Search Results (1,038)

The rhythm of epileptiform activity occurs in various brain injuries (ischemia, stroke, concussion, mechanical damage, AD, PD). The epileptiform rhythm is accompanied by periodic Ca²⁺ pulses, which are necessary for the neurotransmitter release, the repair of damaged connections between neurons, and the growth of new projections. The duration and amplitude of these pulses depend on intracellular calcium-binding proteins. The effect of the synthetic fast calcium buffer BAPTA on the epileptiform activity of neurons induced by the GABA(A)-receptor inhibitor, bicuculline, was investigated in a 14-DIV rat hippocampal culture. In the epileptiform activity mode, neurons periodically synchronously generate action potential (AP) bursts in the form of paroxysmal depolarization shift (PDS) clusters and their corresponding high-amplitude Ca²⁺ pulses. Changes in the paroxysmal activity and Ca²⁺ pulses were recorded continuously for 10–11 min as BAPTA accumulated. It was shown that during BAPTA accumulation, transformation of neuronal patch activity occurs. Moreover, GABAergic and glutamatergic neurons respond differently to the presence of calcium buffer. Experiments were performed on two populations of neurons: a population of GABAergic neurons that responded selectively to ATPA, a calcium-permeable GluK1 kainate receptor agonist, and a population of glutamatergic neurons with a large amplitude of cluster depolarization (greater than −20 mV). These neurons made up the majority of neurons. In the population of GABAergic neurons, during BAPTA accumulation, the amplitude of PDS clusters decreases, which leads to a switch from the PDS mode to the classical burst mode with an increase in the electrical activity of the neuron. In glutamatergic neurons, the duration of PDS clusters decreased during BAPTA accumulation. However, the amplitude changed little. The data obtained showed that endogenous calcium-binding proteins play a significant role in switching the epileptiform rhythm to the recovery rhythm and perform a neuroprotective function by reducing the duration of impulses in excitatory neurons and the amplitude of impulses in inhibitory neurons. Full article

The activation mechanism of the reproductive axis in Kazakh ewes during the non-breeding season was explored by supplementation with glycerol complex (7% glycerol + tyrosine + vitamin B9). The experiment divided 50 ewes into five groups (n = 10). After 90 days of intervention, it was found that significant changes in serum DL-carnitine, N-methyl-lysine and other differential metabolites were observed in the GLY-Tyr-B9 group (p < 0.05, “p < 0.05” means significant difference, “p < 0.01” means “highly significant difference”). The bile acid metabolic pathway was specifically activated (p < 0.01). The group had a 50% estrus rate, ovaries contained 3–5 immature follicles, and HE staining showed intact granulosa cell structure. Serum E2/P4 fluctuated cyclically (p < 0.01), FSH/LH pulse frequency increased (p < 0.01), peak Glu/INS appeared on day 60 (p < 0.05), and LEP was negatively correlated with body fat percentage (p < 0.01). Molecular mechanisms revealed: upregulation of hypothalamic kiss-1/GPR54 expression (p < 0.01) drove GnRH pulses; ovarian CYP11A1/LHR/VEGF synergistically promoted follicular development (p < 0.05); the HSL of subcutaneous fat was significantly increased (p < 0.05), suggesting involvement of lipolytic supply. Glycerol activates the reproductive axis through a dual pathway—L-carnitine-mediated elevation of mitochondrial β-oxidation efficacy synergizes with kisspeptin/GPR54 signalling enhancement to re-establish HPO axis rhythms. This study reveals the central role of metabolic reprogramming in regulating seasonal reproduction in ruminants. Full article

Understanding how prey and predator species partition activity patterns across time and space is essential for elucidating behavioral adaptation and ecological coexistence. In this study, we examined the diel and seasonal activity rhythms of two sympatric rodent species—Rhombomys opimus (Great gerbil) and Meriones meridianus (Midday gerbil)—and their primary predators, Otocolobus manul (Pallas’s cat) and Vulpes vulpes (Red fox), in a desert-steppe ecosystem on the northern slopes of the Qilian Mountains, China. Using over 8000 camera trap days and kernel density estimation, we quantified their activity intensity and spatiotemporal overlap. The two rodent species showed clear temporal niche differentiation but differed in their synchrony with predators. R. opimus exhibited a unimodal diurnal rhythm with spring activity peaks, while M. meridianus showed stable nocturnal activity with a distinct autumn peak. Notably, O. manul adjusted its activity pattern to partially align with that of R. opimus, whereas V. vulpes maintained a crepuscular–nocturnal rhythm overlapping more closely with that of M. meridianus. Despite distinct temporal rhythms, both rodent species shared high spatial overlap with their predators (overlap index OI = 0.64–0.83). These findings suggest that temporal partitioning may reduce predation risk for R. opimus, while M. meridianus co-occurs more extensively with its predators. Our results highlight the ecological role of native carnivores in rodent population dynamics and support their potential use in biodiversity-friendly rodent management strategies under arid grassland conditions. Full article

Background/Objectives: Rest–activity rhythm (RAR) disturbances can contribute to aging and dementia via metabolic dysregulation. Hydroxycholesterol (OH) is thought to mediate the link between hypercholesterolemia and neurodegeneration. This study compared sleep and RAR parameters between amnestic mild cognitive impairment (aMCI) patients and normal controls (NCs), and examined their associations with plasma 27-OH levels, reflecting peripheral cholesterol metabolism. Methods In total, 18 aMCI patients (76.6 ± 6.1 years) and 21 NCs (70.4 ± 6.7 years) underwent five-day actigraphy and dim light melatonin onset assessment. Plasma 27-OH levels were measured via high-performance liquid chromatography-mass spectrometry. Generalized linear models (GLMs) were used to analyze the relationships between sleep, RAR, and 27-OH levels. Results: The aMCI group had significantly lower 27-OH levels and 27-OH/total cholesterol ratios (p < 0.05). GLM revealed that longer sleep onset latency (SOL) was associated with higher 27-OH levels in aMCI, distinguishing them from NCs. Additionally, in aMCI, longer SOL, lower sleep efficiency (SE), and higher fragmentation index (FI) were associated with an increased 27-OH/total cholesterol ratio (p < 0.05). Higher relative amplitude of RAR was linked to lower 27-OH levels across groups (p < 0.01), but RAR parameters showed no significant association with the 27-OH/total cholesterol ratio. Sleep disturbances, including prolonged SOL, reduced SE, and increased FI, were associated with altered peripheral cholesterol oxygenation in aMCI. Conclusions: Greater RAR amplitude correlated with lower 27-OH levels, regardless of cognitive status. These findings suggest that peripheral cholesterol oxygenation in aMCI is related to both sleep disturbances and circadian rhythm dysregulation, highlighting their role in cholesterol metabolism and neurodegeneration. Full article

Disruption of circadian rhythms by abnormal light exposure and reduced melatonin secretion has been linked to heightened pain sensitivity and opioid tolerance. This study evaluated how environmental light manipulation and exogenous melatonin supplementation influence pain perception and morphine tolerance in a rat model of neuropathic pain induced by partial sciatic nerve transection (PSNT). Rats were exposed to constant darkness, constant light, or a 12 h/12 h light–dark cycle for one week before PSNT surgery. Behavioral assays and continuous intrathecal (i.t.) infusion of morphine, melatonin, or their combination were conducted over a 7-day period beginning immediately after PSNT. On Day 7, after discontinued drugs infusion, an acute intrathecal morphine challenge (15 µg, i.t.) was administered to assess tolerance expression. Constant light suppressed melatonin levels, exacerbated pain behaviors, and accelerated morphine tolerance. In contrast, circadian-aligned lighting preserved melatonin rhythms and mitigated these effects. Melatonin co-infusion attenuated morphine tolerance and enhanced morphine analgesia. Reduced pro-inflammatory cytokine expression and increase anti-inflammatory cytokine IL-10 level and suppressed astrocyte activation were also observed by melatonin co-infusion during morphine tolerance induction. These findings highlight the potential of melatonin and circadian regulation in improving opioid efficacy and reduced morphine tolerance in managing neuropathic pain. Full article

Understanding the activity patterns of a species is essential for developing sound conservation and management plans. In this study, we used a camera-trapping technique to determine the activity patterns of bharal (Pseudois nayaur) in a marginal population in Wolong National Nature Reserve, Sichuan, China. Our results showed that these animals preferred to be active in the daytime from 08:00 to 20:00, with an activity peak between 10:00 and 14:00. In addition, we found that the species had a seasonal activity pattern with higher activity frequency in summer than in winter and that bharal were most active in a temperature range of 3–11 °C and at night with a waxing crescent moon, implying that the activity rhythm of the species is an adaptation to a subtropical high-altitude alpine area with vertical zonation in temperature. The pattern of movement and activity was also correlated with the moon phase. Full article

Heart rate (HR) is strongly affected by the autonomic nervous system (ANS), while its spontaneous fluctuations, called heart rate variability (HRV), report about the dynamics of the complex, vegetative regulation of the heart rhythm. Hence, HRV is widely considered an important marker of the ANS effects on the cardiac system, and as such, a crucial diagnostic tool in cardiology. In order to obtain nontrivial results from HRV analysis, it would be desirable to establish exact, universal interrelations between the typical HRV parameters and HR itself. That, however, has not yet been fully accomplished. Hence, our aim was to perform a comparative statistical analysis of ECG recordings from a public database, with a focus on the HR dependence of typical HRV parameters. We revealed their fundamental connections, which were substantiated by basic mathematical considerations, and were experimentally demonstrated via the analysis of 24 h of ECG recordings of more than 200 healthy individuals. The large database allowed us to perform unique age-cohort analyses. We confirmed the HR dependence of typical time-domain parameters, such as RMSSD and SDNN, frequency-domain parameters such as the VLF, LF, and HF components, and nonlinear indices such as sample entropy and DFA exponents. In addition to shedding light on their relationship, we are the first, to our knowledge, to identify a new, diffuse structure in the VHF regime as an important indicator of SNS activity. In addition, the demonstrated age dependence of the HRV parameters gives important new insight into the long-term changes in the ANS regulation of the cardiac system. As a possible molecular physiological mechanism underlying our new findings, we suggest that they are associated with Piezo2 channel function and its age-related degradation. We expect our results to be utilized in HRV analysis related to both medical research and practice. Full article

Continuous blood pressure (BP) monitoring provides valuable insight into the body’s dynamic cardiovascular regulation across various physiological states such as physical activity, emotional stress, postural changes, and sleep. Continuous BP monitoring captures different variations in systolic and diastolic pressures, reflecting autonomic nervous system activity, vascular compliance, and circadian rhythms. This enables early identification of abnormal BP trends and allows for timely diagnosis and interventions to reduce the risk of cardiovascular diseases (CVDs) such as hypertension, stroke, heart failure, and chronic kidney disease as well as chronic stress or anxiety disorders. To facilitate continuous BP monitoring, we propose an AI-powered estimation framework. The proposed framework first uses an expert-driven feature engineering approach that systematically extracts physiological features from photoplethysmogram (PPG)-based arterial pulse waveforms (APWs). Extracted features include pulse rate, ascending/descending times, pulse width, slopes, intensity variations, and waveform areas. These features are fused with demographic data (age, gender, height, weight, BMI) to enhance model robustness and accuracy across diverse populations. The framework utilizes a Tab-Transformer to learn rich feature embeddings, which are then processed through an ensemble machine learning framework consisting of CatBoost, XGBoost, and LightGBM. Evaluated on a dataset of 1000 subjects, the model achieves Mean Absolute Errors (MAE) of 3.87 mmHg (SBP) and 2.50 mmHg (DBP), meeting British Hypertension Society (BHS) Grade A and Association for the Advancement of Medical Instrumentation (AAMI) standards. The proposed architecture advances non-invasive, AI-driven solutions for dynamic cardiovascular health monitoring. Full article

Risk zone delineation and mobility behavior control constitute critical measures in pandemic containment. Numerous studies utilize static demographic data or dynamic mobility data to calculate the high–risk zones present in cities; however, these studies fail to concurrently consider activity and mobility patterns of populations in both space and time, which results in many studies only being able to employ static geostatistical analytical methods, neglecting the transmission risks associated with human mobility. This study utilized the mobile phone signaling data of Shenzhen residents from 2019 to 2020 and developed a CP tensor decomposition algorithm to decompose the long-sequence spatiotemporal trajectory data to detect high risk zones in terms of detecting overlapped community structures. Tensor decomposition algorithms revealed community structures in 2020 and the overlapping regions among these communities. Based on the overlap in spatial distribution and the similarity in temporal rhythms of these communities, we identified regions with spatiotemporal co-location as high–risk zones. Furthermore, we calculated the degree of population mixing in these areas to indicate the level of risk. These areas could potentially lead to rapid virus spread across communities. The research findings address the shortcomings of currently used static geographic statistical methods in delineating risk zones, and emphasize the critical importance of integrating spatial and temporal dimensions within behavioral big data analytics. Future research should consider utilizing non-aggregated individual trajectories to construct tensors, enabling the inclusion of individual and environmental attributes. Full article

Autoimmune diseases such as systemic lupus erythematosus and Sjögren’s syndrome show pronounced sex disparities in prevalence, severity, and clinical outcomes, with females disproportionately affected. Emerging evidence highlights sex-based differences in immune and inflammatory responses as key contributors to this bias. Genetic factors—including sex chromosomes, skewed X chromosome inactivation, and sex-biased microRNAs—as well as sex hormones and pregnancy modulate gene expression and immune cell function in a sex-specific manner. Additionally, sex hormone-dependent epigenetic modifications influence the transcription of critical immune regulators. These genetic and hormonal factors collectively shape the activation, differentiation, and effector functions of diverse immune cell types. Environmental factors—including infections, gut microbiota, environmental chemicals and pollutants, and lifestyle behaviors such as diet, smoking, UV exposure, alcohol and caffeine intake, physical activity, and circadian rhythms—further modulate immune function and autoimmune disease pathogenesis in a sex-dependent manner. Together, these mechanisms contribute to the heightened risk and distinct clinical features of autoimmunity in females. A deeper understanding of sex-biased immune regulation will facilitate the identification of novel biomarkers, enable patient stratification, and inform the development of sex-specific diagnostic and therapeutic strategies for autoimmune diseases. Full article

To investigate the group behavioral characteristics of Schizothorax wangchiachii during the spawning period, we used acoustic telemetry to track 10 mature individuals (4 females, 12 males) in a semi-controlled stream section (28.1 m × 5.8 m) simulating natural spawning microhabitats from 23 to 26 January 2024. By integrating trajectory similarity analysis and wavelet transform, we examined the aggregation patterns and activity rhythms during natural spawning events. The population formed two relatively stable subgroups, with significantly shorter inter-individual distances during the day (1.69 ± 0.72 m) than at night (2.54 ± 0.85 m, p < 0.01). Aggregation behavior exhibited a dominant ultradian rhythm of 16.5 h, with stable clustering between 09:00 and 16:00 (spawning window: 13:40–14:20) and dispersal from 19:00 to 00:00. Group activity followed a decreasing-then-increasing trend, with higher nighttime activity. Males were more active than females (F = 51.89, p < 0.01); female activity peaked on the spawning day and was influenced by reproductive progression, while male activity was mainly driven by diel rhythms (p < 0.01). A weak positive correlation was found between active time and inter-individual distance in both sexes (r = 0.32, p < 0.05), indicating reduced activity when aggregated. These findings provide insight into the temporal coordination and spatial regulation of reproductive behavior under semi-controlled conditions. However, due to the short monitoring period and experimental setup, caution is warranted when generalizing to the full reproductive season or fully natural habitats. Full article

Background: Digital technologies offer innovative opportunities for recovering and maintaining intellectual and mental health. The use of a multitask approach that combines motor component with various cognitive tasks in a virtual environment can optimize cognitive and physical functions and improve the quality of life of cardiac surgery patients. This study aimed to localize current sources of theta and alpha power in patients who have undergone virtual multitask training (VMT) and a control group in the early postoperative period of coronary artery bypass grafting (CABG). Methods: A total of 100 male CABG patients (mean age, 62.7 ± 7.62 years) were allocated to the VMT group (n = 50) or to the control group (n = 50). EEG was recorded in the eyes-closed resting state at baseline (2–3 days before CABG) and after VMT course or approximately 11–12 days after CABG (the control group). Power EEG analysis was conducted and frequency-domain standardized low-resolution tomography (sLORETA) was used to assess the effect of VMT on brain activity. Results: After VMT, patients demonstrated a significantly higher density of alpha-rhythm (7–9 Hz) current sources (t > −4.18; p < 0.026) in Brodmann area 30, parahippocampal, and limbic system structures compared to preoperative data. In contrast, the control group had a marked elevation in the density of theta-rhythm (3–5 Hz) current sources (t > −3.98; p < 0.017) in parieto-occipital areas in comparison to preoperative values. Conclusions: Virtual reality-based multitask training stimulated brain regions associated with spatial orientation and memory encoding. The findings of this study highlight the importance of neural mechanisms underlying the effectiveness of multitask interventions and will be useful for designing and conducting future studies involving VR multitask training. Full article

The circadian clock is a self-sustaining oscillator with a period of approximately 24 h, enabling organisms to anticipate daily recurring events, such as sunrise and sunset. Since the circadian period is not exactly 24 h and the environmental day length varies throughout the year, the clock must be periodically reset to align an organism’s physiology with the natural light/dark cycle. This synchronization, known as entrainment, is primarily regulated by nocturnal light, which can be replicated in laboratory settings using a 15 min light pulse (LP) and by assessing locomotor activity. An LP during the early part of the dark phase delays the onset of locomotor activity, resulting in a phase delay, whereas an LP in the late dark phase advances activity onset, causing a phase advance. The clock gene Period 2 (Per2) plays a key role in this process. To investigate its contributions, we examined the effects of Per2 deletion in neurons versus astrocytes using glia-specific GPer2 (Per2/GfapCre) knockout (KO) and neuronal-specific NPer2KO (Per2/NesCre) mice. All groups were subjected to Aschoff type II protocol, where an LP was applied at ZT14 or ZT22 and the animals were released into constant darkness. As control, no LP was applied. Phase shift, period, amplitude, total activity count, and rhythm instability were assessed. Our findings revealed that mice lacking Per2 in neurons (NPer2) exhibited smaller phase delays and larger phase advances compared to control animals. In contrast, mice with Per2 deletion specifically in glial cells including astrocytes (GPer2) displayed normal clock resetting. Interestingly, the absence of Per2 in either of the cell types resulted in a shorter circadian period compared to control animals. These results suggest that astrocytic Per2 is important for maintaining the circadian period but is not required for phase adaptation to light stimuli. Full article

Background/objectives: In some cases of concomitant use of direct oral anticoagulants (DOAC) and certain anticancer medications, pharmacokinetic interactions are expected; however, clinical data is scarce. This report reviews the recommendations on the use of DOAC concurrently with anticancer drugs according to different clinical decision support systems and sources, with a focus on discrepancies. Methods: We reviewed the recommendations from the American Heart Association (AHA), European Heart Rhythm Association (EHRA), summary of product characteristics (SPC) in FASS (Swedish medicine information portal), the Swedish clinical decision support system Janusmed, and information from the Food and Drug Administration (FDA) on the concomitant use of apixaban, edoxaban, and rivaroxaban (activated factor X (FXa) inhibitors) and 80 anticancer drugs from 11 categories (240 drug pairs). Results: No warnings of expected pharmacokinetic drug interactions between FXa inhibitors and anticancer drugs were found for 155 drug pairs (65%) across all sources. The remaining 35% of drug pairs were flagged as having possible interactions with FXa inhibitors according to at least one source. Discrepancies in the recommendations from the different sources were reported. The reported discrepancies were, for the most part, associated with different assessments of the mechanism and the extent of pharmacokinetic interactions of each anticancer medication. Also, knowledge sources have different approaches to reporting potential interactions, in some cases reporting clinically relevant strictly pharmacokinetic interactions, whereas others include even patient-specific factors. Conclusions: The lack of clinical data and different recommendations can make clinical decisions on the concomitant use of DOAC and anticancer drugs difficult. Our compilation is meant to assist clinicians in making decisions based on the available evidence, even if it is scarce. Full article

Background and Clinical Significance: Evaluating wide complex rhythms in patients with permanent pacemakers can be a diagnostic challenge, particularly when the rhythm is irregular. While pacemaker-mediated rhythms are typically regular and predictable, the appearance of wide complex irregular rhythms raises concerns ranging from lead malfunction to life-threatening arrhythmias, such as ventricular tachycardia. Understanding the interplay between intrinsic cardiac activity and device function is crucial for timely and accurate diagnosis in this increasingly common clinical scenario. Case presentation: We report on a 74-year-old female with a VVI pacemaker implanted for binodal disease, who presented with intermittent palpitations and an irregular rhythm. The patient has a recent history of falling on her right shoulder, which is also the site of the device implantation. We used a clinical step-by-step approach to rule out pacemaker malfunction and to establish the need for an unscheduled device interrogation. Conclusions: This case presentation highlights the important role of clinical reasoning and the approach to such a patient, especially when a key method of pacemaker evaluation, such as device interrogation, is not readily available. Full article