PurposeTo examine the relationship between fall-related mortality, disability-adjusted life years (DALY), healthcare expenditures, and research funding and determine whether fall prevention funding is proportional to fall-related public health impact.DesignCross-sectional.SettingUnited States.SampleNot applicable.MeasuresMortality rates (2018-2022) for leading causes of death were obtained from CDC WONDER. Disability-adjusted life-year (DALY) rates (2021) were obtained from the World Health Organization. Healthcare expenditures (2016) were obtained from the Institute for Health Metrics and Evaluation. Research funding data (2018-2022) were obtained from NIH ExPORTER and linked to causes of death using MeSH term searches.AnalysisLinear regression models were used with log-transformed research funding as the dependent variable and log-transformed mortality rates, DALY rates, and healthcare expenditures as predictors.ResultsFall mortality rate was 13.1 deaths per 100 000 individuals, fall-related DALY rate was 713.2 per 100 000, and fall-related healthcare expenditures were $106.6 billion. Falls ranked 12th in mortality, 8th in DALY, and 5th in healthcare costs but 20th in research funding, receiving $489 million over 5 years. Falls received significantly less funding than expected based on mortality rates (predicted $1.95 billion), DALY rates (predicted $3.27 billion) and healthcare expenditures (predicted $5.63 billion).ConclusionAlthough falls have a significant impact on older adults' health and mortality, fall research funding is disproportionately low. To reduce mortality and mitigate rising healthcare costs associated with falls, federal investment in fall prevention research should be a higher priority.
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Artificial intelligence (AI) is rapidly transforming surgical practice, with applications spanning preoperative planning, intraoperative guidance, postoperative management, and surgical education. Despite accelerating research activity, the structure, thematic evolution, and funding landscape of AI research in general surgery remain incompletely characterized. This study aimed to systematically evaluate scientific production on AI in general surgery in the United States over the past 5 years using a bibliometric approach. A bibliometric analysis was conducted following Preliminary Guideline for Reporting Bibliometric Reviews of the Biomedical Literature and Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines using Web of Science. English-language articles published between 2020 and 2025 with a U.S.-affiliated senior author and focused on AI use in general surgery were included. Publications were analyzed across five primary domains: authorship metrics, thematic endpoints, journal characteristics, country of origin, and funding patterns. Bibliometric indicators included H-index, citation counts, Article Influence Score (AIS), and Bradford's Law classification. Funding distribution across endpoints was evaluated using chi-square or Fisher's exact tests, with effect sizes estimated using Cramér's V and odds ratios. Temporal trends in endpoints and keywords were assessed using Poisson and negative binomial regression models. Fifty-nine studies met inclusion criteria, comprising 20 reviews and 39 original investigations. Scientific production increased consistently from one study in 2019 to 17 in 2023 and 16 in 2024, demonstrating sustained growth. Surgical workflow recognition (n = 19) and clinical decision support (n = 18) were the predominant research domains, representing 63% of the included literature. Temporal analysis demonstrated significant annual growth in reviews (Incidence rate ratios [IRR] 2.09, P = .002) and workflow-focused studies (IRR 1.37, P = .031). Keyword analysis revealed sustained prominence of AI and machine learning, with limited emergence of new thematic directions. Most studies reported no funding (57.6%). Although overall funding distribution did not significantly differ across application categories (P = .846), clinically actionable AI applications were significantly more likely to receive funding compared with other research areas (OR 4.0, 95% CI 1.22-13.13; P = .029). AI research in U.S. general surgery is growing but remains concentrated in workflow and decision-support domains. Funding favors clinically actionable applications, highlighting the need for broader, equity-focused AI development.
To review the literature on psychosocial care and experiences of young adults with early-onset type 2 diabetes (EOT2D), to identify what is known, current gaps and to develop recommendations to help advance psychosocial care and support for the population. We searched Medline (Ovid), Google Scholar and diabetes-specific journals for English-language articles focused on psychosocial aspects in young adults (aged 18-45 years) with EOT2D. Two people with lived experience reviewed and commented on the review findings. Growing evidence indicates that a diagnosis of EOT2D is associated with an increased risk of developing diabetes-related psychological comorbidities. Experiences of diabetes-related stigma, compounded by age-related negative preconceptions, contribute to heightening the psychosocial impact of EOT2D. Some population sub-groups appear to be more likely to experience adverse psychological effects. However, the evidence base is limited by a dearth of diverse research specifically focused on the psychosocial experiences and needs of this population (e.g., longitudinal and qualitative studies). Adults with EOT2D also experience unmet education, care and support needs relevant to optimising their psychosocial well-being and diabetes management. Overall, they require enhanced, tailored care and support that is age-appropriate, person-centred and responsive to their psychosocial needs. Digital technology and support-based strategies may help to address current gaps and improve the psychological well-being of this group, but these require further exploration. Despite the importance of psychosocial factors in young adults' diabetes management and outcomes, there remain gaps in research and practice and the need for further research, alongside changes in practice.
Surgical wounds healing by secondary intention occur if a surgical wound is not closed or dehisces following primary closure. Surgical wounds healing by secondary intention are common and adversely affect patients' quality of life. Treatment is often prolonged, complex and expensive. Negative pressure wound therapy applies a controlled vacuum to the wound and is increasingly used to promote surgical wound healing by secondary intention despite limited rigorous evidence for the clinical and cost-effectiveness of negative pressure wound therapy to augment surgical wound healing by secondary intention. Assess the clinical and cost-effectiveness of negative pressure wound therapy versus usual care (no negative pressure wound therapy) in treating surgical wounds healing by secondary intention. A pragmatic, two-arm, parallel-group, randomised controlled superiority trial. Twenty-eight UK NHS Trusts randomised adult patients with a surgical wounds healing by secondary intention to receive negative pressure wound therapy or usual care (no negative pressure wound therapy). The planned sample size was 696 participants. Participants were followed up for 12 months via weekly telephone contact to collect the primary outcome (time to healing: full cover with no scab in days since randomisation) and clinical secondary outcomes: wound healing, surgical site infection, pain, hospital re-admission, current treatment and reasons for treatment change (if applicable), reoperation, amputation, antibiotic use, death. Patient-reported outcomes (pain, health-related quality of life and resource use) were collected by postal questionnaire at 3, 6 and 12 months. Validation of the Bluebelle Wound Healing Questionnaire, a patient-reported measure of surgical site infection, was also undertaken. A cost-effectiveness decision model considering all available evidence, and a within-trial cost-utility analysis, was also undertaken to evaluate the cost-effectiveness of negative pressure wound therapy against usual care. Neither participants nor the investigators were blind to treatment allocation. Between 15 May 2019 and 13 January 2023, 686 participants were recruited, randomised and included in the analysis (negative pressure wound therapy n = 349; usual care n = 337). Most participants had a single surgical wound healing by secondary intention (n = 622, 90.7%), located on the foot (n = 551, 80.3%) or leg (n = 69, 10.1%) arising following vascular surgery (n = 619, 90.2%). Most participants had comorbidities; diabetes (n = 549, 80.0%), cardiovascular disease (n = 446, 65.0%) and/or peripheral vascular disease (n = 349, 50.9%). Median time to healing was 187 days (negative pressure wound therapy) versus 195 days (usual care), with no evidence that negative pressure wound therapy reduced the time to wound healing compared to usual care (hazard ratio 1.08, 95% CI 0.88 to 1.32; p = 0.47). Odds of re-admission, reoperation, surgical site infection and antibiotic use were slightly higher, and odds of amputation or death slightly lower for negative pressure wound therapy participants. These results were not clinically or statistically significant. Bluebelle Wound Healing Questionnaire, quality of life and wound pain scores were not statistically significantly different at any time point. Serious adverse events were rare (nine negative pressure wound therapy vs. five usual-care participants). Both cost-effectiveness analyses concluded that negative pressure wound therapy generates higher costs and marginally higher quality-adjusted life-years than usual care, although findings were statistically insignificant. The probability of negative pressure wound therapy being cost-effective was under the recommended National Institute for Health and Care Excellence cost-effectiveness thresholds. The Bluebelle Wound Healing Questionnaire was acceptable to participants, had low levels of missing data and demonstrated good levels of sensitivity and specificity in the detection of surgical site infection in surgical wounds healing by secondary intention. The trial included a high proportion of diabetic participants with foot wounds, which may affect study generalisability. Negative pressure wound therapy use for 'wound management', common in certain surgical specialties, was not assessed in this study. Negative pressure wound therapy is not clinically or cost-effective in augmenting healing in patients with surgical wounds healing by secondary intention, particularly those with comorbidities. Evaluation of methods to treat or prevent infection of surgical wounds healing by secondary intention and evaluation of negative pressure wound therapy for 'wound management' are recommended. This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 17/42/94. After an operation, most wounds are closed using stitches or staples. Some wounds cannot be closed and are left open. Some closed wounds may reopen. These ‘open’ wounds are usually left to heal slowly from the bottom up. Negative pressure wound therapy is commonly used to treat ‘open’ wounds. Negative pressure wound therapy uses a machine to apply gentle suction to a wound, which removes wound fluid, and may help keep the wound clean and perhaps aid healing. We do not know if negative pressure wound therapy is as good as, better than or worse than standard wound dressings that are also used for healing ‘open’ surgical wounds. We also do not know if negative pressure wound therapy is good value for money. There has not been enough, high quality, independent research to enable doctors and nurses to decide on the best treatment. Between May 2019 and January 2023, 686 patients with an open wound agreed to take part and were equally randomly assigned to standard dressings or negative pressure wound therapy. Most of the wounds were on patient’s feet. Most patients had diabetes, and many patients also had conditions affecting their heart and/or blood vessels. We collected wound healing data, treatment information and health outcomes for each participant for a year. We found no clear evidence that negative pressure wound therapy provided any significant benefits for patients and specifically that negative pressure wound therapy did not reduce the time it took for wounds to heal compared to standard wound care. Negative pressure wound therapy was also more expensive than standard dressings and so was not likely to be a good use of healthcare resources. Patients and doctors will be able to make more informed decisions about which dressing to use to help wounds heal. The National Health Service can save money by recommending the use of standard dressings for open wounds instead of using the more expensive negative pressure wound therapy.
BackgroundResearch on the mitochondrial genome variants of Alzheimer's disease (AD) in Chinese populations is lacking.ObjectiveThe study aimed to identify mitochondrial DNA (mtDNA) variants associated with AD risk and explore the relationship between mtDNA variants and plasma biomarkers in AD patients.MethodsWhole genome sequencing was performed in 1509 AD patients and 2010 controls from the Chinese population. mtDNA variants were called according to GATK's best practice mitochondrial pipeline. We evaluated the association of AD risk with mtDNA variants and mitochondrial haplogroup. Common variant (MAF≥0.01) based association analysis and gene-based tests of rare variants (MAF<0.01) were carried out with PLINK 1.9 and SKAT-O, respectively. Spearman correlation analysis was performed to assess the association between the burden of mtDNA variants and plasma biomarker levels.ResultsThe frequency of mitochondrial haplogroup G in AD group was nominally higher than control group (p = 0.019, OR = 1.48). Rare variants of MT-CYB gene were significantly enriched in controls compared to AD patients (p = 2.81 × 10-4, OR = 0.886). Besides, the control group exhibited considerably lower mRNA expression of MT-CYB in brain regions compared to AD patients in GEO database. Furthermore, the number of mtDNA indel variants per individual correlated positively with plasma Aβ42 levels.ConclusionsMitochondrial haplogroup G may serve as a risk factor for AD, while rare variants of MT-CYB gene acted as protective factor against AD in mainland China. Moreover, mtDNA variants were related to AD plasma biomarker levels. Our findings highlighted the role of mitochondrial genome variants in the pathogenesis of AD.
The COVID-19 pandemic caused 10.5 million children and adolescents worldwide to lose a caregiver, with South Africa facing this crisis alongside the world's largest HIV epidemic. This study examines how overlapping crises shape HIV-related risk behaviours and mental health among affected young people. Using longitudinal data from 389 participants aged 9-18; researchers assessed HIV risk behaviours, mental health symptoms and social risks at two time points. Half the sample (50.4%) experienced COVID-19-associated orphanhood. Overall, HIV risk behaviours were common, reported by 78.9% at baseline and 73.5% at follow-up. However, reductions occurred only among non-orphaned children; those experiencing COVID-19 orphanhood showed a slight increase in risk behaviours over time. Orphanhood, older age, bullying, domestic violence and community violence were associated with higher HIV risk, while female sex and larger households were protective. Mental health symptoms were significantly worse among children living in HIV-affected households who also experienced COVID-19 orphanhood (66.7% at baseline), a pattern that persisted at follow-up. These findings highlight the heightened vulnerability of children facing multiple, overlapping crises. Effective HIV prevention and support strategies must account for the compounded impacts of pandemic-related loss, violence and pre-existing HIV burdens to protect long-term wellbeing.
Three-dimensional (3D) printing has rapidly developed from a niche hobbyist activity into a widely accessible and indispensable technology across multiple scientific disciplines. Within microscopy, optical engineering laboratories and imaging core facilities, 3D printing enables creating customised solutions for sample holders, optical components and everyday laboratory tools that traditionally required specialised machining. By providing rapid prototyping, low-cost production and reproducibility, 3D printing facilitates innovation and efficiency in facility operations. This article provides a perspective on the possibilities, challenges, and practical aspects of implementing 3D printing within microscopy core facilities. Instead of providing technical review about 3D printing, we focus on service organisation, user engagement, resource management and community-driven repositories for design dissemination. Our aim is to share insights with those considering the implementation of 3D printing as a service for developing add-on components to ease the operation of different aspects of the machine-park driven services and those who are managing advanced instrumentation within research groups.
People with severe mental illness (SMI) are at an increased risk of infection mortality compared to the general population. Little is known about how this risk might differ across infection types, and the potential impact of sociodemographic and clinical factors. We investigated associations between SMI and infection mortality in a population-based cohort, examining variation by infection type and potential moderating factors. This retrospective matched cohort study (January 1, 2000 to December 31, 2019) used national primary care data from the UK Clinical Practice Research Datalink linked with Office of National Statistics mortality data. Competing risks regression and cause-specific hazard models assessed risk of infection mortality in people with SMI versus non-SMI controls. We examined risk across different infection types and assessed the impact of sociodemographic and clinical factors. Our cohort comprised 84 494 people with SMI matched on age, gender, and GP practice with 84 494 non-SMI controls. Fully adjusted models showed that people with SMI were more likely to die from any infection compared to non-SMI controls (adjusted hazards ratio (aHR) = 1.58, 95% CI, 1.44-1.74). Infection-specific analyses revealed increased risk of death from respiratory (aHR = 1.69, 95% CI, 1.51-1.89), gastrointestinal (aHR = 2.01, 95% CI, 1.16-3.48), and renal/urinary (aHR = 1.70, 95% CI, 1.32-2.19) infections in the SMI group. People with SMI are at increased risk of infection mortality, especially from respiratory, gastrointestinal, and renal/urinary infections. We recommend prioritizing this group for preventative measures including influenza and pneumococcal vaccines.
Healthcare providers in Ethiopia require validated tools to screen paediatric patients for suicide risk in Amharic, the official language of Ethiopia. This study aimed to examine the psychometric properties of the Ask Suicide-Screening Questions (ASQ) tool in Amharic among Ethiopian paediatric patients. This cross-sectional instrument validation study was conducted from February 2021 to September 2022. Paediatric patients were recruited from the emergency department, outpatient clinics, and medical inpatient units at Tikur Anbessa Specialised Hospital in Addis Ababa, Ethiopia. Paediatric patients (aged 10 to 18 years, inclusive) were enrolled. Participants completed the Amharic language version of the ASQ, the index test. A brief suicide safety assessment administered by a clinician served as the reference standard for validation. A total of 159 paediatric patients were enrolled; 42 youth (26%) screened positive on the ASQ, and 10 (6%) were deemed "at risk" for suicide by a clinician. Compared to the reference standard, the ASQ had a sensitivity of 1.000 (95% confidence interval [CI]: 1.000 to 1.000), specificity of 0.785 (95% CI: 0.719 to 0.851), and area under the curve value of 0.890 (95% CI: 0.860 to 0.926). While most youth (n = 117; 74%) felt comfortable being screened for suicide risk, only 52.2% (n = 83) thought medical providers should ask youth about suicide. The Amharic version of the ASQ demonstrated strong psychometric properties and appears to be a valid suicide risk screening tool in the sample population. Future research should explore the feasibility and acceptability of screening Ethiopian paediatric patients for suicide risk.
Transplantation of insulin-producing cells derived from pluripotent stem cells represents a highly promising approach for the radical treatment of type 1 diabetes (T1D). Informed by a comprehensive understanding of fetal pancreatic development, directed differentiation protocol for generating pancreatic β cells from pluripotent stem cells has been established and has achieved considerable advances, enabling the production of mature, fully functional β cells that closely recapitulate the characteristics of native pancreatic β cells. Preclinical studies have shown that the transplantation of stem cell-derived islets (SC-islets) reverses hyperglycemia in both mouse and nonhuman primate models, with a favorable safety profile. Early-phase clinical trials have further corroborated the safety and efficacy of this approach, a subset of patients with long-standing T1D achieved insulin independence, described as a "functional cure", with no serious adverse events of clinical significance reported. Despite these encouraging results, substantial challenges remain. With respect to differentiation protocols, insufficient functional maturity, pronounced cellular heterogeneity, significant batch-to-batch variability, and the challenges of large-scale manufacturing represent the principal unresolved limitations. Of particular concern, immune rejection remains a critical barrier even after the transplantation of autologous SC-islets, necessitating continued reliance on immunosuppressive therapy. Cell encapsulation and gene editing strategies have emerged as potential approaches to overcome this immunological barrier. In this review, we discuss strategies for obtaining insulin-producing cells from diverse cellular sources, summarize the latest advances in stem cell-based diabetes therapy, and propose future research directions.
Parkinsonian disorders, including Parkinson's disease, Lewy body dementia, multiple system atrophy, and progressive supranuclear palsy, are progressive neurodegenerative conditions with no treatment options to slow disease progression. This systematic review provides an overview of evidence of disease-modifying therapies that have been evaluated in clinical studies across these disorders, based on a comprehensive literature search up to May 2025. Eligible studies included clinical trials investigating pharmacological interventions aimed at slowing disease progression. Most clinical development has focused on Parkinson's disease, with limited progress in other Parkinsonian disorders. Therapies targeting alpha-synuclein, such as monoclonal antibodies and small molecules, have shown target engagement but limited clinical efficacy. Glucocerebrosidase-enhancing agents, particularly ambroxol, demonstrated promising biomarker and clinical signals in early-phase trials. Glucagon-like peptide-1 receptor agonists and kinase inhibitors have yielded mixed results, with some agents progressing to phase 3 trials. Neurotrophic factors, cell survival and neuroprotective therapies, stem cell therapies, and anti-inflammatory agents remain largely investigational, with limited evidence of efficacy. Repurposed drugs, including memantine and riluzole, have shown preliminary signals of benefit, though confirmatory trials are lacking. Despite substantial research efforts, no disease-modifying therapy has been approved for any Parkinsonian disorder. The heterogeneity of disease mechanisms and the limitations of current clinical endpoints, such as the Unified Parkinson's Disease Rating Scale, underscore the need for biomarker-driven approaches and stratified trial designs. Future success will likely depend on improved patient selection, mechanistic targeting, and the integration of fluid and imaging biomarkers to demonstrate disease modification.
To enhance the comprehensive quality of gluten-free biscuits, this study employed pepsin, trypsin, and neutral protease to enzymatically hydrolyze egg yolk plasma, systematically investigating the effects of the resulting hydrolysates on the physicochemical properties, texture, and flavor in dough and final baked products. The results demonstrated that enzymatic hydrolysis effectively modified the structural components of egg yolk plasma. Hydrophilic peptides enhanced system hydration, facilitated water redistribution, reduced free water content, and consequently improved dough rheology. Concurrently, the hydrolysis of lipoproteins triggered the release of encapsulated lipids, which acted as a plasticizer within the dough matrix. During baking, these liberated lipid components mitigated excessive densification of the starch-protein network, significantly reducing cookie hardness. Moreover, lipids and peptides synergistically served as flavor precursors, promoting the generation of diverse and well-balanced volatile flavor compounds. The pepsin and trypsin treatments achieved balanced lipid release and efficient water management, yielding biscuits with uniform honeycomb structures and distinct flavor profiles. In contrast, neutral protease treatment resulted in heterogeneous phase distribution and off-flavor accumulation, leading to inferior textural and sensory attributes. This study demonstrates how enzymatic hydrolysis concurrently optimizes texture and flavor in gluten-free biscuits via structural modifications driven by lipid release and water redistribution, offering a practical basis for the rational design of functional baking ingredients. PRACTICAL APPLICATIONS: This research provides the food industry with a natural ingredient (enzyme-treated egg yolk plasma) to significantly improve the quality of gluten-free biscuits. It effectively solves the common problems of hard textures and bland tastes in gluten-free products by naturally enhancing crunchiness and rich bakery aromas. Food manufacturers can use this clean-label approach to upgrade their commercial recipes, ultimately offering consumers with dietary restrictions a much more enjoyable and flavorful snacking experience.
Over the past three decades, cell sheet technology has evolved from its original scaffold-free approach developed for epithelial cells into a versatile platform applicable to mesenchymal stromal cells (MSC). Despite numerous experimental achievements and convincing preclinical outcomes, MSC-based cell sheets have yet to reach the stage of a clinically reproducible product. This gap reflects not so much the technological limitations of the method as an incomplete understanding of its biological nature. MSC-based cell sheets represent more than a vehicle for cell delivery; they are self-organizing systems governed by intrinsic biophysical and morphogenetic principles. Their structural maturation involves (1) cellular condensation, (2) extracellular matrix deposition, and (3) contractile remodeling-processes that mirror the early phases of granulation tissue formation. Viewing the cell sheet as an in vitro model of connective tissue regeneration opens new research avenues extending beyond its therapeutic applications. This review summarizes the key milestones in the development of MSC-derived cell sheet technology, identifies major challenges and conceptual inconsistencies, and discusses the potential of studying these constructs as autonomous biological systems. The integration of mechanobiology, spatial omics technologies, and tissue engineering approaches may help reconceptualize MSC-based cell sheets both as tools for translational therapy and as a fundamental model for studying self-organizing regenerative processes.
BackgroundCerebrospinal fluid (CSF) pTau181 is used to support Alzheimer's disease (AD) diagnosis but can also rise in amyloid-negative individuals. This CSF profile (Aβ-/pTau181+) lies outside the AD continuum and complicates real-world etiologic diagnosis of neurocognitive disorders.ObjectiveTo determine the prevalence and clinical phenotype associated with the Aβ-/pTau181+ CSF biomarker profile in a real-world memory clinic population.MethodsWe screened the Mount Sinai Hospital database (2015-2024) for patients who underwent ADmark CSF biomarker testing. An Aβ-/pTau181+ group was classified using assay cutoffs (Amyloid-Total-Tau Index>1.2, pTau181 > 54 pg/mL) and compared to an Aβ+ group (Amyloid-Total-Tau Index<0.8) matched for pTau181 and total-Tau. Clinical variables were extracted via chart review, limited to notes preceding CSF and blinded to CSF results.ResultsThe Aβ-/pTau181+ group included 25 individuals (10.1% of the cohort) and had equally impaired cognition but fewer episodic memory complaints. Diagnosis was more often Lewy body or frontotemporal dementia. On neuroimaging, Aβ-/pTau181+ exhibited less white matter hyperintensity burden and temporoparietal atrophy.ConclusionsCSF Aβ-/pTau181+ is frequent in real-world evaluations of cognitive impairment and presents with fewer AD phenotypic features. Further research is required to clarify Aβ-/pTau181+ underlying biology and clinical trajectory.
This research aimed to find the optimal sterilization process for ovarian decellularized extracellular matrix (OV-dECM). OV-dECM was prepared. Four different sterilization processes, such as ultraviolet ray, 1 mg/L CuCl2 + 0.5% H2O2, 70% ethanol, and 0.1% peracetic acid (PAA), were evaluated. The sterilization efficiency and the in vitro and in vivo biocompatibility were assessed. Hematoxylin and eosin, 4',6-diamidino-2-phenylindole staining, and DNA quantitation indicated the successful production of OV-dECM. 0.1% PAA and 70% ethanol achieved better sterilization. The sterilized OV-dECM in the 70% ethanol and 0.1% PAA groups could integrate with human umbilical cord mesenchymal stem cell (between them: 7 days: p = 0.187; 10 days: p = 0.293; both p > 0.05) and keep the cell viability (CCK-8, cell counting kit-8) and cell morphology (F-actin staining). The sterilized OV-dECM in both 70% ethanol and 0.1% PAA groups had good CD31 (a neovascularization maker) fusion indexes (between them: p = 0.288; p > 0.05), while α-smooth muscle actin (another neovascularization maker) in the 0.1% PAA group was higher than that in the 70% ethanol group (between them: p = 0.012; p < 0.05). The assessment of CD68, CD86, and CD206 (macrophage phenotype makers) demonstrated that the 0.1% PAA group had better chance to promote the M1-M2 transformation of macrophage than 70% ethanol after the implantation of OV-dECM in mice. In conclusion, 0.1% PAA is the optimal sterilization process for OV-dECM with better sterilization capacity and biocompatibility.
Fasting and postprandial triglycerides (PPTG) in obese pregnancies may be stronger predictors of fetal overgrowth than glucose, making them a potential novel treatment target. Measurement of TG currently requires venipuncture in a laboratory, a barrier to collecting repeated measures to understand contributions to fetal growth. Our aim was to evaluate agreement between fingerstick capillary TG using an FDA-approved point-of-care (POC) meter and venipuncture plasma TG (vTG) during fasting and controlled fed conditions within pregnant women. Pregnant patients (n = 35) with obesity alone (59%) or GDM (41%) (BMI 33 ± 4 kg/m2) had fasting vTG and POC TG collected, within ≤ 5 min apart at 25 ± 9 weeks' gestation. A subset (n = 23) had PPTG collected at 1- and 2-h after a controlled breakfast test meal (35 ± 2 weeks). Two-way mixed effects intraclass correlations (ICC) and Bland-Altman plots determined agreement. Paired t-tests were used to compare vTG and POC TG (mean ± SD). Sixty-eight paired fasting TG and 52 paired 1- and 2-h PPTG were collected. Fasting vTG were slightly lower than POC TG (181 ± 66 vs. 192 ± 81 mg/dL), as were 1-h (225 ± 65 vs. 260 ± 76) and 2-h PPTG (227 ± 70 vs. 249 ± 77; p < 0.05 all). The ICC for fasting TG was 0.86 [95% CI: 0.78, 0.91] and 0.84 [95% CI: 0.32, 0.94] for PPTG. The mean % difference (vTG minus POC TG) was -4.6% ± 17.8% for fasting TG and -12.0% ± 12.0% for PPTG. These data suggest good agreement between vTG and POC TG in fasting and PPTG during pregnancies complicated by obesity and GDM. Our findings support the novel approach to utilising a POC TG meter, similar to a glucometer, to conveniently discern the contribution of TG and their potential targets in optimising fetal growth in pregnant patients with obesity and GDM.
ObjectiveTo evaluate whether early variability in mean corpuscular volume (MCV) during the first five days of intensive care unit stay is associated with in-hospital mortality in critically ill patients.MethodsWe retrospectively studied all adult patients treated on intensive care units (ICU) at the University Medical Center Mannheim between 2018 and 2022 with more than one MCV measurement within the first five days, including at least one on the day of admission. The primary endpoint was in-hospital mortality. MCV variation, expressed as the coefficient of variation (CV), was analyzed using generalized additive models, multivariable logistic and Cox regression.ResultsAmong 5,327 patients (median age 66 years, 38.9% female, mortality 28.3%), median MCV variation was 1.86% (IQR 1.15-2.74%). Patients with high variation (CV >2.5%) showed higher mortality rates (34.7% vs. 20.1%, p<0.0001). In a baseline-adjusted model, this association remained significant (OR 1.65, 95% CI 1.46-1.87, p<0.001). By contrast, baseline MCV at admission showed a univariat association with mortality but was not independently associated with mortality after multivariate adjustment (OR 1.02, 95% CI 0.98-1.06, p=0.31). Determinants of high variation (>2.5%) included elevated CRP, transfusion volume, respiratory disease, and fluid balance disturbances. In a second, severity-adjusted model including lactate, mean arterial pressure, and fluid balance, the previously observed association between high MCV variation and mortality was no longer significant (adjusted OR 1.16, p = 0.57, CI: 0.84-1.59).ConclusionsEarly variation in MCV during the initial five days after ICU admission is associated with in-hospital mortality in unadjusted analyses. However, this relationship is not independent of established clinical severity markers, suggesting that MCV variability reflects disease severity. Nonetheless, MCV variation may serve as a readily accessible adjunctive marker of physiological instability in critically ill patients, meriting further investigation.
The requirement for hospital admission to initiate clozapine presents a health-systems-related barrier to clozapine prescription and contributes to its underutilization in treatment-resistant schizophrenia (TRS). This study aimed to examine the clinicodemographic characteristics associated with treatment settings for clozapine initiation within a first-episode psychosis (FEP) cohort attending an early intervention in psychosis service. Secondary analysis of a retrospective cohort study of 1220 young people presenting with FEP to the Early Psychosis Prevention and Intervention Centre (EPPIC) in Melbourne between 2011 - 2017. Ninety-one cases of TRS were identified and included in the analysis, with 70 commencing clozapine, of whom 67 had a commencement setting identified. Over half (n = 36, 53.7%) commenced clozapine in the community. When compared to the hospital initiation group, the community initiation group were less likely to have had a hospital admission at baseline (odds ratio (OR) 0.26, 95%CI, 0.09-0.87) or an involuntary admission during the 2 year episode of care with EPPIC (OR 0.25, 95%CI, 0.09-0.70). The community initiated group had presented with less severe delusion scores on short form Scale for Assessment of Positive Symptoms at baseline (mean 3.08 vs 3.94, P = .031). First generation migrants were less likely to initiate clozapine in the community (OR 0.29, 95%CI, 0.09-0.97). The community initiation group also had reduced odds of clozapine discontinuation until discharge from EPPIC (OR 0.22, 95%CI, 0.06-0.76). Community initiation provides an alternative route to clozapine treatment and may be associated with a reduced rate of clozapine discontinuation.