Abstract
Study Objectives
Multisensor wearable consumer devices allowing the collection of multiple data sources, such as heart rate and motion, for the evaluation of sleep in the home environment, ...are increasingly ubiquitous. However, the validity of such devices for sleep assessment has not been directly compared to alternatives such as wrist actigraphy or polysomnography (PSG).
Methods
Eight participants each completed four nights in a sleep laboratory, equipped with PSG and several wearable devices. Registered polysomnographic technologist-scored PSG served as ground truth for sleep–wake state. Wearable devices providing sleep–wake classification data were compared to PSG at both an epoch-by-epoch and night level. Data from multisensor wearables (Apple Watch and Oura Ring) were compared to data available from electrocardiography and a triaxial wrist actigraph to evaluate the quality and utility of heart rate and motion data. Machine learning methods were used to train and test sleep–wake classifiers, using data from consumer wearables. The quality of classifications derived from devices was compared.
Results
For epoch-by-epoch sleep–wake performance, research devices ranged in d′ between 1.771 and 1.874, with sensitivity between 0.912 and 0.982, and specificity between 0.366 and 0.647. Data from multisensor wearables were strongly correlated at an epoch-by-epoch level with reference data sources. Classifiers developed from the multisensor wearable data ranged in d′ between 1.827 and 2.347, with sensitivity between 0.883 and 0.977, and specificity between 0.407 and 0.821.
Conclusions
Data from multisensor consumer wearables are strongly correlated with reference devices at the epoch level and can be used to develop epoch-by-epoch models of sleep–wake rivaling existing research devices.
Sleep loss is a common phenomenon with consequences to physical and mental health. While the effects of sleep restriction on working memory are well documented, it is unknown how sleep restriction ...affects continuous force control. The purpose of this study was to determine the effects of sleep restriction on visually and memory-guided force production magnitude and variability. We hypothesized that both visually and memory-guided force production would be impaired after sleep restriction. Fourteen men participated in an eleven-day inpatient sleep study and completed a grip force task after two nights of ten hours’ time in bed (baseline); four nights of five hours’ time in bed (sleep restriction); and one night of ten hours’ time in bed (recovery). The force task entailed four 20-second trials of isometric force production with the thumb and index finger targeting 25% of the participant’s maximum voluntary contraction. During visually guided trials, participants had continuous visual feedback of their force production. During memory-guided trials, visual feedback was removed for the last 12 seconds of each trial. During both conditions, participants were told to maintain the target force production. After sleep restriction, participants decreased the magnitude of visually guided, but not memory-guided, force production, suggesting that visual attention tasks are more affected by sleep loss than memory-guided tasks. Participants who reported feeling more alert after sleep restriction and recovery sleep produced higher force during memory-guided, but not visually guided, force production, suggesting that the perception of decreased alertness may lead to more attention to the task during memory-guided visual tasks.
Metabolic routing of nicotinamide (NAM) to NAD+ or 1-methylnicotinamide (MeNAM) has impacts on human health and aging. NAM is imported by cells or liberated from NAD+. The fate of 2H4-NAM in cultured ...cells, mice, and humans was determined by stable isotope tracing. 2H4-NAM is an NAD+ precursor via the salvage pathway in cultured A549 cells and human PBMCs and in A549 cell xenografts and PBMCs from 2H4-NAM-dosed mice and humans, respectively. 2H4-NAM is a MeNAM precursor in A549 cell cultures and xenografts, but not isolated PBMCs. NAM released from NAD+ is a poor MeNAM precursor. Additional A549 cell tracer studies yielded further mechanistic insight. NAMPT activators promote NAD+ synthesis and consumption. Surprisingly, NAM liberated from NAD+ in NAMPT activator-treated A549 cells is also routed toward MeNAM production. Metabolic fate mapping of the dual NAM sources across the translational spectrum (cells, mice, humans) illuminates a key regulatory node governing NAD+ and MeNAM synthesis.
Display omitted
•Exogenous nicotinamide (NAM) produced NAD+ and 1-methylnicotinamide (MeNAM)•NAD+-derived NAM is a poor precursor for MeNAM•Pioneering tracer study with 2H4-NAM in humans•NAMPT activators reprogram the metabolic fate of NAD+-derived NAM
NAD+ and 1-methylnicotinamide (MeNAM), which are produced from nicotinamide (NAM), differentially affect human health and aging. Metabolite tracing with 2H4-NAM unveiled the metabolic fates of exogenous NAM and NAD+-derived NAM in cultured cells, mice, and humans. Exogenous NAM produced NAD+ and MeNAM. NAD+-derived NAM was a poor precursor for MeNAM.
Abstract Background Mitral annular calcium (MAC), commonly identified by cardiac imaging, is associated with cardiovascular events and predisposes to the development of clinically important mitral ...valve regurgitation and mitral valve stenosis. However, its biological determinants remain largely unknown. Objectives The authors sought to evaluate whether a genetic predisposition to elevations in plasma lipids is associated with the presence of MAC. Methods The authors used 3 separate Mendelian randomization techniques to evaluate the associations of lipid genetic risk scores (GRS) with MAC in 3 large patient cohorts: the Framingham Health Study, MESA (Multiethnic European Study of Atherosclerosis), and the AGE-RS (Age, Gene/Environment Susceptibility-Reykjavik Study). The authors provided cross-ethnicity replication in the MESA Hispanic-American participants. Results MAC was present in 1,149 participants (20.4%). In pooled analyses across all 3 cohorts, a triglyceride GRS was significantly associated with the presence of MAC (odds ratio OR per triglyceride GRS unit: 1.73; 95% confidence interval CI: 1.24 to 2.41; p = 0.0013). Neither low- nor high-density lipoprotein cholesterol GRS was significantly associated with MAC. Results were consistent in cross-ethnicity analyses among the MESA Hispanic-Americans cohort (OR per triglyceride GRS unit: 2.04; 95% CI: 1.03 to 4.03; p = 0.04). In joint meta-analysis across all included cohorts, the triglyceride GRS was associated with MAC (OR per triglyceride GRS unit: 1.79; 95% CI: 1.32 to 2.41; p = 0.0001). The results were robust to several sensitivity analyses that limit both known and unknown forms of genetic pleiotropy. Conclusions Genetic predisposition to elevated triglyceride levels was associated with the presence of MAC, a risk factor for clinically significant mitral valve disease, suggesting a causal association. Whether reducing triglyceride levels can lower the incidence of clinically significant mitral valve disease requires further study.
Triple-negative breast cancer (TNBC) is a heterogeneous disease and we have previously shown that rapid relapse of TNBC is associated with distinct sociodemographic features. We hypothesized that ...rapid versus late relapse in TNBC is also defined by distinct clinical and genomic features of primary tumors.
Using three publicly-available datasets, we identified 453 patients diagnosed with primary TNBC with adequate follow-up to be characterized as 'rapid relapse' (rrTNBC; distant relapse or death ≤2 years of diagnosis), 'late relapse' (lrTNBC; > 2 years) or 'no relapse' (nrTNBC: > 5 years no relapse/death). We explored basic clinical and primary tumor multi-omic data, including whole transcriptome (n = 453), and whole genome copy number and mutation data for 171 cancer-related genes (n = 317). Association of rapid relapse with clinical and genomic features were assessed using Pearson chi-squared tests, t-tests, ANOVA, and Fisher exact tests. We evaluated logistic regression models of clinical features with subtype versus two models that integrated significant genomic features.
Relative to nrTNBC, both rrTNBC and lrTNBC had significantly lower immune signatures and immune signatures were highly correlated to anti-tumor CD8 T-cell, M1 macrophage, and gamma-delta T-cell CIBERSORT inferred immune subsets. Intriguingly, lrTNBCs were enriched for luminal signatures. There was no difference in tumor mutation burden or percent genome altered across groups. Logistic regression mModels that incorporate genomic features significantly outperformed standard clinical/subtype models in training (n = 63 patients), testing (n = 63) and independent validation (n = 34) cohorts, although performance of all models were overall modest.
We identify clinical and genomic features associated with rapid relapse TNBC for further study of this aggressive TNBC subset.
Subinternships are integral to medical education as tools for teaching and assessing fourth-year medical students. Social distancing due to COVID-19 has precluded the ability to offer in-person ...subinternships – negatively impacting medical education and creating uncertainty surrounding the residency match. With no precedent for the development and implementation of virtual subinternships, the Society of Academic Urologists (SAU) developed an innovative and standardized curriculum for the Virtual Subinternship in Urology (vSIU).
The vSIU committee's mandate was to create a standardized curriculum for teaching foundational urology and assessing student performance. Thirty-three members from 23 institutions were divided into working groups and given 3 weeks to develop 10 modules based on urologic subspecialties, Accreditation Council for Graduate Medical Education core competencies, technical skills training and student assessment. Working groups were encouraged to develop innovative learning approaches. The final curriculum was assembled into the “vSIU Guidebook.”
The vSIU Guidebook contains 212 pages – 64 pages core content and 2 appendices (patient cases and evaluations). It outlines a detailed 4-week curriculum with a sufficient volume of resources to offer a completely adaptable virtual course with the same rigor as a traditional subinternship. Modules contain curated teaching resources including journal articles, lectures, surgical videos and simulated clinical scenarios. Innovative learning tools include reflective writing, mentorship guidelines, videoconference-based didactics, surgical simulcasting and virtual technical skills training. The guidebook was disseminated to program directors nationally.
The vSIU is the first virtual subinternship in any specialty to be standardized and offered nationally, and it was implemented by at least 19 urology programs. This curriculum serves as a template for other specialties looking to develop virtual programs and feedback from educators and students will allow the curriculum to evolve. As the pandemic continues to challenge our paradigm, this rapid and innovative response exemplifies that the medical community will continue to meet the needs of an ever-changing educational landscape.
Recent breeding efforts in Brassica have focused on the development of new oilseed feedstock crop for biofuels (e.g., ethanol, biodiesel, bio-jet fuel), bio-industrial uses (e.g., bio-plastics, ...lubricants), specialty fatty acids (e.g., erucic acid), and producing low glucosinolates levels for oilseed and feed meal production for animal consumption. We identified a novel opportunity to enhance the availability of nutritious, fresh leafy greens for human consumption. Here, we demonstrated the efficacy of disarming the ‘mustard bomb’ reaction in reducing pungency upon the mastication of fresh tissue—a major source of unpleasant flavor and/or odor in leafy Brassica. Using gene-specific mutagenesis via CRISPR-Cas12a, we created knockouts of all functional copies of the type-I myrosinase multigene family in tetraploid Brassica juncea. Our greenhouse and field trials demonstrate, via sensory and biochemical analyses, a stable reduction in pungency in edited plants across multiple environments. Collectively, these efforts provide a compelling path toward boosting the human consumption of nutrient-dense, fresh, leafy green vegetables.
Urology residency prepares trainees for independent practice. The optimal operative chief resident year experience to prepare for practice is undefined. We analyzed the temporal arc of cases ...residents complete during their residency compared to their chief year in a multi-institutional cohort.
Accreditation Council for Graduate Medical Education case logs of graduating residents from 2010 to 2022 from participating urology residency programs were aggregated. Resident data for 5 categorized index procedures were recorded: (1) general urology, (2) endourology, (3) reconstructive urology, (4) urologic oncology, and (5) pediatric urology. Interactions were tested between the trends for total case exposure in residency training relative to the chief resident year.
From a sample of 479 resident graduates, a total of 1,287,433 total cases were logged, including 375,703 during the chief year (29%). Urologic oncology cases had the highest median percentage completed during chief year (56%) followed by reconstructive urology (27%), general urology (24%), endourology (17%), and pediatric urology (2%). Across the study period, all categories of cases had a downward trend in median percentage completed during chief year except for urologic oncology. However, only trends in general urology (slope of -0.68,
= .013) and endourology (slope of -1.71,
≤ .001) were significant.
Over 50% of cases completed by chief residents are urologic oncology procedures. Current declining trends indicate that residents are being exposed to proportionally fewer general urology and endourology cases during their chief year prior to entering independent practice.
Introduction Social jetlag, the misalignment between the sleep schedule imposed by social obligations (i.e., work, school) versus free days, is associated with increased adolescent body mass index ...(BMI). The goals of the current study were to (1) investigate the association between social jetlag and eating behaviors in adolescents, and (2) determine whether social jetlag is associated with BMI while adjusting for unhealthy eating behaviors and lack of physical activity. Methods Survey data were collected from the age 15 wave of the Fragile Families and Child Wellbeing Study (n = 2,985), a cohort of children born in 20 U.S. cities. Social jetlag (in hours) was calculated as the difference between midpoint of self-reported sleep on the weekend and school nights. Eating behaviors (4 total) included number of days youth eats breakfast, green vegetables or fruit, and fast food during the week, and the number of sweetened drinks consumed daily. Regression models were conducted to test associations of social jetlag with eating behaviors (Poisson) and with BMI (linear), adjusting for school night sleep duration and demographic and household characteristics (e.g., sex, race/ethnicity, family structure, use of electronics near bedtime). A second linear regression with BMI as the outcome also adjusted for physical activity and eating behaviors. Results Greater social jetlag was associated with lower consumption of breakfast and green vegetables/fruit and greater consumption of fast food and sweetened drinks (all p <. 01) after adjusting for school night sleep duration, demographics, and household characteristics. Greater social jetlag also predicted higher BMI (b = .15, p = .042), and this association remained (b = .17, p = .023) after further adjustment for physical activity and eating behaviors. Conclusion In this large sample of adolescents, social jetlag was associated with BMI, even after controlling for school night sleep duration, physical activity, eating behaviors, demographic, and household characteristics. These findings suggest that short sleep duration, lack of physical activity, and unhealthy eating behaviors do not fully explain the association between social jetlag and higher BMI in adolescents. Support (If Any) R01HD073352
Objective: Thyroid storm represents the extreme manifestation of thyrotoxicosis and is a medical emergency with a high mortality rate. The clinical manifestations of a severely thyrotoxic state can ...be devastating, and its most significant effects occur in the cardiovascular system. Cardiac involvement is the leading cause of death in patients with thyroid storm. We report a unique case of thyroid storm precipitated by viral myopericarditis in the setting of exogenous thyroid hormone supplementation.Methods: Case report and review of the literature.Results: We report a case of a previously healthy 26-year-old male with a history of bodybuilding who developed thyroid storm with multi-organ failure, including acute-onset congestive heart failure, leading to cardiogenic shock. Investigations revealed ingestion of exogenous thyroid hormone as the source of his thyrotoxicosis. Initial labs revealed serum thyroid-stimulating hormone 0.015 mU/L, free thyroxine 2.3 ng/dL, free triiodothyronine 8.8 pg/mL, total triiodothyronine of 2.22 ng/mL, and thyroglobulin 4.4 ng/mL. There was also evidence of viral myopericarditis, as demonstrated on cardiac imaging and multiple elevated Coxsackie virus B titer levels.Conclusion: Given the patient's underlying thyrotoxic state from exogenous thyroid hormone ingestion, we believe that his acute myopericarditis was the catalyst that precipitated his thyroid storm. The combination of acute myopericarditis and thyroid storm ultimately led to cardiogenic shock. He showed rapid improvement with cardiopulmonary supportive efforts and treatment for thyroid storm. In considering the etiology of thyroid storm, it is important to exclude the possibility of exogenous thyroid hormone ingestion, especially in the setting of nonregulated, over-the-counter, bodybuilding, or weight-loss supplement use.Abbreviations: MRI = magnetic resonance imaging; SSKI = supersaturated potassium iodide; T3 = triiodothyronine; T4 = thyroxine
PDF
