S-allylmercaptocysteine reduces carbon tetrachloride-induced hepatic oxidative stress and necroinflammation via nuclear factor kappa B-dependent pathways in mice.

Purpose To study the protective effects and underlying molecular mechanisms of SAMC on carbon tetrachloride (CCl4)-induced acute hepatotoxicity in the mouse model. Methods Mice were intraperitoneally injected with CCl4 (50 μl/kg; single dose) to induce acute hepatotoxicity with or without a 2-h pre-treatment of SAMC intraperitoneal injection (200 mg/kg; single dose). After 8 h, the blood serum and liver samples of mice were collected and subjected to measurements of histological and molecular parameters of hepatotoxicity. Results SAMC reduced CCl4-triggered cellular necrosis and inflammation in the liver under histological analysis. Since co-treatment of SAMC and CCl4 enhanced the expressions of antioxidant enzymes, reduced the nitric oxide (NO)-dependent oxidative stress, and inhibited lipid peroxidation induced by CCl4. SAMC played an essential antioxidative role during CCl4-induced hepatotoxicity. Administration of SAMC also ameliorated hepatic inflammation induced by CCl4 via inhibiting the activity of NF-κB subunits p50 and p65, thus reducing the expressions of pro-inflammatory cytokines, mediators, and chemokines, as well as promoting pro-regenerative factors at both transcriptional and translational levels. Conclusions Our results indicate that SAMC mitigates cellular damage, oxidative stress, and inflammation in CCl4-induced acute hepatotoxicity mouse model through regulation of NF-κB. Garlic or garlic derivatives may therefore be a potential food supplement in the prevention of liver damage.

Drugs for diabetes and obesity

14.1 Drugs for diabetes 14.1.1 Diabetes mellitus 14.1.2 Physiology of the pancreas 14.1.3 Insulin replacement therapy 14.1.4 Metformin 14.1.5 Acarbose 14.1.6 Sulfonylureas 14.1.7 Glitazones 14.1.8 Glucagon-like peptide-1, exenatide and sitagliptin 14.2 Drugs for obesity 14.2.1 Introduction 14.2.2 Amphetamine 14.2.3 Phentermine 14.2.5 Orlistat

Randomised controlled trial of an automated, interactive telephone intervention (TLC Diabetes) to improve type 2 diabetes management : Baseline findings and six-month outcomes

Background: Effective self-management of diabetes is essential for the reduction of diabetes-related complications, as global rates of diabetes escalate. Methods: Randomised controlled trial. Adults with type 2 diabetes (n = 120), with HbA1c greater than or equal to 7.5 %, were randomly allocated (4 × 4 block randomised block design) to receive an automated, interactive telephone-delivered management intervention or usual routine care. Baseline sociodemographic, behavioural and medical history data were collected by self-administered questionnaires and biological data were obtained during hospital appointments. Health-related quality of life (HRQL) was measured using the SF-36. Results: The mean age of participants was 57.4 (SD 8.3), 63 % of whom were male. There were no differences in demographic, socioeconomic and behavioural variables between the study arms at baseline. Over the six-month period from baseline, participants receiving the Australian TLC (Telephone-Linked Care) Diabetes program showed a 0.8 % decrease in geometric mean HbA1c from 8.7 % to 7.9 %, compared with a 0.2 % HbA1c reduction (8.9 % to 8.7 %) in the usual care arm (p = 0.002). There was also a significant improvement in mental HRQL, with a mean increase of 1.9 in the intervention arm, while the usual care arm decreased by 0.8 (p = 0.007). No significant improvements in physical HRQL were observed. Conclusions: These analyses indicate the efficacy of the Australian TLC Diabetes program with clinically significant post-intervention improvements in both glycaemic control and mental HRQL. These observed improvements, if supported and maintained by an ongoing program such as this, could significantly reduce diabetes-related complications in the longer term. Given the accessibility and feasibility of this kind of program, it has strong potential for providing effective, ongoing support to many individuals with diabetes in the future.

DRD2/ANKK1 Taq1A (rs 1800497 C>T) genotypes are associated with susceptibility to second generation antipsychotic-induced akathisia

Rationale Although the advent of atypical, second-generation antipsychotics (SGAs) has resulted in reduced likelihood of akathisia, this adverse effect remains a problem. Extrapyramidal adverse effects are associated with increased drug occupancy of dopamine 2 receptors (DRD2). The A1 allele of the DRD2/ANKK1,rs1800497, is associated with decreased striatal DRD2 density. Objectives The aim of this study was to identify whether the A1(T) allele of the DRD2/ANKK1 was associated with akathisia (measured with the Barnes Akathisia Rating Scale) in a clinical sample of 234 patients treated with antipsychotics. Results Definite akathisia (a score≥ 2 for the global clinical assessment of akathisia) was significantly less common in subjects prescribed SGAs (16.8 %) than those prescribed FGAs (47.6%), p<0.0001. Overall, 24.1% of A1+ (A1A2/A1A1) patients treated with SGAs had akathisia compared to 10.8% of A1- (A2A2) patients. A1+ (A1A2/A1A1) patients administered SGAs also had higher global clinical assessment of akathisia scores than A1- subjects (p=0.01). SGAs maintained their advantage over FGAs regarding akathisia even in A1+ patients treated with SGAs. Conclusions These results strongly suggest that A1+ variants of the DRD2/ANKK1 Taq1A allele confer risk for akathisia in patients treated with SGAs and may explain inconsistencies across prior studies comparing FGAs and SGAs.

Near work-induced contrast adaptation in emmetropic and myopic children

Purpose. Contrast adaptation may induce an error signal for emmetropization. This research aims to determine whether reading causes contrast adaptation in children and, if so, to determine whether myopes exhibit greater contrast adaptation than emmetropes. Methods. Baseline contrast sensitivity was determined in 34 emmetropic and 34 spectacle-corrected myopic children for 0.5, 1.2, 2.7, 4.4, and 6.2 cycles per degree (cpd) horizontal sine-wave gratings. Effects of near tasks on contrast sensitivity were determined during periods spent looking at a 6.2 cpd horizontal grating and during periods spent reading lines of English text, with 1.2 cpd row frequency and 6 cpd stroke frequency. Results. Both emmetropic and myopic groups (mean ± SD; age, 10.3 ± 1.4 years) showed reduced contrast sensitivity during both near tasks, with greatest overall adaptation at 6.2 cpd. Adaptation induced by viewing the grating (0.15 ± 0.17 log unit [40%]; range, 0.07-0.27 log unit) was significantly greater than adaptation induced by reading text (0.11 ± 0.18 log unit [29%], 0.08-0.16 log unit) (F(1,594) = 10.7; P = 0.001). Myopic children showed significantly greater adaptation across the tasks (0.15 ± 0.18 log unit [42%]) than emmetropic children (0.10 ± 0.16 log unit [26%]) (F(1,66) = 7.30; P = 0.009), with the greatest difference occurring at 4.4 cpd (mean, 0.11 log unit [30%]). Conclusions. Grating and reading tasks induced contrast adaptation; viewing horizontal gratings induced greater adaptation than reading, and myopes exhibited greater adaptation than emmetropes. Contrast adaptation effects may underlie findings of prolonged near work being associated with myopia. However, our research does not show whether this is consequential or causal.

Change-induced stressors and effective coping strategies in nursing

This study seeks to examine the causality of non-nursing and nursing stressors on the job satisfaction of nurses and how coping strategies have a mediating influence on this relationship in the context of sector-wide reform. To conceptualize the relationships, a mediation path model was developed. Data were collected at two time points using a self-completed online survey over a six monthly interval. During time 1, 306 Australian nurses completed the online survey. In the first wave (time 1), 306 Australian nurses completed the survey. In the second wave (time 2), matched survey data were collected from 119 nurses. The analysis showed a significant causal relationship between time 1 administrative and role stressors and an increase in nursing stress in time 2. A significant relationship was also identified between job specific context stressors and the adoption of effective coping strategies to deal with increased level of change-induced stress and strain and the likelihood of reporting higher level of job satisfaction in time 2. This study contributes by providing an integrated theoretical perspective on how stress affects retention that has so far been elusive. This is useful to researchers wanting to examine this phenomenon further and practitioners responsible for implementing change programs.

Variation in risk seeking behavior in a natural experiment following a large negative wealth shock induced by a natural disaster

An ongoing challenge in behavioral economics is to understand the variations observed in risk attitudes as a function of their environmental context. Of particular interest is the effect of wealth on risk attitudes. The research in this area has however faced two constraints: the difficulty to study the causal effects of large changes in wealth, and the causal effects of losses on risk behavior. The present paper address this double limitation by providing evidence of the variation of risk attitude after large losses using a natural disaster (Brisbane floods) as the setting for a natural experiment.

An extended theory of planned behavior intervention for older adults With Type 2 diabetes and cardiovascular disease

A randomized controlled trial evaluated the effectiveness of a 4-wk extended theory of planned behavior (TPB) intervention to promote regular physical activity and healthy eating among older adults diagnosed with Type 2 diabetes or cardiovascular disease (N = 183). Participants completed TPB measures of attitude, subjective norm, perceived behavioral control, and intention, as well as planning and behavior, at preintervention and 1 wk and 6 wk postintervention for each behavior. No significant time-by-condition effects emerged for healthy eating. For physical activity, significant time-by-condition effects were found for behavior, intention, planning, perceived behavioral control, and subjective norm. In particular, compared with control participants, the intervention group showed short-term improvements in physical activity and planning, with further analyses indicating that the effect of the intervention on behavior was mediated by planning. The results indicate that TPB-based interventions including planning strategies may encourage physical activity among older people with diabetes and cardiovascular disease.

Postpartum diet quality in Australian women following a gestational diabetes pregnancy

BACKGROUND/OBJECTIVES: To describe the diet quality of a national sample of Australian women with a recent history of gestational diabetes mellitus (GDM) and determine factors associated with adherence to national dietary recommendations. SUBJECTS/METHODS: A postpartum lifestyle survey with 1499 Australian women diagnosed with GDM p3 years previously. Diet quality was measured using the Australian recommended food score (ARFS) and weighted by demographic and diabetes management characteristics. Multinominal logistic regression analysis was used to determine the association between diet quality and demographic characteristics, health seeking behaviours and diabetes-related risk factors. RESULTS: Mean (±s.d.) ARFS was 30.9±8.1 from a possible maximum score of 74. Subscale component scores demonstrated that the nuts/legumes, grains and fruits were the most poorly scored. Factors associated with being in the highest compared with the lowest ARFS quintile included age (odds ratio (OR) 5-year increase=1.40; 95% (confidence interval) CI:1.16–1.68), tertiary education (OR=2.19; 95% CI:1.52–3.17), speaking only English (OR=1.92; 95% CI:1.19–3.08), being sufficiently physically active (OR=2.11; 95% CI:1.46–3.05), returning for postpartum blood glucose testing (OR=1.75; 95% CI:1.23–2.50) and receiving riskreduction advice from a health professional (OR=1.80; 95% CI:1.24–2.60). CONCLUSIONS: Despite an increased risk of type 2 diabetes, women in this study had an overall poor diet quality as measured by the ARFS. Women with GDM should be targeted for interventions aimed at achieving a postpartum diet consistent with the guidelines for chronic disease prevention. Encouraging women to return for follow-up and providing risk reduction advice may be positive initial steps to improve diet quality, but additional strategies need to be identified.

BRCA1 is an essential mediator of vinorelbine-induced apoptosis in mesothelioma

The rapeutic options for malignant pleural mesothelioma (MPM) are limited despite the increasing incidence globally. The vinca alkaloid vinorelbine exhibits clinical activity; however, to date, treatment optimization has not been achieved using biomarkers. BRCA1 regulates sensitivity to microtubule poisons; however, its role in regulating vinorelbine-induced apoptosis in mesothelioma is unknown. Here we demonstrate that BRCA1 plays an essential role in mediating vinorelbine-induced apoptosis, as evidenced by (1) the strong correlation between vinorelbine sensitivity and BRCA1 expression level; (2) induction of resistance to vinorelbine by BRCA1 using siRNA oligonucleotides; (3) dramatic down-regulation of BRCA1 following selection for vinorelbine resistance; and (4) the re-activation of vinorelbine-induced apoptosis following re-expression of BRCA1 in resistant cells. To determine whether loss of BRCA1 expression in mesothelioma was potentially relevant in vivo, BRCA1 immunohistochemistry was subsequently performed on 144 primary mesothelioma specimens. Loss of BRCA1 protein expression was identified in 38.9% of samples. Together, these data suggest that BRCA1 plays a critical role in mediating apoptosis by vinorelbine in mesothelioma, warranting its clinical evaluation as a predictive biomarker. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.