Prolong intermittent injection of human parathyroid hormone in rats modulates the expression of several proteins in the neuropil of the cerebellar cortex.

INTRODUCTION: The intermittent use of recombinant human parathyroid hormone (iPTH) alters calcium metabolism and induces osteogenesis in experimental models. However, the real effects of iPTH in excitable cells and neurons that require membrane receptors to undergo membrane depolarization/repolarization (Na+K+ATPase) to generate ATP, voltage-gated calcium channel (calcium-IP3R-calponin) as well as GABAergic (GABAA) signaling remains unclear. OBJECTIVES: In this study, the expression of IP3R, Na+K+-ATPase, GABAA and calmodulin proteins were evaluated in histological sections of the cerebellum of rats following prolonged injection of iPTH. METHODS: Twenty Wistar rats were used in this study and randomly assigned as either or control group. The test group were subcutaneously injected with 20 µg/kg of iPTH, 3×/week for 8 weeks, while the control group received 1 ml/kg of 0.9% saline solution. The rats were euthanized on the 60th day after the first administration, and their cerebellar vermis was removed and submitted to histological and immunohistochemical evaluation for detection of IP3R, Na+K+-ATPase, GABAA and calmodulin proteins. The expression of proteins was evaluated in the areas corresponding to the Purkinje cells as well as in neuropil of molecular layer of cerebellum. All results were transformed into a percentage for each area analyzed to verify significance between groups. RESULTS: Rats that received iPTH demonstrated significant reduction of IP3R, calmodulin and GABAA in Purkinje cells and neuropil of molecular layer while the expression of Na+K+-ATPase was similar. CONCLUSION: It was concluded that iPTH decreased the expression of IP3R and calmodulin while it did not alter the expression of Na+K+-ATPase. These changes insinuate the ionic activity of calcium and sodium/potassium. Yet, the iPTH alters GABAergic signaling in Purkinje cells, suggesting neurotransmission activity changes in the cerebellum.

Bayes Posterior Convergence for Loss Functions via Almost Additive Thermodynamic Formalism.

Statistical inference can be seen as information processing involving input information and output information that updates belief about some unknown parameters. We consider the Bayesian framework for making inferences about dynamical systems from ergodic observations, where the Bayesian procedure is based on the Gibbs posterior inference, a decision process generalization of standard Bayesian inference (see [7, 37]) where the likelihood is replaced by the exponential of a loss function. In the case of direct observation and almost-additive loss functions, we prove an exponential convergence of the a posteriori measures to a limit measure. Our estimates on the Bayes posterior convergence for direct observation are related and extend those in [47] to a context where loss functions are almost-additive. Our approach makes use of non-additive thermodynamic formalism and large deviation properties [39, 40, 57] instead of joinings.

Physical Characterization of Maize Grits Expanded Snacks and Changes in the Carotenoid Profile.

The objective of this work was to evaluate the effects of feed moisture (13-17%, wb) and barrel temperature (120-160 °C) on physicochemical properties, and changes in the carotenoid profile of maize grits extruded snacks. The extrudates were obtained in a single-screw extruder, according to a 32 factorial design with two replicates. The linear coefficients of feed moisture and barrel temperature mainly affected the physicochemical properties. On the other hand, the interaction coefficient ß112 dominated the change in total carotenoids, lutein, zeaxanthin, and ß-carotene. The quadratic coefficients were also important for changes in total color (regarding feed moisture), and for ß-cryptoxanthin, specific mechanical energy, and volumetric expansion index (regarding barrel temperature). ß-cryptoxanthin and ß-carotene increased, whereas lutein and zeaxanthin decreased. The mathematical models developed from responses revealed two feasible operating regions under the domain explored. For a satisfactory process, from a technological and nutritional point of view, it is suggested to extrude at the operating conditions ranging between 13.2-13.7% feed moisture and 120-132 °C barrel temperature. Under these conditions, the specific mechanical energy input required was 410-450 kJ/kg, and extrudates with a volumetric expansion index greater than 12, a crispness work less than 0.4 N.mm, and with moderate increments in the levels of ß-carotene and ß-cryptoxanthin were produced. The use of richer cultivars in carotenoids could contribute to the production of healthier snacks.

Frequent premature ventricular contractions. Association of burden and complexity with prognosis according to the presence of structural heart disease.

INTRODUCTION: Premature ventricular contractions (PVC) have been associated with mortality and heart failure (HF) regardless the presence of structural heart disease (SHD). The aim of this study was assessing the impact of burden and complexity of PVCs on prognosis, according to presence of SHD. METHODS: 312 patients were retrospectively evaluated out of 1967 consecutive patients referred for 24-hr Holter at a single hospital, with a PVC count >1% of total beats. Two groups with and without SHD. PVC burden (PVC%), presence of complex forms, incidence of all-cause death, combined outcomes of all-cause death and cardiovascular hospitalizations, HF death and HF hospitalizations and, sudden death (SD) or hospitalizations due to ventricular arrhythmias (VA)were assessed. RESULTS: Premature ventricular contraction burden was 2.7 (IQR: 1.6-6.7). SHD patients had more polymorphic PVCs, 77% versus 65%, p = .022, triplets and episodes of non-sustained ventricular tachycardia (NSVT): 44% versus 27%, p = .002; 30% versus 12%, p < .0001. In idiopathic patients, a PVC% in the third quartile was independently associated with all-cause mortality hazard ratio (HR) 2.288 (1.042-5.026) p = .039, but not in SHD. The complexity of the PVCs was not independently associated with outcomes in both groups. In SHD group, NSVT was associated with lower survival free from SD and VA hospitalizations, p = .028; after multivariable, there was a trend for a higher arrhythmic outcome with NSVT, HR 3.896 (0.903-16.81) p = .068. CONCLUSION: Premature ventricular contractions in SHD showed more complex patterns. In idiopathic patients, a higher PVC count was associated with higher mortality but not is SHD patients. Complexity was not independently associated with worse prognosis.

Fatores Associados ao Atraso entre o Diagnóstico e o Início do Tratamento de Câncer de Mama: um Estudo de Coorte com 204130 Casos no Brasil / Factors Associated with Delay between Diagnosis and Initiation of Breast Cancer Treatment: a Cohort Study with 204130 Cases in Brazil / Factores Asociados con el Retardo entre el Diagnóstico y el Inicio del Tratamiento del Cáncer de Mama: un Estudio de Cohorte con 204130 Casos en Brasil

Introdução: O câncer de mama é considerado um problema de saúde pública, tendo crescente incidência mundial. Diversos fatores contribuem para o diagnóstico tardio e dificultam o início do tratamento, repercutindo em um pior prognóstico. Objetivos: Analisar o intervalo de tempo entre o diagnóstico e o início do primeiro tratamento oncológico na população brasileira, além de avaliar os fatores associados aos maiores intervalos. Método: Trata-se de um estudo de coorte retrospectivo com 540.529 pacientes cadastrados no Sistema de Registros Hospitalares de Câncer (SisRHC)no período de 2000 a 2017. Utilizou-se como desfecho o intervalo de tempo entre o diagnóstico e o início do primeiro tratamento oncológico, considerando-se como atraso o intervalo maior do que 60 dias. Para análise das variáveis, foram realizadas análise descritiva e regressão logística simples (IC95%; p<0,05). Resultados: Foram analisados 204.130 casos que apresentaram média de idade de 55,8 anos (±13,24), sendo predominantemente do sexo feminino (99,1%), 55,1% eram da Região Sudeste e 71,4% residiam em cidades não capitais. A mediana do intervalo de tempo entre o diagnóstico e o início do primeiro tratamento oncológico foi de 63 dias (variação interquartil = 36-109). As variáveis sociodemográficas, clínicas e relacionadas ao tratamento mostraram impacto no intervalo de tempo, com exceção da variável sexo. Conclusão: O tempo entre o diagnóstico e o início do primeiro tratamento oncológico foi elevado. Fatores sociodemográficos, clínicos e relacionados ao tratamento influenciam nos intervalos de tempo. Identificá-los precocemente pode contribuir para o direcionamento de ações a esses grupos mais vulneráveis ao atraso.

Breast cancer is considered a public health problem with an increasing incidence worldwide. Several factors contribute to late diagnosis and hinder the initiation of the treatment, resulting in a worse prognosis. Objectives:To analyze the time interval between diagnosis and the beginning of the first oncologic treatment in the Brazilian population, in addition to assessing the factors associated with the longest time intervals. Method: Retrospective cohort study with 540,529 patients registered in the Hospital Cancer Registry System (SisRHC) from 2000 to 2017. The outcome was the time between diagnosis and the beginning of the first oncologic treatment, considering the interval greater than 60 days as delay. Descriptive analysis and simple logistic regression were performed (95% CI; p <0.05) to analyze the variables. Results: 204,130 cases were analyzed, mean age of 55.8 years (± 13.24), predominantly females (99.1%), 55.1% were from the southeast region and 71% lived in non-capital cities. The median of the time interval between diagnosis and the beginning of the first oncologic treatment was 63 days (interquartile range = 36-109). Sociodemographic, clinical and treatment-related variables affect the time interval, except the gender variable. Conclusion: The time between diagnosis and the beginning of the first oncologic treatment was high. Sociodemographic, clinical and treatment-related factors influence time intervals. Their early identification can contribute to guide the actions toward these most vulnerable groups to delay.

Introducción: El cáncer de mama se considera un problema de salud pública con una incidencia mundial creciente. Varios factores contribuyen al diagnóstico tardío y dificultan el inicio del tratamiento, resultando en un peor pronóstico. Objetivos:Analizar el intervalo de tiempo entre el diagnóstico y el comienzo del primer tratamiento oncologico en la población brasileña, además de evaluar los factores asociados con los intervalos de tiempo más largos. Método: Este es un estudio de cohorte retrospectivo con 540.529 pacientes registrados en el Hospital Cancer Registry System (SisRHC) desde 2000 hasta 2017. El resultado fue el intervalo de tiempo entre el diagnóstico y el comienzo del primer tratamiento oncologico, considerando como retraso el intervalo superior a 60 días. Para el análisis de las variables, se realizó un análisis descriptivo y una regresión logística simple (IC 95%; p <0,05). Resultados: Se analizaron 204,130 casos, con una edad media de 55,8 años (±13,24), predominantemente mujeres (99,1%), 55,1% de la región sureste y 71,4% residentes en ciudades no capitales.La mediana del intervalo de tiempo entre el diagnóstico y el comienzo del primer tratamiento contra el cáncer fue de 63 días (rango intercuartil = 36-109). Las variables sociodemográficas, clínicas y relacionadas con el tratamiento tuvieron un impacto en el intervalo de tiempo, con la excepción de la variable de género. Conclusión: El intervalo de tiempo promedio entre el diagnóstico y el comienzo del primer tratamiento oncologico fue alto. Además, se observó que los factores sociodemográficos, clínicos y relacionados con el tratamiento influyen en los intervalos de tiempo, por lo que identificarlos temprano puede contribuir a acciones directas para estos grupos más vulnerables al retraso.

Excessive Atrial Ectopic Activity Worsens Prognosis and Predicts the Type of Major Adverse Cardiac Events in Patients With Frequent Premature Ventricular Contractions.

BACKGROUND: The aim of the study was to evaluate the impact of premature atrial contractions (PACs) burden, and the presence of non-sustained ventricular tachycardia (NSVT) on prognosis and type of major adverse cardiovascular events in patients with frequent premature ventricular contractions (PVCs). METHODS: We retrospectively studied 285 consecutive patients with frequent PVCs defined as PVC count equal or higher than 1% of total beats assessed with 24-h Holter recording. Patients with atrial fibrillation (AF) were excluded. We evaluated the impact of PAC burden and the presence of NSVT on the primary end points of all-cause mortality, stroke and new-onset AF, and secondary end points; arrhythmic end point (arrhythmic death or hospitalizations for ventricular arrhythmias) or heart failure (HF)-related end point (death or hospitalizations due to HF). RESULTS: The PAC number showed an adjusted hazard ratio (HR) (95% confidence interval (CI), P value) of 1.077 (1.014 - 1.145, P = 0.017) for all-cause mortality, 1.250 (1.080 - 1.447, P = 0.003) for stroke, 1.090 (1.006 - 1.181, P = 0.036) for new-onset AF and 1.376 (1.128 - 1.679, P = 0.002) for the HF end point. The presence of NSVT showed an adjusted HR (95% CI) of 3.644 (1.147 - 11.57, P = 0.028) for the arrhythmic end point. CONCLUSIONS: In patients with frequent PVCs a high PAC count was independently associated with increased mortality, higher rate of AF, stroke and HF adverse events, but not with arrhythmic adverse events. The presence of NSVT was independently associated with increased arrhythmic adverse events, but not with overall mortality, AF, stroke or HF events.

Stenosis of the branches of the neopulmonary artery after the arterial switch operation: A cardiac magnetic resonance imaging study.

BACKGROUND: The neonatal arterial switch operation (ASO) is now the standard of care for children born with transposition of the great arteries. Stenosis of the neopulmonary artery on long-term follow up is a known complication. METHODS: We performed a retrospective analysis of eleven patients who underwent a cardiac magnetic resonance imaging (MRI) due to echocardiographic evidence suggestive of stenosis of the neopulmonary artery or its branches (mean estimated Doppler gradient 48 mmHg, min 30 mmHg, max 70 mmHg). A comprehensive evaluation of anatomy and perfusion was done by cardiac MRI. RESULTS: The branches of the neopulmonary artery (neo PA) showed decreased caliber in three patients unilaterally and in two patients, bilaterally. Magnetic resonance (MR) perfusion studies showed concomitant decreased flow, with discrepancy between the two lungs of 35/65% or worse, only in the three patients with unilateral obstruction, by two different MR perfusion methods. CONCLUSIONS: Cardiac MR can be used as a comprehensive non-invasive imaging technique to diagnose stenosis of the branches of the neopulmonary after the ASO, allowing evaluation of anatomy and function of the neoPA, its branches, and the differential perfusion to each lung, thus facilitating clinical decision making.

Exercise-induced intraventricular obstruction in a child with near syncope and chest pain during exercise.

We report the case of a 10-year-old girl with two episodes of light-headedness and chest pain during exercise. She had an unremarkable clinical record, physical examination, ECG, and echocardiogram. Noninvasive ischemia tests were positive, but coronary angiography was normal. Exercise stress echocardiogram revealed an exercise-induced intra-left-ventricular obstruction with a peak gradient of 78 mmHg and replicated her symptoms. After starting beta-blocker therapy her clinical status improved and no residual obstruction was detected. The authors review this unsuspected clinical condition, seldom reported in the adult population and, to our knowledge, never before in a child.

Stent fracture: case report and literature review.

We report the case of a man presenting with acute myocardial infarction and a history of percutaneous coronary intervention with implantation of a drug-eluting stent, which was now fractured. This case highlights the growing recognition of stent fracture as a potential mechanism for late stent thrombosis in the drug-eluting stent era. Following the case report, we review the literature on the incidence, contributing factors and clinical impact of stent fracture.

Percutaneous treatment of pulmonary atresia with intact ventricular septum: pulmonary valve perforation using radiofrequency energy and arterial duct stenting.

Pulmonary atresia with intact ventricular septum (PA/IVS) is a rare congenital heart disease with a poor prognosis. It displays great anatomical diversity with varying degrees of right ventricular (RV) hypoplasia, which determine the therapeutic approach. Ideally, the goal is to establish a biventricular circulation. This may be achieved through surgical or percutaneous techniques. Pulmonary valve perforation using radiofrequency energy is indicated in patients with membranous atresia, moderate RV hypoplasia (bipartite or tripartite) and non-RV dependent coronary circulation. Arterial duct stenting is occasionally necessary to ensure adequate pulmonary flow. It is thus possible to treat some patients using exclusively percutaneous techniques. We report the first known case in Portugal of a neonate with PA/IVS treated by radiofrequency perforation and subsequent stenting of the arterial duct.

[Cardiomyopathy: first clinical manifestation of a pheochromocytoma--case report]. / Miocardiopatia de stress: primeira manifestação de feocromocitoma--caso clínico.

Stress cardiomyopathy clinical presentation mimics an acute coronary syndrome. It is characterized by left ventricular multi-segmental commitment, absence of significant coronary artery disease and by the complete resolution of all the findings. Its pathophysiology is not yet clear, but the main theory suggests a catecholamine-mediated cardiotoxicity mechanism. Pheochromocytoma is a neuroendocrine tumor producer of catecholamines with several cardiovascular manifestations. We report a case of stress cardiomyopathy that was the first clinical manifestation of an unknown pheochromocytoma.