Two-year carcinogenicity study of acrylamide in Wistar Han rats with in utero exposure

AbstractAcrylamide is an important chemical with widespread industrial and other uses in addition to generalized population exposure from certain cooked foods. Previous rat studies to assess the carcinogenic potential of acrylamide have been carried out exclusively in the Fischer 344 rat with identification of a number of tumors amongst which mesotheliomas of the tunica vaginalis is an important tumor endpoint in the classification of acrylamide as a ‘probably human carcinogen. In a rat carcinogenicity study to determine the human relevance of mesotheliomas Wistar Han rats were exposed to 0, 0.5, 1.5, or 3.0mg acrylamide/kg body weight/day in drinking water starting at gestation day 6. At the end of two years, mammary gland fibroadenomas in females and thyroid follicular cell tumors in both sexes were the only tumors increased in acrylamide treated rats. These tumor endpoints have rat-specific modes of action suggesting less likelihood of human cancer risk than previously estimated. This study demonstrates that tunica vaginalis mesotheliomas are strain specific and not likely of genotoxic origin

Customers' perspectives on the impact of the Pathways to Work Condition Management Programme on their health, wellbeing and vocational activity

Aims: Pathways to Work is a UK initiative aimed at supporting customers on incapacity benefits to return to work. This qualitative study complements previous evaluations of Pathways to Work by exploring customers’ perceptions of the impact of the Condition Management Programme (CMP) offered to claimants with long-term health conditions. Methods: 39 customers took part in focus groups held at the seven sites where Pathways was originally piloted. The main focus of the discussions was on perceptions of the ways in which participation had impacted on health, well-being and return to work. The discussions were audio-recorded and fully transcribed for analysis using a text analysis framework to enable the development and refinement of categories and overarching patterns in the data. Results: Perceived impacts on health and wellbeing included a more positive outlook, social contact, changed perceptions of conditions and improvements in health. Some customers also reported an increase in their vocational activity and others felt ready to embark on new activities. Factors associated with positive outcomes included the extent and quality of contact with CMP staff and practical advice about condition management. Factors impeding positive employment outcomes related mainly to obstacles to returning to work. Conclusions: The results indicated that CMP can assist customers to learn about and manage their health conditions and increase their vocational activity, and that CMP therefore provides a promising means of enabling people with long-term health conditions to regain a fulfilling, productive life

Review of battery electric vehicle propulsion systems incorporating flywheel energy storage

The development of battery electric vehicles (BEV) must continue since this can lead us towards a zero emission transport system. There has been an advent of the production BEVs in recent years; however their low range and high cost still remain the two important drawbacks. The battery is the element which strongly affects the cost and range of the BEV. The batteries offer either high specific power or high specific energy but not both. To provide the BEVs with the characteristic to compete with conventional vehicles it is beneficial to hybridize the energy storage combining a high energy battery with a high power source. This shields the battery from peak currents and improves its capacity and life. There are various devices which could qualify as a secondary storage system for the BEV such as high power battery, supercapacitor and high speed flywheel (FW). This paper aims to review a specific type of hybridisation of energy storage which combines batteries and high speed flywheels. The flywheel has been used as a secondary energy system in BEVs from the early 1970s when the oil crises triggered an interest in BEVs. Since the last decade the interest in flywheels has strengthened and their application in the kinetic energy recovery system (KERS) in Formula 1 has further bolstered the case for flywheels. With a number of automotive manufacturers getting involved in developing flywheels for road applications, the authors believe commercial flywheel based powertrains are likely to be seen in the near future. It is hence timely to produce a review of research and development in the area of flywheel assisted BEVs

The positive outlook study- a randomised controlled trial evaluating the effectiveness of an online self-management program targeting psychosocial issues for men living with HIV: a study protocol

Background: The emergence of HIV as a chronic condition means that people living with HIV are required to takemore responsibility for the self-management of their condition, including making physical, emotional and socialadjustments. This paper describes the design and evaluation of Positive Outlook, an online program aiming toenhance the self-management skills of gay men living with HIV.Methods/design: This study is designed as a randomised controlled trial in which men living with HIV in Australiawill be assigned to either an intervention group or usual care control group. The intervention group willparticipate in the online group program ‘Positive Outlook’. The program is based on self-efficacy theory and uses aself-management approach to enhance skills, confidence and abilities to manage the psychosocial issues associatedwith HIV in daily life. Participants will access the program for a minimum of 90 minutes per week over seven weeks.Primary outcomes are domain specific self-efficacy, HIV related quality of life, and outcomes of health education.Secondary outcomes include: depression, anxiety and stress; general health and quality of life; adjustment to HIV;and social support. Data collection will take place at baseline, completion of the intervention (or eight weeks postrandomisation) and at 12 week follow-up.Discussion: Results of the Positive Outlook study will provide information regarding the effectiveness of onlinegroup programs improving health related outcomes for men living with HIV

Isolated hypercholesterolemia leads to steatosis in the liver without affecting the pancreas

Abstract Background Lipid accumulation in the liver and pancreas is primarily caused by combined hyperlipidemia. However, the effect of isolated hypercholesterolemia without hypertriglyceridemia is not fully described. Therefore, our aim was to investigate whether hypercholesterolemia alone leads to alterations both in hepatic and pancreatic lipid panel and histology in rats. Methods Male Wistar rats were fed with 2% cholesterol +0.25% cholate-supplemented diet or standard chow for 12 weeks. Blood was collected at weeks 0, 4, 8 and 12 to measure serum cholesterol and triglyceride levels. At week 12, both the pancreas and the liver were isolated for further histological and biochemical analysis. Hepatic and plasma fatty acid composition was assessed by gas chromatography. Expression of mRNA of major enzymes involved in saturated/unsaturated fatty acid synthesis was analyzed by qPCR. In separate experiments serum enzyme activities and insulin levels were measured at week 9. Results At week 12, rats fed with 2% cholesterol +0.25% cholate-supplemented diet were characterized by elevated serum cholesterol (4.09 ± 0.20 vs. 2.89 ± 0.22 mmol/L, *p < 0.05) while triglyceride (2.27 ± 0.05 vs. 2.03 ± 0.03 mmol/L) and glucose levels (5.32 ± 0.14 vs. 5.23 ± 0.10 mmol/L) remained unchanged. Isolated hypercholesterolemia increased hepatic lipid accumulation, hepatic cholesterol (5.86 ± 0.22 vs. 1.60 ± 0.15 ng/g tissue, *p < 0.05) and triglyceride contents (19.28 ± 1.42 vs. 6.78 ± 0.71 ng/g tissue, *p < 0.05), and hepatic nitrotyrosine level (4.07 ± 0.52 vs. 2.59 ± 0.31 ng/mg protein, *p < 0.05). The histology and tissue lipid content of the pancreas was not affected. Serum total protein level, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities remained unchanged in response to isolated hypercholesterolemia while serum alkaline phosphatase activity (ALP) significantly increased. Plasma insulin levels did not change in response to isolated hypercholesterolemia suggesting an intact endocrine function of the pancreas. Isolated hypercholesterolemia caused a significantly increased hepatic and serum fatty acid level associated with a marked alteration of fatty acid composition. Hepatic expression of Δ9-desaturase (SCD1) was increased 4.92×, while expression of Δ5-desaturase and Δ6-desaturase were decreased (0.447× and 0.577×, respectively) due to isolated hypercholesterolemia. Conclusions Isolated hypercholesterolemia leads to hepatic steatosis and marked alterations in the hepatic lipid profile without affecting the pancreas. Altered fatty acid profile might mediate harmful effects of cholesterol in the liver

Programming of metabolic effects in C57BL/6JxFVB mice by in utero and lactational exposure to perfluorooctanoic acid

Perfluorooctanoic acid (PFOA) is known to cause developmental toxicity and is a suggested endocrine disrupting compound (EDC). Early life exposure to EDCs has been implicated in programming of the developing organism for chronic diseases later in life. Here we study perinatal metabolic programming by PFOA using an experimental design relevant for human exposure. C57BL/6JxFVB hybrid mice were exposed during gestation and lactation via maternal feed to seven low doses of PFOA at and below the NOAEL used for current risk assessment (3–3000 μg/kg body weight/day). After weaning, offspring were followed for 23–25 weeks without further exposure. Offspring showed a dose-dependent decrease in body weight from postnatal day 4 to adulthood. Growth under high fat diet in the last 4–6 weeks of follow-up was increased in male and decreased in female offspring. Both sexes showed increased liver weights, hepatic foci of cellular alterations and nuclear dysmorphology. In females, reductions in perigonadal and perirenal fat pad weights, serum triglycerides and cholesterol were also observed. Endocrine parameters, such as glucose tolerance, serum insulin and leptin, were not affected. In conclusion, our study with perinatal exposure to PFOA in mice produced metabolic effects in adult offspring. This is most likely due to disrupted programming of metabolic homeostasis, but the assayed endpoints did not provide a mechanistic explanation. The BMDL of the programming effects in our study is below the current point of departure used for calculation of the tolerable daily intake.The authors wish to acknowledge the support of the biotechnicians from the team of Hans Strootman at the RIVM animal facilities. Further technical support was provided by Piet Beekhof, Hennie Hodemaekers, Sandra Imholz (RIVM), Mirjam Koster (UU), Stefan van Leeuwen (RIKILT), Jacco Koekkoek and Marja Lamoree (VU). This study was funded by the European Community’s Seventh Framework Programme [FP7/2007–2013] under grant agreement OBELIX 227391

Development of a supported self-management intervention for adults with type 2 diabetes and a learning disability

Background: Although supported self-management is a well-recognised part of chronic disease management, it has not been routinely used as part of healthcare for adults with a learning disability. We developed an intervention for adults with a mild or moderate learning disability and type 2 diabetes, building on the principles of supported self-management with reasonable adjustments made for the target population. Methods: In five steps, we: 1. Clarified the principles of supported self-management as reported in the published literature 2. Identified the barriers to effective self-management of type 2 diabetes in adults with a learning disability 3. Reviewed existing materials that aim to support self-management of diabetes for people with a learning disability 4. Synthesised the outputs from the first three phases and identified elements of supported self-management that were (a) most relevant to the needs of our target population and (b) most likely to be acceptable and useful to them 5. Implemented and field tested the intervention Results: The final intervention had four standardised components: (1) establishing the participant’s daily routines and lifestyle, (2) identifying supporters and their roles, (3) using this information to inform setting realistic goals and providing materials to the patient and supporter to help them be achieved and (4) monitoring progress against goals. Of 41 people randomised in a feasibility RCT, thirty five (85%) completed the intervention sessions, with over three quarters of all participants (78%) attending at least three sessions. Twenty-three out of 40 (58%) participants were deemed to be very engaged with the sessions and 12/40 (30%) with the materials; 30 (73%) participants had another person present with them during at least one of their sessions; 15/41 (37%) were reported to have a very engaged main supporter, and 18/41 (44%) had a different person who was not their main supporter but who was engaged in the intervention implementation. Conclusions: The intervention was feasible to deliver and, as judged by participation and engagement, acceptable to participants and those who supported them. Trial registration: Current Controlled Trials ISRCTN41897033 (registered 21/01/2013)