Search Results (1,156)

Calcific aortic stenosis (CAS) is a newly emerging pandemic in elderly individuals due to the aging of the population in the world. Surgical Aortic Valve Replacement (SAVR) and Transcatheter Aortic Valve Replacement (TAVR) are the cornerstone of the management of severe aortic stenosis accompanied by one or more symptoms. Moreover, an appropriate interventional treatment of CAS, in elderly patients, is a very complex decision for heart teams, to avoid bad outcomes such as operative mortality, cardiovascular and all-cause death, hospitalization for heart failure, worsening of quality of life. In fact, CAS in the elderly is not only a focal valve disease, but a very complex clinical picture with different risk factors and etiologies, differing underlying pathophysiology, large phenotypic heterogeneity in a context of subjective biological, phenotypic and functional aging until frailty and disability. In this review, we analyzed separately and in a more integrated manner, the natural and prognostic histories of the progression of aortic stenosis, the phenotypes of myocardial damage and heart failure, within the metrics and aging trajectory. The aim is to suggest, during the clinical timing of valve disease, the best interval time for an appropriate and effective interventional treatment in each older patient, beyond subjective symptoms by integration of clinical, geriatric, chemical, and advanced imaging biomarkers. Full article

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

Objective: Hearing rehabilitation using hearing aids keeps increasing in the general population. Patient-related outcome measures are essential to evaluate benefits. Although the IOI-HA is routinely used in France, its translated version from 2002 has never been validated. This study aimed to assess the psychometric properties of the French version of the IOI-HA questionnaire. Design: Controlled, prospective, monocentric study performed between February 2024 and January 2025. The forward–backward technique was used for translation of the questionnaire. Study Sample: 100 patients fitted with hearing aids completed the questionnaire. Thirty-five patients were retested 15 days after first completion. Results: Internal consistency, assessed by Cronbach’s alpha, was 0.863. Mean IOI-HA item scores ranged from 3.3 to 4.57. All seven items had a high degree of consistency with the total score, except for item Q1 which had a moderate score (0.45). Cronbach’s alpha after item deletion confirmed internal consistency. Intra-class correlation coefficients ranged from 0.622 (Q7) to 0.767 (Q5) and were all statistically significant (p < 0.001), revealing high reliability over time. No significant correlation was found between item scores and age, unilateral or bilateral hearing aid use or accompanying symptoms (tinnitus, dizziness). Conclusions: The French translation of the IOI-HA questionnaire, published in 2002, is a valid and reliable questionnaire evaluating hearing aid satisfaction. This validated questionnaire can now be used in daily clinical practice. Full article

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease with limited therapeutic options and increasing global incidence, with a median survival of only 2–5 years. The clinical utility of macrophage polarization to regulate the progression of pulmonary fibrosis remains understudied. This study determined the efficacy of nintedanib and pexidartinib (PLX3397) combination therapy for treating IPF. Combination treatment effectively inhibited the progression of radiation-induced pulmonary fibrosis (RIPF) and prolonged survival in bleomycin-treated mice. Micro-CT analysis revealed a significant tissue repair efficacy. The therapy significantly normalized the abnormal vascular structure observed during RIPF and bleomycin-induced pulmonary fibrosis progression and was accompanied by a decrease in the M2 population. Polarized M1 macrophages enhanced normalized tube formation of irradiated endothelial cells (ECs) in vitro; M2 macrophages increased adhesion in irradiated ECs and abnormal tube formation. Single-cell RNA sequencing data from patients with IPF further supports colony stimulating factor (CSF) 1 upregulation in macrophages and downregulation of capillary EC markers. This study highlights a promising combination strategy to overcome the therapeutic limitations of monotherapy with nintedanib for the treatment of IPF. Full article

Polycystic ovary syndrome (PCOS) is a complex condition affecting women of reproductive age, characterized by menstrual irregularities, hyperandrogenism, polycystic ovarian morphology, and low-grade inflammation accompanied by oxidative stress and increased autoimmune risk, particularly Hashimoto’s thyroiditis. Many studies have examined thyroid autoantibodies—anti-thyroid peroxidase antibodies (anti-TPO) and anti-thyroglobulin antibodies (anti-TG)—in PCOS; however, observed differences in baseline thyroid-stimulating hormone (TSH) levels and body mass indices (BMIs) impede a direct interpretation of the results. This systematic review and meta-analysis aimed to summarize the available evidence on the prevalence and levels of anti-TPO and anti-TG in women with PCOS. We conducted a systematic search of PubMed, Scopus, and Embase, which yielded 40 eligible, observational studies including 6045 women with PCOS and 4527 controls. Subgroup analyses were conducted separately for TSH- and BMI-matched populations. Anti-TPO prevalence (odds ratio [OR] = 2.03; 95% confidence interval [CI]: 1.35–3.04; p = 0.0006) and levels (standardized mean difference [SMD] = 0.63; 95% CI: 0.37–0.88; p < 0.00001) were significantly higher in PCOS patients. Anti-TG prevalence (OR = 1.92; 95% CI: 1.23–3.01; p = 0.004) and levels (SMD = 0.41; 95% CI: 0.18–0.64; p = 0.0004) were also significantly elevated. In matched subgroups, prevalence differences were no longer significant, though anti-TPO levels remained significantly elevated and anti-TG levels were borderline significant in the TSH-matched subgroup of PCOS women. Although differences in thyroid autoantibody prevalence in women with PCOS appear to be driven by elevated TSH levels and BMIs, the persistently increased antibody levels in the majority of matched subgroups suggest that PCOS itself may contribute independently to heightened autoimmune activation. Full article

Projections indicate that the global urban population is anticipated to reach 67.2% by 2050, accompanied by a threefold increase in urban built-up areas worldwide. Urbanization has profoundly transformed Earth’s natural environment, notably characterized by the drastic reduction and fragmentation of wildlife habitats. These changes contribute to local species extinction, leading to biodiversity loss and profoundly impacting ecological processes and regional sustainable development. However, within urban settings, certain ‘generalist’ species demonstrate survival capabilities contingent upon phenotypic plasticity. The co-evolution of gut microbiota with their hosts emerges as a key driver of this phenotypic plasticity. The presence of diverse gut microbiota constitutes a crucial adaptive mechanism essential for enabling hosts to adjust to rapid environmental shifts. This review comprehensively explores amniote gut microbial changes in the context of urbanization, examining potential drivers of these changes (including diet and environmental pollutants) and their potential consequences for host health (such as physiology, metabolism, immune function, and susceptibility to infectious and non-infectious diseases). Ultimately, the implications of the gut microbiome are highlighted for elucidating key issues in ecology and evolution. This understanding is expected to enhance our comprehension of species adaptation in the Anthropocene. Full article

Sampling with replacement occurs when drawing without removing individuals from finite populations. It is a common distribution technique used in physics, biology, and medicine. It is used in state analysis of qubits, the physics of particle interactions, studies of genetic variation and variability, and analyzing the treatment effects from clinical trial analyses. When applied, sample statistics should be accompanied by confidence intervals. The major difficulty in expressing the confidence intervals in sampling with replacement consists of discreetness regarding the probability distribution. As a result, no mathematical formula can handle an optimum solution. Using a simple algorithm is proposed in order to obtain confidence intervals for sampling with replacement variables (x from m trials with replacement) and their proportion ($x/m$). A question-based discussion is presented. Traditional confidence intervals often require large sample sizes. Confidence intervals, constructed in a deterministic way provided by the proposed algorithm for sampling with replacement, allow constructing intervals without constraints. Full article

Intermittent fasting (IF) and caloric restriction (CR) have garnered attention for their potential to enhance cognitive function, particularly in aging and metabolically compromised populations. This narrative review critically examines whether the cognitive benefits of IF are attributable to its specific fasting patterns or are instead mediated by the production of weight loss, fat loss, and improvements in insulin sensitivity. Evidence from human trials suggests that reductions in body weight, especially visceral adiposity, and improvements in insulin resistance are key factors linked to enhanced cognitive performance. Comparisons between the results of IF and CR trials show comparable cognitive outcomes, supporting the idea that negative energy balance, rather than fasting or altered eating patterns, drive these effects. However, further investigation of specific types of IF patterns, as well as possible cognitive domains to be affected, may identify mechanisms through which IF can yield benefits on neurocognitive health beyond those of loss of body fat and its accompanying inflammatory state. Full article

Background: Mass casualty events in conflict-affected regions can lead to the displacement of civilians and are often accompanied by substantial psychological and emotional impact on those affected. While physical activity is known to support mental health, the ways in which it relates to anxiety, resilience, and well-being in conflict-affected populations are still being explored. Objective: This study examined the associations among physical activity, anxiety, resilience, and well-being in evacuees from a conflict-affected zone. We hypothesized that higher levels of intense physical activity would be associated with higher levels of resilience and well-being and lower levels of anxiety. Methods: In this cross-sectional study, 107 evacuees completed an online survey in December 2023. The questionnaire assessed the frequency and intensity of physical activity, generalized anxiety, resilience, and well-being. Participants were categorized by weekly total physical activity levels. Data was analyzed using ANOVA, Pearson correlations, and multiple linear regression. Results: Evacuees engaging in more than three hours of vigorous-intensity physical activity exhibited significantly higher resilience and better well-being compared to those with lower activity levels. Although not statistically significant, the data suggested a possible pattern of lower anxiety among evacuees engaging in higher levels of physical activity. Regression analysis identified higher resilience and lower anxiety as significant predictors of greater mental well-being. Additionally, residing in a community exposed to a higher number of traumatic events was associated with reduced well-being. The overall model explained a substantial portion of the variance in mental well-being. Conclusions: Physical activity, especially intense exercise, is associated with improved mental health and resilience among evacuees, supporting its inclusion in interventions for trauma-affected populations. Full article

This study focuses on the Triangle of Central China and investigates the spatiotemporal evolution, driving factors, and impacts of population aging on regional sustainable development from 2000 to 2020. The study adopts an innovative two-scale analytical framework at the prefecture and district/county level, integrating spatial autocorrelation analysis, the Geodetector model, and geographically weighted regression. The results show a significant acceleration in population aging across the study area, accompanied by pronounced spatial clustering, particularly in western Hubei and the Wuhan metropolitan area. Over time, the spatial distribution has evolved from a relatively dispersed pattern to one of high concentration. Key drivers of the spatial heterogeneity of aging include economic disparities, demographic transitions, and the uneven spatial allocation of public services such as healthcare and education. These aging patterns profoundly affect the region’s potential for sustainable development. Accordingly, the study proposes a multi-scale collaborative governance strategy: At the prefecture level, efforts should focus on promoting the coordinated development of the silver economy and optimizing the spatial redistribution of healthcare resources; At the district and county level, priorities should include strengthening infrastructure, curbing the outflow of young labor, and improving access to basic public services. By integrating spatial analysis techniques with sustainable development policy recommendations, this study provides a basis for scientifically measuring, understanding, and managing demographic transitions. This is essential for achieving long-term socioeconomic sustainability in rapidly aging regions. Full article

Urbanization is accompanied by an increased use of building materials. However, the lack of high-resolution building material stock (BMS) maps limits our understanding of the relationship between BMS and urban heat. To address this, we estimated BMS across eight typical Chinese megacities using multi-source geographic data and investigated the relationship between BMS and land surface temperature (LST). The results showed that (1) the total BMS for the eight megacities was 9175.07 Mt, with Beijing and Shanghai having the largest shares. While BMS correlated significantly with population, growth patterns varied across cities. (2) Spatial autocorrelation between BMS and LST was evident. Around 16% of urban areas exhibited High–High clustering between BMS and LST, decreasing to 10% during the daytime. The relationship between BMS and LST is nonlinear, and also prominent at night, especially in Beijing. (3) Diverse building forms, especially building height, contribute to a nonlinear relationship between BMS and LST. Full article

Bacterial persisters are dormant cells that survive antibiotic treatment, serving as a reservoir for the emergence of resistant mutations. The evolution of antibiotic resistance poses a significant challenge to public health. In this study, we investigated the development of resistance in Pseudomonas aeruginosa persister cells by exposing the reference strain PA14 to meropenem and tracked the emergence of resistance mutations over serial passages. Whole-genome sequencing of the populations or individual resistant strains revealed evolutionary trajectories. In the initial passages, low-level meropenem-resistant mutants harbored various mutations, accompanied by increasing population survival. Then, mutations in the oprD gene appeared, followed by mutation in the mexR gene in most of the cells, leading to high-level meropenem resistance and collateral resistance to ciprofloxacin. Our study provides insights into the evolutionary pathways of P. aeruginosa under lethal antibiotic pressure, highlighting the dynamic interplay between persister cells and the emergence of resistance mutations. Full article

Introduction: Unilateral cleft lip and palate (CLP) is a severe orofacial birth defect characterized by improper fusion of facial parts and disturbed orofacial functions. The defect manifests as a gap in the orofacial tissues that is accompanied by defective healing patterns and chronic inflammation. The immune system’s defense factors modulate immunity, inflammation, and healing. Angiogenesis factors control blood-vessel formation. Therefore, these factors are vital in the immunological assessment and understanding of CLP morphopathogenesis. The aim of the study is to assess the distribution of vascular endothelial growth factor (VEGF), transforming growth factor beta 1 (TGF- β1), the total macrophage population and the M2 subtype, heat-shock proteins (HSP) 60 and 70, and nuclear factor kappa B (NF-κB) p50 and p65 subtypes in the affected tissue of children with CLP before and during primary dentition. Materials and Methods: Tissue samples were obtained from 15 patients aged from 3 to 8 months during veloplastic surgery. Five controls were used for comparison of data. Immunohistochemistry, light microscopy, semi-quantitative evaluation (from 0 to ++++), and statistics (Mann–Whitney U test and Spearman’s rank correlation) were used to evaluate the data for statistically significant differences and correlations between the groups. Results: Epithelial tissues affected by CLP presented with statistically significant increases in levels of VEGF (p = 0.007), total macrophages (p = 0.007), HSP60 (p = 0.001), NF-κB p65 (p = 0.000), and p50 (p = 0.045), but with a decrease in M2 macrophages (p = 0.025). Blood vessels in CLP-affected tissues showed a statistically significant increase in levels of NF-κB p65 (p = 0.003) and a statistically significant decrease in M2 numbers (p = 0.014). Connective tissue presented with no statistically significant differences. Spearman’s rank correlation revealed multiple statistically significant correlations—26 positive and 5 negative. Conclusions: Statistically significant changes in levels of VEGF and both NF-κB subtypes and numbers of total macrophages and M2 macrophages suggest a possible alteration of variable immune and inflammatory reactions and macrophage functions associated with the initiation and maintenance of the chronic process and the resulting damage. Full article

Peripheral artery disease (PAD) is a common vascular disorder in the elderly, often accompanied by frailty syndrome, which is associated with increased inflammation, oxidative stress, and functional decline. Nutritional strategies, particularly those involving bioactive compounds like flavonoids and omega-3 fatty acids, have been suggested as potential approaches to modulate these pathological processes. This narrative review summarizes current evidence regarding the anti-inflammatory and antioxidant effects of flavonoids and omega-3 fatty acids, and their possible roles in mitigating frailty syndrome in patients with PAD. We examine mechanistic pathways including NF-κB, AMPK, PI3K/Akt/mTOR, and Nrf2, which are implicated in chronic inflammation, endothelial dysfunction, and muscle wasting. Although studies in general and aging populations suggest beneficial effects of these compounds on vascular and muscle health, specific evidence in PAD patients remains limited. Flavonoids may reduce pro-inflammatory cytokine production and enhance antioxidant responses, while omega-3 fatty acids have shown potential in modulating inflammatory signaling and supporting vascular repair. Current data provide a basis for further investigation into the dietary modulation of frailty syndrome in PAD. Understanding the impact of these nutrients may offer insights into adjunctive strategies for improving patient outcomes. Full article