Cisplatin and taxol activate different signal pathways regulating cellular injury-induced expression of GADD153.

Signal transduction pathways activated by injury play a central role in coordinating the cellular responses that determine whether a cell survives or dies. GADD153 expression increases markedly in response to some types of cellular injury and the product of this gene causes cell cycle arrest. Using induction of GADD153 as a model, we have investigated the activation of the cellular injury response after treatment with taxol and cisplatin (cDDP). Activation of the GADD153 promoter coupled to the luciferase gene and transfected into human ovarian carcinoma 2008 cells correlated well with the increase in endogenous GADD153 mRNA after treatment with taxol but not after treatment with cDDP. Following treatment with cDDP, the increase in endogenous GADD153 mRNA was 10-fold greater than the increase in GADD153 promoter activity. Likewise, at equitoxic levels of exposure (IC80), cDDP produced a 5-fold greater increase in endogenous GADD153 mRNA than taxol. The tyrosine kinase inhibitor tyrophostin B46 had no significant effect on the ability of taxol to activate the GADD153 promoter, but inhibited activation of the GADD153 promoter by cDDP in a concentration-dependent manner. Tyrphostin B46 synergistically enhanced the cytotoxicity of cisplatin; however, the same exposure had no significant effect on the cytotoxicity of taxol. We conclude that (1) taxol and cDDP activate GADD153 promoter activity through different mechanisms; (2) the signal transduction pathway mediating induction by cDDP involves a tyrosine kinase inhibitable by tyrphostin B46; and (3) that inhibition of this signal transduction pathway by tyrphostin synergistically enhances cDDP toxicity

Virtual worlds as a tool to facilitate weight management for young people.

Childhood obesity is a serious problem in the UK, with around 20% of children aged 10-11 being overweight or obese. Lifestyle interventions can be effective, but there is limited evidence of their effectiveness in delivering sustained weight loss. The present research explored potential of web-based, 3-dimensional virtual worlds (VWs) for facilitation of weight-management, well-being and patient and public involvement (PPI) for young people. Attendees of a weight management camp took part in induction sessions for use of the VW of Second Life. All participants successfully learned how to interact with one another and navigate the virtual environment. Participant appraisals of Second Life were varied. Some found it complicated and difficult to use, and some found it fun and the majority stated that they would choose to use VWs again. There is considerable potential for use of VWs to promote weight management, and Second Life or a similar VW could be used to deliver this. Potential barriers include members of the target sample having limited access to computers with necessary system requirements for running VWs, and that some may find VW-based educational experiences unappealing or challenging to navigate. For some however, VWs may provide a useful mode for provision of education, PPI and support relating to weight management

The use of commitment techniques to support weight loss maintenance in obese adolescents

Objectives: Obesity is a rising problem in adolescents related to unhealthy behaviours. Commitment devises are one type of behavioural intervention that may help people change their behaviours. The current pilot trial tests whether commitment devices delivered via text message help adolescents maintain their recent weight loss. Methods: During a 12-week pilot trial adolescents who attended a weight loss camp were randomly assigned to either received text messages that contained only information, i.e., advice, about weight loss management (n=13) or asked for them to commit to following the same advise (n=14). Results: The BMI of the adolescents in the commitment group did not change. In contrast, the BMI of adolescents in the information group increased. A linear regression revealed that group was a significant predictor of BMI change. A logistic regression revealed that adolescents in the information group were nearly eight times more likely to regain weight than those in the commitment group. Conclusions: This is the first study with adolescents to show weight maintenance using a commitment device. The results suggest that commitment devices can help adolescents maintain their recent weight loss

Measuring perceived exercise capability and investigating its relationship with childhood obesity: a feasibility study.

BACKGROUND/OBJECTIVES: According to the COM-B ('Capability', 'Opportunity', 'Motivation' and 'Behaviour') model of behaviour, three factors are essential for behaviour to occur: capability, opportunity and motivation. Obese children are less likely to feel capable of exercising. The implementation of a new methodological approach to investigate the relationship between perceived exercise capability (PEC) and childhood obesity was conducted, which involved creating a new instrument, and demonstrating how it can be used to measure obesity intervention outcomes. SUBJECTS/METHODS: A questionnaire aiming to measure perceived exercise capability, opportunity and motivation was systematically constructed using the COM-B model and administered to 71 obese children (aged 9-17 years (12.24±0.2.01), body mass index (BMI) standard deviation scores (SDS) 2.80±0.660) at a weight-management camp in northern England. Scale validity and reliability was assessed. Relationships between PEC, as measured by the questionnaire, and BMI SDS were investigated for the children at the weight-management camp, and for 45 Spanish schoolchildren (aged 9-13 years, (10.52±1.23), BMI SDS 0.80±0.99). A pilot study, demonstrating how the questionnaire can be used to measure the effectiveness of an intervention aiming to bring about improved PEC for weight-management camp attendees, was conducted. No participants withdrew from these studies. RESULTS: The questionnaire domain (exercise capability, opportunity and motivation) composite scales were found to have adequate internal consistency (a=0.712-0.796) and construct validity (χ(2)/degrees of freedom=1.55, root mean square error of approximation=0.072, comparative fit index=0.92). Linear regression revealed that low PEC was associated with higher baseline BMI SDS for both UK (b=-0.289, P=0.010) and Spanish (b=-0.446, P=0.047) participants. Pilot study findings provide preliminary evidence for PEC improvements through intervention being achievable, and measurable using the questionnaire. CONCLUSIONS: Evidence is presented for reliability and validity of the questionnaire, and for feasibility of its use in the context of a childhood obesity intervention. Future research could investigate the link between PEC and childhood obesity further

Positive nutrition: shifting the focus from nutrients to diet for a healthy lifestyle.

PURPOSE AND METHODS: This summary is based on a scientific symposium organized by the Mediterranean Diet Roundtable and the American Italian Food Coalition titled, 'Positive Nutrition: shifting focus from nutrients to diet for a healthy lifestyle.' It was held at the Embassy of Italy in Washington DC in September of 2022. The panel of experts discussed how science can inform policy, what insights may be gleaned from different countries' approaches to healthy eating and what principles of the Mediterranean diet will inform strategies for a healthy future. Recognizing that isolated actions have limited impact on the complex relationship between diet and obesity, the panel discussed the importance of a system approach. In particular, the panel emphasized that focusing on single ingredients, isolated food categories and narrow approaches to policy have had limited success across the globe. RESULTS AND CONCLUSION: The panel agreed that there is a need for change of perspective that embraces complexity and emphasizes more positive nutrition messaging and policies. LEVEL OF EVIDENCE: V, Opinions of respected authorities, based on descriptive studies, narrative reviews, clinical experience, or reports of expert committees

The effect of discretionary snack consumption on overall energy intake, weight status and diet quality: A systematic review

The consumption frequency and portion size of discretionary snacks are thought to contribute to a greater food intake and risk of overweight or obesity in the developed world but evidence from epidemiological studies is inconclusive. To investigate this, we systematically evaluated evidence on the effects of discretionary snack consumption on weight status, energy intake, and diet quality. Articles involving discretionary snacks reported against the outcome measures of any primary, peer-reviewed study using human participants from free-living conditions for all age groups were included. A total of 14,780 titles were identified and 40 eligible publications were identified. Three key outcomes were reported: weight status (n = 35), energy intake (n = 11), and diet quality (n = 3). Increased discretionary snack consumption may contribute modestly to energy intake, however, there is a lack of consistent associations with increased weight/BMI. Although cross-sectional analyses offered conflicting findings, longitudinal studies in adults showed a consistent positive relationship between discretionary snack intake and increasing weight or body mass index. Given that experimental findings suggest reducing the size of discretionary snacks could lead to decreased consumption and subsequent energy intake, food policy makers and manufacturers may find it valuable to consider altering the portion and/or packaging size of discretionary snacks

Assessing urban methane emissions using column-observing portable Fourier transform infrared (FTIR) spectrometers and a novel Bayesian inversion framework

Cities represent a large and concentrated portion of global greenhouse gas emissions, including methane. Quantifying methane emissions from urban areas is difficult, and inventories made using bottom-up accounting methods often differ greatly from top-down estimates generated from atmospheric observations. Emissions from leaks in natural gas infrastructure are difficult to predict and are therefore poorly constrained in bottom-up inventories. Natural gas infrastructure leaks and emissions from end uses can be spread throughout the city, and this diffuse source can represent a significant fraction of a city\u27s total emissions. We investigated diffuse methane emissions of the city of Indianapolis, USA, during a field campaign in May 2016. A network of five portable solar-tracking Fourier transform infrared (FTIR) spectrometers was deployed throughout the city. These instruments measure the mole fraction of methane in a total column of air, giving them sensitivity to larger areas of the city than in situ sensors at the surface. We present an innovative inversion method to link these total column concentrations to surface fluxes. This method combines a Lagrangian transport model with a Bayesian inversion framework to estimate surface emissions and their uncertainties, together with determining the concentrations of methane in the air flowing into the city. Variations exceeding 10 ppb were observed in the inflowing air on a typical day, which is somewhat larger than the enhancements due to urban emissions (<5 ppb downwind of the city). We found diffuse methane emissions of 73(±22) mol s−1, which is about 50 % of the urban total and 68 % higher than estimated from bottom-up methods, although it is somewhat smaller than estimates from studies using tower and aircraft observations. The measurement and model techniques developed here address many of the challenges present when quantifying urban greenhouse gas emissions and will help in the design of future measurement schemes in other cities

Understanding how local authorities in England address obesity: A wider determinants of health perspective

© 2019 Elsevier B.V. Local government organisations (LAs) have a major role in the prevention and treatment of obesity in England. This study aims to 1) understand what actions are being taken by LAs to address obesity, and 2) determine how actions counter the perceived causes of obesity when mapped against the Wider Determinants of Health (WDoH) model. Thirty-two LAs were invited to complete an Action Mapping Tool, 10 participated. The tool requires LAs to document actions being implemented locally to address obesity. This then enables LAs to map their actions against the perceived causes of obesity, using the WDoH model as an analytical lens. We collated data from the 10 LAs and used an adapted framework synthesis method for analysis. 280 actions were documented across the 10 LAs; almost 60% (n = 166) targeted Individual Lifestyle Factors (ILF), with 7.1% (n = 20), 16.8% (n = 47) and 16.4% (n = 46) targeting Social and Community Factors (SCF), Living and Working Conditions (LWC) and Wider Conditions (WC) respectively. Conversely, 60% of causes were spread across the LWC and WC, with 16.4% regarded as ILF. Physical activity-, weight management-, and health improvement- programmes were most frequently implemented by LAs. There is a stark mismatch between LA actions on obesity and its perceived causes. Given that LAs acknowledge the complex aetiology of obesity, an equally comprehensive approach should be implemented in the future