Search Results (278)

Right ventricular apex (RVA) pacing has historically been the default approach for cardiac pacing; however, it is associated with the development of progressive left ventricular dysfunction and heart failure (HF), particularly in patients with high pacing burdens. While advances in device programming and modern algorithms have sought to mitigate these effects, preserving physiological activation has proven to be more critical than reducing ventricular pacing. Conduction system pacing (CSP) techniques—namely, His-bundle pacing (HBP) and particularly left bundle branch area pacing (LBBAP)—have emerged as superior alternatives, enabling improved left ventricular function and reduced rates of pacing-induced cardiomyopathy (PICM). Nevertheless, despite the clinical advantages of these procedures over RVA, they face limitations including variable implantation success rates, increased pacing thresholds and lead revision rates, technical challenges, and occasional procedure prolongation. Thus, while CSP approaches represent the future of physiological pacing, RVA pacing continues to provide a necessary and reliable option in the current clinical practice. Full article

Background: Neisseria meningitidis B is one of the main causative pathogens of meningitis and other forms of severe meningococcal disease. In the past decade, meningococcal B vaccines have been developed to address this infection and its sequelae. Objective: This article aims to present an example of how the EU regulatory framework allowed the early authorisation of two life-saving vaccines initially based on immunogenicity surrogates of clinical evidence. This was subsequently followed by post-marketing surveillance providing real-world evidence to support their safety profile and impact on the paediatric population in the EU. Methods: We review the evidence supporting the initial regulatory approval of the vaccines, the confirmatory data demonstrating vaccine effectiveness post-authorisation, and the real-world impact of these vaccines on the paediatric population. Results: Two vaccines were approved in the EU for active immunisation to prevent IMD caused by MenB (4CMenB in 2013 and MenB-fHBP in 2017). Both marketing authorisations were based on immunogenicity data (efficacy studies were not feasible due to the rarity of the disease) and safety data generated from pre-authorisation studies. Additional pharmacovigilance activities to further investigate the safety profile and effectiveness studies were requested to be conducted after approval. Both the effectiveness and safety profile of the vaccines were confirmed by these data. Conclusions: This paper illustrates that the EU medicines regulatory framework and safety monitoring system are robust. By supplementing the initial evidence with post-authorisation studies, further effectiveness and safety data enabled regulators to confirm the positive benefit–risk of the vaccines without delaying their access to the people who need them. Full article

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors primarily located in the stomach and small intestine; their occurrence in the terminal ileum is particularly rare. Although GISTs can develop throughout the gastrointestinal tract, cases of perforation in elderly individuals are even less common, posing significant diagnostic and therapeutic challenges. This case report describes an 86-year-old male patient with an acute abdomen caused by a terminal ileum perforated GIST requiring urgent surgical intervention. An immunohistochemical examination of the tumor confirmed a GIST with a GILT (gastrointestinal leiomyogenic tumor) immunophenotype. The rarity of this condition makes it diagnostically challenging, as its symptoms are often nonspecific, and GISTs are frequently overlooked, particularly in older patients. This case supplements the existing literature by emphasizing the importance of considering GIST perforation in the differential diagnosis of an acute abdomen, even in elderly patients and in rare anatomical locations. Full article

Galectin-3 (Gal-3) is a β-galactoside-binding lectin that mediates diverse signaling events in multiple cell types, including immune cells. It is also a prognostic indicator for multiple clinically important disorders, including cardiovascular disease. Gal-3 binds to cell surface glycans to form lattices that modulate surface receptor signaling and internalization. However, the tissue-specific regulation of Gal-3 surface expression remains poorly understood. Here, we review evidence for the involvement of Gal-3 in cell surface signaling, intranuclear events, and intracellular trafficking. Our focus will be on the O-GlcNAc modification as a regulator of Gal-3 biosynthesis, non-canonical secretion, and recycling. We argue that the nutrient-driven cytoplasmic hexosamine biosynthetic pathway (HBP) and endomembrane transport mechanisms generate unique pools of nucleotide sugars. The differing levels of nucleotide sugars in the cytosol, endoplasmic reticulum (ER), and Golgi apparatus generate differential thresholds for the responsiveness of O-GlcNAc cycling, N- and O-linked glycan synthesis/branching, and glycolipid synthesis. By regulating Gal-3 synthesis and non-canonical secretion, O-GlcNAc cycling may serve as a nexus constraining Gal-3 cell surface expression and lattice formation. This homeostatic feedback mechanism would be critical under conditions where extensive glycan synthesis and branching in the endomembrane system and on the cell surface are maintained by elevated hexosamine synthesis. Thus, O-GlcNAc cycling and Gal-3 synergize to regulate Gal-3 secretion and influence cellular signaling. In humans, Gal-3 serves as an early-stage prognostic indicator for heart disease, kidney disease, viral infection, autoimmune disease, and neurodegenerative disorders. Since O-GlcNAc cycling has also been linked to these pathologic states, exploring the interconnections between O-GlcNAc cycling and Gal-3 expression and synthesis is likely to emerge as an exciting area of research. Full article

Anion exchange membranes (AEMs) are vital for electrochemical energy devices such as alkaline fuel cells and water electrolyzers, enabling the use of non-precious metal catalysts despite challenges from alkaline degradation. Hyperbranched polymers (hbPs) with their globular structure, high functional group density, and simple synthesis, offer a promising platform for enhancing transport and stability. In this study, multifunctional hbPs were synthesized from 4-vinylbenzyl chloride (VBC) and 2-hydroxyethyl methacrylate (HEMA) via atom transfer radical self-condensing vinyl polymerization (ATR-SCVP) and crosslinked into polyurethane-based AEMs. Characterization confirmed successful copolymerization and crosslinking, with excellent alkaline stability. Membranes crosslinked with higher molecular weight (MW) and VBC-richer hbPs (e.g., OH-hbP1-PU) exhibited high water uptake (75%) but low ion-exchange capacity (1.54 mmol/g) and conductivity (186 µS/cm), attributed to steric hindrance and insufficient ionic network connectivity. In contrast, OH-hbP2-PU exhibited optimal properties, with the highest OH⁻ conductivity (338 µS/cm) and IEC (2.64 mmol/g), highlighting a balanced structure for efficient ion transport. This work offers a tunable strategy for high-performance AEM development through tailored hbP architecture. Full article

The curing reaction of hydroxyl-terminated polybutadiene (HTPB) solid propellant slurry alters its internal molecular structure, leading to variations in rheological properties. This study investigates the evolution of the rheological behaviour of HTPB propellant slurry during the curing process. Rheological parameters of the slurry at different curing stages were measured using a rotational rheometer, and its time-dependent rheological characteristics were systematically analysed. Building upon the Herschel–Bulkley–Papanastasiou (HBP) viscosity model, a temporal variable was innovatively incorporated to extend the model into the time domain, resulting in the development of the Herschel–Bulkley–Papanastasiou–Wang (HBPW) constitutive viscosity model. Model parameters were determined through experimental data, and the accuracy of the HBPW model was rigorously validated by comparing numerical simulations with experimental results. The findings demonstrate that the HBPW model effectively captures the viscosity variation patterns of HTPB propellant slurry with respect to both shear rate and curing time, exhibiting a minimal discrepancy of 1.7525% between simulations and experimental data. This work establishes a novel theoretical framework for analysing the rheological properties of HTPB propellant slurry, providing a scientific foundation for optimised propellant formulation design and processing techniques. Full article

Endocrine disruptors (EDCs) in food pose a significant threat to health. This study developed a method for detecting seven EDCs (triclosan (TCS), triclocarban (TCC), methyltriclosan (MTCS), methylparaben (MeP), propylparaben (PrP), bisphenol F (BPF), and 4-hydroxybenzophenone-3-ethylcarboxylate (4HBP)) in honey. The method combines ultrasonic-assisted dispersive liquid–liquid microextraction with high-performance liquid chromatography. It achieved a recovery rate of 89.70–102.2%, with an RSD value of 1.1–3.9%. Additionally, this study tested 47 honey samples from seven countries, revealing detection rates of TCS at 29.79%, TCC at 19.15%, BPF at 97.87%, 4HBP at 36.17%, MeP at 82.98%, and PrP at 80.85%. Among the 12 nectar sources, citrus flower nectar had the highest TCS detection rate, mother grass nectar had the highest TCC detection rate, and multi-flower nectar had the highest 4HBP detection rate. Moreover, imported honey samples showed higher levels of TCS, BPF, and MeP contamination compared to domestic samples. Honey stored in PET bottles contained the highest levels of EDCs. Finally, health risk assessments indicated that, while the risk for adults is lower, monitoring EDC contamination in food should be strengthened to ensure consumer safety. Full article

Background: Conduction system pacing (CSP), encompassing His bundle pacing (HBP) and left bundle branch area pacing (LBBAP), has emerged as an alternative to conventional pacing methods such as right ventricular pacing (RVP) and biventricular pacing (BVP). This meta-analysis aimed to compare the effects of CSP versus conventional pacing on left ventricular function and selected clinical and electrophysiological outcomes. Methods: Prospective and retrospective studies (randomized, observational, registry-based) reporting pre-post data or direct comparisons between CSP (HBP, LBBAP) and conventional methods (BVP, RVP) for at least one of LVEF, LVESV, LVEDV, QRS duration, NYHA class, NT-proBNP, R-wave, or pacing threshold were included. PubMed and Web of Science databases were searched up to 31 March 2025. Quality assessment (QualSyst), publication bias (Egger’s test, trim-and-fill), subgroup analyses, and meta-regression (follow-up duration) were performed. The review was registered in the INPLASY database (INPLASY202540050). Results: 28 studies (8777 patients, 47 comparisons) were included. CSP significantly improved LVEF (SMD = 1.16; 95%CI: 0.94–1.38), shortened QRS duration (SMD = 0.75; 95%CI: 0.24–1.26), and reduced NYHA class (SMD = 1.94; 95%CI: 1.59–2.29), NT-proBNP levels (SMD = 1.27; 95%CI:0.85–1.69), LVEDV (SMD = 0.90; 95%CI: 0.42–1.38), and LVESV (SMD = 1.31; 95%CI: 0.81–1.81). In head-to-head comparisons, LBBAP and HBP showed similar efficacy, both superior to conventional pacing. Improvement in LVEF significantly correlated with longer follow-up (p = 0.004). Publication bias was non-significant (Egger p = 0.15), despite high heterogeneity (I² > 90%). Conclusions: CSP demonstrated superior clinical and echocardiographic outcomes compared to conventional pacing. Limitations include the predominance of non-randomized studies, high heterogeneity, and variability in follow-up duration, supporting the need for high-quality randomized trials. Full article

Background: Adrenal incidentalomas are detected in various medical and surgical healthcare departments, including primary healthcare. One up to three out of ten individuals confirmed with nonfunctioning adrenal incidentalomas (NFAs) actually present a mild autonomous cortisol secretion (MACS), which is distinct from Cushing’s syndrome. Objective: We aimed to assess the cortisol secretion in newly detected adrenal incidentalomas in patients who were referred by their primary healthcare physician upon accidental detection of an adrenal tumor at abdominal computed tomography (CT) scan that was performed for unrelated (non-endocrine) purposes. Methods: This retrospective study included adults diagnosed with an adrenal incidentaloma via CT during the previous 3 months. Inclusion criteria: age ≥ 40 years (y). A triple stratification of exclusion criteria involved: (1) Clinical aspects and medical records such as active malignancies or malignancies under surveillance protocols, subjects under exogenous glucocorticoid exposure (current or during the previous year), or suggestive endocrine phenotypes for any hormonal ailment; (2) Radiological appearance of suspected/confirmed (primary or secondary) adrenal malignancy, adrenal cysts, or myelolipomas; (3) Endocrine assays consistent with active endocrine tumors. Protocol of assessment included baseline ACTH, morning plasma cortisol (C-B), cortisol at 6 p.m. (C-6 pm), and after 1 mg dexamethasone suppression testing (C-1 mg-DST), 24-h urinary free cortisol (UFC), and a second opinion for all CT scans. MACS were defined based on C-1 mg-DST ≥ 1.8 and <5 µg/dL (non-MACS: C-1 mg-DST < 1.8 µg/dL). Results: The cohort (N = 60, 78.33% female; 60.72 ± 10.62 y) associated high blood pressure (HBP) in 66.67%, respectively, type 2 diabetes (T2D) in 28.37% of the patients. Females were statistically significantly older than males (62.40 ± 10.47 vs. 54.62 ± 9.11 y, p = 0.018), while subjects with unilateral vs. bilateral tumors (affecting 26.67% of the individuals) and those with MACS-positive vs. MACS-negative profile had a similar age. Body mass index (BMI) was similar between patients with unilateral vs. bilateral incidentalomas, regardless of MACS. Patients were divided into five age groups (decades); most of them were found between 60 and 69 years (40%). Left-gland involvement was found in 43.33% of all cases. The mean largest tumor diameter was 26.08 ± 8.78 mm. The highest rate of bilateral tumors was 46.67% in the 50–59 y decade. The rate of unilateral/bilateral and tumor diameters was similar in females vs. males. The MACS-positive rate was similar in females vs. males (23.40% vs. 23.08%). A statistically significant negative correlation (N = 60) was found between BMI and C-B (r = −0.193, p = 0.03) and BMI and UFC (r = −0.185, p = 0.038), and a positive correlation was found between C-B and C-6 pm (r = 0.32, p < 0.001), C-B and UFC (r = 0.226, p = 0.011), and C-6 pm and C-1 mg-DST (r = 0.229, p = 0.010), and the largest tumor diameter and C-1 mg-DST (r = 0.241, p = 0.007). Conclusions: Adrenal incidentalomas belong to a complex scenario of detection in the modern medical era, requiring a multidisciplinary collaboration since the patients might be initially detected in different departments (as seen in the current study) and then referred to primary healthcare for further decision. In these consecutive patients, we found a higher female prevalence, a MACS rate of 23.33%, regardless of uni/bilateral involvement or gender distribution, and a relatively high rate (than expected from general data) of bilateral involvement of 26.67%. The MACS-positive profile adds to the disease burden and might require additional assessments during follow-up and a protocol of surveillance, including a tailored decision of tumor removal. The identification of an adrenal incidentaloma at CT and its hormonal characterization needs to be integrated into the panel of various chronic disorders of one patient. The collaboration between endocrinologists and primary healthcare physicians might improve the overall long-term outcomes. Full article

Epoxy resins (ERs) are esteemed for their mechanical robustness and adhesive qualities, particularly in steel bridge deck applications. Nonetheless, their intrinsic brittleness limits broader utility. This study addresses this limitation by modulating ER crosslink density through adjustments in curing agent concentration, incorporation of hyperbranched polymers (HBPs), and optimization of curing conditions. Employing a multi-objective optimization strategy, this research aims to enhance toughness while minimizing strength degradation. Non-isothermal curing kinetics, realized using the differential scanning calorimetry (DSC) method, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), tensile testing, and thermogravimetric analysis (TGA), were employed to investigate the effects of curing agent and HBP content on the curing reaction, mechanical properties, and thermal stability, respectively. Response surface methodology facilitated comprehensive optimization. Findings indicate that both curing agent and HBP contents significantly influence curing dynamics and mechanical performance. Curing agent content below 40% or above 50% can induce side reactions, adversely affecting properties. While a curing agent content exceeding 45% or an HBP content exceeding 5% improves the toughness of ER, these increases concurrently reduce mechanical strength and thermal stability. The study identifies an optimal formulation comprising 45.21% curing agent, a curing temperature of 60.45 °C, and 5.77% HBP content. Full article

Background: Neisseria meningitidis (N. meningitidis) is a leading cause of acute meningitis and is classified into 13 serogroups, six of which are predominantly associated with invasive meningococcal disease. This study aimed to investigate the genotype, subgenotype, and antigenic profiles of N. meningitidis serogroup B strains isolated in Vietnam. Methods: Genotyping was performed on 106 N. meningitidis strains isolated from clinical samples from Vietnamese patients and nasopharyngeal swabs of healthy adolescents between 2019 and 2024. The genetic profiles, including the porA, porB, fetA, fHbp, abcZ, adk, aroE, fumC, gdh, pdhC, and pgm genes, were analyzed using Sanger sequencing and bioinformatic methods. Results: We found that 84.9% of the strains carried VR3 families 36 or 35-1, with VR1, VR2, and VR3 families 22-25, 14, and 36 being the most prevalent. Among the 106 serogroup B isolates, 20 variants of the porB allele 3 were identified, with porB 3-1212 being the most frequent (30.2%). Dominant PorB variable loops included L1.6, L4.5, L5.7, L6.6, and L7.13. fHbp variant group 2 was predominant (104/106 strains), and 12 FetA allele variants were identified, with F1-7 being the most common (47.2%). Three clonal complexes were identified, and clonal complex ST-32 was the most predominant. Fifty-five strains (51.9%) belonged to sequence types that have not yet been assigned to any clonal complexes, and 15 strains (14.1%) with allelic profiles were not assigned to STs. The 3-253 and 3-1212 alleles of porB, the F1-7 variant of FetA, the ST-44 and ST-1576 sequence types, and the ST-41/44 complex were observed more frequently in patients compared to asymptomatic carriers, suggesting their association with more virulence. Conclusions: This study showed a high genetic and antigenic diversity of N. meningitidis serogroup B isolates in Vietnam, with VR3 family 36 most common and porB 3-1212 as the predominant allele. fHbp variant group 2 and FetA allele F1-7 were most frequent. ST-32 was the dominant clonal complex, though many strains remained unassigned, highlighting the need for ongoing molecular surveillance. Full article

Biodesulfurization (BDS) is a clean technology that uses microorganisms to efficiently remove sulfur from recalcitrant organosulfur compounds present in fuels (fossil fuels or new-generation fuels resulting from pyrolysis and hydrothermal liquefaction). One of the limitations of this technology is the low desulfurization rates. These result in the need for greater amounts of biocatalyst and lead to increased production costs. To mitigate this issue, several approaches have been pursued, such as the use of alternative carbon sources (C-sources) from agro-industrial waste streams or the co-production of high-added-value products by microorganisms. The main goal of this work is to assess the potential of strawberry tree fruit residue (STFr) as an alternative C-source for a BDS biorefinery using Gordonia alkanivorans strain 1B, a well-known desulfurizing bacterium with high biotechnological potential. Hence, the first step was to produce sugar-rich liquor from the STFr and employ it in shake-flask assays to evaluate the influence of different pretreatments (treatments with 1–4% activated charcoal for prior phenolics removal) on metabolic parameters and BDS rates. Afterwards, the liquor was used as the C-source in chemostat assays, compared to commercial sugars, to develop and optimize the use of STFr-liquor as a viable C-source towards cost-effective biocatalyst production. Moreover, the high-market-value bioproducts simultaneously produced during microbial growth were also evaluated. In this context, the best results, considering both the production of biocatalysts with BDS activity and simultaneous bioproduct production (carotenoids and gordofactin biosurfactant/bioemulsifier) were achieved when strain 1B was cultivated in a chemostat with untreated STFr-liquor (5.4 g/L fructose + glucose, 6:4 ratio) as the C-source and in a sulfur-free mineral-minimized culture medium at a dilution rate of 0.04 h⁻¹. Cells from this steady-state culture (STFr L1) achieved the highest desulfurization with 250 mM of dibenzothiophene as a reference organosulfur compound, producing a maximum of ≈213 mM of 2-hydroxibyphenil (2-HBP) with a corresponding specific rate (q_2-HBP) of 6.50 µmol/g(_DCW)/h (where DCW = dry cell weight). This demonstrates the potential of STFr as a sustainable alternative C-source for the production of cost-effective biocatalysts without compromising BDS ability. Additionally, cells grown in STFr L1 also presented the highest production of added-value products (338 ± 15 µg/g_(DCW) of carotenoids and 8 U/mL of gordofactin). These results open prospects for a future G. alkanivorans strain 1B biorefinery that integrates BDS, waste valorization, and the production of added-value products, contributing to the global economic viability of a BDS process and making BDS scale-up a reality in the near future. Full article

After cannabidiol was extracted from the hemp biomass using supercritical CO₂ extraction, the residual could be utilized as a source of other valuable ingredients. The stability of the extracted CBD in pre- and post- encapsulation states were evaluated. Dynamic macerations with ethanol and hexane were compared for CBD extraction. The ethanol extract yielded 0.11% ± 0.10 CBD and 1.83% ± 0.00 cannabidiolic acid (CBDA), while the hexane extraction yielded 0.08% ± 0.04 CBD, 1.06% ± 0.04 CBDA, and 0.30% ± 0.04 delta-9-tetrahydrocannabinol (Δ9-THC). Ethanol extraction was selected due to the low THC detection in the extract. The CBD extract was encapsulated using water soluble yellow mustard mucilage (WSM), maltodextrin (MD), gum Arabic (GA), and protein extracted from the hemp biomass waste (HBP) via freeze drying. The WSM-MD-GA 1:5 particle formulation exhibited superior thermal stability over 72 h, whereas the WSM-HBP-GA 1:5 formulation offered the most protection against UVa-induced degradation within the same duration. Incorporating hemp biomass protein as an encapsulation material enhanced protection against light exposure through UV absorption, although it did not grant thermal protection. These findings indicated that encapsulation significantly protects against CBD degradation when subjected to thermal and light conditions compared to non-encapsulated CBD. Full article

This research developed a biodegradable absorbent pad using polybutylene adipate terephthalate (PBAT) and thermoplastic starch (TPS) films, combined with hairy basil (Ocimum basilicum) seed powder (HBP) to extend the shelf life of fresh pork during cold storage. To form the biocomposite film, PBAT was blended with TPS in ratios of 100:0, 90:10, 70:30, and 50:50. The PBAT:TPS ratio of 70:30 (PB7T3) was the most suitable in terms of mechanical properties and water permeation. Therefore, PB7T3 was selected to fabricate the absorbent pad for extending the shelf life of fresh pork during cold storage. For the storage test, 100 g of pork pieces was placed in PET trays (12 cm × 12 cm), each containing a different absorbent: the control (no pad), a commercial absorbent pad, and the PB7T3 absorbent pad. The pork samples were stored at 4 °C for 8 days and analyzed for color change, total plate count (TPC), total volatile basic nitrogen (TVB-N), pH, and drip loss on days 0, 2, 4, 6, and 8. The results indicated that the PB7T3 absorbent pad effectively extended the shelf life of fresh pork compared to the control, with no significant difference compared to the commercial absorbent pad made from plastic. This research opens new avenues for developing sustainable absorbent pads, contributing to reduced reliance on conventional non-biodegradable plastics. Full article

Conduction system pacing started with His bundle pacing (HBP) and then rapidly switched gears into left bundle branch pacing (LBBP). We describe our center’s experience with LBBP using either lumenless leads (LLLs) or stylet-driven leads (SDLs). Patients who were admitted to two tertiary centers between 1 April 2021 and 30 June 2024 and met the guidelines for pacing were recruited and prospectively followed up. A total of 124 patients underwent permanent pacemaker (PPM) implantation using the LBBP technique with a mean follow-up of 19.7 ± 13.3 months. In total, 90 patients were implanted with LLLs and 34 with SDLs. There was no significant difference in the procedural time and final paced QRS duration, but fluoroscopy time was significantly longer in the SDLs (26.2 ± 17.7 min vs. 17.5 ± 13.0 min, respectively, p = 0.026). The on-table impedance values were also significantly higher in the LLLs, and this persisted throughout the follow-up. There were no differences in the rates of complications. The success of conduction system pacing implantation with SDLs and LLLs is comparable with reasonable safety and reliable outcomes. Good pre-implant patient selection will contribute to improved outcomes. Full article