Patient empowerment, eating behaviours and illness control: pre-post outcomes from DWELL delivery in UK and France

Diabetes self-management programmes can improve clinical and healthy lifestyle outcomes. Research has demonstrated that improved engagement with type 2 diabetes (T2D) care is associated with greater empowerment beliefs and a perceived internal control over their illness. As part of the DWELL evaluation study, an interim subset of 139 participants in the UK and 53 participants in France were assessed pre- and post-intervention on measures of weight, BMI, waist circumference and glycated haemoglobin (HbA1c), as well as self-efficacy beliefs (DES-SF), healthy eating behaviours (DEBQ) and perceptions of illness (IPQ-R). Pre-post comparisons in both countries demonstrated statistically significant decreases in weight (UK: Z = 6.71, p<.001, FR: Z = 3.33, p<.05), BMI (UK: Z = 6.70, p<.001, FR: Z = 3.21, p<.05), waist circumference (UK: Z = 6.71, p<.001, FR: Z = 3.24, p<.05) ,and HbA1c (UK: Z = 6.29, p<.001, FR: Z = 4.18, p <.001). Importantly, participation in the DWELL programme was associated with increased self-efficacy beliefs (UK: Z = 5.63, p<.001, FR: Z = 5.54, p<.001), greater perceived personal control over their diabetes (UK: Z = 3.17, p<.05, FR: Z = 2.20, p<.05), reduced negative feelings about their illness (UK: Z = 3.01, p <.05, FR: Z = 2.19, p<.05) and decreased eating in response to external food cues (UK: Z = 3.79, p<.001, FR: Z = 2.34, p<.05). In the UK, participants also reported an increased optimism for treatment control of their diabetes (Z = 3.06, p <.05) and for their long-term prognosis (Z = 1.99, p<.05). These preliminary findings support the efficacy of the DWELL programme in improving diabetes-related biomedical outcomes, as well as improvements in patient empowerment, healthy eating habits and increased perceived illness control. Further analysis, available at a later date, will include a larger sample of participants, including longitudinal data with follow-ups six- and 12- months post participation in the DWELL programme

The Diabetes and WELLbeing programme: protocol of a multi-site European complex intervention study

A quasi-experimental design evaluation study examines long-term impact of the 12-week DWELL programme, a self-management intervention for people with type 2 diabetes (T2D), based on adult learning and person-centred approaches, delivered in 5 community and hospital sites in 4 European countries. Overall target is 780 people with T2D. Staff are trained in motivational interviewing, group facilitation, diabetes education, and programme approach which consists of core and ‘pick and mix’ sessions on diabetes education, physical activity, healthy eating and wellbeing. Pre-post measures are taken at baseline (T0), end-of-programme (T1), at 6 months (T2) and 12 months (T3). There is a non-equivalent control group of 190 at T2/T3. Biomedical data are collected by staff and psychosocial data are collected via self-completed validated scales. Metabolic measures include: HbA1c, BMI and waist circumference. Demographics capture: age, gender, ethnicity, household composition, education, employment, income. Psychosocial data are collected on illness perception, patient empowerment, eating behaviours, physical activity, physical/mental health status, health-related quality of life (EQ-5D), use of diabetes-related health services and self-care activities. Participant experiences are recorded via motivational interviews at T0 and T1 and focus groups at T1. Process evaluation data are collected via interviews with staff and patient ambassadors. The DWELL programme started in 2018 and results will be available in 2021. The study will produce rich data on long-term impact of intervention to allow replication and further development. It will permit cross-border conclusions on sustainability and embeddedness of model in varied service settings, and empowerment-based public health approach to T2D self-management

Metabolomic Characterization of Ovarian Epithelial Carcinomas by HRMAS-NMR Spectroscopy

Objectives. The objectives of the present study are to determine if a metabolomic study by HRMAS-NMR can (i) discriminate between different histological types of epithelial ovarian carcinomas and healthy ovarian tissue, (ii) generate statistical models capable of classifying borderline tumors and (iii) establish a potential relationship with patient's survival or response to chemotherapy. Methods. 36 human epithelial ovarian tumor biopsies and 3 healthy ovarian tissues were studied using 1H HRMAS NMR spectroscopy and multivariate statistical analysis. Results. The results presented in this study demonstrate that the three histological types of epithelial ovarian carcinomas present an effective metabolic pattern difference. Furthermore, a metabolic signature specific of serous (N-acetyl-aspartate) and mucinous (N-acetyl-lysine) carcinomas was found. The statistical models generated in this study are able to predict borderline tumors characterized by an intermediate metabolic pattern similar to the normal ovarian tissue. Finally and importantly, the statistical model of serous carcinomas provided good predictions of both patient's survival rates and the patient's response to chemotherapy. Conclusions. Despite the small number of samples used in this study, the results indicate that metabolomic analysis of intact tissues by HRMAS-NMR is a promising technique which might be applicable to the therapeutic management of patients

GSK3-mediated raptor phosphorylation supports amino acid-dependent Q2 mTORC1-directed signalling

The mammalian or mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) is a ubiquitously expressed multimeric protein kinase complex that integrates nutrient and growth factor signals for the co-ordinated regulation of cellular metabolism and cell growth. Herein, we demonstrate that suppressing the cellular activity of glycogen synthase kinase-3 (GSK3), by use of pharmacological inhibitors or shRNA-mediated gene silencing, results in substantial reduction in amino acid (AA)-regulated mTORC1-directed signalling, as assessed by phosphorylation of multiple downstream mTORC1 targets. We show that GSK3 regulates mTORC1 activity through its ability to phosphorylate the mTOR-associated scaffold protein raptor (regulatory-associated protein of mTOR) on Ser(859). We further demonstrate that either GSK3 inhibition or expression of a S859A mutated raptor leads to reduced interaction between mTOR and raptor and under these circumstances, irrespective of AA availability, there is a consequential loss in phosphorylation of mTOR substrates, such as p70S6K1 (ribosomal S6 kinase 1) and uncoordinated-51-like kinase (ULK1), which results in increased autophagic flux and reduced cellular proliferation

Thermal and mechanical characterization of epoxy resins (ELO and ESO) cured with anhydrides

In this work we have developed polymeric materials from epoxidized vegetable oils in order to obtain materials with excellent mechanical properties for use as green matrix composites. Epoxidized soybean oil (ESO), epoxidized linseed oil (ELO) and different mixtures of the two oils were used to produce the polymers. Phthalic anhydride (17 mol%) and maleic anhydride (83 mol%) which has a eutectic reaction temperature of 48 °C were used as crosslinking agents while benzyl dimethyl amine (BDMA) and ethylene glycol were used as the catalyst and initiator, respectively. The results showed that samples 100ELO and 80ELO20ESO could be used as a matrix in green composites because they demonstrated good mechanical properties. © 2012 AOCS (outside the USA).This work is part of the project IPT-310000-2010-037,''ECOTEXCOMP: Research and development of textile structures useful as reinforcement of composite materials with marked ecological character'' funded by the "Ministerio de Ciencia e Innovacion", with financial aid of 189,540.20 EUR, within the "Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica 2008-2011" and funded by the European Union through FEDER funds, Technology Fund 2007-2013, Operational Programme on R + D + i for and on behalf of the companies.Samper Madrigal, MD.; Fombuena Borrás, V.; Boronat Vitoria, T.; García Sanoguera, D.; Balart Gimeno, RA. (2012). Thermal and mechanical characterization of epoxy resins (ELO and ESO) cured with anhydrides. Journal of the American Oil Chemists' Society. 89(8):1521-1528. https://doi.org/10.1007/s11746-012-2041-yS15211528898Averous L (2004) Biodegradable multiphase systems based on plasticized starch: a review. J Macromol Sci Polym Rev C44:231–274Bledzki AK, Jaszkiewicz A (2010) Mechanical performance of biocomposites based on PLA and PHBV reinforced with natural fibres—a comparative study to PP. Compos Sci Technol 70:1687–1696Raquez JM, Deleglise M, Lacrampe MF, Krawczak P (2010) Thermosetting (bio)materials derived from renewable resources: a critical review. Prog Polym Sci 35:487–509Charlet K, Jernot JP, Gomina M, Bizet L, Breard J (2010) Mechanical properties of flax fibers and of the derived unidirectional composites. J Compos Mater 44:2887–2896Barreto ACH, Esmeraldo MA, Rosa DS, Fechine PBA, Mazzetto SE (2010) Cardanol biocomposites reinforced with jute fiber: microstructure, biodegradability, and mechanical properties. Polym Compos 31:1928–1937Thakur VK, Singha AS (2010) Physico-chemical and mechanical characterization of natural fibre reinforced polymer composites. Iran Polym J 19:3–16Schmitz WR, Wallace JG (1954) Epoxidation of methyl oleate with hydrogen peroxide. J Am Oil Chem Soc 31:363–365La Scala J, Wool RP (2002) Effect of FA composition on epoxidation kinetics of TAG. J Am Oil Chem Soc 79:373–378de Espinosa LM, Ronda JC, Galia M, Cadiz V (2008) A new enone-containing triglyceride derivative as precursor of thermosets from renewable resources. J Polym Sci Pol Chem 46:6843–6850Gerbase AE, Petzhold CL, Costa APO (2002) Dynamic mechanical and thermal behavior of epoxy resins based on soybean oil. J Am Oil Chem Soc 79:797–802Boquillon N, Fringant C (2000) Polymer networks derived from curing of epoxidised linseed oil: influence of different catalysts and anhydride hardeners. Polymer 41:8603–8613Montserrat S, Flaque C, Calafell M, Andreu G, Malek J (1995) Influence of the accelerator concentration on the curing reaction of an epoxy-anhydride system. Thermochim Acta 269:213–229Zacharuk M, Becker D, Coelho LAF, Pezzin SH (2011) Study of the reaction between polyethylene glycol and epoxy resins using N,N-dimethylbenzylamine as catalyst. Polimeros 21:73–77Lozada Z, Suppes GJ, Tu YC, Hsieh FH (2009) Soy-based polyols from oxirane ring opening by alcoholysis reaction. J Appl Polym Sci 113:2552–256

Amino Acid Availability Controls TRB3 Transcription in Liver through the GCN2/eIF2α/ATF4 Pathway

In mammals, plasma amino acid concentrations are markedly affected by dietary or pathological conditions. It has been well established that amino acids are involved in the control of gene expression. Up to now, all the information concerning the molecular mechanisms involved in the regulation of gene transcription by amino acid availability has been obtained in cultured cell lines. The present study aims to investigate the mechanisms involved in transcriptional activation of the TRB3 gene following amino acid limitation in mice liver. The results show that TRB3 is up-regulated in the liver of mice fed a leucine-deficient diet and that this induction is quickly reversible. Using transient transfection and chromatin immunoprecipitation approaches in hepatoma cells, we report the characterization of a functional Amino Acid Response Element (AARE) in the TRB3 promoter and the binding of ATF4, ATF2 and C/EBPβ to this AARE sequence. We also provide evidence that only the binding of ATF4 to the AARE plays a crucial role in the amino acid-regulated transcription of TRB3. In mouse liver, we demonstrate that the GCN2/eIF2α/ATF4 pathway is essential for the induction of the TRB3 gene transcription in response to a leucine-deficient diet. Therefore, this work establishes for the first time that the molecular mechanisms involved in the regulation of gene transcription by amino acid availability are functional in mouse liver

Genetic changes in human pluripotent stem cells: implications for basic biology and regenerative medicine

Chronic tissue and organ failure caused by an injury, disease, ageing or congenital defects represents some of the most complex therapeutic challenges and poses a significant financial healthcare burden. Regenerative medicine strategies aim to fulfil the unmet clinical need by restoring the normal tissue function either through stimulating the endogenous tissue repair or by using transplantation strategies to replace the missing or defective cells. Stem cells represent an essential pillar of regenerative medicine efforts as they provide a source of progenitors or differentiated cells for use in cell replacement therapies. Whilst significant leaps have been made in controlling the stem cell fates and differentiating them to cell types of interest, transitioning bespoke cellular products from an academic environment to off-the-shelf clinical treatments brings about a whole new set of challenges which encompass manufacturing, regulatory and funding issues. Notwithstanding the need to resolve such issues before cell replacement therapies can benefit global healthcare, mounting progress in the field has highlighted regenerative medicine as a realistic prospect for treating some of the previously incurable conditions

CD98 Increases Renal Epithelial Cell Proliferation by Activating MAPKs

CD98 heavy chain (CD98hc) is a multifunctional transmembrane spanning scaffolding protein whose extracellular domain binds with light chain amino acid transporters (Lats) to form the heterodimeric amino acid transporters (HATs). It also interacts with β1 and β3 integrins by its transmembrane and cytoplasmic domains. This interaction is proposed to be the mechanism whereby CD98 mediates cell survival and growth via currently undefined signaling pathways. In this study, we determined whether the critical function of CD98-dependent amino acid transport also plays a role in cell proliferation and defined the signaling pathways that mediate CD98-dependent proliferation of murine renal inner medullary collecting duct (IMCD) cells. We demonstrate that downregulating CD98hc expression resulted in IMCD cell death. Utilizing overexpression studies of CD98hc mutants that either lacked a cytoplasmic tail or were unable to bind to Lats we showed that CD98 increases serum-dependent cell proliferation by a mechanism that requires the CD98hc cytoplasmic tail. We further demonstrated that CD98-dependent amino acid transport increased renal tubular epithelial cell proliferation by a mechanism that does not require the CD98hc cytoplasmic tail. Both these mechanisms of increased renal tubular epithelial cell proliferation are mediated by Erk and p38 MAPK signaling. Although increased amino transport markedly activated mTor signaling, this pathway did not alter cell proliferation. Thus, these studies demonstrate that in IMCD cells, the cytoplasmic and extracellular domains of CD98hc regulate cell proliferation by distinct mechanisms that are mediated by common MAPK signaling pathways