Estrogen modulates gene expression through interactions with estrogen receptors (ERs) that bind chromosomal target genes. Recent studies have suggested an interaction between the cytoskeletal system and estrogen signaling; these have implicated a role of cytoplasmic microtubules in scaffolding ERalpha and enhancing nongenomic function; in addition, other experiments demonstrate that dynein light chain 1 may chaperone ERalpha to the nucleus, indirectly increasing transcriptional potency. Actin/myosin and dynein light chain 1 are also required for estrogen-mediated chromosomal movement that is required for transcriptional up-regulation of ERalpha targets. We present evidence that the dynactin component, p150/glued, directly influences the potency of nuclear ER function. Increasing the stoichiometric ratio of p150/glued and ERalpha by overexpression enhances estrogen responses. ERalpha enhancement by p150/glued does not appear to be influenced by shifts in subcellular localization because microtubule disruption fails to increase nuclear ERalpha. Rather, we find that modest amounts of p150/glued reside in the nucleus of cells, suggesting that it plays a direct role in nuclear transcription. Notably, p150/glued is recruited to the pS2 promoter in the presence of hormone, and, in MCF-7 cells, knockdown of p150/glued levels reduces estrogen-dependent transcription. Our results suggest that p150/glued modulates estrogen sensitivity in cells through nuclear mechanisms.
Subclinical levels of orthostatic hypotension (OH) have been linked to a variety of emotional and behavioral outcomes across the life span. These connections are not surprising, given the multitude of correlated conditions, including autonomic control, cardiovascular functioning, baroreceptor activity, and dopamine and serotonin. The current study assessed blood pressure regulation in healthy preschool children ages 3-5 (n = 61). The Conner's Parent Rating Scale Revised was used to assess indexes of attention deficit hyperactivity disorder (ADHD). With the difference between standing and supine pulse pressure as the index of orthostatic blood pressure regulation, the results indicated that efficient pulse pressure regulation was significantly correlated with lower ADHD scores. Poorer orthostatic pulse pressure regulation in response to an orthostatic challenge may be a risk for symptoms of ADHD.
Purpose of review
Jehovah's Witnesses have religious beliefs that preclude transfusion of blood products and certain medical interventions. This presents a unique dilemma and ethical challenge to healthcare providers, especially in a surgical setting.
Recent findings
The growing number of followers of this faith warrants a deeper look at the ethical, legal, and clinical implications of their beliefs. Advances in patient blood management now allow timely optimization before surgery.
Summary
Anticipating the challenges associated with managing and optimizing patients who refuse blood products allows for more favorable outcomes in the preoperative period.
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