RESUMEN
Derivation of cardiomyocytes from induced pluripotent stem cells (iPS-CMs) allowed us to probe the Ca(2+)-signaling parameters of human iPS-CMs from healthy- and catecholaminergic polymorphic ventricular tachycardia (CPVT1)-afflicted individuals carrying a novel point mutation p.F2483I in ryanodine receptors (RyR2). iPS-CMs were dissociated on day 30-40 of differentiation and patch-clamped within 3-6 days. Calcium currents (ICa) averaged â¼8pA/pF in control and mutant iPS-CMs. ICa-induced Ca(2+)-transients in control and mutant cells had bell-shaped voltage-dependence similar to that of ICa, consistent with Ca(2+)-induced Ca(2+)-release (CICR) mechanism. The ratio of ICa-activated to caffeine-triggered Ca(2+)-transients was â¼0.3 in both cell types. Caffeine-induced Ca(2+)-transients generated significantly smaller Na(+)-Ca(2+) exchanger current (INCX) in mutant cells, reflecting their smaller Ca(2+)-stores. The gain of CICR was voltage-dependent as in adult cardiomyocytes. Adrenergic agonists enhanced ICa, but differentially altered the CICR gain, diastolic Ca(2+), and Ca(2+)-sparks in mutant cells. The mutant cells, when Ca(2+)-overloaded, showed longer and wandering Ca(2+)-sparks that activated adjoining release sites, had larger CICR gain at -30mV yet smaller Ca(2+)-stores. We conclude that control and mutant iPS-CMs express the adult cardiomyocyte Ca(2+)-signaling phenotype. RyR2 F2483I mutant myocytes have aberrant unitary Ca(2+)-signaling, smaller Ca(2+)-stores, higher CICR gains, and sensitized adrenergic regulation, consistent with functionally altered Ca(2+)-release profile of CPVT syndrome.
Asunto(s)
Señalización del Calcio/fisiología , Calcio/metabolismo , Catecolaminas/metabolismo , Miocitos Cardíacos/metabolismo , Células Madre Pluripotentes/metabolismo , Taquicardia Ventricular/metabolismo , Agonistas Adrenérgicos/farmacología , Adulto , Cafeína/farmacología , Diferenciación Celular , Línea Celular , Células Cultivadas , Humanos , Técnicas In Vitro , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Técnicas de Placa-Clamp , Células Madre Pluripotentes/patología , Mutación Puntual/genética , Canal Liberador de Calcio Receptor de Rianodina/genética , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Taquicardia Ventricular/patologíaRESUMEN
With the aging of the population in the United States, elder abuse is now recognized as a significant problem. However, health care providers lack knowledge regarding detection, reporting, and appropriate interventions in cases of suspected or substantiated abuse. Whereas six types of elder abuse are identified in the literature, physical abuse and neglect are thought to be the most prevalent. Nurses in acute care and outpatient settings are in an ideal position to detect physical abuse and neglect. To act as patient advocates, they must have increased awareness of the problem, as well as pertinent knowledge and skills to assess and intervene appropriately in cases of elder abuse.
Asunto(s)
Abuso de Ancianos/prevención & control , Evaluación en Enfermería , Atención de Enfermería , Anciano , Estudios Transversales , Educación Continua en Enfermería , Abuso de Ancianos/legislación & jurisprudencia , Humanos , Factores de Riesgo , Estados UnidosRESUMEN
There is a conflict in the literature on selective attention. Suppose a subject is briefly presented an item followed by a multiple-alternative recognition test. If the items are pictures, the subject's performance is facilitated by presenting the alternatives beforehand (a before facilitation), but when the items are letters the subjects' performance is disrupted by presenting the alternatives beforehand (a before disruption). Five experiments were conducted to resolve this conflict, and all involved a comparison of tachistoscopic recognition when alternatives were either presented beforehand or not. The first two studies showed that the before disruption with letters was not due to certain task parameters. Experiments 3-5 demonstrated that this effect was due to masking conditions. Experiments 3 and 4 revealed that the disruption occurred only when a mask is used, while the last experiment indicated the disruption effect was sensitive to the type of mask employed. Preseumably, the before disrption arises because a subject erroneously considers the features of a mask along with those of the test item in arriving at a perceptual decision.