La prueba cardiopulmonar de ejercicio contribuye a determinar con precisión el riesgo en pacientes con hipertensión pulmonar de bajo riesgo / Cardiopulmonary Exercise Testing Contributes to Accurate Risk Assessment in Patients with Low-risk Pulmonary Hypertension

RESUMEN Introducción : Las guías europeas de hipertensión arterial pulmonar (HAP) estratifican el riesgo valiéndose de características clínicas y estudios complementarios entre los cuales está la prueba cardiopulmonar de ejercicio (PCPE), de la cual toma en cuenta 3 parámetros: el consumo de O2 (VO2) pico, su porcentaje respecto del predicho y la pendiente ventilación minuto/ producción de dióxido de carbono (VE/VCO2). Sin embargo, ninguno de los modelos que validaron esta forma de estratificar el riesgo incluyeron la PCPE entre sus variables. Objetivos : Determinar qué proporción de pacientes con HAP del grupo I considerados de bajo riesgo y que caminan >440 metros en la prueba de caminata de 6 minutos (PC6M) tienen en la PCPE parámetros considerados de riesgo moderado o alto. Material y métodos : Se incluyeron pacientes >18 años con diagnóstico de HAP del grupo I considerados de bajo riesgo con una PC6M >400 metros a los que se les realizó una PCPE en la que se registró el VO2 pico, su porcentaje respecto del VO2 predicho y la pendiente VE/VCO2. Se determinó qué proporción de pacientes presentaban estos parámetros en un estrato de riesgo mayor a bajo riesgo (VO2 pico <15 ml/kg/min, su porcentaje respecto del predicho <65% y la pendiente VE/VCO2 >36). Resultados : Se incluyeron 18 pacientes. A pesar de ser pacientes de bajo riesgo y con buena clase funcional todos presentaron un VO2 pico menor al 85% del predicho, lo cual determina un deterioro al menos leve de la capacidad funcional. Un único paciente (6%) presentó los tres parámetros evaluados en bajo riesgo, 8 pacientes (44%) tuvieron al menos un parámetro alterado, 7 pacientes (39%) presentaron 2 parámetros alterados y en 2 pacientes (11%) todos los parámetros estuvieron alterados. Los parámetros que más frecuentemente se vieron alterados fueron el porcentaje respecto del VO2 predicho y la pendiente VE/VCO2, en el 67% de los casos. Solo 4 pacientes presentaron un VO2 pico <15 ml/k/m. Ningún paciente presentó valores de VO2 pico o porcentaje respecto del predicho en la categoría de alto riesgo. Sin embargo, 6 pacientes (33%) presentaron una pendiente VE/VCO2 considerada de alto riesgo. Conclusión : El 94% de los pacientes considerados de bajo riesgo presentaron al menos una variable en la PCPE que no corresponde a un perfil de riesgo bajo. La pendiente VE/VCO2 y el porcentaje de VO2 pico respecto del predicho fueron las variables más frecuentemente alteradas. La pendiente VE/VCO2 fue la única que mostró valores considerados de alto riesgo. La PCPE podría tener un lugar en la estratificación de precisión de pacientes de bajo riesgo. El valor de este hallazgo deberá ser evaluado en estudios prospectivos, al tiempo que genera las bases para el planteo de hipótesis respecto de la estratificación de riesgo y la intensidad del tratamiento en pacientes que aparentan estar en bajo riesgo.

ABSTRACT Background : European guidelines for pulmonary arterial hypertension (PAH) stratify the risk using clinical characteristics and complementary studies, including the cardiopulmonary exercise test (CPET). This takes into account 3 parameters: peak O2 consumption (peak VO2), its percentage with respect to the predicted VO2, and the minute ventilation/carbon dioxide production (VE/VCO2) slope. However, none of the models that validated this way of stratifying risk included PCPE among their variables. Objectives : To determine what proportion of patients with group I PAH considered to be at low risk and who walk >440 meters in the 6-minute walk test (6MWT) have parameters considered to be of moderate or high risk in the PCPE. Methods : Patients >18 years of age, diagnosed with group I PAH at low risk of events, who walked >440 meters in the 6MWT and had NT-proBNP value <300 pg/dL were included. A CPET was performed in which the peak VO2, its percentage with respect to the predicted VO2, and the VE/VCO2 slope were recorded. It was determined what proportion of patients presented these parameters in a higher than low risk stratum (peak VO2 consumption ≤15 ml/min/Kg, its percentage with respect to the predicted VO2 ≤65% and the VE/VCO2 slope ≥36). Results : Eighteen patients were included. Despite being low-risk patients with a good functional class, all patients presented a peak VO2 less than 85% of predicted, which determines a deterioration of functional capacity. A single patient (6%) presented the three parameters evaluated at low risk, 8 patients (44%) had at least one altered parameter, 7 patients (39%) presented 2 altered parameters and in 2 patients (11%) all parameters were altered. The parameters that were most frequently altered were the percentage of predicted peak VO2 and the VE/VCO2 slope in 67% of the cases. Only 4 patients presented a peak VO2 <15 ml/kg/m. No patient presented peak VO2 values or percentage of predicted VO2 in the high-risk category. However, 6 patients (33%) presented a high-risk VE/VCO2 slope. Conclusion : Majority (92%) of the patients considered low risk and who walk more than 440 meters in 6 minutes presented at least one altered variable in the CPET. The VE/VCO2 slope and the percentage of predicted peak VO2 consumption were the most frequently altered variables. The VE/VCO2 slope was the only one that showed values considered high risk. CPET could have a place in the precision stratification of low-risk patients. The value of this finding should be evaluated in prospective studies.

Heat tolerance of marine ectotherms in a warming Antarctica.

Global warming is affecting the Antarctic continent in complex ways. Because Antarctic organisms are specialized to living in the cold, they are vulnerable to increasing temperatures, although quantitative analyses of this issue are currently lacking. Here we compiled a total of 184 estimates of heat tolerance belonging to 39 marine species and quantified how survival is affected concomitantly by the intensity and duration of thermal stress. Species exhibit thermal limits displaced toward colder temperatures, with contrasting strategies between arthropods and fish that exhibit low tolerance to acute heat challenges, and brachiopods, echinoderms, and molluscs that tend to be more sensitive to chronic exposure. These differences might be associated with mobility. A dynamic mortality model suggests that Antarctic organisms already encounter temperatures that might be physiologically stressful and indicate that these ecological communities are indeed vulnerable to ongoing rising temperatures.

El calentamiento global está afectando al continente antártico de formas complejas. Dado que los organismos antárticos están especializados a vivir en el frío, son vulnerables al aumento de las temperaturas, aunque en la actualidad hay carencia de análisis cuantitativos al respecto. Aquí recopilamos un total de 184 estimaciones de tolerancia al calor pertenecientes a 39 especies marinas, y cuantificamos cómo la supervivencia de estos organismos se ve afectada concomitantemente por la intensidad y la duración de un estrés térmico. Efectivamente las especies antárticas muestran límites térmicos desplazados hacia temperaturas más frías, con estrategias contrastadas entre los artrópodos y los peces que muestran una baja tolerancia a los desafíos térmicos agudos, y los braquiópodos, equinodermos y moluscos que tienden a ser más sensibles a la exposición crónica. Estas diferencias podrían estar asociadas con la movilidad. Un modelo dinámico de mortalidad sugiere que los organismos antárticos ya se enfrentan a temperaturas que podrían ser fisiológicamente estresantes e indican que estas comunidades ecológicas son realmente vulnerables al aumento continuo de las temperaturas.

Rehabilitación cardiorrespiratoria en hipertensión pulmonar: experiencia en un centro de referencia / Cardiorespiratory rehabilitation in pulmonary hypertension: experience in a reference center

RESUMEN Introducción: La hipertensión pulmonar (HP) abarca un grupo heterogéneo de enfermedades que genera discapacidad y aumento de la morbimortalidad. La rehabilitación cardiorrespiratoria (RC) es un recurso terapéutico subutilizado en esta condición. Objetivo: Estimar los efectos de un programa de RC en una prueba de caminata de campo y en la calidad de vida de pacientes con diagnóstico de HP de los grupos I y IV. Materiales y Métodos: Los pacientes fueron evaluados antes y después de la intervención mediante la prueba de caminata de 6 minutos (PC6M) y el Saint George's Respiratory Questionnaire (SGRQ). El programa de RC consistió en 8 semanas de ejercicios supervisados con modalidad institucional. Resultados: Se incluyeron 19 pacientes con diagnóstico de HP precapilar por cateterismo cardíaco derecho, 18 mujeres (94,7%) con una media de edad de 45,5 ± 14,3 años. Trece (68,4%) presentaron HP del grupo I, y 6 (31,6%) HP del grupo IV. Se observaron cambios estadísticamente significativos en la PC6M (diferencia de medias -DM- 31 ± 27,3 metros; p <0,001), y en el SGRQ (DM 8,2 ± 10,2; p<0,01). No se reportaron eventos adversos graves durante el programa. Conclusiones: Nuestro estudio sugiere que un programa de RC supervisado en pacientes con HP podría mejorar la distancia caminada y la calidad de vida.

ABSTRACT Background: Pulmonary hypertension (PH) comprises a heterogeneous group of diseases resulting in disability and increased morbidity and mortality. Cardiopulmonary rehabilitation (CR) is a therapeutic resource not widely used in this condition. Objective: The aim of this study was to evaluate the effects of a CR program on a walking test and on the quality of life in patients with group 1 and group 4 PH Methods: Patients were evaluated before and after the intervention with the six-minute walk test (6MWT) and Saint George's Respiratory Questionnaire (SGRQ). The program consisted of 8 weeks of supervised exercises within the institution. Results: Nineteen patients with precapillary PH diagnosed by right heart catheterization were included; 18 were women (94.7%) with a mean age of 45.5±14.3 years. Thirteen (68.4%) patients had group 1 PH and 6 (31.6%) had group 4 PH. There were statistically significant changes in the 6MWT [mean difference (MD) 31±27.3 m; p<0.001], and in the SGRQ (MD 8.2±10.2; p<0.01). No adverse events were reported during the program. Conclusions: Our study suggests that a supervised CR program in patients with PH could improve the distance walked and the quality of life.

[Analysis of advertising on neurological drugs received during the medical consultation]. / Análisis de publicidades sobre medicamentos neurológicos recibidos durante la consulta médica.

Drug promotion and advertisement by pharmaceutical industry influence medical prescription and, in some cases, the information provided is incomplete or biased. The objective was to analyze the advertisements delivered by medical representatives and determine if the information was appropriate for rational prescribing. It is a prospective study (March to November 2018) by collecting print advertisements randomly received in neurology centers. It was evaluated if they met the ethical criteria established by the WHO, using as a reference leaflets from Administración Nacional de Medicamentos, Alimentos y Tecnología Médica (ANMAT), Food and Drugs Administration (FDA) and pharmacology books. A committee of pharmacology physicians analyzed if the content of the pamphlets was misleading according to the WHO. Sixty advertisements were analyzed, being anti-epileptics and antidepressants the most advertised drugs. The 33.3% (n = 20) of them included leaflets in accordance to ANMAT. One case presented an "off-label" indication. Drug action was presented in 31.7% (n = 19) of the pamphlets, adverse reactions in 40% (n = 24), posology in 45% (n = 27), contraindications in 38.3% (n = 23) and the necessary precautions in 36.7% (n = 22) of them. The information provided was false in 80% (n = 48) and 53.3% (n = 32) contained misleading images; and 69.2% (n = 18) of the graphics were false. The information provided by medical advertisements analyzed in this study would be insufficient to know and prescribe a new drug. Lack of information in posology, contraindication, drug action and adverse reactions do not contribute to rational use of medications.

La publicidad y promoción de medicamentos por parte de la industria farmacéutica ejerce influencia sobre la prescripción médica y, en algunos casos, la información provista es incompleta o sesgada. El objetivo fue analizar las publicidades entregadas por representantes médicos y determinar si la información era apropiada para la prescripción racional. Es un estudio prospectivo (marzo a noviembre 2018) mediante la recolección de publicidades impresas recibidas aleatoriamente en centros de neurología. Se evaluó si cumplían los criterios éticos establecidos por la OMS, utilizando como referencia prospectos de la Administración Nacional de Medicamentos, Alimentos y Tecnología médica (ANMAT), la Food and Drugs Administration (FDA) y libros de farmacología. Un comité de médicos farmacólogos analizó si el contenido de los folletos era engañoso según la OMS. Se analizaron 60 publicidades, siendo antiepilépticos y antidepresivos los más publicitados. El 33.3% (n = 20) incluían prospectos acordes según ANMAT. Un caso presentaba indicación off-label. Los folletos exponían el mecanismo de acción en el 31.7% (n = 19), las reacciones adversas medicamentosas 40% (n = 24), la posología en el 45% (n = 27), las contraindicaciones 38.3% (n = 23) y en 36.7% (n = 22) las precauciones necesarias. La información brindada era falaz en el 80% (n = 48) y el 53.3% (n = 32) tenían imágenes capciosas. El 69.2% (n = 18) de los gráficos eran capciosos. En el presente trabajo, la información brindada por la publicidad médica sería insuficiente para conocer y prescribir nuevos fármacos. La falta de información en la posología, contraindicaciones, mecanismos de acción y reacciones adversas no contribuyen al uso racional de medicamentos.

Análisis de publicidades sobre medicamentos neurológicos recibidos durante la consulta médica / Analysis of advertising on neurological drugs received during the medical consultation

Resumen La publicidad y promoción de medicamentos por parte de la industria farmacéutica ejerce influencia sobre la prescripción médica y, en algunos casos, la información provista es incompleta o sesgada. El objetivo fue analizar las publicidades entregadas por representantes médicos y determinar si la información era apropiada para la prescripción racional. Es un estudio prospectivo (marzo a noviembre 2018) mediante la recolección de publicidades impresas recibidas aleatoriamente en centros de neurología. Se evaluó si cumplían los criterios éticos establecidos por la OMS, utilizando como referencia prospectos de la Administración Nacional de Medicamentos, Alimentos y Tecnología médica (ANMAT), la Food and Drugs Administration (FDA) y libros de farmacología. Un comité de médicos farmacólogos analizó si el contenido de los folletos era engañoso según la OMS. Se analizaron 60 publicidades, siendo antiepilépticos y antidepresivos los más publicitados. El 33.3% (n = 20) incluían prospectos acordes según ANMAT. Un caso presentaba indicación off-label. Los folletos ex ponían el mecanismo de acción en el 31.7% (n = 19), las reacciones adversas medicamentosas 40% (n = 24), la posología en el 45% (n = 27), las contraindicaciones 38.3% (n = 23) y en 36.7% (n = 22) las precauciones necesarias. La información brindada era falaz en el 80% (n = 48) y el 53.3% (n = 32) tenían imágenes capcio sas. El 69.2% (n = 18) de los gráficos eran capciosos. En el presente trabajo, la información brindada por la publicidad médica sería insuficiente para conocer y prescribir nuevos fármacos. La falta de información en la posología, contraindicaciones, mecanismos de acción y reacciones adversas no contribuyen al uso racional de medicamentos.

Abstract Drug promotion and advertisement by pharmaceutical industry influence medical prescription and, in some cases, the information provided is incomplete or biased. The objective was to analyze the advertisements deliv ered by medical representatives and determine if the information was appropriate for rational prescribing. It is a prospective study (March to November 2018) by collecting print advertisements randomly received in neurology centers. It was evaluated if they met the ethical criteria established by the WHO, using as a reference leaflets from Administración Nacional de Medicamentos, Alimentos y Tecnología Médica (ANMAT), Food and Drugs Ad ministration (FDA) and pharmacology books. A committee of pharmacology physicians analyzed if the content of the pamphlets was misleading according to the WHO. Sixty advertisements were analyzed, being anti-epileptics and antidepressants the most advertised drugs. The 33.3% (n = 20) of them included leaflets in accordance to ANMAT. One case presented an "off-label" indication. Drug action was presented in 31.7% (n = 19) of the pam phlets, adverse reactions in 40% (n = 24), posology in 45% (n = 27), contraindications in 38.3% (n = 23) and the necessary precautions in 36.7% (n = 22) of them. The information provided was false in 80% (n = 48) and 53.3% (n = 32) contained misleading images; and 69.2% (n = 18) of the graphics were false. The information provided by medical advertisements analyzed in this study would be insufficient to know and prescribe a new drug. Lack of information in posology, contraindication, drug action and adverse reactions do not contribute to rational use of medications.

Collaborative registry of pulmonary hypertension in Argentina (RECOPILAR). Final analysis / Registro colaborativo de hipertensión pulmonar en Argentina (RECOPILAR): análisis final

Abstract The epidemiology of pulmonary hypertension (PH), especially pulmonary arterial hypertension (PAH), has not been evaluated in our country, therefore there is no reference parameter to establishing the representativeness of this information in the national order. This registry represents the first collaborative effort to provide a knowledge base of this disease, including 5 scientific societies that represent different specialties (pediatrics, rheumatology, pulmonology and cardiology) with data from 23 Argentine provinces. These efforts involved five societies of various adult (cardiology, rheumatology, and pulmonology) and pediatric (cardiology) specialties. Subjects were grouped (1-5) in accord with the 2013 Nice classification. A total of 627 patients (mean age, 50.8±18 years; women, 69.2%) were recruited. Incident cases accounted for 53%. Functional class III-IV accounted for 69% at time of diagnosis and 33.4% at time of inclusion. Distributions in groups 1-5 were 63.6%, 15.9%, 8.3%, 9.7%, and 2.4%, respectively. Treatment consisted of diuretics (51.2%), mineralocorticoid receptor antagonists (44.7%), digoxin (16.6%), anticoagulants (39.2%), renin-angiotensin antagonists (15.5%), beta blockers (15.6%), and calcium channel blockers (8%). Rates of specific therapies usage in PAH vs. non-PAH group were 80.5% vs. 40.8% (phosphodiesterase-5 inhibitors: 71% vs. 38.6%; endothelin receptor antagonists: 54.4% vs. 14.5%; prostanoids: 14.3 vs. 3.1%; all p < 0.001). Three-year survival in PAH and non-PAH differed significantly (82.8% vs. 73.3%; p = 0.001). In the Argentine RECOPILAR registry, the clinic-epidemiologic profile was that of advanced-stage disease. Diagnostic workups and therapeutics interventions, including use of specific therapy for PAH, were consistent with current recommendations. Despite delays in diagnosis, survival was aligned with other contemporary registries.

Resumen La epidemiología de la hipertensión pulmonar (HP), especialmente la arterial (HAP), no ha sido evaluada en nuestro país, por lo cual no existe un parámetro de referencia para establecer la representatividad de esta información en el orden nacional. El presente registro representa el primer esfuerzo colaborativo para una base de conocimiento de esta enfermedad, incluyendo 5 sociedades científicas que representan a distintas especiali dades médicas (pediatría, reumatología, neumonología y cardiología) con datos de 23 provincias argentinas. Los sujetos se agruparon (1-5) de acuerdo con la clasificación de Niza de 2013. El seguimiento se completó en 583 pacientes (93%) un año después del final de la inscripción. Se incluyeron 627 pacientes (edad media, 50.8 ± 18 años; mujeres, 69.2%). Los casos incidentes representaron el 53%. La clase funcional III-IV representaba 69% en el momento del diagnóstico y 33.4% en el momento de la inclusión. Las manifestaciones clínicas fueron disnea (81.8%), fatiga (54.1%), síncope (10.8%), dolor torácico (14.7%), palpitaciones (20.9%) e insuficiencia cardíaca (20.4%). Las tasas de uso de terapias específicas en la hipertensión arterial pulmonar (HAP) frente al grupo sin HAP fueron del 80.5% frente al 40.8%. La supervivencia a tres años en los subconjuntos de HAP y no HAP difirió significativamente (82.8% vs. 73.3%; p = 0.001). En el registro RECOPILAR argentino, que aborda principalmente la HAP, el perfil clínico-epidemiológico fue el d e una enfermedad en estadios avanzados. El diag nóstico y las intervenciones terapéuticas, incluido el uso de terapia específica para la HAP, fueron consistentes con las recomendaciones actuales.

Collaborative registry of pulmonary hypertension in Argentina (RECOPILAR). Final analysis.

The epidemiology of pulmonary hypertension (PH), especially pulmonary arterial hypertension (PAH), has not been evaluated in our country, therefore there is no reference parameter to establishing the representativeness of this information in the national order. This registry represents the first collaborative effort to provide a knowledge base of this disease, including 5 scientific societies that represent different specialties (pediatrics, rheumatology, pulmonology and cardiology) with data from 23 Argentine provinces. These efforts involved five societies of various adult (cardiology, rheumatology, and pulmonology) and pediatric (cardiology) specialties. Subjects were grouped (1-5) in accord with the 2013 Nice classification. A total of 627 patients (mean age, 50.8 ± 18 years; women, 69.2%) were recruited. Incident cases accounted for 53%. Functional class III-IV accounted for 69% at time of diagnosis and 33.4% at time of inclusion. Distributions in groups 1-5 were 63.6%, 15.9%, 8.3%, 9.7%, and 2.4%, respectively. Treatment consisted of diuretics (51.2%), mineralocorticoid receptor antagonists (44.7%), digoxin (16.6%), anticoagulants (39.2%), renin-angiotensin antagonists (15.5%), beta blockers (15.6%), and calcium channel blockers (8%). Rates of specific therapies usage in PAH vs. non-PAH group were 80.5% vs. 40.8% (phosphodiesterase-5 inhibitors: 71% vs. 38.6%; endothelin receptor antagonists: 54.4% vs. 14.5%; prostanoids: 14.3 vs. 3.1%; all p < 0.001). Three-year survival in PAH and non-PAH differed significantly (82.8% vs. 73.3%; p = 0.001). In the Argentine RECOPILAR registry, the clinic-epidemiologic profile was that of advanced-stage disease. Diagnostic workups and therapeutics interventions, including use of specific therapy for PAH, were consistent with current recommendations. Despite delays in diagnosis, survival was aligned with other contemporary registries.

La epidemiología de la hipertensión pulmonar (HP), especialmente la arterial (HAP), no ha sido evaluada en nuestro país, por lo cual no existe un parámetro de referencia para establecer la representatividad de esta información en el orden nacional. El presente registro representa el primer esfuerzo colaborativo para una base de conocimiento de esta enfermedad, incluyendo 5 sociedades científicas que representan a distintas especialidades médicas (pediatría, reumatología, neumonología y cardiología) con datos de 23 provincias argentinas. Los sujetos se agruparon (1-5) de acuerdo con la clasificación de Niza de 2013. El seguimiento se completó en 583 pacientes (93%) un año después del final de la inscripción. Se incluyeron 627 pacientes (edad media, 50.8 ± 18 años; mujeres, 69.2%). Los casos incidentes representaron el 53%. La clase funcional III-IV representaba 69% en el momento del diagnóstico y 33.4% en el momento de la inclusión. Las manifestaciones clínicas fueron disnea (81.8%), fatiga (54.1%), síncope (10.8%), dolor torácico (14.7%), palpitaciones (20.9%) e insuficiencia cardíaca (20.4%). Las tasas de uso de terapias específicas en la hipertensión arterial pulmonar (HAP) frente al grupo sin HAP fueron del 80.5% frente al 40.8%. La supervivencia a tres años en los subconjuntos de HAP y no HAP difirió significativamente (82.8% vs. 73.3%; p = 0.001). En el registro RECOPILAR argentino, que aborda principalmente la HAP, el perfil clínico-epidemiológico fue el d e una enfermedad en estadios avanzados. El diagnóstico y las intervenciones terapéuticas, incluido el uso de terapia específica para la HAP, fueron consistentes con las recomendaciones actuales.

Thermal effects vary predictably across levels of organization: empirical results and theoretical basis.

Thermal performance curves have provided a common framework to study the impact of temperature in biological systems. However, few generalities have emerged to date. Here, we combine an experimental approach with theoretical analyses to demonstrate that performance curves are expected to vary predictably with the levels of biological organization. We measured rates of enzymatic reactions, organismal performance and population viability in Drosophila acclimated to different thermal conditions and show that performance curves become narrower with thermal optima shifting towards lower temperatures at higher levels or organization. We then explain these results on theoretical grounds, showing that this pattern reflects the cumulative impact of asymmetric thermal effects that piles up with complexity. These results and the proposed framework are important to understand how organisms, populations and ecological communities might respond to changing thermal conditions.

Is the Clinician's Eye a Valid and Reproducible Tool for Diagnosing Patella Alta on a Lateral Knee Radiography?

INTRODUCTION: Validity and reproducibility of the clinician's eye (CE) to diagnose patella alta (PA) on a lateral knee radiography (radiograph) is unknown. METHODS: Cross-sectional study of 46 lateral knee x-rays. Three blind observers used CE, Insall-Salvati (IS), modified Insall-Salvati (mIS), and Caton-Deschamps (C-D) to determine patellar height. Sensitivity and specificity of each observer was compared with the musculoskeletal radiologist's C-D measurements. Intraobserver and interobserver agreement were assessed with intraclass correlation coefficient and Fleiss κ, respectively. Time needed to estimate patellar height for every method was recorded in seconds. Statistical differences between observers were calculated with a generalized estimating equation. Analysis of variance and post hoc Bonferroni test compared duration of each method (P < 0.05). Data were analyzed using Stata 15 (StataCorp). RESULTS: CE, IS, mIS, and C-D's sensitivity and specificity values are as follows: 77%, 92%; 94%, 52%; 67%, 58%; and 53%, 89%, respectively. Intraclass correlation coefficient and Fleiss κ of CE, IS, mIS, and C-D values are as follows: 0.66 and 0.43, 0.88 and 0.68, 0.54 and 0.09, and 0.68 and 0.59, respectively. CE was the second most sensitive and most specific method for diagnosis of PA, with moderate intraobserver and interobserver agreement. IS was the most sensitive method with good intraobserver and interobserver agreement. CE was significantly faster (P < 0.05) than all other conventional radiographic ratios. CONCLUSION: CE's sensitivity increases with observer's experience and is highly specific. If normal patellar height is diagnosed, no other ratios are necessary, even in the less experienced clinician. Intraobserver and interobserver reproducibilities were moderate and only inferior to the IS ratio. In case patellar height is uncertain with the CE, the IS ratio is the most sensitive and reproducible method to confirm the diagnosis of PA.

Vitamin D deficiency among patients with pulmonary hypertension.

BACKGROUND: There is little information about vitamin D (Vit D) deficiency in patients with pulmonary hypertension (PH). The objective of this study was: 1) compare Vit D levels between patients with PH, left ventricular failure (LVF) and healthy subjects (HS); 2) correlate, in patients with PH, Vit D levels with prognosis-related variables, such as the 6-min walk test (6MWT). METHODS: Vitamin D levels were measured in a cross-sectional study in 126 patients from one of three groups: patients with PH (n = 53), patients with LVF (n = 42) and healthy subjects (n = 31). In all groups, 8-h fasting blood samples were obtained in the morning. In the PH and the LVF group, functional class (WHO criteria), metres covered in the 6MWT and echocardiographic parameters were analysed. In the PH group, plasma N terminal pro B type natriuretic peptide (NT-proBNP) level was analysed and a complete haemodynamic evaluation by right heart catheterisation was made. RESULTS: Mean Vit D levels were lower in PH than in both other groups (ng/ml, mean ± SD): PH 19.25 ± 10, LVF 25.68 ± 12, HS 28.8 ± 12 (PH vs LVF p = 0.017, PH vs HS p = 0.001 and HS vs LVF p = 0.46). Vit D deficiency prevalence was higher in PH as compared to the other groups (PH 53.8%, LVF 45.2%, HS 25%, p = 0.01). Patients with PH in functional class (FC; WHO criteria) III-IV had higher Vit D deficiency prevalence than those in FC I-II (86.7% vs 40.5%, p = 0.003). There was a significant linear correlation between the 6MWT and Vit D levels in PH (p < 0.01), but not in LVF (p = 0.69). CONCLUSIONS: Vit D levels were lower in patients with PH as compared to patients with LVF and HS and correlated directly with 6-min walk distance.

El déficit de hierro en pacientes con hipertensión arterial pulmonar es altamente prevalente / Iron Deficiency is Highly Prevalent in Patients with Pulmonary Arterial Hypertension

RESUMEN Objetivos: Evaluar la prevalencia del déficit de hierro en hipertensión pulmonar y compararlo con otras poblaciones de pacientes. Establecer su valor pronóstico. Material y métodos: Estudio prospectivo, observacional. Se midieron parámetros de hierro sérico en pacientes consecutivos con diagnóstico de hipertensión pulmonar. Se compararon con pacientes con insuficiencia cardíaca y con controles sanos. Se buscó correlación entre los valores séricos de hierro y la clase funcional, la distancia recorrida en TC6M y el NT-proBNP. Resultados: Participaron 107 pacientes: 60 con hipertensión pulmonar, 26 con insuficiencia cardíaca y 21 controles sanos. El déficit de hierro fue del 78,3% en los pacientes con hipertensión pulmonar; del 45,8%, en aquellos que presentaban insuficiencia cardíaca; y del 23,8% (p < 0,001) en los controles sanos. La prevalencia de anemia resultó del 25% en los pacientes con hipertensión pulmonar; del 26,9% en los que padecían insuficiencia cardíaca; y del 19% (p < 0,8) en los controles sanos. En el subgrupo de pacientes en clase funcional I-II, la prevalencia de DFe fue del 78% en los pacientes con hipertensión pulmonar vs. el 43,5% (p < 0,005) en los que tenían insuficiencia cardíaca, y la anemia resultó del 17,1%% vs. el 28%% (p < 0,2). Se halló correlación significativa entre ferremia y saturación de transferrina con distancia caminada en TC6M (r: 0,35; p < 0,01 y r: 0,34; p < 0,01) y no hubo correlación para ferritina y transferrina. No se encontró significancia estadística entre déficit de hierro y clase funcional o NT-proBNP. Conclusiones: El déficit de hierro en la hipertensión arterial es altamente prevalente y superior al observado en la insuficiencia cardíaca y en los sujetos control, y no se establece relación con prevalencia de anemia, la cual fue similar en los tres grupos. El hierro sérico tiene una clara relación con la distancia caminada, no así con clase funcional, lo que, tal vez, obedezca al bajo número de pacientes.

ABSTRACT Objective: The aim of this study was to assess the prevalence of iron deficiency in pulmonary hypertension, to compare it with other patient populations and to establish its prognostic value. Methods: This was a prospective, observational study. Serum iron parameters were measured in consecutive patients diagnosed with pulmonary hypertension and compared with heart failure patients and healthy controls. A correlation was sought between serum iron levels and functional class, distance walked in the 6-minute walk test and NT-proBNP. Results: A total of 107 patients were included in the study: 60 with pulmonary hypertension, 26 with heart failure and 21 healthy controls. Iron deficiency was 78.3% in patients with pulmonary hypertension, 45.8% in those with heart failure and 23.8% in healthy controls (p<0.001). The prevalence of anemia was 25% in pulmonary hypertension, 26.9% in heart failure and 19% in healthy controls (p<0.8). In patients with functional class I-II, iron deficiency was: 78% in pulmonary hypertension vs. 43.5% in heart failure (p<0.005), and anemia was 17.1% vs. 28%, respectively (p<0.2). A significant correlation was found between serum iron and transferrin saturation with the distance walked in the 6-minute walk test (r: 0.35; p<0.01 and r: 0.34; p<0.01, respectively) and no correlation was found for transferrin and ferritin. Also, no significant correlation was found between iron deficiency and functional class or NT-proBNP. Conclusions: Iron deficiency is highly prevalent in pulmonary hypertension, and superior to that found in heart failure patients and healthy controls. No relationship was established with anemia, which was similar in the three groups. Serum iron is clearly related with the distance walked, but not with functional class, a result which may be attributed to the limited number of patients.

von Kármán-Howarth equation for three-dimensional two-fluid plasmas.

We derive the von Kármán-Howarth equation for a full three-dimensional incompressible two-fluid plasma. In the long-time limit and for very large Reynolds numbers we obtain the equivalent of the hydrodynamic "four-fifths" law. This exact law predicts the scaling of the third-order two-point correlation functions, and puts a strong constraint on the plasma turbulent dynamics. Finally, we derive a simple expression for the 4/5 law in terms of third-order structure functions, which is appropriate for comparison with in situ measurements in the solar wind at different spatial ranges.

Evaluación de estructuras cerebrales por resonancia magnética en personas infectadas con el virus de la inmunodeficiencia humana (VIH) y adherentes al tratamiento antirretroviral / Evaluation by MRI of brain structures of HIV subjects with adherence to antiretroviral therapy

Introducción: los cambios estructurales del cerebro se pueden observar en fases tempranas de la infección por VIH y acelerarse en estadios avanzados, aunque queda por profundizar con más estudios clínicos la relación que pueda existir entre la adherencia al tratamiento antirretroviral y los cambios en los volúmenes de las estructuras cerebrales. Objetivo: identificar los cambios en estructurascerebrales de personas infectadas con VIH por medio de la resonancia magnética y explorar su relación con el tratamiento antirretroviral. Materiales y métodos: se eligieron 2 grupos, cada uno con 16 individuos; el primero conformado por personas infectadas con VIH y tratamiento adherente y el segundo con individuos no infectados (grupo control). Los volúmenes de las estructuras corticales, subcorticales, las regiones superficiales de la sustancia blanca y gris fueron calculados para los dos hemisferios, en los cuales se utilizaron algoritmos automáticos de la plataforma de análisis de imágenesFreeSurfer. Los datos anatómicos de los individuos fueron adquiridos en un equipo de resonancia magnética 3T en el Instituto de Alta Tecnología Médica (IATM), Medellín, Colombia. Resultados: el análisis de las estructuras corticales y subcorticales no arrojó diferencias significativas entre las volumetríasdel grupo control y los individuos infectados con VIH/adherentes al tratamiento. Conclusión: los hallazgos muestran que el cerebro puede estar posiblemente sin alteraciones en sus estructuras corticales y subcorticales en los individuos con VIH adherentes al tratamiento, en primera o segunda línea de tratamiento antirretroviral, y, a la vez, estos resultados pueden aportar nuevas estrategias de neuroprotección ante el autocuidado frente al esquema de tratamento.

Introduction: structural brain changes can be detected in early stages of HIV infection and may be accelerated in advanced stages, however it still important to have more clinic studies for analyze the relationship between the adherence to antiretroviral therapy and changes in the volume of brain structures. Objective: To identify changes in brain structures from HIV subjects by using Magnetic Resonance Imaging (MRI) and to correlate the findings with the antiretroviral treatment. Materials and methods: Two groups with 16 subjects were chosen: a HIV group of subjects with medication adherence and healthy subjects (control group). By using the automatic segmentation software for brain Freesurfer, cortical and subcortical structures volumes as well as grey and white matter surface area were calculated for both brain hemispheres. Data were acquired through 3T MRI scanner in the Instituto de Alta Tecnología Médica (IATM) from Medellin (Colombia). Results: There were not statistically significant differences in cortical and subcortical structures between control group and subjects HIV infected with adherence to treatment. Conclusion: These findings show that subjects infectedwith VIH in first or second line of antiretroviral treatment probably do not have any change on the brain cortical and subcortical structures. In addition, this allows developing new neuroprotection and self-care strategies during the current treatment plans.

Genomic variation and population structure detected by single nucleotide polymorphism arrays in Corriedale, Merino and Creole sheep.

THE AIM OF THIS STUDY WAS TO INVESTIGATE THE GENETIC DIVERSITY WITHIN AND AMONG THREE BREEDS OF SHEEP: Corriedale, Merino and Creole. Sheep from the three breeds (Merino n = 110, Corriedale n = 108 and Creole n = 10) were genotyped using the Illumina Ovine SNP50 beadchip(®). Genetic diversity was evaluated by comparing the minor allele frequency (MAF) among breeds. Population structure and genetic differentiation were assessed using STRUCTURE software, principal component analysis (PCA) and fixation index (FST). Fixed markers (MAF = 0) that were different among breeds were identified as specific breed markers. Using a subset of 18,181 single nucleotide polymorphisms (SNPs), PCA and STUCTURE analysis were able to explain population stratification within breeds. Merino and Corriedale divergent lines showed high levels of polymorphism (89.4% and 86% of polymorphic SNPs, respectively) and moderate genetic differentiation (FST = 0.08) between them. In contrast, Creole had only 69% polymorphic SNPs and showed greater genetic differentiation from the other two breeds (FST = 0.17 for both breeds). Hence, a subset of molecular markers present in the OvineSNP50 is informative enough for breed assignment and population structure analysis of commercial and Creole breeds.

Molecular dynamics of water in the neighborhood of aquaporins.

Present knowledge obtained by molecular dynamics (MD) simulation studies regarding the dynamics of water, both in the vicinity of biological membranes and within the proteinaceous water channels, also known as aquaporins (AQPs), is reviewed. A brief general summary of the water models most extensively employed in MD simulations (SPC, SPC/E, TIP3P, TIP4P), indicating their most relevant pros and cons, is likewise provided. Structural considerations of water are also discussed, based on different order parameters, which can be extracted from MD simulations as well as from experiments. Secondly, the behaviour of water in the neighbourhood of membranes by means of molecular dynamics simulations is addressed. Consequently, the comparison with previous experimental evidence is pointed out. In living cells, water is transported across the plasma membrane through the lipid bilayer and the aforementioned AQPs, which motivates this review to focus mostly on MD simulation studies of water within AQPs. Relevant contributions explaining peculiar properties of these channels are discussed, such as selectivity and gating. Water models used in these studies are also summarised. Finally, based on the information presented here, further MD studies are encouraged.

Estudo retrospectivo (2007-2011) da casuística de cães com mastocitomas cutâneos atendidos em um hospital-escola PT / Retrospective study (2007-2011) of dogs with cutaneous mast cell tumors attended at a teaching hospital PT / Un estudio retrospectivo (2007-2011) de perros con tumores de mastocitos cutáneos tratados en un hospital escuela ES

Na maioria das espécies animais, as neoplasias de origem mastocitária são incomuns. Raros são os casos de mastocitoma cutâneo (MC) em seres humanos; no entanto, na espécie canina, é a segunda neoplasia mais diagnosticada, representando aproximadamente 20% dos casos de tumores cutâneos. A faixa etária de maior ocorrência é entre oito a nove anos, podendo ocorrer em animais jovens com até três semanas de idade. Este estudo objetivou descrever as características epidemiológicas, hematológicas e histopatológicas de cães portadores de mastocitoma cutâneo atendidos pelo Serviço de Oncologia Veterinária de um hospital-escola do estado de São Paulo, entre os anos de 2007 e 2011, totalizando 73 pacientes. Foram obtidos os dados referentes a raça, idade, sexo, peso, região cutânea acometida, resultado do hemograma no momento da primeira consulta e graduação histopatológica de cães com diagnóstico da neoplasia.(AU)

Neoplasms of mast cell origin are uncommon in most animal species. Although cases of cutaneous mastocitoma (CM) are rare in humans, it is the second most diagnosed cancer in dogs, accounting for approximately 20% of cutaneous tumors in this species. The age group most frequently affected is between eight and nine years, but it may occur in animals up to three weeks old. This study aimed to describe the epidemiological, hematological and histopathological characteristics of 73 dogs with cutaneous mast cell tumors attended between 2007 and 2011 by the Oncology Service of a teaching hospital in the state of São Paulo. Data collected included race, age, sex, weight, skin region affected, blood tests results at the first consultation and histopathological grading of dogs diagnosed with this neoplasia.(AU)

En la mayoría de las especies animales, las neoplasias de origen mastocitaria son poco frecuentes. En medicina humana los casos de mastocitoma cutáneo (MC) suelen ser raros; no obstante, en la especie canina son la segunda neoplasia mas diagnosticada, representando aproximadamente el 20% de los tumores cutáneos. El rango etario con mayor frecuencia es entre los ocho y nueve años, pudiendo presentarse en animales jóvenes con hasta tres semanas de edad. Este estudio tuvo como objetivo describir las características epidemiológicas, hematológicas e histopatológicas de los perros con mastocitoma cutáneo, atendidos en el Servicio de Oncología Veterinaria de un hospital escuela en el estado de São Paulo, entre los años de 2007 y 2011, que representaron un total de 73 pacientes. Se obtuvieron datos referentes a la raza, edad, sexo, peso, región cutánea afectada, resultado de hemograma en la primer consulta y grado histopatológico de los perros diagnosticados con esta neoplasia.(AU)

Estudo retrospectivo (2007-2011) da casuística de cães com mastocitomas cutâneos atendidos em um hospital-escola / Retrospective study (2007-2011) of dogs with cutaneous mast cell tumors attended at a teaching hospital / Un estudio retrospectivo (2007-2011) de perros con tumores de mastocitos cutáneos tratados en un hospital escuela

Na maioria das espécies animais, as neoplasias de origem mastocitária são incomuns. Raros são os casos de mastocitoma cutâneo (MC) em seres humanos; no entanto, na espécie canina, é a segunda neoplasia mais diagnosticada, representando aproximadamente 20% dos casos de tumores cutâneos. A faixa etária de maior ocorrência é entre oito a nove anos, podendo ocorrer em animais jovens com até três semanas de idade. Este estudo objetivou descrever as características epidemiológicas, hematológicas e histopatológicas de cães portadores de mastocitoma cutâneo atendidos pelo Serviço de Oncologia Veterinária de um hospital-escola do estado de São Paulo, entre os anos de 2007 e 2011, totalizando 73 pacientes. Foram obtidos os dados referentes a raça, idade, sexo, peso, região cutânea acometida, resultado do hemograma no momento da primeira consulta e graduação histopatológica de cães com diagnóstico da neoplasia.

Neoplasms of mast cell origin are uncommon in most animal species. Although cases of cutaneous mastocitoma (CM) are rare in humans, it is the second most diagnosed cancer in dogs, accounting for approximately 20% of cutaneous tumors in this species. The age group most frequently affected is between eight and nine years, but it may occur in animals up to three weeks old. This study aimed to describe the epidemiological, hematological and histopathological characteristics of 73 dogs with cutaneous mast cell tumors attended between 2007 and 2011 by the Oncology Service of a teaching hospital in the state of São Paulo. Data collected included race, age, sex, weight, skin region affected, blood tests results at the first consultation and histopathological grading of dogs diagnosed with this neoplasia.

En la mayoría de las especies animales, las neoplasias de origen mastocitaria son poco frecuentes. En medicina humana los casos de mastocitoma cutáneo (MC) suelen ser raros; no obstante, en la especie canina son la segunda neoplasia mas diagnosticada, representando aproximadamente el 20% de los tumores cutáneos. El rango etario con mayor frecuencia es entre los ocho y nueve años, pudiendo presentarse en animales jóvenes con hasta tres semanas de edad. Este estudio tuvo como objetivo describir las características epidemiológicas, hematológicas e histopatológicas de los perros con mastocitoma cutáneo, atendidos en el Servicio de Oncología Veterinaria de un hospital escuela en el estado de São Paulo, entre los años de 2007 y 2011, que representaron un total de 73 pacientes. Se obtuvieron datos referentes a la raza, edad, sexo, peso, región cutánea afectada, resultado de hemograma en la primer consulta y grado histopatológico de los perros diagnosticados con esta neoplasia.

A molecular dynamics approach to ligand-receptor interaction in the aspirin-human serum albumin complex.

In this work, we present a study of the interaction between human serum albumin (HSA) and acetylsalicylic acid (ASA, C(9)H(8)O(4)) by molecular dynamics simulations (MD). Starting from an experimentally resolved structure of the complex, we performed the extraction of the ligand by means of the application of an external force. After stabilization of the system, we quantified the force used to remove the ASA from its specific site of binding to HSA and calculated the mechanical nonequilibrium external work done during this process. We obtain a reasonable value for the upper boundary of the Gibbs free energy difference (an equilibrium thermodynamic potential) between the complexed and noncomplexed states. To achieve this goal, we used the finite sampling estimator of the average work, calculated from the Jarzynski Equality. To evaluate the effect of the solvent, we calculated the so-called "viscous work," that is, the work done to move the aspirin in the same trajectory through the solvent in absence of the protein, so as to assess the relevance of its contribution to the total work. The results are in good agreement with the available experimental data for the albumin affinity constant for aspirin, obtained through quenching fluorescence methods.

Especialista en cardiología: diferentes caminos, ¿iguales resultados? / Do the Different Pathways to Become Specialist in Cardiology Have Similar Results? / Do the Different Pathways to Become Specialist in Cardiology Have Similar Results?

Una especialidad médica puede definirse como un conjunto de conocimientos correspondientes a un área específica. Estos conocimientos son adquiridos por medio de estudios de posgrado luego de obtener el título de médico. El propósito de este trabajo es hacer una revisión de las diferentes opciones disponibles en nuestro país para llegar a ser médico especialista en cardiología y, así, tratar de determinar si estos diferentes caminos podrían conducir a formaciones similares y equiparables entre los profesionales. La formación debe entenderse como un proceso de largo alcance a través del cual se modelan el pensamiento y el comportamiento socioprofesional. Este proceso debe ser permanente y debería ser regulado en forma centralizada de modo que permita asegurar la equidad y la homogeneidad en la formación del especialista. Existen diferentes maneras para llegar a ser médico especialista en cardiología, muchas son combinables y todas emplean diversas herramientas de selección, formación, supervisión, evaluación y control. En conclusión, esta heterogeneidad en la forma de instruir y peritar al especialista podría devenir en diferentes niveles de profesionales formados.

A medical specialty may be defined as the body of knowledge corresponding to a specific medical field. This knowledge is provided by postgraduate training programs after completing the medical doctor degree. The goal of the present study is to review the different options available in our country to become a specialist in cardiology and, thus, determine if these diverse pathways produce equally trained cardiologists. Training should be understood as a long-term process that shapes professional thinking and social behavior. This process must be permanent and should have core regulations to ensure equal and homogenous training in the specialty. There are many ways of becoming a specialist in cardiology; most of these pathways may be combined and all of them use different tools for selecting, training, supervising, evaluating and controlling trainees. Thus, these differences in training and evaluating specialists might produce professionals with different levels of competencies.

Especialista en cardiología: diferentes caminos, ¿iguales resultados? / Do the Different Pathways to Become Specialist in Cardiology Have Similar Results? / Do the Different Pathways to Become Specialist in Cardiology Have Similar Results?

Una especialidad médica puede definirse como un conjunto de conocimientos correspondientes a un área específica. Estos conocimientos son adquiridos por medio de estudios de posgrado luego de obtener el título de médico. El propósito de este trabajo es hacer una revisión de las diferentes opciones disponibles en nuestro país para llegar a ser médico especialista en cardiología y, así, tratar de determinar si estos diferentes caminos podrían conducir a formaciones similares y equiparables entre los profesionales. La formación debe entenderse como un proceso de largo alcance a través del cual se modelan el pensamiento y el comportamiento socioprofesional. Este proceso debe ser permanente y debería ser regulado en forma centralizada de modo que permita asegurar la equidad y la homogeneidad en la formación del especialista. Existen diferentes maneras para llegar a ser médico especialista en cardiología, muchas son combinables y todas emplean diversas herramientas de selección, formación, supervisión, evaluación y control. En conclusión, esta heterogeneidad en la forma de instruir y peritar al especialista podría devenir en diferentes niveles de profesionales formados.(AU)

A medical specialty may be defined as the body of knowledge corresponding to a specific medical field. This knowledge is provided by postgraduate training programs after completing the medical doctor degree. The goal of the present study is to review the different options available in our country to become a specialist in cardiology and, thus, determine if these diverse pathways produce equally trained cardiologists. Training should be understood as a long-term process that shapes professional thinking and social behavior. This process must be permanent and should have core regulations to ensure equal and homogenous training in the specialty. There are many ways of becoming a specialist in cardiology; most of these pathways may be combined and all of them use different tools for selecting, training, supervising, evaluating and controlling trainees. Thus, these differences in training and evaluating specialists might produce professionals with different levels of competencies.(AU)