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Candidate Scaffolds for the Treatment of Stress Urinary Incontinence: A Narrative Review
No full textAims: Biodegradable scaffolds have emerged as a promising alternative to polypropylene (PP) meshes for the treatment of stress urinary incontinence (SUI) due to their biocompatibility and potential for tissue regeneration. Methods: A narrative review was conducted focusing on articles published within the last 10 years. Results: Polymeric materials such as small intestinal submucosa (SIS), poly(lactic acid) (PLA), poly(Chitosan-g-lactic Acid) (PCLA), poly(glycolic acid) (PGA), and poly(lactic-co-glycolic acid) (PLGA) have been explored for their ability to provide mechanical support, facilitate tissue repair, and degrade in a controlled manner. Each material offers unique advantages, such as SIS\u27s enhanced biocompatibility, PLA\u27s mechanical strength, and PGA\u27s rapid degradation. However, challenges remain in optimizing these materials for clinical use, including controlling degradation rates, minimizing inflammatory responses, and addressing issues related to scaffolds\u27 mechanical properties. Moreover, integrating adipose-derived stem cells (ADSCs) has shown promise in enhancing tissue regeneration and angiogenesis. The primary obstacles preventing clinical implementation have been premature scaffold degradation before adequate tissue ingrowth and insufficient tensile strength in dynamic pelvic environments. Conclusions: This review discusses the current state of biodegradable scaffolds for SUI treatment, highlighting their potential benefits, ongoing challenges, and the need for further research to ensure their safety and efficacy in clinical applications
Using Performance Frontiers to Evaluate Non-Or Anesthesia (Nora) Efficiency
No full textIntroduction: In high-cost, high-revenue operating room (OR) suites, dashboards displaying key performance indicators are commonplace to optimize efficiency. Given the significant successes attained, further gains may risk compromising safety. In contrast, challenges unique to non-operating room anesthesia (NORA) sites have hindered operational efficiency. Existing productivity evaluation frameworks often fall short in guiding strategic and tactical improvements in NORA delivery. Performance frontiers have proven effective in evaluating OR systems, but their application to NORA remains unexplored. This study applies performance frontiers to assess NORA site efficiency and formulates potential operational strategies. Methods: We evaluated anesthesia billing records at our primary hospital from 1 April 2022 to 30 March 2023. Cases from operating room and NORA locations were included, except for sites with irregular volume or financial arrangements. We included only non-holiday weekdays, defining NORA block time as 7 AM to 5 PM. For each room, we calculated under-utilized (time with no anesthesia billing) and over-utilized minutes (time billed outside of NORA block hours). Data for each location were plotted as rolling 4-week sums, normalized to scheduled NORA block time. Performance frontiers were then developed and plotted. Results: Over 246 non-holiday weekdays, 42,424 cases had billable minutes during NORA block time, comprising 20,003 (47.2%) NORA cases and 22,421 (52.8%) OR cases. Performance frontiers revealed significant variability, with nonparametric tests confirming statistical significance and non-equivalence. Discussion: Performance frontiers reveal substantial efficiency variability across NORA sites, underscoring the need for targeted interventions. Some sites matched OR efficiency levels, while others showed substantial differences, particularly those with high variability and urgency. Efficient sites can leverage performance frontiers to optimize resource allocation, while inefficient locations may benefit from a shared anesthesia resource pool for real-time resource allocation. Performance frontiers provide a novel approach for operational leaders to make more effective strategic decisions
The Effects of Space Radiation on the Transcriptome of Heart Right Ventricle Tissue
No full textDeep space represents a challenging environment for human exploration and can be accompanied by harmful health-related risks. We aimed to assess the effect of simplified galactic cosmic ray simulated (simGCRsim) and gamma (γ) ionizing radiation (IR) on transcriptome changes in right ventricular (RV) tissue after a single low dose (0.5 Gy, 500 MeV/nucleon) full body exposure in C57BL/6J male and female mice. In females, no differentially expressed genes (DEGs) and only 2 upregulated genes in males exposed to γ-IR were revealed. In contrast, exposure to simGCRsim-IR resulted in 4 DEGs in females and 371 DEGs in males, suggesting longer-lasting and sex-biased DEGs after simGCRsim-IR. Overrepresentation analysis of DEGs in simGCRsim-IR males revealed significant enrichment in pathways related to muscle contraction, hypertrophic cardiomyopathy, oxytocin release, the regulation of cytoskeleton, and genes associated with Alzheimer’s, Huntington’s, and Parkinson’s diseases. Our results suggested the RV transcriptome exhibits distinct responses after exposure based on both the IR and sex
Persistent Imbalance: Women\u27s Representation in North American Pediatric Cardiology Leadership Roles
No full textBackground: Despite recent gender parity of physicians entering pediatric cardiology, representation of women leaders lags their male colleagues. Objectives: We sought to better understand the variation in women in leadership roles in pediatric cardiology. Methods: The gender of physicians in 16 prespecified leadership positions was collected by survey between July 2022 and January 2023 from pediatric cardiology programs with \u3e5 cardiologists in North America. We analyzed the association of women leaders with center size (based on surgical volume), geographic region, presence of categorical fellowship program, and gender of division chief and department chair. Results: Across 99 centers, a median of 13 (Q1-Q3: 10-15) roles/center were identified. Women held 36.8% of all leadership roles and 35.1% of cardiology-specific roles. Only 13% of pediatric cardiology chiefs were women. Their programs had more women in subsection leadership roles than male-led centers (47% vs 36%, P = 0.028). A minority of leadership posts were shared among 2 physicians, yet more women than men shared their roles (5.4% women vs 2.5% men, P = 0.010). More men than women have dual leadership positions (15.1% men vs 9.9% women, P = 0.012). We found no association of center size, geographic region, presence of fellowship program, or gender of department chair with percent women leadership. Conclusions: Women hold fewer leadership positions across most subsections of pediatric cardiology programs, with more equitable distribution at centers led by women division chiefs. Women are more likely to share a leadership position with another cardiologist and less likely than men to hold more than 1 leadership post concurrently
Interoperability as a Catalyst for Digital Health and Therapeutics: A Scoping Review of Emerging Technologies and Standards (2015–2025)
No full textBackground: Interoperability is fundamental for advancing digital health and digital therapeutics, particularly with the integration of technologies such as artificial intelligence (AI), blockchain, and federated learning. Low- and middle-income countries (LMICs), where digital infrastructure remains fragmented, face specific challenges in implementing standardized and scalable systems. Methods: This scoping review was conducted using the Arksey and O’Malley framework, refined by Levac et al., and the Joanna Briggs Institute guidelines. Five databases (PubMed, Scopus, IEEE Xplore, ACM Digital Library, and Google Scholar) were searched for peer-reviewed English language studies published between 2015 and 2025. We identified 255 potentially eligible articles and selected a 10% random sample (n = 26) using Stata 18 by StataCorp LLC, College Station, TX, USA, for in-depth data charting and thematic synthesis. Results: The selected studies spanned over 15 countries and addressed priority technologies, including mobile health (mHealth), the use of Health Level Seven (HL7)’s Fast Healthcare Interoperability Resources (FHIR) for data exchange, and blockchain. Interoperability enablers include standards (e.g., HL7 FHIR), data governance frameworks, and policy interventions. Low- and Middle-Income Countries (LMICs) face common issues related to digital capacity shortages, legacy systems, and governance fragmentation. Five thematic areas were identified: (1) policy and governance; (2) standards-based integration; (3) infrastructure and platforms; (4) emerging technologies; and (5) LMIC implementation issues. Conclusions: Emerging digital health technologies increasingly rely on interoperability standards to scale their operation. Although global standards such as FHIR and the Trusted Exchange Framework and Common Agreement (TEFCA) are gaining momentum, LMICs require dedicated governance, infrastructure, and capacity investments to make equitable use feasible. Future initiatives can benefit from using science- and equity-informed frameworks
Impact of Acute Alcohol Intoxication and Alcohol Dependence on Outcomes After Subarachnoid Hemorrhage
No full textBackground: Non-traumatic subarachnoid hemorrhage (SAH) is most commonly caused by a ruptured aneurysm. Risk factors for rupture include hypertension, smoking, and substance use, but the relationship between alcohol use and clinical outcomes after SAH is poorly understood. The objective of this population-based, longitudinal, study is to characterize the relationships between alcohol use, alcohol dependence, and adverse clinical outcomes following SAH. Methods: Patients with alcohol use disorder (International Classification of Disease 10th Revision Diagnostic Code F10) in the TriNetX Research Network were compared to patients with no substance use disorders (None of F10-F19). Short-term (30-day) outcomes were assessed among patients with blood alcohol concentrations tested on the day of SAH. Outcome frequencies and Cox proportional hazard models used propensity score matching on demographics, comorbidities, blood counts, substance use, and SAH severity. Results: We identified 216,894 patients with non-traumatic SAH. Of these, 11,648 were tested for alcohol and 27,079 patients had alcohol use disorder. Blood alcohol levels of 1–100 mg/dL and above at the time of SAH were associated with decreased 30-day mortality in acute alcohol use compared to 0 mg/dL, and alcohol concentrations of 201–300 mg/dL and higher were further protective relative to 1–100 mg/dL. Patients with alcohol use disorder exhibited an increased hazard of mortality (HR = 1.175 [95% CI: 1.129, 1.223]; p \u3c 0.0001) compared to patients with no substance use disorders (n = 151,377). Patients with severe alcohol dependence had an even higher hazard of mortality compared to patients with mild/moderate use disorder (HR = 1.139 [1.128, 1.150] p \u3c 0.0001). Conclusions: In patients with non-traumatic SAH, alcohol in the blood at the time of SAH is protective against 30-day mortality, and increased alcohol concentration adds increased protection. Paradoxically, alcohol use disorder leads to a worsening of clinical outcomes, including mortality. There appears to be a significant dose-dependent effect of severity of alcohol dependence on mortality
Long-Term Pathway Activation in Cardiac Ventricular Tissues After Gamma and Simgcrsim Irradiation
No full textSpace radiation represents a significant health risk for deep-space exploration, yet its long-term effects on cardiovascular function remain poorly understood. While our previous studies have highlighted persistent transcriptional changes in left ventricular (LV) and right ventricular (RV) tissues after a single whole-body irradiation in mice, a systems-level understanding of pathway activity deregulation is lacking. To address this gap, we applied the Pathway Signal Flow (PSF) algorithm to analyze long-term pathway activity alterations in LV and RV tissues of C57Bl/6J mice exposed to gamma radiation (100 cGy 137Cs) or the simplified Galactic Cosmic Ray simulation (simGCRsim, 50 cGy 500 MeV/n) composition of ion beams. RNA sequencing data were analyzed to assess pathway activity changes, sex-specific effects, and ventricular differences 440 days post-irradiation. We observed marked sex- and ventricle-specific differences in pathway deregulation. Left ventricular tissues in females exhibited broad signaling pathway alterations after simGCRsim exposure, particularly in immune response, cytoskeletal remodeling, and survival-related pathways (e.g., NF-κB, VEGF, and MAPK). In contrast, male RV tissues demonstrated higher pathway deregulation than LV, particularly in PPAR, NF-κB, and HIF-1 pathways, implicating metabolic disruption and survival adaptations. Furthermore, simGCRsim exposure induced greater long-term pathway perturbations than gamma rays. Our findings suggest that sex-dependent and ventricle-specific signaling alterations contribute to long-term cardiovascular risks following space irradiation. Notably, VEGF and NF-κB signaling emerge as key regulators of cardiac adaptation in females. Future studies in larger cohorts, incorporating early-stage molecular responses and broader pathway analyses, are needed to refine cardiovascular risk assessments for space travel
Cannabinoids Shift the Basal Ganglia Microrna M6a Methylation Profile Towards an Anti-Inflammatory Phenotype in SIV-Infected Rhesus Macaques
No full textEpitranscriptomic modifications [N6-methyladenosine (m6A)] regulate various diseases, including cancer and inflammation. Despite their functional relevance in neural development and differentiation, the role of m6A modifications in HIV neuropathogenesis is unknown. Using anti-N6-methyladenosine (m6A) antibody-immunoprecipitation and microarray profiling, we identified m6A modifications in miRNAs in basal ganglia (BG) of uninfected (VEH) and SIV-infected Rhesus macaques (RMs) on combination anti-retroviral therapy (ART) and either VEH-treated (VEH/SIV/ART) or THC:CBD-treated (THC:CBD/SIV/ART). HIV/SIV infection promoted an overall hypomethylated miRNA m6A profile. While THC:CBD did not significantly impact the overall hypomethylated m6A profile, specific miRNAs predicted to target proinflammatory genes showed marked m6A hypomethylation compared to VEH-treated RMs. Additionally, specific BG m6A-modified miRNAs were detected in BG-derived extracellular vesicles. Mechanistically, the DRACH motif in the miR-194-5p seed region was significantly m6A hypomethylated in THC:CBD/SIV/ART RMs. Unlike wild-type, in-vitro transfected m6A-modified miR-194-5p mimics failed to downregulate STAT1 protein expression. Further, compared to VEH/SIV/ART RMs, THC:CBD significantly reduced m6A methylation of 44 miRNAs directly involved in regulating CNS network genes. Our findings indicate that m6A epi-transcriptomic marks in the seed nucleotides can impair miRNA function and that cannabinoids may preserve it by reducing m6A methylation levels, thus providing a mechanistic explanation underlying their anti-neuroinflammatory effects in HIV/SIV infection
A Small Molecule Compound, Berberine Reduces Ige but Not Igg Production via Promoting Mirna-34a-P53 Axis
No full textCurrent therapeutic strategies for IgE-mediated diseases are limited. The drawbacks include adverse reactions, ineffectiveness, and relapses. Natural compound berberine (BBR) may combat this therapeutic gap through sustained transcriptional regulation of IgE. Human tonsil cells were cultured in the presence or absence of BBR to establish dose-dependent effects on IgE, IgG, and cell viability. IgE-producing plasma cells (U266, IgE plasma cells) and IgG-producing plasma cells (ARH-77, IgG plasma cells) were used as surrogate cells to validate dose-dependent effects on IgE and IgG production, respectively. At 10 μg/mL BBR, cell viability and proliferation were determined, and cells were harvested for protein, RNA, and miRNA and analyzed by Western blot and qPCR. BBR treatment of human tonsil samples resulted in reduced IgE production (p \u3c 0.001) with no effect on IgG levels or cell viability. BBR demonstrated sustained, dose-dependent inhibition of IgE production by IgE plasma cells (p \u3c 0.001), without affecting IgG production by IgG plasma cells. There was no significant reduction in cell viability of either cell type. Proliferation was reduced in IgE plasma cells (p = 0.02), but not IgG plasma cells. Assessment of IgE regulation and cell cycle at the RNA level revealed that BBR reduced IgE heavy chain expression and CCND1 (p \u3c 0.01), with increased the GADD45A expression of IgE plasma cells, only (p = 0.016). At the protein level, BBR increased p53 (p = 0.02) and CDKN1C (p = 0.03), and decreased CDK2 (p = 0.01) expression of IgE plasma cells, only. Investigation of miRNAs implicated in B cell and p53 regulation demonstrated increased p53 and GADD45A activator, miR-34a (p = 0.04). miRNAs that are present in IgE plasma cells allow for specific effects on B cells and cell cycle genes by BBR, that are not present in IgG plasma cells. A novel mechanism for specific suppression of IgE by BBR highlights miR-34a, involved in the p53 pathway and B cell development, and may be crucial to pathological IgE production