Serum Apolipoproteins and Apolipopprotein-Defined Lipoprotein Subclasses: A Hypothesis-Generation Prospective Study of Cardiovascular Events in Type 1 Diabetes

Apolipoproteins and apolipoprotein-defined lipoprotein subclasses have been associated with dyslipidemia and cardiovascular disease (CVD). Our main objective was to define associations of serum apolipoproteins and ADLS with any CVD and major atherosclerotic cardiovascular events (MACE) in a prospective study of T1D. Serum apolipoproteins and ADLS (14 biomarkers in total) were measured in sera (obtained 1997-2000) from a subset (n=465) of the Epidemiology of Diabetes Interventions and Complications (EDIC) cohort. Prospective associations of any CVD (myocardial infarction, stroke, confirmed angina, silent MI, revascularization, or congestive heart failure) and MACE (fatal or nonfatal myocardial infarction or stroke), over 5942 and 6180 patient-years follow-up respectively, were investigated using Cox proportional hazards models, unadjusted and adjusted for risk factors. During 15 years follow-up, 50 any CVD and 24 MACE events occurred. Nominally significant positive univariate associations with any CVD were APOB, APOC3 and its sub-fractions [heparin precipitate (HP), heparin soluble (HS)], and ADLS-defined Lp-B. Nominally significant positive univariate associations with MACE were APOC3 and sub-fractions, and Lp-B:C; those with total APOC3 and APOC3-HS persisted in adjusted analyses. However, these associations did not reach significance after adjustment for multiple testing. There were no significant associations of APOA1, APOA2, APOE, or other ADLS with either any CVD or MACE. These hypothesis-generating data suggest that total serum APOC3 and APOC3 in HDL are potentially important predictive biomarkers for any CVD and MACE in T1D adults

Venous ulcer: risk factors and the Nursing Outcomes Classification

Venous ulcer: risk factors and the Nursing Outcomes Classification Objective. To explore the relationship between the risk factors for the development of venous ulcers and the indicators of tissue integrity from the Nursing Outcomes Classification. Methodology. A cross-sectional study conducted in 2013 in a university hospital in Natal/RN (Brazil). Fifty individuals selected by consecutive sampling participated in an interview and physical examination. Results. The most important risk factors were: 44% presented with arterial hypertension, 26% allergy, 20% diabetes mellitus, 4% participated in some physical activity, 6% were smokers and 14% drank alcohol. There was a statistically significant association between diabetes mellitus and the texture of the lesion (p=0.015) and tissue perfusion (p=0.026); allergy and texture (p=0.034); physical activity and hydration (p = 0.034); smoking and thickness (p = 0.018); and alcoholism and exudate of the ulcer (p=0.045). Conclusion. The relationship between risk factors and the nursing outcome indicators generated information relevant to the development of guidelines for the monitoring and treatment of venous ulcer information. Key words: venous ulcer; nursing; risk factors; nursing assessment Úlcera venosa: Relación entre los factores de riesgo y la clasificación de los resultados de enfermería Objetivo. Explorar la relación entre los factores de riesgo para el desarrollo de las úlceras venosas y los indicadores de integridad tisular de la clasificación de resultados de enfermería. Metodología. Estudio transversal realizado en 2013 en un hospital universitario de Natal / RN (Brasil). Participaron 50 individuos seleccionados por muestreo consecutivo; se les hizo entrevista y examen físico. Resultados. Los factores de riesgo más importantes fueron: 44% presentaba hipertensión arterial; 26%, alergia; 20%, Diabetes Mellitus; 4% realizaba alguna actividad física; 6%, fumadores y 14% bebía alcohol. Hubo asociación estadísticamente significativa entre la Diabetes Mellitus con la textura de la lesión (p=0.015) y la perfusión tisular (p=0.026), la alergia y la textura (p=0.034), la actividad física y la hidratación (p=0.034), el tabaquismo y el grosor (p=0.018); y el alcoholismo y el exudado de la úlcera Invest Educ Enferm. 2014;32(2) • 253 (p=0.045). Conclusión. La relación entre algunos factores de riesgo y los indicadores de resultado de enfermería genera información relevante para la elaboración de directrices para el seguimiento y tratamiento de las úlceras venosas. Palabras clave: úlcera venosa; enfermagem; fatores de risco; avaliação em enfermagem. Úlcera venosa: relação entre os fatores de risco e a classificação dos resultados de enfermagem Objetivo. Explorar a relação entre os fatores de risco para o desenvolvimento das úlceras venosas e os indicadores de integridade tissular da classificação de resultados de enfermagem. Metodologia. Estudo transversal realizado em 2013 num hospital universitário de Natal / RN (Brasil. Participaram 50 indivíduos selecionados por amostragem consecutiva, foi feita entrevista e exame físico. Resultados. Os fatores de risco mais importantes foram: 44% apresentavam hipertensão arterial, 26% alergia, 20% Diabete Mellitus, 4% realizava alguma atividade física, 6% eram fumantes e 14% bebiam álcool. Teve associação estatisticamente significativa entre a Diabete Mellitus com a textura da lesão (p=0.015) e a perfusão tissular (p=0.026), a alergia e a textura (p=0.034), a atividade física e a hidratação (p=0.034), o tabagismo e a gordura (p=0.018); e o alcoolismo e o exsudado da úlcera (p=0.045). Conclusão. A relação entre alguns fatores de risco e os indicadores de resultado de enfermagem gera informação relevante para a elaboração de diretrizes para o seguimento e tratamento das úlceras venosas. Palavras chave: úlcera venosa; enfermería; factores de riesgo; evaluación en enfermería. Venous ulcer: risk factors and the Nursing Outcomes Classificatio

Aspectos genéticos de las epilepsias: una visión actualizada

Es reconocido que los factores genéticos están involucrados en la etiología de diversas epilepsias, sin embargo los genes causales se han logrado identificar principalmente en las epilepsias monogénicas, que representan sólo el 1 a 2% de los síndromes epilépticos. El presente artículo describe algunos de los principales genes identificados hasta el momento en los síndromes mendelianos y no mendelianos. También se hace mención de los principales genes involucrados en la etiología de las malformaciones del desarrollo cortical y de las epilepsias mioclónicas progresivas

Hydrochlorothiazide Potentiates Contractile Activity of Mouse Cavernosal Smooth Muscle

Introduction: Hydrochlorothiazide has a negative influence on penile erection but little is known about the mechanism(s) involved. Aims: To characterize the effects of this diuretic on mouse corpus cavernosum (CC) smooth muscle in vitro and ex vivo. Methods: CC strips of C57BL/6 mice (12–16 weeks old) were mounted in organ baths containing Krebs-Henseleit solution and tissue reactivity was evaluated. Expression of genes encoding diuretic targets and enzymes involved in penile erection were evaluated by polymerase chain reaction. Main Outcome Measures: Stimulation-response curves to phenylephrine (10 nmol/L–100 μmol/L) or to electrical field stimulation (1–32 Hz) were constructed, with or without hydrochlorothiazide. Strips of CC from mice after long-term hydrochlorothiazide treatment (6 mg/kg/day for 4 weeks) with or without amiloride (0.6 mg/kg/day for 4 weeks) in vivo also were studied. Nitric oxide and Rho-kinase pathways were evaluated. Results: Hydrochlorothiazide (100 μmol/L) increased the maximum response to phenylephrine by 64% in vitro. This effect was unaffected by the addition of indomethacin (5 μmol/L) but was abolished by N(ω)-nitro-L-arginine methyl ester (100 μmol/L). Hydrochlorothiazide (100 μmol/L) potentiated electrical field stimulation-induced contraction in vitro, but not ex vivo. Long-term treatment with hydrochlorothiazide increased the maximum response to phenylephrine by 60% and resulted in a plasma concentration of 500 ± 180 nmol/L. Amiloride (100μmol/L) caused rightward shifts in concentration-response curves to phenylephrine in vitro. Long-term treatment with hydrochlorothiazide plus amiloride did not significantly increase the maximum response to phenylephrine (+13%). Reverse transcriptase polymerase chain reaction did not detect the NaCl cotransporter in mouse CC. Hydrochlorothiazide did not change Rho-kinase activity, whereas amiloride decreased it in vitro and ex vivo (approximately 18% and 24% respectively). A 40% decrease in Rock1 expression also was observed after long-term treatment with hydrochlorothiazide plus amiloride. Conclusion: Hydrochlorothiazide potentiates contraction of smooth muscle from mouse CC. These findings could explain why diuretics such as hydrochlorothiazide are associated with erectile dysfunction

An application of the SF-6D to create heath values in Portuguese working age adults Original Research

Abstract Objectives : This study describes the health-related quality of life (HRQOL) of the Portuguese working age population and investigates sociodemographic differences. Methods : Subjects randomly selected from the working age population ( n =2,459) were assessed using the SF-36v2 and converted into the preference-based SF-6D. Results : The mean SF-6D utility value was 0.70 (range 0.63-0.73). The mean utility value was lower for the lower educational level than for the highest. Women, people living in rural areas and older adults reported lower levels of utility values. Non-parametric tests showed that health utility values were signifi cantly related to employment; unskilled manual workers reported utility values lower than non-manual workers. For different diseases, mean utility values ranged from 0.58 (sexual diseases) to 0.66 (hepatic conditions). Cluster analysis was adopted to classify individuals into three groups according to their answers to the SF-6D dimensions. Multinomial logit regression was used to detect sociodemographic characteristics affecting the probability of following each cluster pattern. This study yielded normative data by age and gender for the SF-6D. Conclusions : The authors conclude that SF-6D is an effective tool for measuring HRQOL in the community so that different population groups can be compared. The preference-based measure used seems to discriminate adequately across sociodemographic differences. These results allow a better understanding of the impact of sociodemographic variables on the burden of illness perception

Aspectos genéticos das epilepsias: uma visão atual

Fatores genéticos estão sabidamente envolvidos na etiologia de diferentes epilepsias, porém a identificação de genes causais tem ocorrido, em grande maioria, nas epilepsias monogênicas, que perfazem apenas 1-2% das síndromes epilépticas. O presente artigo lista alguns principais genes identificados até o momento para síndromes Mendelianas e não mendeliana. Também são relatados os principais genes descritos envolvidos na etiologia das malformações do desenvolvimento cortical e epilepsias mioclônicas progressivas

Beta-adrenergic pathway activation enhances aggressiveness and inhibits stemness in head and neck cancer

Chronic stress leads to the activation of the beta-adrenergic pathway. Its activation has been implicated in the progression of different types of cancer but its role on head and neck squamous cell carcinomas (HNSCCs) remains undefined. The aim of this study was to investigate the influence of the beta-adrenergic pathway activation in the progression of HNSCCs and offer a panel of potential treatments for patients with the active beta-adrenergic pathway. Five hundred and twenty TCGA patients with primary HNSCCs were divided in two groups: ADRB2low / SLC6A2low and ADRB2high / SLC6A2high. Differentially expressed genes (DEGs) were identified through differential expression analysis. The association of clinicopathological and genomic features between the groups was analyzed using a bioinformatic approach. Potential drugs for treatment of HNSCC were identified based on the DEGs. There was association between ADRB2 and SLC6A2 expressions with age, race, tumor site, histologic grade, perineural invasion, and HPV p16 status. It was identified 898 DEGs between the groups. High ADRB2/SLC6A2 expression stimulated HNSCC proliferation, adhesion, invasion, and angiogenesis. On the other hand, genes related to cell stemness were downregulated in patients with activation of the beta- adrenergic pathway. Finally, 56 FDA-approved antineoplastic and immunotherapeutic drugs were identified as potential targets for the personalized treatment

The Effect of Clown Intervention on Self-Report and Biomarker Measures of Stress and Fatigue in Pediatric Osteosarcoma Inpatients: A Pilot Study

Background: Pediatric cancer patients experience different psychological processes during hospitalization that may regulate the immune response and affect recovery and response to cancer treatment. In this study, we aimed to examine the feasibility of longitudinal testing of psychophysiological parameters of stress and fatigue in pediatric osteosarcoma patients hospitalized for chemotherapy submitted to clown intervention; and to investigate whether changes in the levels of biomarkers are associated with psychological stress and fatigue levels in these patients after the clown intervention. Methods: A pretest-posttest quasi-experimental pilot study was conducted at the pediatric oncology inpatient unit in a comprehensive cancer care center in Brazil including children and adolescents with osteosarcoma hospitalized for chemotherapy. Eight saliva samples were collected, comprising 4 at baseline (pre-intervention) and 4 after the clown intervention (+1, +4, +9, and +13 hours post-awakening). Salivary cortisol, α-amylase (sAA), cytokines, and matrix metalloproteinase-9 (MMP-9) levels were determined using high-sensitivity enzyme-linked immunosorbent assay (ELISA) kits. Stress and fatigue were measured by Child Stress Scale–ESI and PedsQL Multidimensional Fatigue Scale respectively. Bivariate association analysis between stress and fatigue scores and biomarker levels were investigated using nonparametric statistics. Effect sizes were calculated for each outcome variable. Results: Six pediatric osteosarcoma patients were enrolled with no missing data. No significant effects sizes were observed for psychophysiological outcomes. Effect sizes ranged from 0.54 (cortisol) to 0 (interleukin-1β [IL-1β]). Decreasing overall trends were observed for cortisol levels for all 6 pediatric osteosarcoma patients over time. In addition, a similar pattern of tumor necrosis factor–α (TNF-α) levels over time was found for all 6 patients. Patients with metastatic osteosarcoma showed a linear trend for a decrease in MMP-9 levels between 1 and 9 hours after the clown intervention and restoration to basal levels after 13 hours. Conclusions: The results of this pilot study suggest that it is feasible longitudinally measure psychophysiological outcomes in the pediatric osteosarcoma inpatients for chemotherapy. Clown intervention merits further study as a way to reduce stress as well as fatigue, since that the stress and cytokines measurements are feasible based on our work