Maximizing diabetes education efforts in vulnerable populations - newer delivery concepts.

PURPOSE OF REVIEW: Patients from ethnic/minority backgrounds or low socioeconomic status face numerous barriers to achieving ideal diabetes care goals. The purpose of this review is to describe the burden of diabetes in vulnerable populations; discuss the etiologic factors leading to health disparities in diabetes; and present challenges and solutions to improving diabetes care through novel diabetes self-management education and support interventions. RECENT FINDINGS: Recent interventions to alleviate health disparities utilize a combination of community health workers, peer leaders and technology-based approaches to provide diabetes self-management education and support and overcome barriers to diabetes control such as low literacy, difficulty with transportation, and cultural beliefs. These interventions achieve clinically meaningful improvements in blood glucose control as measured by haemoglobin A1C and are effective in addressing psychosocial outcomes such as diabetes distress. Research is underway to address food insecurity through food delivery and use behavioural economics principles to provide financial incentives to diabetes control. SUMMARY: Combining human interaction through peer or community health worker led diabetes educational efforts and support with technology-based interventions shows promise in improving diabetes outcomes for vulnerable populations.

Postoperative outcomes and functional results after Deloyer's procedure - a retrospective cohort study / Desfechos pós-operatórios e resultados funcionais após o procedimento de Deloyer ­ um estudo de coorte retrospectivo

ABSTRACT Introduction: The objective of our study was to describe surgical outcomes of Deloyers procedure in our referral center, and to compare the results of patients with and without protective ileostomy. Methods: Patients undergoing a Deloyers procedure from 2013 to 2016 were prospectively included. General characteristics, intraoperative variables, postoperative course, and functional outcomes were analyzed. Patients were compared into two groups: group (1) patients undergoing Deloyers procedure without ileostomy, and group (2) Deloyers procedure with protective ileostomy. Results: Sixteen patients undergoing isoperistaltic transposition of the right colon remnant were included, of which 9 (63%) were males with a median age of 47 (range 22-76) years. The main surgical indication was the restoration of bowel transit (62.5%). There was higher major morbidity rate in the Deloyers procedure with protective ileostomy group, but without statistical significance (20% vs. 9%, p = 0.92). No leaks or deaths were reported. The length of hospital stay was 7 days. The mean number of bowel movements per day was 4 at 18 months of follow up. Only four (25%) patients used irregularly loperamide. Conclusions: The Deloyers procedure has satisfactory results and is reproducible with low morbidity. The major and minor morbidity rates were similar between groups, suggesting that the costs and risks of a second procedure can be avoided by providing a safe primary anastomosis.

RESUMO Introdução: O objetivo de nosso estudo foi descrever os resultados cirúrgicos do procedimento de Deloyer em nosso centro de referência e comparar os resultados de pacientes com e sem ileostomia de proteção. Métodos: Pacientes submetidos ao procedimento de Deloyer de 2013 a 2016 foram incluídos prospectivamente. Foram analisadas as características gerais, as variáveis intraoperatórias, o curso pós-operatório e os desfechos funcionais. Os pacientes foram comparados em dois grupos: Grupo 1) pacientes submetidos ao procedimento de Deloyer (PD) sem ileostomia, e grupo 2) procedimento de Deloyer com ileostomia de proteção (IP). Resultados: Foram incluídos 16 pacientes submetidos à transposição isoperistáltica da porção remanescente do cólon direito, dos quais 9 (63%) eram do sexo masculino com idade média de 47 anos (variação de 22-76) anos. A principal indicação cirúrgica foi a restauração do trânsito intestinal (62,5%). Houve maior morbidade maior no grupo IP, mas sem significância estatística (20% vs. 9%, p = 0,92). Nenhum vazamento ou óbito foi relatado. A duração da hospitalização foi de 7 dias. O número médio de evacuações por dia foi 4, aos 18 meses de seguimento. Apenas quatro (25%) pacientes utilizaram irregularmente a loperamida. Conclusões: O procedimento de Deloyer tem resultados satisfatórios e é reprodutível com baixa morbidade. As taxas de morbidades maiores e menores foram semelhantes entre os grupos, sugerindo que os custos e riscos de um segundo procedimento podem ser evitados proporcionando-se uma anastomose primária segura.

miRIAD-integrating microRNA inter- and intragenic data.

MicroRNAs (miRNAs) are a class of small (∼22 nucleotides) non-coding RNAs that post-transcriptionally regulate gene expression by interacting with target mRNAs. A majority of miRNAs is located within intronic or exonic regions of protein-coding genes (host genes), and increasing evidence suggests a functional relationship between these miRNAs and their host genes. Here, we introduce miRIAD, a web-service to facilitate the analysis of genomic and structural features of intragenic miRNAs and their host genes for five species (human, rhesus monkey, mouse, chicken and opossum). miRIAD contains the genomic classification of all miRNAs (inter- and intragenic), as well as classification of all protein-coding genes into host or non-host genes (depending on whether they contain an intragenic miRNA or not). We collected and processed public data from several sources to provide a clear visualization of relevant knowledge related to intragenic miRNAs, such as host gene function, genomic context, names of and references to intragenic miRNAs, miRNA binding sites, clusters of intragenic miRNAs, miRNA and host gene expression across different tissues and expression correlation for intragenic miRNAs and their host genes. Protein-protein interaction data are also presented for functional network analysis of host genes. In summary, miRIAD was designed to help the research community to explore, in a user-friendly environment, intragenic miRNAs, their host genes and functional annotations with minimal effort, facilitating hypothesis generation and in-silico validations. Database URL: http://www.miriad-database.org.

Src as a novel therapeutic target for endometriosis.

BACKGROUND: Endometriosis is a common condition that is associated with an increased risk of developing ovarian carcinoma. Improved in vitro models of this disease are needed to better understand how endometriosis, a benign disease, can undergo neoplastic transformation, and for the development of novel treatment strategies to prevent this progression. METHODS: We describe the generation and in vitro characterization of novel TERT immortalized ovarian endometriosis epithelial cell lines (EEC16-TERT). RESULTS: Expression of TERT alone was sufficient to immortalize endometriosis epithelial cells. TERT immortalization induces an epithelial-to-mesenchymal transition and perturbation in the expression of genes involved in the development of ovarian cancer. EEC16-TERT was non-tumorigenic when xenografted into immunocompromised mice but grew in anchorage-independent growth assays in an epidermal growth factor and hydrocortisone dependent manner. Colony formation in agar was abolished by inhibition of Src, and the Src pathway was found to be activated in human endometriosis lesions. CONCLUSIONS: This new in vitro model system mimics endometriosis and the early stages of neoplastic transformation in the development of endometriosis associated ovarian cancer. We demonstrate the potential clinical relevance of this model by identifying Src activation as a novel pathway in endometriosis that could be targeted therapeutically, perhaps as a novel strategy to manage endometriosis clinically, or to prevent the development of endometriosis-associated ovarian cancer.

Kinin B1 receptor gene ablation affects hypothalamic CART productionb.

A role for the kinin B1 receptor in energy-homeostatic processes was implicated in previous studies; notably, the studies where kinin B1 receptor knockout mice (B1-/-) were shown to have impaired adiposity, impaired leptin and insulin production, lower feed efficiency, protection from liver steatosis and diet-induced obesity when fed a high fat diet (HFD). In particular, in a model where the B1 receptor is expressed exclusively in the adipose tissue, it rescues the plasma insulin concentration and the weight gain seen in wild type mice. Taking into consideration that leptin participates in the formation of hypothalamic nuclei, which modulate energy expenditure, and feeding behavior, we hypothesized that these brain regions could also be altered in B1-/- mice. We observed for the first time a difference in the gene expression pattern of cocaine and amphetamine related transcript (CART) in the (lateral hypothalamic area (LHA) resulting from the deletion of the kinin B1 receptor gene. The correlation between CART expression in the LHA and the thwarting of diet-induced obesity corroborates independent correlations between CART and obesity. Furthermore, it seems to indicate that the mechanism underlying the 'lean' phenotype of B1-/- mice does not stem solely from changes in peripheral tissues but may also receive contributions from changes in the hypothalamic machinery involved in energy homeostasis processes.

Kinin B1 receptor in adipocytes regulates glucose tolerance and predisposition to obesity.

BACKGROUND: Kinins participate in the pathophysiology of obesity and type 2 diabetes by mechanisms which are not fully understood. Kinin B(1) receptor knockout mice (B(1) (-/-)) are leaner and exhibit improved insulin sensitivity. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that kinin B(1) receptors in adipocytes play a role in controlling whole body insulin action and glucose homeostasis. Adipocytes isolated from mouse white adipose tissue (WAT) constitutively express kinin B(1) receptors. In these cells, treatment with the B(1) receptor agonist des-Arg(9)-bradykinin improved insulin signaling, GLUT4 translocation, and glucose uptake. Adipocytes from B(1) (-/-) mice showed reduced GLUT4 expression and impaired glucose uptake at both basal and insulin-stimulated states. To investigate the consequences of these phenomena to whole body metabolism, we generated mice where the expression of the kinin B(1) receptor was limited to cells of the adipose tissue (aP2-B(1)/B(1) (-/-)). Similarly to B(1) (-/-) mice, aP2-B(1)/B(1) (-/-) mice were leaner than wild type controls. However, exclusive expression of the kinin B(1) receptor in adipose tissue completely rescued the improved systemic insulin sensitivity phenotype of B(1) (-/-) mice. Adipose tissue gene expression analysis also revealed that genes involved in insulin signaling were significantly affected by the presence of the kinin B(1) receptor in adipose tissue. In agreement, GLUT4 expression and glucose uptake were increased in fat tissue of aP2-B(1)/B(1) (-/-) when compared to B(1) (-/-) mice. When subjected to high fat diet, aP2-B(1)/B(1) (-/-) mice gained more weight than B(1) (-/-) littermates, becoming as obese as the wild types. CONCLUSIONS/SIGNIFICANCE: Thus, kinin B(1) receptor participates in the modulation of insulin action in adipocytes, contributing to systemic insulin sensitivity and predisposition to obesity.

The role of kinin B1 and B2 receptors in the scratching behaviour induced by proteinase-activated receptor-2 agonists in mice.

BACKGROUND AND PURPOSE: Activation of the proteinase-activated receptor-2 (PAR-2) induces scratching behaviour in mice. Here, we have investigated the role of kinin B(1) and B(2) receptors in the pruritogenic response elicited by activators of PAR-2. EXPERIMENTAL APPROACH: Scratching was induced by an intradermal (i.d.) injection of trypsin or the selective PAR-2 activating peptide SLIGRL-NH(2) at the back of the mouse neck. The animals were observed for 40 min and their scratching response was quantified. KEY RESULTS: I.d. injection of trypsin or SLIGRL-NH(2) evoked a scratching behaviour, dependent on PAR-2 activation. Mice genetically deficient in kinin B(1) or B(2) receptors exhibited reduced scratching behaviour after i.d. injection of trypsin or SLIGRL-NH(2). Treatment (i.p.) with the non-peptide B(1) or B(2)receptor antagonists SSR240612 and FR173657, respectively, prevented the scratching behaviour caused by trypsin or SLIGRL-NH(2). Nonetheless, only treatment i.p. with the peptide B(2)receptor antagonist, Hoe 140, but not the B(1)receptor antagonist (DALBK), inhibited the pruritogenic response to trypsin. Hoe 140 was also effective against SLIGRL-NH(2)-induced scratching behaviour when injected by i.d. or intrathecal (i.t.) routes. Also, the response to SLIGRL-NH(2) was inhibited by i.t. (but not by i.d.) treatment with DALBK. Conversely, neither Hoe 140 nor DALBK were able to inhibit SLIGRL-NH(2)-induced scratching behaviour when given intracerebroventricularly (i.c.v.). CONCLUSIONS AND IMPLICATIONS: The present results demonstrated that kinins acting on both B(1) and B(2) receptors played a crucial role in controlling the pruriceptive signalling triggered by PAR-2 activation in mice.