Interarm blood pressure difference: Concordance between two methods of automatic simultaneous measurement and between visits reproducibility

Oscilómetro automático; Concordancia; ReproducibilidadAutomatic oscillometer; Concordance; ReproducibilityOscil·lòmetre automàtic; Concordança; ReproduïbilitatObjetivo La diferencia de presión arterial sistólica entre brazos (dPEB) aumentada (≥ 10 mmHg) se ha relacionado con mayor morbimortalidad cardiovascular. Hay poca evidencia sobre cómo determinar la dPEB y su fiabilidad ha sido poco estudiada. Nuestros objetivos fueron evaluar la concordancia entre 2 oscilómetros automáticos de medición simultánea de la dPEB (2 aparatos OMRON y un aparato Microlife WatchBP® [WBP]) y analizar la reproducibilidad de la dPEB entre visitas en población general atendida en un centro de atención primaria. Diseño Estudio descriptivo transversal de concordancia entre los 2 métodos y de fiabilidad de la dPEB entre 2 visitas separadas una semana. Emplazamiento Centro de Atención Primaria de Parets del Vallès, Barcelona. Participantes Población general de 35-74 años. Intervenciones y mediciones principales Ciento cuarenta y nueve pacientes completaron las 2 visitas. En cada visita se midió la dPEB 3 veces con ambos métodos, y se consideró la media de las 3 determinaciones. Mediante revisión de la historia y entrevista con el paciente se recogieron otras variables como sociodemográficas y antropométricas, antecedentes patológicos y tratamiento farmacológico. Se calculó la concordancia entre los dispositivos y la reproducibilidad entre visitas mediante el coeficiente de concordancia de Lin (CCL) para la dPEB expresada de manera continua y los índices kappa (k) para la dPEB categorizada en normal o patológica. Resultados La concordancia entre métodos para la dPEB expresada de forma continua fue baja: CCL: 0,13 (0,02-0,24). La concordancia fue también baja para la dPEB categorizada en normal o patológica (k = −0,03 [−0,05-0,00]). La reproducibilidad entre visitas fue baja para ambos métodos, y tanto para la dPEB continua como categorizada: con OMRON® CCL: 0,19 (0,03-0,34) y k = −0,02 (−0,16-0,12) y para WBP® CCL: 0,14 (−0,01-0,29) y k = 0,49 (0,33-0,64). Conclusiones La concordancia entre 2 oscilómetros automáticos en la determinación simultánea de la dPEB fue baja. La reproducibilidad entre visitas también fue baja para ambos métodos.Objective An increased interarm blood pressure difference (IAD) (≥10 mmHg) has been associated with increased cardiovascular morbidity and mortality. There are few studies determining how IAD has to be measured and its reliability between visits. The objectives of our study were twofold. First, to evaluate the concordance between two automatic oscillometric devices for IAD measurement (two OMRON devices and one Microlife WatchBP™ device (WBP™)) and to analyse the reproducibility of IAD between visits in the general population attending a primary care centre. Design Descriptive cross-sectional study of concordance between the two methods and reproducibility of IAD between two visits separated by one week. Site Parets del Vallès primary care centre (Barcelona). Participants General population aged 35-74 years. Interventions and main measurements One hundred and forty-nine patients completed the two visits. At each visit, IAD was measured three times with both methods and the mean of the three determinations was considered. Other variables such as sociodemographic and anthropometric variables, pathological antecedents and pharmacological treatment were collected through a review of the medical history and an interview with the patient. Concordance between the two devices and between visits reproducibility were calculated using the Lin concordance coefficient (CCL) for IAD expressed continuously and kappa(k) indices for IAD categorised as normal or pathological. Results Concordance for IAD expressed continuously was low: CCL = 0.13 (0.02-0.24). Concordance was also low for IAD categorised as normal or pathological (k = −0.03 (−0.05-0.00)). Reproducibility between visits was low for both methods and for both continuous and categorised IAD: with OMRON™ CCL = 0.19 (0.03-0.34) and k = −0.02 (−0.16-0.12) and for WBP™ CCL = 0.14 (−0.01-0.29) and k = 0.49 (0.33-0.64). Conclusions Concordance between two automatic oscillometers in the simultaneous IAD measurement was low. Reproducibility between visits was also low for both methods.Este estudio fue financiado con una ayuda a proyectos de investigación en atención primaria del Institut Universitari d’Investigació en Atenció Primària (IDIAP Jordi Gol, número de ayuda 4R18/002-1) y con la beca del GERC 2018 (Grup d́Estudi i Recerca Cardiovascular) de la Filial del Vallès Oriental de la Acadèmia de les Ciències Mèdiques de Catalunya i de Balears

Single Intracoronary Injection of Encapsulated Antagomir-92a Promotes Angiogenesis and Prevents Adverse Infarct Remodeling

Small and large preclinical animal models have shown that antagomir-92a-based therapy reduces early postischemic loss of function, but its effect on postinfarction remodeling is not known. In addition, the reported remote miR-92a inhibition in noncardiac organs prevents the translation of nonvectorized miR-targeted therapy to the clinical setting. We investigated whether a single intracoronary administration of antagomir-92a encapsulated in microspheres could prevent deleterious remodeling of myocardium 1 month after acute myocardial infarction AUTHOR: Should "acute" be added before "myocardial infarction" (since abbreviation is AMI)? Also check at first mention in main text (AMI) without adverse effects. In a percutaneous pig model of reperfused AMI, a single intracoronary administration of antagomir-92a encapsulated in specific microspheres (9 μm poly-d,-lactide-co-glycolide [PLGA]) inhibited miR-92a in a local, selective, and sustained manner (n=3 pigs euthanized 1, 3, and 10 days after treatment; 8×, 2×, and 5×-fold inhibition at 1, 3, and 10 days). Downregulation of miR-92a resulted in significant vessel growth (n=27 adult minipigs randomly allocated to blind receive encapsulated antagomir-92a, encapsulated placebo, or saline [n=8, 9, 9]; P =0.001), reduced regional wall-motion dysfunction (P =0.03), and prevented adverse remodeling in the infarct area 1 month after injury (P =0.03). Intracoronary injection of microspheres had no significant adverse effect in downstream myocardium in healthy pigs (n=2), and fluorescein isothiocyanate albumin-PLGA microspheres were not found in myocardium outside the left anterior descending coronary artery territory (n=4) or in other organs (n=2). Early single intracoronary administration of encapsulated antagomir-92a in an adult pig model of reperfused AMI prevents left ventricular remodeling with no local or distant adverse effects, emerging as a promising therapeutic approach to translate to patients who suffer a large AMI

Caveolin-1 is down-regulated in alveolar habdomyosarcomas and negatively regulates tumor growth

Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood and adolescence. Despite advances in therapy, patients with histological variant of rhabdomyosarcoma known as alveolar rhabdomyosarcoma (ARMS) have a 5-year survival of less than 30%. Caveolin-1 (CAV1), encoding the structural component of cellular caveolae, is a suggested tumor suppressor gene involved in cell signaling. In the present study we report that compared to other forms of rhabdomyosarcoma (RMS) CAV1 expression is either undetectable or very low in ARMS cell lines and tumor samples. DNA methylation analysis of the promoter region and azacytidine-induced re-expression suggest the involvement of epigenetic mechanisms in the silencing of CAV1. Reintroduction of CAV1 in three of these cell lines impairs their clonogenic capacity and promotes features of muscular differentiation. In vitro, CAV1-expressing cells show high expression of Caveolin-3 (CAV3), a muscular differentiation marker. Blockade of MAPK signaling is also observed. In vivo, CAV1-expressing xenografts show growth delay, features of muscular differentiation and increased cell death. In summary, our results suggest that CAV1 could function as a potent tumor suppressor in ARMS tumors. Inhibition of CAV1 function therefore, could contribute to aberrant cell proliferation, leading to ARMS development

Remodeling of the Fetal Collecting Duct Epithelium

Congenital urinary tract obstruction induces changes to the renal collecting duct epithelium, including alteration and depletion of intercalated cells. To study the effects of obstruction on the ontogeny of intercalated cell development, we examined normal and obstructed human fetal and postnatal kidneys. In the normal human fetal kidney, intercalated cells originated in the medullary collecting duct at 8 weeks gestation and remained most abundant in the inner medulla throughout gestation. In the cortex, intercalated cells were rare at 18 and 26 weeks gestation and observed at low abundance at 36 weeks gestation. Although early intercalated cells exhibit an immature phenotype, Type A intercalated cells predominated in the inner and outer medullae at 26 and 36 weeks gestation with other intercalated cell subtypes observed rarely. Postnatally, the collecting duct epithelium underwent a remodeling whereby intercalated cells become abundant in the cortex yet absent from the inner medulla. In 18-week obstructed kidneys with mild to moderate injury, the intercalated cells became more abundant and differentiated than the equivalent age-matched normal kidney. In contrast, more severely injured ducts of the late obstructed kidney exhibited a significant reduction in intercalated cells. These studies characterize the normal ontogeny of human intercalated cell development and suggest that obstruction induces premature remodeling and differentiation of the fetal collecting duct epithelium