Over the past decade, mucoadhesive polymers have gained increasing attention as key enablers in the development of advanced drug delivery systems for brain therapies. Among them, hyaluronic acid (HA) stands out for its exceptional tunability, biocompatibility and processability, positioning it as a highly promising candidate for the treatment of central nervous systems (CNS) disorders across multiple administration routes (i.e. parenteral, intranasal, oral). Current discoveries in material science and pharmaceutic formulations offer the chance to design HA based transformative carriers for brain delivery and targeting, promoting a receptor-specific uptake and precise modulation of therapeutic responses within the CNS. Herein, recent advances in the design of HA-based platforms for brain drug delivery were critically examined with a particular focus on emerging strategies for HA synthesis, functionalization and processing. By integrating advanced carrier design to innovative strategies of molecular targeting, HA based systems can enhance brain accumulation, improve safety profiles and unlock multimodal treatments. HA based platforms open new avenues to enhance drug targeting, therapeutic efficacy, and overall patient outcomes. Future challenge will be to overcome manufacturing, scalability, and translational barriers to translate this powerful platform from preclinical promise to clinical reality.

The earless monitor lizard, Lanthanotus borneensis, is a unique living fossil restricted to the island of Borneo and a possible key to understanding the evolution of the venom delivery system and secondary adaptation to water in lizards and snakes (Squamata). We sequenced and de novo assembled the genome of L. borneensis to a total size of 1.5 Gbp, 975 contigs with an N50 of 52 Mbp and an L50 of 9. The genome completeness is estimated to be 93% based on the Sauropsida OrthoDB core gene set. A genome-wide set of Lepidosauria orthologs was compiled to reconstruct and date their phylogeny, resulting in 966 protein-coding sequences amounting to a concatenated alignment of 356 kbp with 188 kbp parsimony-informative sites. Based on this phylogenomic analysis, one of the largest of its kind yet conducted for Squamata, we identified that a Toxicofera clade (comprising Serpentes, Anguimorpha, and Iguania) is supported by a plurality of gene trees, but critically, support for relationships within Toxicofera is almost equally distributed amongst the three possible topologies. Our tree-dating confirms a rapid divergence of all major squamate clades within the first 10% of squamate history, which may have contributed to rampant incomplete lineage sorting. While we did not identify positive selection on genes associated with venom components at the base of Toxicofera, our analyses found strong positive selection on the giant protein titin throughout the main clades of Toxicofera and especially in snakes. Genome-wide heterozygosity is low (HO = 0.0004), as is the effective population size towards the present. Future studies of the evolution of the venom delivery system in Toxicofera require a "true" species tree but also individual gene trees due to incomplete lineage sorting and the concomitant potential for hemiplasy. Titin-a key component of striated muscle elasticity-emerges as a target for future evolutionary studies in Toxicofera and especially in wide-gaped snakes ("Macrostomata"). The low observed genome-wide heterozygosity and the low but stable effective population size of L. borneensis during the large-scale habitat fluctuations on Sundaland in the Quaternary suggest an unexpected resilience to environmental perturbations but also a potentially lowered adaptive potential of this isolated lineage.

Arthritis, an acute inflammatory disease affecting single or multiple joints, causes irreversible damage to cartilage and bone, leading to substantial pain and economic burden. Current treatments lack specificity. Curcumin, with its anti-inflammatory and antioxidant properties, shows promise in arthritis treatment, yet its poor water solubility and low bioavailability hinder clinical use. This study investigates the efficacy of a nanocarrier-based curcumin delivery system for non-infectious arthritis. Four types of nanocarriers-liposomes, biomolecule-based nanoparticles, nanoemulsions, and improved nanocarriers-are reviewed for their ability to target curcumin delivery. These nanocarriers improve curcumin's therapeutic effects by enhancing pharmacokinetics, prolonging circulation, and protecting against degradation. Demonstrating potential in various non-infectious arthritis types, including ankylosing spondylitis, rheumatoid arthritis, juvenile idiopathic arthritis, and gout, this study underscores the efficacy of nanocarrier-based curcumin delivery systems in reducing inflammation, modulating immune responses, and alleviating disease symptoms. Future research should focus on optimizing nanocarrier design for increased bioavailability and conducting more clinical trials to validate safety and effectiveness in humans.

Health care systems should strive to achieve outcomes that matter to patients. Limited data exist on the outcomes achieved by patients with cancer with different treatment outcome preferences. To describe treatment outcome preferences among older adults with advanced cancer and explore differences in outcomes between patients prioritizing survival vs quality of life (QoL), testing the hypothesis that patients prioritizing survival would live longer, while those prioritizing QoL would have fewer treatment-related adverse effects (TRAEs) and hospitalizations. This study was an exploratory secondary analysis of the GAP70+ cluster randomized clinical trial conducted at National Cancer Institute's Community Oncology Research Program centers. Older adults (≥70 years) with incurable solid tumors or lymphoma and 1 or more impaired geriatric assessment domain(s) who were starting a new systemic cancer treatment as part of the GAP70+ trial were eligible. The primary trial took place between July 29, 2014, and March 13, 2019. All secondary analyses were conducted between January 1, 2025, and May 30, 2025. Patients were divided into 2 cohorts based on their reported preference for prioritizing extending survival vs maintaining QoL. Treatment outcome preferences, hospitalization, TRAEs, and survival at 6 months and 1 year. A total of 706 patients were included in the analysis. The mean (SD) patient age was 77.2 (5.4) years; 306 (43.3%) were female, and 400 (56.7%) were male. Gastrointestinal (244 patients [34.6%]), lung (175 patients [24.8%]), and genitourinary (109 patients [15.4%]) cancers were the most common. Only 59 patients (8.4%) preferred to prioritize extending survival over maintaining QoL, while 506 patients (71.7%) preferred to prioritize maintaining QoL. No significant associations were identified between cohorts prioritizing survival vs QoL and treatment modifications (risk ratio, 1.03; 95% CI, 0.84-1.27), grade 3 to 5 TRAEs (hazard ratio [HR], 0.84; 95% CI, 0.57-1.23), hospitalization (HR, 0.74; 95% CI, 0.39-1.41), and survival (at 6 months: HR, 0.72; 95% CI, 0.40-1.29; at 1 year: HR, 1.18; 95% CI, 0.81-1.72). In this secondary analysis of a randomized clinical trial, fewer than 1 in 10 older adults with advanced cancer participating in the trial prioritized extending survival over maintaining QoL. Patient preference for extending survival or maintaining QoL was not associated with up-front treatment modifications or downstream outcomes, suggesting a possible lack of responsiveness of the current oncology care delivery system to patient preference. NCT02054741.

Conventional chemotherapy is significantly hampered by the inherent hydrophobicity of chemotherapeutic agents, limited tumor-specific targeting, and inadequate intratumoral accumulation, all of which undermine its clinical efficacy. Nonselective distribution of cytotoxic agents leads to suboptimal drug concentrations within tumor tissues, causing systemic toxicity in healthy organs. Tumor microenvironment-responsive nanoplatforms offer a promising strategy for enhancing specificity and efficacy. This study demonstrates the successful development of a nanodrug delivery system, CASS@PTX nanoparticles, where CASS is a cinnamaldehyde-based, disulfide-containing polymer engineered with dual-stimulus responsiveness to glutathione (GSH) depletion and reactive oxygen species (ROS) amplification. This system disrupts intracellular redox homeostasis in tumor cells, triggering the release of encapsulated paclitaxel (PTX) while enhancing chemotherapeutic efficacy through redox-dependent sensitization. GSH consumption and ROS overproduction create a prooxidative microenvironment that enhances PTX-induced apoptosis. Preclinical validation using in vitro cytotoxicity assays and in vivo tumor models demonstrates potent synergistic anti-tumor effects with minimal systemic toxicity. This cascading ROS self-generation strategy represents a promising approach for overcoming multidrug resistance and improving the therapeutic outcomes of cancer chemotherapy.

Despite advances in mesothelioma treatment, malignant pleural mesothelioma (MPM) continues to present a poor prognosis due to its aggressive progression and resistance to conventional therapies. Current treatment modalities, including surgery, chemotherapy, radiation, and immunotherapy, offer limited efficacy, with a five-year survival rate of approximately 12%. To address the limitations of systemic drug delivery, this study investigates the therapeutic potential of osimertinib (OSI), a third-generation tyrosine kinase inhibitor, delivered via inhalation using poly(lactic-co-glycolic acid) (PLGA) nanoparticles. The optimized PLGA-OSI formulation exhibited an encapsulation efficiency of 43.1 ± 4.8%, drug loading of 4.4 ± 0.4%, particle size of 198.5 ± 9.3nm, and zeta potential of -17.6 ± 1.2mV. In vitro cytotoxicity assays revealed IC₅₀ values of 13.5 ± 0.1µM (MSTO-211H), 27.7 ± 0.3µM (H2452), and 8.1 ± 0.2µM (H226) after 48h. Compared to free OSI, PLGA-OSI enhanced cellular uptake, increased GFP-positive cells by 1.7-fold, and elevated fluorescence intensity by 5.3-fold. Clonogenic and scratch assays confirmed significant inhibition of cell proliferation and migration. Moreover, spheroid models demonstrated superior tumor suppression with multi-dose treatments. These findings highlight the potential of inhaled PLGA-OSI nanoparticles to improve drug delivery and therapeutic outcomes in MPM, supporting their further development as a targeted treatment strategy against this challenging malignancy.

Gastric fluids, allowing it to remain buoyant in the stomach for a prolonged period. This system is used to: Prolong gastric residence time (GRT) to improve drug absorption, especially for drugs that are absorbed in the upper part of the gastrointestinal tract. Provide a slow, continuous release of the drug at a desired rate. Better control fluctuations in plasma drug concentrations. These systems work by using effervescent reactions or low-density materials to remain buoyant in the stomach without affecting the normal gastric emptying rate. A floating drug delivery system (FDDS) is a type of gastroretentive drug delivery system designed to have a bulk density lower than While floating, the system slowly releases the drug at a controlled rate, which enhances the drug's bioavailability and therapeutic effect by increasing the time it stays in the upper gastrointestinal tract. FDDS have a lower density than gastric fluids (~1.004 g/cm³), so they float on the stomach contents. While floating, the drug is released slowly, and the system gradually empties from the stomach once the release is complete. The development of Floating Drug Delivery Systems (FDDS) represents a promising approach to achieve prolonged gastric retention and controlled drug release

Chronic respiratory diseases (CRDs) affect over 545 million individuals globally, with COPD alone causing approximately 3.2 million deaths annually. Flavonoids have shown promise in reducing lung inflammation and disease risk; however, their clinical application is hindered by poor solubility and low bioavailability. Nanocarrier-based pulmonary delivery systems offer a solution by enabling targeted, controlled release and improved solubility. This review explores the preclinical and clinical potential of flavonoid-loaded nanocarriers in mitigating CRDs by regulating inflammation and cellular senescence, while offering sustained release and enhanced biocompatibility. A comprehensive analysis of flavonoid mechanisms in modulating inflammatory pathways (e.g. NF-κB, Nrf2/Keap1) and enzymes (COX, 5-LOX, iNOS) was conducted using data from electronic databases (PubMed, ScienceDirect, Web of Science, TRIP, Springer). MeSH terms included 'Flavonoids,' 'Preclinical Studies,' 'Clinical Trials,' and 'Lung Health.' Taxonomy, epidemiology, and chemical data were verified using World Flora Online, WHO factsheets, and ChemSpider. Flavonoid-loaded nanocarriers demonstrated significant anti-inflammatory and antioxidant effects. PLGA-based systems reduced TNF-α and IL-6 levels by up to 80%. Lipid-based carriers (SLNs, NLCs) enhanced bioavailability 2-5 fold, while liposomes improved cell viability (40-50%) and reduced oxidative stress (>60%). Inhalable nanoformulations, such as quercetin achieved 3-fold higher lung concentration and 50% longer retention compared with oral formulations. Flavonoid-loaded nanocarriers, especially liposomes, show enhanced pulmonary targeting, bioavailability, and therapeutic efficacy in CRDs. Their ability to suppress inflammation and cellular aging highlights their potential as a promising nanomedicine strategy for improving lung health.

Health plan disenrollment may interrupt treatment for opioid use disorder (OUD) and overall care, increasing risk for serious outcomes, including overdose and death. There is limited evidence on the association of disenrollment with all-cause and overdose mortality after initiating medications for OUD (MOUD) treatment. To assess the association of health plan disenrollment with all-cause and overdose mortality in patients treated with MOUD. This cohort study included privately and publicly insured patients aged 16 years or older who initiated buprenorphine or naltrexone for OUD treatment between January 1, 2012, and December 31, 2021, at 3 integrated health insurance and care delivery systems in 2 US states. Patients were followed up to 2 years until December 31, 2022. Data were analyzed July 2024 to November 2025. Health plan disenrollment following MOUD initiation. All-cause mortality and drug-related and alcohol-related overdose mortality within 2 years of MOUD initiation ascertained from the National Death Index. Survival analyses were adjusted for patient sociodemographic and clinical characteristics. Among 20 011 patients (mean [SD] age 38.7 [15.1] years; 12 299 males [61.5%]) who were treated for OUD, 6948 (34.7%) experienced disenrollment and 586 (2.9%) died during follow-up. The crude rate was 15.3 (95% CI, 14.1-16.6) per 1000 person-years for all-cause mortality and 6.2 (95% CI, 5.4-7.0) per 1000 person-years for overdose mortality. Ever experiencing disenrollment showed elevated all-cause mortality (17.6 [95% CI, 14.9-20.8] vs 14.7 [95% CI, 13.4-16.1] per 1000 person-years) and overdose mortality (8.9 [95% CI, 7.1-11.3] vs 5.4 [95% CI, 4.7-6.3] per 1000 person-years) relative to remaining enrolled. In adjusted analyses, ever experiencing disenrollment was associated with increased hazards of all-cause (hazard ratio [HR], 1.51; 95% CI, 1.23-1.84) and overdose mortality (HR, 1.56; 95% CI, 1.17-2.09). Compared with remaining enrolled and receiving MOUD treatment, being disenrolled (HR, 4.34; 95% CI, 3.19-5.89) and being enrolled and not receiving MOUD treatment (HR, 4.19; 95% CI, 3.24-5.43) were associated with overall mortality. In this cohort study of patients who initiated MOUD, experiencing health plan disenrollment was associated with increased mortality risk compared with remaining enrolled. Strategies are needed to improve continuity of health coverage and mitigate the elevated mortality risk during insurance transitions for patients receiving medications for OUD.

In this study, a stable nanocrystalline drug delivery system for indomethacin (IND) was rapidly developed by integrating machine learning methods with Hummer Acoustic Resonance (HAR) technology. This system effectively enhanced the solubility of IND and demonstrated excellent scalability. High-throughput screening using HAR technology identified P188-PVA as the optimal composite stabilizer for IND nanocrystal suspensions. Molecular dynamics simulations were employed to thoroughly investigate the interaction mechanisms between the drug and stabilizers. Systematic design and optimization of IND nanocrystal formulation parameters and HAR process conditions were conducted using an integrated modeling approach combining Box-Behnken design (BBD) and artificial neural networks (ANN). Various statistical metrics were employed to evaluate and compare the predictive accuracy and generalization capability of BBD-RSM and ANN models, thereby identifying the optimal formulation. HAR technology was successfully used to scale up the optimal formulation by 5- and 50-fold, demonstrating its initial potential for scalability. Freeze-drying, spray-drying, and fluidized-bed drying techniques were evaluated for solidifying the prepared nanocrystal suspensions. Multiple analytical techniques were employed to characterize the particle size and solid-state properties of IND nanocrystals. PXRD and DSC analyses confirmed the crystalline nature of the IND nanocrystals. In vitro dissolution experiments indicated that IND nanocrystals exhibited significantly improved dissolution compared to raw IND. Additionally, the concepts and methodologies proposed in this study could also be applied to the development of other poorly water-soluble drugs.

Robotic arms are widely used in various aspects of human-robot collaboration. The primary goal of this study is to explore the usability of robotic arms for delivering objects to humans in dynamic environments. Traditional robotic arms often face limitations in path planning, such as difficulties adapting to dynamic environments and complex developmental processes. To overcome these challenges, this study employs reinforcement learning (RL) to train four models-the Approach RL Model, Delivery RL Model, Decision RL Model, and Merged Model-as alternatives to conventional path planning control. Typically, there exists a significant discrepancy between simulated data and real-world features. Although image segmentation can substantially reduce the gap between virtual and real environments, notable differences remain in hand features. Therefore, to further bridge the simulation-to-reality gap, this study applies CycleGAN to transform real hand features into virtual hand features, thereby enhancing the model's transferability. Experimental results show that the Decision RL Model achieved an accuracy of 99.17%, while the Merged Model achieved 99.92%. The proposed method effectively improves the stability and accuracy of human-robot collaboration in complex scenarios. Overall, this study validates the feasibility of integrating RL, image segmentation, and image translation techniques, offering a scalable and efficient task-solving solution for robotic arms in highly dynamic application domains.

Purpose of review Vaccination is a key measure for protecting workers against infectious diseases. Immunization schedules are adapted to age, health status, and occupational risks, yet global vaccination coverage remains suboptimal. Declining interest, hesitancy, and refusal contribute to insufficient uptake. In occupational settings, the feasibility and effectiveness of workplace vaccination programs are increasingly explored. Expanding vaccine offerings and providing free access for all workers could substantially improve coverage. The main aim of the article was to reflect on various aspects of vaccination at work in the current era of growing global problems with acceptance, questioning and refusal of vaccination and possibility of occupational health professionals to contributing to improving employee's vaccination. Recent findings Adult vaccination rates remain low despite recommendations from health authorities. Most studies focus on healthcare workers, but recent research examines delivery systems, attitudes, and barriers influencing vaccination among broader worker populations. Workplace-based vaccination and determinants of hesitancy are key areas of interest. The most frequently studied vaccines are for influenza, COVID-19, and diseases resurging due to declining childhood immunization. New directions include cancer prevention, especially through HPV vaccination. Summary Employers and occupational health services should comply with legal health protection duties while promoting voluntary health initiatives, including routine vaccination of adults. Workplace vaccination programs, particularly those organized or supported by employers, are effective strategies to increase immunization coverage and contribute to improved employee health and well being.

Gene therapies are promising for diseases previously considered incurable. Adeno-associated virus serotype 9 (AAV9) demonstrates remarkable tropism for motor neurons (MNs) and represents an exciting candidate to target genetic causes of motor neuron diseases like amyotrophic lateral sclerosis (ALS). However, systemic delivery risks immunogenicity and off-target effects, therefore localised delivery to the CNS is advantageous. We assessed MN transduction in wild-type post-natal mice using AAV9-controlled, cytomegalovirus-promoter driven, enhanced GFP expression. Intra-cisterna magna (ICM) and intra-cerebroventricular (ICV) methods were compared. Four weeks post-delivery, GFP positivity in MN and astrocytes were quantified via immunohistochemical approaches and viral genome copy number determined by qPCR. All delivery methods achieved high MN transduction in lumbar spinal cord (> 68%). Unilateral ICV delivery provided the highest and most consistent levels (89 ± 3%), and minimal peripheral viral copies. ICV delivery resulted in higher astrocytic transduction, most notably in the cortex. Brainstem MN transduction was high with all methods (> 55%). We failed to find evidence of neuronal transduction in motor cortex. Viral genome copies trended higher in spinal cord and brainstem with ICV approaches, however further work is required to understand how bilateral repeated dose delivery leads to more profound increases. Whilst several routes of administration into cerebrospinal fluid exist, direct comparisons for targeting MNs in vivo remain limited. Overall, all methods of CNS-directed delivery result in high levels of motor neuron transduction in the lumbar spinal cord and brainstem, but not in motor cortex. Unilateral ICV appears to provide the best balance between consistent, high levels of transduction and low off-target effects. However, ICM might be the better option if seeking to avoid astrocytic transduction.

Liposomes remain one of the most utilized drug delivery systems due to their numerous advantages. However, they face significant challenges primarily due to their low colloidal stability as well as their rapid clearance by the reticuloendothelial and mononuclear phagocyte systems. Surface modifications have been identified as a highly effective approach to address these challenges. Various molecules can be utilized as surface modifiers. However, polysaccharides are widely employed in this regard, due to their unique characteristics, such as biocompatibility, biodegradability, and non-toxicity, as well as their ability to interact with the liposomal surface through different mechanisms. The aim of the present review is to provide a thorough analysis of polysaccharide-modified liposomes, highlighting recent advancements in their design, synthesis, and therapeutic applications. The utilization of polysaccharides as surface modifiers has been demonstrated to have several notable effects on liposomes. These effects include the enhancement of liposome properties, the provision of “stealth” properties, and the augmentation of colloidal stability. This review provides a comprehensive, polysaccharide-oriented analysis of liposomal surface modification strategies, along with a novel focus on the correlation between polysaccharide structure, modification method, and the resulting physicochemical and biological performance of the designed hybrid liposomes across a wide range of applications.

Apoptotic bodies are membrane-bound vesicles generated during the terminal stages of programmed cell death and traditionally viewed as inert cellular debris. Emerging evidence, however, positions apoptotic bodies as dynamic mediators of intercellular communication with critical roles in renal physiology and pathology. In the healthy kidney, efficient efferocytosis of apoptotic bodies maintains tissue homeostasis by ensuring immunologically silent clearance of apoptotic remnants. In acute kidney injury (AKI), extensive tubular epithelial apoptosis generates a high burden of apoptotic bodies that can amplify inflammation, endothelial dysfunction, and adaptive immune activation when clearance is impaired, yet promote resolution and epithelial repair when efficiently removed. In chronic kidney disease (CKD), persistent low-grade apoptosis combined with defective efferocytosis leads to progressive accumulation of apoptotic bodies in the interstitium, where their bioactive cargo-including DAMPs, cytokines, growth factors, and profibrotic microRNAs-drives fibroblast activation, extracellular matrix expansion, and fibrosis. In the vasculature, apoptotic bodies derived from vascular smooth muscle cells act as nucleation sites for calcium-phosphate crystal deposition, linking apoptosis to the development of medial vascular calcification in CKD. Together, these findings highlight apoptotic bodies as active regulators of injury, inflammation, fibrosis, regeneration, and vascular pathology. Understanding the determinants of their pathogenic versus reparative effects could yield new biomarkers and therapeutic strategies, including modulation of efferocytosis, targeting apoptotic body-derived signaling pathways, and engineering apoptotic bodies-based delivery systems.

Nonviral Gene Delivery Systems Based on Cationic Benzimidazolium Surfactants and Fusogenic Lipids

Background: Chimeric antigen receptor (CAR) T-cell therapy is clinically limited by lentiviral vector dependence, ex vivo activation/expansion requirements, complex processes, high costs, and impaired antitumor functions. For advanced cancer, the long manufacturing cycle of traditional CAR-T cells further compromises the treatment timeliness, creating an urgent need for optimized preparation strategies. Materials and methods: A gene delivery system was constructed using microtubule-associated sequence and nuclear localization signal peptide–modified poly(β-amino ester) nanoparticles, combined with microfluidic technology. Nonactivated primary human T cells were transfected without ex vivo activation. The transfection efficiency, gene expression persistence, and in vitro cytotoxicity against the B7-H3-positive bladder cancer cell line T24 were evaluated. Results: The system achieved gene delivery to nonactivated T cells within 2 to 6 hours, with a transfection efficiency that was 7-fold higher than that of unmodified nanoparticles. Target genes were stably expressed for over 5 days. The resulting CAR-T cells exhibited potent, specific cytotoxicity against T24 cells, avoiding viral vector risks and reducing manufacturing costs. Conclusions: This strategy innovates CAR-T-cell preparation by targeting nonactivated T cells and overcoming traditional bottlenecks. This provides a simpler, faster, cost-effective, and safe approach for adoptive cellular immunotherapy with significant translational value for bladder cancer and other solid tumors.

DNA aptamers are short, single-stranded DNA molecules that bind specifically to a range of targets such as proteins, cells, and small molecules. Typically, they are utilized in the development of therapeutic agents, diagnostics, drug delivery systems, and biosensors. Although aptamers perform well in controlled extracellular environments, their intracellular use has been less explored due to challenges of expressing them in vivo. In this study, we employed the bacterial retron system Eco2 to express a DNA light-up aptamer in Escherichia coli . Our data confirms that structure-guided insertion of the aptamer domain into the non-coding region of the retron enables reverse transcription and biosynthesis of functional aptamer constructs in bacteria. The purified DNA aptamer synthesized under intracellular conditions shows comparable activity to a chemically synthesized control. Our findings demonstrate that retrons can be used to express short DNA aptamers within living cells, potentially broadening and optimizing their application in intracellular settings.

Intra-articular drug delivery systems (DDS) are emerging as promising therapies for osteoarthritis (OA), yet their efficacy in spontaneous clinical cases remains largely untested. This uncontrolled, descriptive pilot study was designed to provide a proof of concept for the feasibility, safety, and preliminary clinical effects of intra-articular administration in sport horses with naturally occurring OA. The study involved a peptide-functionalized nanogel composed of chitosan and hyaluronic acid, delivering endothelin type A (BQ-123) and bradykinin B1 (R-954) receptor antagonists, which have previously demonstrated anti-inflammatory and chondroprotective properties in preclinical models. Eight client-owned sport horses with moderate OA of the metacarpophalangeal (MCPJ) or distal interphalangeal joint (DIPJ) received a single intra-articular injection of 2.4mL nanogel and were followed for 12months. No major adverse events were observed. Two horses developed mild, transient joint swelling that resolved within three days. Seven of eight horses showed improvement in lameness scores by week 12, although complete resolution on hard ground circles was observed in only two horses. All horses were sound on soft ground and returned to competition, with a median time of 128days post-treatment. Six horses remained in active competition at one year without additional intervention. Four horses (50%) met the predefined primary outcome of return to the same level and frequency of competition as before lameness onset. Horses treated for DIPJ OA and those showing radiographic joint space narrowing were overrepresented among treatment failures. Intra-articular administration of a peptide-functionalized nanogel was feasible and well tolerated in sport horses with naturally occurring OA and was associated with partial but prolonged clinical improvement. Although only half of the horses achieved full return to pre-lameness performance, most showed sustained clinical benefit without additional treatment over one year. These findings support further investigation of this drug delivery system in larger, randomized controlled trials to better define its therapeutic efficacy and optimal indications.

Utilization of ivabradine in the pediatric population has been centered on the goal of chronotropic control in patients with arrhythmias and heart failure. Tachycardia is known to be detrimental when it impairs hemodynamics by increasing myocardial oxygen demand, increasing ventricular end-diastolic pressures, and decreasing cardiac output in certain patients. The acute hemodynamic effects of ivabradine have not yet been studied in real time. This study was performed leveraging the Sickbay platform (Medical Informatics Company, Houston, TX). The primary aim of this study was to characterize the effect of enteral ivabradine on heart rate in patients in a pediatric cardiac intensive care unit within 24 hours of initiation. Secondary aims were to characterize the effects of ivabradine on arterial saturation, respiratory rate, mean arterial blood pressure, central venous pressure, and renal near infrared spectroscopy for the same time frame. Heart rate decreased approximately 17% in the first 15 hours after ivabradine administration. Changes were seen in the secondary aims that varied depending on time after first and second doses. Specifically, decreases in central venous pressure and increased renal tissue oxygen saturation (rSO2) were observed by the end of the 24 hours. Ivabradine seems safe in pediatric patients. It is associated with 3 distinct hemodynamic response phases: the first phase is associated with decreased heart rate and unchanged systemic oxygen delivery, the second phase is associated with increased heart rate and worsened systemic oxygen delivery, and the third phase being associated with decreased heart rate and improved systemic oxygen delivery. These phases coincide with the pharmacokinetic properties of ivabradine.