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INTRODUCTION: Insufficient sleep increases the risk of weight gain and metabolic dysfunction, while obesity is linked to disrupted sleep and metabolic impairment. Although both conditions are tightly interconnected, it remains unclear whether body weight status determines how acute sleep loss alters metabolite levels. We aimed to assess whether acute sleep loss elicits different metabolic responses in individuals with and without obesity, and whether these responses are modified by sex.

METHODS: In a within-subject, randomized crossover study, 42 adults (mean age 24.9 years; 18 women, 24 men; 18 with obesity; 24 with normal weight) completed one night of total sleep deprivation (TSD) and one night of normal sleep (NS; 8 h). Morning fasted blood samples were analyzed using targeted metabolomics. Mixed-effects models were used to assess within-individual changes from NS to TSD, and to determine the magnitude and direction of these changes within each body weight group and sex.

RESULTS: In response to TSD compared with NS, tryptophan levels increased (+12%, FDR < 0.05) only in participants with obesity, while histidine, L-kynurenine, and creatinine levels decreased (4-21%, FDR < 0.05) only in normal-weight individuals. Notably, the kynurenine-to-tryptophan ratio decreased after TSD in both groups, and levels of circulating medium-chain acylcarnitines (+26-39%) increased within both weight groups - together indicating shared metabolic responses to acute sleep deprivation. Exploratory sensitivity analyses indicated that several of these responses were sex-specific. Polysomnography-based sleep architecture during NS, available in a subset of 36 participants, was largely comparable between body weight groups, suggesting that observed metabolic differences were not attributable to baseline differences in sleep structure.

CONCLUSIONS: Acute sleep loss elicits both shared and body-weight-specific changes in circulating metabolites in young adults. These findings indicate that body-weight status shapes which metabolic pathways respond to a single night of sleep loss, and in what direction, but larger studies are required to confirm the body weight- and sex-specific findings. Given that acute sleep loss is a common metabolic stressor that increases cardiometabolic risk, these differences may contribute to mechanistic hypotheses about the heightened vulnerability to metabolic dysregulation in individuals with obesity who are frequently exposed to sleep loss.

UNLABELLED: Accurate evaluation of kidney function is vital in the pediatric intensive care unit (PICU), where even small changes in cystatin C and creatinine concentrations can affect clinical decision-making. Diurnal patterns in renal biomarkers have been reported in adults, but their relevance in critically ill children remains unclear. Understanding whether sampling time contributes to biological variability is essential for reliable interpretation of kidney function tests. This retrospective study included 8619 cystatin C and 9314 creatinine results collected in a tertiary PICU between April 2014 and September 2025. The hourly distribution of sampling and hourly biomarker percentiles (0.10, 0.25, and 0.50) were evaluated across the 24-h cycle. Diurnal variation was quantified using coefficients of variation (CVs). Sampling was strongly clustered in the early morning, with 38.6% of cystatin C and 37.4% of creatinine samples drawn at 5:00-5:59 AM. The 0.10-0.50 percentiles of cystatin C showed minimal diurnal variation (CV 4.5-6.3%). Creatinine exhibited slightly greater variability, with CVs of 7.4-11.6% across the same percentiles. Median creatinine was significantly higher in the afternoon/evening than in the early morning, while cystatin C showed no clinically relevant hourly fluctuations.

CONCLUSION: In critically ill children, cystatin C demonstrates limited diurnal variation, while creatinine shows modest but measurable fluctuations across the 24-h period. These findings suggest that cystatin C is relatively robust to sampling time in the PICU, whereas creatinine may vary enough to influence interpretation in borderline cases. Incorporating knowledge of sampling time may improve the accuracy of kidney function assessment and AKI classification in pediatric critical care.

WHAT IS KNOWN: • Creatinine and cystatin C can show biological and circadian variability in adults and older children, with creatinine generally exhibiting greater within-day fluctuation than cystatin C.

WHAT IS NEW: • In critically ill children, cystatin C shows minimal diurnal variation, whereas creatinine displays modest but measurable time-of-day-related increases, indicating that sampling time may influence creatinine interpretation but not cystatin C in the PICU setting.

Background: Tacrolimus is a key immunosuppressive drug used to prevent organ rejection after transplantation. Its narrow therapeutic window and high interindividual pharmacokinetic variability make therapeutic drug monitoring (TDM) essential. This study aimed to (1) characterize long-term trends in tacrolimus concentrations; (2) assess potential seasonal variation; and (3) evaluate the suitability of patient medians as a tool for laboratory quality monitoring. Methods: A retrospective analysis was conducted on 113,735 tacrolimus whole-blood results obtained between 2006 and 2024 at Uppsala University Hospital, Sweden. Samples were analyzed using immunoassays on the Hitachi 912 (Microgenics) until 2008, the Abbott Architect until 2021, and the Roche Cobas Pro e 801 thereafter. Annual patient medians and percentiles (10th, 25th, 50th, 75th, and 90th) were calculated. Seasonal variation was assessed by comparing monthly test volumes and concentration distributions. Results: The annual number of tacrolimus results increased from 5616 in 2006 to 7320 in 2024, comprising 67,133 male and 46,602 female patient results. All distribution metrics declined steadily over the study period, with median tacrolimus concentrations decreasing by 20–30%. The July test volume was approximately 15% lower than in other months, but no meaningful seasonal variation in tacrolimus concentrations was observed; monthly medians and percentiles remained stable throughout the year. Conclusions: Tacrolimus concentrations at the population level have decreased consistently over nearly two decades. These findings likely reflect evolving clinical practice, including dose minimization strategies to reduce toxicity. Patient medians proved robust over time and may serve as a useful adjunct to conventional quality control, particularly when commercial control materials do not fully mimic patient sample behavior.

Shift workers exhibit a higher incidence of coronary heart disease (CHD) than daytime workers. We examined whether this difference in CHD incidence between shift workers and daytime workers is associated with two dietary factors linked to lower CHD risk-daily fiber intake and meat avoidance-using UK Biobank data. The study included 222,801 participants (53.8% women; mean age 52.6 years), categorized as daytime workers, shift workers with no or occasional night shifts, or regular night shift workers. Dietary habits were assessed via touchscreen dietary questionnaires. During a median follow-up of 12.6 years, 12,265 fatal and non-fatal CHD events occurred. Compared with daytime workers, regular night shift work-but not shift work with no or occasional night shifts-was associated with higher CHD incidence (hazard ratio [HR] 1.10, 95% CI 1.01-1.20). HRs for CHD were higher (vs. daytime work) in both shift work groups among participants with lower daily fiber intake, whereas they were attenuated among those with higher fiber intake (p < 0.05 for interaction). Meat avoidance was associated with a 10.4% lower CHD HR compared with meat consumption (p = 0.020), although no significant interaction with work schedule was observed. In summary, while our finding that meat avoidance is associated with modestly lower CHD HR across work schedules aligns with established cardiovascular recommendations, our observation that higher fiber intake may reduce CHD differences specifically linked to night shift work highlights an additional, shift-specific dietary consideration that could complement the American Heart Association's Life's Essential 8.

Circadian rhythms coordinate physiology with the 24 h light-dark cycle, and their disruption contributes to diseases spanning metabolic, cardiovascular, and neuropsychiatric domains. Whether the temporal coherence between wearable-derived activity and temperature rhythms predicts long-term health outcomes in free-living humans remains unknown. Analyzing week-long concurrent wrist-worn acceleration and device temperature recordings from approximately 90000 UK Biobank participants, the authors decomposed the circular cross-correlation between behavioral and device temperature signals into three alignment features: 24 h coupling strength (M24), phase deviation from expected antiphase (D24), and 12 h harmonic magnitude (M12). Over 7-11 years of follow-up, higher M24 was associated with lower risk of type 2 diabetes, cardiovascular disease, depression, sleep apnea, and all-cause mortality, whereas higher D24 was associated with increased cardiometabolic risk. Higher M12 was associated with lower risk of gastrointestinal and psychiatric conditions. Replication in the SHARE cohort supported the portability of the feature-extraction framework. These findings identify wearable-derived cross-domain diurnal alignment as a scalable prospective predictor of disease risk with implications for population health surveillance.

Chronic sleep disruption and shift work elevate the risk of neurodegeneration and Alzheimer's disease (AD). While disrupted sleep affects canonical AD biomarkers, its impact on other mechanisms, such as circulating microRNAs (miRNAs), remains less understood. Therefore, we here examined the effects of overnight wakefulness on plasma levels of several miRNAs implicated in neurodegeneration and AD, as well as in sleep and circadian regulation-namely miR-127-3p, miR-132-3p, and miR-142-3p. Following a baseline period in each highly controlled in-lab session, in total 15 healthy normal-weight young men underwent two conditions on separate occasions, in randomised order: a night of normal sleep, and a night of sustained wakefulness. After overnight wakefulness, morning plasma levels of miR-127-3p and miR-142-3p were significantly elevated compared with post-sleep levels. These changes were not associated with the significant increase in self-reported morning stress levels observed after wakefulness compared with sleep. This study is the first to demonstrate that a single night of wakefulness-mimicking overnight shift work-significantly elevates circulating levels of miR-127-3p and miR-142-3p in humans. These findings, though based on a limited sample size, suggest a potential molecular link between sleep loss and neurodegeneration, warranting further investigation. Trial Registration: Clinical Trial number: NCT01800253; www.clinicaltrials.gov.

BACKGROUND: Lifestyle choices, such as dietary patterns and sleep duration, significantly impact the health of the digestive system and may influence the risk of mortality from digestive system cancer.

METHODS: This study aimed to examine the associations between sleep duration, dietary habits, and mortality from digestive system cancers. The analysis included 406,584 participants from the UK Biobank cohort (54.1% women; age range: 38-73 years), with sleep duration classified as short (≤ 6 h, 24.2%), normal (7-8 h, 68.4%), and long (≥ 9 h, 7.4%). Healthy eating habits were defined as a daily intake of at least 25 g of fibre, seven portions of fruits and vegetables, and fewer than four servings of meat per week. These dietary factors were combined into a score ranging from 0 (least healthy) to 3 (healthiest). Cox proportional hazards regression analyses were conducted, with a median follow-up period of 12.6 years, ending on September 30, 2021.

RESULTS: 3949 participants died from cancer of the digestive system. Both short and long sleep duration were associated with an increased risk of mortality from cancer of the digestive system (1.09 (1.01-1.18) and 1.14 (1.03-1.27), respectively). Additionally, a diet score ≥ 1 was linked to a lower cancer risk (0.72-0.91 (0.59-0.96)). Adjusting for smoking, type 2 diabetes, and body mass index (BMI) status eliminated the association between sleep duration and digestive cancer mortality. The association between healthy dietary patterns and the risk of digestive system cancer mortality did not vary by sleep duration.

CONCLUSIONS: Aberrant sleep durations may increase the risk of mortality from digestive system cancer, potentially through smoking, higher BMI, and type 2 diabetes. However, aberrant sleep durations do not seem to reduce the protective effects of a healthy dietary pattern.

Background

Hypersomnolence, defined as excessive daytime sleepiness (EDS), excessive quantity of sleep (EQS), sleep inertia, and fatigue reduce quality of life. We assessed associations of the COVID-19 pandemic, infection without long-term sequalae (short COVID, SC), and long COVID (LC) on hypersomnolence and fatigue in a large population across different countries.

Methods

As part of an online questionnaire (ICOSS-2), we assessed EDS via the Epworth Sleepiness Scale (ESS), fatigue via Fatigue Severity Scale (FSS), and sleep duration at night and per 24 h. We also assessed the associations with EDS, sleep inertia, fatigue and napping by their frequencies, during the pandemic in COVID-negative, SC and LC participants.

Results

The final cohort comprised 13,656 participants (69.1 % women, 42.7 ± 16.6 years), with 12.4 % classified SC and 7.5 % LC. ESS scores were higher in LC (9.16, 95 % CI [8.78, 9.53]) compared to SC (7.26, [6.97, 7.55]) and COVID-negative (6.53, [6.43, 6.63]). LC also had higher odds of ESS>10 (OR 1.58, [1.18,2.09]). FSS scores were higher in LC (median 51, IQR 39–59) than SC (34, 25–44) and COVID-negative (35, 25–45), with LC having 2.22 higher odds of severe fatigue. LC cases also reported more EQS (≥10/24 h) than COVID-negative. Worsening of EDS, fatigue, sleep inertia, and napping was reported during pandemic to a greater extent in LC.

Conclusions

LC was associated with higher levels of hypersomnolence and fatigue than in SC or COVID-negative participants, highlighting the need for interventions and future research focusing on sleep symptoms and their relation to long-term health outcomes.