Demographic, hemodynamic characteristics, and therapeutic trends of pulmonary hypertension patients: The Pulmonary Hypertension Mexican registry (REMEHIP).

Data on demographic characteristics and therapeutic approaches in Latin American pulmonary arterial hypertension (PAH) patients are scarce. Pulmonary Hypertension Mexican registry (REMEHIP) is a multicenter Mexican registry of adult and pediatric patients, including prevalent and incident cases. Objective: assess clinical characteristics, treatment trends, and in-hospital outcomes. Inclusion: age >2 years, diagnosis of pulmonary hypertension (PH) (groups 1 and 4), right heart catheterization with mPAP ≥25 mmHg, PWP ≤ 15 mmHg, and PVR > 3 Wood unit (WU). We included 875 PH patients, 619 adults, 133 pediatric idiopathic PAH (IPAH), and 123 chronic thromboembolic pulmonary hypertension (CTEPH) patients. We enrolled 48.4% of the incident and 51.6% of the prevalent adult and pediatric patients. PAH adults: age 43 ± 15, females 81.9%, functional class (FC) (I/II) 66.5%, 6-min walk distance (6MWD) 378 ± 112 m, mPAP 57.3 ± 19.0 mmHg, confidence interval (CI) 3.3 ± 1.5 L/min/m2, PVR 12.0 ± 8.1 WU. PAH pediatrics: age 9 ± 5, females 51.1%, FC (I/II) 85.5%, 6MWD 376 ± 103 m, mPAP 49.7 ± 13.4 mmHg, CI 2.6 ± 0.9 L/min/m2, PVR 16.4 ± 13.5 WU. CTEPH: age 44 ± 17, females 56.1%, FC (I/II) 65.5%, 6MWD 369 ± 126 m, mPAP 49.7 ± 13.4 mmHg, CI 2.6 ± 0.9 L/min/m2, PVR 10.5 + 6.5 WU. When we analyzed the IPAH group separately, it sustained a high functional class I/II incidence. REMEHIP shows better functional class in young females with severe PAH than in American and European patients. Also, PAH pediatric patients had a better functional class than other registries. However, our registry also shows that our population's access to specific pharmacologic treatments is still far from optimal.

Percepción de estudiantes de Enfermería sobre la adquisición de habilidades clínicas en tiempos de COVID-19 / Perception by Nursing students about clinical skill acquisition in times of COVID-19

Objetivo: identificar la percepción que tienen los estudiantes de Enfermería sobre la adquisición de habilidades clínicas durante la pandemia por COVID-19 y analizar si está asociada con el semestre que están cursando y con haber realizado práctica clínica en escenarios reales. Método: se llevó a cabo un estudio descriptivo transversal con estudiantes de Enfermería de una universidad pública de Zacatecas, México (N= 1.033). Se administró vía electrónica el segundo apartado del cuestionario Clinical Competency Questionnaire traducido al español con un alfa de Cronbach= 0,969. Se analizó la asociación de las habilidades clínicas con el semestre cursado y la experiencia mediante la prueba de Chi cuadrado con una significancia estadística de p≤ 0,05. Resultados: respondieron un total de N= 82 estudiantes. La media de edad fue de 20,7 (DE:1,40), el 87,8% era mujer en su mayoría del séptimo semestre (40,2%). Un 50% se percibió con habilidades clínicas deficientes; un 34,1%, sin habilidades clínicas y un 15,9%, con habilidades clínicas competentes. Los estudiantes de quinto semestre se percibieron con menores habilidades clínicas (p= 0,006), al igual que aquellos que no habían cursado práctica clínica antes de la pandemia (p= 0,005). Conclusiones: a partir de la pandemia, las habilidades en la práctica clínica son percibidas como nulas o deficientes por los estudiantes de Enfermería, por lo que se requiere implementar cambios en la metodología de enseñanza-aprendizaje, transitar a un modelo híbrido e integrador con intervenciones educativas efectivas y que demuestren el desarrollo de los dominios en este tipo de habilidades para cumplir con el perfil de egreso planteado.(AU)

Objective: to understand the perception by Nursing students about the acquisition of clinical skills during the COVID-19 pandemic, and to analyse if this is associated with the semester they are currently taking and with conducting clinical practice in real settings. Method: a cross-sectional descriptive study was conducted with Nursing students from a public university in Zacatecas, Mexico (N= 1,033). The second section of the Clinical Competency Questionnaire in its Spanish translation was administered online, with Cronbach’s alpha= 0.969. The association between the clinical skills and the semester studied and experience was analysed through Chi-squared test withp≤ 0.05 as statistical significance. Results: in total, N= 82 students participated. Their mean age was 20.7 (SD:1.40), 87.8% were female, and the majority were in their seventh semester (40.2%). 50% of them perceived that their clinical skills were poor, 34.1% stated they had no clinical skills, and 15.9% perceived that their clinical skills were proficient. Students in their fifth semester perceived their clinical skills as lower (p= 0.006), as well as those who had not had any clinical practice before the pandemic (p= 0.005). Conclusions: after the pandemic, clinical practice skills are perceived as non-existent or poor by Nursing students; therefore, it is necessary to implement changes in the teaching-learning methodology, to move to a hybrid and inclusive model with effective educational interventions which demonstrate the development of domains in this type of skills, in order to meet the proposed profile of graduation.

Structures of Two Human Astrovirus Capsid/Neutralizing Antibody Complexes Reveal Distinct Epitopes and Inhibition of Virus Attachment to Cells.

Human astrovirus is an important cause of viral gastroenteritis worldwide. Young children, the elderly, and the immunocompromised are especially at risk for contracting severe disease. However, no vaccines exist to combat human astrovirus infection. Evidence points to the importance of antibodies in protecting healthy adults from reinfection. To develop an effective subunit vaccine that broadly protects against diverse astrovirus serotypes, we must understand how neutralizing antibodies target the capsid surface at the molecular level. Here, we report the structures of the human astrovirus capsid spike domain bound to two neutralizing monoclonal antibodies. These antibodies bind two distinct conformational epitopes on the spike surface. We add to existing evidence that the human astrovirus capsid spike contains a receptor-binding domain and demonstrate that both antibodies neutralize human astrovirus by blocking virus attachment to host cells. We identify patches of conserved amino acids which overlap or border the antibody epitopes and may constitute a receptor-binding site. Our findings provide a basis for developing therapies to prevent and treat human astrovirus gastroenteritis. IMPORTANCE Human astroviruses infect nearly every person in the world during childhood and cause diarrhea, vomiting, and fever. Despite the prevalence of this virus, little is known about how antibodies block astrovirus infection. Here, we determined the crystal structures of the astrovirus capsid protein in complex with two virus-neutralizing antibodies. We show that the antibodies bind to two distinct sites on the capsid spike domain, however, both antibodies block virus attachment to human cells. Importantly, our findings support the use of the human astrovirus capsid spike as an antigen in a subunit-based vaccine to prevent astrovirus disease.

[Relevance of right ventricle in the clinical management of pulmonary arterial hypertension]. / Manejo clínico de la hipertensión arterial pulmonar. Relevancia del ventrículo derecho.

Pulmonary arterial hypertension (PAH) requires structured processes of diagnosis and risk stratification, being the function of the right ventricle (RV) a hallmark prognosis determinant. The main therapeutic goals in PAH are to improve and try to revert RV dysfunction and maintaining a low risk. Currently, there are multiple treatments with different mechanisms of action, the combination of which in double or triple therapy has shown improved results compared to monotherapy. Recent clinical evidence shows the importance of early incorporation of parenteral prostanoids to the scheme, improving RV function and survival. In this review, we discuss the role of the RV function in the diagnosis, prognosis, and follow-up of PAH. We recommend the systematic and standardised evaluation of the RV as well as the early initiation of combined treatment in cases of intermediatehigh risk to try to reach and keep the patient with PAH at a low risk and / or avoid the progression of PAH.

La hipertensión arterial pulmonar (HAP) requiere procesos estructurados de diagnóstico y estratificación de riesgo, siendo la función del ventrículo derecho (VD) un marcador pronóstico central. Los principales objetivos terapéuticos en la HAP son mejorar y/o intentar revertir la disfunción del VD y mantener condición de bajo riesgo. Actualmente existen múltiples fármacos con diferentes mecanismos de acción cuya combinación en doble o triple terapia ha mostrado mejores resultados que la monoterapia. Evidencia actual demuestra la importancia de incorporar tempranamente prostanoides parenterales al esquema, mejorando la funcionalidad del VD y la supervivencia. En esta revisión se refleja el papel de la función del VD en el diagnóstico, pronóstico y seguimiento de la HAP. Se recomienda la evaluación sistemática y estandarizada del VD, así como el inicio temprano de tratamiento combinado en riesgo intermedio-alto para obtener las metas de alcanzar y mantener un riesgo bajo y/o evitar la progresión de la HAP.

Manejo clínico de la hipertensión arterial pulmonar. Relevancia del ventrículo derecho / Relevance of right ventricle in the clinical management of pulmonary arterial hypertension

Resumen La hipertensión arterial pulmonar (HAP) requiere procesos estructurados de diagnóstico y estratificación de riesgo, siendo la función del ventrículo derecho (VD) un marcador pronóstico central. Los principales objetivos terapéuticos en la HAP son mejorar y/o intentar revertir la disfunción del VD y mantener condición de bajo riesgo. Actualmente existen múltiples fármacos con diferentes mecanismos de acción cuya combinación en doble o triple terapia ha mostrado mejores resultados que la monoterapia. Evidencia actual demuestra la importancia de incorporar tempranamente prostanoides parenterales al esquema, mejorando la funcionalidad del VD y la supervivencia. En esta revisión se refleja el papel de la función del VD en el diagnós tico, pronóstico y seguimiento de la HAP. Se recomienda la evaluación sistemática y estandarizada del VD, así como el inicio temprano de tratamiento combinado en riesgo intermedio-alto para obtener las metas de alcanzar y mantener un riesgo bajo y/o evitar la progresión de la HAP.

Abstract Pulmonary arterial hypertension (PAH) requires structured processes of diagnosis and risk stratifica tion, being the function of the right ventricle (RV) a hallmark prognosis determinant. The main therapeutic goals in PAH are to improve and try to revert RV dysfunction and maintaining a low risk. Currently, there are multiple treatments with different mechanisms of action, the combination of which in double or triple therapy has shown improved results compared to monotherapy. Recent clinical evidence shows the importance of early incorpora tion of parenteral prostanoids to the scheme, improving RV function and survival. In this review, we discuss the role of the RV function in the diagnosis, prognosis, and follow-up of PAH. We recommend the systematic and standardised evaluation of the RV as well as the early initiation of combined treatment in cases of intermediate-high risk to try to reach and keep the patient with PAH at a low risk and / or avoid the progression of PAH.

Protein Disulfide Isomerase A4 Is Involved in Genome Uncoating during Human Astrovirus Cell Entry.

Although human astroviruses (HAstVs) are important agents of gastroenteritis in young children, the studies aimed at characterizing their biology have been limited, in particular regarding their cell entry process. It has been shown that HAstV serotype 8 enters human cells by a classical clathrin-mediated endocytosis pathway; however, the cell receptor or other cell entry factors that may be relevant for an efficient viral infection are unknown. In this work we used a far-Western blotting approach to identify cellular proteins that interact with the recombinant capsid spike proteins of HAstV serotypes 1, 2, and 8, synthesized in Escherichia coli. We identified the 72 kDa protein disulfide isomerase A4 (PDIA4) as a binding partner for HAstV-1 and -8 spikes, but not for the HAstV-2 spike. In agreement with this observation, the PDI inhibitor 16F16 strongly blocked infection by HAstV serotypes 1 and 8, but not serotype 2. RNA interference of PDIA4 expression selectively blocked HAstV-8 infectivity. We also showed that the PDI activity does not affect virus binding or internalization but is required for uncoating of the viral genome.

The actin cytoskeleton is important for rotavirus internalization and RNA genome replication.

Numerous host factors are required for the efficient replication of rotavirus, including the activation and inactivation of several cell signaling pathways. One of the cellular structures that are reorganized during rotavirus infection is the actin cytoskeleton. In this work, we report that the dynamics of the actin microfilaments are important at different stages of the virus life cycle, specifically, during virus internalization and viral RNA synthesis at 6 h post-infection. Our results show that the actin-binding proteins alpha-actinin 4 and Diaph, as well as the Rho-family small GTPase Cdc42 are necessary for an efficient virus entry, while GTPase Rac1 is required for maximal viral RNA synthesis.

Right ventricular longitudinal strain predicts acute kidney injury and short-term prognosis in patients with right ventricular myocardial infarction.

Right ventricular (RV) systolic dysfunction due to acute myocardial infarction is associated with serious complications in the short-term. Acute kidney injury (AKI) is a frequent and unrecognized complication. This study aimed to assess whether RV longitudinal strain predicts AKI and short-term prognosis in patients with RV infarction. Prospective cohort of patients with RV infarction. RV function was evaluated with global and free wall right ventricular longitudinal strain (GRVLS and FWRVLS), tricuspid annular plane systolic excursion, and tricuspid S' wave. The primary endpoint was AKI defined as an increase ≥ 50% in serum creatinine and/or a decrease ≥ 25% in glomerular filtration rate during follow-up at 7 days. The secondary endpoint was death from any cause at 30 days. We included 101 patients with RV infarction (male 67%, age 66 ± 11 years). During follow-up at 7 days, 40% of patients developed AKI. At 30 days, 8% of patients died. At univariate analysis, FWRVLS was significantly associated with AKI (Hazard ratio [HR] 1.11, 95% confidence interval [CI] 1.03-1.20, p = 0.006). At multivariate analysis, only age, temporary pacemaker implant, and FWRVLS remained as independent predictors of AKI (HR 1.05, 95% CI 1.02-1.08, p = 0.002; HR 2.12, 95% CI 1.11-4.07, p = 0.023; HR 1.10, 95% CI 1.02-1.19, p = 0.018, respectively). At 30 days, patients with FWRVLS ≥ - 15.5% showed a lower survival rate than those with lower strain (84 ± 6 vs. 97 ± 2%, p = 0.021). In patients with RV infarction, FWRVLS was an independent predictor of AKI and was associated with higher mortality in the short-term.

Minimal capsid composition of infectious human astrovirus.

Human astrovirus is an important etiological agent of acute gastroenteritis in young children. Despite advances in the characterization of the structure of the virion by cryo-electron microscopy and of capsid proteins by x-ray crystallography, the definition of the minimal polypeptide composition of infectious virus particles has been elusive. In this work we show that mature infectious particles are composed by only two proteins; VP34 that forms the core domain of the virus, and VP27 that constitutes the 30 dimeric spikes present on the virus surface. Our results also indicate that during the transition of immature (90 spikes) to mature (30 spikes) virus particles, that occur during trypsin activation, the viral protein VP25, that most likely forms the 60 spikes that are lost during maturation, detaches from the virus particle. This information is relevant to better understand the biology of virus entry and also for the efficient development of subunit vaccines.

El control de la diabetes mellitus y sus complicaciones en Medellín, Colombia, 2001-2003 / Controlling diabetes mellitus and its complications in Medellín, Colombia, 2001-2003

OBJETIVOS: Identificar las principales características sociodemográficas, clínicas y conductuales de los pacientes que participaban en los programas de atención al diabético en Medellín, Colombia, y evaluar el cumplimiento de las metas de control metabólico y de los estándares de control en el diabético. MÉTODOS: Se realizó un estudio descriptivo transversal mediante el análisis de las historias clínicas de todos los pacientes que asistían a los programas de atención al diabético desde al menos 6 meses en nueve instituciones de salud entre enero de 2001 y diciembre de 2003. Se tomaron datos sociodemográficos (edad y sexo), clínicos (tiempo de evolución de la enfermedad, tipo y tratamiento de la diabetes y enfermedades concurrentes y su tratamiento), sobre los hábitos de vida (práctica de ejercicios físicos, hábito de fumar y consumo de azúcar y grasas) y sobre las complicaciones crónicas y los resultados de las pruebas de laboratorio del último año. Todos los datos confusos o faltantes se registraron como ausentes. RESULTADOS: De las 3 583 historias clínicas evaluadas, se logró conocer el tipo de diabetes que padecían 3 554 pacientes, de ellos 95,1 por ciento correspondieron a pacientes con diabetes tipo 2. En general, 56,9 por ciento (intervalo de confianza de 95 por ciento [IC95 por ciento]: 55,2 a 58,6 por ciento) de los pacientes realizaban ejercicios periódicos; 15,1 por ciento (IC95 por ciento: 13,9 a 16,3 por ciento) aún fumaba en el momento del corte, 17,7 por ciento (IC95 por ciento: 16,4 a 19,0 por ciento) había dejado de fumar y 67,2 por ciento (IC95 por ciento: 65,6 a 68,8 por ciento) nunca había fumado. En total, 21,0 por ciento (IC95 por ciento: 19,6 a 22,5 por ciento) de los pacientes consumía azúcar regularmente, mientras 24,8 por ciento (IC95 por ciento: 23,3 a 26,3 por ciento) consumía grasas y solo 19,5 por ciento (IC95 por ciento: 17,8 a 21,3 por ciento) realizaba automonitoreo de la glucemia con una frecuencia semanal...

OBJECTIVES: To identify the principal sociodemographic, clinical, and behavioral characteristics of patients participating in diabetic care programs in the city of Medellín, Colombia, and to evaluate progress toward the goal of metabolic control and diabetic care standards. METHODS: A cross-sectional, descriptive study was done, analyzing the clinical records of patients who had been participating for at least 6 months in the diabetic care programs of nine health care centers in Medellín. The study period ran from January 2001 to December 2003. The following data were collected: sociodemographic (age and sex), clinical (time since disease onset, diabetes type and treatment, and concurrent illnesses and their treatment), lifestyle habits (exercise routine, smoking, and sugar and fat consumption), chronic complications, and laboratory test results from the prior year. Questionable or missing data were categorized as unavailable. RESULTS: Of the 3 583 clinical histories evaluated, we were able to confirm the form of diabetes for 3 554 patients. Of those 3 554, 95.1 percent had type 2 diabetes. Overall, 56.9 percent (95 percent confidence interval (95 percent CI): 55.2 percent to 58.6 percent) of the patients exercised regularly, 15.1 percent (95 percent CI: 13.9 percent to 16.3 percent) were current smokers, 17.7 percent (95 percent CI: 16.4 percent to 19.0 percent) were former smokers, and 67.2 percent (95 percent CI: 65.6 percent to 68.8 percent) had never smoked. In all, 21.0 percent (95 percent CI: 19.6 percent to 22.5 percent) of the patients consumed sugar regularly, while 24.8 percent (95 percent CI: 23.3 percent to 26.3 percent) consumed fats and only 19.5 percent (95 percent CI: 17.8 percent to 21.3 percent) were self-monitoring their glucose levels at least weekly. Among the type 2 diabetics, 68.8 percent had high blood pressure, and 98.2 percent had dyslipidemia. The average body mass index was 28.0 kg/m² (95 percent CI: 27.8 to...

[Controlling diabetes mellitus and its complications in Medellín, Colombia, 2001-2003]. / El control de la diabetes mellitus y sus complicaciones en Medellín, Colombia, 2001-2003.

OBJECTIVES: To identify the principal sociodemographic, clinical, and behavioral characteristics of patients participating in diabetic care programs in the city of Medellín, Colombia, and to evaluate progress toward the goal of metabolic control and diabetic care standards. METHODS: A cross-sectional, descriptive study was done, analyzing the clinical records of patients who had been participating for at least 6 months in the diabetic care programs of nine health care centers in Medellín. The study period ran from January 2001 to December 2003. The following data were collected: sociodemographic (age and sex), clinical (time since disease onset, diabetes type and treatment, and concurrent illnesses and their treatment), lifestyle habits (exercise routine, smoking, and sugar and fat consumption), chronic complications, and laboratory test results from the prior year. Questionable or missing data were categorized as unavailable. RESULTS: Of the 3 583 clinical histories evaluated, we were able to confirm the form of diabetes for 3 554 patients. Of those 3 554, 95.1% had type 2 diabetes. Overall, 56.9% (95% confidence interval (95% CI): 55.2% to 58.6%) of the patients exercised regularly, 15.1% (95% CI: 13.9% to 16.3%) were current smokers, 17.7% (95% CI: 16.4% to 19.0%) were former smokers, and 67.2% (95% CI: 65.6% to 68.8%) had never smoked. In all, 21.0% (95% CI: 19.6% to 22.5%) of the patients consumed sugar regularly, while 24.8% (95% CI: 23.3% to 26.3%) consumed fats and only 19.5% (95% CI: 17.8% to 21.3%) were self-monitoring their glucose levels at least weekly. Among the type 2 diabetics, 68.8% had high blood pressure, and 98.2% had dyslipidemia. The average body mass index was 28.0 kg/m(2) (95% CI: 27.8 to 28.2). The average number of medications that the patients were taking to treat type 2 diabetes was 1.3; to treat high blood pressure, 1.9; and to treat dyslipidemia, 0.6. There were no data on low-density lipoprotein (LDL) cholesterol in 44.8% of the clinical records, and no data on high-density lipoprotein (HDL) cholesterol in 16.4% of the records. Among the complications, the most common were ocular ones (31.8%; 95% CI: 30.1% to 33.5%), followed by renal ones (25.9%; 95% CI: 24.4% to 27.5%), and cardiovascular ones (22.5%; 95% CI: 21.1% to 23.8%). Cholesterol control achievement was inadequate for LDL (reached by only 14.2% of the patients), for triglycerides (36.9% of patients), and HDL (47.4% of patients). CONCLUSIONS: Among the study population in Medellín, the three chronic complications with the greatest impact on prognosis and health care costs of the diabetics were nephropathy, retinopathy, and dyslipidemia. The noticeable amount of unavailable data in the clinical records could be greatly reduced by standardizing the clinical record forms and by periodic quality checks of the records themselves.