Developing bioresorbable energy sources that eliminate the need for secondary surgery for device removal remains a major challenge in resorbtronics. In this work, we present an alternative fabrication strategy for new bioresorbable quasi-solid Na-ion batteries using Mo or Mg thin films as current collectors. The assembled batteries were characterized using scanning electron microscopy, spectroscopic techniques including X-ray photoelectron spectroscopy, physicochemical, and electrochemical characterization techniques. Results demonstrate that the choice of current collector strongly influences electrochemical performance. Mo-based batteries delivered a discharge capacity of 6.8 mAh cm- 2 at a C/2 rate, approximately twice that of Mg-based counterparts whose performance is limited by oxidation reactions. Moreover, Mo-based batteries exhibited stable cycling with 86% capacity retention after 100 cycles at 2C. In vitro cytotoxicity assays showed cell viability above the 70% threshold indicating that the tested materials are non-cytotoxic according to ISO 10993 guidelines. Implantation studies confirmed safe degradation of Mo-based batteries supported by in vivo monitoring of animal health behavior and ex vivo organ analyses, including organ weight, ALT measurements, and histological evaluation of skin at the implantation site after three months. Additionally, the operational lifetime of implanted batteries can be tuned from days to months by controlling encapsulation layer thickness.
To compare clinical outcomes following hip arthroscopy for femoroacetabular impingement syndrome using either limited interportal (IP) or T-capsulotomy (TC) technique, with routine capsular closure. This retrospective cohort study included patients ≤50 years old who underwent primary hip arthroscopy for femoroacetabular impingement syndrome between May 2021 and January 2024 with a minimum of 12-month follow-up. Patients were treated with either IP or TC, and all underwent standardized capsular repair. Patient-reported outcomes (PROs) were collected preoperatively and at final follow-up. Cohort-specific minimum clinically important difference thresholds were calculated for each PROs and compared between groups. Improvements in scores were compared with established thresholds for the patient acceptable symptomatic state (PASS). Statistical significance was set at P < .05. A total of 116 patients met the inclusion criteria (54 IP, 62 TC; mean age 34.5 ± 8.8 years; 55% female). Mean follow-up was 15.5 ± 5.4 months. Both groups showed significant improvements in all PROs. Although mean improvements were not statistically different, the interportal group showed consistently higher average postoperative scores. Cohort-specific minimum clinically important difference thresholds were achieved at similar rates in both groups, whereas exploratory analyses using previously published PASS thresholds showed higher PASS achievement in the interportal group for International Hip Outcomes Tool (76% vs 54%) and Patient Reported Outcome Measurement Information System Physical Function (58% vs 46%). No revisions or Clavien-Dindo grade ≥2 complications occurred in either group. Both IP and TC techniques led to significant improvements in PROs following hip arthroscopy with capsular repair, with similar rates of cohort-specific minimum clinically important difference achievement and no differences in revision surgery or major complications. Exploratory analyses showed higher PASS rates for International Hip Outcomes Tool and Patient Reported Outcome Measurement Information System Physical Function in the IP group, suggesting that a more limited capsulotomy may confer functional advantages. Level III, retrospective comparative case series.
Digital services allow patients to efficiently access healthcare. These services work more effectively than traditional paper-based systems by delivering better patient outcomes, helping address global health challenges, and promoting the universal adoption of health technology. This study examined the impact of digital healthcare adoption and service quality on patient satisfaction in Pakistan's public healthcare sector and the moderating effect of telehealth services on this relationship. This study adopted the technology acceptance model to understand technology sophistication and how electronic medical records, digital patient systems, and technology impact healthcare through efficiency and communication. Simultaneously, the study examined the role of doctor services, nurse services, pharmacy services, and laboratory services in the patient experience. Random sampling techniques were employed, and questionnaires were distributed to 573 respondents across five central districts of Punjab, Pakistan. The hypotheses were tested using IBM SPSS Statistics, Amos, and structural equation modeling. These findings show that digital healthcare adoption and service quality significantly improve patient satisfaction, whereas telehealth services reinforce these relationships by overcoming geographical and logistical hurdles. The conclusions of this study offer pragmatic guidance to policymakers and healthcare administrators for devising digital healthcare strategies to improve patient outcomes.
The stable modulation of the local charge distribution behavior induced by unsaturation sites within photocatalysts continues to pose a significant challenge in the quest to achieve notable enhancements in photocatalytic activity. Herein, we harnessed the hydrogen annealing reduction technique to deliberately introduce oxygen vacancies (OVs) into the BiOCl lattice for constructing the OVs-Bi-O structure, which decreases the valence state of Bi, and diminishes the Bi─O coordination, further establishing a charge asymmetric region within the material. This distinctive structural arrangement facilitates the sufficient migration of electrons to adjacent Bi sites that are closely linked to the OVs, significantly promoting the capture capability of electrons, leading to more adsorption and activation of water and oxygen as well as the conversion of reactive oxygen radicals. The engineered OVs-BiOCl variant showcases potential photocatalytic prowess, boasting a satisfactory photocatalytic application than that of its unmodified BiOCl counterpart. Under low-light conditions, this variant impressively achieves a ∼98.1% removal efficiency for RhB, while concurrently achieving an almost complete elimination of E. coli. This finding presents an insightful approach for manipulating unsaturation coordination active sites through the strategic introduction of controllable defects and elucidates the impact of unsaturation coordination on photocatalytic efficiency.
Lateral lengthening calcaneal osteotomy (LLOT, Evans and Hintermann) is widely used to treat progressive collapsing foot deformity (PCFD). In the Evans osteotomy, the cut is performed proximal to the calcaneocuboid joint, carrying a risk of violating the anterior or middle subtalar facet. Hintermann proposed a modified technique placing the osteotomy between the middle and posterior facets to reduce risks. Although anatomical studies have shown potential facet involvement, clinical data on the actual incidence and its impact on long-term outcomes remain scarce. This study aimed to determine the incidence of subtalar facet penetration after LLOT and to evaluate its effect on clinical and radiographic results. All patients aged ≥18 years who underwent LLOT (Evans or Hintermann osteotomy) at our institution between January 1, 2010, and December 31, 2020, were included. Postoperative computed tomography (CT) was performed 6 weeks after surgery to assess possible subtalar facet violation. At a minimum follow-up of 5 years, magnetic resonance imaging (MRI) was obtained to evaluate cartilage and ligament integrity. Clinical outcomes at the time of MRI were assessed using the Foot Function Index (FFI) and the American Orthopaedic Foot & Ankle Society (AOFAS) score. Demographic variables, including type of osteotomy and outcome measures, were compared between patients with and without facet penetration. Thirty-one patients met inclusion criteria. Subtalar facet penetration was detected in 11 patients (35%) on postoperative CT. No significant differences were observed between groups with respect to demographic variables. MRI analysis revealed no relevant differences in cartilage degeneration. FFI and AOFAS scores were comparable between groups. Subtalar facet penetration occurred in one-third of patients after LLOT (Evans and Hintermann). With the numbers available, no significant differences in clinical or radiographic outcomes were detected at a minimum 5-year follow-up, suggesting that minor facet violations may have limited clinical relevance. Level III, retrospective cohort study.
Automated right ventricular (RV) analysis in 2D echocardiography is limited by the morphological complexity of RV segmentation and the domain fragility of single-center deep learning models across ultrasound vendors. No prior framework has jointly addressed both challenges for RV-specific segmentation. To develop and prospectively validate TACA-Net (Bi-Phase Adversarial Cross-Attention Network), a unified multi-center framework for simultaneous RV endocardial segmentation and three-class functional severity classification (normal, mildly reduced, significantly reduced) in 2D apical four-chamber echocardiography. Data were prospectively collected from three clinical sites within a single tertiary hospital network, each equipped with a different ultrasound vendor. Centers A and B (n = 1,240 patients) were used for training and 5-fold cross-validation; Center C (n = 320 patients) served as the fully held-out external test set. TACA-Net integrates a gradient reversal layer-based domain discriminator for vendor-agnostic feature learning, a bidirectional bi-phase cross-attention module encoding the complementary information between end-diastolic and end-systolic representations, and a dual-head decoder jointly optimizing segmentation and classification with an auxiliary bi-phase consistency loss. Performance was benchmarked against six segmentation baselines (U-Net, Attention U-Net, TransUNet, Swin-UNETR, nnU-Net, MACS) and five classification baselines (ResNet-50, EfficientNet-B4, ViT-B/16, segmentation-then-classify pipeline, MACS + head). Primary segmentation endpoints were Dice Similarity Coefficient (DSC) and Hausdorff Distance 95th percentile (HD95); primary classification endpoint was macro-averaged area under the receiver operating characteristic curve (AUC). On the external test set, TACA-Net achieved a DSC of 0.903 ± 0.013 and an HD95 of 7.1 ± 1.0 mm for RV segmentation, and a macro-averaged AUC of 0.911 (95% CI: 0.885-0.937) for functional classification, statistically significantly superior to all six segmentation and five classification baselines (all p < 0.01). Ablation analyses demonstrated independent contributions of domain alignment (ΔDSC = -0.038 when removed), bi-phase cross-attention (ΔAUC = -0.032), and multi-task joint training (ΔDSC = -0.014). No significant differential performance was detected across diagnosis subgroups, sex, or image quality strata. GradientSHAP attribution maps revealed highest feature importance in the RV lateral free wall, consistent with established RV pathophysiology. Expected calibration error for TACA-Net was 0.041 on the external test set, the lowest among all classification models evaluated. TACA-Net achieves vendor-agnostic RV segmentation and functional classification from routinely acquired 2D echocardiography, with robust multi-vendor generalization demonstrated under rigorous prospective external validation. The framework provides a clinically interpretable and methodologically transparent foundation for AI-assisted right heart assessment at scale.
Atypical gaze patterns are consistently reported in autism, reflecting differences in social attention and interest. Gaze-tracking paradigms provide an objective way to quantify these differences and may serve as early indicators of autism. This diagnostic test accuracy systematic review and meta-analysis evaluated the performance of eye-tracking-based gaze measures in children. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy (PRISMA-DTA) guidance, studies published between 2015 and 2025 that compared gaze-tracking paradigms with standardized autism diagnoses were synthesized. Pooled diagnostic odds ratio (DOR), sensitivity, and specificity were estimated using random-effects and hierarchical summary receiver operating characteristic models. Risk of bias was assessed with QUADAS-2 and funnel plots. Seventeen studies (n = 4,256) from six countries met the inclusion criteria. Tasks included social-geometric preference, motherese-nonsocial speech, and visual-orienting paradigms analyzed with rule-based or machine-learning methods. The pooled area under the hierarchical summary receiver operating characteristic curve (HSROC AUC) was 0.845; DOR 15.03 (95% CI 8.00-28.50); sensitivity 0.77 (95% CI 0.65-0.85); and specificity 0.80 (95% CI 0.75-0.84). Although heterogeneity was high (I2 = 87.78%), effect directions were consistent. Dynamic social stimuli and higher-frequency tracking systems achieved the best performance. Gaze-tracking tests distinguished autistic and nonautistic children across diverse settings, supporting their potential role as a quantitative, observer-independent adjunct for early identification and clinical decision support.Lay abstractAutism is a form of neurodiversity characterized by differences in social communication, sensory processing, and patterns of attention and interest, which often shape how autistic people look at and interpret the world around them. Eye-tracking technology records where a person looks on a screen and how long their gaze remains on elements, such as people, faces, or objects. Because it is objective and does not rely on language or complex instructions, eye-tracking may support earlier identification of autism. This study reviewed 17 research papers published between 2015 and 2025 that explored how eye-tracking distinguishes autistic and nonautistic children. Together, these studies included over 4,000 participants and compared attention to social scenes, like people talking or playing, with attention to nonsocial or geometric patterns. On average, eye-tracking correctly identified autism about 77% of the time and nonautistic children about 80% of the time, with the best results achieved with dynamic social videos and high-quality tracking cameras. These findings suggest that gaze-based measures capture meaningful differences in social attention and could complement existing diagnostic approaches through earlier, more objective assessment.
To investigate outcomes among patients undergoing total hip arthroplasty after hip arthroscopy (HA-THA) compared with a matched cohort undergoing primary THA without prior arthroscopy (Only-THA). Patients who underwent THA after primary hip arthroscopic labral repair from 2009 to 2022 at a single institution were identified. Cases were propensity-matched 1:4 to primary THA controls by age at THA, sex, body mass index (BMI), surgical approach, and year of surgery. At minimum 2-year follow-up, patient-reported outcomes (PROs)-Forgotten Joint Score (FJS), modified Harris Hip Score (mHHS), and Hip Disability and Osteoarthritis Outcome Score Pain (HOOS-Pain)-were analyzed. Sixty-two hips (age: 47.5 ± 9.3 years, BMI: 29.7 ± 6.2 kg/m2) were matched to 248 Only-THA hips (age: 47.9 ± 10 years, BMI: 29.5 ± 5.8 kg/m2). Although both HA-THA and Only-THA patients showed significant (P < .001) postoperative improvements in PROs, HA-THA patients reported significantly lower postoperative FJS, mHHS, HOOS-Pain, and inferior Visual Analog Scale pain scores (P < .001) compared with Only-THA controls. A cohort-specific minimal clinical important difference for mHHS was calculated as 9.6 points, with 75.7% of HA-THA and 87.5% Only-THA patients achieving this threshold (P = . 077). At mean 6.6 ± 3.3 years follow-up, HA-THA patients with preoperative Tönnis grades 1 reported significantly decreased FJS, mHHS, and HOOS-Pain compared with HA-THA patients with preoperative Tönnis grade 2-3 (P ≤ .05). HA-THA patients with Tönnis grade 1 also exhibited worse PROs (P < .001) compared with Only-THA controls. Although there were no differences in complication rates between HA-THA and Only-THA patients (8% vs. 5%, P = .49), all-cause reoperation was greater amongst HA-THA (10% vs. 2%, P = .01). Patients undergoing THA after prior hip arthroscopy showed modestly inferior subjective outcomes at mid-term follow up compared with an age-matched cohort without prior arthroscopy. Although both groups showed meaningful improvement, a smaller proportion of HA-THA patients achieved the cohort-specific MCID for mHHS compared with Only-THA controls. Level III, retrospective cohort study.
To describe public awareness of the Centre antipoison du Québec (CAPQ), expectations regarding acute poisoning management and service delivery, and satisfaction among prior users. We conducted a cross-sectional, bilingual online survey of Quebec residents aged ≥ 14 years between April 13, 2024, and June 27, 2025. The questionnaire collected demographic data, assessed awareness and prior use of the CAPQ, explored past poisoning events and expectations for acute poisoning management, and measured satisfaction among previous users using a 5-point Likert scale, with open-ended questions for qualitative input. Participants were recruited through convenience and snowball sampling via public settings, social media, and CIUSSS newsletters. Descriptive statistics summarized responses and explored trends. A total of 611 respondents were included; 541 (88.5%) were aware of the CAPQ, including 152 prior users, while 70 (11.5%) were unaware. Unawareness was more common among females (60.0%), non-healthcare workers (91.4%), respondents with a non-North American ethnic background (34.2% vs. 10.1%), and those not primarily French-speaking (12.9% vs. 3.0%). Regional variation was observed, with Capitale-Nationale contributing the largest number of unaware respondents (35/70) and Laurentides showing the highest proportion (26.7%). Among respondents without prior CAPQ use who reported a poisoning event, most contacted emergency services or presented to the emergency department. Expectations were similar among aware and unaware respondents, particularly for acute poisoning management, with nurses expected to respond within five minutes. Among prior users, overall satisfaction was high across all domains, though communication and outreach were identified as areas for improvement. Key service expectations included rapid 24/7 access (76.9%), responder expertise (69.9%), and clear, adapted recommendations (56.1%). Most respondents preferred French (84.9%), telephone communication (94.1%), and follow-up calls (81.7%). User satisfaction with the CAPQ was high, but gaps in public awareness and service expectations remain. These findings highlight opportunities to improve accessibility, communication and outreach strategies. RéSUMé: OBJECTIFS: Décrire la sensibilisation du public au Centre antipoison du Québec (CAPQ), les attentes concernant la gestion des intoxications aiguës et la prestation de services, ainsi que la satisfaction des utilisateurs antérieurs. MéTHODES: Nous avons mené une enquête en ligne transversale et bilingue auprès de résidents du Québec âgés de ≥14 ans entre le 13 avril 2024 et le 27 juin 2025. Le questionnaire a permis de recueillir des données démographiques, d’évaluer la connaissance et l’utilisation antérieure du CAPQ, d’explorer les événements d’intoxication passés et les attentes en matière de gestion des intoxications aiguës, et de mesurer la satisfaction des utilisateurs précédents à l’aide d’une échelle de Likert à 5 points, avec des questions ouvertes pour l’apport qualitatif. Les participants ont été recrutés par commodité et par échantillonnage de boules de neige via des lieux publics, les réseaux sociaux et les bulletins d’information du CIUSSS. Les statistiques descriptives résument les réponses et explorent les tendances. RéSULTATS: Un total de 611 répondants ont été inclus; 541 (88,5 %) étaient au courant du CAPQ, y compris 152 utilisateurs précédents, tandis que 70 (11,5 %) n’étaient pas au courant. L’ignorance était plus fréquente chez les femmes (60,0 %), les non-travailleurs de la santé (91,4 %), les répondants d’origine ethnique non nord-américaine (34,2 % contre 10,1 %) et ceux qui n’étaient pas principalement francophones (12,9 % contre 3,0 %). Une variation régionale a été observée, la Capitale-Nationale ayant contribué au plus grand nombre de répondants ignorants (35/70) et les Laurentides affichant la proportion la plus élevée (26,7 %). Parmi les répondants n’ayant pas utilisé le CAPQ qui ont signalé un événement d’empoisonnement, la plupart ont contacté les services d’urgence ou se sont présentés au service des urgences. Les attentes étaient similaires chez les répondants conscients et inconscients, en particulier pour la prise en charge des intoxications aiguës, les infirmières étant censées répondre dans les cinq minutes. Parmi les utilisateurs précédents, la satisfaction globale était élevée dans tous les domaines, bien que la communication et la sensibilisation aient été identifiées comme des domaines à améliorer. Les principales attentes en matière de services comprenaient un accès rapide 24/7 (76,9 %), l’expertise des intervenants (69,9 %) et des recommandations claires et adaptées (56,1 %). La plupart des répondants préfèrent le français (84,9 %), les communications téléphoniques (94,1 %) et les appels de suivi (81,7 %). CONCLUSIONS: La satisfaction des utilisateurs à l’égard du CAPQ était élevée, mais il subsiste des lacunes dans la sensibilisation du public et les attentes en matière de services. Ces résultats mettent en évidence les possibilités d’améliorer l’accessibilité, la communication et les stratégies de sensibilisation.
Foot-and-mouth disease (FMD), caused by the FMD virus (FMDV), is a highly contagious transboundary animal disease of cloven-hooved animals that causes significant economic losses worldwide, including in Bangladesh. This cross-sectional study was designed to assess FMDV antibodies and associated risk factors among sheep and goats in selected districts of Bangladesh. The present study was conducted from July to December 2023 in three districts of Dhaka Division in Bangladesh to assess the seroprevalence of FMDV in unvaccinated sheep and goats. For this, a total of 372 (n = 372) blood samples were collected aseptically for serum separation and tested for antibodies against FMDV-nonstructural protein (NSP) using a commercially available ELISA kit. The hypothesized risk factors data were collected through a structured questionnaire and analysed via chi-square tests and logistic regression models to identify their association with FMD seropositivity. Overall seroprevalence of FMDV was 20.97% (78/372); sheep 50.0% (20/40), goats 17.5% (58/332). Firth's penalized multivariable logistic regression identified species (sheep) (AOR = 17.2, 95% CI = 6.77-48.2, p < 0.001), district (Narsingdi) (AOR = 0.32, 95% CI = 0.13-0.7, p < 0.001), (Gazipur) (AOR = 17.1, 95% CI = 5.21-69, p < 0.001), feeding system (grazing) (AOR = 9.53, 95% CI = 3.45-29.6, p < 0.001), river-basin ecology (AOR = 6.32, 95% CI = 2.09-22.8, p < 0.001), and animal introduction (AOR = 2.33, 95% CI = 1.02-5.45, p = 0.044) as independent risk factors for FMD seropositivity. This study observed a high seroprevalence of FMDV in sheep and goats within the Dhaka division and highlights the need for broader and routine surveillance of FMD in small ruminants across Bangladesh, alongside cattle and buffaloes, to better understand its epidemiology and inform control strategies.
Eosinophilic colitis (EC) is a rare eosinophilic gastrointestinal disorder with increasing frequency in recent years. Although normal eosinophil density varies substantially by colonic segment, several proposed eosinophil thresholds have been used in the literature to support the diagnosis in the appropriate clinical context. However, some patients with clinical features suggestive of eosinophilic colitis (EC) do not demonstrate increased tissue eosinophil counts on histopathologic examination. To compare eosinophil-derived cell-free granules based on expression of their surface markers between two groups of patients with symptoms consistent with EC: those with increased tissue eosinophils and those without tissue eosinophilia. This study included 10 pediatric patients with histologically confirmed EC and 13 patients with clinical suspicion of EC. Eosinophil-derived cell-free granules were evaluated in colonic tissue samples using immunohistochemistry (IHC), with antibodies against MBP and CCR3. Eosinophil-derived cell-free granules were detected in all specimens from patients with suspected EC and in the majority of specimens from patients with confirmed EC. Degranulating eosinophils were identified in all specimens from both groups, although the proportion of degranulating eosinophils varied among patients. Furthermore, the abundance of granules was significantly associated with the percentage of degranulating eosinophils. Our findings indicate that IHC can be used to detect eosinophil-derived granules in colonic tissue. The presence of cell-free eosinophil granules with varying abundance, along with evidence of eosinophil degranulation in all specimens from patients with suspected EC, may provide supportive histopathological features that contribute to improving the diagnostic assessment of EC.
Canine parvovirus (CPV) is a major cause of haemorrhagic enteritis in juvenile dogs, yet its potential ocular effects have not been systematically investigated. To evaluate whether naturally acquired CPV infection in juvenile dogs is associated with alterations in tear production, intraocular pressure, corneal integrity, fundoscopic findings, and ocular ultrasonographic measurements. Seventy client-owned dogs under 6 months of age were included: 35 with confirmed CPV infection and 35 healthy controls. Before treatment, all animals underwent standardised ophthalmic examination including Schirmer tear test-I (STT-I), intraocular pressure (IOP) measurement, fluorescein staining, fundoscopic examination, and ocular ultrasonography. In CPV-infected dogs, dehydration severity (mild 5%-8%, moderate 8%-10%, severe ≥10%) was graded clinically for exploratory analyses. Continuous variables were compared using Student's t-test or Mann-Whitney U test, and categorical variables using χ2 or Fisher's exact tests. CPV-infected dogs had significantly lower STT-I and IOP values than controls. Fluorescein staining was positive in 27/35 (77.1%) infected dogs and absent in controls. Fundoscopic abnormalities, including retinal vessel beading, chorioretinitis, and optic neuritis, were detected in 28/35 (80%) infected dogs, whereas all controls had normal findings. Ocular ultrasonographic parameters did not differ between groups. Dehydration severity did not significantly affect STT-I, IOP, or fluorescein results. CPV infection in juvenile dogs is associated with reduced tear production, ocular hypotony, frequent corneal epithelial defects, and posterior segment abnormalities, indicating that CPV may involve both the ocular surface and fundus in addition to the gastrointestinal system.
Accelerated high-frequency repetitive transcranial magnetic stimulation (aHF-rTMS) is an emerging modality in both human and veterinary medicine. Although previous studies show brain changes and behavioral improvements in healthy and patient dogs, the effects of aHF-rTMS on neurotransmitter levels remain poorly understood. This study aimed to compare monoaminergic metabolite profiles in healthy and anxious dogs, and to evaluate short-term, long-term, and dose-dependent effects of aHF-rTMS on these metabolites. A total of 79 dogs were included, comprising 59 healthy controls and 20 anxious dogs. Cerebrospinal fluid samples were collected to measure dopaminergic (3,4-dihydroxyphenylacetic acid [DOPAC] and homovanillic acid [HVA]) and serotonergic (5-hydroxyindoleacetic acid [5-HIAA]) metabolites before and after various aHF-rTMS protocols with varying dosing and duration. Generalized linear mixed-effects models were used to assess baseline differences and stimulation-induced changes across protocols and timepoints. Patient dogs consistently showed lower baseline levels of all three metabolites (DOPAC, HVA, and 5-HIAA) than healthy controls, supporting a neurochemical basis for canine anxiety. Furthermore, neuromodulatory effects of aHF-rTMS were selective and dependent on protocol and timing. In healthy dogs, the short-term stimulation increased 5-HIAA whereas longer protocols reduced HVA. In patient dogs, long-term follow-up revealed significant fluctuations in DOPAC, whereas HVA and 5-HIAA remained stable. These findings indicate baseline monoaminergic deficits in anxious dogs and support a neurochemical basis for canine anxiety. Moreover, aHF-rTMS induces distinct, state- and duration-dependent neurochemical responses. Overall, this study provides novel insights into the neurobiology of anxious dogs and supports further investigation of aHF-rTMS as a neuromodulatory approach in dogs with translational relevance.
Silica-based nanomaterials have shown promise for remediating heavy metal-contaminated soils. However, their remediation stability may be compromised by natural and anthropogenic activities such as rainfall and irrigation. This work systematically investigates the leaching behavior of Cd from soils amended with unmodified SiO2 and thiol-functionalized SiO2 (SH-SiO2) nanoparticles, along with nanoparticle-mediated Cd release and transport through soil porous media. The results demonstrated that the leaching concentrations of Cd2+ from the soil remediated by SH-SiO2 were the least and followed the order of SH-SiO2 < SiO2 ≈ control (untreated Cd-contaminated soil) under simulated acid rain conditions (pH 5.6). This confirms that thiol-functionalized silica effectively immobilizes Cd due to its strong chelating ability. However, co-transport experiments revealed that both SiO2 and SH-SiO2 nanoparticles could act as carriers that enhanced Cd2+ transport, governed by their Cd-binding capacity and intrinsic mobility over a pH range of 5.0-8.0, with greater facilitation at higher pH levels. Notably, SH-SiO2 exhibited a much stronger facilitation effect, attributable to its higher affinity for Cd2+, greater mobility in porous media, and resistance to desorption of SH-SiO2-bound Cd2+. At a nanoparticle concentration of 50 mg/L, the maximum breakthrough of Cd2+ reached 10.1% for SiO2 and 75.2% for SH-SiO2. While SH-SiO2 demonstrates excellent Cd immobilization capacity and acid-rain resistance, any disturbance that remobilizes these nanoparticles may facilitate the mobility of Cd2+, potentially expanding the scope of heavy metal contamination. Therefore, when applying remediation agents for soil rehabilitation, it is crucial to consider their long-term effectiveness and stability.
Polycystic liver disease and other manifestations of ductal plate malformation (DPM) may be incidental or indeed develop significant complications. The genetic basis of 'isolated' DPM differs from that associated with polycystic kidney disease and remains incompletely understood. We sought to genetically characterize a sizeable single-center cohort of patients with 'isolated' DPM, defined as absence of polycystic kidney disease. 55 consecutive patients with isolated DPM were analyzed retrospectively with next-generation sequencing used to identify genetic variants. 54/55 completed genetic characterization. 40 patients had polycystic liver disease (PCLD) as the primary phenotype, 9 had congenital hepatic fibrosis (CHF), 1 had Caroli disease and 5 had multiple biliary hamartomas. 10 patients had mixed phenotype. The majority were female (78%) and mean age at presentation was 47 years. Of patients with PCLD, previous estrogen exposure was associated with cyst complications. Of the 54 genetically analyzed patients, pathogenic or likely pathogenic variants were identified in 31. PCLD was mainly associated with SEC63, PRKCSH and GANAB heterozygous variants with a minor contribution from PKHD1 and ALG8. PRKCSH followed by GANAB was associated with the most severe PCLD presentation. CHF was represented solely by PKHD1 variants half of which were missense, as opposed to truncating in all but one of the other genotypes. Importantly, 5 novel variants were identified (4 SEC63, 1 PRKCSH). We have shown that current genetic testing methods are often revealing in isolated DPM. Future broadening of genetic analysis will enhance diagnosis and understanding within this heterogeneous disease spectrum.
Natural Killer (NK) cells are innate lymphoid cells that eliminate malignant cells via perforin/granzyme-mediated cytotoxicity. This study investigates whether Olive Leaf Extract (OLE), rich in oleuropein and hydroxytyrosol, can enhance NK-cell cytotoxicity against colorectal cancer (CRC) cells. Although OLE exhibits direct anticancer effects, its therapeutic utility is constrained by poor bioavailability, requiring supraphysiological concentrations for direct cytotoxicity. To evaluate the effect of OLE on the cytotoxic activity of NK-92 cells against HT-29 colorectal cancer cells within a co-culture model. Olive leaves obtained from Balıkesir, Türkiye were dried and extracted with 70% methanol. The effects of OLE on the viability of HT-29 cells and NK-92 cells were evaluated using MTT and ATP assays. Additionally, the cytotoxic activity of NK-92 cells against HT-29 cells was assessed in a direct co-culture system. Granzyme B and perforin levels were measured using ELISA kits. OLE inhibited the proliferation of HT-29 cells in a dose-dependent manner, with an IC₅₀ values of 548 µg/mL. In NK-92 cells, low concentrations of OLE (100-200 µg/mL) promoted cell proliferation, whereas higher concentrations exerted cytotoxic effects. In co-culture experiments, NK-92-mediated cytotoxicity against HT-29 cells was significantly enhanced by the addition of OLE at non-toxic concentrations (100 and 200 µg/mL). This enhanced cytotoxicity was further supported by a significant increase in granzyme B and perforin levels following OLE treatment. Our findings suggest that OLE can elicit a potent anticancer response via NK cells at lower, physiologically achievable doses. These results highlight a promising therapeutic strategy for CRC, leveraging OLE's immunomodulatory effects to enhance innate antitumor defenses.
Orientia tsutsugamushi (OT), an obligate intracellular Gram-negative bacterium of the Rickettsiaceae family, causes scrub typhus (ST), a re-emerging vector-borne infectious disease with significant morbidity and mortality in South and Southeast Asia. Despite its widespread prevalence and mortality rates reaching up to 30% in untreated individuals, no effective vaccines or targeted therapeutics are currently available.Compounding these challenges are limitations in existing diagnostic methods, increasing antibiotic resistance, and complex interactions among host, pathogen, and vector. To address these critical gaps, this study conducted a comprehensive genome-wide comparative analysis across 23 OT strains, including UT 76, Karp, Kato, Gilliam, and Wuj/2014, using an in-house R-based computational pipeline. This analysis identified a conserved core genome of 744 genes, of which 19 are unique and pathogen- specific proteins. Subcellular localisation analyses revealed that nine of these proteins are membrane- associated, highlighting their potential accessibility to therapeutic agents. Additionally, proteins were prioritised through an integrative analysis that incorporates protein- protein interaction networks, druggability assessments, and antigenicity profiling. Six key proteins- dnaK, fusA, fabG, infB, nuoN and fabI were identified based on their essential roles in pathogen- specific pathways. These proteins are involved in membrane transport, transcription regulation, and biosynthesis, making them promising drug targets. Notably, this study employs in silico methodologies to overcome limitations inherent to traditional wet-lab approaches. Computational strategies are cost-effective for identifying conserved targets and supporting hypothesis- driven drug discovery. The findings presented here not only reveal previously uncharacterized therapeutic targets but also establish a genomic framework to improve diagnostic accuracy and guide future drug development against ST.
Electrochemical conversion of nitrogen oxides (NOx, mainly NO and NO2) to ammonia (NH3) transforms a pollutant into a valuable chemical, providing a direct link between emissions control and low-carbon NH3 production under mild conditions. However, NOx reduction competes with hydrogen evolution (HER) and can diverge to N2/N2O, while many catalysts restructure under bias, making results difficult to compare and design rules hard to extract. Cu-MXene hybrids are emerging as a compelling platform because the 2D interface can be engineered to control adsorption, electron (e-) transfer, and local proton (H+) activity through Cu speciation (single sites, clusters, oxides, reconstructed surfaces) and MXene terminations/defects. This critical review summarizes the interfacial control of these catalysts to achieve selective NOx-to-NH3 electroconversion. The review provides a comprehensive analysis of intermediates and performance, quantifying using device-relevant metrics (Faradaic efficiency, NH3 yield/partial current, energy efficiency, durability, and selectivity against N2/N2O and HER). Special emphasis is placed on reactor design, including flow-cell and gas-diffusion electrode (GDE) configurations, which enhance mass transport, stabilize the three-phase boundary, and enable long-term operational stability. Finally, the review emphasizes the use of in situ/operando methods to investigate the reaction mechanisms, outlines design rules and scale-up priorities for practical NOx upcycling into green ammonia.
Fatty liver is highly prevalent in dairy cows and poses a significant challenge to the dairy industry by reducing both milk yield and quality, thereby inflicting substantial economic losses. Although dietary betaine supplementation has been demonstrated to enhance milk protein content, the underlying molecular mechanisms remain to be fully elucidated. This study aimed to elucidate the role of betaine in milk protein synthesis and the underlying mechanisms. Blood, liver and mammary gland samples were obtained from healthy and fatty liver-affected bovines. The serum NEFA levels, oxidation and antioxidant enzyme systems and milk protein synthesis-related proteins expression were determined. In vitro, the bovine mammary epithelial cells (BMECs) were pretreated with 25 mM betaine/10 mM N-acetyl-L-cysteine (NAC) and then stimulated with NEFA. The results indicated an elevation in serum NEFA levels accompanied by enhanced oxidative stress (OS) and reduced protein levels related to milk protein synthesis (phosphorylated (p)-mechanistic target of rapamycin (mTOR)/mTOR, p-ribosomal protein S6 kinase 1 (S6K1)/S6K1, p-Janus kinase 2 (JAK2)/JAK2, p-signal transducer and activator of transcription 5 (STAT5)/STAT5 and β-casein) in dairy cows with fatty liver. In vitro, the results revealed betaine decreased the hydrogen peroxide (H2O2), malondialdehyde (MDA), and oxygen free radicals (OFR) contents, and lactate dehydrogenase (LDH) activity in the supernatant, but increased the glutathione peroxidase (GPX), catalase (CAT), superoxide dismutase (SOD) and thioredoxin reductase (TrxR) activities; the reduced glutathione-to-oxidised glutathione (GSH/GSSG) ratio; and the total antioxidant capacity (T-AOC); and elevated protein levels related to milk protein synthesis in NEFA-treated BMECs. These findings indicate that betaine reduces NEFA-induced OS and enhances milk protein synthesis, suggesting its potential as a nutritional intervention for enhancing milk protein content in dairy cows with metabolic disorders.
Streptococcus pneumoniae remains a leading cause of community-acquired pneumonia. Severe pulmonary inflammation and subsequent tissue damage are driven significantly by the overexpression of both the Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Mitogen-Activated Protein Kinase (MAPK) signaling pathways. To investigate the immunomodulatory effects of rhein in a mouse model of Streptococcus pneumoniae-induced pneumonia. Forty male C57BL/6 mice were randomly assigned to four experimental groups: healthy control, S. pneumoniae infected control, and two rhein-treatment groups (10 mg/kg and 30 mg/kg). Expression levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-10, transforming growth factor (TGF)-β, monocyte chemoattractant protein-1 (MCP-1), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in lung tissues and bronchoalveolar lavage fluid (BALF) were quantified using reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Additionally, ELISA and Western blotting were employed to assess the phosphorylation profiles of MAPK and NF-κB. Rhein significantly decreased the lung wet/dry weight ratio, reduced bacterial load, and downregulated COX-2 and iNOS expression. Cytokine analysis revealed marked reductions in pro-inflammatory mediators (IL-6, IL-1β, TNF-α, and MCP-1) alongside elevated levels of the anti-inflammatory cytokine IL-10 in both lung tissues and BALF. Furthermore, ELISA and Western blotting confirmed that rhein significantly inhibited the phosphorylation of MAPK and NF-κB. Rhein attenuates S. pneumoniae-induced pulmonary inflammation and injury by modulating the MAPK/NF-κB signaling pathways. These findings highlight Rhein as a promising potential therapeutic agent for pneumococcal pneumonia and related inflammatory lung diseases.