To evaluate completeness of operative note documentation in a vascular surgery service and to assess whether introduction of standardised procedure-specific templates was associated with improved documentation in a repeat audit cycle. We conducted a single-centre two-cycle closed-loop audit within a UK vascular surgery department. In Cycle 1, 63 consecutive operative notes from May 2024 were retrospectively reviewed against predefined documentation standards derived from Royal College of Surgeons guidance. Following identification of recurrent omissions, standardised procedure-specific templates were collaboratively developed, disseminated, and introduced at a departmental governance meeting. In Cycle 2, 72 consecutive operative notes from March 2025 were reviewed using the same data collection framework. The primary process measures were documentation rates for four safety-critical fields: indication for surgery, estimated blood loss, distal pulse status, and postoperative plan. Between-cycle differences were compared using Fisher's exact test and expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Baseline documentation was incomplete across all four variables. Following template introduction, statistically significant improvements were observed for indication for surgery (43.2% to 79.5%; OR 5.07, 95% CI 2.38-10.80; p < 0.0001) and distal pulse status (19.6% to 65.4%; OR 7.99, 95% CI 3.61-17.68; p < 0.0001). No statistically significant improvement was observed for estimated blood loss (16.3% to 19.2%; OR 1.28, 95% CI 0.52-3.12; p = 0.66) or postoperative plan (39.1% to 44.9%; OR 1.22, 95% CI 0.61-2.42; p = 0.60). Standardised procedure-specific templates were associated with substantial, statistically significant improvements in two documentation domains. The absence of equivalent improvement in blood loss and postoperative plan recording, confirmed by formal hypothesis testing, indicates that these variables require distinct intervention strategies beyond structured prompting alone. This closed-loop audit supports continued template refinement, targeted behavioural and systems-level interventions, and further re-audit.
Within a context of considerable cannabis market expansion and product diversification, cannabis consumers must manage their use across a range of potencies and modes of consumption. This study aimed to provide deeper understandings of how cannabis consumers would perceive the introduction of a standard THC (tetrahydrocannabinol) unit system. Qualitative study. United States, 2023-2024. Adult cannabis consumers (n = 50) across criminalized and legalized cannabis states. Within a study focused on the experiences of dosing cannabis among adults in contexts of evolving cannabis markets with product diversification, subjects were provided with a description of a standard THC unit and with the analog of a standard drink. They were then asked about their perceptions of a standard THC unit. Interviewers probed for personal attitudes, practical utility and potential for reducing harm. Broadly, cannabis consumers were enthusiastic about the introduction of a standard THC unit system, although a minority expressed some skepticism about how it would be implemented. Standard THC units were viewed as most beneficial for novices and infrequent consumers, although some experienced consumers indicated it would be valuable for tolerance management and avoiding dependence. It was also seen as valuable for avoiding risks related to driving under the influence and overconsumption. Standard metrics for cannabis consumption may be received with enthusiasm from cannabis consumers. Experienced consumers indicated they would have benefited from a standard THC (tetrahydrocannabinol) unit when initiating cannabis use and highly recommended it for novices. It was also viewed as an opportunity to manage risks. Successful implementation would require managing misunderstandings about the concept of a standard THC unit as well as how regular, experienced consumers would incorporate such a metric into established consumption routines.
Aims To explore teachers' perspectives on incorporating oral health education within schools, since its statutory introduction in the National Curriculum in England in 2020.Methods An online survey including open and closed questions was designed and distributed via postal invitations to selected schools in North West England, and via social media between September 2024 and January 2025. Quantitative data were analysed descriptively, while directed content analysis was used for free-text responses.Results Fifty-four responses were received. Oral health education was reported as inconsistent with different methods and frequencies of delivery reported; 21% (n = 11) teachers taught the topic less than once a year. Challenges included lack of curriculum time (44%, n = 23), and resources to help deliver (27%, n = 14) or plan the teaching (19%, n = 10). Most teachers (93%, n = 50) expressed confidence in their oral health knowledge, but free-text responses highlighted that teachers valued dental professionals' involvement with schools, and parental engagement to reinforce oral health at home.Conclusions Oral health education in schools remains inconsistent despite statutory requirements. Sustainable resources and multi-agency partnerships can help embed oral health promotion within a whole-school framework.
The UNICORN (undermining iatrogenic coronary obstruction with radiofrequency needle) technique was developed in 2022 to reduce the risk for coronary obstruction during valve-in-valve transcatheter aortic valve replacement. The procedure involves traversing the target leaflet with an electrified wire, followed by serial dilation with coronary and peripheral balloons. A balloon-expandable valve is then delivered into the de novo fenestration for intraleaflet deployment. As the balloon-expandable valve expands, the target leaflet is opened and displaced away from the at-risk coronary ostium, resulting in a minimal neoskirt on the target side. Since its introduction, the technique has been adopted at numerous centers worldwide, with various modifications and adaptations. In this paper, a step-by-step description of the UNICORN procedure is provided, and troubleshooting strategies for potential challenges are discussed.
Enhancing energy recovery from organic waste using microbial fuel cells (MFCs) remains constrained by inefficient extracellular electron transfer (EET) and unstable interfacial electron flux. Here, a multiscale engineered bioanode is developed by integrating a bimetallic Ni/Co metal-organic framework (MOF) with a conductive polyaniline (PANI) network on carbon felt to improve bioelectrochemical performance. The hierarchical structure provides abundant redox-active sites, continuous conductive pathways, and a favorable microenvironment for microbial colonization, thereby promoting efficient coupling between microbial metabolism and electrode electron acceptance. The optimized system achieves a high power density of 2265 mW m-2 (318 % higher than pristine carbon felt) and a coulombic efficiency of ∼ 81 %, demonstrating enhanced substrate-to-electricity conversion. Importantly, the introduction of pseudocapacitive charge buffering mitigates the mismatch between microbial electron generation and electrode electron acceptance, resulting in stabilized electron flux under dynamic conditions. Microbial community analysis reveals enrichment of electroactive bacteria and suppression of methanogenic pathways, indicating effective regulation of microbial metabolism toward electricity generation. This study highlights a coupled bio-abiotic interfacial engineering strategy for improving both efficiency and stability in MFC systems, providing new insights into sustainable wastewater-to-energy conversion.
Phloretin has garnered significant interest due to its substantial value in the pharmaceutical, cosmetic, and food industries. However, its supply via plant extraction remains constrained by low yield and complex processing. In this study, an engineered Saccharomyces cerevisiae strain was constructed for high-level de novo phloretin biosynthesis via multi-module carbon-flux rewiring. In the downstream phloretin-forming module, an integrated three-route network was constructed, consisting of two direct phloretin-forming routes and a phloretic acid recycling route. Specifically, introduction of naringenin chalcone reductase re-channeled flux at the chalcone node, while enzyme screening and copy-number optimization of 4-coumarate:coenzyme A ligase and chalcone synthase reduced phloretic acid accumulation, effectively recovering carbon otherwise lost to byproduct formation. In the aromatic amino-acid supply module, key pathway steps were reinforced and feedback regulation was relieved, with careful balancing of key pathway genes to prevent metabolic imbalance. In the malonyl-coenzyme A supply module, cytosolic acetyl-coenzyme A generation was enhanced and organelle-to-cytosol carbon partitioning was rewired, thereby expanding the cytosolic malonyl-coenzyme A pool required for chalcone synthase-mediated condensation. The resulting engineered strain achieved phloretin titers of 460.6 mg/L in shake-flask cultures and 1.817 g/L in 5-L fed-batch fermentation, representing the highest reported de novo titer in yeast to date. This study demonstrates that coordinated control of branch-point flux, byproduct recycling, and precursor supply is essential for high-level microbial phloretin production and provides a scalable framework for microbial production of phloretin and related derivatives.
Controlled cell death (CCD) is becoming a focus as a successful practice in cancer therapy, especially when triggered specifically by light-based therapies, including photodynamic therapy (PDT) and photoactivated chemotherapy (PACT). Photosensitizers (PSs) made of metal are of particular interest in this respect since the excited-state behaviour of these complexes can be rationally designed, depending on the rational design of the metal centre, ligand and oxidation state. Despite extensive literature on CCD induced by PDT, little work has given a cohesive view on metal-based PSs as inducers of particular CCD pathways. This review will highlight the decade progress in Iridium metal-based PSs that induce ferroptosis, immunogenic cell death, and pyroptosis with focus on its characteristics, mechanisms and commonalities among Iridium systems. Moreover, methods of improving biological selectivity, especially by bioconjugation of Iridium polypyridyl complexes are described. On the whole, this review is intended to gain an understanding of the logical construction of metal-based PSs to induce RCD in a controlled fashion and to stimulate the future introduction of photoactivating metal complexes to treat cancer.
Target vessel (TV) catheterization during fenestrated-branched endovascular aortic aneurysm repair (FBEVAR) relies primarily on fluoroscopy. Fiber optic real-time shape (FORS) technology (Philips Medical Systems, Best, Netherlands) uses light refracted through optical fibers to generate real-time renderings of wires and catheters in three-dimensional (3D) space allowing their navigation without radiation. The LumiGuide is an enhanced longer version of the standard guidewire that is coupled with a 3D Hub connector to enhance visualization of commercially available catheters. This study aims to compare the outcomes and radiation exposure using the standard FORS enabled guidewire vs. the LumiGuide for FBEVAR. Data collected from 218 FBEVARs (129 standard FORS, 89 LumiGuide) included 931 TV catheterizatons (590 with standard FORS and 341 with LumiGuide). Technical success was defined as the successful catheterization of the TVs using only FORS. FORS and LumiGuide were compared in terms of technical success rates, procedure times, catheterization duration, fluoroscopy times, and cumulative dose-area products (DAP). Welch's t-test was used for continuous variables, while a z-test was applied for proportions. Patient characteristics did not demonstrate significant differences between groups. FORS technical success was 56.2% with standard FORS vs. 79.4% with LumiGuide (P<.001). Compared to standard FORS, the use of LumiGuide resulted in non-significant reduced navigation time per TV (6.4±7.4 vs 6.7 min±9.6; P=.6), DAP per TV (3.2±5.3 Gy·cm2 vs 3.36±9.3 Gy·cm2, P=.79), and significant reduction in procedure time (257 ± 91 minutes vs 298 ± 100 minutes; P = .002), fluoroscopy time (58±38 min vs 80±40; P=.01) and contrast dose (130±40 vs 150±50 mL; P=.05). Cumulative DAP remained similar between groups (59±38 Gy·cm2 for LumiGuide vs. 64±43 with standard FORS; P=.5). The introduction of LumiGuide and the 3D-Hub for FBEVAR improved FORS technical success and reduced procedure times compared to earlier FORS procedures. The ability to use different commercially available catheters with LumiGuide results in enhanced convenience and lower radiation exposure, thereby improving efficiency and safety.
Helicopter emergency medical services (HEMS) provide rapid evacuation of critically ill and injured patients, overcoming the limitations of ground transport in regions with challenging terrain, poor infrastructure, or traffic congestion. In Nepal, mountainous landscapes and dispersed populations make HEMS a vital component of the health care system since its formal introduction in 2013. This study aimed to review the current state of HEMS in Nepal, highlighting operational benefits, key challenges, and potential strategies to enhance service efficiency, safety, and accessibility. A narrative review was conducted using national and international literature, operational reports, and available data on HEMS in Nepal. Challenges were analyzed across financial, infrastructural, logistical, and human resource domains. HEMS significantly reduces evacuation times and facilitates access to multidisciplinary medical teams, improving outcomes in time-critical conditions such as trauma, stroke, myocardial infarction, and obstetric emergencies. However, service delivery is constrained by high operational costs, reliance on private commercial helicopters, limited trained personnel and pilots, centralized communication systems, pilot fatigue, and hazards from mountainous terrain and unpredictable weather. These barriers particularly affect patient access in remote regions. Although HEMS has markedly enhanced prehospital care in Nepal, systemic limitations hinder its full potential. Strategic investment in dedicated medical helicopters, decentralized operational bases, workforce development, and supportive policy frameworks is essential to improve timely access, reduce preventable mortality, and strengthen Nepal's emergency medical system.
IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory condition that can cause irreversible organ dysfunction and life-threatening complications. Although glucocorticoids are the standard first-line therapy, frequent flares necessitate prolonged use, which is in turn associated with toxicity. Inebilizumab, a CD19-targeted antibody approved in Japan in November 2025, demonstrated efficacy in the phase 3 MITIGATE trial. However, the trial's eligibility criteria and controlled environment may not reflect the heterogeneity of the routine clinical setting or the long-term profile in the Japanese population. This study (4SigHT Study) aims to evaluate the long-term effectiveness and safety of inebilizumab in Japan. This multicenter, prospective, observational study plans to enroll 100 patients with definite or probable IgG4-RD who are initiating inebilizumab at up to 40 sites in Japan. The study runs from March 1, 2026 to March 31, 2032. It includes up to 14 scheduled visits over a maximum duration of 312 weeks and reflects real-world decisions without mandated interventions. Comprehensive baseline assessments capture disease characteristics, comorbidities, vaccination history, and clinical history, including the frequency and nature of flares over the preceding 52 weeks. Longitudinal data are collected via an electronic data capture system. To ensure data robustness, the study employs a rigorous adjudication process. Suspected flares treated by investigators are adjudicated by an independent data and safety monitoring board using standardized organ-specific flare criteria. The primary outcome is the proportion of participants with an adjudicated clinical flare through week 52. Secondary outcomes include treatment-free complete remission, glucocorticoid-free complete remission, time to clinical flare, annual clinical flare rate, proportion of patients who initiate additional treatment, time to treatment initiation for new or worsening symptoms, and cumulative glucocorticoid dose. Furthermore, the study evaluates the long-term safety of inebilizumab over 6 years. The study is registered with the Japan Registry of Clinical Trials (jRCT1031250749).
Neuropathic pain is considered the most difficult to manage, with many patients getting inadequate relief from the current pharmacotherapy. While many drugs have been added to the regimen, Lacosamide has emerged as a promising therapeutic option. This systematic review focuses on the efficacy and safety of lacosamide in adult patients with neuropathic pain. Databases such as PubMed, Embase, Scopus, Web of Science, and Cochrane were searched thoroughly for Randomized Controlled Trials (RCTs) published in English through November 2025. The Cochrane Risk of Bias 2 tool was used to assess the risk of bias in the included studies. Eight RCTs involving 976 participants with different neuropathic pain conditions met the inclusion criteria. Across the included studies, Lacosamide (200-600 mg/day) provided a modest reduction in their pain scores. However, it didn't have much of a positive impact on quality of life, limited function, adverse effects were common, and a high dropout rate was observed in several trials. Lacosamide might provide a modest analgesic benefit across multiple neuropathic conditions. But its extensive, long-term use requires more research to confirm its benefits, particularly the optimum dosing protocols.
Telephone-based application of questionnaires may be valuable and cost-effective approaches for remote evaluation of patients. The aim of this study was to examine the concurrent validity of the telephone-based application of the Craig Hospital Inventory of Environmental Factors (CHIEF) in comparison with in-person application, and its measurement properties, in people with rheumatoid arthritis. A methodological study was conducted. Participants were requested to answer the questionnaire on four randomized occasions: three times by telephone, and once in-person. Concurrent validity, test-retest, and inter-rater reliability of the telephone-based application of the CHIEF were reported. Sixty participants (52 women) chronically diagnosed with rheumatoid arthritis were included. There were no significant differences between the mean scores obtained by telephone- and in-person applications of the CHIEF (MD 3; 95% CI -4 to 9; p=0.38). Overall, a high agreement was found (ICC=0.83; 95% CI 0.72 to 0.90). A very high test-retest agreement (ICC=0.99; 95% CI 0.98 to 0.99) and a high inter-rater agreement (ICC=0.88; 95% CI 0.78 to 0.93) of the total scores obtained by telephone applications was found. In people with rheumatoid arthritis, the results suggested that there is no difference when the CHIEF is applied by telephone or during in-person interviews. This could help encourage new studies examining the influence of environmental factors on social participation in people with rheumatoid arthritis. In conclusion, the telephone-based application of the CHIEF showed to be a valid and reliable method for the assessment of barriers to participation in people with rheumatoid arthritis.
Direct oral anticoagulant (DOAC) resumption guidelines after traumatic subdural hemorrhage (tSDH) remain unclear, given the competing risks of worsening hemorrhage and thromboembolic events. This study characterizes real-world DOAC prescription patterns after tSDH in patients with atrial fibrillation (AF) and evaluates outcomes comparing early and late prescription renewal. Using the TriNetX federated research database, we identified adult patients with incident tSDH, a preceding AF diagnosis, and a DOAC prescription within 3 months before injury (2014-2025). Renewal rates and all-cause mortality were tracked at 1, 2, 4, 8, and 12 weeks post-injury. Patients were stratified into early (≤4 weeks) and late (>4 weeks) renewal cohorts and compared following propensity score matching for 1-year rates of cerebral infarction, nontraumatic intracerebral hemorrhage (ICH), gastrointestinal (GI) bleeding, and all-cause mortality RESULTS: Among 4328 patients (mean age 78.2 years; 61% male), apixaban was the most prescribed pre-injury DOAC (76.7%). Renewal reached 17% at 1 week and 40% by 12 weeks; cumulative mortality was 18% by 12 weeks. After propensity score matching (750 patients per cohort), early renewal was not associated with significantly different rates of cerebral infarction, nontraumatic ICH, or GI bleeding. However, all-cause mortality was significantly higher in the early-renewal cohort (HR [95% CI]: 3.06 [2.33-4.01]) CONCLUSIONS: Early DOAC prescription renewal was associated with markedly higher all-cause mortality without a significant reduction in thromboembolic events. These findings may reflect residual confounding by AF severity, but underscore the need for prospective, injury-specific research to guide anticoagulation decision-making after tSDH.
Endothelial activation and stress index (EASIX) is a biomarker of endothelial dysfunction and has been validated previously as a prognostic score for mortality in various diseases, including oncologic diseases, sepsis, and cardiac disease. Since endothelial dysfunction is an established mediator of adverse outcomes in acute ischemic stroke, this study investigates the prognostic value of EASIX for risk of mortality in these patients. We analyzed data from the Heidelberg (n = 4,188) and Vienna (n = 2,273) prospective acute ischemic stroke registries. EASIX was calculated as creatinine [mg/dL] × LDH [U/L] / platelet count [109/L]. An EASIX cut-off was established using maximal Youden index. Validation was performed using Brier score and C-statistics. Higher EASIX was associated with higher risk of mortality in the training cohort in a multivariable Cox regression (HR of all-cause mortality per log2 increase: 1.20 (95% CI 1.12-1.28), p < 0.001). An optimal EASIX cut-off value of 1.211 was identified in the derivation cohort. In the independent validation cohort, this cut-off was associated with risk of 3-month mortality in a multivariable binary logistic regression model (OR 1.86 (1.28-2.70), p < 0.01). Brier score and C-statistics validated the superior predictive performance of EASIX in the multivariable model. EASIX predicts mortality in acute ischemic stroke patients and retained prognostic validity across two heterogeneous European cohorts. Incorporation of EASIX improved risk stratification beyond established clinical scores. EASIX may serve as a useful tool for risk stratification and outcome prediction in acute ischemic stroke patients.
Traditional dental composite resins faced persistent challenges regarding biofilm accumulation and hydrolytic degradation. This study aimed to develop a novel resin monomer fluorinated polyurethane dimethacrylate (FPUDMA) and surface-modified polyether ether ketone (PEEK) fillers to enhance the comprehensive performance of composite resins. FPUDMA was synthesized via solution polymerization, while PEEK was hydroxylated and grafted with KH570 to introduce C=C bonds. Experimental composite resins were formulated with varying concentrations of PEEK-C=C at 0%, 2.5%, 5%, and 7.5% by weight. Key properties evaluated included degree of conversion, depth of curing, water sorption/solubility, mechanical properties (before/after aging), polishability, initial bacterial adhesion, and cytocompatibility. FPUDMA and PEEK-C=C were confirmed by FTIR, NMR, and XPS. Increasing PEEK-C=C content reduced the degree of conversion and curing depth, but all values met ISO standards. There was no significant difference in water absorption/solubility among the groups. As the increase of PEEK-C=C content, the flexural strength, elastic modulus, and surface hardness significantly increased, but decreased at 7.5% group, whether before or after aging (P<0.05). All groups exhibited favorable polishing performance and cytocompatibility (cell viability >90%). The FPUDMA monomer could still maintain anti-bacterial adhesion properties when incorporated into the resin. The novel composite resin with FPUDMA and 5 wt% PEEK-C=C fillers demonstrated optimized mechanical properties, acceptable polymerization characteristics, resistance to bacterial adhesion, and favorable biocompatibility. These improvements are expected to mitigate degradation at the tooth-restoration interface, thereby reducing the risk of secondary caries and restoration fracture. Consequently, the novel resin represents a clinically viable option for durable dental restorations.
Emerging infectious diseases (EIDs) cause significant health and economic burdens in the USA and globally. Existing methods and analyses fall short of what is required to prioritise diseases for health technology research and development (R&D), including for medical countermeasure (MCM) development within rapid response frameworks by the Center for Biomedical Advanced Research and Development Authority, part of the Administration for Strategic Preparedness and Response within the U.S. Department of Health and Human Services. We developed a method for quantifying and ranking health and economic disease burdens ('full burdens') and applied it to 15 high-priority EIDs for 223 countries and territories, including the USA and US territories, historically from 2000 to 2022 and prospectively from 2025 to 2034. Health burdens consisted of disability-adjusted life-year losses, converted into monetary values using the value of a statistical life-year. Economic burdens consisted of direct and indirect costs during the acute stage of illness for hospitalised cases. We computed unweighted and weighted burden measures, the latter controlling for global disparities in ability-to-pay to avoid EID burdens. We projected future disease burdens using Monte Carlo simulation. Pandemics caused the largest historical and projected unweighted and weighted full burdens in the USA and globally. Among non-pandemics, across unweighted and weighted burdens, dengue and cholera imposed the largest historical and projected full burdens globally; West Nile Virus imposed the largest historical and projected full burdens in the USA, and dengue imposed the largest historical full burdens in the US territories. Weighted full burdens exceeded five times the unweighted ones. Regionally, the Americas and Africa faced the largest per capita weighted burdens while the Western Pacific region faced the smallest. R&D priority-setting, including MCM development, depends on multiple criteria, including disease burdens. Our full burden quantification methods and results, along with other such criteria, can inform optimal priority-setting.
Although technology has been widely implemented in Parkinson's disease (PD) research, little is known about its efficacy on participants' psychosocial domains. This study assessed the potential effect and usability of the Voice-Activated Intelligent Personal Assistant (VIPA) on participants' sense of coherence and psychosocial well-being. This single-blinded, 2-arm pilot randomised controlled trial, with 7 post-intervention interviews, recruited 48 participants. Intervention group participants received a user protocol for their 8-week VIPA usage, while the control group received usual care. Primary outcome was the Sense of Coherence 13-item scale (SOC-13). Other outcomes were Mental Health Continuum-Short Form (MHC-SF), UCLA Three-Item Loneliness Scale, Parkinson's Disease Questionnaire-8, Brief Resilient Coping Scale, and System Usability Scale. Generalized Estimating Equation (GEE) was selected as the primary analysis, with multiple imputation performed as sensitivity analysis. A significant reduction of positive emotion in IG was identified for the MHC-SF emotional well-being at post-intervention (β = -1.69, p = 0.028) but not at week 12 follow-up (β = -0.96, p = 0.31). Exploratory effect sizes were identified for SOC-13 meaningfulness (d = 0.27), manageability (d = 0.19), and MHC-SF psychological well-being (d = 0.27). Interviewee reportedly internalised their failed interaction attempts into speech characteristics, and it resembled being ignored by a real person. The study identified preliminary trends of improvements in participants' meaningfulness domain and psychological well-being. The decrease in emotional well-being could be attributed to the reported technical difficulties and VIPA's fair usability. A future VIPA redesign is required to avoid similar adverse effects.
This article analyzes the prolonged trough phase in the epidemic curve associated with COVID-19 dynamics in Chile during the period July-December 2020, characterized by a relatively stable daily record of 1 000-2500 cases. Unlike traditional (, )-SIR models, with constant parameters and associated respectively with the transmission and removal rates in the infectious process, which predict unimodal behavior, we propose an approach based on Contagion Mechanics that incorporates a dynamic law for the transmission rate . Using official data from the Department of Health Statistics and Information, we demonstrate how this approach quantitatively captures the observed stabilization, resulting from sustained adherence to non-pharmaceutical measures by the Chilean population. The model reveals that maintaining the infection rate below its intrinsic value required sustained collective effort, enabling controlled management of hospital demand during the pre-vaccination stage. Our results validate the usefulness of Contagion Mechanics in explaining complex epidemiological dynamics and offer new perspectives on the population response to prolonged health interventions. Este artículo analiza la prolongada fase valle en la curva epidémica asociada a la dinámica de COVID-19 en Chile durante el periodo de julio a diciembre de 2020, caracterizada por un registro relativamente estable entre 1000 y 2500 casos diarios. A diferencia de los modelos (, )-SIR tradicionales, con parámetros constantes y asociados respectivamente a la tasa de transmisión y de remoción en el proceso infectocontagioso, los cuales predicen comportamientos unimodales; proponemos un enfoque basado en la mecánica del contagio que incorpora una ley dinámica para la tasa de transmisión . Utilizando datos oficiales del Departamento de Estadísticas e Información de Salud, demostramos cómo esta aproximación captura cuantitativamente la estabilización observada, resultado de la adherencia sostenida a medidas no farmacéuticas por parte de la población chilena. El modelo revela que mantener una tasa de contagio por debajo de su valor intrínseco requirió un esfuerzo colectivo constante. Ello permitió un manejo controlado de la demanda hospitalaria en la etapa prevacunal. Nuestros resultados validan la utilidad de la mecánica del contagio para explicar dinámicas epidemiológicas complejas. Además, ofrecen nuevas perspectivas sobre la respuesta poblacional frente a intervenciones sanitarias prolongadas.
Kidney fibrosis is a common pathological pathway of chronic kidney disease (CKD), driven by the formation of fibrogenic niche. Fibroblasts undergo proliferation and activation in this specialized microenvironment, but the precise mechanism by which the fibrogenic niche modulates fibroblast behavior remains elusive. This study aimed to clarify how fibrillin-1 (FBN1), a core structural component of the fibrogenic niche, governs fibroblast proliferation and activation. We further evaluated targeted disruption of the FBN1-EGFR interaction as a therapeutic strategy to block kidney fibrosis progression. Spatial transcriptomics localized FBN1 within the fibrogenic niche. Validation was performed using decellularized kidney scaffolds (KTS), NRK-49F cells, and primary renal fibroblasts. Mechanistic studies included co-immunoprecipitation, RNA sequencing, and genetic knockdown models. Tubule-specific Fbn1 knockout mice provided in vivo evidence. High-throughput screening identified FBN1-EGFR disruptors. FBN1 was enriched in the fibrogenic niche and potently stimulated fibroblast activation. Mechanistically, tubule-derived FBN1 bound fibroblast EGFR, triggering persistent MAPK signaling that accelerated fibrosis. Pharmacological inhibition of EGFR/MAPK signaling blocked these effects. High-throughput screening revealed fucosterol as a potent FBN1-EGFR interaction disruptor that competitively blocked binding, subsequently suppressing MAPK activation and attenuating renal fibrosis. FBN1 acts as a core functional molecule to shape and maintain the fibrogenic niche, and further drives kidney fibrosis by activating the downstream EGFR/MAPK cascade within this niche. By disrupting the FBN1-EGFR interaction, fucosterol provides a promising therapeutic strategy for inhibiting fibrogenic niche formation and blocking kidney fibrosis progression at the source.
Aortic intramural hematoma (IMH) has an unpredictable clinical course depending on the extent of disease. Management remains unclear for patients with type B IMH with concomitant type A IMH. We examine our experience with thoracic endovascular aortic repair (TEVAR) for this patient subset. The study design and research was approved by our Institutional Review Board and the need for informed consent was waived. This is a single-institution retrospective study of patients with type B IMH with an ulcer-like projection (ULP) in the descending thoracic aorta, as well as retrograde type A IMH, who underwent TEVAR between 2018-2024. IMH thickness and extent was examined on CTA imaging to assess for resolution and positive aortic remodeling after TEVAR. We identified 65 patients between 2018-2024 treated at our institution for IMH. Of those, 7 patients had a type B IMH with ulcer-like projection with concomitant retrograde arch extension of the IMH, treated with TEVAR. In our series, 5 patients had resolution of the retrograde type A IMH by 5 months, and as early as 3-5 weeks in 2 of those patients. The type B component of IMH had resolved in 5 patients by 10 months, and as early as 11-14 days in 2 patients. One of the 7 patients was lost to follow up. Early TEVAR for patients with type B IMH with ulcer-like projection with concomitant retrograde ascending aortic or arch IMH, is a management strategy that can promote favorable aortic remodeling, without the need for open ascending aortic repair.