Association between Mean Platelet Volume and Resistance to Aspirin and P2Y12 Receptor Inhibitors in Elderly Patients with Acute Coronary Syndrome

Background: Antiplatelet resistance and mean platelet volume (MPV) are event predictors in acute coronary syndrome (ACS), buttheir association has been poorly studied.Objective: The aim of this study was to evaluate the association between MPV and resistance to aspirin (ASA) and P2Y12 receptorinhibitors (P2Y12i) in elderly patients with ACS.Methods: Patients over 65 years old diagnosed with ACS were included in the study. They were divided into group 1 (resistance toboth antiplatelet agents), group 2 (resistance to one antiplatelet agent) and group 3 (no resistance to antiplatelet agents). Plateletaggregation was measured between 12 and 24 hours postloading (by light transmission aggregometry). Resistance to P2Y12i wasconsidered as maximum percentage of aggregation (MPA) with adenosine diphosphate (ADP) >60% and resistance to ASA as MPAwith arachidonic acid (ARA) >20%. The composite endpoint of global death and cardiovascular re-hospitalization was consideredduring follow-up.Results: One hundred and ninety five patients included in the study received ASA and P2Y12i (120 received clopidogrel and 75ticagrelor). Nineteen percent of patients belonged to group 1, 34.4% to group 2 and 46.6% to group 3. Mean platelet volume wasassociated with resistance to both antiplatelet agents [OR 1.02 (95% CI 1.01-1.05), p=0.03], while MPV and the GRACE score wereindependent predictors of the composite endpoint [HR 1.03 (95% CI 1.01-1.07), p=0.04, and HR 1.02 (95% CI 1.01-1.04), p=0.02,respectively].Conclusions: Mean platelet volume was associated with the presence of resistance to both antiplatelet agents. During follow-up,MPV and the GRACE score were predictors of the composite endpoint.Introducción La presencia de resistencia a antiagregantes y el volumen plaquetario medio (VPM) son predictores de eventos en el síndrome coronario agudo (SCA). La asociación entre ambos ha sido poco estudiada. Objetivo Evaluar si existe asociación entre la presencia de resistencia a la aspirina (AAS) e inhibidores del receptor P2Y12 (iP2Y12) y el VPM en pacientes mayores de 65 años con SCA. Materiales y Métodos Se incluyeron pacientes mayores de 65 años con diagnóstico de SCA. Se dividieron en: grupo 1 (resistencia a ambos antiagregantes), grupo 2 (a uno de los antiagregantes) y grupo 3 (a ningún antiagregante). Se midió agregación plaquetaria entre las 12 y 24 horas postcarga (por light transmission aggregometry ). Se consideró resistencia a iP2Y12 a un porcentaje máximo de agregación (PMA) con ADP > 60% y a la AAS a un PMA con ARA > 20%.  En el seguimiento se consideró el punto final combinado de muerte global y reinternación cardiovascular. Resultados Se incluyeron 195 pacientes, todos recibieron AAS e iP2y12 (120 recibieron clopidogrel y 75 Ticagrelor). Grupo 1 (19%), Grupo 2 (34.4%) y grupo 3 (46.7%). El VPM  se asoció a la resistencia a ambos antiagregantes (OR 1.02 (IC95% 1.01-1.05), p=0.03. A su vez, el VPM y el GRACE fueron predictores independientes del punto combinado (HR 1.03 (IC95% 1.01-1.07), p=0.04 y HR 1.02 (IC95% 1.01-1.04), p=0.02), respectivamente. Conclusiones El VPM se asoció a la presencia de resistencia a ambos antiagregantes. En el seguimiento, el VPM y el score GRACE fueron predictores del punto combinado

Morphology-Dependent Interaction of Silica Nanoparticles with Intestinal Cells: Connecting Shape to Barrier Function

The intestinal compartment ensures nutrient absorptionand barrierfunction against pathogens. Despite decades of research on the complexityof the gut, the adaptive potential to physical cues, such as thosederived from interaction with particles of different shapes, remainsless understood. Taking advantage of the technological versatilityof silica nanoparticles, spherical, rod-shaped, and virus-like materialswere synthesized. Morphology-dependent interactions were studied ondifferentiated Caco-2/HT29-MTX-E12 cells. Contributions of shape,aspect ratio, surface roughness, and size were evaluated consideringthe influence of the mucus layer and intracellular uptake pathways.Small particle size and surface roughness favored the highest penetrationthrough the mucus but limited interaction with the cell monolayerand efficient internalization. Particles of a larger aspect ratio(rod-shaped) seemed to privilege paracellular permeation and increasedcell-cell distances, albeit without hampering barrier integrity.Inhibition of clathrin-mediated endocytosis and chemical modulationof cell junctions effectively tuned these responses, confirming morphology-specificinteractions elicited by bioinspired silica nanomaterials.11Nsciescopu

Fetal Glucocorticoid Exposure Is Associated with Preadolescent Brain Development

BACKGROUND: Glucocorticoids play a critical role in normative regulation of fetal brain development. Exposure to excessive levels may have detrimental consequences and disrupt maturational processes. This may especially be true when synthetic glucocorticoids are administered during the fetal period, as they are to women in preterm labor. The present study investigated the consequences for brain development and affective problems of fetal exposure to synthetic glucocorticoids. METHODS: Brain development and affective problems were evaluated in fifty-four children (56% female), ages 6 to 10, who were full term at birth. Children were recruited into two groups: those with and without fetal exposure to synthetic glucocorticoids. Structural magnetic resonance imaging (MRI) scans were acquired and cortical thickness was determined. Child affective problems were assessed using the Child Behavior Checklist. RESULTS: Children in the fetal glucocorticoid exposure group showed significant and bilateral cortical thinning. The largest group differences were in the rostral anterior cingulate cortex (rACC). Over 30% of the rACC was thinner among children with fetal glucocorticoid exposure. Further, children with more affective problems had a thinner left rACC. CONCLUSIONS: Fetal exposure to synthetic glucocorticoids has neurological consequences that persist for at least 6 to 10 years. Children with fetal glucocorticoid exposure had a thinner cortex primarily in the rACC. Our data indicating that the rACC is associated with affective problems in conjunction with evidence that this region is involved in affective disorders raises the possibility that glucocorticoid associated neurological changes increase vulnerability to mental health problems