OBJECTIVE: To better understand the effects of aging, metabolic syndrome, diurnal variation, and seasonal variation on serum testosterone levels in the context of current guideline statements on testosterone deficiency.
METHODS: This cross-sectional study utilized the United Kingdom Biobank. Physical examination, anthropomorphic measurements, and laboratory evaluation were performed at the time of enrollment from 2006 to 2010. The primary outcomes were the effect of age, the presence of metabolic syndrome, the time of day, and the month of the year on serum testosterone levels.
RESULTS: Among 197,883 included men, the 5th, 25th, 50th, 75th and 95th percentile testosterone levels in men without metabolic syndrome were significantly higher than those in men with metabolic syndrome at every decade of life (p < 0.001). The average testosterone level within each group (men without metabolic syndrome vs. men with) was clinically similar across decade of life (12.43 in 40\'s 12.29 in 50\'s 12.24 in 60\'s vs. 10.69 in 40\'s 10.56 in 50\'s 10.63 in 60\'s respectively). Average testosterone levels decreased with blood draws later in the day ranging from 10.91 to 12.74 nmol/L (p < 0.01). Similarly, there was seasonal variation in serum testosterone ranging from 11.86 to 12.18 nmol/L (p < 0.01).
CONCLUSIONS: We found significant variation in serum testosterone according to the presence of metabolic syndrome and time of laboratory draw, but not according to age. These data challenge the prior dogma of age-related hypogonadism and favor an individualized approach towards serum testosterone measurement and interpretation. However, further studies are needed to correlate these population-based data with individuals\' hypogonadal symptoms.

Background The diurnal variation of testosterone in women has received limited attention, despite its growing recognition as a crucial factor in female health and well-being. This study aims to investigate the diurnal fluctuations of total testosterone levels in apparently healthy women with regular menstrual cycles. Methodology A cross-sectional study was conducted at Faiha Specialized Diabetes Endocrine and Metabolism Center in July 2023. This study involved 46 apparently healthy women volunteers aged between 21 and 40 years. To explore diurnal variations in total testosterone, blood samples were collected from each participant at two distinct time points, i.e., 8:30 AM and 1:30 PM. These samples were collected regardless of fasting status with the exclusion of the menstruating phase. Results The mean total testosterone level at 8:30 AM was 23.4 ± 12.4 ng/dL and at 1:30 PM was 21.7 ± 12.9 ng/dL, with a p-value of 0.03. Neither age nor body mass index demonstrated a significant impact on testosterone levels. Conclusions This study showed a significant diurnal variation in serum total testosterone levels among apparently healthy women, with higher levels observed in the morning.

Remote sensing of Solar-induced chlorophyll fluorescence (SIF) has been widely used in estimating Gross Primary Productivity (GPP) and detecting stress in terrestrial ecosystems. Water stress adversely impacts the growth, development, and productivity of a plant. Recently, the characterizing and understanding of the diurnal cycling of plant functioning and ecosystem processes has been explored using SIF. However, the diurnal response of SIF to different levels of water stress remains unclear. This study conducted field experiments on winter wheat by subjecting it to different levels of water stress including well-watered (CK) and, mild, moderate, and severe water stress (D1, D2, D3), and collected the spectral data using an automated SIF measurement system. The results observed the strong SIF-PAR (photosynthetically active radiation) correlations and that these relationships gradually decoupled with increasing water stress, which further decreased the accuracy of temporal upscaling of far-red SIF from an instantaneous to daily scale. To quantify the characteristics of diurnal far-red SIF, five indices including peak time, peak value, curve opening coefficient (leading coefficient of the parabola), and left/right slopes of the peak were proposed. The results demonstrated that diurnal far-red SIF was characterized by an earlier peak time, decreasing peak value, wider curve opening, and flattening right slope from the CK plot to the D3 plot. There were certain mechanisms linking the different indices, for example, between peak size and opening coefficient. Furthermore, the response of far-red SIF to water stress was most pronounced at noon. SIF/PAR exhibited a more significant response to varying water stress compared to far-red SIF, which mitigated the negative influence of PAR variations on diurnal SIF. These findings contribute to the monitoring of plant water dynamics at fine temporal scales.

OBJECTIVE: To prospectively investigate the determinants of diurnal variations in lumbar intervertebral discs and paraspinal muscles.
METHODS: 71 females aged 19 ∼ 31 years were examined by morning-evening T2 mapping/diffusion kurtosis imaging (DKI), with weight and lifestyle information (time in night bed-rest [TIB], bed-napping, activity time, and sitting time) assessed by standardized questionnaires. Diurnal shifts in T2, mean diffusivity and mean kurtosis (T2-DS, MD-DS and MK-DS; morning-value minus evening-value) were evaluated for L4-S1 discs (normal, Pfirrmann grade Ⅰ/Ⅱ; degenerative, III/IV). T2 and T2-DS were assessed for L4/5 multifidus and erector spinalis.
RESULTS: For normal discs, bed-napping correlated with MD-DS and MK-DS in disc entirety (p = 0.001 and 0.004); increased activity time suggested higher T2-DS in nucleus pulposus (p = 0.004); prolonged sitting time predicted greater T2-DS in disc entirety and posterior inner annulus fibrosus (PI-AF, p ≤ 0.011); decreased TIB and weight suggested lower T2-DS and higher MK-DS in PI-AF (p = 0.001 ∼ 0.035). For degenerative discs, bed-napping predicted lower T2-DS in nucleus pulposus and PI-AF (p = 0.019); increased TIBsuggested higher T2-DS and lower MK-DS in PI-AF (p = 0.006 and 0.034); longer sitting time predicted higher MK-DS in PI-AF (p = 0.020). Paraspinal muscles exhibited diurnal T2 variation (p < 0.001) which did not correlate with lifestyle factors (p > 0.050).
CONCLUSIONS: Lifestyle and weight have causal effects on the diurnal variation of lumbar discs. Bed-rest may correlate with disc hydration and microstructural stability reserves for subsequent daytime activities. Sitting behavior could induce greater dehydration in normal discs and may alleviate diurnal microstructural rearrangement in degenerative discs. T2 mapping and DKI are promising tools to evaluate disc biomechanics in clinics.

Few functional measures related to time-trial display diurnal variation. The diversity of tests/protocols used to assess time-trial performance on diurnal effects and the lack of a standardised approach hinder agreement in the literature. Therefore, the aims of the present study were to investigate and systematically review the evidence relating to time-of-day differences in time-trial measures and to examine the main aspects related to research design important for studies of a chronobiological nature. The entire content of Manipal Academy of Higher Education electronic library and Qatar National Library, and electronic databases: PubMed (MEDLINE), Scopus and Web of Science were searched. Research studies published in peer-reviewed journals and non-peer reviewed studies, conducted in male adult participants aged ≥18 y before November 2021 were screened/included. Studies assessing tests related to time-trials in any modality between a minimum of 2 time-points during the day (morning [06:30-10:30 h] vs evening [14:30-20:00 h]) were deemed eligible. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used to assess the evidence to inform recommendations. The primary search revealed that a total of 10 from 40 articles were considered eligible and subsequently included. Six were conducted using cycling, two using running and two using swimming as the mode of exercise. Distances ranged from 1 to 16.1-km in distance or 15 to 20-min time in the cycling and running time-trials, and 50 to 200-m in the swimming time-trials. Only four studies found one or several of their performance variables to display daily variations, with significantly better values in the evening; while six studies found no time-of-day significance in any variables assessed. The magnitude of difference ranged from 2.9% to 7.1% for performance time to complete a cycling time-trial, while running and swimming did not find any differences for performance time. Power output during a 16.1-km time trial in cycling also found evening performance to be significantly better by 10%. The only other observed differences were stroke rate and stroke length during a swimming time-trial and stroke rate (cycles.min-1) during a cycling time-trial. The magnitude of difference is dependent on exercise modality, individual chronotype, the training status of the individual and sample size differences. The lack of diurnal variation present in the majority of studies can in-part be explained with some of the methodological limitations and issues present related to quality and control. It is paramount that research assessing diurnal variation in performance uses appropriate session timings around the core body temperature minimum (~05:00 h; morning) and maximum (~17:00 h; evening). Although, differences in motivation/arousal, habitual training times, chronotypes and genotypes could provide an explanation as to why some studies/variables did not display time-of-day variation, more work is needed to provide an accurate conclusion. There is a clear demand for a rigorous, standardised approach to be adopted by future investigations which control factors that specifically relate to investigations of time-of-day, such as appropriate familiarisation, counterbalancing the order of administration of tests, providing sufficient recovery time between sessions and testing within a controlled environment.

Much evidence on the adverse health effects of endocrine-disrupting chemicals (EDCs) has accumulated during recent decades. EDCs are commonly found in various foods and personal care products (PCP). Data documenting a diurnally varying EDC metabolism in humans is scarce. This study examined (i) the time-of-day effect on the diurnal magnitude and variance of urinary biomarkers of exposure to EDCs, and (ii) the association between EDC exposures and oxidative damage in a Norwegian adult subpopulation. This was a cross-sectional panel study using biobanked samples from the EuroMix project. During a typical weekday, participants were asked to collect all day’s urine voids and record dietary and PCP habitual uses in a diary. Collected time stamps of urine voids were classified into three distinct periods in the day (morning 6 a.m.−12 p.m., mid-day 12 p.m.−6 p.m., evening 6 p.m.−6 a.m.). Questionnaires regarding demographic characteristics, personal care product usage, and dietary habits were completed. Urinary levels of EDCs (phthalates, parabens, and bisphenols) were measured using mass spectrometry and adjusted for urinary volume using specific gravity. Urinary 4-hydroxynonenal (4HNE), a lipid peroxidation marker, was measured using an immunoassay kit. Linear mixed-effect models identified EDCs under the influence of a diurnal variation effect that was adjusted for dietary habits and PCP use and examined associations between EDC and 4HNE. p-values were FDR-adjusted. Most phthalates appeared to be diurnally varying with higher urinary levels towards the evening (q < 0.001) than those measured during mid-day; this strong diurnal variation effect was not present for parabens and bisphenols. Significant (q < 0.001) positive associations were observed between all phthalates, parabens, and bisphenols (except bisphenol S) and 4HNE. This study’s findings highlighted the diurnal variation of excretion for certain EDC, but not for others, in real-life conditions. The degree of EDC chronotoxicity in distinct diurnal windows of the day warrants further investigation with longitudinal human studies.

Diffusing capacity for carbon monoxide (DLCO) was measured in a phase I single ascending dose study after inhalation of AZD8154 or placebo in healthy participants at baseline (DLCOBaseline) and follow-up (DLCOFollow-up) 6 days after dosing. Initially, DLCOFollow-up timepoint was 2 h earlier than the DLCOBaseline timepoint and clinically significant decreases in DLCOFollow-up (absolute change up to 19% from baseline and DLCO%predicted values less than 70) were observed then. The observed reduction in DLCOFollow-up was confirmed as a false positive finding after alignment of DLCO timings. As a consequence, when DLCO is used in clinical studies, measurements should be strictly standardized in relation to time of the day.

Amino acid neurotransmitters are responsible for many physiological and pathological processes, and their cerebral concentrations respond to external influences such as the light-dark cycle and to the synthesis, release, and recapture rhythms and form part of the biochemical relationships derived from excitatory-inhibitory (E/I), glutamine-glutamate sum (GLX), glutamatergic processing (glutamine-glutamate ratio) and excitotoxic indexes. The changes in these variables during a 24-h period (1 day) are important because they allow organisms to adapt to external stimuli and form part of physiological processes. Under pathological conditions, the damage produced by acute events may depend on diurnal variations. Therefore, it is important to analyze the extracellular levels of amino acids as well as the above-mentioned indexes over a 24-h period. We focused on determining the cerebrospinal fluid levels of different amino acid neurotransmitters, and the E/I, GLX, glutamatergic processing and excitotoxic indexes, determined by microdialysis over a 24-h cycle. Our results showed significant changes during the 24-h light/dark cycle. Specifically, we found increments in the levels of glutamate (325%), GABA (550%), glutamine (300%), glycine (194%), alanine (304%) and the GLX index (263%) throughout the day, and the maximum levels of glutamate, glutamine, glycine, and alanine were obtained during the last period of the light period. In conclusion, the concentration of some amino acid neurotransmitters and the GLX index show variations depending on the light-dark cycle.

Although childhood adversity (CA) increases risk for subsequent mental illnesses, developmental mechanisms underpinning this association remain unclear. The hypothalamic-pituitary-adrenal axis (HPAA) is one candidate system potentially linking CA with psychopathology. However, determining developmental effects of CA on HPAA output and differentiating these from effects of current illness has proven difficult. Different aspects of HPAA output are governed by differentiable physiological mechanisms. Disaggregating HPAA output according to its biological components (baseline tonic cortisol, background diurnal variation, phasic stress response) may improve precision of associations with CA and/or psychopathology. In a novel proof-of-principle investigation we test whether different predictors, CA (distal risk factor) and current depressive symptoms, show distinct associations with dissociable HPAA components. A clinical group (aged 16-25) at high-risk for developing severe psychopathology (n = 20) were compared to age and sex matched healthy controls (n = 21). Cortisol was measured at waking (x4), following stress induction (x8), and during a time-environment-matched non-stress condition. Using piecewise multilevel modeling, stress responses were disaggregated into increase and decrease, while controlling for waking cortisol, background diurnal output and confounding variables. Elevated waking cortisol was specifically associated with higher CA scores. Higher non-stress cortisol was specifically associated with higher depressive scores. Following stress induction, depressive symptoms attenuated cortisol increase, whilst CA attenuated cortisol decrease. The results support a differential HPAA dysregulation hypothesis where physiologically dissociable components of HPAA output are differentially associated with distal (CA) or proximal (depressive symptoms) predictors. This proof-of-principle study demonstrates that future cortisol analyses need to disaggregate biologically independent mechanisms of HPAA output.