Search Results (3,679)

Background and Objectives: Coronavirus disease 2019 (COVID-19) is characterized by excessive inflammatory responses, including the so-called cytokine storm, which contributes substantially to morbidity and mortality in hospitalized patients. The vagus nerve, through the cholinergic anti-inflammatory pathway, represents a theoretically attractive therapeutic target for modulating systemic inflammation. Vagus nerve stimulation (VNS) has emerged as a potential adjunctive treatment for COVID-19, with several randomized controlled trials (RCTs) investigating its efficacy on inflammatory biomarkers and clinical outcomes. The quality of this evidence base has not been rigorously evaluated. This systematic review critically appraises all available RCT evidence for VNS in hospitalized COVID-19 patients. Materials and Methods: We systematically searched PubMed, Scopus, Cochrane (CENTRAL), and Web of Science from database inception to January 2026, for RCTs evaluating any form of VNS (invasive, non-invasive, cervical, or auricular) in hospitalized patients with confirmed acute COVID-19. Two reviewers independently screened titles, abstracts, and full texts according to pre-specified eligibility criteria. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool, with assessments initially performed using multiple artificial intelligence tools and subsequently validated by the authors in accordance with PRISMA 2020 guidelines. Given substantial heterogeneity and high risk of bias, narrative synthesis was performed rather than meta-analysis. Also, GRADE assessment was performed. Results: From 437 records identified, six RCTs comprising 221 patients met the inclusion criteria. Five trials (83%) were rated as high risk of bias, primarily due to inadequate blinding, substantial baseline imbalances, significant missing data and extensive multiple testing without statistical correction. The single double-blind trial with a credible sham control (Rangon et al.) found null results across all outcomes, including clinical progression, ICU transfer, and mortality, while the five “high” risk-of-bias trials generally reported positive findings on various inflammatory markers and clinical outcomes. One trial (Corrêa et al.) measured heart rate variability as a direct indicator of vagal activation and found no change despite claiming anti-inflammatory effects, contradicting the proposed mechanism of action. Significant cognitive findings from an interim analysis (Uehara et al., n = 21) disappeared in the larger completed trial (Corrêa et al., n = 52), providing empirical demonstration of false positive findings in small, underpowered studies. Conclusions: Currently available evidence supporting the use of VNS for acute COVID-19 remains scarce; however, the physiological rationale remains sound, although the absence of reliable target engagement markers in the included studies limits confidence in this treatment method. Large-scale, double-blind, sham-controlled trials are required before VNS can be firmly recommended for COVID-19 management. Full article

Radiation-associated soft tissue fibrosis represents a progressive structural remodeling process characterized by extracellular matrix accumulation, septal thickening, and reduced tissue compliance, which complicates reconstructive interventions. Reliable longitudinal experimental frameworks capable of non-invasive structural monitoring remain limited. This study aimed to develop and implement a standardized ultrasonographic protocol for the evaluation of bleomycin-induced subcutaneous fibrosis and to assess remodeling dynamics following autologous fat grafting in a rat model. Twenty-two adult female Wistar rats were included. Subcutaneous fibrosis was induced using submaximal bleomycin administration (1 mg/kg/day for three consecutive days). High-frequency ultrasonography (12 MHz) was performed at baseline (Day 0), post-bleomycin (Day 17), and post-lipofilling (Day 31). A predefined semi-quantitative 0–3 scoring system was applied to characterize global echogenicity, septal thickening, and architectural organization. At Day 17, all animals demonstrated structural alteration with a mean score of 2.15 ± 0.58. At Day 31, the mean score decreased to 1.50 ± 0.50, with complete disappearance of high-grade architectural disorganization (score 3). Focal hypoechoic areas consistent with graft integration were observed in 88.9% of animals without ultrasonographic signs of necrosis or fluid collection. This standardized imaging-based framework enables reproducible longitudinal monitoring of early-stage subcutaneous fibrotic remodeling and provides a non-invasive tool for evaluating regenerative interventions in translational soft tissue engineering research. Full article

Apathy is a neuropsychiatric symptom that is present in various disorders, including dementia and Mild Cognitive Impairment (MCI). Patients with MCI who exhibit symptoms of apathy are at a higher risk of progressing to dementia compared to those with depressive symptoms. The aim of the present study was to investigate the psychometric properties of the clinician-rated version of the Apathy Evaluation Scale (AES-C) in a Greek sample of MCI patients and healthy older adults. The translation and adaptation of the scale were conducted using the forward–backward method. The final sample consisted of 100 participants, 14 men (n = 14) and 86 women (n = 86), with a mean age of 72 years. Participants were administered the translated and adapted version of the AES-C, as well as the Greek version of the Beck Depression Inventory. In terms of reliability, Cronbach’s alpha was found to be high (α = 0.91), indicating excellent internal consistency. Confirmatory Factor Analysis (CFA) revealed a one-factor solution with a very good model fit (RMSEA = 0.018, CFI = 0.985, TLI = 0.983, SRMR = 0.076). The AES-C can serve as an important addition to neuropsychological assessment for detecting apathy symptoms in patients with MCI, thereby contributing to the early prognosis of dementia. Full article

Background/Objectives: There are significant gaps in knowledge regarding the heterogeneity of heart failure (HF) phenotypes, particularly among patients with preserved left ventricular ejection fraction (HFpEF). Our aim was to identify phenotypes within the hospitalized North-Eastern Romanian HFpEF cohort and their impact on short-term outcomes. Methods and Results: We derived a cluster model from 924 patients with HFpEF hospitalized over an 18-month interval in the Internal Medicine II Department of the “Sf. Spiridon” Emergency Clinical County Hospital in Iași, Romania. The median age of the patients was 74 years [range 30–101], 59.8% were women, and the most frequent comorbidities were arterial hypertension (93.2%), valvular heart disease (68.7%), atherosclerotic cardiovascular disease (ASCVD, 64.6%) and atrial fibrillation (43%). Statistical analysis identified five distinct phenotypes: cluster 1 (21.6% of patients) consisted of normal-weight patients with valvular disease predominance; cluster 2 (18.2%) described a severe cardiometabolic phenotype; cluster 3 (19.6%) defined a young, hypertensive, and atherosclerotic phenotype; cluster 4 (21.26%) described a hypertensive–atrial fibrillation phenotype; and cluster 5 (18.9%) included elderly, hypertensive non-diabetic patients with severe vascular burden (ASCVD 100%). Conclusions: This study defines five distinct phenotypes within the HFpEF population in our region which differ in terms of clinical characteristics and heart failure pharmacological therapy. These results confirm the significant heterogeneity of HFpEF. The identified phenotypes were not associated with significant differences in composite short-term outcomes, including in-hospital mortality and 30-day rehospitalization for heart failure. Full article

Global population growth has intensified the demand for productive and sustainable livestock systems. Lithothamnium calcareum, a calcareous marine alga, has been investigated as a natural feed additive for cattle diets. This study evaluated the effects of L. calcareum supplementation on performance, carcass traits, nutrient digestibility, nitrogen metabolism, urinary and fecal pH, and enteric methane emissions in Nellore heifers during the finishing phase. Thirty-six heifers (BW = 268.8 ± 7.3 kg) were assigned to individual pens in a completely randomized design and fed ad libitum diets (25:75 forage-to-concentrate ratio, DM basis). Treatments were: (1) sodium bicarbonate (110 g/heifer/day) and (2) L. calcareum (60 g/heifer/day). The 96-day trial included 12 days of adaptation and 84 days on the finishing diet. Methane emissions were measured using the sulfur hexafluoride (SF₆) tracer technique. L. calcareum did not affect performance, carcass traits, nitrogen metabolism, or apparent total tract digestibility (all p ≥ 0.106), but reduced urine pH (p ≤ 0.001) and tended to lower methane emissions (−8.2%; p = 0.079). Thus, L. calcareum appears to be a viable natural alternative to sodium bicarbonate in finishing diets for Nellore heifers, maintaining productive performance and potentially reducing enteric methane output. Full article

Soybean mosaic virus (SMV) is a major constraint on global soybean (Glycine max (L.) Merr.) production, causing substantial economic losses worldwide. Despite these losses, the potential of resistance genes as a solution remains largely unexplored. In this study, the COPPER CHAPERONE FOR SUPEROXIDE DISMUTASE (GmCCS) was initially employed as a bait to screen the soybean cDNA library, leading to the identification of a protein homologous to Arabidopsis thaliana COP9 signalosome complex subunit 5B (AtCSN5B), designated as GmCSN5B. Quantitative real-time PCR (qRT-PCR) analysis revealed differential expression of GmCSN5B in the SMV-resistant (Qihuang No.1, QH) and susceptible (Nannong 1138-2, NN) variety following SMV-SC3 strain inoculation. Knockdown of GmCSN5B via Bean pod mottle virus (BPMV)-induced gene silencing (VIGS) significantly enhanced SMV resistance compared to control plants. This work further demonstrated that GmCSN5B can interact with the downstream GmVTC1 protein, which was potentially associated with ascorbic acid (AsA; Vitamin C) synthesis. Moreover, GmVTC1 also responded to SMV infection, and its knockdown led to a reduction in endogenous AsA levels within the host, thereby compromising the plant’s resistance to SMV. Together, these findings suggest that the GmCCS-GmCSN5B-GmVTC1 pathway in soybean modulates host resistance to SMV through the regulation of AsA synthesis. Full article

Pomacea canaliculata, as a significant invasive alien species, poses severe threats to agricultural development. Currently, chemical applications demonstrate notable efficacy in controlling this pest. However, metaldehyde exhibits overly singular toxicity towards P. canaliculata; niclosamide sulfate is not a molluscicide; and fentin acetate is a fungicide. Currently, these findings fail to elucidate the physiological and biochemical effects of the compounds after they enter the P. canaliculata’s body. In this study, we evaluated the toxicity of metaldehyde (ME), niclosamide sulfate (NS), and fentin acetate (FA) against P. canaliculata and analyzed the morphological and physiological changes in response to chemical stress. The results indicated that three chemicals exhibited potent molluscicidal activity, especially in the NS treatment group. After 12 h exposure to LC₅₀ concentrations (48 h LC₅₀), the surface area of livers was reduced significantly by 12.1%, 13.9%, and 2.8% compared to the control group, while the kidneys expanded significantly by 6.4%, 3.2%, and 16.7%, respectively. The heart showed marked enlargement by 152.1% and 44.2% under niclosamide sulfate and metaldehyde treatments. The pulmonary sac significantly contracted by 23.6% under niclosamide sulfate stress but expanded by 6.1% under fentin acetate exposure. The stomach enlarged significantly after niclosamide sulfate treatment, whereas it shrank by 2.1% and 5.7% under metaldehyde and fentin acetate treatments, respectively. Metabolomic analysis of liver tissues revealed 553, 99, and 585 differential metabolites compared to the control group, respectively. KEGG pathway enrichment analysis showed that the metabolism pathway, lysine degradation, and bile secretion are likely related to the response to chemical stress in P. canaliculata. Further examination showed a significant decrease in total protein content and the activities of malondialdehyde (MDA), acetylcholinesterase (AChE), superoxide dismutase (SOD), and catalase (CAT) under chemical stress. These findings enhance our understanding of the targeted mechanisms of molluscicides against P. canaliculata. Metaldehyde may exert neurotoxic effects on the P. canaliculata, while niclosamide sulfate may interfere with its respiratory system. Additionally, both chemicals affect metabolic pathways in the snail’s liver, including lipid metabolism and metabolic pathways associated with energy metabolism. These findings provide valuable insights for designing a novel snail control agent and formulating scientific management strategy. Full article

Peroxisomes are ubiquitous organelles that play vital roles in various physiological and biochemical processes, including fatty acid β-oxidation and reactive oxygen species (ROS) metabolism. These organelles have been implicated in the pathogenicity of many plant fungal pathogens. In this study, CaPex8, a homolog of Saccharomyces cerevisiae Pex8, was identified and characterized in Colletotrichum aenigma. CaPEX8 was found to localize to peroxisomes, and its deletion impaired the mutant’s ability to utilize fatty acids as a carbon source. Using a green fluorescent protein (GFP) fused to the peroxisomal targeting signal PTS1, the import of peroxisomal matrix proteins was shown to be defective in ΔCapex8 mutants. Additionally, the mutants exhibited elevated conidiation, increased sensitivity to osmotic stress and oxidative stress, and impaired cell wall integrity. Peroxisome biogenesis was also disrupted in the absence of CaPEX8. Taken together, these results demonstrate that CaPex8 is essential for maintaining peroxisomal structure and function, and it significantly influences fungal growth, development, and pathogenicity in C. aenigma. Full article

We previously demonstrated that human herpesvirus 6A infects papillary thyroid cancer cells (BCPAP), inducing molecular changes compatible with a tumor-promoting phenotype, including increased expression of R273H mutant TP53 (mutp53), upregulation of c-Myc, and enhanced secretion of IL-6. To investigate whether and how epigenetic mechanisms contribute to these virus-induced effects, we examined the histone methyltransferase EZH2, a key regulator of chromatin repression frequently altered in cancer. HHV-6A infection reduced EZH2 expression and global H3K27me3 levels. Pharmacological inhibition of EZH2 using DS-3201 reproduced some of the molecular effects of viral infection, including increased mutp53 stability. Both viral infection and EZH2 inhibition induced delayed upregulation of SIRT1, which mediated deacetylation-dependent stabilization of mutp53 while reducing c-Myc expression. Indeed, the inhibition of SIRT1 with EX-527 reversed mutp53 accumulation but restored c-Myc expression and increased extracellular IL-6 release. This drug also reduced cell survival, suggesting that SIRT1 supports cellular adaptation to oncogenic stress triggered by EZH2 loss. Overall, our findings identify an epigenetic axis in which the HHV-6A-mediated downregulation of EZH2 induces SIRT1, regulating mutp53 stability and c-Myc expression and reshaping inflammatory signaling to maintain cell viability. These results establish a mechanistic link between viral infection, epigenetic remodeling, and oncogenic dependency. They also suggest that targeting IL-6 signaling could represent a therapeutic vulnerability in HHV-6A-associated thyroid cancer, particularly in combination with SIRT1 inhibitors. Full article

Therapeutic termination of pregnancy (TToP) represents an intervention that is performed for medical reasons, such as risks to maternal health or severe fetal anomalies. Advances in prenatal screening and diagnostic tools—including serum markers, ultrasound, cell-free fetal DNA, chorionic villus sampling and amniocentesis—have significantly improved early detection and clinical decision-making. This narrative review synthesizes current knowledge on the genetic, environmental and psychosocial determinants that influence the decision of the patients to pursue TToP. The literature search was performed primarily using PubMed database, while Scopus and Google Scholar were used to identify additional relevant studies. Some of the selected studies, as well as certain sections of this review, address both therapeutic and voluntary termination of pregnancy, whereas others focus exclusively on TToP. Moreover, this review describes the types of abortion (medical or surgical/aspiration) along with their management strategies to prevent or address potential complications. It is well known that demographic, cultural and socio-economic factors continue to influence the access to TToP, as well as the perceptions of it. Psychiatric comorbidities (such as anxiety, affective and psychotic disorders) are observed with a higher prevalence among women undergoing TToP and may influence both the decision and psychological outcomes post-procedure. While most women report emotional relief after TToP, some of them experience depression, post-traumatic stress disorder or substance misuse. Legal and ethical considerations further complicate access to safe abortion, leading to situations where patients may resort to unsafe procedures, which result in higher rates of morbidity and mortality. Data from the EUROCAT network show rising trends in congenital anomalies like trisomy 13, trisomy 18 and caudal regression syndrome (conditions commonly associated with TToP). Therefore, it is mandatory to form a multidisciplinary team in these cases, integrating medical, psychological and ethical dimensions. Ensuring safe, evidence-based and compassionate access to TToP remains a critical component of reproductive healthcare. Full article

The chemical composition of natural products is complex and the investigation of bioactivities of compounds of interest demands their isolation. S. terebinthifolia Raddi is a tree belonging to the Anacardiaceae family and is used in Brazilian folk medicine; its fruit (pink peppers) are used in cooking and its bark in phytomedicine. Extracts of other parts of this plant contain a plethora of components and merit further studies. Countercurrent chromatography (CCC) is frequently employed with natural products due to the high sample recovery rate. The objective of this work was to determine the best solvent system (SS) to fraction the ethanol extracts of leaves, flowers and fruit of Schinus terebinthifolia by CCC and isolate compounds of interest and elucidate their structures through nuclear magnetic resonance (NMR) and mass spectrometry (MS). In addition, antiproliferative, potential cell regeneration and antioxidant activities of the fractions of interest were evaluated. In the present work, three compounds were isolated; two were identified as anacardic acids [(6-(8′, 11′-heptadecadienyl)-salicylic acid and 6-(8′-heptadecenyl)-salicylic acid], as well as (Z)-masticadienoic acid. These compounds showed antiproliferative and potential cell regeneration activities as well as varying degrees of antioxidant capacity. Although these compounds present potential therapeutic activity, more studies are necessary to confirm their safety. Full article

Background: Radiotherapy (RT) combined with androgen deprivation therapy (ADT) is a standard treatment for non-metastatic high-risk (HR) prostate cancer (PC). However, the benefit of elective nodal irradiation (ENI) in clinically node-negative (cN0) patients, although suggested, remains controversial, particularly in the elderly. We report the outcomes of elderly HR PC patients treated with prostate-only RT (PORT) and ADT in a “real-word” setting. Methods: Between 2016 and 2022, 43 consecutive elderly patients (median age 76 years) with HR- or very HR-PC according to NCCN criteria version 1.2026 (cN0, cT3-cT4 and/or ISUP Grade Group 4–5 and/or PSA serum levels at diagnosis ≥ 20 ng/mL) were treated at our institution. All patients were staged with abdominal MRI or CT and bone scan; nineteen patients (44.2%) also underwent 68Ga-PSMA-11 or 18F-fluorocholine PET/CT. All patients received PORT (predominantly moderate hypofractionation, 67.5–70 Gy in 25–28 fractions) and ADT (median duration 24 months). To ensure consistency, all oncological endpoints—Biochemical Failure-Free Survival (BFFS; Phoenix criteria), Disease-Free Survival (DFS), Metastasis-Free Survival (MFS), Prostate Cancer-Specific Survival (PCSS), and Overall Survival (OS)—were calculated from a unified time-zero (initiation of first oncological treatment). DFS was defined as a composite endpoint including biochemical failure, radiological recurrence, or initiation of salvage therapy. Results: at a median follow-up of 60 months, no patient reached the Phoenix threshold, resulting in a 100% 5- and 7-year BFFS. However, 4 patients (9.3%) experienced radiological recurrence detected via PET/CT before reaching the nadir + 2 threshold, yielding an estimated 5-year and 7-year DFS of 94.7% and 71.8%, respectively. The 5- and 7-year MFS was of 97.6% and 88.7%, respectively. Seven deaths occurred, all non-PC related, resulting in a 5-year OS of 86.7% and a Prostate Cancer-Specific Survival of 100%. Gastrointestinal toxicity was notably low (no acute or late G3-G4 events). Conclusions: Our findings suggest that PORT, when combined with long-term ADT and modern staging, provides excellent disease control and a favorable safety profile in elderly HR PC patients. Given the high rate of competing mortality in this population, treatment de-escalation via PORT appears to be a clinically reasonable strategy. These results are hypothesis-generating and warrant validation in prospective randomized trials. Full article

Simple shear testing is a widely used method in geotechnical engineering for evaluating soil liquefaction susceptibility, deformation characteristics, and shear strength under controlled loading conditions. This study presents a bibliometric analysis of research trends in simple shear testing based on 367 publications indexed in the Scopus database between 2000 and 2024, analyzed using VOS-viewer. It appears that the current research output on this topic has greatly increased lately. The number of research articles reached a peak in 2024 with a total of 42 research articles. The most frequently cited journals on this topic are Soil Dynamics and Earthquake Engineering, with a total of 48 research articles (1173 citations); the Journal of Geotechnical and Geo-environmental Engineering, with a total of 34 research articles (772 citations); and the Canadian Geotechnical Journal, with a total of 10 research articles (250 citations). This indicates substantial research interest in earthquake engineering and soil mechanics. The output shows that there is a major emphasis on research done in the USA, with a total of 104 research articles (1215 citations). The highest average citations per document belong interestingly to the research done by Taiwanese, with a total of 36.73 citations. Similarly, it appears that there is a good impact on soil liquefaction studies. The research findings show that confining pressure, strain rates, and volume ratio affect the shear strength of the soil. Advances in boundary control and shear testing techniques have improved the reliability of experimental results. The study underscores the growing need for more sophisticated numerical modeling techniques and field verification to bridge the gap between laboratory findings and real geotechnical applications. These findings contribute to improving soil characterization methods, which enable safer and more efficient geotechnical designs for infrastructure development. Full article

Background and Objectives: Difficult venous access (DVA) affects 10–26% of hospitalized patients and up to 60% in high-risk populations, leading to increased patient discomfort, delayed diagnosis, and substantial healthcare costs estimated at $4.7 billion annually in the United States. This meta-analysis aimed to systematically evaluate the effectiveness, safety, and implementation considerations of traditional and emerging strategies for obtaining blood samples in patients with DVA. Materials and Methods: We conducted a comprehensive systematic review and meta-analysis following PRISMA guidelines. We searched MEDLINE, Embase, CINAHL, and Cochrane databases from January 2016 to December 2023. Inclusion criteria encompassed randomized controlled trials, systematic reviews, and observational studies examining DVA interventions in adult and pediatric populations. Primary outcomes included first-attempt success rates, overall success rates, and complication rates. Statistical analysis used random-effects models with risk ratios and 95% confidence intervals. Results: Forty-seven studies involving 12,847 patients met the inclusion criteria. Technology-assisted approaches demonstrated superior outcomes compared to traditional techniques. Ultrasound guidance showed the highest effectiveness with a first-attempt success increase of 42% (RR 1.42, 95% CI 1.26–1.58, p < 0.001), followed by near-infrared visualization with a 28% increase (RR 1.28, 95% CI 1.14–1.42, p < 0.001). Population-specific approaches yielded significant benefits, including the use of scalp veins for infants and external jugular approaches for extreme DVA cases. Cost-effectiveness analysis revealed that ultrasound guidance achieved break-even within 8–14 months in high-volume centers. Conclusions: A systematic, stepwise approach integrating appropriate technology and techniques significantly improves success rates while reducing patient discomfort and healthcare costs. Healthcare institutions should implement comprehensive DVA protocols with adequate training, equipment access, and quality monitoring. The proposed algorithm achieved a 93% overall success rate in validation studies, representing a substantial improvement over traditional approaches. Full article

Liver fibrosis is driven by persistent oxidative stress and inflammatory signaling, with transforming growth factor-β (TGF-β) acting as a key profibrotic mediator. Rutin (Ru) is a plant-derived flavonoid with antioxidant and anti-inflammatory effects, but its low bioavailability limits therapeutic efficacy. This study investigated whether rutin-phytoreduced gold nanoparticles (RuAuNPs) enhanced rutin delivery leading to antifibrotic and anti-inflammatory effects in a rat model of liver fibrosis. Liver fibrosis was induced by oral administration of thioacetamide (TAA, 150 mg/kg body weight, p.o.) for six weeks. Following fibrosis induction, the animals were treated with free rutin (30 mg/kg body weight), RuAuNPs (0.3 mg/kg body weight), or AuNPs (0.3 mg/kg body weight), both expressed as nanoparticle mass, all administered orally for four weeks. RuAuNPs were synthesized by green rutin-mediated reduction and further characterized by TEM, DLS, and FTIR spectroscopy; they were spherical, showing an average hydrodynamic size of 104.1 nm (PDI 0.345). FTIR confirmed rutin capping. Biological effects were evaluated by liver morphology (H&E histology, TEM), biochemical assessment of liver aminotransferases and glico-lipidic status, ELISA and spectrophotometry measurement of redox biomarkers (lipid peroxidation, glutathione status, antioxidant enzymes), cytokines (TNF-α, IL-1β, IL-6), and TGF-β. TAA-induced hepatic injury and remodeling with increased profibrotic signaling, oxidative stress, and inflammation. Free rutin slightly ameliorated the liver damage, whereas RuAuNP improved histological features, reduced TGF-β and pro-inflammatory cytokines, decreased lipid peroxidation, and supported antioxidant defenses. Overall, RuAuNP may enhance rutin efficacy in TAA-induced liver fibrosis, with novelty stemming from the integrated in vivo evaluation of tissue changes and key profibrotic/oxidative/inflammatory pathway. Full article