Expectations of integrating health and social care providers have driven the development of digital solutions aimed at overcoming interoperability challenges and ensuring access to information needed for integrated care across fragmented services. However, challenges persist in aligning diverse coding practices, heterogeneous data-sharing mechanisms, and stakeholder needs. We examine how expectations of interoperability and integrated care have shaped the growth of regional information infrastructures in Scotland, using the Key Information Summary (KIS), a summary record that shares key patient information from general practitioner records with out-of-hour services, ambulance services, hospitals, social workers, and caregivers across multiple care settings, as a case study. This qualitative study examined the development, implementation, and adoption of KIS in Lothian, Scotland, across health and care settings, where it has been in use for 13 years. Multisited ethnography was used to understand how technology design, implementation, and adoption were shaped by social, organizational, cultural, and political factors. Data were collected through interviews with users, vendors, and implementers; observations of technology use and multidisciplinary team meetings; and documentary analysis of policies, user guides, and internal reports. A hybrid analytical approach was applied: the Technology, People, Organization, and Macroenvironment framework guided initial coding, while the sociology of expectations and information infrastructure theory were used inductively to trace evolving visions of integration, and the long-term development of regional information infrastructure. Data included 54 qualitative interviews, 20 hours of observation, and 59 documents collected between April 2024 and March 2025. Findings illustrate how information infrastructures for integrating health and care providers evolved through successive concerted efforts, conceptualized as waves. Three waves were identified, each characterized by attempts to interlink disparate information systems used by various health and care providers. The first wave focused on linking health care providers by developing networks and architectures required for sharing clinical information, which later supported the development and sharing of KIS. Subsequent waves sought to interlink information systems used by health care providers with those used by local authorities and social care providers. In the absence of shared data standards across these sectors, interoperability was achieved by extending the existing health care-centric infrastructure to different social care settings through workarounds such as providing proxy access to hospital systems and secure emailing networks. This work illustrates how regional information infrastructures for integrated care evolve through orchestrated waves of change. Some expectations for change required coordinated, system-level action, such as setting up standards, networks, and architecture, while others were realized through local adaptations. Integrating health and care providers through digitalization is a long-term process requiring sustained coordination, with progress often occurring through incremental, local extensions. Policies must support adaptive, long-term coordination, balancing system-level initiatives with local adaptations to achieve meaningful integration.
Road injuries are a leading cause of mortality and morbidity worldwide. Years of international efforts have aimed to strengthen policy engagement, including the 2020 UN General Assembly's proclamation of the Second Decade of Action for Road Safety (2021-30), targeting a 50% reduction in road traffic deaths and serious injuries by 2030. The aim of this study is to provide estimates to monitor progress and identify intervention gaps. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2023, we estimated incidence, mortality, and morbidity of road injuries for 204 countries and territories from 1990 to 2023. Four road injury types and 47 nature-of-injury categories were examined. Morbidity and mortality data from clinical records, vital registration, and police reports were harmonised using meta-analytic techniques to ensure consistency and correct for systematic bias. Incidence was modelled with the meta-regression tool Disease Modelling-Meta-Regression version 2.1 and cause-specific mortality with the Cause of Death Ensemble model, both incorporating location-specific covariates to support interpolation. Years of life lived with disability (YLDs) were estimated from the prevalence and severity of the nature of road injury, and years of life lost (YLLs) from the number of cause-specific deaths multiplied by the standard life expectancy at the age of death. Disability-adjusted life-years (DALYs) were the sum of YLLs and YLDs. All metrics were calculated with 95% uncertainty intervals (UIs). In 2023, there were 50·9 million (95% UI 46·1-56·1) road injury incident cases, 1·34 million (1·04-1·58) deaths, and 75·3 million (59·8-89·2) DALYs globally. Road injuries were the leading global cause of death among males aged 10-39 years. Between 1990 and 2023, age-standardised incidence decreased by 38·3% (95% UI 36·9-39·7) and mortality decreased by 32·3% (6·1-49·0), but progress varied widely by World Bank income group. Mortality in low-income countries (43·8 [95% UI 31·7-56·0] deaths per 100 000 population) was approximately six times higher than in high-income countries (7·5 [7·1-7·9] deaths per 100 000), despite the high-income countries showing the highest age-standardised incidence rates (858·1 [95% UI 781·9-947·1] cases per 100 000). In the past decade, many countries achieved notable reductions in road injuries, but others, including Ghana and the USA, saw increases. More severe injuries tended to occur in low-income and middle-income countries. Although global incidence, mortality, and DALY rates from road injuries have declined, progress remains uneven, with pronounced disparities across income groups reflecting systemic inadequacies in infrastructure, vehicle standards, enforcement, and post-crash care. Strengthening emergency response, improving road design, enforcing safety measures, and adapting policies to the evolving demographics remain essential. Gates Foundation.
Trauma, obstetric haemorrhage and severe anaemia lead to millions of deaths every year. Many of these deaths occur in regions known as 'blood deserts' where there is virtually no access to blood transfusions. A community or civilian walking blood bank (CWBB) is a low-resource strategy that can provide just-in-time, point-of-care tested blood transfusions in blood deserts when banked blood is not readily available and the alternative is almost-certain death. This protocol is designed to evaluate the effectiveness and implementation of a CWBB at Lodwar County Referral Hospital located in a blood desert in rural north-west Kenya. We will use a mixed-methods approach relying on an implementation science design to evaluate effectiveness, acceptability, applicability and impact of a CWBB. The study will be conducted over 1 year in two parts: pre-emergency and post-emergency transfusion protocol (ETP) implementation. First, a previously developed ETP will be validated and finalised by key hospital stakeholders. Effectiveness will be assessed quantitatively and qualitatively. Prospective laboratory-based data collection will measure changes in blood ordering practices. We expect a sample size of approximately 140 (20/month) unmet blood transfusion requests, with 40 (5/month) of those being emergent (requiring blood in less than 2 hours). These cohorts will be compared pre-implementation and post implementation. Qualitatively, key informant interviews of hospital staff and the community will explore clinical blood demand and general understanding and perceptions about blood donation and transfusion. Lastly, we will determine the adaptability and scalability of a CWBB to other low-resource settings with in-depth interviews and a modified Delphi approach to achieve consensus regarding key components of a CWBB and its transferability to other settings. Ethical approval was granted by the Strathmore University Institutional Scientific and Ethics Review Committee (SU-ISERC2234/24) and the Mass General Brigham (MGB) Hospital's Institutional Review Board (#2024P001878; #2024P001879; #2024P001885; #2024P001887). The study team also secured a research licence from the National Commission for Science, Technology and Innovation (#168094) before initiating the study. Interviews will be voluntary and consent will be obtained prior to participation. Blood transfusion consent will be collected as per standard hospital process. The findings will be disseminated through academic publications, conference presentations and workshops, contributing valuable insights into emergency blood transfusion protocols. These findings will also be conveyed to Lodwar County Referral Hospital in order to facilitate quality improvement.
Shrimp processing generates substantial quantities of nutrition-rich by-products that are often underutilized sources of bioactive compounds exhibiting numerous functions, which include anti-inflammatory, antimicrobial, antitumor, antioxidant, and cardiovascular disease-prevention. Despite their effects and applications, limited research has focused on the extraction, recovery, and large-scale exploitation, which remain scarce. The study aims to elucidate the impact of plasma bubbling, applied for varying durations (10, 15, 20, 25, and 30 min at 180 V), along with conventional solvent extraction (Control), to extract and enhance the release of bioactives and to evaluate their changes on physicochemical characteristics. Results showed increased total phenolic content (TPC; 1.91 mg/100 g) and total flavonoid content (TFC; 1.74 mg/100 g) at 20 min compared to other treatments, along with higher concentrations of macro- and micro-minerals, but reduced antioxidant activity. Similarly, at 20 min of treatment, 11% antioxidant activity and 60% astaxanthin content were increased compared to the control, and FTIR analysis revealed notable changes in the functional group. A significant increase in color differences was observed. Fatty acid profiling identified 32 fatty acids, with a predominance of polyunsaturated and monounsaturated fats rich in ω-3 and ω-6, along with 17 volatile compounds. The quality of the shrimp waste bioactive compounds (SWBCs) was analyzed. These findings demonstrate that plasma bubbling is an effective, scalable, and sustainable approach for producing functional bioactive ingredients, natural food colorants, and flavor enhancers in instant seafood products. PRACTICAL APPLICATIONS: The method uses shrimp to extract bioactive compounds and serves as an effective technology in terms of cost, ease of operation, and sustainable production of high-end bioactive compounds with health benefits, utilizing by-products as a nutraceutical and functional ingredient, supporting innovation and its application in various instant food products that serve health and palatability.
Rosacea, a chronic inflammatory skin disorder, severely impairs patients' quality of life and imposes substantial medical burdens. Existing treatments are hampered by unsatisfactory therapeutic effects and high recurrence rates, driving urgent research into novel pathogenic mechanisms. As a common spice and cosmetic preservative, cinnamaldehyde's safety risks in rosacea patients remain poorly characterized. This study aimed to integrate network toxicology with in vitro cellular assays to clarify its pathogenic roles and molecular pathways, providing novel theoretical support for its adverse impacts on rosacea sufferers. First, we predicted the target genes of cinnamaldehyde using the PubChem, SwissTargetPrediction, SuperPred, and ChEMBL databases. Second, we obtained relevant targets for rosacea using the GeneCards and CTD databases and identified the intersection targets with toxic substances. Then, we constructed a protein-protein interaction network of the core toxic substance combination using the STRING database and performed Gene Ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis to predict possible mechanisms. Subsequently, molecular docking validation of the active ingredients with the main targets was performed using AutoDock Vina software. Finally, cinnamaldehyde was added to the rosacea-like cellular model in HaCaT cells to assess its effects and molecular mechanisms by Cell Counting Kit-8, reverse transcription quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay. Database screening revealed 43 overlapping targets between the 195 predicted targets of cinnamaldehyde and the 1889 disease-related targets for rosacea, which included notable proteins such as prostaglandin‑endoperoxide synthase 2 (cyclooxygenase‑2; PTGS2), matrix metallopeptidase 9 (MMP9), and epidermal growth factor receptor (EGFR). Protein-protein interaction analysis identified PTGS2 as a pivotal hub protein, while Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that interleukin-17 signaling and lipid metabolism are vital mechanisms involved in rosacea. Molecular docking studies demonstrated strong binding affinities between cinnamaldehyde and the identified core targets. Furthermore, cell culture experiments confirmed that cinnamaldehyde exacerbates rosacea by upregulating the expression of PTGS2, MMP9, and EGFR, along with increasing the production of inflammatory cytokines such as interleukin-8 and interleukin-1 beta. In summary, our findings elucidate the potential pathogenic mechanisms by which cinnamaldehyde may induce rosacea, highlighting the roles of the core targets PTGS2, MMP9, and EGFR in mediating inflammation. This research provides new scientific insights that could inform preventive strategies and therapeutic interventions aimed at managing the toxicity associated with rosacea.
Multiple myeloma (MM) has experienced rapid therapeutic innovation over the past two decades, leading to a substantial increase in clinical trial activity. However, the geographic distribution of these trials and the representation of different economic regions remain poorly characterized. We evaluated the global distribution, growth patterns, and phase-specific trends of MM clinical trials and trial sites across different economic settings. We conducted a retrospective registry-based analysis interventional MM clinical trials registered on ClinicalTrials.gov between January 2006 and January 2026. Trials were categorized based on the economic classification of participating countries using World Bank income groups and Economic Co-operation and Development (OECD) status. Trial characteristics including phase, geographic distribution, number of participating sites, and site-years were analyzed. Population-adjusted trial density and compound annual growth rates (CAGR) were calculated to assess temporal trends and geographic representation. A total of 845 interventional MM clinical trials were identified during the study period. Trial activity was highest in the United States (337 trials, 39.9%), followed by international trials (271, 32.1%), high-income-OECD countries (129, 15.3%), and upper-middle-income countries (103, 12.2%), while high-income non-OECD countries contributed only a small fraction of trials. Trial activity increased substantially over time across all regions with the highest growth observed in upper-middle-income countries (CAGR 18.5%). The US demonstrated the highest population-adjusted trial density (0.99 per million population) and accounted for the largest number of trial sites and site-years. Phase-specific analyses revealed distinct geographic patterns. Phase 1 trials were predominantly conducted in the US and in international collaborative trials. Phase 3 trials were largely international, although the majority of participating sites remained located in the US and High-income countries that are members of the OECD (HIC-OECD). Over the past two decades, MM clinical trial activity has expanded globally but remains highly concentrated in the United States and high income-OECD countries, particularly with respect to trial sites and population-adjusted trial density. Although upper-middle-income countries have shown the fastest growth in trial activity expanding clinical trial infrastructure and strengthening international collaboration will be essential to promote a more equitable global distribution of MM research.
Osteoporosis (OP) and osteoarthritis (OA) are two common degenerative musculoskeletal disorders associated with aging and are traditionally classified and managed as distinct disease entities. Emerging evidence suggests that OP and OA may share bidirectional associations and common biological mechanisms, and that under specific pathological conditions they may develop into a mutually reinforcing comorbid state. The comorbidity of osteoporosis and osteoarthritis (OP-OA) is not a simple superimposition of bone loss and cartilage degeneration; rather, it represents a disorder of the osteochondral unit centered on disruption of the subchondral bone microenvironment. Alterations in the structural strength, remodeling dynamics, vascular and neural status, and bone marrow lesions of subchondral bone collectively reshape the local microenvironment, thereby directly affecting mechanical signal transmission and cellular behavior within the joint. Focusing on the subchondral bone microenvironment as the central pathological nexus, this review systematically summarizes how mechanical imbalance, aberrant bone remodeling, inflammatory activation, metabolic dysregulation, and cellular senescence jointly remodel the local niche in OP-OA comorbidity. These microenvironmental changes further induce phenotypic remodeling and fate deviation of bone marrow mesenchymal stem cells, bone remodeling-related cells, osteoimmune cells, and chondrocytes. On this basis, we integrate the regulatory roles of developmental signaling, mechanotransduction pathways, and inflammatory-immune signaling networks, and propose that microenvironment-driven cell fate plasticity may serve as a key mechanistic hub promoting the initiation and progression of OP-OA comorbidity as well as the persistent destabilization of the osteochondral unit. This perspective may help overcome the limitations of current studies that address OP and OA separately, and may provide a theoretical framework for early identification and stratification, biomarker discovery, and combined precision-targeted interventions for this comorbid condition.
Power plants, major emitters of air pollutants and greenhouse gases, must achieve pollution and carbon reduction synergy for low-carbon development and competitiveness. This study focuses on the enterprise-level challenges of thermal power plants by evaluating the pollution and carbon emission reduction path of a state-owned thermal power plant in northern China. The research applies the LEAP (Long-range Energy Alternatives Planning) model for the emission analysis of pollutants and carbon dioxide from the power plants, and SWOT (Strengths, Weaknesses, Opportunities, and Threats) analysis to evaluate the internal strengths and weaknesses as well as external opportunities and threats of power enterprises. The results indicate that 2.31 million t of CO2 were emitted during the thermal power production process in 2022. The company produced 3.89 billion kWh of clean energy, reducing CO2 emissions by 14,700 t from photovoltaic energy and 2.59 million t from hydropower. By 2030, clean energy is expected to exceed 80.00 % of installed capacity, reaching 20.00 million kW. This study predicts the emissions of pollutants and CO2 from power plants based on different development scenarios. Under comprehensive Scenario, CO2 emissions nearing zero by 2060, while SO2 and NOx emissions decrease by 97.29 % and 94.69 %. Cost-effectiveness ratio (CER) analysis shows initial increases to 1.80 by 2035 due to investments in clean energy and Carbon Capture, Utilization, and Storage (CCUS) technology, then declines to 0.37 by 2060 with technological maturity and economies of scale. The study proposes a strategic low-carbon development plan emphasizing renewable energy expansion, technological innovation, and policy support to achieve sustainable power generation and improve market competitiveness.
Accurate species-level diagnosis of dermatophytes, particularly Trichophyton rubrum, is important for guiding targeted antifungal therapy and improving the management of recurrent or atypical superficial mycoses. However, routine microscopy has only moderate sensitivity and cannot resolve fungal species; fungal culture is time-consuming, and real-time quantitative PCR (qPCR) requires costly instrumentation. To develop and clinically evaluate CRI-RUB, a CRISPR-Cas12a-based assay integrating recombinase-aided amplification (RAA) and a quantum-dot (QD) fluorescent lateral-flow strip for rapid species-level detection of T. rubrum. Analytical sensitivity and specificity were assessed using plasmid standards and a panel of common cutaneous fungi. A total of 140 clinical specimens were tested by both CRI-RUB and TaqMan qPCR. Discrepant or grey-zone qPCR results (Ct 33-34), together with a subset of concordant cases, were further arbitrated by internal transcribed spacer (ITS) sequencing to establish a composite reference standard. CRI-RUB achieved a visual limit of detection of 2.3 × 101 copies/μL and showed no cross-reactivity with other common cutaneous fungi. Among the 140 clinical specimens, CRI-RUB showed a sensitivity of 96.1% (73/76), specificity of 100.0% (64/64), positive predictive value of 100.0% (73/73), negative predictive value of 95.5% (64/67) and Cohen's κ of 0.96 compared with the composite reference standard, indicating excellent concordance. The complete workflow required approximately 85 min. CRI-RUB provides a rapid, sensitive, and specific approach for species-level detection of T. rubrum. By combining CRISPR-Cas12a detection with QD-based lateral-flow readout, this assay shows potential for near-patient or point-of-care dermatophyte diagnosis.
Despite known brain alterations in insomnia-particularly prevalent in older females-how it affects sleep-dependent glymphatic clearance remains understudied due to in vivo human measurement challenges. To investigate altered neurofluid dynamics in women with insomnia using indirect neuroimaging markers. Prospective. 46 healthy controls (HC; 56.3 ± 5.5 years) and 28 females with insomnia disorder (ID; 58.2 ± 4.9 years). 3.0 T, 3D T1-weighted magnetization-prepared rapid acquisition gradient echo, resting-state fMRI using gradient-echo echo-planar imaging, and multi-shell diffusion MRI using spin-echo-planar sequence. (1) Blood oxygen level dependent cerebral spinal fluid (BOLD-CSF) coupling measuring temporal coordination between neurovascular and CSF oscillations, (2) diffusion tensor image analysis along the perivascular space (DTI-ALPS) quantifying directional diffusivity in periventricular white matter, (3) choroid plexus (ChP) volume reflecting morphology of primary CSF-producing structures, and (4) nucleus basalis of Meynert (NBM) volume evaluating cholinergic system integrity potentially relevant to vascular regulation; (5) all participants completed self-reported sleep measures, including the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), and Fatigue Severity Scale (FSS), and also underwent cognitive function testing. Analysis of covariance evaluated between-group differences controlling for demographic and clinical covariates. Relationships with cognitive and sleep scores were assessed using partial correlations, stratified by group only when significant interaction effects were detected. Multiple comparisons were false discovery rate corrected (p < 0.05). Classification model performance was evaluated using the area under the receiver operating characteristic curve (AUC). Model comparisons were performed using DeLong's tests (ΔAUC) and stepwise likelihood ratio tests (LRT) to assess classification gain and the independent incremental contribution of each biomarker; all tests were two-sided with α = 0.05. Compared to controls, insomnia patients showed significantly reduced BOLD-CSF coupling (-0.18 ± 0.20 vs. -0.32 ± 0.17), indicating altered temporal coordination between neurovascular and CSF dynamics. ChP volume was significantly enlarged in the insomnia group (1.72% ± 0.42% vs. 1.55% ± 0.39% of total intracranial volume), potentially reflecting compensatory CSF production upregulation, inflammatory changes, or vascular remodeling. NBM volume was significantly reduced in insomnia patients (201.75 ± 17.66 vs. 217.47 ± 21.04 mm3), suggesting cholinergic system alterations. In contrast, the DTI-ALPS index did not differ between groups (p = 0.85). BOLD-CSF coupling positively correlated with PSQI (r = 0.34), ISI (r = 0.41), and FSS (r = 0.40); ChP volume positively correlated with ISI (r = 0.32) and FSS (r = 0.35) (all FDR-corrected). A dataset consists of 74 participants (46 HC and 28 ID) were included, the four-marker classification model achieved moderate performance (AUC = 0.785, accuracy = 71.9%). Multiple indirect neuroimaging markers potentially related to neurofluid dynamics were altered in middle-aged and older women with chronic insomnia, except for DTI-ALPS. These findings include altered neurovascular-CSF coordination, ChP enlargement, and cholinergic system volume reduction. 2. Stage 2. Insomnia is common in middle‐aged and older women, but its effect on the brain's waste‐clearance system, known as glymphatic system, remains unclear. Using several magnetic resonance imaging (MRI) to compare 28 women with insomnia and 46 women who slept well. Three measures differed between the groups. Insomnia group showed weaker coordination between brain activity and cerebrospinal fluid flow, a larger choroid plexus (the tissue that makes this fluid), and a smaller nucleus basalis of Meynert (a region that helps control brain blood flow). A fourth, diffusion‐based measure did not differ. These results link insomnia to measurable changes in how the brain manages its fluids.
Oncolytic viruses represent a promising class of anticancer therapeutics, and rapid, accurate quantification of viral titers is critical for ensuring both efficacy and safety during clinical development. Conventional viral titering methods, such as 50% cell culture infectious dose (CCID50), are time-consuming and limited in sensitivity, thereby restricting their application in real-time clinical monitoring. This study aimed to develop and validate a rapid titer assay for oHSV2-PD-L1/CD3-BsAb, an oncolytic herpes simplex virus expressing a PD-L1/CD3 bispecific antibody, to support preclinical and clinical monitoring. A dual-reporter cell system was established using Vero-PD-L1-GFP (Vero cells expressing PD-L1 and GFP) cells as target cells and Jurkat-NFAT-Fluc (Jurkat cells expressing NFAT and Fluc) cells as effector cells. Viral infection activates the NFAT signaling pathway, driving Fluc expression, thereby enabling rapid quantification of infectious virus. The assay was evaluated for specificity, limit of detection (LOD), and lower limit of quantification (LLOQ), and compared with the conventional CCID50 method. Its applicability was further assessed using clinical simulation samples, including PBMCs and swabs. The rapid titer assay accurately quantified virus at 103 CCID50/mL after 8 h of incubation, consistent with CCID50 results, while extending the incubation to 18 h improved the LLOQ to 102.5 CCID50/mL, demonstrating enhanced sensitivity. The assay exhibited high reproducibility and stability in both PBMC and swab samples, enabling reliable quantification of low-titer virus in complex biological matrices. Compared with CCID50, the method substantially reduced assay time (from 3-5 days to 8-18 h) while improving sensitivity and specificity. The developed rapid titer assay for oHSV2-PD-L1/CD3-BsAb provides a sensitive and specific platform for viral quantification. It offers a valuable tool for oncolytic virus development, production quality control, and clinical monitoring, facilitating efficient safety evaluation and risk management in ongoing and future clinical applications.
This study aimed to examine the associations of oral frailty, social support, and technophobia with depressive symptoms in Chinese older adults with chronic diseases. A hospital-based cross-sectional study was conducted from February to April 2025 in selected departments of a tertiary hospital in Anhui Province, China. Participants were adults aged 60 years or older with at least one physician-diagnosed chronic disease. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9), with a score of ≥ 10 indicating depressive symptoms. Oral frailty, social support, and technophobia were measured using the Oral Frailty Index-8 (OFI-8), Oslo Social Support Scale-3 (OSSS-3), and Technophobia Scale, respectively. Pearson correlation analysis was used to examine correlations between PHQ-9 total scores and the main study variables. Multivariable binary logistic regression was performed to examine factors associated with depressive symptoms, adjusting for demographic, social, health-related variables, and the number of chronic diseases. A total of 525 participants were included, and 108 participants (20.6%) had depressive symptoms. PHQ-9 total scores were positively correlated with OFI-8 total scores (r = 0.616) and technophobia total scores (r = 0.635), and negatively correlated with OSSS-3 total scores (r = - 0.576). In the fully adjusted logistic regression model, oral frailty was associated with higher odds of depressive symptoms (adjusted OR = 7.148, 95% CI: 2.740-18.653), higher social support was associated with lower odds of depressive symptoms (adjusted OR = 0.264, 95% CI: 0.177-0.396), and higher technophobia was associated with higher odds of depressive symptoms (adjusted OR = 1.246, 95% CI: 1.158-1.340). In the technophobia subdomain model, techno-anxiety and privacy concerns were significantly associated with depressive symptoms, whereas techno-paranoia was not independently associated with depressive symptoms. Oral frailty, social support, and technophobia remained associated with depressive symptoms among Chinese older adults with chronic diseases after adjustment for potential confounders. These findings suggest that oral functional status, perceived social support, and technology-related concerns may be considered in multidimensional assessment of depressive symptoms in this population. Longitudinal and intervention studies are needed to clarify causal relationships and intervention effects.
Spore-forming Bacillus species are increasingly explored for their potential applications in antimicrobial activity and environmental bioremediation. However, comparative functional characterization of closely related strains with respect to biofilm inhibition, pathogen suppression, and ammonia removal remains limited. In this study, two bacterial isolates (PWR04 and SHPS6) were characterized using morphological, biochemical, and 16S rRNA gene sequencing analyses. Spore-forming ability, stress tolerance (bile salt and pH), antibiotic susceptibility, antibacterial activity, biofilm inhibition, auto-aggregation, and ammonia-removal efficiency were systematically evaluated. Statistical analyses included t-test, one-way ANOVA, and two-way ANOVA. Both isolates were identified as members of the Bacillus cereus group, showing ≥ 99.80% sequence similarity. High spore survival was observed under bile salt (82.21%-95.99%) and acidic conditions (81.60%-99.48%). No inhibition zones were detected for ampicillin or cloxacillin, whereas inhibition zones reached up to 25.33 mm for chloramphenicol. Limited antibacterial activity was detected in agar well diffusion assays, whereas biofilm inhibition reached 91.79% in PWR04 and 90.00% in SHPS6 under specific conditions. Auto-aggregation increased over time, reaching 76.24% in PWR04 and 71.84% in SHPS6 at 24 h. Ammonia-removal efficiency was significantly affected by concentration and time (p < 0.01), with maximum values of 20.00% (PWR04) and 18.00% (SHPS6). Although both isolates showed multifunctional antimicrobial and bioremediation traits, each displayed β-hemolysis on sheep blood agar-a virulence-associated phenotype that constitutes a clear safety concern. Genome-based screening for hemolysin and enterotoxin genes and antimicrobial resistance determinants, together with in vivo validation, is therefore required before application.
Rapid digital transformation is reshaping health care, but many digital initiatives struggle to deliver sustained organizational value when they are introduced as stand-alone technologies rather than as part of an institutional strategy. In Saudi Arabia, Vision 2030 has intensified pressure on academic medical centers to strengthen digital capability, localize innovation, and reduce dependence on externally driven solutions. This study aimed to examine organizational factors shaping digital health innovation at King Saud University Medical City (KSUMC) and to develop a preliminary strategic planning framework for a digital health innovation hub tailored to that setting. We conducted a qualitative exploratory case study at KSUMC between April and June 2025. Fourteen stakeholders from clinical, administrative, research, governance, educational, and innovation-related roles were recruited using maximum variation purposive sampling. Semistructured interviews were audio-recorded, transcribed verbatim, and analyzed using reflexive thematic analysis. Reporting was guided by the COREQ (Consolidated Criteria for Reporting Qualitative Research). Diffusion of innovation theory and systems thinking informed interpretation, while a context-actor-mechanism-outcome lens was used to examine how institutional conditions shaped innovation processes. No patient data were collected. Five interrelated themes were identified. First, leadership support existed at a symbolic level, but middle-management translation and risk tolerance were inconsistent. Second, innovation was constrained by workload, fragmented systems, and weak operational support, which meant that project work was often treated as discretionary rather than embedded. Third, knowledge transfer and commercialization pathways were fragmented; participants repeatedly described unclear routes from idea generation to prototyping, regulatory review, and market engagement. Fourth, incentives and innovation capability were misaligned with institutional expectations, particularly for clinicians and trainees. Fifth, Vision 2030 created strategic legitimacy and momentum, but participants also cautioned that an overreliance on consultant-led or vendor-led approaches could weaken internal capability building. These findings informed a preliminary framework centered on governance, knowledge transfer, partnership structures, workforce development, and phased implementation rather than a validated institutional model. At KSUMC, digital health innovation is shaped not only by technology availability but also by organizational culture, intermediary structures, governance design, and the extent to which innovation work is made operationally feasible. The framework proposed here should therefore be understood as a preliminary planning model derived from one qualitative case study. Its main contribution is to specify how knowledge transfer, commercialization, and institutional capability building can be integrated into a digital health strategy within a Saudi academic medical center.
Combining digital and traditional treatment elements as part of a hybrid care delivery model may strengthen the sustainability of mental health care. However, implementation problems permeate efforts of digitalizing routine care. The objective of this formative study is to explore current unmet stakeholder needs and the potential value of hybrid care models for the treatment of severe mental disorders, in order to guide further research and inform practical implementation strategies. We applied Step Up, an early health technology assessment (eHTA) framework. We performed (a) a template analysis of qualitative data from a stakeholder workshop mapping unmet needs, potential effects of hybrid care models, and conditions relevant for implementation and (b) exploratory economic simulations of the impact of increasing video consultation use in routine services on quantitative sustainability parameters. The template analysis revealed stakeholder-anticipated value from hybrid care models across all domains: patient, clinician, and next-of-kin user experiences; clinical variables; organizational setup; and economy. Two recommendations for enhancing implementation were identified: promoting nuanced perceptions of digitalized care and developing clinician incentives. The simulations demonstrated that a moderate increase in video consultations may impact clinical capacity, as well as economic and environmental sustainability. This study provides early decision support concerning hybrid care models during the conceptual stage of service innovation. It reveals that conservative changes toward digitalized practices can create new opportunities for organizing services and have a substantial impact on sustainability parameters. Successful implementation across clinical contexts requires continuous consideration of the clinician user perspective, starting from the conceptual phase.
This study explores the risk of delayed psychomotor development (PMD) in children treated for severe acute malnutrition (SAM) in the Democratic Republic of Congo. The present research is a sub-study of the EfRAMAS clinical trial conducted in health zones in the province of Kasaï Oriental. Children aged 6-59 months with SAM according to WHO criteria and no congenital malformations affecting child development were enrolled in the study. The risk of delayed psychomotor development was assessed among repeated cross-sectional samples of children at admission, discharge and 6 months after recovery, using the Ages and Stages Questionnaires (ASQ3). Mixed-effects linear regression with health center as random intercept was performed to identify potential predictors of the risk of psychomotor delay in children. A total of 413 children were included at admission, 143 at discharge and 581 at 6 months post-discharge. At admission, the risk of delayed psychomotor development was greatest in the domains of fine motor skills (21.3%), gross motor skills (23.7%) and problem solving (21.5%). At discharge, the risk of delay was considerably reduced, with 0% risk of delay in communication, while the three most affected domains hovered around 2%. At 6 months post-discharge, the risk of delay in gross motor skills and problem-solving was still present in over 10% of children. Age, sex, MUAC < 115 mm or WHZ < -3 as admission criteria, breastfeeding, episodes of illness during treatment, measles vaccination, mother's education level, and living in a female-headed household were predictors of the risk of psychomotor development delay. Globally, gross and fine motor skills and problem solving were the domains most affected for children with SAM. Regarding our findings, we recommend investing in the integration of children's psychosocial stimulation within the undernutrition management care pathway by trained health care workers, as well as in caregivers' parental skills. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Network (ISRCTN15258669). Registered 25/01/2022.
The wheat powdery mildew fungus Blumeria graminis f. sp. tritici (Bgt) is a devastating pathogen for wheat production in the core wheat-producing regions of China, including Hebei, Henan, and Shandong provinces. The demethylation inhibitor fungicide tebuconazole has been a cornerstone for Bgt management. However, its intensive and prolonged application has led to the development of resistance, reducing its field efficacy. This study presents findings on the spatiotemporal dynamics of tebuconazole resistance in Bgt populations across these provinces, reveals the resistance mechanisms, and describes applications for sustainable resistance management. The sensitivity of Bgt populations to tebuconazole in China's major wheat-producing regions gradually decreased from 2007 to 2024. Despite the absence of highly resistant isolates, the frequency of moderately resistant isolates increased over time, exceeding 40% by 2020. Compared with sensitive isolates, resistant isolates exhibited greater ecological fitness, evidenced by superior pathogenicity, sporulation capacity, and competitive ability, suggesting that they could become dominant in wheat fields. The resistance mechanisms of Bgt to tebuconazole are attributed to multiple mechanisms, including target-site CYP51 gene mutations, enhanced efflux pump activity, and upregulation of detoxification enzymes such as glutathione S-transferase and cytochrome P450 monooxygenase. Field trials revealed that tebuconazole applied alone exhibited poor control efficacy against wheat powdery mildew. In contrast, its combination formulations with fungicides of different modes of action, such as fluazinam-tebuconazole and cyflufenamid-tebuconazole, maintained significantly better control efficacy. Understanding the spatiotemporal distribution, resistance mechanisms, and field efficacy of tebuconazole against Bgt is crucial for developing effective resistance management strategies and optimizing chemical control measures.
Cyclodextrins are cyclic carbohydrates capable of forming inclusion complexes with a wide range of molecules, thereby improving their solubility, stability, and bioavailability. Traditionally, cyclodextrins have been extensively applied in the food industry owing to their functionality and safety profile. However, their use in cosmeceuticals, a rapidly growing area that lies between cosmetics and pharmaceuticals, remains relatively underexplored. Given the increasing demand for scientifically validated, high-performance skincare formulations, cyclodextrins are emerging as promising compounds that can address several formulation challenges. The principal question is whether cyclodextrins represent a worthwhile investment for the future of cosmeceutical innovation. This article aims to provide a comprehensive, evidence-based overview of the current and potential roles of cyclodextrins as safe, effective, and multifunctional carriers in advanced skincare science. The current state of research on the application of cyclodextrins in cosmeceutical formulations is evaluated, with particular focus on active ingredients commonly used in dermatological care, such as vitamins A and C, coenzyme Q10, kojic acid, arbutin, and UV filters. For each of these compounds, relevant in vitro, in vivo, and clinical studies are reviewed in order to assess how cyclodextrin complexation influences key parameters, including solubility, stability, controlled release, skin penetration, and the reduction in adverse reactions. In addition, the use of cyclodextrins in the treatment of dermatological conditions such as acne, psoriasis, and rosacea is examined, highlighting their potential value, particularly in combination with azelaic acid and salicylic acid, well-known agents used to manage these conditions. Beyond their advantages, the limitations and challenges that currently restrict broader implementation of cyclodextrins in cosmeceuticals are also discussed, including cost variability, solubility constraints with certain substances, formulation incompatibilities, and regulatory considerations. Future perspectives are explored, particularly the development of novel modified and amphiphilic cyclodextrins, as well as their integration into nanotechnology-based systems and into intelligent, personalized skincare.
Chronic atrophic gastritis (CAG) is a pivotal precancerous condition in gastric carcinogenesis, with progression typically following the classic Correa cascade. Although Helicobacter pylori (H. pylori) infection is widely recognized as the principal etiological factor, the persistence of gastric cancer (GC) risk in a subset of patients after successful eradication suggests that gastric microbiota dysbiosis may also contribute to CAG progression. In recent years, high-throughput sequencing technologies have revealed distinct microbial restructuring in patients with CAG, characterized by decreased microbial diversity, depletion of commensal taxa, and enrichment of opportunistic pathogens. These compositional changes are accompanied by metabolic dysfunction, activation of inflammatory signaling pathways, and disruption of immune homeostasis, which may contribute to a microenvironment permissive for precancerous transformation of the gastric mucosa. Probiotics and related microbiome-based therapeutics, including prebiotics, synbiotics, and postbiotics, have emerged as promising adjunctive strategies for H. pylori eradication and disease management. Their beneficial effects are mediated through multiple mechanisms, including remodeling of the microbial community, inhibition of pathogen colonization, modulation of host immune responses, and restoration of mucosal barrier integrity. However, whether these interventions can reverse established atrophic or metaplastic lesions remains unclear. In addition, how strain specificity, dose dependency, and interindividual heterogeneity influence clinical efficacy has yet to be fully elucidated. In this review, we summarize the compositional and functional features of gastric microbiota dysbiosis in patients with CAG, as well as the mechanisms and clinical applications of microbiome-based interventions. We further highlight current limitations in the field and discuss future directions for precision microecological therapies integrating multi-omics approaches, engineered probiotics, and artificial intelligence. These advances may provide a theoretical framework and practical guidance for the diagnosis and management of CAG and the prevention of GC.
Hypertension and diabetes are rising causes of morbidity and mortality in sub-Saharan Africa, yet rural community-level data remain limited. National surveys often obscure local variation, hindering targeted prevention. We conducted a population-based cross-sectional study in Kakum-Kombewa, Siaya County, Kenya (Dec 2024-Jun 2025). Multistage sampling identified 816 households, yielding 1,046 adults aged ≥ 18 years. Participants underwent household screening for blood pressure, random blood glucose, and anthropometry. Individuals with screened positive values were referred to linked primary healthcare facilities for diagnostic confirmation. Prevalence was estimated using descriptive statistics, and associations were assessed with chi-square tests and generalized linear models. The prevalence of known hypertension, diabetes, and comorbidity was 13.9%, 8.7%, and 4.9%, respectively. Diagnostic confirmation identified an additional 4.2% newly confirmed hypertension, 2.3% newly confirmed diabetes, and 2.5% newly confirmed comorbidity, yielding total prevalence estimates of 18.1% (95% CI: 15.8-20.6), 11.0% (95% CI: 9.2-13.1), and 7.4% (95% CI: 5.9-9.2). Risk factors included age ≥ 50 years, overweight/obesity, central adiposity, family history, and physical inactivity. Female sex, central adiposity, low activity, and family history remained significant predictors in multivariable models. This study reveals a substantial burden of both known and previously undiagnosed hypertension and diabetes in rural Western Kenya. Community-based screening, followed by referral and confirmatory testing, was effective in detecting new cases and identifying poor disease control among those with prior diagnoses. Strengthening routine NCD screening and linkage to primary care could improve early detection and management in similar rural settings.