Search Results (5,752)

Older adults are vulnerable to changes in sleep with age. Poor sleep quality is associated with self-reported cognitive changes, which can occur before the onset of objective cognitive decline associated with Mild Cognitive Impairment and Alzheimer’s disease. The objective of this study was to examine associations between self-reported sleep complaints, objective sleep quality, and self-reported cognitive changes and their relations to symptoms of depression and anxiety in a group of community-dwelling older adults. Adults aged ≥ 50 without dementia (n = 45) were recruited and completed 1–2 weeks of rest-activity monitoring using a wrist-worn device, underwent a test of global cognitive functioning (Mini-Mental State Examination; MMSE), and completed questionnaires assessing insomnia (Insomnia Severity Index; ISI), subjective sleep quality (Pittsburgh Sleep Quality Index; PSQI), self-reported cognitive changes (Cognitive Function Instrument; CFI), and symptoms of depression and anxiety (Beck Depression Inventory-II; BDI-II and Generalized Anxiety Disorder 7-item assessment; GAD-7). Pearson partial correlations assessed relations among subjective and objective sleep quality, insomnia ratings, CFI ratings, and global cognition, while controlling for BDI-II and GAD-7 ratings. Exploratory analyses examined the correlation between PSQI component scores and CFI ratings and global cognition. Greater ISI (r = 0.50, p ≤ 0.001) ratings significantly correlated with higher CFI scores. PSQI total ratings and actigraphy-based measures (n = 41) did not significantly correlate with CFI scores. Exploratory PSQI subscale analyses revealed that worse subjective sleep quality (r = 0.31, p = 0.048), shorter sleep duration (r = 0.32, p = 0.04), and greater use of sleep medications (r = 0.31, p = 0.048) correlated with higher CFI scores. Poorer sleep quality due to less time spent asleep, fragmented or disturbed sleep, and requiring medications to sleep, may be associated with greater memory concerns. Alternatively, worries about cognition may deleteriously affect sleep. Subjective measures of sleep quality may be useful to identify older adults at increased risk of cognitive decline. Full article

Advances in geroscience suggest that aging is modulated by molecular pathways that are amenable to dietary and pharmacological intervention. We conducted an integrative critical review of caloric restriction (CR), intermittent fasting (IF), and caloric restriction mimetics (CR-mimetics) to compare shared mechanisms, clinical evidence, limitations, and translational potential. Across modalities, CR and IF consistently activate AMP-activated protein kinase and sirtuins, inhibit mTOR (mechanistic target of rapamycin) signaling, and enhance autophagy, aligning with improvements in insulin sensitivity, lipid profile, low-grade inflammation, and selected epigenetic aging measures in humans. CR-mimetics, such as metformin, resveratrol, rapamycin, and spermidine, partially reproduce these effects; however, long-term safety and efficacy in healthy populations remain incompletely defined. Methodological constraints—short trial duration, selective samples, intermediate (nonclinical) endpoints, and limited adherence monitoring—impede definitive conclusions on hard outcomes (frailty, disability, hospitalization, mortality). We propose the Active Management of Aging and Longevity (AMAL) model, a three-level biomarker-guided framework that integrates personalized diet, chrono-nutrition, exercise, and the selective use of CR-mimetics, along with digital monitoring and decision support. AMAL emphasizes epigenetic clocks, multi-omics profiling, inflammatory and microbiome metrics, and adaptive protocols to enhance adherence and clinical relevance. Overall, CR, IF, and CR mimetics constitute promising, complementary strategies to modulate biological aging; rigorous long-term trials with standardized biomarkers and clinically meaningful endpoints are needed to enable their scalable implementation. Full article

Antinuclear antibodies, especially anti-DNA antibodies, are known to be a hallmark of systemic lupus erythematosus (SLE) and represent a diverse pool of autoantibodies with different origins, antigenic properties, and physicochemical features. Antibodies with catalytic properties have been found among the antibody repertoire in SLE, but the specific features and clinical associations of such antibodies have not been sufficiently studied. This study showed that chromatographically purified IgG from the serum of SLE patients effectively hydrolyzed DNA and DNA-associated proteins such as histones and high-mobility group box 1 (HMGB1) compared to healthy individuals. Remarkably, the level of hydrolysis of DNA and DNA-associated proteins was closely correlated. At the same time, these antibodies did not hydrolyze the control protein, tumor necrosis factor-α (TNFα), which does not possess DNA-binding properties. IgG DNase activity levels varied significantly, so patients were divided into high- and low-activity subgroups using the DBSCAN algorithm, with the difference between median values being greater than 49 times. The subgroup with high IgG DNase activity was characterized by an increase in anti-DNA antibodies (p < 0.04) than the subgroup with low activity, which had a shorter duration of the disease (p = 0.03) and was more often characterized by a subacute rather than a non-chronic course of the disease (p = 0.048). High catalase-like activity of IgG was also detected in SLE. Thus, the antibody pool in SLE contains not only high-affinity antinuclear autoantibodies but also catalytic antibodies capable of hydrolyzing DNA and DNA-associated proteins. These findings expand our understanding of the heterogeneity of the repertoire of catalytic autoantibodies among SLE patients. Full article

Background. Physical activity enhances cognitive performance in adolescents, yet the role of circadian timing within the school day remains poorly understood. Purpose. This study examined whether the timing of school-based physical activity (morning, midday, afternoon) influences cognitive performance, subjective alertness, and mood states in early adolescents. Methods. A 12-week crossover intervention was conducted with 102 students (aged 12–13 years) from southern Italy. Each class participated in three 4-week conditions of structured physical activity scheduled in the morning (8:10–9:10), midday (12:10–13:10), and afternoon (15:10–16:10), separated by one-week washouts. Cognitive outcomes (d2-R, Digit Span backward, TMT-A), subjective alertness (KSS), and mood (PANAS-C) were assessed at baseline and after each condition. Analyses employed linear mixed-effects models and repeated-measures ANOVAs, adjusting for sex, BMI, chronotype, and sleep duration. Results. Morning activity produced the strongest improvements in attention (d2-R, η²p = 0.16), working memory (Digit Span backward, η²p = 0.06), processing speed (TMT-A, η²p = 0.08), alertness (KSS, η²p = 0.19), and positive affect (PANAS-C, η²p = 0.05). Midday sessions yielded moderate benefits (d2-R, η²p = 0.09; Digit Span backward, η²p = 0.05; TMT-A, η²p = 0.07; KSS, η²p = 0.09), while afternoon activity showed the weakest or nonsignificant changes (all η²p < 0.05). Chronotype moderated the effects on attention and working memory, with morning types deriving the largest gains. Conclusions. The timing of physical activity is a critical determinant of its cognitive and affective benefits. Incorporating morning exercise into school timetables may represent a low-cost, scalable strategy to optimize both learning readiness and well-being in adolescents. Full article

Background: Advanced heart failure (HF) carries high morbidity and mortality, and deterioration on the heart transplantation (HT) waiting list remains a major challenge. Intermittent outpatient levosimendan has been proposed as a bridge strategy, but the optimal regimen and its impact on peri-transplant outcomes remain uncertain. Within a personalized-medicine framework, we targeted a low-output/INTERMACS 3 phenotype and operationalized an adaptable, protocolized levosimendan pathway focused on perfusion/congestion stabilization to preserve transplant candidacy. Methods: We conducted a single-center, retrospective cohort study of 25 consecutive adults actively listed for HT between 2019 and 2024, treated with a standardized outpatient program of a 14-day interval of 6 h intravenous levosimendan infusions (target 0.2 μg/kg/min infusions) continued until transplant. Personalization in this program was operationalized through (i) phenotype-based eligibility (low CI and elevated filling pressures despite GDMT), (ii) predefined titration and safety rules for blood pressure, arrhythmias, and renal function, and (iii) individualized continuation until transplant with nurse-supervised monitoring and review of patient trajectories. Baseline characteristics, treatment exposure and safety, changes in hospitalizations and biomarkers, and peri-transplant outcomes were analyzed. Results: Patients were predominantly male (68%), with a mean age of 47.9 ± 17.5 years and severe LV dysfunction (LVEF 30.6 ± 9.8%). Median treatment duration was 131 days (IQR 60–241). No infusions required discontinuation for hypotension or arrhythmia, and no adverse events were directly attributed to levosimendan. Two patients (8%) died on the waiting list, both unrelated to therapy. During treatment, HF hospitalizations decreased significantly compared with the previous 6 months (48% vs. 20%, p = 0.033), renal function remained stable, and NT-proBNP trended downward. Of the 23 patients transplanted, two (9%) underwent urgent HT during decompensation. Post-transplant, vasoplegia occurred in 26% (n = 6 of 23), and 30-day mortality was 9% (n = 2 of 23). Conclusions: By defining the target phenotype, therapeutic goals, and adaptation rules, this study shows how a standardized but flexible outpatient levosimendan regimen can function as a personalized bridge strategy for low-output advanced HF. The approach was associated with fewer hospitalizations, stable renal function, and acceptable peri-transplant outcomes, and merits confirmation in multicenter cohorts with attention to patient heterogeneity and treatment effect refinement. Full article

Cannabidiol (CBD) and other phytocannabinoids are gaining attention for their therapeutic potential in cardiovascular disease (CVD), the world’s leading cause of death. This review highlights advances in understanding the endocannabinoid system, including CB1 and CB2 receptors, and the mechanisms by which CBD exerts anti-inflammatory, antioxidative, vasoprotective, and immunomodulatory effects. Preclinical and translational studies indicate that selective activation of CB2 receptors may attenuate atherogenesis, limit infarct size in ischemia–reperfusion injury, decrease oxidative stress, and lessen chronic inflammation, while avoiding the psychotropic effects linked to CB1. CBD also acts on multiple molecular targets beyond the CB receptors, affecting redox-sensitive transcription factors, vascular tone, immune function, and endothelial integrity. Early clinical trials and observational studies suggest that CBD may lower blood pressure, improve endothelial function, and reduce sympatho-excitatory peptides such as catestatin, with a favorable safety profile. However, limited bioavailability, small sample sizes, short study durations, and uncertainty about long-term safety present challenges to its clinical use. Further research is needed to standardize dosing, refine receptor targeting, and clarify the role of the endocannabinoid system in cardiovascular health. Overall, current evidence supports CBD’s promise as an adjunct in CVD treatment, but broader clinical use requires more rigorous, large-scale studies. Full article

The aim of the study was to determine the effect of storage conditions and gelatin concentration on changes in selected physical properties of freeze-dried coated carrot bars. Freeze-dried carrot snacks were prepared and coated with an addition of 8% and 12% porcine gelatin. They were stored at different temperatures (4 °C, 25 °C, and 40 °C) for 3 and 6 months. After this time, selected physical properties of coated freeze-dried products were tested. The study’s results indicated that time and temperature significantly impacted water activity, dry matter content, hygroscopicity, mechanical properties, and color. Based on most of the tested features, the coated freeze-dried product should be stored for 3 months at 25 °C. The water activity was low (0.261), with high dry matter content (96%), a porosity value at 81%, and high hardness, while the total color difference was at 18.2. However, there were no notable changes in the porosity and internal structure of the samples based on storage temperature and duration. The most substantial effect of gelatin concentration on the tested features was observed in the control samples (coated and not stored). Developing sustainable packaging for freeze-dried carrot bars is a future challenge. Edible packaging allows for the use of food industry byproducts and is ecological. Full article

Cave systems are a kind of natural laboratory for interdisciplinary research on karstogenesis in the context of global changes. In this study, we investigate the concentration of ²²²Rn at 65 points in 37 representative caves of Bulgarian karst through continuous monitoring with passive and active detectors with a duration of 1 to 13 years. The concentration changes strongly both in the long term and seasonally, with values from 0.1 to 13 kBq m⁻³. These variations are analyzed from different perspectives (location and morphological features of the cave system, cave climate, ventilation regime, etc.). The seasonal change in the direction and intensity of ventilation is a leading factor determining the gas composition of the cave atmosphere during the year. Parallel measurements of ²²²Rn and CO₂ concentrations in the cave air show that both gases have a similar seasonal fluctuation. Cases of coincidences of an anomalous increase in the concentration of ²²²Rn with manifestations of seismic activity and micro-displacements along tectonic cracks in the caves have also been registered. The dependencies between the ²²²Rn concentration in the caves and in the soil above them are also discussed, as well as the possible connections between global trends in climate change and trends in ²²²Rn emissions. Special attention is paid to the risks of radiation exposure in show caves. A calculation procedure has been developed to achieve the realistic assessment of the effective dose of cave guides. It is based on information about the annual course of the ²²²Rn concentration in the respective cave and the time schedule of the guides’ stay in it. The calculation showed that the effective dose may exceed the permitted limits, and it is thus necessary to control it. Full article

A novel, cost-effective, label-free biosensing strategy has been established for real-time quantification of alkaline phosphatase (ALP) activity, integrating the Tyndall effect with smartphone imaging technology. This method utilizes a handheld laser diode to probe the enzyme-triggered in situ assembly of Cu-guanosine monophosphate (Cu-GMP) coordination polymers, which exhibit tunable Tyndall scattering properties. In the absence of ALP, Cu²⁺ ions chelate with GMP to form Cu-GMP coordination polymers, generating an intense Tyndall effect. Conversely, ALP-mediated hydrolysis of GMP disrupts the formation of Cu-GMP coordination polymers, resulting in diminished light scattering. The intensity of the Tyndall effect is directly proportional to the concentration of Cu-GMP coordination polymers, which in turn correlates with ALP activity levels. A comprehensive investigation of experimental parameters was conducted, including pH, incubation temperature, GMP concentration, incubation time, synthesis duration, and CuSO₄ concentration. Under optimized conditions, the developed smartphone-assisted colorimetric assay enables the detection of ALP activity within the range of 0.375–3.75 U/mL, with a limit of detection of 0.184 U/mL. The application of this method to serum samples yielded recovery rates ranging from 102.6% to 109.0%. In summary, this smartphone-based colorimetric platform offers a portable and versatile approach for instrument-free detection of ALP activity, with potential applications in point-of-care diagnostics and resource-limited settings. Full article

This study investigated the effects of ultrasonic treatment of olive paste prior to malaxation on oil yield (Y), enzyme activity and virgin olive oil (VOO) quality in four Croatian olive varieties: Istarska Bjelica, Rosulja, Oblica and Levantinka. The oils were extracted using the Abencor system according to a central composite experiment design, with treatment durations of 3–17 min and power levels of 256–640 W. The parameters analyzed included Y, oxidative stability index (OSI), antioxidant capacity (AC), phenolic and α-tocopherol content, volatile compounds, fatty acid profile, and the activity of lipoxygenase, β-glucosidase, polyphenol oxidase, and peroxidase. Olive variety was the most influential factor in all variables. The response surface methodology showed that ultrasonic treatment at low-to-medium intensity improved several quality attributes. For example, Y increased by 4% in Oblica, phenolic content increased by up to 17% in Istarska Bjelica, and OSI and AC increased by 13–15% in Istarska Bjelica and Levantinka. In contrast, longer treatment and higher ultrasound power had a negative effect. No significant differences were found in other parameters examined. Overall, the application of ultrasound led to measurable, though moderate, improvements in Y and VOO quality, with results strongly dependent on olive variety and treatment conditions. These results underline the need for further optimization tailored to each variety. Full article

Therapeutic plasma exchange (TPE) is increasingly recognized as a critical escalation therapy for managing acute multiple sclerosis (MS) relapses refractory to high-dose corticosteroids. Neuropathological and clinical evidence implicate humoral immune mechanisms, particularly autoantibodies, immune complexes, and complement activation, as key pathogenic drivers in a subset of MS attacks, notably those consistent with immunopathological pattern II. By removing these circulating immune effectors, TPE provides a rational strategy to dampen inflammation and promote neurological recovery. This review integrates current mechanistic insights with clinical efficacy data and practical implementation strategies for TPE in corticosteroid-refractory MS. Evidence from randomized controlled trials and observational cohorts demonstrates moderate-to-marked functional improvement in 40–60% of patients, with the greatest benefit observed when therapy is initiated within 14 days of symptom onset and cases demonstrating active inflammatory lesions on MRI. Predictors of a favorable response include younger age, short disease duration, severe syndromes involving optic nerve, brainstem, or spinal cord, and CSF markers of intrathecal B-cell activity. Although TPE is generally well tolerated in experienced centers, its broader adoption of TPE is limited by variability in access, institutional protocols, and provider familiarity. Standardization of treatment algorithms, validation of predictive biomarkers, and incorporation into streamlined clinical pathways are critical to maximizing its clinical impact. Future priorities include comparative trials against alternative escalation therapies, biomarker-guided patients’ selection, and comprehensive health-economic evaluations. Taken together, current evidence and recommendations from major neurology and apheresis societies support TPE as a valuable therapeutic modality capable of significantly improving relapse outcomes in appropriately selected MS patients. Full article

Spaceflight imposes unique physiological stressors that profoundly disrupt immune regulation, including impaired lymphocyte activation, latent viral reactivation, and chronic low-grade inflammation. While structured exercise is the cornerstone countermeasure for musculoskeletal and cardiovascular health, current protocols rarely integrate immune endpoints into their design. This review aims to synthesize current evidence on the immunological effects of exercise in spaceflight and propose a novel framework for immune-focused physical activity guidelines tailored to long-duration missions. Evidence indicates that exercise intensity and modality critically determine immune outcomes. Acute strenuous exercise may transiently suppress immunity via cortisol and reactive oxygen species pathways, whereas chronic moderate-to-vigorous training enhances immune surveillance, reduces systemic inflammation, and supports T-cell and NK-cell function. Exerkines such as IL-15, IL-7, and irisin emerge as central mediators of exercise-induced immunomodulation, with potential applications for spaceflight countermeasures. Incorporating immune health into exercise guidelines represents a necessary paradigm shift for astronaut care. A structured framework—emphasizing aerobic, resistance, and HIIT modalities; moderate-to-vigorous intensity; daily training; immune biomarker monitoring; and integration with nutrition and sleep—can enhance resilience against infection, viral reactivation, and cancer risk. Immune-focused countermeasures will be essential to safeguard astronaut health and ensure mission success on future deep-space expeditions. Full article

This paper proposes a transfer learning-based approach to enhance video-driven safety risk detection in industrial environments, addressing the critical challenge of limited generalization across diverse operational scenarios. Conventional deep learning models trained on specific operational contexts often fail when applied to new environments with different lighting, camera angles, or machinery configurations, exhibiting a significant drop in performance (e.g., F1-score declining below 0.85). To overcome this issue, an incremental feature transfer learning strategy is introduced, enabling efficient adaptation of risk detection models using only small amounts of data from new scenarios. This approach leverages prior knowledge from pre-trained models to reduce the reliance on large-labeled datasets, particularly valuable in industrial settings where rare but critical safety risk events are difficult to capture. Additionally, training efficiency is improved compared with a classic approach, supporting deployment on resource-constrained edge devices. The strategy involves incremental retraining using video segments with average durations ranging from 2.5 to 25 min (corresponding to 5–50% of new scenario data), approximately, enabling scalable generalization across multiple forklift-related risk activities. Interpretability is enhanced through SHAP-based analysis, which reveals a redistribution of feature relevance toward critical components, thereby improving model transparency and reducing annotation demands. Experimental results confirm that the transfer learning strategy significantly improves detection accuracy, robustness, and adaptability, making it a practical and scalable solution for safety monitoring in dynamic industrial environments. Full article

Background: Shoulder subluxation and pain are common complications of stroke that impair upper limb function. Objectives: This study conducted a systematic review and network meta-analysis to compare multiple therapeutic interventions for post-stroke shoulder subluxation, establishing an evidence-based hierarchy of treatment efficacy to optimize rehabilitation strategies and guide clinical practice. Methods: A comprehensive search was conducted using the MEDLINE, EMBASE, Cochrane, Scopus, and Web of Science databases until 8 August 2025. Randomized controlled trials evaluating treatments for shoulder subluxation, including neuromuscular electrical stimulation (NMES), Kinesio taping, corticosteroid injections, slings, repetitive peripheral magnetic stimulation, and electroacupuncture, were included. The follow-up duration in the included trials ranged from 1 to 12 weeks. Effect sizes were calculated using standardized mean differences with a random-effects model, and treatment rankings were determined using surface under the cumulative ranking curve (SUCRA). Results: Thirteen studies including 402 patients were analyzed. NMES was the most effective intervention for reducing subluxation distance (SUCRA: 84.9), while corticosteroid injections provided the greatest pain relief at rest (SUCRA: 73.6). Kinesio taping was most effective for functional recovery, as measured by the Fugl–Meyer Assessment (SUCRA: 98.5), and for pain relief during activity (SUCRA: 87.7). Conclusions: Our network meta-analysis suggests that different interventions are optimal for specific aspects of post-stroke shoulder impairment. NMES most effectively reduces subluxation distance, whereas corticosteroid injections are most effective for alleviating pain at rest. Kinesio taping appears superior for enhancing functional recovery and reducing pain during movement. These findings, based on short-term follow-up durations (1–12 weeks), provide an evidence-based ranking of interventions to support multimodal rehabilitation and inform clinical decision-making. The observed heterogeneity across studies underscores the need for standardized treatment protocols and rigorous long-term investigations. Full article

Background/Objectives: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder marked by insulin resistance, hyperglycemia, systemic inflammation, and immune imbalance. This randomized, double-blind, placebo-controlled, crossover trial investigated the effects of Bifidobacterium animalis subsp. lactis TISTR 2591 (BA-2591), a probiotic strain isolated in Thailand, on metabolic, immunologic, and safety parameters. Methods: A total of 44 Thai adults (aged 35–65) with T2DM receiving metformin monotherapy were administered BA-2591 (1 × 10⁹ CFU/g/day) or placebo for 6 weeks, followed by a 4-week washout and crossover. Results: Compared to placebo, BA-2591 significantly attenuated fasting blood glucose elevation (Δ = +1.143 mg/dL vs. +12.570 mg/dL; p < 0.001), minimized the increase in insulin resistance (HOMA-IR: Δ = +0.567 vs. +0.980; p = 0.006), and enhanced β-cell function (HOMA-β: Δ = +6.791% vs. −8.313%; p < 0.001). It also elevated immunoglobulin levels (IgM: +150.300 mg/dL; IgG: +261.500 mg/dL; p < 0.001), reduced LDL-C (p = 0.009), and decreased cathepsin D activity (p = 0.005), with no significant changes in IL-6, adiponectin, MDA, hs-CRP, or body composition. No severe adverse effects were reported. Conclusions: BA-2591 was safe and demonstrated modest, adjunctive benefits for fasting glycemia and immunologic profiles over 6 weeks, without changes in body weight or fat mass. These findings support BA-2591 as a potential adjunct to standard care in early T2DM; larger and longer-duration trials are needed to define its effects on longer-term outcomes. Full article