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Background: Educators now use reported observations when assessing trainees’ performance. Unfortunately, they have little information about how to design and implement assessments based on reported observations. Objective: The purpose of this scoping review was to map the literature on the use of reported observations in judging health professions education (HPE) trainees' performances. Methods: Arksey and O'Malley’s (2005) method was used with four databases (sources: ERIC, CINAHL, MEDLINE, PsycINFO). Eligibility criteria for articles were: documents in English or French, including primary data, and initial or professional training; (2) training in an HPE program; (3) workplace-based assessment; and (4) assessment based on reported observations. The inclusion/exclusion, and data extraction steps were performed (agreement rate > 90%). We developed a data extraction grid to chart the data. Descriptive analyses were used to summarize quantitative data, and the authors conducted thematic analysis for qualitative data. Results: Based on 36 papers and 13 consultations, the team identified six steps characterizing trainee performance assessment based on reported observations in HPE: (1) making first contact, (2) observing and documenting the trainee performance, (3) collecting and completing assessment data, (4) aggregating assessment data, (5) inferring the level of competence, and (6) documenting and communicating the decision to the stakeholders. Discussion: The design and implementation of assessment based on reported observations is a first step towards a quality implementation by guiding educators and administrators responsible for graduating competent professionals. Future research might focus on understanding the context beyond assessor cognition to ensure the quality of meta-assessors’ decisions.

Throughout the COVID-19 pandemic, scenario modeling played a crucial role in shaping the decision-making process of public health policies. Unlike forecasts, scenario projections rely on specific assumptions about the future that consider different plausible states-of-the-world that may or may not be realized and that depend on policy interventions, unpredictable changes in the epidemic outlook, etc. As a consequence, long-term scenario projections require different evaluation criteria than the ones used for traditional short-term epidemic forecasts. Here, we propose a novel ensemble procedure for assessing pandemic scenario projections using the results of the Scenario Modeling Hub (SMH) for COVID-19 in the United States (US). By defining a “scenario ensemble” for each model and the ensemble of models, termed “Ensemble2”, we provide a synthesis of potential epidemic outcomes, which we use to assess projections’ performance, bypassing the identification of the most plausible scenario. We find that overall the Ensemble2 models are well-calibrated and provide better performance than the scenario ensemble of individual models. The ensemble procedure accounts for the full range of plausible outcomes and highlights the importance of scenario design and effective communication. The scenario ensembling approach can be extended to any scenario design strategy, with potential refinements including weighting scenarios and allowing the ensembling process to evolve over time.

Abstract Background Hearing loss predicts cognitive decline and falls risk. It has been argued that degraded hearing makes listening effortful, causing competition for higher-level cognitive resources needed for secondary cognitive or motor tasks. Therefore, executive function training has the potential to improve cognitive performance, in turn improving mobility, especially when older adults with hearing loss are engaged in effortful listening. Moreover, research using mobile neuroimaging and ecologically valid measures of cognition and mobility in this population is limited. The objective of this research is to examine the effect of at-home cognitive training on dual-task performance using laboratory and simulated real-world conditions in normal-hearing adults and older hearing aid users. We hypothesize that executive function training will lead to greater improvements in cognitive-motor dual-task performance compared to a wait-list control group. We also hypothesize that executive function training will lead to the largest dual-task improvements in older hearing aid users, followed by normal-hearing older adults, and then middle-aged adults. Methods A multi-site (Concordia University and KITE-Toronto Rehabilitation Institute, University Health Network) single-blinded randomized controlled trial will be conducted whereby participants are randomized to either 12 weeks of at-home computerized executive function training or a wait-list control. Participants will consist of normal-hearing middle-aged adults (45–60 years old) and older adults (65–80 years old), as well as older hearing aid users (65–80 years old, ≥ 6 months hearing aid experience). Separate samples will undergo the same training protocol and the same pre- and post-evaluations of cognition, hearing, and mobility across sites. The primary dual-task outcome measures will involve either static balance (KITE site) or treadmill walking (Concordia site) with a secondary auditory-cognitive task. Dual-task performance will be assessed in an immersive virtual reality environment in KITE’s StreetLab and brain activity will be measured using functional near infrared spectroscopy at Concordia’s PERFORM Centre. Discussion This research will establish the efficacy of an at-home cognitive training program on complex auditory and motor functioning under laboratory and simulated real-world conditions. This will contribute to rehabilitation strategies in order to mitigate or prevent physical and cognitive decline in older adults with hearing loss. Trial registration Identifier: NCT05418998. https://clinicaltrials.gov/ct2/show/NCT05418998

Abstract Neuroblastoma, the most common type of pediatric extracranial solid tumor, causes 10% of childhood cancer deaths. Despite intensive multimodal treatment, the outcomes of high-risk neuroblastoma remain poor. We urgently need to develop new therapies with safe long-term toxicity profiles for rapid testing in clinical trials. Drug repurposing is a promising approach to meet these needs. Here, we investigated disulfiram, a safe and successful chronic alcoholism treatment with known anticancer and epigenetic effects. Disulfiram efficiently induced cell cycle arrest and decreased the viability of six human neuroblastoma cell lines at half-maximal inhibitory concentrations up to 20 times lower than its peak clinical plasma level in patients treated for chronic alcoholism. Disulfiram shifted neuroblastoma transcriptome, decreasing MYCN levels and activating neuronal differentiation. Consistently, disulfiram significantly reduced the protein level of lysine acetyltransferase 2A (KAT2A), drastically reducing acetylation of its target residues on histone H3. To investigate disulfiram’s anticancer effects in an in vivo model of high-risk neuroblastoma, we developed a disulfiram-loaded emulsion to deliver the highly liposoluble drug. Treatment with the emulsion significantly delayed neuroblastoma progression in mice. These results identify KAT2A as a novel target of disulfiram, which directly impacts neuroblastoma epigenetics and is a promising candidate for repurposing to treat pediatric neuroblastoma.

Abstract Sleep restriction is associated with increased cardiovascular risk, which is more pronounced in female than male persons. We reported recently first causal evidence that mild, prolonged sleep restriction mimicking “real-life” conditions impairs endothelial function, a key step in the development and progression of cardiovascular disease, in healthy female persons. However, the underlying mechanisms are unclear. In model organisms, sleep restriction increases oxidative stress and upregulates antioxidant response via induction of the antioxidant regulator nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Here, we assessed directly endothelial cell oxidative stress and antioxidant responses in healthy female persons (n = 35) after 6 weeks of mild sleep restriction (1.5 h less than habitual sleep) using randomized crossover design. Sleep restriction markedly increased endothelial oxidative stress without upregulating antioxidant response. Using RNA-seq and a predicted protein–protein interaction database, we identified reduced expression of endothelial Defective in Cullin Neddylation-1 Domain Containing 3 (DCUN1D3), a protein that licenses Nrf2 antioxidant responses, as a mediator of impaired endothelial antioxidant response in sleep restriction. Thus, sleep restriction impairs clearance of endothelial oxidative stress that over time increases cardiovascular risk. Trial Registration: NCT02835261

We recently developed a series of nalfurafine analogs (TK10, TK33, and TK35) that may serve as non-addictive candidate analgesics. These compounds are mixed-action agonists at the kappa and delta opioid receptors (KOR and DOR, respectively) and produce antinociception in a mouse warm-water tail-immersion test while failing to produce typical mu opioid receptor (MOR)-mediated side effects. The warm-water tail-immersion test is an assay of pain-stimulated behavior vulnerable to false-positive analgesic-like effects by drugs that produce motor impairment. Accordingly, this study evaluated TK10, TK33, and TK35 in a recently validated assay of pain-related behavioral depression in mice that are less vulnerable to false-positive effects. For comparison, we also evaluated the effects of the MOR agonist/analgesic hydrocodone (positive control), the neurokinin 1 receptor (NK1R) antagonist aprepitant (negative control), nalfurafine as a selective KOR agonist, SNC80 as a selective DOR agonist, and a nalfurafine/SNC80 mixture. Intraperitoneal injection of dilute lactic acid (IP lactic acid) served as a noxious stimulus to depress vertical and horizontal locomotor activity in male and female ICR mice. IP lactic acid-induced locomotor depression was alleviated by hydrocodone but not by aprepitant, nalfurafine, SNC80, the nalfurafine/SNC80 mixture, or the KOR/DOR agonists. These results suggest that caution is warranted in advancing mixed-action KOR/DOR agonists as candidate analgesics.

Chrononutrition is a rapidly evolving field of nutritional epidemiology that addresses the complex relationship between temporal eating patterns, circadian rhythms, and metabolic health, but most prior research has focused on the cardiometabolic consequences of time-restricted feeding and intermittent fasting. The purpose of this topical review is to summarize epidemiological evidence from observational and intervention studies regarding the role of chrononutrition metrics related to eating timing and regularity in cardiometabolic health preservation and cardiovascular disease prevention. Observational studies are limited due to the lack of time-stamped diet data in most population-based studies. Findings from cohort studies generally indicate that breakfast skipping or the later timing of the first eating occasion, a later lunch and dinner, and a greater proportion of caloric intake consumed in the evening are associated with adverse cardiometabolic outcomes, including higher risk for coronary heart disease, hypertension, type 2 diabetes, obesity, dyslipidemia, and systemic inflammation. Randomized controlled trials are also limited, as most in the field of chrononutrition focus on the cardiometabolic consequences of time-restricted feeding. Overall, interventions that shift eating timing patterns to earlier in the day and that restrict evening caloric intake tend to have protective effects on cardiometabolic health, but small sample sizes and short follow-up are notable limitations. Innovation in dietary assessment approaches, to develop low-cost validated tools with acceptable participant burden that reliably capture chrononutrition metrics, is needed for advancing observational evidence. Culturally responsive pragmatic intervention studies with sufficiently large and representative samples are needed to understand the impact of fixed and earlier eating timing schedules on cardiometabolic health. Additional research is warranted to understand the modifiable determinants of temporal eating patterns, to investigate the role of chrononutrition in the context of other dimensions of diet (quantity, quality, and food and nutrition security) in achieving cardiometabolic health equity, and to elucidate underlying physiological mechanisms.

Background: The widespread implementation of longitudinal assessment (LA) to document trainees' progression to independent practice rests more on speculative rather than evidence-based benefits. We aimed to document stakeholders' knowledge of- and attitudes towards LA, and identify how the supports and barriers can help or hinder the uptake and sustainable use of LA. Methods: We interviewed representatives from four stakeholder groups involved in LA. The interview protocols were based on the Theoretical Domains Framework (TDF), which contains a total of 14 behaviour change determinants. Two team members coded the interviews deductively to the TDF, with a third resolving differences in coding. The qualitative data analysis was completed with iterative consultations and discussions with team members until consensus was achieved. Saliency analysis was used to identify dominant domains. Results: Forty-one individuals participated in the study. Three dominant domains were identified. Participants perceive that LA has more positive than negative consequences and requires substantial resources. All the elements and characteristics of LA are present in our data, with differences between stakeholders. Conclusion: Going forward, we could develop and implement tailored and theory driven interventions to promote a shared understanding of LA, and maintain potential positive outcomes while reducing negative ones. Furthermore, resources to support LA implementation need to be addressed to facilitate its uptake.

Background Sleep variability and social jetlag are associated with adverse cardiometabolic outcomes via circadian disruption. Variable eating patterns also lead to circadian disruption, but associations with cardiometabolic health are unknown. Methods and Results Women (n=115, mean age: 33±12 years) completed a 1-week food record using the Automated Self-Administered 24-Hour Dietary Assessment Tool at baseline and 1 year. Timing of first and last eating occasions, nightly fasting duration, and %kcal consumed after 5 pm (%kcal 5 pm) and 8 pm (%kcal 8 pm) were estimated. Day-to-day eating variability was assessed from the SD of these variables. Eating jetlag was defined as weekday-weekend differences in these metrics. Multivariable-adjusted linear models examined cross-sectional and longitudinal associations of day-to-day variability and eating jetlag metrics with cardiometabolic risk. Greater jetlag in eating start time, nightly fasting duration, and %kcal 8 pm related to higher body mass index and waist circumference at baseline (P

Abstract The seismic potential of the Lesser Antilles subduction zone is poorly known and highly debated. Only two damaging earthquakes have been reported in the historical period, in 1839 and 1843, but their sources and magnitude are still uncertain. Global Navigation Satellite Systems and coral data contradict each other, and no conclusion has been reached on the coupling ratio of the plate interface. Given the threat posed by the possible occurrence of a large megathrust earthquake, it is crucial to gain information on prehistorical events. We present the results of a submarine paleoseismological study that covers an exceptional ∼120 Kyr‐long period. We studied the sediments sampled in six up to 26 m‐long piston cores collected in deep fore‐arc basins located over the epicentral region of the 1843 earthquake. Using a multiproxy approach combining geophysical, geochemical, and sedimentological analysis, biostratigraphy and radiocarbon dating, we identified, characterized, and dated numerous event deposits that we then correlated with the sampled basins over an up to 160 km‐long area. We show that at least 33 earthquakes likely triggered these sediment remobilizations in the last 120 Kyr. Four of these events promoted exceptional deposits of turbidites + homogenites. From peak ground acceleration calculated for potential earthquakes occurring on various faults, and the absence of deposits linked to the historical earthquakes, we propose that the sources are likely megathrust earthquakes. Over the last 60 Kyr, we inferred at least three 15–25 Kyr‐long seismic cycles in which the recurrence times of earthquakes shortens from ∼5 to ∼2 Kyr.

This study examined whether an educational television show would affect young Haitian children’s gender perceptions. We first collected data on children’s beliefs about male and female characteristics and roles. Among 862 participating 6- and 7-year-olds from urban, peri-urban, and rural settings, we saw gender stereotypical beliefs about activities, traits, and occupations. We conducted a school-based intervention over a 10-week period, in which children were randomly assigned to watch a children’s television program in either of two groups: one that watched Lakou Kajou or one that watched Dora the Explorer. Each group saw 21 episodes of its assigned show, spread over 3 screenings of 7 episodes each. Lakou Kajou is an educational television show created in Haiti that purposely incorporates overt counter-stereotypical gender messaging. Among those children who watched Lakou Kajou and recalled more characters from the show, beliefs around gender became less stereotypical. In countries like Haiti, where pronounced gender disparities and biases exist, it is encouraging to see that a locally produced educational television show can change beliefs.

Remote sensing of spectral reflectance is a crucial parameter in precision agriculture. In particular, the visual color produced from reflected light can be used to determine plant health (VIS-IR) or attract pollinators (Near-UV). However, the UV spectral reflectance studies largely focus on non-crop plants, even though they provide essential information for plant-pollinator interactions. This literature review presents an overview of UV-reflectance in crops, identifies gaps in the literature, and contributes new data based on strawberry cultivars. The study found that most crop spectral reflectance studies relied on lab-based methodologies and examined a wide spectral range (Near UV to IR). Moreover, the plant family distribution largely mirrored global food market trends. Through a spectral comparison of white flowering strawberry cultivars, this study discovered visual differences for pollinators in the Near UV and Blue ranges. The variation in pollinator visibility within strawberry cultivars underscores the importance of considering UV spectral reflectance when developing new crop breeding lines and managing pollinator preferences in agricultural fields.

Conservation initiatives led by Indigenous peoples are a relatively recent phenomenon gaining momentum around the world. Initiatives to establish Indigenous protected areas are also taking root in Canada. We studied the Akumunan Biodiversity Reserve (ABR) in the province of Quebec to assess (1) the approach followed by the Essipit Innu First Nation (EIFN) Band Council to implement the ABR; (2) the EIFN’s vision that led to the creation of the ABR; and (3) the role the EIFN would like to play in the governance of the ABR. Six focus groups conducted with 22 community members have shown that the process which led to the creation of the ABR was fraught with challenges. The EIFN’s vision for the ABR is holistic — “everything” must be protected to respect the memory of the Elders and ensure natural resource sustainability. To ensure the respect of this vision, the community wants to play a leading role in governing the ABR. The EIFN faced many challenges, notably administrative hurdles, opposition due to cultural and value differences, lack of long-term funding, and disregard for the relationship that Indigenous people have with the land. Respecting EIFN’s vision also demands that traditional activities on the land be allowed to continue in protected areas, in order to guarantee that the identity, culture, health, and well-being of current and future generations will be maintained. The community management model developed by the EIFN Band Council provides useful insights on the process leading to the acknowledgement of the Indigenous Protected and Conserved Area status. Moreover, it could be a source of inspiration for other Indigenous conservation projects.

The COVID-19 pandemic provoked an urgency for many educators to integrate digital information and communication technologies in their educational practices. We explored how faculty members tackled the task of adapting their assessment practices during the pandemic to identify what is required to sustain and favour future quality development and implementation of e-assessment in higher education. Employing a qualitative descriptive approach, we conducted semi-structured interviews with thirty-one individuals six months into the COVID-19 pandemic. We identified four major themes in participants' discourse about the integration of e-assessment during the COVID-19 pandemic: (a) the considerations they had for the potential consequences on students and how they considered this while deciding how to move forward, (b) the preoccupations for the potential for cheating, (c) the importance of pedagogical alignment, and (d) the affordances available to them. While the COVID-19 pandemic highlighted the fact that higher education institutions were not prepared for a pivot to- or greater integration of- e-assessment, it also provided the tipping-point to do so. In other words, it offered an unprecedented opportunity to critically appraise and change assessment practices, this opportunity was also a very challenging balancing act of considering the social consequences of assessment, and the alignment within set affordances.

Assessment is more educationally effective when learners engage with assessment processes and perceive the feedback received as credible. With the goal of optimizing the educational value of assessment in medical education, we mapped the primary literature to identify factors that may affect a learner's perceptions of the credibility of assessment and assessment-generated feedback (i.e., scores or narrative comments). For this scoping review, search strategies were developed and executed in five databases. Eligible articles were primary research studies with medical learners (i.e., medical students to post-graduate fellows) as the focal population, discussed assessment of individual learners, and reported on perceived credibility in the context of assessment or assessment-generated feedback. We identified 4705 articles published between 2000 and November 16, 2020. Abstracts were screened by two reviewers; disagreements were adjudicated by a third reviewer. Full-text review resulted in 80 articles included in this synthesis. We identified three sets of intertwined factors that affect learners' perceived credibility of assessment and assessment-generated feedback: (i) elements of an assessment process, (ii) learners' level of training, and (iii) context of medical education. Medical learners make judgments regarding the credibility of assessments and assessment-generated feedback, which are influenced by a variety of individual, process, and contextual factors. Judgments of credibility appear to influence what information will or will not be used to improve later performance. For assessment to be educationally valuable, design and use of assessment-generated feedback should consider how learners interpret, use, or discount assessment-generated feedback.

The Go Red for Women movement was initiated by the American Heart Association (AHA) in the early 2000s to raise awareness concerning cardiovascular disease (CVD) risk in women. In 2016, the AHA funded 5 research centers across the United States to advance our knowledge of the risks and presentation of CVD that are specific to women. This report highlights the findings of the centers, showing how insufficient sleep, sedentariness, and pregnancy-related complications may increase CVD risk in women, as well as presentation and factors associated with myocardial infarction with nonobstructive coronary arteries and heart failure with preserved ejection fraction in women. These projects were augmented by collaborative ancillary studies assessing the relationships between various lifestyle behaviors, including nightly fasting duration, mindfulness, and behavioral and anthropometric risk factors and CVD risk, as well as metabolomic profiling of heart failure with preserved ejection fraction in women. The Go Red for Women Strategically Focused Research Network enhanced the evidence base related to heart disease in women, promoting awareness of the female-specific factors that influence CVD.

Executing flight operations demand that military personnel continuously perform tasks that utilize low- and high-order cognitive functions. The autonomic nervous system (ANS) is crucial for regulating the supply of oxygen (O2) to the brain, but it is unclear how sustained cognitive loads of different complexities may affect this regulation. Therefore, in the current study, ANS responses to low and high cognitive loads in hypoxic and normoxic conditions were evaluated. The present analysis used data from a previously conducted, two-factor experimental design. Healthy subjects (n = 24) aged 19 to 45 years and located near Fort Novosel, AL, participated in the parent study. Over two, 2-h trials, subjects were exposed to hypoxic (14.0% O2) and normoxic (21.0% O2) air while simultaneously performing one, 15-min and one, 10-min simulation incorporating low- and high-cognitive aviation-related tasks, respectively. The tests were alternated across five, 27-min epochs; however, only epochs 2 through 4 were used in the analyses. Heart rate (HR), HR variability (HRV), and arterial O2 saturation were continuously measured using the Warfighter MonitorTM (Tiger Tech Solutions, Inc., Miami, FL, USA), a previously validated armband device equipped with electrocardiographic and pulse oximetry capabilities. Analysis of variance (ANOVA) regression models were performed to compare ANS responses between the low- and high-cognitive-load assessments under hypoxic and normoxic conditions. Pairwise comparisons corrected for familywise error were performed using Tukey’s test within and between high and low cognitive loads under each environmental condition. Across epochs 2 through 4, in both the hypoxic condition and the normoxic condition, the high-cognitive-load assessment (MATB-II) elicited heightened ANS activity, reflected by increased HR (+2.4 ± 6.9 bpm) and decreased HRV (−rMSSD: −0.4 ± 2.7 ms and SDNN: −13.6 ± 14.6 ms). Conversely, low cognitive load (ADVT) induced an improvement in ANS activity, with reduced HR (−2.6 ± 6.3 bpm) and increased HRV (rMSSD: +1.8 ± 6.0 ms and SDNN: vs. +0.7 ± 6.3 ms). Similar observations were found for the normoxic condition, albeit to a lower degree. These within-group ANS responses were significantly different between high and low cognitive loads (HR: +5.0 bpm, 95% CI: 2.1, 7.9, p < 0.0001; rMSSD: −2.2 ms, 95% CI: −4.2, −0.2, p = 0.03; SDNN: −14.3 ms, 95% CI: −18.4, −10.1, p < 0.0001) under the hypoxic condition. For normoxia, significant differences in ANS response were only observed for HR (+4.3 bpm, 95% CI: 1.2, 7.4, p = 0.002). Lastly, only high cognitive loads elicited significant differences between hypoxic and normoxic conditions but just for SDNN (−13.3 ms, 95% CI, −17.5, −8.9, p < 0.0001). Our study observations suggest that compared to low cognitive loads, performing high-cognitive-load tasks significantly alters ANS activity, especially under hypoxic conditions. Accounting for this response is critical, as military personnel during flight operations sustain exposure to high cognitive loads of unpredictable duration and frequency. Additionally, this is likely compounded by the increased ANS activity consequent to pre-flight activities and anticipation of combat-related outcomes.

This observational pilot study examined the association between diet, meal pattern and glucose over a 2-week period under free-living conditions in 26 adults with dysglycemia (D-GLYC) and 14 with normoglycemia (N-GLYC). We hypothesized that a prolonged eating window and late eating occasions (EOs), along with a higher dietary carbohydrate intake, would result in higher glucose levels and glucose variability (GV). General linear models were run with meal timing with time-stamped photographs in real time, and diet composition by dietary recalls, and their variability (SD), as predictors and glucose variables (mean glucose, mean amplitude of glucose excursions [MAGE], largest amplitude of glucose excursions [LAGE] and GV) as dependent variables. After adjusting for calories and nutrients, a later eating midpoint predicted a lower GV (β = −2.3, SE = 1.0, p = 0.03) in D-GLYC, while a later last EO predicted a higher GV (β = 1.5, SE = 0.6, p = 0.04) in N-GLYC. A higher carbohydrate intake predicted a higher MAGE (β = 0.9, SE = 0.4, p = 0.02) and GV (β = 0.4, SE = 0.2, p = 0.04) in N-GLYC, but not D-GLYC. In summary, our data suggest that meal patterns interact with dietary composition and should be evaluated as potential modifiable determinants of glucose in adults with and without dysglycemia. Future research should evaluate causality with controlled diets.

Background Insufficient sleep is associated with increased cardiovascular disease risk, but causality is unclear. We investigated the impact of prolonged mild sleep restriction (SR) on lipid and inflammatory profiles. Methods and Results Seventy‐eight participants (56 women [12 postmenopausal]; age, 34.3±12.5 years; body mass index, 25.8±3.5 kg/m2) with habitual sleep duration 7 to 9 h/night (adequate sleep [AS]) underwent two 6‐week conditions in a randomized crossover design: AS versus SR (AS–1.5 h/night). Total cholesterol, low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol, triglycerides, and inflammatory markers (CRP [C‐reactive protein], interleukin 6, and tumor necrosis factor‐α) were assessed. Linear models tested effects of SR on outcomes in the full sample and by sex+menopausal status (premenopausal versus postmenopausal women+men). In the full sample, SR increased high‐density lipoprotein cholesterol compared with AS (β=1.2±0.5 mg/dL; P=0.03). Sex+menopausal status influenced the effects of SR on change in total cholesterol (P‐interaction=0.04), LDL‐C (P‐interaction=0.03), and interleukin 6 (P‐interaction=0.07). Total cholesterol and LDL‐C decreased in SR versus AS in premenopausal women (total cholesterol: β=−4.2±1.9 mg/dL; P=0.03; LDL‐C: β=−6.3±2.0 mg/dL; P=0.002). Given paradoxical effects of SR on cholesterol concentrations, we explored associations between changes in inflammation and end point lipids under each condition. Increases in interleukin 6 and tumor necrosis factor‐α during SR tended to relate to lower LDL‐C in premenopausal women (interleukin 6: β=−5.3±2.6 mg/dL; P=0.051; tumor necrosis factor‐α: β=−32.8±14.2 mg/dL; P=0.027). Conclusions Among healthy adults, prolonged insufficient sleep does not increase atherogenic lipids. However, increased inflammation in SR tends to predict lower LDL‐C in premenopausal women, resembling the “lipid paradox” in which low cholesterol associates with increased cardiovascular disease risk in proinflammatory conditions. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02835261, NCT02960776.

BackgroundPrevious studies have shown mixed results on the association between carbohydrate intake and insomnia. However, any influence that refined carbohydrates have on risk of insomnia is likely commensurate with their relative contribution to the overall diet, so studies are needed that measure overall dietary glycemic index (GI), glycemic load, and intakes of specific types of carbohydrates.ObjectiveWe hypothesized that higher GI and glycemic load would be associated with greater odds of insomnia prevalence and incidence.MethodsThis was a prospective cohort study with postmenopausal women who participated in the Women's Health Initiative Observational Study, investigating the relations of GI, glycemic load, other carbohydrate measures (added sugars, starch, total carbohydrate), dietary fiber, and specific carbohydrate-containing foods (whole grains, nonwhole/refined grains, nonjuice fruits, vegetables, dairy products) with odds of insomnia at baseline (between 1994 and 1998; n = 77,860) and after 3 y of follow-up (between 1997 and 2001; n = 53,069).ResultsIn cross-sectional and longitudinal analyses, higher dietary GI was associated with increasing odds of prevalent (fifth compared with first quintile OR: 1.11; CI: 1.05, 1.16; P-trend = 0.0014) and incident (fifth compared with first quintile OR: 1.16; CI: 1.08, 1.25; P-trend

Nightly fasting duration (NFD) and eating timing and frequency may influence cardiometabolic health via their impact on circadian rhythms, which are entrained by food intake, but observational studies are limited. This 1-year prospective study of 116 US women (33 ± 12y, 45% Hispanic) investigated associations of habitual NFD and eating timing and frequency with cardiovascular health (CVH; American Heart Association Life's Simple 7 score) and cardiometabolic risk factors. NFD, eating timing and frequency, and nighttime eating levels were evaluated from 1-week electronic food records completed at baseline and 1 y. In multivariable-adjusted linear regression models, longer NFD was associated with poorer CVH (β = -0.22, p = 0.016 and β = -0.22, p = 0.050) and higher diastolic blood pressure (DBP) (β = 1.08, p < 0.01 and β = 1.74, p < 0.01) in cross-sectional and prospective analyses, respectively. Later timing of the first eating occasion at baseline was associated with poorer CVH (β = -0.20, p = 0.013) and higher DBP (β = 1.18, p < 0.01) and fasting glucose (β = 1.43, p = 0.045) at 1 y. After adjustment for baseline outcomes, longer NFD and later eating times were also associated with higher waist circumference (β = 0.35, p = 0.021 and β = 0.27, p < 0.01, respectively). Eating frequency was inversely related to DBP in cross-sectional (β = -1.94, p = 0.033) and prospective analyses (β = -3.37, p < 0.01). In cross-sectional analyses of baseline data and prospective analyses, a higher percentage of daily calories consumed at the largest evening meal was associated with higher DBP (β = 1.69, p = 0.046 and β = 2.32, p = 0.029, respectively). Findings suggest that frequent and earlier eating may lower cardiometabolic risk, while longer NFD may have adverse effects. Results warrant confirmation in larger multi-ethnic cohort studies with longer follow-up periods.

Abstract We have previously shown that neoadjuvant chemotherapy can induce the degradation of tumour ribosomal RNA (rRNA) in patients with advanced breast cancer, a phenomenon we termed “RNA disruption”. Extensive tumour RNA disruption during chemotherapy was associated with a post-treatment pathological complete response and improved disease-free survival. The RNA disruption assay (RDA), which quantifies this phenomenon, is now being evaluated for its clinical utility in a large multinational clinical trial. However, it remains unclear if RNA disruption (i) is manifested across many tumour and non-tumour cell types, (ii) can occur in response to cell stress, and (iii) is associated with tumour cell death. In this study, we show that RNA disruption is induced by several mechanistically distinct chemotherapy agents and report that this phenomenon is observed in response to oxidative stress, endoplasmic reticulum (ER) stress, protein translation inhibition and nutrient/growth factor limitation. We further show that RNA disruption is dose- and time-dependent, and occurs in both tumourigenic and non-tumourigenic cell types. Northern blotting experiments suggest that the rRNA fragments generated during RNA disruption stem (at least in part) from the 28S rRNA. Moreover, we demonstrate that RNA disruption is reproducibly associated with three robust biomarkers of cell death: strongly reduced cell numbers, lost cell replicative capacity, and the generation of cells with a subG1 DNA content. Thus, our findings indicate that RNA disruption is a widespread phenomenon exhibited in mammalian cells under stress, and that high RNA disruption is associated with the onset of cell death.

A meta-analysis of 17 cohorts of mitochondrial disease patients reveals that OxPhos defects are associated with signs of hypermetabolism. Experiments in patient-derived fibroblast show that mitochondrial OxPhos defects trigger hypermetabolism in a cell-autonomous manner and this is linked to accelerated telomere shortening and epigenetic aging.