The sleep-wake cycle and circadian rhythmicity both contribute to brain function, but whether this contribution differs between men and women and how it varies across cognitive domains and subjective dimensions has not been established. We examined the circadian and sleep-wake-dependent regulation of cognition in 16 men and 18 women in a forced desynchrony protocol and quantified the separate contributions of circadian phase, prior sleep, and elapsed time awake on cognition and sleep. The largest circadian effects were observed for reported sleepiness, mood, and reported effort; the effects on working memory and temporal processing were smaller. Although these effects were seen in both men and women, there were quantitative differences. The amplitude of the circadian modulation was larger in women in 11 of 39 performance measures so that their performance was more impaired in the early morning hours. Principal components analysis of the performance measures yielded three factors, accuracy, effort, and speed, which reflect core performance characteristics in a range of cognitive tasks and therefore are likely to be important for everyday performance. The largest circadian modulation was observed for effort, whereas accuracy exhibited the largest sex difference in circadian modulation. The sex differences in the circadian modulation of cognition could not be explained by sex differences in the circadian amplitude of plasma melatonin and electroencephalographic slow-wave activity. These data establish the impact of circadian rhythmicity and sex on waking cognition and have implications for understanding the regulation of brain function, cognition, and affect in shift-work, jetlag, and aging.cognition | biological rhythms | gender | slow wave sleep | melatonin C ircadian rhythms are generated by a set of core "clock" genes and are present in nearly every cell of the body and brain (1). These local clocks and rhythms are synchronized by neural and endocrine pathways originating from the master circadian pacemaker located in the suprachiasmatic nucleus (SCN) (2, 3). In addition, the timing of behaviors such as food intake and sleep and associated changes in local and systemic cues contribute to the temporal organization in peripheral tissues outside the SCN (4, 5). In view of the pervasiveness of circadian rhythms, it is not surprising that they affect many aspects of physiology, behavior, and cognition in health and in disease. Indeed, circadian abnormalities have been implicated in disorders of sleep, mood, and cognition (6), in deleterious responses to shift work (7), depression (8), and Alzheimer's disease (9). The prevalence of most of these disorders is higher in women than in men (10), and their impact on psychological functions and quality of life of patients differs between the sexes (11).Women are underrepresented in both circadian and sleep research (12), although sex differences in human circadian and sleep characteristics are emerging from the few studies that contrast men and women. (Note: Throughout thi...

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SummaryGR32191, a potent selective thromboxane receptor antagonist, has been shown to inhibit completely prostaglandin endoperoxide and thromboxane A2 (TxA2)-induced platelet aggregation, [14C]-serotonin secretion and β-thromboglobulin secretion. Deposition of human platelets onto damaged rabbit aorta in vitro is reduced in the presence of GR32191 which appears to inhibit aggregation of platelets but not direct adhesion of platelets to subendothelium. The effects of non-prostanoid platelet activating agents whose mode of action requires the biosynthesis of TxA2 are also inhibited by GR32191. Prostanoids which inhibit platelet function, such as prostacyclin or PGD2, retain their inhibitory properties in the presence of GR32191 which does not inhibit phospholipase A2, prostaglandin cyclooxygenase, thromboxane synthase, 12-lipoxygenase or cAMP phosphodiesterase activity. The inhibitory action of GR32191 on platelet aggregation, mural thrombus formation and platelet protein storage granule secretion suggests that it has potential in treatingthrombotic disease in man.

The prevalence and clinical features of Wilson's disease in Scotland were investigated. Thirty three cases were identified but adequate information was available on only 28. In 1989, the prevalence rate was 4 per million.

Goal: To evaluate the impact of Karnofsky Performance Status score (KPSS) at the time of liver transplantation (LT) on post-LT survival. Background: While the Model for End-Stage Liver Disease (MELD) score is used to prioritize individuals for LT, it does not specifically incorporate functional status into patient assessment for LT. Methods: Using 2005 to 2016 United Network for Organ Sharing data, all adults (age 18 y and above) undergoing LT were identified. The association of KPSS at the time of LT (KPSS 1: functional status 80% to 100%, KPSS 2: 60% to 70%, KPSS 3: 40% to 50%, KPSS 4: 10% to 30%) with post-LT survival was evaluated using Kaplan-Meier methods and adjusted multivariate logistic regression models. Results: Among 66,397 LT recipients (68% male, 72% non-Hispanic white, 22% hepatocellular carcinoma, median age: 55 to 57), women were more likely to be KPSS 4 at the time of LT compared with men (27.95% vs. 22.79%; P<0.001) and African Americans (25.43% vs. 23.03%; P<0.001) and Hispanics (31.69% vs. 23.03%; P<0.001) were more likely to be KPSS 4 than non-Hispanic whites. Worse KPSS at LT correlated with higher post-LT mortality [compared with KPSS 1: Hazard Ratio (HR) for KPSS 2: 1.16, 95% confidence interval (CI): 1.10-1.22; HR for KPSS 3: 1.40; 95% CI: 1.32-1.49; HR for KPSS 4: 1.67; 95% CI: 1.55-1.79]. This increased mortality seen with worse KPSS was observed among all liver disease etiologies and in patients with and without hepatocellular carcinoma. Conclusions: Worse functional status at the time of LT is strongly associated with higher risk of mortality following LT, emphasizing the importance of optimizing performance status in the preoperative period.

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