Search Results (193)

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant pathogen in both healthcare-associated (HA-MRSA) and community-associated (CA-MRSA) infections, posing major challenges due to its evolving antimicrobial resistance (AMR) and genetic diversity. This study investigates the prevalence, antimicrobial resistance patterns, and molecular characteristics of HA-MRSA and CA-MRSA isolates in Saudi Arabia. A retrospective analysis was conducted on 178 MRSA isolates obtained from clinical samples. MRSA identification was performed using cefoxitin disk diffusion, and antimicrobial susceptibility testing for vancomycin, linezolid, and ciprofloxacin was conducted using the BD Phoenix M50 system. Molecular characterization included SCCmec typing, spa typing, and PCR-based detection of virulence genes (pvl, tst, eta, etb, lukS, lukF). Statistical analysis was carried out using SPSS, with a significance threshold of p < 0.05. Among 1496 S. aureus isolates, 178 (11.9%) were confirmed as MRSA, with HA-MRSA (61.8%) being more prevalent than CA-MRSA (38.2%). Notably, 7.8% of HA-MRSA isolates exhibited heteroresistant vancomycin-intermediate S. aureus (hVISA). Ciprofloxacin resistance was significantly higher in HA-MRSA (85.0%) compared to CA-MRSA (38.9%). SCCmec type V was the predominant genotype (87.1%), suggesting increased infiltration of CA-MRSA strains into hospital settings. Spa typing revealed high genetic diversity, with t037 being the most common (27%). Virulence genes were detected in 6% of isolates, indicating limited dissemination of these factors. The findings highlight the increasing prevalence of MRSA, the emergence of hVISA, and shifts in clonal distribution, underscoring the need for ongoing molecular surveillance and stringent antimicrobial stewardship programs to control MRSA spread in both healthcare and community environments. Full article

This article aims to examine the transformations of the concept of pulchrum that took place in the thirteenth century between Thomism and early Franciscan thought. Specifically, it explores and compares the theme of “pulchra enim dicuntur quae visa placent”, introduced by Thomas Aquinas in the Summa Theologiae, and the theme of “creatural” beauty, introduced by Francis of Assisi and then taken up above all by Bonaventure of Bagnoregio, identifying these as pivotal moments of transition in the medieval discourse on the pulchrum. Full article

Background: Treatment of chronic painful insertional Achilles tendinopathy is known to be challenging. If non-surgical treatment does not give sufficient relief of symptoms, surgery may be indicated. Treatment with ultrasound (US)- and colour Doppler (CD)-guided wide-awake-local-anaesthetic-no-tourniquet (WALANT) surgery for insertional Achilles tendinopathy is a new approach with promising clinical results. This study aimed to evaluate clinical results of this new approach on patients suffering from insertional Achilles tendinopathy. Methods: Forty-eight consecutive patients with 53 symptomatic tendons (33 men with 34 tendons, mean age 49.3 ± 12.0 years; 14 women with 18 tendons, mean age 55.0 ± 7.4 years) and a duration of more than 12 months with painful insertional Achilles tendinopathy (including tendon, bursae, bone, and plantaris pathology) were included. US- and CD-guided WALANT surgery with removal of pathological bursae, bone, and tendons was used. Immediate weight-bearing loading was allowed, followed by a structured rehabilitation protocol for the first 12 weeks after surgery. VISA-A scores before and after surgery and a questionnaire that evaluated subjective satisfaction with the treatment and current activity level were used. Results: In total, 42/48 patients with 46/53 tendons participated in a 3-year follow-up (mean 34 ± 9 months) by an independent examiner; 39/42 patients with 43/46 tendons were satisfied (n = 37) with the treatment. The mean VISA-A score increased significantly from 41.9 ± 18.2 pre-operatively to 87.7 ± 18.2 post-operatively (p < 0.001). There were three surgical complications, two superficial wound infections, and one minor wound rupture. Conclusions: Patients who suffered from chronic painful insertional Achilles tendinopathy treated with US- and CD-guided WALANT surgery followed by immediate weight-bearing showed high patient subjective satisfaction rates and better functional scores at the 3-year follow-up with a low complication rate. This novel treatment approach warrants more study, including randomised trials comparing it against traditional surgical procedures according to Nunley and Keck and Kelly. Full article

Upon RNA virus infection, viral RNA is sensed by the RIG-I-like receptors (RLRs), which signal through the adaptor protein VISA/MAVS to induce an innate antiviral response. How the VISA-mediated innate antiviral response is regulated and whether it can be targeted for drug development against diseases caused by RNA virus infection needs to be further investigated. Here we report that physalin F, a natural secosteroid isolated from Physalis angulata L., inhibits innate immune response to RNA virus. Mechanistically, physalin F binds to and promotes the activation of the mitochondrial m-AAA protease AFG3L2, which subsequently mediates the degradation of VISA. Knockdown of AFG3L2 promotes RLR-mediated innate antiviral signaling, whereas physalin F inhibits innate immune response to RNA virus both in cells and mice. Our study discovers physalin F as an inhibitor of VISA-mediated innate antiviral response as well as a candidate compound for the treatment of related diseases. More importantly, our findings suggest that AFG3L2 constitutively mediates degradation of VISA under physiological conditions, which represents a novel negative regulatory mechanism of RLR-mediated innate antiviral response. Full article

Muscle weakness is a key contributor to functional limitation in individuals with hip (HOA) or knee osteoarthritis (KOA). Identifying accessible and objective tools to estimate muscle strength could improve clinical assessment and rehabilitation monitoring. This exploratory cross-sectional study investigated the relationship between parameters derived from the instrumented Timed Up and Go test (iTUG), and isokinetic quadriceps and hamstring strength in individuals with KOA or HOA. Thirty-six participants with KOA and 21 with HOA were assessed. Quadriceps and hamstring peak torques were measured at 60°/s using an isokinetic dynamometer. The iTUG was performed with a sacrum-mounted inertial measurement unit. Correlations between iTUG parameters and lower-limb muscle strength were weak-to-moderate in KOA (r = −0.398 to −0.516, p < 0.05) and moderate-to-strong in HOA (r= −0.537 to −0.843, p < 0.05). Total iTUG duration strongly correlated with the traditional stopwatch TUG (r = 0.91, p < 0.01), suggesting that the classic stopwatch-based TUG may offer comparable clinical insights to certain iTUG-derived temporal metrics. The iTUG test reflects lower-limb muscle weakness, especially in HOA, with vertical push-off power and temporal metrics showing the strongest relationships. These results support the use of iTUG as an accessible tool for estimating muscle weakness when isokinetic testing is unavailable. However, these findings should be interpreted with caution given the small sample size. Full article

Background/Objectives: Inborn errors of metabolism (IEM) are chronic, life-threatening genetic disorders with a significant cumulative prevalence worldwide. Advances in early diagnosis and treatment have significantly increased life expectancy, underscoring the need for specialised adult care units and the establishment of structured transition programmes from paediatric to adult services. We hereby present a functional transition model for IEM patients and share our implementation experience. Methods: Initiated in 2012, the partnership between the paediatric Hospital Sant Joan de Déu (HSJD) and the adult-care centre at Hospital Clinic of Barcelona (HCB) culminated in 2019 with the transference of the first IEM patients under the structured A10! Programme. This model is structured around the transition units of paediatric and adult centres to guarantee communication and functional management. Regular monthly meetings at each centre and joint quarterly sessions allowed for protocol harmonisation and personalised care planning. Coordinated engagement of the multidisciplinary health care teams with patients and families smoothed the transfer process. Results: Between 2019 and 2024, 94 IEM patients were successfully transferred. Diagnoses included intermediary metabolism defects (71.23%), lipid metabolism and transport disorders (4.25%), heterocyclic compound metabolism (2.12%), complex molecules and organelle dysfunction (6.37%), cofactor and mineral metabolism (2.12%), signalling defects (5.31%), and unclassified cases (8.51% of rare disorders, maybe non-IEM). Transition formats included 21 in-person joint visits in HSJD, 37 remote transitions during the COVID-19 pandemic, and 36 streamlined transfers via standardised protocols. Sessions, trainings, and meetings allowed the exchange of patients’ needs and protocols. Conclusions: The successful transference of IEM patients requires structured programmes with interdisciplinary paediatric and adult teams, joining efforts with the patient, families, and caregivers. Communication between paediatric and adult transition units is essential to promote continuity of care and patient empowerment. While constantly updated, this model has proven effective, gaining positive evaluations from healthcare professionals and patients alike, representing a scalable framework for lifelong management of IEM in adult care settings. Full article

Contamination of natural water sources with zinc ions poses serious ecological and health risks due to its toxicity and persistence. In this context, this study presents the preparation of new adsorbents based on acrylonitrile-divinylbenzene networks functionalized with aminophosphonate groups, selected for their strong chelating affinity towards Zn(II) ions. Both unmodified and functionalized materials were evaluated in adsorption experiments towards zinc ions. The adsorption capacity was evaluated as a function of the contact time and the initial zinc concentration. The functionalized adsorbents exhibited a significantly higher adsorption of zinc, attributed to the presence of aminophosphonate groups. In case of functionalisation with ethyl phosphonate group is achieved a maximum adsorption capacity of 101 mg/g. The equilibrium data followed the Langmuir isotherm, indicating monolayer adsorption, while the kinetic analysis followed the pseudo-second-order model, consistent with chemisorption. The optimal contact time was 60 min. Functionalized polymeric supports show strong potential for zinc ion removal, supporting their use in environmental remediation. Overall, the results demonstrate that aminophosphonate-functionalized polymers are highly effective adsorbents for the removal of zinc ions from contaminated waters. Full article

Large vision–language models (VLMs) can describe images fluently, yet their anomaly decisions often rely on opaque heuristics and manual thresholds. We present ThinkAnomaly, a rationale-first vision–language framework for industrial anomaly detection. The model generates a concise structured rationale and then issues a calibrated yes/no decision, eliminating per-class thresholds. To supervise reasoning, we construct chain-of-thought annotations for MVTec-AD and VisA via synthesis, automatic filtering, and human validation. We fine-tune Llama-3.2-Vision with a two-stage objective and a rationale–label consistency loss, yielding state-of-the-art classification accuracy while maintaining a competitive detection AUC: MVTec-AD—93.9% accuracy and 93.8 Image-AUC; VisA—90.3% accuracy and 85.0 Image-AUC. This improves classification accuracy over AnomalyGPT by +7.8 (MVTec-AD) and +12.9 (VisA) percentage points. The explicit reasoning and calibrated decisions make ThinkAnomaly transparent and deployment-ready for industrial inspection. Full article

Phenylketonuria (PKU) is a rare inherited metabolic disorder caused by phenylalanine hydroxylase deficiency, leading to phenylalanine (Phe) accumulation and neurological dysfunction if untreated. While metabolomics holds promise for biomarker discovery in PKU, few studies have examined urinary metabolites using untargeted approaches. This study applied untargeted metabolomics using HPLC-QTOF-MS to analyze urine from 36 adult patients with PKU and 34 healthy controls. Biomarker Analysis was performed with MetaboAnalyst 6.0. A total of 73 significant metabolites (FDR < 0.05; VIP > 1) were identified, with 29 upregulated and 44 downregulated in PKU. A 23% of these metabolites were related to Phe metabolism, while 77% were associated with alterations across more than 10 metabolic pathways, including leucine and tryptophan metabolism, acylcarnitines, vitamins, and diet- or microbiota-derived compounds, among others. Specifically, upregulated metabolites with an AUC > 0.9 included several Phe-derived compounds, the nucleoside 8-hydroxy-7-methylguanine, and indole compounds (1H-indole-3-carboxaldehyde). Conversely, downregulated metabolites with an AUC > 0.9 included N-acetyl(iso)leucine and a heptenoylcarnitine isomer. The Random Forest-based model demonstrated enhanced predictive performance when integrating 10 metabolites, supporting their potential utility as biomarkers for PKU. These findings improve the biological understanding of metabolic disturbances beyond Phe, and may support the development of new therapeutic and dietary strategies. Full article

Industrial visual inspection demands high-precision anomaly detection amid scarce annotations and unseen defects. This paper introduces a zero-shot framework leveraging multimodal feature fusion and stabilized attention pooling. CLIP’s global semantic embeddings are hierarchically aligned with DINOv2’s multi-scale structural features via a Dual-Modality Attention (DMA) mechanism, enabling effective cross-modal knowledge transfer for capturing macro- and micro-anomalies. A Stabilized Attention-based Pooling (SAP) module adaptively aggregates discriminative representations using self-generated anomaly heatmaps, enhancing localization accuracy and mitigating feature dilution. Trained solely in auxiliary datasets with multi-task segmentation and contrastive losses, the approach requires no target-domain samples. Extensive evaluation across seven benchmarks (MVTec AD, VisA, BTAD, MPDD, KSDD, DAGM, DTD-Synthetic) demonstrates state-of-the-art performance, achieving 93.4% image-level AUROC, 94.3% AP, 96.9% pixel-level AUROC, and 92.4% AUPRO on average. Ablation studies confirm the efficacy of DMA and SAP, while qualitative results highlight superior boundary precision and noise suppression. The framework offers a scalable, annotation-efficient solution for real-world industrial anomaly detection. Full article

Background/Objectives: Silodosin (SLD) is a selective α1A-adrenoceptor antagonist used in the treatment of benign prostatic hyperplasia. Bioequivalence failures have been reported for hard capsule formulations, largely due to the effect of disintegrant excipients, making soft capsules a promising alternative dosage form. This study investigated the stability of SLD soft capsules stored in two different packaging materials, PVC/PVDC and AquaBa^®. Methods: Storage temperatures at 25 °C/60%, 30 °C/65% RH, 30 °C/75% RH, and 40 °C/75% RH, and sampling were performed according to the International Council for Harmonisation (ICH) stability conditions. Assays were performed by HPLC and UV, and mass detection. Results: Degradation analysis revealed that temperature played a critical role in SLD degradation and the formation of its primary degradation products, dehydrosilodosin and impurity 1. Conclusions: AquaBa^® demonstrated superior protective properties compared to PVC/PVDC, preserving SLD content above 95% for over 12 months under 25 °C and 30 °C conditions while limiting the formation of degradation products. Nevertheless, impurity 1 exceeded its ICH Q3B (R2) specification limit (0.3%) after six months under all conditions tested, suggesting a critical interaction between SLD and excipients such as Capryol^® 90. Kinetic modeling confirmed first-order degradation kinetics for both dehydrosilodosin and impurity 1, with a faster degradation rate observed in PVC/PVDC blisters. These findings highlight the critical role of packaging in pharmaceutical stability. While AquaBa^® emerges as the preferred option for SLD soft capsules, formulation optimization remains necessary to limit impurity formation, extend shelf life, and ensure regulatory compliance. Full article

In advanced economies characterized by sustained immigration, rising inequality, and chronically underdeveloped social housing sectors, demand-side welfare interventions risk being capitalized into higher rents rather than improving housing affordability. This study investigates how Spain’s welfare state transformation—particularly the rollout of IPREM-indexed policies such as the Minimum Living Income (IMV) and the Youth Rental Voucher—interacted with migration flows and tourism-driven housing competition to reshape private rental markets between 2008 and 2025. Using harmonized national data from OPI, Idealista, INE, and the Bank of Spain (2010–2024), we apply a descriptive time-series approach that combines structural break tests (Chow and Bai–Perron), pre/post-2021 correlation comparisons, regional heterogeneity analysis, and robustness checks (including Spearman correlations and jackknife sensitivity analyses). We identify a pronounced structural break in 2021: while consular visa issuances—a proxy for combined migration and tourism inflows—showed no significant association with advertised rental prices before 2021 (r ≈ 0.27, p = 0.41), a remarkably strong co-movement emerged thereafter (r ≈ 0.90–0.92). This shift aligns precisely with the nationwide implementation of IMV, institutionalization of the Youth Voucher, and disbursement of EU Recovery and Resilience Facility funds. The effect is most acute in regions with rigid housing supply and high exposure to tourist-use dwellings (VUT)—notably the Balearic Islands, Murcia, Cantabria, and Navarre—suggesting that increased effective demand may have been absorbed primarily through price increases rather than expanded access. While our observational design precludes causal inference and the findings should be interpreted as exploratory and hypothesis-generating, the convergence of timing, magnitude, and institutional context renders a policy-mediated demand channel plausible. The results caution that, without complementary supply-side measures—such as social housing investment, rehabilitation incentives, or VUT regulation—demand-side subsidies may inadvertently reinforce housing inequality and reduce fiscal efficiency, thereby undermining the sustainability goals they aim to advance. Full article

This study examines how Israel’s legal and institutional arrangements, including migration policies, health-insurance eligibility rules, and safety enforcement mechanisms, shape health risks for Thai migrant agricultural workers, and identifies policy levers to mitigate preventable harm. Using a legal policy analysis informed by syndemics and labor frameworks, we mapped laws, regulatory oversight, and enforcement chains, and synthesized evidence from worker surveys, affidavits, and civil society reports to link institutional structures with barriers experienced in workplaces and healthcare settings. The findings reveal that health inequalities stem from structural design rather than isolated failures, including exclusion from public insurance, dependence on employer-based plans, employer-tied visas, opaque injury-claim procedures, fragmented oversight, absence of occupational-health surveillance, limited language access, poor housing conditions, and weak inspections. These interlocking features reinforce one another, resulting in under-reporting, delayed medical attention, and cumulative physical and psychological harm. The study concludes that structural legal and administrative reforms—rather than individual adaptation—are required to address these inequities. Policy priorities include integrating migrant workers into public insurance or ensuring equivalent coverage, decoupling residency from single employers, guaranteeing multilingual access, establishing independent health monitoring, and enforcing safety, housing standards and other social determinants of health through transparent inspections, positive incentives and meaningful sanctions. Full article

Prescriptive building culture, as a form of determinism, shapes architects’ tectonic approaches by imposing prescriptive technical limits (PTLs) during the building process. Exploring PTLs provides a foundation for describing overarching tectonic approaches in practice that have not been systematically studied. This research provides a comprehensive overview of emerging PTLs among Turkish Cypriot architects in Northern Cyprus, examining their types, sources, emergence stages, root causes, and impact on tectonic design strategies. The study employed mixed-methods Sequential Explanatory Design (SED), combining survey and interview data. Findings reveal that architects mainly adopt conservative tectonic approaches in response to PTLs, reflecting limited innovative attitudes in technical and structural design, with rare tendencies towards more innovative strategies. Qualitative analysis maps structural engineers and legal frameworks as primary initiators, while PTLs mainly occur during preliminary design, construction documentation, and application visa stages. The key contributions are: (i) a transferable coding framework linking PTLs’ initiators, stages, and effects; (ii) empirical evidence of predominant affirmative tectonic approaches in a prescriptive, seismic context; (iii) identified innovative design attitudes; and (iv) a regionally grounded dataset informing comparative studies. The uncovered indicative patterns also provide an applicable model for examining PTLs and tectonic approaches worldwide across other prescriptive cultures and seismic regions. Full article

This work investigates the physicochemical characterization of two poly(styrene-co-divinylbenzene) copolymer supports, containing 6.7% and 15% divinylbenzene, functionalized with glycine. The resulting copolymers were characterized using Fourier transform infrared spectroscopy, thermogravimetric analysis, energy-dispersive X-ray spectroscopy, and scanning electron microscopy. The degree of amino acid functionalization was estimated by statistical modeling of the repeating structural units and through analysis of nitrogen content. Thermogravimetric analysis (TGA) was further employed to investigate the impact of grafted amino acid groups on the thermal stability and decomposition behavior of the copolymers. Full article