Search Results (692)

Septic cardiomyopathy is recognized as an acute, transient, and reversible condition. However, septic insult may induce latent changes characteristic of cardiac remodeling, with future consequences. Therefore, the present study aimed to evaluate the morphological and functional cardiac changes in the acute and subacute phases (with 7-day follow-up) in male Wistar rats subjected to experimental sepsis using a cecal ligation and puncture (CLP) model. In the acute phase, the animals underwent echocardiographic assessment at baseline and 48 h after the induction of sepsis. In the subacute 7 days follow-up, animals were allocated in control and sepsis groups. After this period, the animals underwent echocardiographic assessment, followed by euthanasia, papillary muscle testing, and subsequent morphometric and biochemical analyses. Fecal samples from six animals per group were collected at baseline and after 7 days for microbiota analysis. In the acute phase, echocardiographic assessment revealed that, following sepsis, animals exhibited reduced systolic function. In the subacute 7 days follow-up, both echocardiogram and papillary muscles revealed cardiac dysfunction in the sepsis group. Cardiomyocyte cross-sectional area and collagen content were significantly greater in the sepsis group compared with that in the control group. Analysis of maximal enzymatic activities involved in cardiac energy metabolism and oxidative stress biomarkers revealed no significant differences between groups. Considering microbiota assessment, beta diversity analysis revealed significant differences between septic animals and controls. In conclusion, sepsis was associated with persistent systolic/diastolic dysfunction, cardiomyocyte hypertrophy, and fibrosis after 7 days. These data suggest that septic cardiomyopathy should not be considered merely an acute, transient, and reversible condition in this experimental context. Full article

Background/Objectives: High liver fat content is closely associated with hepatic disease and multiple comorbidities including cancer, diabetes and cardiovascular accidents. Therefore, accurate quantification of hepatic steatosis, especially of borderline cases, is essential for clinical management. Although MRI non-invasively assesses hepatic steatosis, current approaches remain limited by the data variability introduced through use of region-of-interest measurements or classification models that predict discrete fat grades without providing uncertainty estimates. This study proposes a probabilistic approach for hepatic steatosis quantification based on combining a neural network and beta distribution, enabling prediction of hepatic fat percentage with corresponding confidence intervals. Methods: Single in-phase Dixon MRI liver images from a cohort of prepubertal males (n = 84) were used as input to a probabilistic neural network combined with a beta distribution framework to estimate hepatic fat content along with associated confidence intervals. The predicted fat fractions were then compared against reference MRI-derived measurements (ground truth). Results: The methodology achieved a low prediction error and demonstrated good performance for the test set, with predicted values in good agreement with the ground truth measurements. This was reflected by the mean absolute error (MAE = 0.44 percentage points) and the coefficient of determination (R² = 0.98). The empirical standard deviation of the prediction errors on a logarithmic scale was σ = 0.0609. Conclusions: By incorporating uncertainty quantification into hepatic steatosis estimation, this probabilistic framework provides an interpretable measure of variability alongside point estimates. The approach is demonstrated in a specific cohort and requires further validation in broader populations. Full article

This study presents a sensor-based condition monitoring framework for the diagnosis and prognosis of neurophysiological states using electroencephalographic (EEG) signals. Leveraging a comparative deep learning architecture, we evaluate a baseline Variational Autoencoder against a Transformer-based Autoencoder to model latent representations of EEG dynamics across three therapeutic phases: pre-intervention, during intervention, and post-intervention. The proposed methodology aligns with sensor-based fault diagnosis principles by treating deviations from stable neurophysiological states as diagnostic indicators and temporal phase transitions as markers of therapeutic stage progression. Using a dataset of 94 EEG sessions from six subjects with diverse neurological conditions, we demonstrate that the Transformer Autoencoder, through its self-attention mechanism, captures cross-band spectral relationships more effectively than the VAE, resulting in denser within-phase clusters and improved separation between therapeutic stages. Quantitative evaluation reveals small but statistically significant effects between pre- and during-intervention phases (${\eta }_{\mathrm{partial}}^2=0.0388$) and pre- and post-intervention phases (${\eta }_{\mathrm{partial}}^2=0.0470$), predominantly driven by delta, theta, beta, and gamma rhythms. These findings illustrate how sensor-based latent state monitoring can provide interpretable, data-driven insights for condition assessment and phase transition assessment between sessions in complex dynamic systems, with potential applicability beyond clinical domains to industrial condition monitoring and fault diagnosis tasks. The framework confirms that it offers qualitative indicators, rather than predictive clinical outputs. Full article

Alzheimer’s disease (AD) research has primarily focused on amyloid beta (Aβ) and tau protein; however, drug development targeting these two proteins has been disappointing. Therefore, there is an urgent need to explore the novel pathogenic mechanisms underlying AD. Recently, we found that expression of the K670N/M671L-mutated amyloid precursor protein (APP) in 293T cells significantly reduced membrane ferroportin (FPN) levels. Furthermore, 2-month-old APP/PS1 mice exhibited a marked decrease in membrane FPN levels, while total FPN expression and Aβ levels remained unchanged. Further studies revealed that features of ferroptosis were present in the brains of 2-month-old APP/PS1 mice, and that treatment with ferroptosis inhibitors or iron chelation significantly alleviated early pathological changes and cognitive impairment in these animals. In addition, supplementation with an APP–FPN binding peptide during the early phase ameliorated AD-related pathologies, including Aβ deposition, neuroinflammation, oxidative stress, and synapse-associated protein deficits, in APP/PS1 mice. Collectively, our findings suggest that APP mutations may contribute to early brain pathological changes and subsequent memory impairment in AD by downregulating membrane trafficking of FPN and inducing ferroptosis, thereby providing new molecular targets for drug development. Full article

Mesenchymal stromal/stem cells (MSCs) are increasingly explored for immune-mediated diseases, yet standardized analytical readouts that capture coordinated immunomodulatory output across complementary secretory pathways remain limited. Here, we report the feasibility of an HPLC-based multi-analyte secretome characterization panel that quantifies two small-molecule outputs—adenosine and kynurenine—alongside two immunomodulatory proteins—interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β)—in conditioned media from canine adipose-derived MSCs (cAD-MSCs). Canine immune-mediated hemolytic anemia (IMHA) was used as a disease context to motivate the selection of these analytes, given the pro-inflammatory cytokine environment characteristic of this condition. Three independent cAD-MSC lines were evaluated under baseline conditions and following cytokine stimulation with recombinant interferon-gamma (IFN-γ; 100 ng/mL) and tumor necrosis factor-alpha (TNF-α; 50 ng/mL), referred to herein as inflammatory priming or licensing. Conditioned media were collected at 72 h for metabolite analysis and 48 h for protein analysis, and quantified by HPLC using external calibration and peak integration. Across all three lines, licensing produced directionally consistent increases: mean adenosine increased 2.3-fold, mean kynurenine increased 3.1-fold, mean IL-10 increased 1.6-fold, and mean TGF-β increased 1.7-fold compared with unlicensed controls. Metabolite measurements for adenosine and kynurenine are reported with full chromatographic selectivity data; IL-10 and TGF-β measurements by reversed-phase HPLC with UV detection are presented as exploratory/semi-quantitative outputs and will require orthogonal confirmation (e.g., immunoassay) in future work. These findings are preliminary, derived from three independent donor lines with no comparator group, and are intended to support feasibility of the analytical framework rather than establish definitive performance specifications. Collectively, the data support the potential of a multi-analyte HPLC-based characterization panel to capture licensing-responsive secretory shifts across mechanistically complementary pathways, providing a foundation for expanded development and validation. Full article

Background/Objectives: Goal-directed praxis actions (GOPAs) integrate perception, motor planning, and executive control. While neural correlates of single actions are known, less is understood about how complexity conditions and their hierarchical organization into elementary tasks shape neural dynamics during ecologically manual assembly tasks. This study tested how electrophysiological (EEG) activity reflects global complexity and selective engagement of executive and sensorimotor systems across GOPAs. Methods: 38 healthy young adults completed two assembly conditions differing in complexity (basic and advanced) decomposed into four elementary tasks: identification, handling, alignment, and joining. EEG was recorded across five frequency bands (delta, theta, alpha, beta, and gamma) and four regions of interest (ROI): frontal, fronto-central, temporo-central, and parieto-occipital. Results: Neural activity varied significantly depending on different complexity, elementary task, and ROI. The advanced-complexity condition elicited stronger neural responses compared to the basic-complexity condition, reflecting greater cognitive, and sensorimotor demands. A task-related gradient emerged, with joining showing the highest activity, followed by alignment, while identification and handling showed lower activation. Frontal regions, particularly in theta activity, were more involved under higher complexity, suggesting increased executive control. In contrast, beta and gamma activity predominated in temporo-central and parieto-occipital regions, supporting visuomotor and sensorimotor integration. Conclusions: EEG oscillatory dynamics during ecological GOPAs are selectively modulated by complexity condition and hierarchical task organization. Neural activity tracks functional demands of specific action phases rather than general arousal, highlighting dynamic coordination between executive and sensorimotor systems during complex manual behavior. Full article

Biological differences between sexes—particularly due to fluctuating levels of 17β-estradiol and menstrual cycle dynamics—may influence exercise-induced reactive oxygen species (ROS) formation, inflammation and exercise performance. Despite these considerations, there is a lack of research exploring how estradiol and menstrual cycle phases may impact exercise performance, exercise-induced ROS formation and inflammation. This study aimed to examine whether estradiol concentration or menstrual cycle phase may be significantly associated with resistance circuit high-intensity interval training (HIIT) performance, as well as exercise-induced formation of ROS and Interleukin-6 (IL-6). A total of 30 young healthy female participants completed a single bout of resistance-based HIIT in a fasted state. Blood samples were collected at four time points: at baseline after overnight fasting, two hours after consumption of 0.5 L of water (pre-HIIT), immediately post exercise (post-HIIT) and after 15 min of recovery (15-post-HIIT). Additionally, participants attended six fasting baseline assessments scheduled across various menstrual cycle days. These sessions enabled the assessment of estradiol, ROS and IL-6 concentrations throughout the menstrual cycle without being confounded by nutritional factors. Neither baseline levels of ROS nor IL-6 differed significantly between menstrual cycle phases (luteal vs. follicular ROS: 0.013 µmol/min, p = 0.716; IL-6: 0.052, p = 0.679) menstruation status (yes vs. no ROS: −0.056 µmol/min, p = 0.259; IL-6: −0.302 pg/mL, p = 0.088) or 17β-estradiol concentrations (low (11–≤72.5 pg/mL) vs. high (>72.5–394 pg/mL) ROS: −0.038 µmol/min, p = 0.266; IL-6: +0.015 pg/mL, p = 0.906). On the resistance-circuit-HIIT intervention day, no significant differences in ROS or IL-6 were observed between estradiol concentrations (ROS: p = 0.477; IL-6: p = 0.249), menstrual cycle phase (ROS; p = 0.752; IL-6: p = 0.557) or menstruation status (ROS: p = 0.383; IL-6: p = 0.808) from baseline to pre-HIIT, post-HIIT or 15-post-HIIT. These findings should be interpreted with caution, as the menstrual cycle phases were assigned using a calendar-based approach without biochemical ovulation confirmation and the subgroup sizes were relatively small. These findings suggest that natural 17-beta-Estradiol fluctuations within the menstrual cycle, as well as differences in the menstrual cycle itself, may not substantially modulate ROS or IL-6 responses to acute resistance-based HIIT in young healthy female adults. Full article

Metal anodes offer substantially higher specific and volumetric capacities than conventional anode materials such as graphite in lithium-ion batteries or hard carbon in sodium-ion batteries. However, the integration of metal anodes into solid-state batteries poses significant challenges, particularly with respect to processing, interfacial stability, and cell assembly. Anode-free solid-state batteries (AFSSBs) address these challenges by eliminating the pre-installed metal anode, instead forming the metal in situ during the initial charging (formation) step. In anode-free solid-state batteries, the quality of the interfacial contact is particularly critical, as insufficient contact can lead to locally increased current densities. Consequently, the initial metal plating during the formation step plays a decisive role in determining the homogeneity and stability of the anode interface. Furthermore, conventional battery-grade copper foils (~10 µm) are considerably thicker than required for the targeted C-rates and are difficult to use as stand-alone anode-free current collectors, thereby hindering the industrial production of anode-free solid-state batteries. In this publication, we demonstrate the application of atmospheric plasma spraying (APS) to fabricate thin copper current collectors directly on the ceramic solid electrolytes LAGP (lithium aluminium germanium phosphate) and BASE (beta-alumina solid electrolyte) with superior interface contact. No mechanical damage or diffusion of copper into the solid electrolyte nor formation of secondary phases at the interfaces were observed in SEM or EDS despite the elevated process temperature. LAGP with a thickness as low as 300 µm was successfully coated and subsequently used for plating/stripping experiments. Finally, dense sodium metal was plated at the copper-substrate interface of a 1.4 mm thick BASE sample. Full article

Background: Hippotherapy, a sensorimotor-rich intervention proposed for children with Autism Spectrum Disorder (ASD), is suggested to influence executive function (EF). However, the underlying electrophysiological mechanisms, particularly changes observed in resting-state Electroencephalography (EEG), remain underexplored. Methods: A total of forty-eight children with ASD, aged 9–12 years, participated in this quasi-experimental, non-randomized pre-test–post-test study. Participants were assigned to either a standardized 12-session hippotherapy program (n = 24) or a waitlist Control group (n = 24). EF was evaluated pre- and post-intervention using validated measures: the Wisconsin Card Sorting Test, Stroop Color–Word Test, Corsi Block-Tapping Task, and Tower of London. Resting-state EEG data (19 channels, 250 Hz) were recorded before and after the intervention and analyzed for spectral power, pairwise Pearson correlation, phase-based functional connectivity using the Phase Lag Index (PLI), and directed effective connectivity using Phase Transfer Entropy (PTE). EEG effects were tested with linear mixed models in MATLAB (fitlme), with the measured values in each ROI as the dependent variable, group and time as fixed effects, and SubjectID included as a random intercept; EF outcomes were analyzed with ANCOVA/MANCOVA, adjusting post-test scores for baseline. The assumptions of homogeneity of slopes, Levene’s test, and the Shapiro–Wilk test were examined, and the Holm–Bonferroni correction together with partial η² effect sizes were reported. Results: Following baseline adjustment, the hippotherapy group showed substantial and statistically significant improvements across all EF measures compared with controls partial η² range = 0.473–0.855; all adjusted p < 0.001; e.g., Stroop Incongruent Reaction Time (F(1,45) = 265.80, p < 0.001, ηp² = 0.855). EEG analyses revealed localized Group × Time interaction effects involving frontal delta power as well as selected alpha-, theta-, and beta-band connectivity measures within frontally anchored networks. In addition to these focal interaction effects, the hippotherapy group exhibited a narrower distribution of pre–post EEG changes across spectral power and connectivity metrics compared with controls, indicating greater temporal consistency in resting-state electrophysiological dynamics across sessions. Because group allocation was non-random (based on scheduling feasibility and parental preference), results should be interpreted as associations rather than causal effects. While the hippotherapy group exhibited significant EF improvements and relative stabilization in EEG spectral and connectivity metrics, particularly in frontal delta/theta/alpha/beta bands, a direct mapping between individual EEG changes and behavioral gains was not observed. Conclusions: A standardized 12-session hippotherapy program was associated with substantial improvements in EF and with relative stabilization of resting-state electrophysiological dynamics in children with ASD. However, the direct mechanistic link between these EEG and behavioral changes warrants further investigation. Larger randomized trials employing active control conditions, task-evoked electrophysiological measures, and extended longitudinal follow-up are needed to confirm efficacy, clarify mechanisms, and establish the durability of effects. Full article

Alzheimer’s disease is a complex neurodegenerative condition characterized by progressive cognitive decline, neuroinflammation, metabolic dysregulation, and abnormal protein deposition. While genetic factors and amyloid-beta-focused hypotheses have been extensively investigated, they fail to fully account for the prolonged prodromal phase or the early susceptibility of olfactory and limbic regions. Emerging evidence suggests chronic peripheral and mucosal infections may influence disease risk; however, mechanisms by which microbial activity outside the central nervous system contributes to persistent neuropathology remain poorly understood. This review explores the emerging concept that bacterial outer membrane vesicles act as mobile, lipid-rich vectors linking peripheral microbial reservoirs to neuroimmune and metabolic dysfunction in the aging brain. We discuss evidence suggesting vesicles originating from oral, olfactory, and upper airway niches can access the central nervous system via vascular routes and direct neural pathways, including olfactory and trigeminal nerves, where they influence glial and endothelial cell function. We also propose the Accumulative Vesicle Load Hypothesis, which describes how cumulative lifetime exposure to bacterial vesicles shapes disease onset, anatomical vulnerability, and progression, and incorporates components of other hypotheses proposed for Alzheimer’s disease. This offers a system-level perspective for early diagnosis and upstream therapeutic strategies, including minimally invasive vesicle profiling in nasal fluid, saliva, blood, and cerebrospinal fluid. This work is a conceptual review that summarizes current evidence in a hierarchically organized manner and proposes a testable model; it does not assert causality where direct human evidence is currently limited. Full article

Background/Objectives: Impairment in pulsatile insulin release contributes to insulin resistance and is one of the earliest markers of developing type 2 diabetes. Insulin delivered to the liver in pulses has a stronger glucose-lowering effect than continuous insulin delivery. Whether pulsatility benefits the islet itself is an open question. We previously showed that reducing glucokinase activity with the glucokinase inhibitor D-mannoheptulose (MH) improves function in islets exposed to prolonged hyperglycemic conditions. In this study, we test whether pulsatile vs. continuous delivery impacts the effectiveness of MH in islets. Methods: Islets were exposed to high-glucose conditions (20 mM glucose) for 24 or 48 h to induce early adaptations to hyperglycemia. We then used a specially designed perifusion system to impose pulsatile activity by exposing mouse islets to 3 min of MH in 20 mM glucose and 3 min of only high levels of glucose. Islets given intermittent MH for 18 h were compared with continuous delivery of MH at a full (2.5 mM) or half (1.25 mM) dose. Results: MH delivered by the forced oscillatory system reversed the effects of hyperglycemia and restored glucose sensing more effectively than continuous delivery. Specifically, fura-2AM imaging of intracellular calcium showed that islets given pulsatile MH had greater reductions in the elevated basal calcium caused by hyperglycemic conditions, improved the glucose stimulation index, and improved phase 0 response (indicating glucose-stimulated calcium uptake by the endoplasmic reticulum). Conclusions: These findings suggest that the loss of oscillatory glucose metabolism in islets contributes directly to beta-cell dysfunction. Full article

The responsiveness of the stress axis is fundamental for maintaining health and sustaining productive performance; however, the effect of modulating this stress axis with bovine appeasing substance and its effects on biochemical, immunological, oxidative parameters and uterine involution have not been determined, which are the objectives of this experiment. To elucidate these questions, Holstein cows, from the prepartum to lactation period in a cross-ventilation system, received an application of a bovine appeasing substance (treated group) and a 0.9% saline solution (control group) at the time of calving, and blood samples were collected on calving day and on days 3, 7, 14 and 21 postpartum for analysis. Modulation of the stress axis by bovine appeasing substance increased magnesium levels on days 7 and 14 postpartum, with a reduction in fructosamine levels on days 3, 7, 14, and 21 postpartum. A reduction in ferritin levels, an acute-phase protein, and a reduction in interleukin 1 beta and interleukin 6 were also observed, demonstrating an anti-inflammatory effect in cows of the treated group. Creatine kinase activity decreased on day 21 postpartum in cows treated with bovine appeasing substances. An increase in cholinesterase activity on day 7 and a marked decrease on day 21 postpartum in treated cows were observed compared to the control. This was accompanied by a reduction in beta-hydroxybutyrate levels on day 7 and a reduction in reactive oxygen species levels on day 14 in animals of the treated group, indicating modulation of ketogenesis and reduced oxidation through an anti-inflammatory effect. Mean uterine thickness was also affected by the bovine appeasing substance, with a lower mean thickness on day 21 postpartum in treated cows. Modulation of the stress axis by the bovine appeasing substance reduces inflammation, improving energy dynamics and reducing oxidation, thus facilitating tissue repair associated with postpartum uterine involution in dairy cows. Full article

This study analyses the behaviour of brass CB773S with extra-low-lead content in relation to corrosion and the corrosion–cavitation phenomenon. Electrochemical corrosion tests, both potentiodynamic and potentiostatic, as well as corrosion–cavitation tests, were conducted. Various potentials were applied to brass, alongside cavitation generated by an ultrasonic bath. Artificial seawater and artificial brackish water were used as electrolytes. Surface damage was evaluated using a stereo microscope and scanning electron microscopy. The results indicate that the interfaces between alpha and beta phases of brass serve as preferential sites for the nucleation and collapse of vapour bubbles under cavitation conditions, leading to a deep pitting, especially in artificial brackish water under this synergy. Susceptibility to a selective corrosion of the Zn-rich phase was observed, highly dependent on the test solution, as well as on the applied potential during the tests. The corrosion–cavitation synergistic damage was strongly dependent on the electrochemical parameters, particularly the applied potential, which plays a key role under cathodic protection conditions. In general, it can be concluded that low-lead brass behaviour is governed by a complex interaction between applied potential, electrolyte chemistry, microstructure, and mechanical effect. These findings provide valuable insights into brass’s performance under service conditions where corrosion and cavitation may appear simultaneously in marine environments. Full article

Music therapy (MT) is increasingly being integrated into intensive care unit (ICU) settings to modulate pain, stress, and emotional dysregulation. Although clinically promising, objective biomarkers for quantifying its neurophysiological effects are still missing. In this context, the electroencephalogram (EEG) represents a valid tool to assess cortical dynamics associated with cognitive–affective engagement elicited by MT. Our study aims to evaluate the role of electroencephalography as an objective tool for monitoring cortical responses to MT in the ICU. EEGs acquired from nine burn patients undergoing MT in the ICU were considered. Signals were preprocessed to improve the signal-to-noise ratio. Then, six frequency bands (delta, theta, alpha, beta, gamma, and sensorimotor rhythm) were extracted to compute band powers and derive 37 involvement indexes, which were statistically compared across three experimental phases: before, during, and after MT. Results demonstrate that involvement indexes effectively capture neurophysiological shifts induced by MT. Significant differences were observed in 22 indexes when comparing During-MT and Post-MT phases, with 2 indexes being statistically different also when comparing During-MT and Pre-MT phases; 5 indexes differed statistically when comparing Pre-MT and Post-MT phases. These results suggest a transient cortical engagement elicited during MT in ICU settings. Our findings align with previous research reporting EEG (and certain EEG-derived involvement indexes) sensitivity to capture music-induced cognitive and emotional modulation. This confirms electroencephalography potential to objectively reflect MT effects and support its integration in multidisciplinary burn care; however, analysis on larger cohorts is necessary to validate EEG as a clinical tool in MT. Full article

Wastewater-based epidemiology (WBE) is an approach that uses information obtained from the analysis of various metabolites or residues in wastewater with the aim of assessing the consumption of or exposure to chemicals or pathogens in a population connected to a sewage system. The aim of this work was to develop methods for the isolation and analysis of seven beta-blockers (acebutolol, atenolol, betaxolol, metoprolol, nadolol, pindolol and propranolol) in wastewater samples collected from the influent of the wastewater treatment plant in Cluj-Napoca, Romania, in order to estimate their consumption among the population in two time periods (February and October 2024) using WBE. The selected beta-blockers were extracted by solid phase extraction using a Strata C18-U cartridge and analyzed by liquid chromatography coupled with tandem mass spectrometry. The consumption was estimated using the daily mass load of pharmaceutical products reported per 1000 inhabitants (mg/day/1000inh) and varied in the following ranges: atenolol 0.03–3.74, nadolol 0.03–0.1, propranolol 0.04–0.72, betaxolol 0.07–0.38, and metoprolol 54.85–276.45. From the obtained results, it can be observed that metoprolol is the most used beta-blocker in the investigated population, followed by atenolol, propranolol and betaxolol. Other beta-blockers are consumed in small quantities or occasionally. Full article