Participation in clinical trials often involves uncertainty despite high patient interest. To summarize patient perspectives and derive recommendations for patient-centered clinical trial design in ophthalmology. Structured review integrating the literature and experiences from patient organizations and clinical trial centers. Understandable clarification, realistic communication of expectancy, accessible information and study centers, continuity of care and contact persons, transparent cost regulation and reduction of logistical burdens are crucial for participation and retention in studies. Patient self-help organizations and ophthalmologists play a key role in information dissemination. After trial completion, participants expect feedback on group allocation, study results and further treatment options. Early patient involvement and patient-oriented study design improve feasibility, recruitment, retention and ethical quality of clinical research. A timely incorporation of self-help, comprehensible communication and practical study trajectories are decisive. HINTERGRUND: Die Teilnahme an klinischen Studien erfordert eine informierte Entscheidung, ist jedoch häufig mit Unsicherheiten verbunden. Es erfolgt die Darstellung patientenrelevanter Erwartungen und Empfehlungen zur patientenzentrierten Gestaltung klinischer Studien in der Augenheilkunde. Es wird eine strukturierte Übersicht unter Einbezug publizierter Literatur, Perspektiven der Patientenselbsthilfe und Erfahrungen klinischer Studienzentren gegeben. Zentrale Faktoren für Teilnahme und Verbleib in Studien sind verständliche Aufklärung, realistische Erwartungskommunikation, barrierefreie Informationen, erreichbare Studienzentren, konstante Ansprechpersonen und transparente Kostenregelungen. Selbsthilfeorganisationen unterstützen mit der Weitergabe von Informationen und bei der Rekrutierung. Nach Studienende wünschen sich Teilnehmende Informationen über Gruppenzuteilung, Ergebnisse und weitere Behandlungsmöglichkeiten. Patientenzentrierte Studienplanung verbessert Rekrutierung, Retention und ethische Qualität klinischer Forschung. Frühzeitige Einbindung der Selbsthilfe sowie verständliche Kommunikation und praxisnahe Studienabläufe sind entscheidend.
Globally, access to menstrual cycle and hygiene information is limited, especially for women who are largely hearing impaired. Interactive games offer a promising approach as they increase knowledge about menstrual health. This study was conducted to determine the effect of an interactive game played with women of reproductive age with hearing disabilities on their perception of the menstrual cycle and hygiene. This quasi-experimental pre-test-post-test study was conducted between May 30 and August 31, 2025, with 82 women with hearing disabilities (40 control, 42 intervention). In the intervention group, the interactive game was played once, and the post-test was administered four weeks later. No intervention was applied to the control group. Data were collected using a questionnaire including demographic information and sections on menstrual cycle and hygiene perception. Analyses were performed using the Independent Sample T-Test, ANOVA, Paired T-Test, and Mixed ANOVA. The mean post-test scores of menstrual cycle and hygiene perceptions were statistically significantly higher in the intervention group compared to the control group (F: 126.197, p < 0.001, ηp²: 0.612). It was also determined that all women in the intervention group (100%) were satisfied with the interactive game. This study found that the interactive game had a significant effect on the menstrual cycle and hygiene perception of women with hearing disabilities. Therefore, it is recommended that health professionals use the interactive game-based training model when providing menstrual cycle education and counselling, to support the knowledge levels of women with hearing disabilities. Statement of SignificanceProblemThe menstrual cycle and hygiene perceptions of hearing-impaired women of reproductive age have not been previously determined. And no interactive application has been developed on this subject.Current KnowledgeWomen of reproductive age with disabilities obtain information about menstrual cycles and hygiene from their mothers. However, the level of knowledge is insufficient.Contribution of This ArticleThis study measured the level of awareness of menstrual cycles and hygiene among hearing-impaired women of reproductive age. It also found that interactive games have a strong impact on awareness of menstrual cycles and hygiene.
Breast cancer is the most prevalent malignancy among women worldwide. Smoking increases the risk of breast cancer and is associated with poorer treatment outcomes. Although smoking behaviour and cessation have been studied among breast cancer patients, the existing evidence remains heterogeneous, and the timing of cessation around diagnosis is not fully understood. The aim of this study was to determine the proportion of breast cancer patients who quit smoking after diagnosis and to identify factors associated with smoking cessation. In this retrospective study, the smoking status of 6456 consecutive breast cancer patients from years 2010 to 2022 was evaluated. All patients were requested to complete a baseline questionnaire including information on their smoking status. The follow-up information was collected from the patient records. At the time of diagnosis, 851 patients (13.2%) were actively smoking. Follow-up data were available for 736 patients (86.5%), of whom 189 (25.7%) quit smoking at the time of diagnosis despite the absence of a formal cessation program. Nearly half (44.7%) of all smoking cessation events occurring within the 5-year period before and after diagnosis took place within the year of diagnosis. Smoking cessation was significantly more likely at the time of diagnosis than during subsequent years. Cancer diagnosis provides a timely opportunity for smoking cessation and highlights the potential value of integrating smoking cessation interventions at the time of diagnosis.
A precise economic representation of the central emergency department (ZNA) is a challenge for most hospitals. Due to the complex interrelationship of revenues from various systems, internal service billing, costs associated with the German Association of Statutory Health Insurance Physicians (KV), and process indicators, there are currently no analytical models that provide full transparency regarding the economic reality of the ZNA, and, thus, there is no solid basis for differentiated management. In a retrospective, quantitative study based on routine data (n = 150 cases) from 2024 from the Charité - Universitätsmedizin Berlin emergency department, which was selected based on specific criteria, a cost and revenue analysis was performed. In addition, resource intensive formal "hybrid cases" that were billed formally as outpatients but with inpatient characteristics were defined and included in the analysis, which until now have not been adequately reflected in any renumeration system. The term "hybrid" describes formal outpatient but resource intensive processes with inpatient characteristics. Personnel costs were not analyzed based on each case due to lack of a reliable method to assign these to the individual cases. Remuneration was inadequate in nearly all outpatient cases (-242 to -346 €/case depending on the Charité site). Hybrid cases form an especially critical group (-205 to -290 € per case depending on the site) due to the longer hospital stay and higher costs in the internal cost allocation (ILV). In some cases, inpatient cases had more favorable remuneration ratios and thus appear to be more cost-effective due to internal splitting logic. However, because only about 22 % of cases are hospitalized, while 78 % remain outpatients, the inpatient minority can not compensate for the structural deficits of the outpatient majority. The economic outcome is also negatively affected by the about 10 % costs associated with the KV. The systematic integration of cost, revenue, and process data is feasible and generates new information for management, but it remains incomplete due to limitations in the routine data. The results show that the economic difficulties of the ZNA are not primary due to the inefficient provision of services, but are due to structural causes of renumeration logic in the German healthcare system. The internal establishment of specific management tools, especially the linking of ILV, hospital stay duration and case type ("hybrid flag"), can contribute to improvements, but can not overcome the structural deficit. This structural underfinancing of emergency preparedness exacerbates the already strained financial situation of hospitals and requires future reform that explicitly takes into consideration aspects of standby capacity components and the actual provision of services. HINTERGRUND: Die präzise ökonomische Abbildung zentraler Notaufnahmen (ZNA) stellt sich für die meisten Krankenhäuser als Herausforderung dar. Durch die komplexe Verknüpfung von Erlösen aus verschiedenen Systemen, interner Leistungsverrechnung, Absetzungen der Kassenärztlichen n Vereinigung (KV) und Prozesskennzahlen fehlen bisher Analysemodelle, die eine vollständige Transparenz über die ökonomische Realität der ZNA herstellen und damit die Grundlage für eine differenziertere Steuerung bilden. In einem retrospektiven, quantitativen Studiendesign auf Basis von Routinedaten von n = 150 Fällen des Jahrs 2024 aus den Notaufnahmen der Charité – Universitätsmedizin Berlin, die nach differenzierten Kriterien ausgewählt wurden, wurde eine Kosten- und Erlösanalyse durchgeführt. Zusätzlich wurden ressourcenintensive, formal ambulant abgerechnete „hybride Fälle“ mit stationären Merkmalen definiert und in die Analyse einbezogen, die bislang in keiner Abrechnungssystematik adäquat abgebildet sind. Der Begriff „hybrid“ beschreibt dabei formal ambulante, jedoch ressourcenintensive Verläufe mit stationären Charakteristika. Personalkosten wurden aufgrund der fehlenden Möglichkeit, diese einzelnen Fällen eindeutig zuzuordnen, nicht fallbezogen analysiert. Ambulante Fälle weisen nahezu durchgängig wirtschaftlich ungünstige Deckungswerte auf (−242 bis −346 €/Fall je nach Charité-Standort). Hybride Fälle bilden aufgrund langer Aufenthaltsdauern und hoher Kosten in der internen Leistungsverrechnung (ILV) ein besonders kritisches Segment (−205 bis −290 € pro Fall je nach Standort). Stationäre Fälle weisen in der internen Splitting-Logik teilweise wirtschaftlich günstigere Deckungswerte auf und erscheinen damit ökonomisch günstiger. Da jedoch nur rund 22 % der Fälle stationär sind, während 78 % ambulant verbleiben, kann die stationäre Minderheit die strukturellen Defizite der ambulanten Mehrheit nicht kompensieren. Das ökonomische Ergebnis wird zusätzlich durch etwa 10 %ige Absetzungen durch die Kassenärztliche Vereinigung belastet. Die systematische Verknüpfung von Kosten‑, Erlös- und Prozessdaten ist möglich und schafft neue Steuerungsinformationen, bleibt aber durch die Limitationen der Routinedaten unvollständig. Die Ergebnisse zeigen, dass die ökonomische Schieflage der ZNA nicht primär auf ineffiziente Leistungserbringung, sondern auf strukturelle Ursachen der Vergütungslogik im deutschen Gesundheitssystem zurückzuführen ist. Die interne Etablierung spezifischer Steuerungsinstrumente, insbesondere die Verknüpfung von ILV, Aufenthaltsdauer und Fallart („hybrid flag“), kann zur Verbesserung beitragen, aber das Strukturdefizit nicht überwinden. Diese strukturelle Unterfinanzierung der Notfallbereitschaft verschärft die ohnehin angespannte wirtschaftliche Lage der Krankenhäuser und erfordert eine künftige Reform, die Vorhaltekomponenten und die tatsächliche Leistungserbringung explizit berücksichtigt.
This study investigated how aging affects the perceptual span, the spatial limit of visual processing, in traditional Chinese with the gaze-contingent moving-window paradigm. The viewing was either unrestricted or involved varying window sizes where a constant one-character left window was paired with a manipulated right window that revealed two, three, or four upcoming characters. Older readers had slower reading speed, although they did not differ from young readers in gaze durations. In addition, while reading performance was statistically comparable between the four-character window and full-line conditions in both groups, the two groups differed in their reliance on near- and far-foveal information. In particular, there was a larger boost in reading performance for the older readers than for the young readers when the window increased from two to three upcoming characters. In contrast, the young readers exhibited a larger gain than the older readers when the window included the fourth upcoming characters. Together, older Chinese readers appear to be more sensitive to information within three upcoming characters, but were less so to further ones. These findings highlight the interplay between script characteristics and cognitive aging in reading and constrain the range of parameters in developmentally valid computational models of eye-movement control in reading.
This unit provides information to aid in the selection and proper use of a laboratory balance. Laboratory balances are used for measuring the mass of an object and come in two main types: mechanical and electronic. Electronic balances generally come with a computer interface to facilitate the collection, storage, and manipulation of the data. In addition to weighing objects, electronic balances also perform a range of computations, including counting objects, measuring density, statistics, and pipet volume calibration. Balances vary widely in terms of their capacity (how heavy an object they can accurately weigh), precision, accuracy, repeatability, and robustness. Understanding the various characteristics of a laboratory balance is necessary to be sure that the balance is well suited for your particular scientific or industrial needs. This unit also discusses the proper use and maintenance of a laboratory balance. In general, laboratory balances are relatively easy to use and require little maintenance. © 2026 Wiley Periodicals LLC. Basic Protocol 1: Measuring mass using a top-loading balance Basic Protocol 2: Measuring mass using an analytical balance.
The physical separation of memory and processing in conventional architectures results in significant energy dissipation during data movement. This has motivated research into brain-inspired information processing, where memory and learning are realized in a single unit using water and ions. Herein, we report biomimetic memristive and synaptic-like ion dynamics in an aqueous environment using ion-track etched smart nanochannels. Our experiments demonstrate that driving ions through asymmetric bipolar surface charges generates a memristive effect capable of withstanding hours of endurance stress, and that the memristor type can be dynamically changed by the local chemical environment due to counterion over-screening. We identify ion accumulation and depletion as the single unifying mechanism underlying both memristive switching and synaptic plasticity. These controllable ion dynamics emulate a broad spectrum of plasticity: from short-term plasticity to long-term potentiation and depression (LTP/LTD) with near-linear, low-asymmetry conductance modulation and a low energy consumption of 13.2 pJ per synaptic event. Implementing these reversible weight updates in artificial neural network (ANN) simulations yields a recognition accuracy of 94.54% for handwritten digit recognition (small-digit MNIST), rivaling solid-state memristors. These findings demonstrate that systematic control of ion interactions within nanochannels provides a high-performance, energy-efficient foundation for neuromorphic computing.
Our understanding and utilization of genetics in healthcare continues to increase, but historically excluded and underrepresented groups (e.g., racial minority groups, those living in rural areas, and individuals from lower socioeconomic backgrounds) are often left behind due to barriers in accessing genetic healthcare and research. Although research priorities have shifted toward greater inclusion, underrepresentation persists, potentially driven by ongoing negative healthcare experiences that compound barriers to accessing genetic research and healthcare services, creating a cycle of genomic healthcare disparities. However, there is limited research about how healthcare experiences may contribute to genomic healthcare disparities. We examined this knowledge gap by using data from the All of Us Research Program to investigate healthcare experiences of participants from underrepresented groups as well as participants with clinically diagnosed genetic conditions. We explored three survey questions which documented self-reported experiences when receiving healthcare (i.e., inclusion in medical decisions, being treated with respect by providers, and receiving easy to understand medical information). Survey question responses were analyzed within a regression framework which included self-identified race, age, gender identity, health insurance status, education and income levels, having a diagnosed genetic condition, and rural location as predictors. Results suggest many populations (e.g., minoritized racial and gender groups, individuals who have had to delay care due to living in a rural area, and those with genetic conditions) face inequities in healthcare experiences. These findings support the proposed conceptual model of a genomic healthcare disparity cycle and the need to address these negative healthcare experiences to break the cycle.
Mobile behavioral health crisis response services, staffed by clinicians and specialists, can support individuals experiencing urgent mental health or substance use issues. While Medicaid coverage for these services since 2021 has supported growth in their availability, research on family caregivers' experiences with mobile crisis services remains limited. Family caregivers often participate in encounters with crisis services when the person in crisis cannot seek help independently due to their symptoms. This study aimed to explore family members' experiences with a mobile crisis program in the US using qualitative methods. The study examined an expanding, county-level mobile crisis program designed according to SAMHSA guidelines and Medicaid-qualifying standards, staffed by clinicians and peer support workers. We used qualitative methods to understand family caregiver experiences with these services. Data was collected through in-depth interviews with family caregivers (N = 11), the primary source for this analysis, and ethnographic field observations of mobile crisis response teams (N = 29 observation days), which provided contextual information about service delivery and family involvement during crisis. Transcripts and field notes were analyzed for recurrent themes. Family members expressed feeling isolation and being overwhelmed while managing loved ones' constant care. Many worried that without their support, loved ones would face homelessness and worsened mental health. Families identified the mobile crisis service as a substantial improvement over the other options they could turn to for help. They reported that crisis services alleviated isolation, appreciated providers who understood home dynamics, and found comfort in having a safe and responsive resource to call when needed. Families identified the availability mental health responders as a source of relief both during and after crisis episodes. Understanding how features of crisis response service are experienced by family caregivers can inform impact studies by highlighting potential mechanisms of effectiveness.
Thyroid peroxidase (TPO) is a crucial enzyme in thyroid hormone (TH) biosynthesis, catalyzing iodination and coupling reactions for triiodothyronine (T3) and thyroxine (T4) production. In addition to the known enzymatic inhibition mediated by some compounds, increasing evidence indicates that various drugs can modulate TPO mRNA and/or protein expression (e.g., protein kinase activators, cytokines, epigenetic drugs). This review comprehensively explores current evidence on the pharmacological regulation of TPO expression, encompassing its molecular structure, enzymatic function, and involvement in physiological and pathological conditions (e.g., thyroid cancer, autoimmune thyroid diseases, congenital hypothyroidism and hyperthyroidism). Among compounds reported to affect TPO expression, the antithyroid drugs (ATDs) methimazole (MMI) and propylthiouracil (PTU) show variable effects across in vitro and in vivo models, yielding heterogeneous and sometimes conflicting results. Considering that ATDs are the only class of drugs known to directly target TPO and the current lack of works gathering all the related information, there is a need for clarifying ATD-mediated modulation of TPO expression. A systematic PubMed search identified 437 records, of which 22 original studies met inclusion criteria in this work. Overall, available data suggest time-, dose-, and species-dependent ATD effects on TPO expression, highlighting the need for further research to determine clinical relevance.
We document the first records of reef fishes typically associated with mesophotic environments on shallow (<10 m) coral reefs inside a well-studied tropical bay. The vermilion snapper Rhomboplites aurorubens and the pygmy angelfish Centropyge aurantonotus, usually restricted to deeper (>40 m) shelf habitats along the Brazilian coast, were recorded inside Baía de Todos os Santos (BTS). Integrating long-term ecological and oceanographic monitoring, fisheries information and underwater visual records, we show that these occurrences coincided with coastal upwelling and the advection of cooler shelf waters. We propose that cold-water intrusions act as thermal corridors enabling cross-shelf movements.
Adolescents are at increased risk of developing mental health disorders, making mental health literacy a key component of early prevention and recognition. Although school-based interventions are considered effective, they remain insufficiently implemented within the French education system. This study assessed the impact of a universal school-based mental health literacy intervention, IDEO (Inform, Destigmatize, Evaluate, and Orient), on adolescents' knowledge of mental health and support services. A pre-post comparative study was conducted in all high schools of the Aube department (France) between January 2023 and December 2024. The IDEO intervention was delivered by mental health professionals and educators through two interactive sessions. Students aged 15-16 years completed self-administered digital questionnaires before and after the intervention, assessing mental health knowledge, misconceptions, and awareness of available support services. Knowledge acquisition was measured using a score based on the number of 18 possible correct answers. Multivariable and sensitivity analyses were performed to identify factors associated with knowledge improvement. Paired pre- and post-intervention data were available for 2,480 students. The mean (SD) knowledge score increased significantly from 5.8 (2.6) at baseline to 8.5 (3.6) post-intervention (p < 0.001). Improvements were observed across all knowledge domains, although awareness of support services remained comparatively low (mean score 1.8 ± 2.2; maximum 9). Greater knowledge gains were associated with female gender, higher baseline knowledge, and awareness of the positive impact of sleep on mental health (p < 0.05). Students enrolled in vocational education showed lower post-intervention knowledge scores (p < 0.001). Overall, 93.7% of participants reported being satisfied or very satisfied with the intervention. The IDEO program significantly improved mental health literacy among French high school students. These findings support the integration of universal, school-based mental health education into the French educational curriculum.
In 2023, the National Comprehensive Cancer Network® (NCCN®) updated its guidelines for managing breast cancer risk in patients with a CHEK2 p.I157T variant, recommending de-escalation of enhanced screening based on this variant alone. This shift reflects evidence that some missense variants carry a lower cancer risk than CHEK2 loss-of-function variants. A reduced cancer risk is particularly well established for the CHEK2 p.I157T variant, prompting the updated guidelines. This study examines healthcare providers' understanding of these updated guidelines and explores how providers communicate these changes to patients affected by hereditary cancer risks. We conducted a survey targeting healthcare providers involved in hereditary cancer management, capturing their perceptions of the clinical implications of CHEK2 p.I157T and the approaches used to communicate de-escalated management recommendations. Additionally, a retrospective records review was performed to approximate the percentage of patients impacted by these de-escalation recommendations. This research aims to evaluate factors shaping provider recommendations and communication following guideline changes in hereditary cancer care. Results may inform best practice considerations for patient-provider communication in hereditary cancer care, particularly when new evidence leads to modified screening or management recommendations.
To compare the adverse event reporting profiles of tacrolimus combined with everolimus versus tacrolimus combined with sirolimus for immunosuppressive therapy after organ transplantation using the FDA Adverse Event Reporting System (FAERS) database and to generate hypotheses to inform the individualized selection of mTOR inhibitors. As FAERS does not record drug dose, the two combinations are compared without reference to tacrolimus dosing. Adverse event reports from the FAERS database spanning the first quarter of 2004 to the fourth quarter of 2025 were extracted. Disproportionality analysis was performed using four methods: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayesian geometric mean (EBGM). Analyses were conducted at the system organ class (SOC) and preferred term (PT) levels, as well as age-stratified (< 60 years vs. ≥ 60 years), sex-stratified, and time-to-onset analyses. A total of 3101 reports for tacrolimus combined with everolimus (ta_ev) involving 13,237 adverse events, and 3093 reports for tacrolimus combined with sirolimus (ta_si) involving 13,356 adverse events were retrieved. The ta_ev regimen generated 459 PT signals covering 25 SOCs, with the three strongest SOCs being renal and urinary disorders (ROR = 4.85), infections and infestations (ROR = 3.55), and blood and lymphatic system disorders (ROR = 3.48). The ta_si regimen generated 413 PT signals also covering 25 SOCs, with the three strongest SOCs being immune system disorders (ROR = 5.22), renal and urinary disorders (ROR = 3.52), and blood and lymphatic system disorders (ROR = 2.98). Both regimens generated strong renal/urinary and haematological disproportionality signals, but the reporting patterns diverged in several respects: the ta_ev regimen had a significantly stronger signal for hepatobiliary disorders (ROR = 3.12 vs. 1.89), whereas the ta_si regimen showed a stronger signal for cardiac disorders (ROR = 1.14 vs. 0.81) and a stronger association with wound healing complications. A formal between-regimen comparison (ratio of reporting odds ratios (rROR), with 95% CIs) indicated that these differences in reporting were statistically distinguishable (Table 5), although the magnitudes were modest for the cardiac and several other classes. Age-stratified analysis indicated that patients under 60 years of age had a higher frequency and greater variety of adverse events; male patients accounted for a higher proportion of reports in both groups. The median time to adverse event onset was approximately 3-3.5 months, but more than 10% of events occurred after one year of treatment. Tacrolimus combined with everolimus and with sirolimus show distinct adverse event reporting profiles in FAERS: the everolimus-based combination was relatively enriched for hepatobiliary, BK-related renal and infectious events, and the sirolimus-based combination for cardiac, immune system, and wound healing events. These disproportionality signals describe reporting rather than measured risk and are hypothesis-generating; they require confirmation in controlled studies before they can guide the individualized choice of an mTOR inhibitor, with closer monitoring suggested for recipients under 60 years of age and for male patients.
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Nature-based interventions (NBIs) have been identified to support a recovery-oriented approach for people experiencing mental health issues. However, there is still limited knowledge related to how mental health service users experience their recovery process when engaged in NBIs. To explore and explain how mental health service users experience the process of personal recovery from participating in a newly developed NBI. The study was conducted using constructivist grounded theory and included 20 participants. The NBI, including equine-assisted therapy, was delivered in groups at a farm-based rehabilitation centre. Purposeful sampling was used, and in-depth interviews were performed on site. Data were analysed in an iterative, comparative process. During the analysis, NVIVO 14 was used to organise and manage the data systematically. The grounded theory of the core concept 'A process of embodied recovery', described the participants' experiences of personal recovery during the NBI and included three concepts: 'Experiencing interconnection' through transactions with the environment, 'Processing inner connection' through reflection and 'Feeling intra-connected' through integration of self and body as a whole in everyday life. The NBI provides positive multisensory experiences to support personal recovery among mental health service users. The findings hold significant implications for the advancement of recovery-oriented services in mental health care, including occupational therapy.
To synthesize recent evidence on how environmental exposures influence stroke risk, with emphasis on air pollution, thermal stress, circadian and occupational disruption, built and social environments, and selected toxicants. Long-term and episodic air pollution, especially fine particulate matter with aerodynamic diameter ≤ 2.5 μm (PM₂.₅) and wildfire smoke, remain most consistently associated with stroke risk. Extreme heat combined with heat-humidity metrics is emerging as an important acute stroke trigger. Noise, artificial light at night, shift work, and long working hours show smaller but plausible associations, while greener and more walkable environments may be modestly protective. Social and structural disadvantage clusters, multiple exposures and inequities play an integrated role in risk and prevention. Environmental determinants are increasingly relevant to stroke risk. The strongest current links are realted to pollution, heat, sleep, and work disruption, as well as environmental inequity. Future research should move beyond single-exposure models toward combined-exposure as well as intervention-focused approaches.
In patients with asymptomatic severe aortic stenosis (AS), exercise stress testing is recommended to unmask symptoms and guide the timing of intervention, yet it is infrequently used in clinical practice. This registry-based follow-up of the Evaluation of TAVR Compared to Surveillance for Patients With Asymptomatic Severe Aortic Stenosis (EARLY TAVR) trial evaluates how treadmill stress testing (TST), used during screening for EARLY TAVR to confirm asymptomatic status, informed subsequent aortic valve replacement and clinical outcomes. To evaluate clinical outcomes in patients with asymptomatic severe AS and a positive TST result and to identify predictors of a positive TST result. This prespecified TST registry of the EARLY TAVR trial involved 75 clinical sites across the US. Between July 2017 and December 2021, apparently asymptomatic patients with severe AS underwent standardized TST. Those with normal TST results were randomized to transcatheter aortic valve replacement or clinical surveillance, whereas those with positive TST results were invited to enroll in a prospective registry and were followed up with through 2 years. Of 1250 patients screened, 962 met trial criteria. Of these, 816 (84.8%) had a normal TST result and 146 (15.2%) had a positive TST result. Of these, 105 consented to enroll in the EARLY TAVR Treadmill Registry. Data were analyzed from August 2025 to January 2026. Positive TST result. TST-related safety, 2-year all-cause mortality, and rates of subsequent aortic valve replacement (AVR). Baseline predictors of a positive TST result were identified using multivariable logistic regression models. Of the 105 patients included in the present analysis, the mean (SD) age was 76.1 (6.5) years, and 80 participants (76.2%) were male. TST was found to be safe, with no reported deaths, syncope, or cardioversions. Multivariable baseline predictors of a positive TST included higher peak velocity, lower ejection fraction, prior coronary artery bypass, and prior stroke. The 2-year Kaplan-Meier rate for all-cause mortality was 5.7%. Among patients with positive TST results, the rates of AVR at 1 and 2 years were 79.9% and 85.9%, respectively. Rates of mortality and AVR were similar for patients who had a class I indication for AVR (symptoms during testing) and those with a class IIa indication (drop in systolic blood pressure). In patients with asymptomatic severe AS, TST was found to be safe and identified symptoms and AVR indication in approximately 15% of patients. However, 20% of those patients remained untreated at 1 year, despite having an indication for prompt treatment. ClinicalTrials.gov Identifier: NCT03042104.
Despite the global decline in COVID-19 incidence, the continued emergence of immune-evasive SARS-CoV-2 variants underscores the urgent need for next-generation vaccines capable of providing broad protection. To characterise and design a broad-spectrum recombinant multiepitope vaccine candidate against pathogenic human coronaviruses using an immunoinformatics approach. Conserved antigenic regions within the spike (S), nucleocapsid (N) and membrane (M) proteins were identified from multiple SARS-CoV-2 variants through multiple sequence alignment. High-affinity T-cell and B-cell epitopes were screened and assembled into recombinant vaccine construct (RVC). The RVC was evaluated for antigenicity, allergenicity, toxicity and physicochemical properties, followed by tertiary structure prediction and validation. Molecular docking with Toll-like receptor 3 (TLR-3) and molecular dynamics (MD) simulations with MM-GBSA binding free energy calculations were performed, alongside in silico immune simulation. The RVC comprised four HLA class I-restricted epitopes, 27 HLA class II-restricted epitopes and five linear B-cell epitopes, with predicted global population coverage of 99.99%. The construct demonstrated high antigenicity, non-allergenicity and favourable physicochemical stability. Molecular docking showed stable interaction with TLR-3, supported by MD simulations and a favourable MM-GBSA binding free energy of - 5.19 kcal/mol. In silico immune simulation predicted robust humoral and cellular immune responses, including sustained memory cell populations following three-dose immunisation. These computational findings support the RVC as a promising broad-spectrum human coronavirus vaccine candidate. However, experimental validation, including immunogenicity, safety and protective efficacy studies in relevant in vitro and in vivo models, is warranted to substantiate its translational applicability.
Plasmonic metal-semiconductor heterostructures are widely studied for light-harvesting applications, yet the role of localized surface plasmon resonance (LSPR) in carrier extraction on the semiconductor side remains poorly understood. Here, we show that engineering the dielectric environment in Au/CeO2 using ultrathin nanoporous Ceria transforms plasmonically activated volume (PAV) on CeO2 side from interface-confined plasmonic excitation into a spatially extended, volume-activated process. meV-resolution electron energy-loss spectroscopy visualizes LSPR propagation throughout the porous framework, while photoluminescence spectroscopy reveals an enhanced contribution from fast charge-transfer channels. Quantitative analysis establishes the correlation among the PAV, fast charge transfer, and carrier utilization efficiency. These findings highlight the importance of semiconductor-side carrier dynamics in plasmonic heterostructures and establish dielectric-environment engineering as an effective strategy for extending plasmonic functionality beyond the immediate metal-semiconductor interface.