Dietary glycaemic index, glycaemic load and breast cancer risk: a systematic review and meta-analysis

This systematic review aimed to examine if an association exists between dietary glycaemic index (GI) and glycaemic load (GL) intake and breast cancer risk. A systematic search was conducted in Medline and Embase and identified 14 relevant studies up to May 2008. Adjusted relative risk estimates comparing breast cancer risk for the highest versus the lowest category of GI/GL intake were extracted from relevant studies and combined in meta-analyses using a random-effects model. Combined estimates from six cohort studies show non-significant increased breast cancer risks for premenopausal women (relative risk (RR) 1.14, 95% CI 0.95-1.38) and postmenopausal women (RR 1.11, 95% CI 0.99-1.25) consuming the highest versus the lowest category of GI intake. Evidence of heterogeneity hindered analyses of GL and premenopausal risk, although most studies did not observe any significant association. Pooled cohort study results indicated no association between postmenopausal risk and GL intake (RR 1.03, 95% CI 0.94-1.12). Our findings do not provide strong support of an association between dietary GI and GL and breast cancer risk. © 2008 Cancer Research UK.


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Glycemic index, glycemic load, and risk of digestive tract neoplasms: a systematic review and meta-analysis

Background: Habitual consumption of diets with a high glycemic index (GI) and a high glycemic load (GL) may influence cancer risk via hyperinsulinemia and the insulin-like growth factor axis.
Objective: The objective was to conduct a systematic review to assess the association between GI, GL, and risk of digestive tract cancers.
Design: Medline and Embase were searched for relevant publications from inception to July 2008. When possible, adjusted results from a comparison of cancer risk of the highest compared with the lowest category of GI and GL intake were combined by using random-effects meta-analyses.
Results: Cohort and case-control studies that examined the risk between GI or GL intake and colorectal cancer (n = 12) and adenomas (n = 2), pancreatic cancer (n = 6), gastric cancer (n = 2), and squamous-cell esophageal carcinoma (n = 1) were retrieved. Most case-control studies observed positive associations between GI and GL intake and these cancers. However, pooled cohort study results showed no associations between colorectal cancer risk and GI intake [relative risk (RR): 1.04; 95% CI: 0.92, 1.12; n = 7 studies] or GL intake (RR: 1.06; 95% CI: 0.95, 1.17; n = 8 studies). Furthermore, no significant associations were observed in meta-analyses of cohort study results of colorectal cancer subsites and GI and GL intake. Similarly, no significant associations emerged between pancreatic cancer risk and GI intake (RR: 0.99; 95% CI: 0.83, 1.19; n = 5 studies) or GL intake (RR: 1.01; 95% CI: 0.86, 1.19; n = 6 studies) in combined cohort studies.
Conclusions: The findings from our meta-analyses indicate that GI and GL intakes are not associated with risk of colorectal or pancreatic cancers. There were insufficient data available regarding other digestive tract cancers to make any conclusions about GI or GL intake and risk.

Spatial attentional bias as a marker of genetic risk, symptom severity, and stimulant response in ADHD

Attention-deficit hyperactivity disorder (ADHD) is a heritable childhood onset disorder that is marked by variability at multiple levels including clinical presentation, cognitive profile, and response to stimulant medications. It has been suggested that this variability may reflect etiological differences, particularly, at the level of underlying genetics. This study examined whether an attentional phenotype-spatial attentional bias could serve as a marker of symptom severity, genetic risk, and stimulant response in ADHD. A total of 96 children and adolescents with ADHD were assessed on the Landmark Task, which is a sensitive measure of spatial attentional bias. All children were genotyped for polymorphisms (30 untranslated (UTR) and intron 8 variable number of tandem repeats (VNTRs)) of the dopamine transporter gene (DAT1). Spatial attentional bias correlated with ADHD symptom levels and varied according to DAT1 genotype. Children who were homozygous for the 10-repeat allele of the DAT1 30-UTR VNTR displayed a rightward attentional bias and had higher symptom levels compared to those with the low-risk genotype. A total of 26 of these children who were medication naive performed the Landmark Task at baseline and then again after 6 weeks of stimulant medication. Left-sided inattention (rightward bias) at baseline was associated with an enhanced response to stimulants at 6 weeks. Moreover, changes in spatial bias with stimulant medications, varied as a function of DAT1 genotype. This study suggests an attentional phenotype that relates to symptom severity and genetic risk for ADHD, and may have utility in predicting stimulant response in ADHD.

Inflammation and Anti-inflammatory strategies for alzheimer disease a mini review

Until recently, the central nervous system (CNS) has been thought to be an immune privileged organ. However, it is now understood that neuroinflammation is linked with the development of several CNS diseases including late-onset Alzheimer's disease (LOAD). The development of inflammation is a complex process involving a wide array of molecular interactions which in the CNS remains to be further characterized. The development of neuroinflammation may represent an important link between the early stages of LOAD and its pathological outcome. It is proposed that risks for LOAD, which include genetic, biological and environmental factors can each contribute to impairment of normal CNS regulation and function. The links between risk factors and the development of neuroinflammation are numerous and involve many complex interactions which contribute to vascular compromise, oxidative stress and ultimately neuroinflammation. Once this cascade of events is initiated, the process of neuroinflammation can become overactivated resulting in further cellular damage and loss of neuronal function. Additionally, neuroinflammation has been associated with the formation of amyloid plaques and neurofibrillary tangles, the pathological hallmarks of LOAD. Increased levels of inflammatory markers have been correlated with an advanced cognitive impairment. Based on this knowledge, new therapies aimed at limiting onset of neuroinflammation could arrest or even reverse the development of the disease.

The perspectives of young children in care about their circumstances and implications for social work practice

Recent reviews of research regarding children in care have concluded that there remains little research which specifically focuses on young children. This paper presents the findings of research carried out with a sample of young children in care (aged 4-7 years) regarding their perspectives of their circumstances. The findings reveal that they have deeply held views regarding living with risk; removal from their families; unresolved feelings of guilt and loss; and not being listened to. This paper considers the implications of these findings for social work practice. It concludes by stressing the capacity of young children in care to express their perspectives, and the importance of practitioners seeking these views and incorporating them into assessment and decision-making processes.

Tumor Risks and Genotype-Phenotype-Proteotype Analysis in 358 Patients With Germline Mutations in SDHB and SDHD

Succinate dehydrogenase B (SDHB) and D (SDHD) subunit gene mutations predispose to adrenal and extraadrenal pheochromocytomas, head and neck paragangliomas (HNPGL), and other tumor types. We report tumor risks in 358 patients with SDHB (n = 295) and SDHD (n = 63) mutations. Risks of HNPGL and pheochromocytoma in SDHB mutation carriers were 29% and 52%, respectively, at age 60 years and 71% and 29%, respectively, in SDHD mutation carriers. Risks of malignant pheochromocytoma and renal tumors (14% at age 70 years) were higher in SDHB mutation carriers; 55 different mutations (including a novel recurrent exon 1 deletion) were identified. No clear genotype-phenotype correlations were detected for SDHB mutations. However, SDHD mutations predicted to result in loss of expression or a truncated or unstable protein were associated with a significantly increased risk of pheochromocytoma compared to missense mutations that were not predicted to impair protein stability (most such cases had the common p.Pro81Leu mutation). Analysis of the largest cohort of SDHB/D mutation carriers has enhanced estimates of penetrance and tumor risk and supports in silicon protein structure prediction analysis for functional assessment of mutations. The differing effect of the SDHD p.Pro81Leu on HNPGL and pheochromocytoma, risks suggests differing mechanisms of tumorigenesis in SDH-associated HNPGL and pheochromocytoma. Hum Mutat 31:41-51, 2010. (C) 2009 Wiley-Liss, Inc.

TheShifting Sands of Uncertainty: Risk Construction and BSE/vCJD

It is more than a decade since scientists in the UK put forward evidence of a link between the emergence of a new variant of Creutzfeldt-Jakob Disease (vCJD) in humans, and a diminishing epidemic of Bovine Spongiform Encephalopathy, or BSE, in cattle. In the wake of this anniversary, the paper revisits two scientific narratives of risk, forged at different points along the developmental pathway of BSE science, including a series of advisory reports provided to the UK government between 1989 and 1994, and a symposium held in 2001 to assess the impact of the Phillips Inquiry. While the primary pathology of BSE became apparent relatively early on, uncertainties remain about the origins of BSE and its human variant, vCJD. The paper examines the handling of this sensitivity, and its communication, within these key documents, noting changes in patterns of uncertainty construction over time.

Risk: A Study of Its Origins, History and Politics

Over a period of several centuries, the academic study of risk has evolved as a distinct body of thought, which continues to influence conceptual developments in fields such as economics, management, politics and sociology. However, few scholarly works have given a chronological account of cultural and intellectual trends relating to the understanding and analysis of risks. Risk: A Study of its Origins, History and Politics aims to fill this gap by providing a detailed study of key turning points in the evolution of society's understanding of risk. Using a wide range of primary and secondary materials, Matthias Beck and Beth Kewell map the political origins and moral reach of some of the most influential ideas associated with risk and uncertainty at specific periods of time. The historical focus of the book makes it an excellent introduction for readers who wish to go beyond specific risk management techniques and their theoretical underpinnings, to gain an understanding of the history and politics of risk.

Concise Review: Stem Cell Effects in Radiation Risk

Stem cells of normal mammalian tissues are defined as nonspecialized cells that have two critical properties: (a) the ability to renew themselves through cell division and (b) the potency to differentiate into other cell types. Therefore, they play a crucial role in development and in tissue homeostasis during adult life. Being long-lived, they can be the targets of environmental carcinogens leading to the accumulation of consecutive genetic changes. Hence, the genome of stem cells must be exceptionally well protected, and several protective mechanisms have evolved to ensure the genetic integrity of the stem cell compartment in any given tissue. Ionizing radiation exposure can disrupt tissue homeostasis both through the induction of cell killing/depletion of radiosensitive stem cells, leading to loss of tissue functionality and by genotoxic damage, increasing overall risk of cancer. We will review the current knowledge about radiation effects in adult stem cells of specific normal tissues, including skin, breast, and brain, examine parallels, as well as differences with cancer stem cells, and discuss the relevance of stem cell effects to radiation risk and radiotherapy. STEM CELLS 2011;29:1315-1321

Unfunded pension liabilities and sponsoring firm credit risk: an international analysis of corporate bond spreads

This paper tests empirically whether pension information derived by corporate pension accounting disclosures is priced in corporate bond spreads. The model represents a hybrid of more traditional accounting ratio-based models of credit risk and structural models of bond spreads initiated by Merton (1974). The model is fitted to 5 years of data from 2002 to 2006 featuring companies from the US and Europe. The paper finds that while unfunded pension liabilities are priced in the overall sample, they are not priced as aggressively as traditional leverage. Furthermore, an extended model shows that the pension–credit risk relation is most evident in the US and Germany, where unfunded pension liabilities are priced more aggressively than traditional forms of leverage. No pension–credit risk relation is found in the other countries sampled, notably the UK, Netherlands and France.

Evidence for Alteration of EZH2, BMI1, and KDM6A and Epigenetic Reprogramming in Human Papillomavirus Type 16 E6/E7-Expressing Keratinocytes

A number of epigenetic alterations occur in both the virus and host cellular genomes during human papillomavirus (HPV)-associated carcinogenesis, and investigations of such alterations, including changes in chromatin proteins and histone modifications, have the potential to lead to therapeutic epigenetic reversion. We report here that transformed HPV16 E6/E7-expressing primary human foreskin keratinocytes (HFKs) (E6/E7 cells) demonstrate increased expression of the PRC2 methyltransferase EZH2 at both the mRNA and protein levels but do not exhibit the expected increase in trimethylated H3K27 (H3K27me3) compared to normal keratinocytes. In contrast, these cells show a reduction in global H3K27me3 levels in vitro, as well as upregulation of the KDM6A demethylase. We further show for the first time that transformation with the HPV16 E6 and E7 oncogenes also results in an increase in phosphorylated EZH2 serine 21 (P-EZH2-Ser21), mediated by active Akt, and in a downregulation of the PRC1 protein BMI1 in these cells. High-grade squamous cervical intraepithelial lesions also showed a loss of H3K27me3 in the presence of increased expression of EZH2. Correlating with the loss of H3K27me3, E6/E7 cells exhibited derepression of specific EZH2-, KMD6A-, and BMI1-targeted HOX genes. These results suggest that the observed reduction in H3K27me3 may be due to a combination of reduced activities/levels of specific polycomb proteins and increases in demethylases. The dysregulation of multiple chromatin proteins resulting in the loss of global H3K27me3 and the transcriptional reprogramming in HPV16 E6/E7-infected cells could provide an epigenetic signature associated with risk and/or progression of HPV16-associated cancers, as well as the potential for epigenetic reversion in the future.

Dynamic mechanical analysis of polymeric systems of pharmaceutical and biomedical significance

Dynamic mechanical analysis (DMA) is an analytical technique in which an oscillating stress is applied to a sample and the resultant strain measured as functions of both oscillatory frequency and temperature. From this, a comprehensive knowledge of the relationships between the various viscoelastic parameters, e.g. storage and loss moduli, mechanical damping parameter (tan delta), dynamic viscosity, and temperature may be obtained. An introduction to the theory of DMA and pharmaceutical and biomedical examples of the use of this technique are presented in this concise review. In particular, examples are described in which DMA has been employed to quantify the storage and loss moduli of polymers, polymer damping properties, glass transition temperature(s), rate and extent of curing of polymer systems, polymer-polymer compatibility and identification of sol-gel transitions. Furthermore, future applications of the technique for the optimisation of the formulation of pharmaceutical and biomedical systems are discussed. (C) 1999 Elsevier Science B.V. All rights reserved.

The Governance of Sexual Offending Across Europe: Penal Policies, Political Economies and the Institutionalization of Risk

This article examines why England and Wales have comparatively one of the most stringent systems for the governance of sexual offending within Western Europe. While England and Wales, like the USA, have adopted broadly exclusionary, managerialist penal policies based around incapacitation and targeted surveillance, many other Western European countries have opted for more inclusionary therapeutic interventions. Divergences in state approaches to sex offender risk, particularly in relation to notification and vetting schemes, are initially examined with reference to the respective theoretical frameworks of ‘policy transfer’ and differing political economies. Chiefly, however, differences in penal policies are attributed to the social and political construction of risk and its control. There may be multiple expressions of risk relating to expert, lay, moral or emotive aspects. It is argued, however, that it is the particular convergence and alignment of these dimensions on the part of the various stakeholders in the UK – government, media, public and professional – that leads to risk becoming institutionalized in the form of punitive regulatory policies for managing the dangerous.

Breast Cancer Risk in Relation to Occupations with Exposure to Carcinogens and Endocrine Disruptors:a Canadian Case-Control Study

Background

Endocrine disrupting chemicals and carcinogens, some of which may not yet have been classified as such, are present in many occupational environments and could increase breast cancer risk. Prior research has identified associations with breast cancer and work in agricultural and industrial settings. The purpose of this study was to further characterize possible links between breast cancer risk and occupation, particularly in farming and manufacturing, as well as to examine the impacts of early agricultural exposures, and exposure effects that are specific to the endocrine receptor status of tumours.

Methods

1005 breast cancer cases referred by a regional cancer center and 1147 randomly-selected community controls provided detailed data including occupational and reproductive histories. All reported jobs were industry- and occupation-coded for the construction of cumulative exposure metrics representing likely exposure to carcinogens and endocrine disruptors. In a frequency-matched case?control design, exposure effects were estimated using conditional logistic regression.

Results

Across all sectors, women in jobs with potentially high exposures to carcinogens and endocrine disruptors had elevated breast cancer risk (OR = 1.42; 95% CI, 1.18-1.73, for 10 years exposure duration). Specific sectors with elevated risk included: agriculture (OR = 1.36; 95% CI, 1.01-1.82); bars-gambling (OR = 2.28; 95% CI, 0.94-5.53); automotive plastics manufacturing (OR = 2.68; 95% CI, 1.47-4.88), food canning (OR = 2.35; 95% CI, 1.00-5.53), and metalworking (OR = 1.73; 95% CI, 1.02-2.92). Estrogen receptor status of tumors with elevated risk differed by occupational grouping. Premenopausal breast cancer risk was highest for automotive plastics (OR = 4.76; 95% CI, 1.58-14.4) and food canning (OR = 5.70; 95% CI, 1.03-31.5).

Conclusions

These observations support hypotheses linking breast cancer risk and exposures likely to include carcinogens and endocrine disruptors, and demonstrate the value of detailed work histories in environmental and occupational epidemiology.