducted a national survey in Israel among oncologists and family physicians to explore their views on access to care, coverage decisions and treatment recommendations for cancer and congestive heart failure (CHF) patients.

Methods

We administered a web-based survey to 300 family physicians and 156 oncologists. The questionnaire included 24 statements and physicians were asked to indicate their level of agreement with each statement on a 5-point Likert scale, ranging from “strongly agree” to “strongly disagree”. Where relevant, physicians were asked to express their views on interventions for cancer and CHF respectively.

Results

Response rates were 39% for family physicians and 36% for oncologists. Participants expressed similar views on cancer and CHF care and no significant differences were found between the two medical specialties. More than 85% of physicians believe that inclusion of a treatment in the National List of Health Services (NLHS) strongly affects their patients’ access to care. Approximately 80% suggest that more use of comparative-effectiveness and cost-effectiveness analysis is needed in coverage decisions. The vast majority of respondents (75%) suggest that assessment of value-for-money should be made by an independent (academic) institution or the national committee responsible for recommending coverage decisions, Seventy percent believe that treatments not included in the NLHS should be included in supplementary health insurance programs and only a small minority of respondents (<30%) believe that cancer-related interventions should receive higher priority than non-cancer interventions in coverage decisions.

Conclusions

Our findings suggest that both oncologists and family physicians value cancer and CHF interventions equally. We could not find evidence for a “cancer premium” as implied from previous surveys and analysis of coverage decisions in various countries.

     

HIV epidemic control—a model for optimal allocation of prevention and treatment resources

With 33 million people living with human immunodeficiency virus (HIV) worldwide and 2.7 million new infections occurring annually, additional HIV prevention and treatment efforts are urgently needed. However, available resources for HIV control are limited and must be used efficiently to minimize the future spread of the epidemic. We develop a model to determine the appropriate resource allocation between expanded HIV prevention and treatment services. We create an epidemic model that incorporates multiple key populations with different transmission modes, as well as production functions that relate investment in prevention and treatment programs to changes in transmission and treatment rates. The goal is to allocate resources to minimize R ₀, the reproductive rate of infection. We first develop a single-population model and determine the optimal resource allocation between HIV prevention and treatment. We extend the analysis to multiple independent populations, with resource allocation among interventions and populations. We then include the effects of HIV transmission between key populations. We apply our model to examine HIV epidemic control in two different settings, Uganda and Russia. As part of these applications, we develop a novel approach for estimating empirical HIV program production functions. Our study provides insights into the important question of resource allocation for a country’s optimal response to its HIV epidemic and provides a practical approach for decision makers. Better decisions about allocating limited HIV resources can improve response to the epidemic and increase access to HIV prevention and treatment services for millions of people worldwide.     

‘At risk by fact of birth’: perceptions and concerns about medical male circumcision for HIV prevention in northern Malawi

In this article, we draw on critical approaches to risk to examine varied and interlaced perceptions of personal risk for HIV which young men in an area of traditionally low male circumcision have to Malawi government’s new policy of medical male circumcision for HIV prevention, locally known as mdulidwe. In this article, we draw on data from in-depth interviews (n = 29) and focus groups (n = 24) with young men aged 18–24 years undertaken in 2013 in an area with traditionally low rates of circumcision, Livingstonia in the northern region district of Malawi. Our findings show that the push for medical male circumcision in this region has given rise to a perception that the penile foreskin is an inborn anomaly that leads to excessive risk for HIV provoking anxiety, confusion, uncertainty, fatalistic views, and waning faith in national response to the epidemic. Our analysis of the data indicates that medical male circumcision has ushered in a layered and sometimes conflicting understanding of risk for HIV/AIDS where established ideas grounded in sexual propriety and risk-taking are being re-evaluated and reinterpreted within an emerging worldview coloured with sensibilities pertaining to notions of bodily normalcy. This indicates that the men in our study had a nuanced understanding of risk for HIV that incorporated notions of sexual risk-taking with corporeal impropriety, necessitating appropriate public risk communication about HIV/AIDS and policy responses for its prevention.     

What is a ‘generic’ hospital model?—a comparison of ‘generic’ and ‘specific’ hospital models of emergency patient flows

The paper addresses the question in the title via a survey of experienced healthcare modellers and an extensive literature review. It has two objectives.

‘Dirty looks’ and ‘trampy places’ in young people's accounts of community and neighbourhood: Implications for health inequalities

This paper draws on preliminary data collected in an ongoing school-based research project for the Health Education Authority (HEA) which is exploring Putnam's (1993) concept of 'social capital' in relation to children and young people's well-being and health. Putnam's conceptualization of social capital consists of the following features: trust, reciprocal support, civic engagement, community identity, and social networks; and the premise is that levels of social capital in a community have an important effect on people's well-being. A range of qualitative methods have been used to elicit 12-15 year olds' views of friendship networks and neighbourhoods: (1) written accounts of out-of-school activities, who is important, definitions of 'friend', future aspirations and social networks (2) visual methods including map drawing and photography by the participants and (3) group discussions exploring use of and perceptions of neighbourhoods, and community and institutional participation. The paper presents data, which suggest that young people face many paradoxes and contradictions in their environments that on the one hand support them and on the other hand exclude them. They often seem to develop their own 'communities' in the face of a strongly felt hostility from the adults around them. The paper concludes firstly that age is an important structuring principle which needs to be taken into account when considering entitlements to use of public space within neighbourhoods, and secondly that how young people use and experience communal areas is likely to have an important effect on their sense of community identity and ultimately their well-being.     

Structure and agency in long-distance truck drivers’ lived experiences of condom use for HIV prevention

Condom promotion has emerged as a mainstay of targeted HIV prevention interventions in India, with its emphasis on individual behaviour change and personal responsibility. However, such approaches often do not account for marginalised populations’ structural vulnerability to HIV, arising from social, economic and political factors in the lived environment. In this paper, I use a critical health communication framework to analyse how structure and agency interact in influencing condom use among long-distance truck drivers in India. Drawing on an abductive discourse analysis of condom-use discourses among truckers and peer educators in two Indian cities, findings reveal that while truckers understand the biomedical logic of condoms as barriers, they also express anxiety about condom breakage and experience structural barriers to condom use. The paper concludes by calling for greater attention to structural vulnerabilities in future HIV prevention efforts with truck drivers.     

HIV prevention: Making male circumcision the ‘right’ tool for the job

In recent years, HIV/AIDS programming has been transformed by an ostensibly ‘new’ procedure: male circumcision. This article examines the rise of male circumcision as the ‘right’ HIV prevention tool. Treating this controversial topic as a ‘matter of concern’ rather than a ‘matter of fact’, I examine the reasons why male circumcision came to be seen as a partial solution to the problem of HIV transmission in the twenty-first century and to what effect. Grounded in a close reading of the primary literature, I suggest that the embrace of male circumcision in HIV prevention must be understood in relation to three factors: (1) the rise of evidence-based medicine as the dominant paradigm for conceptualising medical knowledge, (2) the fraught politics of HIV/AIDS research and funding, which made the possibility of a biomedical intervention attractive and (3) underlying assumptions about the nature of African ‘culture’ and ‘sexuality’. I conclude by stressing the need to expand the parameters of the debate beyond the current polarised landscape, which presents us with a problematic either/or scenario regarding the efficacy of male circumcision.