Seroreactivity Against Tyrosine Phosphatase PTPRN Links Type 2 Diabetes and Colorectal Cancer and Identifies a Potential Diagnostic and Therapeutic Target.

Colorectal cancer (CRC) and diabetes are two of the most prevalent chronic diseases worldwide with dysregulated receptor tyrosine kinase signaling and strong co-occurrence correlation. Plasma autoantibodies represent a promising early diagnostic marker for both diseases before symptoms appear. In this study, we explore the value of autoantibodies against receptor-type tyrosine-protein phosphatase-like N (PTPRN; full-length or selected domains) as diagnostic markers using a cohort of individuals with type 2 diabetes (T2D), CRC, or both diseases or healthy individuals. We show that PTPRN autoantibody levels in plasma discriminated between patients with T2D with and without CRC. Consistently, high PTPRN expression correlated with decreased survival of patients with CRC. Mechanistically, PTPRN depletion significantly reduced invasiveness of CRC cells in vitro and liver homing and metastasis in vivo by means of a dysregulation of the epithelial-mesenchymal transition and a decrease of the insulin receptor signaling pathway. Therefore, PTPRN autoantibodies may represent a particularly helpful marker for the stratification of patients with T2D at high risk of developing CRC. Consistent with the critical role played by tyrosine kinases in diabetes and tumor biology, we provide evidence that tyrosine phosphatases such as PTPRN may hold potential as therapeutic targets in patients with CRC.

Ozone therapy versus surgery for lumbar disc herniation: A randomized double-blind controlled trial.

OBJECTIVES: Surgery is the treatment of choice for symptomatic disc herniation after conservative management. Several studies have suggested the potential utility of intradiscal ozone infiltration in this pathology. The aim of this trial was to compare intradiscal ozone infiltration vs. oxygen infiltration vs. surgery. DESIGN AND INTERVENTIONS: This was a randomized, double-blinded, and controlled trial in patients on a waiting list for herniated disc surgery. There were three treatment groups: surgery; intradiscal ozone infiltration (plus foraminal infiltration of ozone, steroids, and anesthetic); intradiscal oxygen infiltration (plus foraminal infiltration of oxygen, steroids, and anesthetic). MAIN OUTCOME MEASURES: The requirements for surgery. RESULTS: Five years after the treatment of the last recruited patient (median follow-up: 78 months), the requirement for further surgery was 20 % for patients in the ozone group and 60 % for patients in the oxygen group. 11 % of patients initially treated with surgery also required a second surgery. Compared to the surgery group, the ozone group showed: 1) significantly lower number of inpatient days: median 3 days (interquartile range: 3-3.5 days) vs. 0 days (interquartile range: 0-1.5 days), p = 0.012; 2) significantly lower costs: median EUR 3702 (interquartile range: EUR 3283-7630) vs. EUR 364 (interquartile range: EUR 364-2536), p = 0.029. CONCLUSIONS: Our truncated trial showed that intradiscal ozone infiltrations decreased the requirements for conventional surgery, resulting in decreased hospitalization durations and associated costs. These findings and their magnitude are of interest to patients and health services providers. Further validation is ongoing.

Pulsed Ultrasounds Reduce Pain and Disability, Increasing Rib Fracture Healing, in a Randomized Controlled Trial.

INTRODUCTION: Rib fractures are an important health issue worldwide, with significant, pain, morbidity, and disability for which only symptomatic treatment exists. OBJECTIVES: Based on our previous experimental model, the objective of the current study was to assess for the first time whether pulsed ultrasound (PUS) application could have beneficial effects on humans. METHODS: Prospective, double-blinded, randomized, controlled trial of 51 patients. Four were excluded, and 47 were randomized into the control group (N = 23) or PUS group (N = 24). The control group received a PUS procedure without emission, and the PUS group received 1 Mhz, 0.5 W/cm2 for 1 min/cm2. Pain level, bone callus healing rate, physical and work activity, pain medication intake, and adverse events were blindly evaluated at baseline and one, three, and six months. RESULTS: There were no significant differences at baseline between groups. PUS treatment significantly decreased pain by month 1 (P = 0.004), month 3 (P = 0.005), and month 6 (P = 0.025), significantly accelerated callus healing by month 1 (P = 0.013) and month 3 (P < 0.001), accelerated return to physical activity by month 3 (P = 0.036) and work activity (P = 0.001) by month 1, and considerably reduced pain medication intake by month 1 (P = 0.057) and month 3 (P = 0.017). No related adverse events were found in the PUS group. CONCLUSIONS: This study is the first evidence that PUS treatment is capable of improving rib fracture outcome, significantly accelerating bone callus healing, and decreasing pain, time off due to both physical activity and convalescence period, and pain medication intake. It is a safe, efficient, and low-cost therapy that may become a new treatment for patients with stable rib fractures.

PICK1 regulates AMPA receptor endocytosis via direct interactions with AP2 α-appendage and dynamin.

Clathrin-mediated endocytosis (CME) is used to internalize a diverse range of cargo proteins from the cell surface, often in response to specific signals. In neurons, the rapid endocytosis of GluA2-containing AMPA receptors (AMPARs) in response to NMDA receptor (NMDAR) stimulation causes a reduction in synaptic strength and is the central mechanism for long-term depression, which underlies certain forms of learning. The mechanisms that link NMDAR activation to CME of AMPARs remain elusive. PICK1 is a BAR domain protein required for NMDAR-dependent reductions in surface GluA2; however, the molecular mechanisms involved are unclear. In this study, we show that PICK1 makes direct, NMDAR-dependent interactions with the core endocytic proteins AP2 and dynamin. PICK1-AP2 interactions are required for clustering AMPARs at endocytic zones in dendrites in response to NMDAR stimulation and for consequent AMPAR internalization. We further show that PICK1 stimulates dynamin polymerization. We propose that PICK1 is a cargo-specific endocytic accessory protein required for efficient, activity-dependent AMPAR endocytosis.

Endocytosis and lysosomal degradation of GluA2/3 AMPARs in response to oxygen/glucose deprivation in hippocampal but not cortical neurons.

Global cerebral ischemia results in oxygen and glucose deprivation (OGD) and consequent delayed cell death of vulnerable neurons, with hippocampal CA1 neurons more vulnerable than cortical neurons. Most AMPA receptors (AMPARs) are heteromeric complexes of subunits GluA1/GluA2 or GluA2/GluA3, and the presence of GluA2 renders AMPARs Ca2+-impermeable. In hippocampal CA1 neurons, OGD causes the synaptic expression of GluA2-lacking Ca2+-permeable AMPARs, contributing to toxic Ca2+ influx. The loss of synaptic GluA2 is caused by rapid trafficking of GluA2-containing AMPARs from the cell surface, followed by a delayed reduction in GluA2 mRNA expression. We show here that OGD causes endocytosis, lysosomal targeting and consequent degradation of GluA2- and GluA3-containing AMPARs, and that PICK1 is required for both OGD-induced GluA2 endocytosis and lysosomal sorting. Our results further suggest that GluA1-containing AMPARs resist OGD-induced endocytosis. OGD does not cause GluA2 endocytosis in cortical neurons, and we show that PICK1 binding to the endocytic adaptor AP2 is enhanced by OGD in hippocampal, but not cortical neurons. We propose that endocytosis of GluA2/3, caused by a hippocampal-specific increase in PICK1-AP2 interactions, followed by PICK1-dependent lysosomal targeting, are critical events in determining changes in AMPAR subunit composition in the response to ischaemia.

The PICK1 Ca2+ sensor modulates N-methyl-d-aspartate (NMDA) receptor-dependent microRNA-mediated translational repression in neurons.

MicroRNAs (miRNAs) are important regulators of localized mRNA translation in neuronal dendrites. The presence of RNA-induced silencing complex proteins in these compartments and the dynamic miRNA expression changes that occur in response to neuronal stimulation highlight their importance in synaptic plasticity. Previously, we demonstrated a novel interaction between the major RNA-induced silencing complex component Argounaute-2 (Ago2) and the BAR (bin/amphiphysin/rvs) domain protein PICK1. PICK1 recruits Ago2 to recycling endosomes in dendrites, where it inhibits miRNA-mediated translational repression. Chemical induction of long-term depression via NMDA receptor activation causes the dissociation of Ago2 from PICK1 and a consequent increase in dendritic miRNA-mediated gene silencing. The mechanism that underlies the regulation of PICK1-Ago2 binding is unknown. In this study, we demonstrate that the PICK1-Ago2 interaction is directly sensitive to Ca2+ ions so that high [Ca2+]free reduces PICK1 binding to Ago2. Mutating a stretch of C-terminal Ca2+-binding residues in PICK1 results in a complete block of NMDA-induced PICK1-Ago2 disassociation in cortical neurons. Furthermore, the same mutant also blocks NMDA-stimulated miRNA-mediated gene silencing. This study defines a novel mechanism whereby elevated [Ca2+] induced by NMDA receptor activation modulates Ago2 and miRNA activity via PICK1. Our work suggests a Ca2+-dependent process to regulate miRNA activity in neurons in response to the induction of long-term depression.

Adherence to antiretrovirals in people coinfected with the human immunodeficiency virus and tuberculosis.

OBJECTIVE: assess the adherence levels to antiretroviral therapy in people coinfected with HIV/tuberculosis and correlate these levels with the sociodemographic and clinical variables of the study population. METHOD: cross-sectional study involving 74 male and female adults coinfected with HIV/tuberculosis. For the data collection, a sociodemographic and clinical assessment form and the Antiretroviral Treatment Adherence Assessment Questionnaire were used. For the data analysis, the software STATA version 11 was used, through descriptive statistics, Fisher's chi-square exact test and the probability test. RESULTS: men were predominant (79.7%), between 30 and 39 years of age (35.1%), low income (75.7%) and pulmonary tuberculosis (71.6%). Adherence to antiretroviral therapy was inappropriate in 78.1% of the men; 61.0% of single people; 47.0% unemployed and 76.5% among people gaining less than one minimum wage. A significant difference was observed between compliance and length of use of antiretrovirals (p=0.018), sexual orientation (p=0.024) and number of children (p=0.029). CONCLUSION: the coinfected patients presented inappropriate adherence to the antiretrovirals, a fact that negatively affects the health conditions of the people living with HIV/tuberculosis coinfection. A statistically significant correlation was found between the levels of adherence and some sociodemographic and clinical characteristics.

Adherence to antiretrovirals in people coinfected with the human immunodeficiency virus and tuberculosis / Adesão aos antirretrovirais em pessoas com coinfecção pelo vírus da imunodeficiência humana e tuberculose / Adhesión a los antiretrovirales en personas coinfectadas por el virus de la inmunodeficiencia humana y tuberculosis

Objective: assess the adherence levels to antiretroviral therapy in people coinfected with HIV/tuberculosis and correlate these levels with the sociodemographic and clinical variables of the study population. Method: cross-sectional study involving 74 male and female adults coinfected with HIV/tuberculosis. For the data collection, a sociodemographic and clinical assessment form and the Antiretroviral Treatment Adherence Assessment Questionnaire were used. For the data analysis, the software STATA version 11 was used, through descriptive statistics, Fisher's chi-square exact test and the probability test. Results: men were predominant (79.7%), between 30 and 39 years of age (35.1%), low income (75.7%) and pulmonary tuberculosis (71.6%). Adherence to antiretroviral therapy was inappropriate in 78.1% of the men; 61.0% of single people; 47.0% unemployed and 76.5% among people gaining less than one minimum wage. A significant difference was observed between compliance and length of use of antiretrovirals (p=0.018), sexual orientation (p=0.024) and number of children (p=0.029). Conclusion: the coinfected patients presented inappropriate adherence to the antiretrovirals, a fact that negatively affects the health conditions of the people living with HIV/tuberculosis coinfection. A statistically significant correlation was found between the levels of adherence and some sociodemographic and clinical characteristics.

Objetivo: avaliar os níveis de adesão à terapia antirretroviral em coinfectados pelo HIV/tuberculose e correlacionar esses níveis com as variáveis sociodemográficas e clínicas da população em estudo. Método: estudo transversal, com 74 pessoas adultas, de ambos os sexos, coinfectadas por HIV/tuberculose. Utilizou-se, para coleta de dados, um formulário de avaliação sociodemográfica e clínica e o Questionário de Avaliação da Adesão ao Tratamento Antirretroviral. A análise dos dados ocorreu mediante o uso do STATA, versão11, por meio de estatística descritiva, do teste qui-quadrado exato de Fisher e de probabilidade. Resultados: predominaram homens (79,7%), com idade entre 30 e 39 anos (35,1%), com baixa renda (75,7%) e tuberculose pulmonar (71,6%). A adesão à terapia antirretroviral mostrou-se inadequada em 78,1% dos homens; 61,0% dos solteiros; 47,0% dos desempregados e 76,5% entre pessoas com renda inferior a um salário-mínimo. Observou-se diferença significativa entre a adesão e o tempo de uso dos antirretrovirais (p=0,018), orientação sexual (p=0,024) e número de filhos (p=0,029). Conclusão: os coinfectados apresentaram adesão inadequada aos antirretrovirais, fato que repercute de modo negativo nas condições de saúde das pessoas que vivem com a coinfecção HIV/tuberculose. Constatou-se correlação estatisticamente significante entre os níveis de adesão e algumas características sociodemográficas e clínicas.

Objetivo: evaluar los niveles de adhesión a la terapia antiretroviral en coinfectados por el VIH/tuberculosis y correlacionar esos niveles con las variables sociodemográficas e clínicas de la población estudiada. Método: estudio trasversal con 74 personas adultas, de ambos sexos, coinfectadas por HIV/tuberculosis. Fue utilizado para recolectar los datos un formulario de evaluación sociodemográfica y clínica y el Cuestionario de Evaluación de la Adhesión al Tratamiento Antirretroviral. El análisis de los datos fue efectuado con el uso de STATA, versión 11, mediante estadística descriptiva, la prueba ji-cuadrado exacto de Fisher y de probabilidad. Resultados: predominaron hombres (79,7%), con edad entre 30 y 39 años (35,1%), baja renta (75,7%) y tuberculosis pulmonar (71,6%). La adhesión a la terapia antiretroviral se mostró inadecuada en 78,1% de los hombres; 61,0% de los solteros; 47,0% de los desempleados y 76,5% entre personas con renta inferior a un salario-mínimo. Se observó diferencia significativa entre la adhesión y el tiempo de uso de los antiretrovirales (p=0,018), orientación sexual (p=0,024) y número de hijos (p=0,029). Conclusión: los coinfectados presentaron adhesión inadecuada a los antiretrovirales, hecho que influye negativamente en las condiciones de salud de las personas que viven con la coinfección HIV/tuberculosis. Se constató correlación estadísticamente significante entre los niveles de adhesión y algunas características sociodemográficas y clínicas.

Social support for people living with acquired immunodeficiency syndrome / Apoyo social de las personas que viven con síndrome de inmunodeficiencia adquirida / Suporte social de pessoas que vivem com a síndrome da imunodeficiência adquirida

ABSTRACT The aim of this study was to evaluate the social support for people with AIDS. It was a cross-sectional study, with 215 outpatients at a University Hospital in Northeastern Brazil. Data were collected from August to December 2012, through interviews, using a Socio-demographic and Clinical Form and a Social Support Scale for People Living with HIV/AIDS. Statistical Package for the Social Science was used for data analysis. Results showed that average scores of social emotional and instrumental support were satisfactory and not influenced by sex (p=0.954; p=0.508), education (p=0.756; p=0.194), marital status (p=0.076; p=0.446) and length of antiretroviral therapy (p=0.480; p=0.120). People diagnosed for less than three years had more instrumental support (p=0.048) than those diagnosed over three years (p=0.370). Neighbors, employers and health professionals provided less support. The conclusion was that people with AIDS have satisfactory social support, especially from friends and family not living in the same household.

RESUMEN Este estudio objetivó evaluar el apoyo social a personas con SIDA. Estudio transversal con muestra de 215 pacientes ambulatorios de un hospital universitario del nordeste de Brasil. Los datos recolectados entre agosto y diciembre de 2012, a través de entrevistas utilizando el formulario sociodemográfico y clínico y la Escala de Apoyo Social para las Personas que Viven con VIH/SIDA. El Statistical Package for the Social Science fue utilizado para análisis de datos. Los resultados evidenciaron que las puntuaciones medias de apoyo social emocionales e instrumentales fueron satisfactorios, y no influenciados por el sexo (p=0,954; p=0,508), educación (p=0,756; p=0,194), estado civil (p=0,076; p=0,446) y tiempo de terapia antirretroviral (p=0,480; p=0,120). Las personas diagnosticadas en menos de tres años tenían más apoyo instrumental (p=0,048) que los diagnosticados hace más de tres años (p=0,370). Los vecinos, jefe y profesionales de salud proporcionaban menos apoyo. Se concluyó que personas con SIDA tienen un apoyo social satisfactorio, principalmente por parte de amigos y familiares que no viven en el mismo hogar.

RESUMO Teve-se como objetivo avaliar o suporte social de pessoas com aids. Estudo transversal, com amostra de 215 pacientes ambulatoriais de um hospital universitário do Nordeste brasileiro. Dados coletados de agosto a dezembro de 2012, por meio de entrevista, utilizando formulário sociodemográfico e clínico e Escala de Suporte Social para Pessoas Vivendo com HIV/aids. O Statistical Package for the Social Science foi utilizado para análise de dados. Resultados mostraram que médias de escores de suporte social emocional e instrumental foram satisfatórias e não influenciadas pelo sexo (p=0,954; p=0,508), escolaridade (p=0,756; p=0,194), situação conjugal (p=0,076; p=0,446) e tempo de terapia antirretroviral (p=0,480; p=0,120). Pessoas diagnosticadas há menos de três anos tiveram mais suporte instrumental (p=0,048) que os diagnosticados há mais de três anos (p=0,370). Vizinhos, chefe e profissionais da saúde forneceram menos apoio. Concluiu-se que pessoas com aids possuem suporte social satisfatório, principalmente, de amigos e familiares que não moram no mesmo domicílio.

Quality of life of men with AIDS and the model of social determinants of health.

OBJECTIVE: to analyze the quality of life (QoL) of men with AIDS from the perspective of the model of social determinants of health (MSDH). METHOD: cross-sectional study conducted in an outpatient infectious diseases clinic from a Brazilian university hospital over the course of one year with a sample of 138 patients. A form based on the MSDH was used to collect sociodemographic data addressing individual, proximal, intermediate determinants and the influence of social networks together with an instrument used to assess the QoL of people with HIV/AIDS. The project was approved by the Institutional Review Board (Protocol No. 040.06.12). RESULTS: according to MSDH, most men with AIDS were between 30 and 49 years old (68.1%), mixed race (59.4%), heterosexual (46.4%), single (64.5%), Catholic (68.8%), had a bachelor's degree (39.2%), had no children (61.6%), and had a formal job (71.0%). The perception of QoL in the physical, level of independence, environment, and spirituality domains was intermediate, while QoL was perceived to be superior in the domains of psychological and social relationship. A perception of lower QoL was presented by homosexual (p=0.037) and married men (p=0.077), and those with income below one times the minimum wage (p=0.042). A perception of greater QoL was presented by those without a religion (p=0.005), living with a partner (p=0.049), and those who had a formal job (p=0.045). CONCLUSION: social determinants influence the QoL of men with AIDS.

Quality of life of men with AIDS and the model of social determinants of health / Qualidade de vida de homens com AIDS e o modelo da determinação social da saúde / Calidad de vida de hombres con Sida y el modelo de la determinación social de la salud

OBJECTIVE: to analyze the quality of life (QoL) of men with AIDS from the perspective of the model of social determinants of health (MSDH). METHOD: cross-sectional study conducted in an outpatient infectious diseases clinic from a Brazilian university hospital over the course of one year with a sample of 138 patients. A form based on the MSDH was used to collect sociodemographic data addressing individual, proximal, intermediate determinants and the influence of social networks together with an instrument used to assess the QoL of people with HIV/AIDS. The project was approved by the Institutional Review Board (Protocol No. 040.06.12). RESULTS: according to MSDH, most men with AIDS were between 30 and 49 years old (68.1%), mixed race (59.4%), heterosexual (46.4%), single (64.5%), Catholic (68.8%), had a bachelor's degree (39.2%), had no children (61.6%), and had a formal job (71.0%). The perception of QoL in the physical, level of independence, environment, and spirituality domains was intermediate, while QoL was perceived to be superior in the domains of psychological and social relationship. A perception of lower QoL was presented by homosexual (p=0.037) and married men (p=0.077), and those with income below one times the minimum wage (p=0.042). A perception of greater QoL was presented by those without a religion (p=0.005), living with a partner (p=0.049), and those who had a formal job (p=0.045). CONCLUSION: social determinants influence the QoL of men with AIDS. .

OBJETIVO: analisar a qualidade de vida (QV) de homens com AIDS, na perspectiva do modelo da determinação social da saúde (MDSS). MÉTODO: Estudo transversal, realizado em ambulatório de infectologia de um hospital universitário no Brasil durante um ano, com amostra de 138 pacientes. Para coleta de dados, utilizaram-se o formulário de caracterização sociodemográfica baseado no MDSS, envolvendo os determinantes individuais, proximais, intermediários e influência das redes sociais, além do instrumento de avaliação da QV de pessoas com HIV/AIDS. Projeto aprovado pelo comitê de ética sob protocolo no 040.06.12. RESULTADOS: segundo o MDSS, a maioria dos homens com AIDS possuíam faixa etária de 30-49 anos (68,1%), cor parda (59,4%), heterossexuais (46,4%), solteiros (64,5%), católicos (68,8%), nível superior (39,2%), sem filhos (61,6%) e com vínculo empregatício (71,0%). A percepção da QV foi intermediária nos domínios físico, nível de independência, meio ambiente e espiritualidade, e para domínios psicológico e relações sociais, foi superior. Houve menor percepção da QV para homossexuais (p=0,037), casados (p=0,077) e com renda menor que um salário mínimo (p=0,042). Houve maior percepção da QV para pessoas sem religião (p=0,005), que moravam com parceiro (p=0,049) e com vínculo empregatício (p=0,045). CONCLUSÃO: os determinantes sociais influenciam na QV de homens com AIDS. .

OBJETIVO: analizar la calidad de vida (CV) de hombres con Sida bajo la perspectiva del modelo de la determinación social de la salud (MDSS). MÉTODO: estudio transversal, realizado en ambulatorio de enfermedades infecciosas de un hospital universitario en Brasil, durante un año, con una muestra de 138 pacientes. Para recolección de datos se utilizaron el formulario de caracterización sociodemográfica basado en el MDSS, conteniendo los determinantes individuales, proximales, intermediarios y la influencia de las redes sociales, además del instrumento de evaluación de la CV de personas con HIV/Sida. Proyecto aprobado por el comité de ética con el protocolo n° 040.06.12. RESULTADOS: según el MDSS, la mayoría de los hombres con Sida se encontraba en el intervalo etario de 30 a 49 años (68,1%), color parda (59,4%), heterosexuales (46,4%), solteros (64,5%), católicos (68,8%), nivel superior (39,2%), sin hijos (61,6%) y con vínculo de empleo (71,0%). La percepción de la CV fue intermedia en los dominios: físico, nivel de independencia, medio ambiente y espiritualidad, y para los dominios psicológicos y relaciones sociales, fue superior. Hubo menor percepción de la CV para homosexuales (p=0,037), casados (p=0,077) y con renta menor que un salario mínimo (p=0,042). Hubo mayor percepción de la CV para personas sin religión (p=0,005), que vivían con compañero (p=0,049) y con vínculo de empleo (p=0,045). CONCLUSIÓN: los determinantes sociales influencian la CV de hombres con Sida. .

Qualidade de vida e adesão à medicação antirretroviral em pessoas com HIV / Quality of life and adherence to antiretroviral medication in people with HIV

Objetivo Avaliar e correlacionar a qualidade de vida e a adesão à terapia antirretroviral em pessoas com HIV. Métodos Estudo transversal, desenvolvido com 45 pessoas com HIV em tratamento ambulatorial. Os instrumentos utilizados foram: questionário para avaliação da adesão ao tratamento antirretroviral (CEAT-VIH) e escala para avaliação da qualidade de vida em pessoas com HIV (HAT-QoL). Foi realizada análise descritiva e empregado o teste de correlação linear de Spearman. Resultados A qualidade de vida mostrou-se comprometida nos domínios relacionados às atividades gerais; sexuais; preocupação com a saúde, com o sigilo, com questões financeiras; e conscientização sobre o HIV. Houve predomínio da adesão inadequada em 51,3% dos participantes. A correlação entre os escores das escalas mostrou significância estatística nos domínios relacionados à medicação e confiança no profissional. Conclusão A qualidade de vida apresentou comprometimento em seis domínios da escala e a adesão encontrou-se inadequada na maioria das pessoas com HIV...

Objectives To assess and correlate the quality of life and adherence to antiretroviral therapy in people with HIV. Methods A cross-sectional study was performed with 45 outpatients with HIV. The instruments used were: a questionnaire to assess adherence to antiretroviral therapy (CEAT- HIV), and a scale for assessing quality of life in people with HIV (HAT-QoL). A descriptive analysis was performed and the Spearman’s linear correlation test was used. Results Quality of life was compromised in the dimensions related to overall function; sexual function; health, disclosure and financial worries; and HIV mastery. Poor adherence prevailed in 51.3% of participants. The correlation between the scores of the scales was statistically significant in the dimensions of medication concerns and provider trust. Conclusion The quality of life was compromised in six dimensions of the scale and adherence scale was inadequate in most people with HIV...

Differential Tiam1/Rac1 activation in hippocampal and cortical neurons mediates differential spine shrinkage in response to oxygen/glucose deprivation.

Distinct neuronal populations show differential sensitivity to global ischemia, with hippocampal CA1 neurons showing greater vulnerability compared to cortical neurons. The mechanisms that underlie differential vulnerability are unclear, and we hypothesize that intrinsic differences in neuronal cell biology are involved. Dendritic spine morphology changes in response to ischemic insults in vivo, but cell type-specific differences and the molecular mechanisms leading to such morphologic changes are unexplored. To directly compare changes in spine size in response to oxygen/glucose deprivation (OGD) in cortical and hippocampal neurons, we used separate and equivalent cultures of each cell type. We show that cortical neurons exhibit significantly greater spine shrinkage compared to hippocampal neurons. Rac1 is a Rho-family GTPase that regulates the actin cytoskeleton and is involved in spine dynamics. We show that Rac1 and the Rac guanine nucleotide exchange factor (GEF) Tiam1 are differentially activated by OGD in hippocampal and cortical neurons. Hippocampal neurons express more Tiam1 than cortical neurons, and reducing Tiam1 expression in hippocampal neurons by shRNA enhances OGD-induced spine shrinkage. Tiam1 knockdown also reduces hippocampal neuronal vulnerability to OGD. This work defines fundamental differences in signalling pathways that regulate spine morphology in distinct neuronal populations that may have a role in the differential vulnerability to ischemia.

Stem cells protect the bronchial stump in rat, increasing Sox6, Col2a1, and Agc1 expression.

BACKGROUND: Post-pneumonectomy bronchopleural fistulas (BPFs) are associated with high morbidity and mortality. Currently, since the management of BPFs is difficult to assess, the best therapeutic approach is prevention. Our objective was to evaluate the effects of adipose-derived stem cells (ASCs) on the healing of the bronchial stump in an experimental animal model. METHODS: Left pneumonectomy was performed in 37 Sprague-Dawley rats. Animals were randomly assigned to a control group (n = 13), an ASC group (n = 12), and an ASC plus Tissucol(®) group (ASCT) (n = 12). The ASCs and ASCTs were locally administered at the bronchial stump after surgical pneumonectomy. Animals were killed at 10 and 20 days. We analyzed histological changes and changes in the expression of relevant genes involved in wound repair in the bronchial stump. RESULTS: Two control animals, one animal from the ASC group, and one from the ASCT group died from early BPF. All the remaining animals had an adequate postoperative outcome. ASCs and ASCTs significantly decreased the necrosis and ulcerations of the bronchial stump at 10 and 20 days. ASCs significantly decreased mRNA expression of Igf1 at 10 days and Igf1, Tgfb1, Vegfa, and Col2a1 at 20 days, whereas there was increased expression of Agc1 and Col2a1 at 10 days and Sox6 at 20 days. CONCLUSIONS: Our findings indicate that local ASCs protected the bronchial stump after pneumonectomy and induced local changes in gene expression related to their protective action. These results could lead to a potential new therapeutic modality for the prevention of BPF.

GluN3A expression restricts spine maturation via inhibition of GIT1/Rac1 signaling.

NMDA-type glutamate receptors (NMDARs) guide the activity-dependent remodeling of excitatory synapses and associated dendritic spines during critical periods of postnatal brain development. Whereas mature NMDARs composed of GluN1 and GluN2 subunits mediate synapse plasticity and promote spine growth and stabilization, juvenile NMDARs containing GluN3A subunits are thought to inhibit these processes via yet unknown mechanisms. Here, we report that GluN3A binds G protein-coupled receptor kinase-interacting protein (GIT1), a postsynaptic scaffold that assembles actin regulatory complexes, including the Rac1 guanine nucleotide exchange factor ßPIX, to promote Rac1 activation in spines. Binding to GluN3A limits the synaptic localization of GIT1 and its ability to complex ßPIX, leading to decreased Rac1 activation and reduced spine density and size in primary cultured neurons. Conversely, knocking out GluN3A favors the formation of GIT1/ßPIX complexes and increases the activation of Rac1 and its main effector p21-activated kinase. We further show that binding of GluN3A to GIT1 is regulated by synaptic activity, a response that might restrict the negative regulatory effects of GluN3A on actin signaling to inactive synapses. Our results identify inhibition of Rac1/p21-activated kinase actin signaling pathways as an activity-dependent mechanism mediating the inhibitory effects of GluN3A on spine morphogenesis.

Grupo de promoção da saúde para portadores do Vírus da Imunodeficiência Humana / Group health promotion for patients with Human Immunodeficiency Virus / Grupo de promoción de la salud para portadores del Virus de Inmunodeficiencia Humano

Objetivou-se apreender temas elaborados por portadores do Vírus da Imunodeficiência Humana (HIV), atendidos em grupo de autoajuda, focalizando a promoção da saúde. Pesquisa descritiva, de caráter qualitativo, desenvolvida no Hospital Universitário Walter Cantídio, em Fortaleza-Ceará, entre fevereiro e outubro de 2010. Constituíram-se como fontes de dados os formulários das atividades grupais com 53 portadores do HIV. As falas foram analisadas conforme a análise de conteúdo. Foram elaboradas quatro categorias: Descoberta da soropositividade; Estigma e preconceito; Mudança de comportamento; e Dificuldades financeiras. Os sentimentos da descoberta, as situações de preconceito e as modificações impostas pela doença, decorrentes do acompanhamento da infecção, retratam o cenário de sofrimento enfrentado por esses pacientes. Em contrapartida, ocorrem mudanças no comportamento em busca de melhorar a saúde e prevenir agravos. Conclui-se que as ações de promoção da saúde incentivadas no grupo em serviço especializado proporcionam esclarecimentos e estimulam os clientes a viverem de forma mais saudável.

This study aimed to grasp subjects developed in a self-help group focusing on health promotion by patients with Human Immunodeficiency Virus (HIV). Descriptive and qualitative study, was made at University Hospital Walter Cantídio in Fortaleza-Ceará, between February and October 2010. Constituted as data sources report of group activities on 53 patients with HIV. The speeches were analyzed according to content analysis. Were prepared four categories: Discovery of HIV status; Stigma and prejudice; Change behavior; and Financial difficulties. The feelings of discovery, the situations of prejudice and the changes imposed by the disease, as a result of monitoring of infection, portray the scene of suffering that these patients face. On the other hand, there are changes in behavior in search of improve health and prevent injuries. In conclusion, the actions of health promotion encouraged in the group provide clarifications and encourage clients to live more healthily.

El objetivo fue aprehender los temas desarrollados por las personas con Virus de Inmunodeficiencia Humano (VIH), atendidos en grupos de autoayuda, enfocando la promoción de la salud. Estudio descriptivo, de carácter cualitativo, desarrollado en el Hospital Universitario Walter Cantidio en Fortaleza-Ceará-Brasil, entre febrero y octubre de 2010. Fueron fuentes de datos los fornularios de las actividades grupales con 53 portadores del VIH. Los discursos fueron analizados de acuerdo con el análisis de contenido. Se establecieron cuatro categorías: Descubrimiento de estado serológico al VIH; Estigma y prejuicio; Cambio de comportamiento; y Dificultades financieras. Las sensaciones de descubrimiento, las situaciones de prejuicio y de los cambios impuestos por la enfermedad, derivadas de la vigilancia de la infección, representan la escena de sufrimiento que enfrentan eses pacientes. Por otro lado, hay cambios en el comportamiento en la búsqueda por mejorar la salud y prevenir lesiones. Así, las acciones de promoción de la salud recomendadas en el grupo en servicio especializado proporcionan clarificaciones y incentivan los clientes a vivir más saludablemente.

Avaliação da prevalência e do grau de conhecimento do cirurgião-dentista em relação às emergências médicas / Assessment of prevalence and knowledge level of dental surgeons regarding medical emergencies

O atendimento clínico odontológico certamente não está restrito a repercussões apenas na cavidade bucal. Devido ao aumento gradativo do número de indivíduos acometidos sistemicamente, as chances de ocorrer eventos emergenciais durante a prática odontológica crescem substancialmente. Sendo assim, os cirurgiões--dentistas devem estar adequadamente preparados para lidar com todos os eventos que podem acontecer no seu ambiente de trabalho. Objetivo: avaliar a prevalência e o conhecimento das emergências médicas na práti-ca odontológica dos cirurgiões-dentistas da cidade de Chapecó-SC. Sujeitos e método: a amostra foi compos-ta por 63 cirurgiões-dentistas atuantes no município de Chapecó-SC. O instrumento de coleta de dados foi um questionário estruturado com 18 questões. Os dados fo-ram analisados através dos programas Microsoft Excel 2010 e SPSS-20. Para análise e associação foi utilizado o teste qui-quadrado. A margem de erro considerada foi 5,0%. Resultados: a maioria dos profissionais (54%) possuía treinamento de suporte básico de vida; 60% jul-gavam-se capacitados a diagnosticar uma emergência médica; 57% já passaram por um quadro de emergên-cia médica, prevalecendo situações de lipotimia (23%). Em relação ao arsenal de equipamentos e medicamen-tos presentes no ambiente odontológico, 17% deixaram essas questões em branco. Quanto aos casos clínicos, o diagnóstico de hipertensão apresentou uma margem alta de erro (62%). Conclusão: apesar de os profissio-nais, em sua maioria, alegarem possuir treinamento de suporte básico de vida e julgarem-se capacitados para diagnosticar um quadro emergencial, é nítida a falta de equipamentos e medicamentos emergenciais nos con-sultórios odontológicos e foi preocupante o número de erros quanto ao diagnóstico dos casos clínicos.

Adesao ao tratamento antirretroviral: assistencia integral baseada no modelo de atencao as condicoes cronicas / Adherencia al tratamiento antirretroviral: atención integral basada en el modelo de atención a las condiciones crónicas / Adherence to antiretroviral treatment: comprehensive care based on the care model for chronic conditions

OBJECTIVE: To evaluate the adherence to antiretroviral therapy (ART), identifying possible interventions based on the Care Model for Chronic Conditions. METHODS: Observational, quantitative, cross-sectional study, involving 215 people with HIV/aids using antiretroviral drugs, between March and June 2012, in Fortaleza, Ceará. From the specific adherence questionnaire, we used nine questions for discussion in the light of the Care Model for Chronic Conditions (MACC). RESULTS: 35.4% failed to adhere to medication at least once. In view of the MACC, gaps were identified, such as the need for more professional intervention, showing possibilities to apply new strategies, such as self-care actions, motivational interviews, operative group and others. CONCLUSION: A significant percentage of non-adherence to ART was found, whose interventions are still incipient. Actions based on the MACC can favor comprehensive care for patients with HIV/aids.

O objetivo deste estudo foi avaliar a adesão à terapia antirretroviral (TARV), identificando possibilidades de intervenções embasadas no modelo de atenção às condições crônicas. MÉTODOS: Estudo observacional, quantitativo, transversal, desenvolvido com 215 pessoas com HIV/ AIDS em uso de antirretrovirais, entre março e junho de 2012, em Fortaleza, Ceará. De um questionário específico para avaliar a adesão utilizaram-se nove quesitos para discussão à luz do Modelo de Atenção às Condições Crônicas (MACC). RESULTADOS: 35,4% das pessoas estudadas deixaram de aderir ao tratamento pelo menos alguma vez, por se sentirem melhor/pior, ou tristes/deprimidas. Sob a luz do MACC, foram identificadas lacunas, como necessidade de mais intervenção profissional, evidenciando possibilidades de aplicar novas estratégias, como ações para o autocuidado, entrevista motivacional, grupo operativo, e outras. CONCLUSÃO: Constatou-se que há um percentual significativo de não adesão à TARV, cujas intervenções ainda são incipientes, e que ações baseadas no MACC podem favorecer uma assistência totalitária aos pacientes com HIV/AIDS.

OBJETIVO: Evaluar la adherencia a la terapia antirretroviral (TARV), identificando las posibles intervenciones basadas en el modelo de atención de las condiciones crónicas. MÉTODOS: Estudio observacional, cuantitativo, transversal, desarrollado con 215 personas con VIH/SIDA con medicamentos antirretrovirales, entre marzo y junio de 2012, en Fortaleza, Ceará. De un cuestionario específico para valorar la adherencia, se utilizaron nueve preguntas para su discusión a la luz del Modelo de Atención a las Condiciones Crónicas (MACC). RESULTADOS: Se observó que 35,4% de los pacientes dejaron de adherir a la medicación por lo menos una vez. A la luz del MACC, fueron identificadas deficiencias, como la necesidad de más intervención profesional, mostrando las posibilidades de implementar nuevas estrategias, como las acciones de autocuidado, entrevista motivacional, grupo operativo y otros. CONCLUSIÓN: Se encontró un porcentaje significativo de no adherencia al tratamiento antirretroviral, cuyas intervenciones son aún incipientes y las acciones basadas en el MACC pueden.

Autologous platelet-poor plasma decreases the bronchial stump necrosis in rat.

BACKGROUND: Necrosis of the bronchial stump is a very important trigger for bronchopleural fistula. The administration of local autologous platelet-poor plasma (PPP) could protect the bronchial stump. MATERIALS AND METHODS: Left pneumonectomy was performed in 25 Sprague-Dawley rats. Animals were randomly assigned to a control group (n=13) and PPP group (n=12). PPP was locally administered on the bronchial stump after pneumonectomy. We analyzed histologic changes in the bronchial stump and messenger RNA expression changes of genes involved in wound repair at 10 and 20 d. RESULTS: Local PPP treatment produced a mass of fibrous tissue surrounding the bronchial stump and significantly decreased the presence of necrosis at 20 d. PPP increased the expression of insulin like growth factor 1 at 10 d although it did not reach statistical significance. CONCLUSIONS: Our findings indicate that local PPP treatment of the bronchial stump after pneumonectomy decreased necrosis and could have a protective effect on the bronchial stump.

Life experiences of hiv/aids carriers in terms of the perspectives of the promotion of health

Aim: The objective was to learn about the experiences of HIV/AIDS carriers attending a self-help group founded as part of the Health Promotion program. Method: This is a descriptive study of a retrospective character, using qualitative analysis. Data was collected from the records of a self-help group involving HIV-infected patients in an outpatient clinic specializing in infectious diseases in Fortaleza, Brazil, between February and October 2010, and analyzed. Result: The results were categorized into: (1) Knowledge: when there is the incorporation of new concepts of fact or phenomenon; (2) Motivation: when it is linked to personal attributes that modify the desire of the subjects; (3) Adherence: when it involves a collaborative process where involves the subjects' participation in their treatment decisions and (4) Behavior Change: when it is associated with a positive or negative conditions in their lives. Conclusion: The educational actions developed in the group activities had great importance in the teaching and learning processes for the creation and transformation of the subjects involved.