A fixed combination of probiotics and herbal extracts attenuates intestinal barrier dysfunction from inflammatory stress in an in vitro model using Caco-2 cells.

Background: Inflammatory Bowel Diseases (IBD), are considered a growing global disease, with about ten million people being affected worldwide. Maintenance of intestinal barrier integrity is crucial for preventing IBD onset and exacerbations. Some recent patents regarding oily formulations containing probiotics (WO2010122107A1 and WO2010103374A9) and the use of probiotics for gastrointestinal complaints (US20110110905A1 and US9057112B2) exist, or are pending application. Objective: In this work, we studied the effect of a fixed combination of registered Lactobacillus reuteri and Lactobacillus acidophilus strains and herbal extracts in an in vitro inflammation experimental model. Methods: Caco-2 cell monolayer was exposed to INF-\u3b3+TNF-\u3b1 or to LPS; Trans Epithelial Electrical Resistance (TEER) and paracellular permeability were investigated. ZO-1 and occludin Tight Junctions (TJs) were also investigated by mean of immunofluorescence. Results: Pre-treatment with the fixed combination of probiotics and herbal extracts prevented the inflammation-induced TEER decrease, paracellular permeability increase and TJs translocation. Conclusions: In summary, the fixed combination of probiotics and herbal extracts investigated in this research was found to be an interesting candidate for targeting the re-establishment of intestinal barrier function in IBD conditions

Effect of partial substitution of fishmeal with insect meal (Hermetia illucens) on gut neuromuscular function in Gilthead sea bream (Sparus aurata)

Alternative nutrient sources to fishmeal for fish feed, such as insect meals, represent a promising sustainable supply. However, the consequences for fish digestive function have not been exhaustively investigated. In the present study we evaluated the effect of partial fishmeal substitution with 10% Hermetia illucens (Hi10) larvae meal on the neuromuscular function of proximal and distal intestine in gilthead sea bream. In animals fed with insect meal, weight and growth parameters were similar to controls fed with conventional fishmeal. In addition, no anomalies in intestinal gross morphology and no overt signs of inflammation were observed. The gastrointestinal transit was significantly reduced in Hi10 fed animals. In the proximal and distal intestine longitudinal muscle, Hi10 feeding downregulated the excitatory cholinergic and serotoninergic transmission. Sodium nitroprussideinduced inhibitory relaxations increased in the proximal intestine and decreased in the distal intestine after Hi10 meal. Changes in the excitatory and inhibitory components of peristalsis were associated with adaptive changes in the chemical coding of both proximal and distal intestine myenteric plexus. However, these neuromuscular function alterations were not associated with considerable variations in morphometric growth parameters, suggesting that 10% Hi meal may represent a tolerable alternative protein source for gilthead sea bream diets

Indicador organizacional de la cultura de seguridad en un hospital universitario

Objetivo: avaliar a cultura de segurança organizacional de um hospital universitário português a partir da percepção dos enfermeiros. Método: estudo transversal, tipo survey, com 567 enfermeiros de um hospital universitário do Porto, Portugal, realizado de abril a dezembro de 2014. Utilizou-se o instrumento do Hospital Survey on Patient Safety Culture. Para análise, realizou-se a recodificação da Escala de Likert e aplicou-se a estatística descritiva. Resultados: as dimensões que apresentaram percentual elevado de respostas positivas foram: Trabalho em equipe dentro das unidades (78,69%) e Expectativa e ações de promoção de segurança do paciente dos supervisores (65,94%). Evidenciou-se que 248 (44,4%) profissionais não notificaram nenhum evento e apenas 13 (2,3%) notificaram mais de seis eventos no último ano. Conclusão: a avalição permitiu identificar uma dimensão forte e algumas fragilidades da organização. Os resultados são relevantes e servem de embasamento para os gestores e líderes de enfermagem, permitindo avançar na cultura de segurança.Objective: to evaluate the organizational safety culture of a Portuguese university hospital on the basis of nurses’ perceptions. Method: this cross-sectional, survey-type study of 567 nurses at a university hospital in Porto, Portugal, was conducted from April to December 2014, using the Survey on Patient Safety Culture instrument. For the analysis, the Likert Scale was recoded, and descriptive statistics were used. Results: the dimensions that returned high percentage positive responses were: Teamwork within units (78.69%) and Supervisor Expectations and Actions Promoting Patient Safety (65.94%). It was found that 248 (44.4%) of personnel did not report any event, and only 13 (2.3%) had reported more than six events in the prior year. Conclusion: the assessment identified one strong dimension in the organization, and some weaknesses. The results are significant and offer a foundation for nursing managers and leaders to improve safety culture. Descriptors: Organizational culture; patient safety; hospitals; quality of nursing care.Objetivo: evaluar la cultura de seguridad de la organización de un hospital universitario portugués desde el punto de vista de las enfermeras. Método: estudio transversal, tipo encuesta, junto a 567 enfermeros de un hospital universitario en Oporto, Portugal, que tuvo lugar entre abril y diciembre de 2014. Utiliza el instrumento de Hospital Survey on Patient Safety Culture. Para el análisis, se realizó recodificación de la Escala de Likert y se utilizó la estadística descriptiva. Resultados: Las dimensiones que presentaron un alto porcentaje de respuestas positivas fueron: Trabajo en equipo dentro de las unidades (78,69%) y Expectativa y acciones de promoción de seguridad del paciente de los supervisores (65,94%). Se evidenció que 248 (44,4%) de los profesionales no notificaron ningún evento y sólo 13 (2,3%) notificaron más de seis eventos el último año. Conclusión: la evaluación permitió identificar una dimensión fuerte y algunas fragilidades de la organización. Los resultados son relevantes y sirven de base para los gestores y líderes de enfermería, permitiendo avanzar en la cultura de seguridad.info:eu-repo/semantics/publishedVersio

Cultura de segurança dos enfermeiros entre os serviços de um hospital universitário

To evaluate nurse safety culture in a teaching hospital, as well as to verify differences in the safety culture dimensions between services.Objetivo: Avaliar a cultura de segurança dos enfermeiros de um hospital de ensino e verificar as diferenças das dimensões dessa cultura entre os serviços. Método: Estudo transversal e quantitativo, realizado em outubro a dezembro de 2015, em um hospital universitário. Foi aplicado o instrumento Hospital Survey on Patient Safety Culture. Resultados: Participaram 195 enfermeiros de quatro serviços. Identificou-se diferença significativa entre os serviços para cinco dimensões de cultura de segurança: aprendizado organizacional (p = 0.012); retorno da informação e comunicação a respeito de erro (p = 0.014); suporte da gestão para segurança do paciente (p = 0.001); percepções gerais sobre segurança do paciente (p = 0.005); e frequência da notificação de eventos (p = 0.003). Conclusão: O serviço de clínica médica apresentou maior diferença estatística entre as dimensões. Essas avaliações permitem que os gestores identifiquem as diferenças entre os serviços do mesmo hospital, servindo de alerta e aperfeiçoando os serviços. Descritores: Segurança do Paciente; Cultura Organizacional; Qualidade da Assistência à Saúde; Hospitais; Gestão de Riscos.info:eu-repo/semantics/publishedVersio

A proposed design for the evaluation of change in a small reference group.

Herpes Simplex Virus type 1 (HSV-1), a neurotropic pathogen widespread in human population, infects the enteric nervous system (ENS) in humans and rodents and causes intestinal neuromuscular dysfunction in rats. Although infiltration of inflammatory cells in the myenteric plexus and neurodegeneration of enteric nerves are common features of patients suffering from functional intestinal disorders, the proof of a pathogenic link with HSV-1 is still unsettled mainly because the underlying mechanisms are largely unknown. In this study we demonstrated that following intragastrical administration HSV-1 infects neurons within the myenteric plexus resulting in functional and structural alterations of the ENS. By infecting mice with HSV-1 replication-defective strain we revealed that gastrointestinal neuromuscular anomalies were however independent of viral replication. Indeed, enteric neurons exposed to UV-inactivated HSV-1 produced monocyte chemoattractant protein-1 (MCP-1/CCL2) to recruit activated macrophages in the longitudinal muscle myenteric plexus. Infiltrating macrophages produced reactive oxygen and nitrogen species and directly harmed enteric neurons resulting in gastrointestinal dysmotility. In HSV-1 infected mice intestinal neuromuscular dysfunctions were ameliorated by in vivo administration of (i) liposomes containing dichloromethylene bisphosphonic acid (clodronate) to deplete tissue macrophages, (ii) CCR2 chemokine receptor antagonist RS504393 to block the CCL2/CCR2 pathway, (iii) Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) and AR-C 102222 to quench production of nitrogen reactive species produced via iNOS. Overall these data demonstrate that HSV-1 infection makes enteric neurons recruit macrophages via production of a specific chemoattractant factor. The resulting inflammatory reaction is mandatory for intestinal dysmotility. These findings provide insights into the neuro-immune communication that occurs in the ENS following HSV-1 infection and allow recognition of an original pathophysiologic mechanism underlying gastrointestinal diseases as well as identification of novel therapeutic targets

Evaluación de la cultura de seguridad del paciente: estudio comparativo en hospitales universitarios

Objective: To conduct a benchmarking comparison of the composites of patient safety culture based on the evaluation of Brazilian and Portuguese nurses working in university hospitals. Method: Quantitative, cross-sectional, comparative survey. Data collected between April and December 2014, in two teaching hospitals, applying the instrument Hospital Survey on Patient Safety Culture, in the versions translated and adapted to the countries. Results: 762 nurses distributed in four services participated in the study, 195 Brazilians and 567 Portuguese. Seven of the 12 composites of safety culture showed significant differences between hospitals. The highlights were those related to: “management support for patient safety” (±17); “handoffs and transitions” (±15); “teamwork across units” (±14); and “overall perceptions of patient safety” (±10). Conclusion: The dimension that had the highest significant difference between the studied institutions was “management support for patient safety”. These data may support the managers of the study hospitals, enabling continuous improvements and advancements.info:eu-repo/semantics/publishedVersio

Antibiotic treatment-induced dysbiosis differently affects BDNF and TrkB expression in the brain and in the gut of juvenile mice

Antibiotic use during adolescence may result in dysbiosis-induced neuronal vulnerability both in the enteric nervous system (ENS) and central nervous system (CNS) contributing to the onset of chronic gastrointestinal disorders, such as irritable bowel syndrome (IBS), showing significant psychiatric comorbidity. Intestinal microbiota alterations during adolescence influence the expression of molecular factors involved in neuronal development in both the ENS and CNS. In this study, we have evaluated the expression of brain-derived neurotrophic factor (BDNF) and its high-affinity receptor tropomyosin-related kinase B (TrkB) in juvenile mice ENS and CNS, after a 2-week antibiotic (ABX) treatment. In both mucosa and mucosa-deprived whole-wall small intestine segments of ABX-treated animals, BDNF and TrKB mRNA and protein levels significantly increased. In longitudinal muscle-myenteric plexus preparations of ABX-treated mice the percentage of myenteric neurons staining for BDNF and TrkB was significantly higher than in controls. After ABX treatment, a consistent population of BDNF-and TrkB-immunoreactive neurons costained with SP and CGRP, suggesting up-regulation of BDNF signaling in both motor and sensory myenteric neurons. BDNF and TrkB protein levels were downregulated in the hippocampus and remained unchanged in the prefrontal cortex of ABX-treated animals. Immunostaining for BDNF and TrkB decreased in the hippocampus CA3 and dentate gyrus subregions, respectively, and remained unchanged in the prefrontal cortex. These data suggest that dysbiosis differentially influences the expression of BDNF-TrkB in the juvenile mice ENS and CNS. Such changes may potentially contribute later to the development of functional gut disorders, such as IBS, showing psychiatric comorbidity

Apple polyphenol extract improves insulin sensitivity in vitro and in vivo in animal models of insulin resistance

Background: Apple polyphenols could represent a novel nutritional approach in the management and control of blood glucose, especially in type 2 diabetics. The aim of this study was to test the therapeutic potential of an apple polyphenol extract (APE) in an insulin-resistant rat model and to determine the molecular basis of insulin sensitivity action in skeletal muscle cells.Methods: Acute effect of APE on the postprandial hyperglycemic response was assayed in 15 week old obese Zucker rats (OZR), by using a meal tolerance test (MTT). The ability of APE to improve whole peripheral insulin sensitivity was also assayed in a chronic study by using the euglycemic-hyperinsulinemic clamp technique. To elucidate the molecular mechanisms, rat L6 myotubes were used. Glucose uptake was measured by using 2-[3H]-Deoxy-Glucose (2-DG) and specific inhibitors, as well as phosphorylation status of key kinases, were used to determine the implicated signaling pathway.Results: In vivo study showed that nutritional intervention with APE induced an increase of insulin sensitivity with an increase of glucose infusion rate (GIR) of 45 %. Additionally, in vitro results showed a synergistic effect between APE and insulin as well as increased glucose uptake through GLUT4 translocation in muscle cells. This translocation was mediated by phosphatydil inositol 3-kinase (PI3K) and peroxisome proliferator-activated receptor-gamma (PPARγ) signaling pathways.Conclusions: As a whole, this study describes the mechanisms involved in the insulin sensitizing effect of APE, which could be considered a promising ingredient for inclusion in nutritional products focused on the management of chronic diseases such as diabetes.This research was supported by funds from Abbott Laboratories S.A

Arthroscopic evaluation of the ACL double bundle structure

In order to describe the arthroscopic presence of the double bundle structure and to evaluate the value of different portals in knee arthroscopy, we assessed the AM and PL bundle anatomy. We prospectively examined the knees of 60 patients undergoing arthroscopic surgery for pathology unrelated to the ACL. Arthroscopy was performed in a two portal technique using an anterolateral (ALP) and an anteromedial (AMP) portal. With the arthroscope in the ALP, we could distinguish an AM and PL bundle in 28%. Switching the arthroscope to the AMP, differentiation of the bundles was possible in 67%. In all remaining cases visualization of the PL bundle was possible after retraction of the AM bundle. Use of AMP increased visualization of the PL bundle. It seems reasonable to perform arthroscopy for ACL reconstruction with the arthroscope in the AMP and to establish an additional medial working portal to increase the visualization of the femoral ACL insertion sites for optimal femoral tunnel placement

Interleukin-15 Plays a Central Role in Human Kidney Physiology and Cancer through the γc Signaling Pathway

The ability of Interleukin-15 (IL-15) to activate many immune antitumor mechanisms renders the cytokine a good candidate for the therapy of solid tumors, particularly renal cell carcinoma. Although IL-15 is being currently used in clinical trials, the function of the cytokine on kidney's components has not been extensively studied; we thus investigated the role of IL-15 on normal and tumor renal epithelial cells. Herein, we analyzed the expression and the biological functions of IL-15 in normal renal proximal tubuli (RPTEC) and in their neoplastic counterparts, the renal clear cell carcinomas (RCC). This study shows that RPTEC express a functional heterotrimeric IL-15Rαβγc complex whose stimulation with physiologic concentrations of rhIL-15 is sufficient to inhibit epithelial mesenchymal transition (EMT) commitment preserving E-cadherin expression. Indeed, IL-15 is not only a survival factor for epithelial cells, but it can also preserve the renal epithelial phenotype through the γc-signaling pathway, demonstrating that the cytokine possess a wide range of action in epithelial homeostasis. In contrast, in RCC in vitro and in vivo studies reveal a defect in the expression of γc-receptor and JAK3 associated kinase, which strongly impacts IL-15 signaling. Indeed, in the absence of the γc/JAK3 couple we demonstrate the assembly of an unprecedented functional high affinity IL-15Rαβ heterodimer, that in response to physiologic concentrations of IL-15, triggers an unbalanced signal causing the down-regulation of the tumor suppressor gene E-cadherin, favoring RCC EMT process. Remarkably, the rescue of IL-15/γc-dependent signaling (STAT5), by co-transfecting γc and JAK3 in RCC, inhibits EMT reversion. In conclusion, these data highlight the central role of IL-15 and γc-receptor signaling in renal homeostasis through the control of E-cadherin expression and preservation of epithelial phenotype both in RPTEC (up-regulation) and RCC (down-regulation)