Background:The ␣-MSH peptide is essential in regulating food intake and energy expenditure. Results: ER stress induced by obesity reduces ␣-MSH, accumulates POMC, and decreases the enzyme PC2. Conclusion: There is a direct link between obesity and ER stress, resulting in altered POMC processing. Significance: These studies bring a new perspective to how ER stress can regulate energy balance by altering POMC processing.

We recently showed that progesterone treatment abolished arrhythmias and sudden cardiac death in a transgenic rabbit model of long QT syndrome type 2 (LQT2). Moreover, levels of cardiac sarco(endo) plasmic reticulum Ca 2ϩ -ATPase type 2a (SERCA2a) were upregulated in LQT2 heart extracts. We hypothesized that progesterone treatment upregulated SERCA2a expression, thereby reducing Ca 2ϩ -dependent arrhythmias in LQT2 rabbits. We therefore investigated the effect of progesterone on SERCA2a regulation in isolated cardiomyocytes. Cardiomyocytes from neonatal (3-to 5-day-old) rabbits were isolated, cultured, and treated with progesterone and other pharmacological agents. Immunoblotting was performed on total cell lysates and sarcoplasmic reticulum-enriched membrane fractions for protein abundance, and mRNA transcripts were quantified using real-time PCR. The effect of progesterone on baseline Ca 2ϩ transients and Ca 2ϩ clearance was determined using digital imaging. Progesterone treatment increased the total pool of SERCA2a protein by slowing its degradation. Using various pharmacological inhibitors of degradation pathways, we showed that progesterone-associated degradation of SERCA2a involves ubiquitination, and progesterone significantly decreases the levels of ubiquitintagged SERCA2a polypeptides. Our digital imaging data revealed that progesterone significantly shortened the decay and duration of Ca 2ϩ transients. Progesterone treatment increases protein levels and activity of SERCA2a. Progesterone stabilizes SERCA2a, in part, by decreasing the ubiquitination level of SERCA2a polypeptides. long QT syndrome; SERCA2a; hormones; cardiomyocytes; neonate INHERITED LONG QT (LQT) syndrome (LQTS) is characterized by a prolonged QT interval, polymorphic ventricular tachycardia, and sudden cardiac death (SCD) (22,24). Together, LQT1 and LQT2 account for 55-65% of LQTS cases. LQT1 is associated with various point mutations in the slow delayed rectifier K ϩ channel (KCNQ1), which diminishes slow delayed rectifier K ϩ currents (I Ks ), thereby slowing repolarization and leading to prolongation of cardiac action potential duration (APD). LQT2 is associated with a point mutation in the ␣-subunit of the rapid delayed rectifier K ϩ channel [human ether-à-go-go (hERG)], which compromises I Kr , the current responsible for early termination of action potential, leading to APD prolongation. LQT2 patients are less susceptible to SCD during pregnancy than postpartum (15, 28). Moreover, in drug-induced LQTS, the risk of polymorphic ventricular tachycardia is higher during menses and the follicular phase, when plasma levels of estradiol are high, than during the luteal phase, when progesterone levels are high (25). These studies suggest that sex hormone may influence arrhythmogenesis in LQTS. Indeed, our recent in vivo study (20) utilizing ovariectomized prepubertal transgenic LQT2 female rabbits showed, for the first time, the direct link between sex hormones and the incidence of arrhythmias and SCD. The study demonstrated that progeste...

Objective. The current International League Against Epilepsy (ILAE) guidelines classify focal seizures based on awareness, defined as successful postictal recall of ictal experiences, and exclude the use of responsiveness during seizures for classification. One reason for this exclusion is that responsiveness was thought to not be commonly tested during seizures. Our goal was to determine whether, in at least some settings, responsiveness testing during seizures is relatively common. Methods. We assessed how often responsiveness and recall were each evaluated in patients with focal epilepsy undergoing surface and intracranial EEG-video monitoring. We performed this evaluation by retrospectively reviewing video recordings from 121 seizures from 48 patients during their stay in the epilepsy monitoring unit between September 2012 and November 2019.Results. We found that responsiveness during seizures was tested more frequently than recall of ictal events after seizures. Of 121 seizures in 48 patients, responsiveness was tested in 101 seizures, whereas recall was tested in only 38. Significance. Evaluating if consciousness is impaired during seizures is of critical importance for guiding recommendations for people with epilepsy, such as whether it is safe for them to drive or operate machinery. The ILAE classification guidelines are intended to be broadly useful, but our findings demonstrate that at least in one important clinical setting, responsiveness was used more commonly than recall to evaluate patients during focal seizures. Although our preliminary findings should be replicated in a larger sample and in other patient groups, they suggest that responsiveness testing during focal seizures might be relatively common in at least some clinical practice settings. With further study, this may lead to a re-evaluation of criteria for classifying focal seizures to include both responsiveness and recall of experiences during seizures, as both may provide important information to guide clinical care.