Baseline characteristics of patients in the reduction of events with darbepoetin alfa in heart failure trial (RED-HF)

<p>Aims: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes.</p> <p>Methods and results: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate <60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L.</p> <p>Conclusion: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.</p&gt

Estrogen Receptor β-Selective Agonists Stimulate Calcium Oscillations in Human and Mouse Embryonic Stem Cell-Derived Neurons

Estrogens are used extensively to treat hot flashes in menopausal women. Some of the beneficial effects of estrogens in hormone therapy on the brain might be due to nongenomic effects in neurons such as the rapid stimulation of calcium oscillations. Most studies have examined the nongenomic effects of estrogen receptors (ER) in primary neurons or brain slices from the rodent brain. However, these cells can not be maintained continuously in culture because neurons are post-mitotic. Neurons derived from embryonic stem cells could be a potential continuous, cell-based model to study nongenomic actions of estrogens in neurons if they are responsive to estrogens after differentiation. In this study ER-subtype specific estrogens were used to examine the role of ERα and ERβ on calcium oscillations in neurons derived from human (hES) and mouse embryonic stem cells. Unlike the undifferentiated hES cells the differentiated cells expressed neuronal markers, ERβ, but not ERα. The non-selective ER agonist 17β-estradiol (E2) rapidly increased [Ca2+]i oscillations and synchronizations within a few minutes. No change in calcium oscillations was observed with the selective ERα agonist 4,4′,4″-(4-Propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (PPT). In contrast, the selective ERβ agonists, 2,3-bis(4-Hydroxyphenyl)-propionitrile (DPN), MF101, and 2-(3-fluoro-4-hydroxyphenyl)-7-vinyl-1,3 benzoxazol-5-ol (ERB-041; WAY-202041) stimulated calcium oscillations similar to E2. The ERβ agonists also increased calcium oscillations and phosphorylated PKC, AKT and ERK1/2 in neurons derived from mouse ES cells, which was inhibited by nifedipine demonstrating that ERβ activates L-type voltage gated calcium channels to regulate neuronal activity. Our results demonstrate that ERβ signaling regulates nongenomic pathways in neurons derived from ES cells, and suggest that these cells might be useful to study the nongenomic mechanisms of estrogenic compounds

Pathways as "signatures in landscape": towards an ethnography of mobility among the Mbya-Guaraní (Northeastern Argentina)

RefereedProcesses of spatial mobility among the Mbya are of interest in anthropological and ethnobiological studies, as these processes are related to transformations in the landscape and the environment. Despite this, ethnographic literature usually focuses itself on the mobility of Guaraní communities from the perspective of population dynamics on a regional scale. Our research among two Mbya-Guaraní communities in the Argentinean province of Misiones has enabled us to recognize patterns of mobility on a micro-scale. Certainly, the mobility of adult members of these communities as they perform hunting and gathering activities delimit spaces of individual use. We consider the different pathways as "signatures in landscape", resulting from processes of spatial mobility inherent to those activities Taking into account the gathering and circulation of medicinal plants for treatment of gastrointestinal illnesses, we have been able to identify different pathways inherent in their search, towards the monte or other spaces away from de settlement. The design and construction of the pathways is determined by the specific personal knowledge of individuals who search for these valuable resources. Using both strategies of direct observation – as members of the community manipulate different resources during these search and gathering trips – and interviews, we have been able to gather and interpret significant information on the strategies used by the Mbya to domesticate the monte areas. As a consequence of our approach we suggest that the landscape design resulting from these trips should not be considered a consensual or collective strategy of the whole community; it is rather the result of the daily strategies of individuals, which involves the selection of resources mainly based on each individual's knowledge and interests.Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)Universidad Nacional de La Plat

Tiempo de estudiar, tiempo de trabajar: la conceptualización de la infancia y la participación de los niños en la vida productiva como experiencia formativa

Numerosos estudios antropológicos sobre la infancia han mostrado que, en tanto categoría social, es un producto histórico y sociocultural asociado a un proceso biológico de crecimiento. A partir de estos avances es posible considerar la incorporación de la cría humana a la sociedad desde la problematización del tiempo como uno de los parámetros fundamentales de la socialidad. Este enfoque conceptual permite discutir la idea moderna de que la infancia constituye la primera etapa de un desarrollo temporal monocrónico y unilineal, un período destinado al aprendizaje que prepara para vida adulta -definida esta última, por contraposición, como una etapa de trabajo. La idea de la infancia como la primera de una sucesión de etapas claramente distinguidas no sólo es sostenida por el sentido común -apropiada por los sujetos a lo largo de su vida-, sino que también sustenta de manera general la normativa de protección de derechos de la infancia. Sin embargo, la antropología puede potenciar los alcances de dichas regulaciones estudiando cómo los niños son atravesados en su experiencia cotidiana por una pluralidad de marcos temporales, por medio de los cuales no sólo aprenden sino que, al estar implicados en ciertos contextos en actividades productivas, pueden también ser partícipes de la producción de conocimiento social.<br>Many anthropological studies establish that childhood, as a social category, is an historical and socio-cultural product associated with a biological development process. From these positions it is possible to consider the human child incorporation into society, considering time as sociality parameter. This conceptualization allows discussion about the modern idea of childhood as first stage of a mono-chronic and linear time development, period devoted to learning adulthood -defined as a working time in opposition to latter. Childhood conceived as a first of a succession of stages clearly distinguished is not only a common sense -and appropriated by subjects among their lifetime-, but also is the general basis for childhood rights protection laws. Even so, anthropology can expand the limits of such regulations studying how children have, in everyday activities, a plurality of time's repertoires in which they learn and also, participating in some productive activities, become part of social knowledge production

β-Arrestin Regulates Estradiol Membrane-Initiated Signaling in Hypothalamic Neurons

Estradiol (E2) action in the nervous system is the result of both direct nuclear and membrane-initiated signaling (EMS). E2 regulates membrane estrogen receptor-α (ERα) levels through opposing mechanisms of EMS-mediated trafficking and internalization. While ß-arrestin-mediated mERα internalization has been described in the cortex, a role of ß-arrestin in EMS, which underlies multiple physiological processes, remains undefined. In the arcuate nucleus of the hypothalamus (ARH), membrane-initiated E2 signaling modulates lordosis behavior, a measure of female sexually receptivity. To better understand EMS and regulation of ERα membrane levels, we examined the role of ß-arrestin, a molecule associated with internalization following agonist stimulation. In the present study, we used an immortalized neuronal cell line derived from embryonic hypothalamic neurons, the N-38 line, to examine whether ß-arrestins mediate internalization of mERα. β-arrestin-1 (Arrb1) was found in the ARH and in N-38 neurons. In vitro, E2 increased trafficking and internalization of full-length ERα and ERαΔ4, an alternatively spliced isoform of ERα, which predominates in the membrane. Treatment with E2 also increased phosphorylation of extracellular-signal regulated kinases 1/2 (ERK1/2) in N-38 neurons. Arrb1 siRNA knockdown prevented E2-induced ERαΔ4 internalization and ERK1/2 phosphorylation. In vivo, microinfusions of Arrb1 antisense oligodeoxynucleotides (ODN) into female rat ARH knocked down Arrb1 and prevented estradiol benzoate-induced lordosis behavior compared with nonsense scrambled ODN (lordosis quotient: 3 ± 2.1 vs. 85.0 ± 6.0; p < 0.0001). These results indicate a role for Arrb1 in both EMS and internalization of mERα, which are required for the E2-induction of female sexual receptivity