Project description:The link between dreams and creativity has been a topic of intense speculation. Recent scientific findings suggest that sleep onset (known as N1) may be an ideal brain state for creative ideation. However, the specific link between N1 dream content and creativity has remained unclear. To investigate the contribution of N1 dream content to creative performance, we administered targeted dream incubation (a protocol that presents auditory cues at sleep onset to introduce specific themes into dreams) and collected dream reports to measure incorporation of the selected theme into dream content. We then assessed creative performance using a set of three theme-related creativity tasks. Our findings show enhanced creative performance and greater semantic distance in task responses following a period of N1 sleep as compared to wake, corroborating recent work identifying N1 as a creative sweet spot and offering novel evidence for N1 enabling a cognitive state with greater associative divergence. We further demonstrate that successful N1 dream incubation enhances creative performance more than N1 sleep alone. To our knowledge, this is the first controlled experiment investigating a direct role of incubating dream content in the enhancement of creative performance.
Project description:Many viruses require the host endoplasmic reticulum protein-folding machinery in order to correctly fold one or more of their glycoproteins. Iminosugars with glucose stereochemistry target the glucosidases which are key for entry into the glycoprotein folding cycle. Viral glycoproteins are thus prevented from interacting with the protein-folding machinery leading to misfolding and an antiviral effect against a wide range of different viral families. As iminosugars target host enzymes, they should be refractory to mutations in the virus. Iminosugars therefore have great potential for development as broad-spectrum antiviral therapeutics. We outline the mechanism giving rise to the antiviral activity of iminosugars, the current progress in the development of iminosugar antivirals and future prospects for this field.
Project description:BackgroundInadequate sleep and physical activity are common during and after hospitalization, but their impact on patient-reported functional outcomes after discharge is poorly understood. Wearable devices that measure sleep and activity can provide patient-generated data to explore ideal levels of sleep and activity to promote recovery after hospital discharge.ObjectiveThis study aimed to examine the relationship between daily sleep and physical activity with 6 patient-reported functional outcomes (symptom burden, sleep quality, physical health, life space mobility, activities of daily living, and instrumental activities of daily living) at 13 weeks after hospital discharge.MethodsThis secondary analysis sought to examine the relationship between daily sleep, physical activity, and patient-reported outcomes at 13 weeks after hospital discharge. We utilized wearable sleep and activity trackers (Withings Activité wristwatch) to collect data on sleep and activity. We performed descriptive analysis of device-recorded sleep (minutes/night) with patient-reported sleep and device-recorded activity (steps/day) for the entire sample with full data to explore trends. Based on these trends, we performed additional analyses for a subgroup of patients who slept 7-9 hours/night on average. Differences in patient-reported functional outcomes at 13 weeks following hospital discharge were examined using a multivariate linear regression model for this subgroup.ResultsFor the full sample of 120 participants, we observed a "T-shaped" distribution between device-reported physical activity (steps/day) and sleep (patient-reported quality or device-recorded minutes/night) with lowest physical activity among those who slept <7 or >9 hours/night. We also performed a subgroup analysis (n=60) of participants that averaged the recommended 7-9 hours of sleep/night over the 13-week study period. Our key finding was that participants who had both adequate sleep (7-9 hours/night) and activity (>5000 steps/day) had better functional outcomes at 13 weeks after hospital discharge. Participants with adequate sleep but less activity (<5000 steps/day) had significantly worse symptom burden (z-score 0.93, 95% CI 0.3 to 1.5; P=.02), community mobility (z-score -0.77, 95% CI -1.3 to -0.15; P=.02), and perceived physical health (z-score -0.73, 95% CI -1.3 to -0.13; P=.003), compared with those who were more physically active (≥5000 steps/day).ConclusionsParticipants within the "sweet spot" that balances recommended sleep (7-9 hours/night) and physical activity (>5000 steps/day) reported better functional outcomes after 13 weeks compared with participants outside the "sweet spot." Wearable sleep and activity trackers may provide opportunities to hone postdischarge monitoring and target a "sweet spot" of recommended levels for both sleep and activity needed for optimal recovery.Trial registrationClinicalTrials.gov NCT03321279; https://clinicaltrials.gov/ct2/show/NCT03321279.
Project description:Sweetness is a sensation that contributes to the palatability of foods, which is the primary driver of food choice. Thus, understanding how to measure the appeal (hedonics) of sweetness and how to modify it are key to effecting dietary change for health. Sweet hedonics is multidimensional so can only be captured by multiple approaches including assessment of elements such as liking, preference, and consumption intent. There are both innate and learned components to the appeal of sweet foods and beverages. These are responsive to various behavioral and biological factors, suggesting the opportunity to modify intake. Given the high amount of added sugar intake in the United States and recommendations from many groups to reduce this, further exploration of current hypothesized approaches to moderate sugar intake (e.g., induced hedonic shift, use of low-calorie sweeteners) is warranted.
Project description:Viral infections are initiated by attachment of the virus to host cell surface receptors, including sialic acid-containing glycans. It is now possible to rapidly identify specific glycan receptors using glycan array screening, to define atomic-level structures of virus-glycan complexes and to alter the glycan-binding site to determine the function of glycan engagement in viral disease. This Review highlights general principles of virus-glycan interactions and provides specific examples of sialic acid binding by viruses with stalk-like attachment proteins, including influenza virus, reovirus, adenovirus and rotavirus. Understanding virus-glycan interactions is essential to combating viral infections and designing improved viral vectors for therapeutic applications.
Project description:IntroductionRandomized trials recruit diverse patients, including some individuals who may be unresponsive to the treatment. Here we follow up on prior conceptual advances and introduce a specific method that does not rely on stratification analysis and that tests whether patients in the intermediate range of disease severity experience more relative benefit than patients at the extremes of disease severity (sweet spot).MethodsWe contrast linear models to sigmoidal models when describing associations between disease severity and accumulating treatment benefit. The Gompertz curve is highlighted as a specific sigmoidal curve along with the Akaike information criterion (AIC) as a measure of goodness of fit. This approach is then applied to a matched analysis of a published landmark randomized trial evaluating whether implantable defibrillators reduce overall mortality in cardiac patients (n = 2,521).ResultsThe linear model suggested a significant survival advantage across the spectrum of increasing disease severity (β = 0.0847, P < 0.001, AIC = 2,491). Similarly, the sigmoidal model suggested a significant survival advantage across the spectrum of disease severity (α = 93, β = 4.939, γ = 0.00316, P < 0.001 for all, AIC = 1,660). The discrepancy between the 2 models indicated worse goodness of fit with a linear model compared to a sigmoidal model (AIC: 2,491 v. 1,660, P < 0.001), thereby suggesting a sweet spot in the midrange of disease severity. Model cross-validation using computational statistics also confirmed the superior goodness of fit of the sigmoidal curve with a concentration of survival benefits for patients in the midrange of disease severity.ConclusionSystematic methods are available beyond simple stratification for identifying a sweet spot according to disease severity. The approach can assess whether some patients experience more relative benefit than other patients in a randomized trial.[Box: see text].
Project description:Transition from homeostatic to reactive matrix remodeling is a fundamental adaptive tissue response to injury, inflammatory disease, fibrosis, and cancer. Alterations in architecture, physical properties, and matrix composition result in changes in biomechanical and biochemical cellular signaling. The dynamics of pericellular and extracellular matrices, including matrix protein, proteoglycan, and glycosaminoglycan modification are continually emerging as essential regulatory mechanisms underlying cellular and tissue function. Nevertheless, the impact of matrix organization on inflammation and immunity in particular and the consequent effects on tissue healing and disease outcome are arguably under-studied aspects of adaptive stress responses. Herein, we review how the predominant glycosaminoglycan hyaluronan (HA) contributes to the structure and function of the tissue microenvironment. Specifically, we examine the evidence of HA degradation and the generation of biologically active smaller HA fragments in pathological settings in vivo. We discuss how HA fragments versus nascent HA via alternate receptor-mediated signaling influence inflammatory cell recruitment and differentiation, resident cell activation, as well as tumor growth, survival, and metastasis. Finally, we discuss how HA fragmentation impacts restoration of normal tissue function and pathological outcomes in disease.
Project description:The objective of this review is to explore the metabolomic environment of epithelial ovarian cancer that contributes to chemoresistance and to use this knowledge to identify possible targets for therapeutic intervention. The Warburg effect describes increased glucose uptake and lactate production in cancer cells. In ovarian cancer, we require a better understanding of how cancer cells reprogram their glycogen metabolism to overcome their nutrient deficient environment and become chemoresistant. Glucose metabolism in ovarian cancer cells has been proposed to be influenced by altered fatty acid metabolism, oxidative phosphorylation, and acidification of the tumor microenvironment. We investigate several markers of altered metabolism in ovarian cancer including hypoxia-induced factor 1, VEGF, leptin, insulin-like growth factors, and glucose transporters. We also discuss the signaling pathways involved with these biomarkers including PI3K/AKT/mTOR, JAK/STAT and OXPHOS. This review outlines potential metabolic targets to overcome chemoresistance in ovarian cancer. Continued research of the metabolic changes in ovarian cancer is needed to identify and target these alterations to improve treatment approaches.
Project description:Although sleep apnea-hypopnea syndrome (SAHS) is highly prevalent in patients with type 2 diabetes (T2D), it is unknown whether or not subjects with and without T2D share the same sleep breathing pattern.A cross-sectional study in patients with SAHS according to the presence (n = 132) or not (n = 264) of T2D. Both groups were matched by age, gender, BMI, and waist and neck circumferences. A subgroup of 125 subjects was also matched by AHI. The exclusion criteria included chronic respiratory disease, alcohol abuse, use of sedatives, and heart failure. A higher apnea hypopnea index (AHI) was observed in T2D patients [32.2 (10.2-114.0) vs. 25.6 (10.2-123.4) events/hours; p = 0.002). When sleep events were evaluated separately, patients with T2D showed a significant increase in apnea events [8.4 (0.1-87.7) vs. 6.3 (0.0-105.6) e/h; p = 0.044), as well as a two-fold increase in the percentage of time spent with oxygen saturation <90% [15.7 (0.0-97.0) vs. 7.9 (0.0-95.6) %; <0.001)], higher rates of oxygen desaturation events, and also higher daily sleepiness [7.0 (0.0-21.0) vs. 5.0 (0.0-21.0); p = 0.006)] than subjects without T2D. Significant positive correlations between fasting plasma glucose and AHI, the apnea events, and CT90 were observed. Finally, multiple linear regression analyses showed that T2D was independently associated with AHI (R2 = 0.217), the apnea index (R2 = 0.194), CT90 (R2 = 0.222), and desaturation events.T2D patients present a different pattern of sleep breathing than subject without diabetes. The most important differences are the severity of hypoxemia and the number of apneas whereas the incidence of hypopnea episodes is similar.