Study Objectives Purposes of this study were to identify subgroups of patients with distinct sleep disturbance profiles and to evaluate for differences in demographic, clinical, and various sleep characteristics, as well for differences in the severity of co-occurring symptoms among these subgroups. Methods Outpatients with breast, gynecological, gastrointestinal, or lung cancer (n = 1331) completed questionnaires six times over two chemotherapy cycles. Self-reported sleep disturbance was evaluated using the General Sleep Disturbance Scale (GSDS). Latent profile analysis was used to identify distinct subgroups. Results Three latent classes with distinct sleep disturbance profiles were identified (Low [25.5%], High [50.8%], Very High [24.0%]) across the six assessments. Approximately 75% of the patients had a mean total GSDS score that was above the clinically meaningful cutoff score of at least 43 across all six assessments. Compared to the Low class, patients in High and Very High classes were significantly younger, had a lower functional status, had higher levels of comorbidity, and were more likely to be female, more likely to have childcare responsibilities, less likely to be employed, and less likely to have gastrointestinal cancer. For all of the GSDS subscale and total scores, significant differences among the latent classes followed the expected pattern (Low < High < Very High). For trait and state anxiety, depressive symptoms, morning and evening fatigue, decrements in attentional function, and decrements in morning and evening energy, significant differences among the latent classes followed the expected pattern (Low < High < Very High). Conclusions Clinicians need to perform in-depth assessments of sleep disturbance and co-occurring symptoms to identify high-risk patients and recommend appropriate interventions.

The Na1.5_G213D mutation is associated with a gain-of-function phenotype, multifocal atrial and ventricular ectopy and dilated cardiomyopathy. Since patients with a MEPPC-like phenotype may specifically benefit from Class-1 antiarrhythmic drugs or amiodarone, clinical identification of this disease entity is important.

The KCNH2 and KCNE2 genes encode the cardiac voltage-gated K+ channel KV11.1 and its auxiliary β subunit KCNE2. KV11.1 is critical for repolarization of the cardiac action potential. In humans, mutations or drug therapy affecting the KV11.1 channel are associated with prolongation of the QT intervals on the ECG and increased risk of ventricular tachyarrhythmia and sudden cardiac death—conditions known as congenital or acquired Long QT syndrome (LQTS), respectively. In horses, sudden, unexplained deaths are a well-known problem. We sequenced the cDNA of the KCNH2 and KCNE2 genes using RACE and conventional PCR on mRNA purified from equine myocardial tissue. Equine KV11.1 and KCNE2 cDNA had a high homology to human genes (93 and 88%, respectively). Equine and human KV11.1 and KV11.1/KCNE2 were expressed in Xenopus laevis oocytes and investigated by two-electrode voltage-clamp. Equine KV11.1 currents were larger compared to human KV11.1, and the voltage dependence of activation was shifted to more negative values with V1/2 = -14.2±1.1 mV and -17.3±0.7, respectively. The onset of inactivation was slower for equine KV11.1 compared to the human homolog. These differences in kinetics may account for the larger amplitude of the equine current. Furthermore, the equine KV11.1 channel was susceptible to pharmacological block with terfenadine. The physiological importance of KV11.1 was investigated in equine right ventricular wedge preparations. Terfenadine prolonged action potential duration and the effect was most pronounced at slow pacing. In conclusion, these findings indicate that horses could be disposed to both congenital and acquired LQTS.

a b s t r a c tSlick and Slack are members of the Slo family of high-conductance potassium channels. These channels are activated by Na + and Cl À and are highly expressed in the CNS, where they are believed to contribute to the resting membrane potential of neurons and the control of excitability. Herein, we provide evidence that Slick and Slack channels are regulated by the phosphoinositide PIP 2 . Two stereoisomers of PIP 2 were able to exogenously activate Slick and Slack channels expressed in Xenopus oocytes, and in addition, it is shown that Slick and Slack channels are modulated by endogenous PIP 2 . The activating effect of PIP 2 appears to occur by direct interaction with lysine 306 in Slick and lysine 339 in Slack, located at the proximal C-termini of both channels. Overall, our data suggest that PIP 2 is an important regulator of Slick and Slack channels, yet it is not involved in the recently described cell volume sensitivity of Slick channels, since mutated PIP 2 -insensitive Slick channels retained their sensitivity to cell volume.

Slick and Slack high-conductance potassium channels have been recently discovered, and are found in the central nervous system and in the heart. Both channels are activated by Na+ and Cl−, and Slick channels are also inhibited by adenosine triphospate (ATP). An important role of setting the resting membrane potential and controlling the basal excitability of neurons has been suggested for these channels. In addition, no specific blockers for these channels are known up to the present. With the purpose of studying the pharmacological characteristics of Slick and Slack channels, the effects of exposure to the antiarrhythmic compound clofilium were evaluated. Clofilium was able to modulate the activity of Slick and Slack channels effectively, with a stronger effect on Slack than Slick channels. In order to evaluate the pharmacological behavior of Slick and Slack channels further, 38 commonly used potassium channel blockers were tested. Screening of these compounds did not reveal any modulators of Slick and Slack channels, except for clofilium. The present study provides a first approach towards elucidating the pharmacological characteristics of Slick and Slack channels and could be the basis for future studies aimed at developing potent and specific blockers and activators for these channels.