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

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

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

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

Rapamycin Blocks Production of KSHV/HHV8: Insights into the Anti-Tumor Activity of an Immunosuppressant Drug

Infection with Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8) often results in the development of fatal tumors in immunocompromised patients. Studies of renal transplant recipients show that use of the immunosuppressant drug rapamycin, an mTOR inhibitor, both prevents and can induce the regression of Kaposi's sarcoma (KS), an opportunistic tumor that arises within a subset of this infected population. In light of rapamycin's marked anti-KS activity, we tested whether the drug might directly inhibit the KSHV life cycle. We focused on the molecular switch that triggers this predominantly latent virus to enter the lytic (productive) replication phase, since earlier work links this transition to viral persistence and tumorigenesis.In latently infected human B cell lines, we found that rapamycin inhibited entry of the virus into the lytic replication cycle, marked by a loss of expression of the lytic switch protein, replication and transcription activator (RTA). To test for viral-specific effects of rapamycin, we focused our studies on a B cell line with resistance to rapamycin-mediated growth inhibition. Using this line, we found that the drug had minimal effect on cell cycle profiles, cellular proliferation, or the expression of other cellular or latent viral proteins, indicating that the RTA suppression was not a result of global cellular dysregulation. Finally, treatment with rapamycin blocked the production of progeny virions.These results indicate that mTOR plays a role in the regulation of RTA expression and, therefore, KSHV production, providing a potential molecular explanation for the marked clinical success of rapamycin in the treatment and prevention of post-transplant Kaposi's sarcoma. The striking inhibition of rapamycin on KSHV lytic replication, thus, helps explain the apparent paradox of an immunosuppressant drug suppressing the pathogenesis of an opportunistic viral infection

A new role for tamoxifen in oestrogen receptor-negative breast cancer when it is combined with epigallocatechin gallate

We have previously shown that tamoxifen+epigallocatechin gallate (EGCG) is synergistically cytotoxic towards oestrogen receptor (ER)-negative breast cancer cells. To determine if this response would correlate with significant tumour suppression in vivo, athymic nude female mice were implanted with MDA-MB-231 cells and treated with tamoxifen, EGCG, EGCG+tamoxifen, or vehicle control for 10 weeks. Tumour volume in EGCG- (25 mg kg−1)+tamoxifen (75 μg kg−1)-treated mice decreased by 71% as compared with vehicle control (P<0.05), whereas tumour weight was decreased by 80% compared with control (P<0.01). Epigallocatechin gallate treatment did not alter ER protein expression in MDA-MB-231 cells and thus was not a mechanism for the observed tumour suppression. However, western blotting of tumour extracts demonstrated that epidermal growth factor receptor (EGFR; 85% lower than control), pEGFR (78% lower than control), mammalian target of rapamycin (mTOR; 78% lower than control), and CYP1B1 (75% lower than control) were significantly lower after the combination treatment as compared with all other treatments. Nuclear factor-κB (NF-κB), b-Raf, p-MEK, S6K, 4EBP1, Akt, vascular EGFR-1 (VEGFR-1) and VEGF expressions were decreased in control but not in the individual treatments, whereas MEK, phospholipase D 1/2, TGFα, and ERK expressions were not changed after any treatment. The results demonstrate that tamoxifen at realistic doses (75 μg kg−1) can suppress the growth of ER-negative breast cancer when combined with EGCG. In addition, the dominant mechanism for tumour suppression is the concomitant decrease in tumour protein expressions of mTOR and the EGFR

Impairing the production of ribosomal RNA activates mammalian target of rapamycin complex 1 signalling and downstream translation factors.

Ribosome biogenesis is a key process for maintaining protein synthetic capacity in dividing or growing cells, and requires coordinated production of ribosomal proteins and ribosomal RNA (rRNA), including the processing of the latter. Signalling through mammalian target of rapamycin complex 1 (mTORC1) activates all these processes. Here, we show that, in human cells, impaired rRNA processing, caused by expressing an interfering mutant of BOP1 or by knocking down components of the PeBoW complex elicits activation of mTORC1 signalling. This leads to enhanced phosphorylation of its substrates S6K1 and 4E-BP1, and stimulation of proteins involved in translation initiation and elongation. In particular, we observe both inactivation and downregulation of the eukaryotic elongation factor 2 kinase, which normally inhibits translation elongation. The latter effect involves decreased expression of the eEF2K mRNA. The mRNAs for ribosomal proteins, whose translation is positively regulated by mTORC1 signalling, also remain associated with ribosomes. Therefore, our data demonstrate that disrupting rRNA production activates mTORC1 signalling to enhance the efficiency of the translational machinery, likely to help compensate for impaired ribosome production