Search Results (29,917)

In healthy humans, insulin at physiological concentrations exerts acute vasodilatory actions on both resistance and terminal arterioles, leading, respectively, to increased total blood flow and the microvascular network volume being perfused. The process of increasing capillary network volume is frequently referred to as “capillary recruitment”. Together these two vascular actions of insulin enhance the delivery of oxygen, nutrients, and insulin itself to tissues. Both processes are diminished by insulin resistance. Here we examined interactions between insulin’s acute (within 2 h) actions on blood pressure (both central and peripheral) and on capillary recruitment in healthy controls and in four distinct groups of people with heightened cardio-metabolic disease (CMD) risk: individuals with obesity, metabolic syndrome, and type 1 or type 2 diabetes. Insulin increased microvascular blood volume (MBV) more effectively in controls than in each of the four CMD risk groups (p < 0.001). Conversely, insulin lowered both central and peripheral systolic pressure (p < 0.05 or less) in each of the CMD risk groups but not in the controls. The insulin-induced blood pressure decrements were greater in the metabolic syndrome, type 2 diabetes, and obesity groups (p < 0.05 or less) than in the controls. The greater blood pressure declines likely reflect decreased sympathetic baroreceptor reflex tone. These effects on blood pressure combined with the diminished dilation of terminal arterioles due to microvascular insulin resistance in the CMD risk subjects led to decreased distal microvascular perfusion as evidenced by changes in MBV. These findings highlight the complex interplay between insulin’s actions on resistance and terminal arterioles in individuals with a high CMD risk, underscoring the importance of addressing microvascular dysfunction in these conditions. Full article

Background: Long-term right ventricular pacing (RVP) can cause electrical and mechanical dyssynchrony, resulting in adverse outcomes. Recently, left bundle branch area pacing (LBBAP) has emerged as a physiological pacing modality and is considered a promising alternative. To date, the long-term outcomes of LBBAP compared with RVP, particularly with respect to sex differences, remain unclear. Methods: Between January 2017 and July 2024, 1211 patients who underwent de novo pacemaker implantation were enrolled and categorized into RVP (n = 789) and LBBAP (n = 422). The primary outcome was a composite of all-cause mortality, heart failure hospitalization (HFH), and pacing-induced cardiomyopathy (PICM). Propensity score matching (PSM) was employed to minimize the selection bias and achieve comparability among the study population. A post hoc power analysis based on the observed effect size and sample size showed a power of 80%, confirming sufficient sensitivity to detect group differences. Results: After PSM, 764 patients were analyzed. The mean age of the patients was 74.6 ± 10.5 years in RVP and 74.5 ± 9.8 years in LBBAP, respectively, and 52.3% patients were male. Patients with LBBAP had a lower incidence of the primary outcome (8.6% vs. 24.6%, p < 0.001), HFH (2.6% vs. 13.6%, p < 0.001), and all-cause mortality (6.5% vs. 13.9%, p < 0.001) compared with RVP. There were no significant differences in the clinical outcomes, including the primary outcome, HFH and all-cause mortality, between the sexes in the group with either RVP or LBBAP. However, during a 2-year follow-up period for survival analysis, male patients with LBBAP had a significant lower incidence of all the endpoints, whereas female patients with LBBAP had a lower incidence of HFH [HR 0.14 (95% CI 0.06–0.32), p = 0.001] compared with those with RVP. Conclusions: Regardless of sex, patients with LBBAP had a lower risk of poor clinical outcomes, including HFH and all-cause mortality, compared to those with RVP. Moreover, compared with RVP, LBBAP decreased the risks of all the major endpoints in male patients and the risk of HFH particularly in female patients. Further research is needed to establish the sex-specific responses to LBBAP. Full article

Perfluorooctanoic acid (PFOA) and its replacement, GenX, are per- and polyfluoroalkyl substances (PFASs) widely used in industrial and consumer applications. Pregnant women are a vulnerable population to environmental pollutants. The maternal effects of GenX and PFOA exposure during pregnancy have not been fully elucidated. In this study, pregnant mice received daily oral doses of GenX (2 mg/kg/day), PFOA (1 mg/kg/day), or Milli-Q water (control) throughout gestation. Histopathological analyses revealed significant liver abnormalities in both exposure groups, including hepatocyte swelling, cellular disarray, eosinophilic degeneration, karyopyknosis, lipid vacuolation, and increased inflammatory responses. Through transcriptomics analyses, it was found that multiple metabolic and inflammatory pathways were enriched in both exposure groups. In the GenX group, overexpression of CYP4A, c-Myc, and Oatp2 proteins and decreased expression of EGFR and β-catenin in the liver suggested disruption of lipid and bile acid metabolism. In the PFOA group, significantly upregulated protein levels of NLRP3, GSDMD, caspase-1, IL-18, and IL-1β indicated hepatic pyroptosis. Despite these distinct pathways, both compounds triggered inflammatory cytokine release in the liver, consistent with the results of the transcriptomics analysis, suggesting shared mechanisms of inflammatory liver injury. Taken together, our findings provided novel insights into the hepatotoxicity mechanisms of GenX and PFOA exposure during pregnancy, underscoring the potential health risks associated with PFAS exposure. Full article

Background: Candida auris (now Candidozyma auris) is an emerging pathogen that causes nosocomial candidemia, particularly in intensive care unit (ICU) settings. Its high resistance rates, prolonged environmental persistence, and outbreak potential underscore the need for robust comparative studies with non-auris Candida species (NACS). Methods: In this retrospective, case–control study, adult ICU patients with candidemia were enrolled between April 2022 and October 2024. Clinical data, risk factors, and mortality at 14, 30, and 90 days were compared between the C. auris and NACS groups. Univariate and multivariate logistic regression analyses were performed to identify mortality-associated factors. Results: Of the 182 patients analyzed, candidemia due to C. auris was identified in 33 (18.1%) cases, while 149 (81.9%) cases involved NACS. Fluconazole resistance (p < 0.001), prior antifungal exposure (p = 0.003), urinary catheter use (p = 0.040), and the length of ICU stay before the onset of candidemia (p < 0.001) were significantly higher in the C. auris cases. However, mortality rates at 14, 30, and 90 days were similar between the groups (p = 0.331, 0.108, and 0.273, respectively). The Sequential Organ Failure Assessment score was the only consistent independent predictor of mortality at all time points. In the NACS cases, the Pitt Bacteremia Score and sepsis also predicted 30- and 90-day mortality. While late recurrence was more frequent in the cases of C. auris, early recurrence and other risk factors were similar between the groups. Conclusion: C. auris candidemia was associated with higher fluconazole resistance, prior antifungal use, longer ICU stay, more frequent urinary catheterization, and later recurrence than the NACS cases. However, the mortality rates at 14, 30, and 90 days were comparable. Outcomes were primarily influenced by illness severity rather than the infecting Candida species, highlighting the importance of timely therapy, stewardship, and infection control. Full article

Background/Objectives: Enriched oral nutritional supplementation (ONS) has been shown to increase muscle mass in cancer patients. This study aims to identify the immunomodulatory effects and predictive biomarkers associated with this intervention. Methods: The soluble levels of 92 immune- and oncology-related mediators were determined before and after an intervention (8 weeks) in 28 patients with cancer receiving either a standard (n = 14) or an enriched ONS (n = 14) using the Olink proteomics analysis pipeline (Olink^® Target 96 Immuno-Oncology panel (Uppsala, Sweden)) Results: Patients receiving enriched ONS experienced an average weight gain of 1.4 kg and a muscle mass increase of 2.2 kg after 8 weeks, both statistically significant (p < 0.05), while no such improvements were observed in the standard ONS group. Inflammatory markers TRAIL and LAMP3 were significantly reduced, along with an increase in Gal-1, suggesting lower inflammation and enhanced myogenic differentiation. However, patients who failed to gain muscle mass with the enriched formula showed a more aggressive inflammatory profile, characterized by higher serum levels of soluble MUC16, ARG, and IL12RB1. Interestingly, muscle mass gain could be predicted before the intervention, as responders had lower baseline levels of PGF, CD28, and IL12RB1. These differences were specific to recipients of the enriched ONS, confirming its immunomodulatory effects. Conclusions: Our findings support the use of enriched oral nutritional supplementation (ONS) as an effective strategy not only to enhance caloric and protein intake but also to promote anabolism and preserve muscle mass in cancer patients. The identification of immune profiles suggests that specific biomarkers could be used to predict which patients will benefit most from this type of intervention. This may allow for the implementation of personalized immunonutrition strategies that optimize resource allocation and improve clinical outcomes, particularly in vulnerable populations at risk of cachexia. Full article

Background: Osteodysplastic syndromes comprise a very diverse group of clinically and genetically heterogeneous disorders characterized by defects in bone and connective tissue development, as well as in bone density. Here, we report the case of a 48-year-old female with a complex medical history characterized by bone dysplasia, hyperostosis, and partial tooth agenesis. Methods: Genetic testing was performed using WES analysis and Sanger sequencing. Molecular modeling analysis and dynamics simulation explored the impact of detected pathogenic variants. Results: The genetic analysis detected multiple pathogenic variants in genes CREB3L1, SLCO2A1, SFRP4, LRP5, and LRP6, each of which has been associated with rare osteodysplastic syndromes. The patient was homozygous for the same rare alleles associated with three of the identified autosomal recessive disorders osteogenesis imperfecta type XVI, primary hypertrophic osteoarthropathy, and metaphyseal dysplasia Pyle type. She also had a variant linked to autosomal dominant endosteal hyperostosis and a variant previously associated with increased risk of osteoporosis and bone fractures. Two of the detected variants are predicted to cause abnormal splicing, while molecular modeling and dynamics simulations analysis suggest that the other three variants probably confer altered local secondary structure and flexibility that may have functionally devastating consequences. Conclusions: Our case highlights the rare coexistence of multiple osteodysplastic syndromes in a single patient that may complicate differential diagnosis. Furthermore, this case emphasizes the necessity for early genetic investigation of such complex cases with overlying phenotypic traits, followed by genetic counseling, facilitating orchestration of clinical interventions and allowing prevention and/or prompt management of manifestations. Full article

This study examines the impact of geopolitical risk (GPR) on the connectedness dynamics among the sovereign bonds of the emerging seven (E7) and the Group of Seven (G7) countries. Initially, a quantile-based vector-autoregressive (Q-VAR) connectedness approach is used to calculate the total connectedness index (TCI) among sovereign bonds under different market states. Then, the impact of GPR on the TCI at the median and tails is estimated to examine if GPR affects the TCI among sovereign bonds. Using daily yields from 30 January 2012, to 17 June 2024, the findings show that the GPR is one of the significant determinants of the TCI among sovereign bonds during normal and extreme market conditions. Other determinants of the TCI include yields on Treasury bills (T-bills), the exchange rate, and the financial market volatility index. The impact of GPR on the TCI varies significantly during different GPR episodes and bond market conditions. The effect of GPR on the TCI among sovereign bonds yields is higher during war times and when bond yields are average. These findings can be utilized by investors seeking to achieve international diversification and policymakers aiming to mitigate the effects of heightened geopolitical risk on financial stability. Furthermore, GPR can be used as an early signal tool for systematic tail risk spillovers among sovereign bonds. Full article

Background: Infectious complications are common after percutaneous nephrolithotomy (PCNL). Clinical guidelines recommend, previous to surgery, prolonged antibiotic regimens in patients with preoperative positive urine cultures to reduce infectious risk. However, such strategies may increase selective pressure and promote antimicrobial resistance. Evidence supporting the use of a single antibiotic dose tailored to culture sensitivity in these cases is limited but emerging. Methods: We conducted a retrospective observational study including 187 PCNL procedures performed between 2021 and 2023 under an individualized antibiotic prophylaxis protocol. Patients with negative or contaminated urine cultures received a single empirical dose, while those with recent positive cultures received a single dose based on antimicrobial susceptibility testing. Postoperative complications—including fever, sepsis, and a composite outcome—were analyzed through multivariable logistic regression, comparing high- and low-risk patients. Results: A total of 67.9% of procedures were performed in patients meeting at least one high-risk criterion, including a positive preoperative urine culture in 32.1%. The overall incidence of infectious complications was 11.9% (fever 8.7%, sepsis 3.2%), with no significant differences between risk groups. A low concordance was observed between preoperative and intraoperative urine cultures (Spearman = 0.3954). Conclusions: A single preoperative antibiotic dose adjusted to the antibiogram, even in patients with a positive urine culture, was not associated with increased infectious complications. This approach is an initial step that supports a rational and individualized prophylactic strategy aligned with the goals of antimicrobial stewardship programs (ASPs). Full article

Background/Objectives: This study aimed to evaluate the impact of an immersive virtual reality (IVR) program on balance, physical fitness, risk of falling, fear of falling, fatigue, and quality of life in older adults compared with an active control group (ACG). Methods: A total of 44 older adults were randomly assigned to either the IVR group (n = 22) or the ACG (n = 22) for an 8-week period. The IVR group participated in 35-min immersive virtual reality sessions three times a week, whereas the ACG followed a home-based traditional exercise program. Evaluations were conducted both before and after the intervention period. Results: Compared with the ACG, the participants in the IVR group demonstrated significant improvements in balance, upper and lower extremity strength, lower extremity flexibility, fatigue levels, and specific aspects of quality of life such as autonomy and social participation. Treatment satisfaction was also higher in the IVR group. Conclusions: An 8-week immersive virtual reality intervention was effective in improving physical function, reducing fatigue, and enhancing specific domains of quality of life among older adults. Full article

Honey bees (Apis mellifera ligustica) are essential pollinators in both ecosystems and agricultural production. However, their populations are declining due to various factors, including pesticide exposure. Despite their importance, the reproductive castes, particularly drones, remain understudied in terms of pesticide effects. To investigate the effects of azoxystrobin and picoxystrobin on honey bee drones, the drones were exposed to different concentrations of azoxystrobin and picoxystrobin for 14 days; the drone survival, body weight, nutrient content, reproductive organs, and sperm concentration were assessed. Results showed that exposure to both fungicides caused a significant reduction in drone survival rates, with survival rates decreasing progressively as the duration of exposure increased. Compared to the control group, the body weights of drones in all treatment groups were significantly lower on days 7 and 14. Nutrient analysis revealed that low concentrations of azoxystrobin and picoxystrobin increased protein levels, while free fatty acid content decreased significantly in all treatment groups. No significant changes were observed in the total carbohydrate content. Morphological examination of reproductive organs showed that the lengths of the mucus glands and seminal vesicles in drones were significantly shorter in the treatment groups compared to the control group. Furthermore, exposure to azoxystrobin and picoxystrobin resulted in a significant decline in sperm concentration in the drones. These findings indicate that azoxystrobin and picoxystrobin have adverse effects on the health and reproductive capacity of honey bee drones. The present study highlights the need to reassess the risks posed by these fungicides to pollinators, particularly given the critical role of drones in maintaining the genetic diversity and resilience of honey bee colonies. Further research is warranted to elucidate the underlying mechanisms of these effects and explore potential mitigation strategies. Full article

Cognitive function is critical for overall health, with vitamin D’s impact under extensive investigation. This review explores the association between vitamin D and cognitive health, its neuroprotective mechanisms, and the therapeutic potential of supplementation in cognitive decline. Observational studies link low vitamin D levels to increased cognitive deterioration risk, particularly in Alzheimer’s disease, vascular dementia, Parkinson’s disease, and schizophrenia. Clinical trial results on vitamin D supplementation’s cognitive benefits are inconclusive. Vitamin D’s neuroprotective effects are complex, influencing cognitive abilities by interacting with neuronal and glial cells, modulating immune responses, and regulating key molecular pathways. Challenges remain in clinical applications, including determining optimal vitamin D levels, effective supplementation forms and doses, and identifying responsive populations. The review advocates for robust clinical trials to address these gaps, facilitating informed use of vitamin D in cognitive health. Future research should focus on the optimal timing, duration, and target groups for supplementation to enhance cognitive outcomes and reduce risks. Full article

Background: Left atrial appendage occlusion (LAAO) is a valuable alternative to long-term anticoagulation in patients with atrial fibrillation (AF) and a high bleeding risk. However, effective vascular closure following large-bore venous access remains a clinical challenge, particularly in patients with multiple comorbidities. This study compares two venous closure techniques—Z-sutures and the suture-mediated ProGlide™ device—regarding their safety and efficacy in patients undergoing LAAO. Methods: We conducted a single-center observational study including 163 patients treated with LAAO between 2021 and 2024. Closure was achieved via a Z-suture (n = 126) or the ProGlide™ (n = 37) based on operator preference. The primary endpoint was clinically relevant bleeding (BARC ≥ 2). The secondary endpoints included 30-day mortality and hospital stay duration. Results: The Z-suture group included older and more comorbid patients. Despite these differences, the bleeding rates were comparable between groups. Clinically relevant bleeding was infrequent (Z-suture: 12.6%; ProGlide™: 13.5%). No 30-day deaths occurred in either group, and their hospital stay durations were similar. Conclusions: Both the Z-suture and ProGlide™ techniques demonstrated comparable safety and efficacy. Due to their simplicity and potential cost advantage, Z-sutures may be a practical alternative in routine care for high-risk patients. Full article

Background/Objectives: Aging is often accompanied by physical and cognitive decline, affecting older adults’ mobility. Virtual reality (VR) offers innovative opportunities to safely practice everyday tasks, such as street crossing. This study was designed as a feasibility and pilot study to explore acceptance, usability, and preliminary effects of a VR-based road-crossing intervention for older adults. It investigates the use of virtual reality (VR) as an innovative training tool to support senior citizens in safely navigating everyday challenges such as crossing roads. By providing an immersive environment with realistic traffic scenarios, VR enables participants to practice in a safe and controlled setting, minimizing the risks associated with real-world road traffic. Methods: A VR training application called “Wegfest” was developed to facilitate targeted road-crossing practice. The application simulates various scenarios commonly encountered by older adults, such as crossing busy streets or waiting at traffic lights. The study applied a single-group pre-post design. Outcomes included the Timed Up and Go test (TUG), Falls Efficacy Scale-International (FES-I), and Montreal Cognitive Assessment (MoCA). Results: The development process of “Wegfest” demonstrates how a highly realistic street environment can be created for VR-based road-crossing training. Significant improvements were found in the Timed Up and Go test (p = 0.002, d = 0.784) and fall-related self-efficacy (FES-I, p = 0.005). No change was observed in cognitive function (MoCA, p = 0.56). Participants reported increased subjective safety (p < 0.001). Discussion: The development of the VR training application “Wegfest” highlights the feasibility of creating realistic virtual environments for skill development. By leveraging immersive technology, both physical and cognitive skills required for road-crossing can be effectively trained. The findings suggest that “Wegfest” has the potential to enhance the mobility and safety of older adults in road traffic through immersive experiences and targeted training interventions. Conclusions: As an innovative training tool, the VR application not only provides an engaging and enjoyable learning environment but also fosters self-confidence and independence among older adults in traffic settings. Regular training within the virtual world enables senior citizens to continuously refine their skills, ultimately improving their quality of life. Full article

Kidney transplant recipients face a substantial burden of premature mortality and morbidity, primarily due to persistent inflammation, cardiovascular risk, and nutritional deficiencies. Traditional nutritional interventions in this population have either focused on supplementing individual nutrients—often with limited efficacy—or required comprehensive dietary overhauls that compromise patient adherence. In this narrative review, we explore the rationale for dietary nut enrichment as a feasible, multi-nutrient strategy tailored to the needs of kidney transplant recipients. Nuts, including peanuts and tree nuts with no added salt, sugar, or oil, are rich in beneficial fats, proteins, vitamins, minerals, and bioactive compounds. We summarize the multiple post-transplant challenges—including obesity, sarcopenia, dyslipidemia, hypertension, immunological dysfunction, and chronic inflammation—and discuss how nut consumption may mitigate these issues through mechanisms involving improved micro-nutrient intake (e.g., magnesium, potassium, selenium), lipid profile modulation, endothelial function, immune support, and gut microbiota health. Additionally, we highlight the scarcity of randomized controlled trials in high-risk populations such as kidney transplant recipients and make the case for studying this group as a model for investigating the clinical efficacy of nuts as a nutritional intervention. We also consider practical aspects for future clinical trials, including the choice of study population, intervention design, duration, nut type, dosage, and primary outcome measures such as systemic inflammation. Finally, potential risks such as nut allergies and oxalate or mycotoxin exposure are addressed. Altogether, this review proposes dietary nut enrichment as a promising, simple, and sustainable multi-nutrient approach to support cardiometabolic and immune health in kidney transplant recipients, warranting formal investigation in clinical trials. Full article

As distant hybridization has profound implications for evolutionary biology, aquaculture, and biodiversity conservation, this study aims to elucidate patterns of maternal inheritance, genetic divergence, and phylogenetic relationships by synthesizing mitochondrial genome (mitogenome) data from 74 distant hybrid fish species. These hybrids span diverse taxa, including 48 freshwater and 26 marine species, with a focus on Cyprinidae (n = 35) and Epinephelus (n = 14), representing the most frequently hybridized groups in freshwater and marine systems, respectively. Mitogenome lengths were highly conserved (15,973 to 17,114 bp); however, the genetic distances between hybrids and maternal species varied from 0.001 to 0.17, with 19 hybrids (25.7%) showing distances >0.02. Variable sites in these hybrids were randomly distributed but enriched in hypervariable regions, such as the D-loop and NADH dehydrogenase subunits 1, 3 and 6 (ND2, ND3, and ND6) genes, likely reflecting maternal inheritance (reported in Cyprinus carpio × Carassius auratus). Moreover, these genes were under purifying selection pressure, revealing their conserved nature. Phylogenetic reconstruction using complete mitogenomes revealed three distinct clades in hybrids: (1) Acipenseriformes, (2) a freshwater cluster dominated by Cypriniformes and Siluriformes, and (3) a marine cluster comprising Centrarchiformes, Pleuronectiformes, Scombriformes, Cichliformes, Anabantiformes, Tetraodontiformes, Perciformes, and Salmoniformes. The prevalence of Cyprinidae hybrids underscores their importance in aquaculture for hybridization, where traits such as rapid growth and disease resistance are enhanced. In contrast, marine hybrids are valued for their market value and adaptability. While mitogenome data robustly support maternal inheritance in most cases, exceptions suggest complex mechanisms, such as doubly uniparental inheritance (DUI), in distantly related crosses. Moreover, AT-skew of genes in hybrids revealed a paternal leakage of traits in mitogenomes. This study also highlights ecological risks, such as genetic swamping in native populations, emphasizing the need for responsible hybridization practices. These findings advance our understanding of the role of hybridization in fish evolution and aquaculture, providing a genomic framework and policy recommendations for optimizing breeding programs, hybrid introduction, and mitigating conservation challenges. Full article