The DISC (Diabetes in Social Context) Study-evaluation of a culturally sensitive social network intervention for diabetic patients in lower socioeconomic groups: a study protocol

<p>Abstract</p> <p>Background</p> <p>Compared to those in higher socioeconomic groups, diabetic patients in lower socioeconomic groups have less favourable metabolic control and experience more diabetes-related complications. They encounter specific barriers that hinder optimal diabetes self-management, including a lack of social support and other psychosocial mechanisms in their immediate social environments. <it>Powerful Together with Diabetes </it>is a culturally sensitive social network intervention specifically targeted to ethnic Dutch, Moroccan, Turkish, and Surinamese diabetic patients in lower socioeconomic groups. For ten months, patients will participate in peer support groups in which they will share experiences, support each other in maintaining healthy lifestyles, and learn skills to resist social pressure. At the same time, their significant others will also receive an intervention, aimed at maximizing support for and minimizing the negative social influences on diabetes self-management. This study aims to test the effectiveness of <it>Powerful Together with Diabetes</it>.</p> <p>Methods/Design</p> <p>We will use a quasi-experimental design with an intervention group (Group 1) and two comparison groups (Groups 2 and 3), N = 128 in each group. Group 1 will receive <it>Powerful Together with Diabetes</it>. Group 2 will receive <it>Know your Sugar</it>, a six-week group intervention that does not focus on the participants' social environments. Group 3 receives standard care only. Participants in Groups 1 and 2 will be interviewed and physically examined at baseline, 3, 10, and 16 months. We will compare their haemoglobin A1C levels with the haemoglobin A1C levels of Group 3. Main outcome measures are haemoglobin A1C, diabetes-related quality of life, diabetes self-management, health-related, and intermediate outcome measures. We will conduct a process evaluation and a qualitative study to gain more insights into the intervention fidelity, feasibility, and changes in the psychosocial mechanism in the participants' immediate social environments.</p> <p>Discussion</p> <p>With this study, we will assess the feasibility and effectiveness of a culturally sensitive social network intervention for lower socioeconomic groups. Furthermore, we will study how to enable these patients to optimally manage their diabetes. This trial is registered in the Dutch Trial Register: NTR1886</p

BOK displays cell death-independent tumor suppressor activity in non-small cell lung carcinoma.

Since the genomic region containing the Bcl-2-related ovarian killer (BOK) locus is frequently deleted in certain human cancers, BOK is hypothesized to have a tumor suppressor function. In the present study, we analyzed primary non-small cell lung carcinoma (NSCLC) tumors and matched lung tissues from 102 surgically treated patients. We show that BOK protein levels are significantly downregulated in NSCLC tumors as compared to lung tissues (P<0.001). In particular, we found BOK downregulation in NSCLC tumors of grades two (P=0.004, n=35) and three (P=0.031, n=39) as well as in tumors with metastases to hilar (pN1) (P=0.047, n=31) and mediastinal/subcarinal lymph nodes (pN2) (P=0.021, n=18) as opposed to grade one tumors (P=0.688, n=7) and tumors without lymph node metastases (P=0.112, n=51). Importantly, in lymph node positive patients, BOK expression greater than the median value was associated with longer survival (P=0.002, Mantel test). Using in vitro approaches, we provide evidence that BOK overexpression is inefficient in inducing apoptosis but that it inhibits TGFβ-induced migration and epithelial-to-mesenchymal transition (EMT) in lung adenocarcinoma-derived A549 cells. We have identified epigenetic mechanisms, in particular BOK promoter methylation, as an important means to silence BOK expression in NSCLC cells. Taken together, our data point toward a novel mechanism by which BOK acts as a tumor suppressor in NSCLC by inhibiting EMT. Consequently, the restoration of BOK levels in low-BOK-expressing tumors might favor the overall survival of NSCLC patients. This article is protected by copyright. All rights reserved

Analysis of the gut bacterial community of wild larvae of Anastrepha fraterculus sp. 1: effect of host fruit, environment, and prominent stable associations of the genera Wolbachia, Tatumella, and Enterobacter

The genus Anastrepha (Diptera Tephritidae) includes some of the most important fruit fly pests in the Americas. Here, we studied the gut bacterial community of 3rd instar larvae of Anastrepha fraterculus sp. 1 through Next Generation Sequencing (lllumina) of the V3-V4 hypervariable region within the 16S rRNA gene. Gut bacterial communities were compared between host species (guava and peach), and geographical origins (Concordia and Horco Molle in Argentina) representing distinct ecological scenarios. In addition, we explored the effect of spatial scale by comparing the samples collected from different trees within each geographic origin and host species. We also addressed the effect of fruit size on bacterial diversity. The gut bacterial community was affected both by host species and geographic origin. At smaller spatial scales, the gut bacterial profile differed among trees of the same species and location at least in one host-location combination. There was no effect of fruit size on the larval gut bacteriome. Operational Taxonomic Units (OTUs) assigned to Wolbachia, Tatumella and Enterobacter were identified in all samples examined, which suggest potential, non transient symbioses. Better knowledge on the larval gut bacteriome contributes valuable information to develop sustainable control strategies against A. fraterculus targeting key symbionts as the Achilles’ heel to control this important fruit fly pest.Instituto de GenéticaFil: Salgueiro, Julieta. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética. Laboratorio de Genética de Insectos de Importancia Económica; ArgentinaFil: Salgueiro, Julieta. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Salgueiro, Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Nussenbaum, Ana Laura. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Nussenbaum, Ana Laura. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Milla, Fabian Horacio. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética. Laboratorio de Genética de Insectos de Importancia Económica; ArgentinaFil: Milla, Fabian Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Asimakis, Elias D. University of Patras. Department of Environmental Engineering; GreciaFil: Goane, Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Goane, Lucía. Universidad Nacional de Tucumán. Facultad de Agronomía y Zootecnia; ArgentinaFil: Ruiz, María Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ruiz, María Josefina. Universidad Nacional de Tucumán. Facultad de Agronomía y Zootecnia; ArgentinaFil: Bachmann, Guillermo Enrique. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética. Laboratorio de Genética de Insectos de Importancia Económica; ArgentinaFil: Bachmann, Guillermo Enrique. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Bachmann, Guillermo Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vera, María Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vera, María Teresa. Universidad Nacional de Tucumán. Facultad de Agronomía y Zootecnia; ArgentinaFil: Stathopoulou, Panagiota. University of Patras. Department of Environmental Engineering; GreciaFil: Bourtzis, Kostas. Vienna International Centre. Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture. Insect Pest Control Laboratory; AustriaFil: Deutscher, Ania T. Biosecurity and Food Safety. Department of Primary Industries, Elizabeth Macarthur Agricultural Institute (EMAI); AustraliaFil: Lanzavecchia, Silvia Beatriz. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética. Laboratorio de Genética de Insectos de Importancia Económica; ArgentinaFil: Lanzavecchia, Silvia Beatriz. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Tsiamis, George. University of Patras. Department of Environmental Engineering; GreciaFil: Segura, Diego Fernando. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Genética. Laboratorio de Genética de Insectos de Importancia Económica; ArgentinaFil: Segura, Diego Fernando. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Segura, Diego Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Therapeutic Concentrations of Mitoxantrone Elicit Energetic Imbalance in H9c2 Cells as an Earlier Event

Mitoxantrone (MTX) is a chemotherapeutic agent that emerged as an alternative to anthracycline therapy. However, MTX also causes late cardiotoxicity, being oxidative stress and mitochondrial-impaired function proposed as possible mechanisms. This work aimed to investigate the relevance of these mechanisms to the MTX toxicity in H9c2 cells, using therapeutic concentrations. The observed cytotoxicity of MTX was time and concentration dependent in both lactate dehydrogenase leakage assay and MTT reduction assay. Two therapeutic concentrations (100 nM and 1 lM) and three time points were selected (24, 48, and 96 h) for further studies. Both MTX concentrations caused a significant increase in caspase-3 activity, which was not prevented by inhibiting MTX CYP450-metabolism. Significant decreases were observed in the total and reduced glutathione levels only in MTX 100 nM at 96 h; however, neither alterations in oxidized glutathione nor increases in the malondialdehyde levels were observed at any time or concentrations tested. On the other hand, changes in the intracellular ATP levels, mitochondrial membrane potential, and intracellular calcium levels were observed in both concentrations and all time tested. Noteworthy, decreased levels of ATP-synthase expression and activity and increases in the reactive species generation were observed at 96 h in both working concentrations. However, the radical scavenger N-acetylcysteine or the mitochondrial function enhancer L-carnitine did not prevent MTX cytotoxicity. Thus, this work evidenced the early MTX-induced energetic crisis as a possible key factor in the cell injury.This work received financial support from ‘‘Fundação para a Ciência e Tecnologia (FCT),’’ Portugal (EXPL/ DTP-FTO/0290/2012) and by ‘‘Fundo Comunitário Europeu’’ (FEDER) under the frame of ‘‘Eixo I do Programa Operacional Fatores de Competitividade (POFC) do QREN’’ (COMPETE: FCOMP- 01-0124-FEDER-027749). The work was also supported by FCT within the framework of Strategic Projects for Scientific Research Units of R&D (project PEst-C/EQB/LA0006/2011). LGR and VVB thank FCT for their PhD Grant (SFRH/BD/63473/2009 and SFRH/ BD/82556/2011, respectively) and VMC thank FCT for her Post-doc Grant (SFRH/BPD/63746/2009)