Extracts of Phlomoides umbrosa Turczaninow alleviate allergic airway inflammation in lipopolysaccharide-stimulated RAW 264.7 cells and ovalbumin-induced hyper-responsiveness mouse model.

Phlomoides umbrosa Turczaninow (PU), a traditional Korean medicinal herb, exhibits osteogenic and anti-inflammatory effects. This research explored the effect of PU extracts on hyperimmune responses within the respiratory tract using lipopolysaccharide-stimulated RAW 264.7 cells and an ovalbumin-induced hyper-responsiveness model. The inflammatory cytokines, protein expression linked to airway inflammation, antioxidant enzyme activity, histopathological observation, and expectorant activity were measured. The results revealed that PU treatment led to a concentration-dependent reduction in Th2 cytokines and the expression of nuclear factor (NF)-κB, phosphatase-tensin homolog, mitogen-activated protein kinase (MAPK), and inducible nitric oxide synthase (iNOS). Simultaneously, antioxidant enzyme activity increased. Furthermore, PU exhibited substantial enhancements in lung tissue condition and expectorant activity relative to the allergic rhinitis-induced group. These findings indicate the potential of PU to mitigate airway inflammation and excessive mucus production by suppressing NF-κB, MAPK, and iNOS pathways. Consequently, PU emerges as a promising anti-inflammatory agent for respiratory tract applications. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-024-01521-3.

Determination of biogenic amine-producing lactic acid bacteria in kimchi varieties through in vitro analysis and low temperature fermentation.

This study analyzed biogenic amine (BA) content in three varieties (types) of kimchi (Baechu kimchi, Baek kimchi, and Yeolmu kimchi), identified the causative bacteria, and evaluated the gene expression associated with the BA formation during kimchi fermentation at 4 °C. Histamine content exceeding the toxicity limit was detected in a single Baechu kimchi product. Tyramine content in most Baechu kimchi products was approximately half of the toxicity limit. Other varieties had relatively lower BA content. Most BA producers isolated from all kimchi varieties were identified as Levilactobacillus brevis, which prominently produced tyramine. To clarify the role of L. brevis in tyramine formation in Baechu kimchi, fermentation experiments were performed using L. brevis BC1M20. The results showed that tyramine content and tyrosine decarboxylase gene (tdc) expression were higher in the inoculated kimchi than in the control. In addition, in the inoculated kimchi, the content decreased while the expression level was almost constant. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-024-01627-8.

Case Report: Leadless and left bundle branch area pacemakers, complementary advantages require a personalized approach.

Traditional transvenous pacemakers consist of a pacemaker generator usually positioned surgically in the upper left chest on the pectoral muscle fascia and one or more leads positioned through the veins to the right atrium and across the tricuspid valve to the right ventricular apex. While these devices reduce symptoms and improve survival among patients with symptomatic bradycardia, they are associated with an increased risk of infection, venous occlusion, heart failure, and tricuspid valve regurgitation. Although new pacemaker designs minimize these risks, none of the current-generation pacemaker designs effectively eliminate all of them. A personalized approach to selecting the appropriate pacemaker for each patient is needed to optimize outcomes.

Variable-stiffness-morphing wheel inspired by the surface tension of a liquid droplet.

Wheels have been commonly used for locomotion in mobile robots and transportation systems because of their simple structure and energy efficiency. However, the performance of wheels in overcoming obstacles is limited compared with their advantages in driving on normal flat ground. Here, we present a variable-stiffness wheel inspired by the surface tension of a liquid droplet. In a liquid droplet, as the cohesive force of the outermost liquid molecules increases, the net force pulling the liquid molecules inward also increases. This leads to high surface tension, resulting in the liquid droplet reverting to a circular shape from its distorted shape induced by gravitational forces. Similarly, the shape and stiffness of a wheel were controlled by changing the traction force at the outermost smart chain block. As the tension of the wire spokes connected to each chain block increased, the wheel characteristics reflected those of a general circular-rigid wheel, which has an advantage in high-speed locomotion on normal flat ground. Conversely, the modulus of the wheel decreased as the tension of the wire spoke decreased, and the wheel was easily deformed according to the shape of obstacles. This makes the wheel suitable for overcoming obstacles without requiring complex control or sensing systems. On the basis of this mechanism, a wheel was applied to a two-wheeled wheelchair system weighing 120 kilograms, and the state transition between a circular high-modulus state and a deformable low-modulus state was realized in real time when the wheelchair was driven in an outdoor environment.

CRISPR/Cas9-mediated suppression of A4GALT rescues endothelial cell dysfunction in a fabry disease vasculopathy model derived from human induced pluripotent stem cells.

BACKGROUND AND AIMS: The objective of this study was to investigate the efficacy of CRISPR/Cas9-mediated A4GALT suppression in rescuing endothelial dysfunction in Fabry disease (FD) endothelial cells (FD-ECs) derived from human induced pluripotent stem cells (hiPSCs). METHODS: We differentiated hiPSCs (WT (wild-type), WTC-11), GLA-mutant hiPSCs (GLA-KO, CMC-Fb-002), and CRISPR/Cas9-mediated A4GALT-KO hiPSCs (GLA/A4GALT-KO, Fb-002-A4GALT-KO) into ECs and compared FD phenotypes and endothelial dysfunction. We also analyzed the effect of A4GALT suppression on reactive oxygen species (ROS) formation and transcriptome profiles through RNA sequencing. RESULTS: GLA-mutant hiPSC-ECs (GLA-KO and CMC-Fb-002) showed downregulated expression of EC markers and significantly reduced α-GalA expression with increased Gb-3 deposition and intra-lysosomal inclusion bodies. However, CRISPR/Cas9-mediated A4GALT suppression in GLA/A4GALT-KO and Fb-002-A4GALT-KO hiPSC-ECs increased expression levels of EC markers and rescued these FD phenotypes. GLA-mutant hiPSC-ECs failed to form tube-like structure in tube formation assays, showing significantly decreased migration of cells into the scratched wound area. In contrast, A4GALT suppression improved tube formation and cell migration capacity. Western blot analysis revealed that MAPK and AKT phosphorylation levels were downregulated while SOD and catalase were upregulated in GLA-KO hiPSC-ECs. However, suppression of A4GALT restored these protein alterations. RNA sequencing analysis demonstrated significant transcriptome changes in GLA-mutant EC, especially in angiogenesis, cell death, and cellular response to oxidative stress. However, these were effectively restored in GLA/A4GALT-KO hiPSC-ECs. CONCLUSIONS: CRISPR/Cas9-mediated A4GALT suppression rescued FD phenotype and endothelial dysfunction in GLA-mutant hiPSC-ECs, presenting a potential therapeutic approach for FD-vasculopathy.

Incidence and Characteristics of Intraocular Lens Dislocation in South Korea from 2002 to 2021: A Nationwide Population-based Study.

Purpose: This study aimed to analyze the incidence and characteristics of intraocular lens (IOL) dislocation after cataract surgery in South Korea. Methods: We retrospectively analyzed the incidence of IOL dislocation after cataract surgery in patients diagnosed between 2002 and 2021. Data of all pseudophakic patients who underwent secondary IOL or IOL exchange surgeries due to IOL dislocation were extracted from the Korean National Health Insurance System (KNHIS) database and the Korean Standard Classification of Diseases-7 codes. The incidence per 1,000,000 person-years and corresponding 95% confidence intervals (CIs) were calculated. Results: Between 2002 and 2021, 39,965 (0.82 %) of the 4,848,125 pseudophakic patients were diagnosed with IOL dislocation and surgically treated. The incidence of IOL dislocation requiring surgery in pseudophakic patients was 28,900/1,000,000 person-years (95% CI: 28,431-29,369), comprising 57,800 cases in male and 10,800 in female patients (95% CI: male: 56,730-58,870 vs. 95% CI: female patients: 10,523-11,077), and mean male-to-female ratio was 5.35. The incidence rate peaked in younger age group below 40 years, showing 107,000 per 1,000,000 person-years (95% CI: 102,900-111,100), and the average age of IOL dislocation requiring surgery was 68.1 ± 10.7 years. The average time lapse from cataract surgery to secondary IOL surgery due to IOL dislocation was 4.1±4.7 years (median, 2.2 years), and the number of secondary IOL surgery due to dislocation of artificial lens rapidly occurred 10 years after cataract surgery among all age groups. Conclusions: The incidence of IOL dislocation requiring surgery was higher in younger and male patients. Our findings could be expected to aid establishing future healthcare policies for South Korean populations with an increased risk of IOL dislocation after cataract surgery.

Integrating ensemble and machine learning models for early prediction of pneumonia mortality using laboratory tests.

Background: The recent use of artificial intelligence (AI) in medical research is noteworthy. However, most research has focused on medical imaging. Although the importance of laboratory tests in the clinical field is acknowledged by clinicians, they are undervalued in medical AI research. Our study aims to develop an early prediction AI model for pneumonia mortality, primarily using laboratory test results. Materials and methods: We developed a mortality prediction model using initial laboratory results and basic clinical information of patients with pneumonia. Several machine learning (ML) models and a deep learning method-multilayer perceptron (MLP)-were selected for model development. The area under the receiver operating characteristic curve (AUROC) and F1-score were optimized to improve model performance. In addition, an ensemble model was developed by blending several models to improve the prediction performance. We used 80,940 data instances for model development. Results: Among the ML models, XGBoost exhibited the best performance (AUROC = 0.8989, accuracy = 0.88, F1-score = 0.80). MLP achieved an AUROC of 0.8498, accuracy of 0.86, and F1-score of 0.75. The performance of the ensemble model was the best among the developed models, with an AUROC of 0.9006, accuracy of 0.90, and F1-score of 0.81. Several laboratory tests were conducted to identify risk factors that affect pneumonia mortality using the "Feature importance" technique and SHapley Additive exPlanations. We identified several laboratory results, including systolic blood pressure, serum glucose level, age, aspartate aminotransferase-to-alanine aminotransferase ratio, and monocyte-to-lymphocyte ratio, as significant predictors of mortality in patients with pneumonia. Conclusions: Our study demonstrates that the ensemble model, incorporating XGBoost, CatBoost, and LGBM techniques, outperforms individual ML and deep learning models in predicting pneumonia mortality. Our findings emphasize the importance of integrating AI techniques to leverage laboratory test data effectively, offering a promising direction for advancing AI applications in medical research and clinical decision-making.

Management of open abdomen complication after laparotomy in an ovarian cancer patient with intraperitoneal metastasis.

This case report highlights the management of complications from an open abdomen following surgery for ovarian mucinous adenocarcinoma, a rare subtype of ovarian cancer. A 63-year-old female underwent extensive surgery, including single-port laparoscopic total bilateral salpingo-oophorectomy, right hemicolectomy, small bowel resection, cholecystectomy, and jejunostomy. Postoperatively, she experienced bile leakage, leading to significant skin and fascial damage and an abdominal skin defect. Early detection and multidisciplinary management were crucial. Treatment involved vacuum-assisted closure dressing, repeated debridement, and closure of the open abdomen with a local flap. This case emphasizes the complexities of managing ovarian mucinous adenocarcinoma and the critical role of a multidisciplinary approach in treating postoperative complications, underscoring the importance of vigilant postoperative care and timely intervention.

Association of liver function markers and apolipoprotein E ε4 with pathogenesis and cognitive decline in Alzheimer's disease.

Background: Alzheimer's disease (AD) is a complex neurodegenerative disorder influenced by various factors, including liver function, which may impact the clearance of amyloid-ß (Aß) in the brain. This study aimed to explore how the apolipoprotein E (APOE) ε4 allele affects the relationship of liver function markers with AD pathology and cognition. Methods: We analyzed data from two independent cohorts, including 732 participants from the Hallym University Medical Center and 483 from the Alzheimer's Disease Neuroimaging Initiative, each group consisting of individuals with and without the APOE ε4 allele. Cross-sectional analyses evaluated the associations of liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase, total bilirubin, and albumin) with AD diagnosis, amyloid positron emission tomography (PET) burden, and cerebrospinal fluid biomarkers for AD (Aß42, total tau, and phosphorylated tau181) at baseline. Longitudinally, we investigated the associations between these liver enzymes and changes in cognitive performance over the course of a year. Logistic and linear regression models were used to analyze these associations and mediation analyses were conducted to assess whether age and amyloid PET burden mediated these associations. Results: Only in the APOE ε4 carrier group, a high AST to ALT ratio and low ALT levels were significantly associated with AD diagnosis, increased amyloid PET burden, and faster longitudinal decline in cognitive function in both cohorts. In particular, the AST to ALT ratio was associated with cerebrospinal fluid Aß42 levels exclusively in the APOE ε4 carrier group in the Alzheimer's Disease Neuroimaging Initiative cohort but not with phosphorylated tau181 or total tau levels. Moreover, mediation analyses from both cohorts revealed that in the APOE ε4 carriers group, age did not mediate the associations between liver enzymes and AD diagnosis or amyloid PET burden. However, amyloid PET burden partially mediated the association between liver enzymes and AD diagnosis exclusively in the APOE ε4 carriers group. Conclusion: This study provides valuable insights into the significant association of the APOE ε4 allele with liver enzymes and their potential role in Aß-related pathogenesis and cognition in AD. Further research is required to elucidate the underlying mechanisms and potential therapeutic implications of these findings.

PanIN and CAF transitions in pancreatic carcinogenesis revealed with spatial data integration.

This study introduces a new imaging, spatial transcriptomics (ST), and single-cell RNA-sequencing integration pipeline to characterize neoplastic cell state transitions during tumorigenesis. We applied a semi-supervised analysis pipeline to examine premalignant pancreatic intraepithelial neoplasias (PanINs) that can develop into pancreatic ductal adenocarcinoma (PDAC). Their strict diagnosis on formalin-fixed and paraffin-embedded (FFPE) samples limited the single-cell characterization of human PanINs within their microenvironment. We leverage whole transcriptome FFPE ST to enable the study of a rare cohort of matched low-grade (LG) and high-grade (HG) PanIN lesions to track progression and map cellular phenotypes relative to single-cell PDAC datasets. We demonstrate that cancer-associated fibroblasts (CAFs), including antigen-presenting CAFs, are located close to PanINs. We further observed a transition from CAF-related inflammatory signaling to cellular proliferation during PanIN progression. We validate these findings with single-cell high-dimensional imaging proteomics and transcriptomics technologies. Altogether, our semi-supervised learning framework for spatial multi-omics has broad applicability across cancer types to decipher the spatiotemporal dynamics of carcinogenesis.

Assessing the Brain Death/Death by Neurologic Criteria Determination Process in Korea: Insights from 10-Year Noncompleted Donation Data.

BACKGROUND: This study aimed to analyze the current status of brain death/death by neurologic criteria (BD/DNC) determination in Korea over a decade, identifying key areas for improvement in the process. METHODS: We conducted a retrospective analysis of data from the Korea Organ Donation Agency spanning 2011 to 2021, focusing on donors whose donations were not completed. The study reviewed demographics, medical settings, diagnoses, and outcomes, with particular emphasis on cases classified as nonbrain death and those resulting in death by cardiac arrest during the BD/DNC assessment. RESULTS: Of the 5047 patients evaluated for potential brain death from 2011 to 2021, 361 were identified as noncompleted donors. The primary reasons for noncompletion included nonbrain death (n = 68, 18.8%), cardiac arrests during the BD/DNC assessment process (n = 80, 22.2%), organ ineligibility (n = 151, 41.8%), and logistical and legal challenges (n = 62, 17.2%). Notably, 25 (36.8%) of them failed to meet the minimum clinical criteria, and 7 of them were potential cases of disagreement between the two clinical examinations. Additionally, most cardiac arrests (n = 44, 55.0%) occurred between the first and second examinations, indicating management challenges in critically ill patients during the assessment period. CONCLUSIONS: Our study highlights significant challenges in the BD/DNC determination process, including the need for improved consistency in neurologic examinations and the management of critically ill patients. The study underscores the importance of refining protocols and training to enhance the accuracy and reliability of brain death assessments, while also ensuring streamlined and effective organ donation practices.

Aromadendrin Inhibits Lipopolysaccharide-Induced Inflammation in BEAS-2B Cells and Lungs of Mice.

Aromadendrin is a phenolic compound with various biological effects such as anti-inflammatory properties. However, its protective effects against acute lung injury (ALI) remain unclear. Therefore, this study aimed to explore the ameliorative effects of aromadendrin in an experimental model of lipopolysaccharide (LPS)-induced ALI. In vitro analysis revealed a notable increase in the levels of cytokine/chemokine formation, nuclear factor kappa B (NF-κB) activation, and myeloid differentiation primary response 88 (MyD88)/toll-like receptor (TLR4) expression in LPS-stimulated BEAS-2B lung epithelial cell lines that was ameliorated by aromadendrin pretreatment. In LPS-induced ALI mice, the remarkable upregulation of immune cells (ICs) and IL-1ß/IL-6/TNF-α levels in the bronchoalveolar lavage fluid (BALF) and inducible nitric oxide synthase (iNOS)/cyclooxygenase-2 (COX-2)/CD68 expression in lung was decreased by the oral administration of aromadendrin. Histological analysis revealed the presence of cells in the lungs of acute lung injury (ALI) mice, which was alleviated by aromadendrin. In addition, aromadendrin ameliorated lung edema. This in vivo effect of aromadendrin was accompanied by its inhibitory effect on LPS-induced NF-κB activation, MyD88/TLR4 expression, and signal transducer and activator of transcription 3 (STAT3) activation. Furthermore, aromadendrin increased the expression of heme oxygenase-1 (HO-1)/ NAD(P)H quinone dehydrogenase 1 (NQO1) in the lungs of ALI mice. In summary, the in vitro and in vivo studies demonstrated that aromadendrin ameliorated endotoxin-induced pulmonary inflammation by suppressing cytokine formation and NF-κB activation, suggesting that aromadendrin could be a useful adjuvant in the treatment of ALI.

Investigating the Immune-Stimulating Potential of ß-Glucan from Aureobasidium pullulans in Cancer Immunotherapy.

ß-glucan, a polysaccharide found in various sources, exhibits unique physicochemical properties, yet its high polymerization limits clinical applications because of its solubility. Addressing this limitation, we introduce PPTEE-glycan, a highly purified soluble ß-1,3/1,6-glucan derived from Aureobasidium pullulans. The refined PPTEE-glycan demonstrated robust immune stimulation in vitro, activated dendritic cells, and enhanced co-stimulatory markers, cytokines, and cross-presentation. Formulated as a PPTEE + microemulsion (ME), it elevated immune responses in vivo, promoting antigen-specific antibodies and CD8+ T cell proliferation. Intratumoral administration of PPTEE + ME in tumor-bearing mice induced notable tumor regression, which was linked to the activation of immunosuppressive cells. This study highlights the potential of high-purity Aureobasidium pullulans-derived ß-glucan, particularly PPTEE, as promising immune adjuvants, offering novel avenues for advancing cancer immunotherapy.

1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol treatment inhibits abnormal tumor growth by regulating neutrophil infiltration in a non-small cell lung carcinoma mouse model.

Excessive neutrophil infiltration into the tumor microenvironment (TME) is an important factor that contributes to tumor overgrowth and limited immunotherapy efficacy. Neutrophils activate various receptors involved in tumor progression, while suppressing the infiltration and activity of cytotoxic T cells and creating optimal conditions for tumor growth. Therefore, the appropriate control of neutrophil infiltration is an effective strategy for tumor treatment. In the present study, 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) inhibited tumor overgrowth by suppressing excessive neutrophil infiltration, resulting in >74.97 % reduction in tumor size in a Lewis lung carcinoma (LLC-1) mouse model. All subjects in the positive control group died during the 90-day survival period, whereas only four subjects in the PLAG treatment group survived. PLAG had a significantly higher tumor growth inhibitory effect and survival rate than other neutrophil infiltration-targeting inhibitors (e.g., Navarixin, lymphocyte antigen 6 complex locus G6D antibody [aLy6G]). The ability of PLAG to regulate neutrophil infiltration and inhibit tumor growth depends on thioredoxin-interacting protein (TXNIP). In tumors lacking TXNIP expression, PLAG failed to control neutrophil infiltration and infiltration-related factor release, and the inhibitory effect of PLAG on tumor growth was reduced. PLAG-mediated inhibition of neutrophil infiltration enhances the efficacy of immune checkpoint inhibitors (ICIs), increasing the antitumor efficacy and survival rate by 30 %. In conclusion, PLAG could be a novel alternative to anti-tumor drugs that effectively targets excessive neutrophil infiltration into cancer tissues.

Human Circulatory/Respiratory-Inspired Comprehensive Air Purification System.

The circulatory and respiratory systems in humans are marvels of biological engineering that exhibit competence in maintaining homeostasis. These systems not only shield the organism from external contaminants but also orchestrate the vital gases via the bloodstream to sustain cellular respiration and metabolic processes across diverse tissues. It is noticed that spaces inhabited encounter challenges akin to those of the human body: protecting the indoor air from external pollutants while removing anthropogenic byproducts like carbon dioxide (CO2), particulate matters (PM), and volatile organic compounds (VOCs) tooutside. A biomimetic approach, composed of a microbubble-based gas exchanger and circulating liquid inspired by alveoli, capillary beds, and bloodstream of the human circulatory/respiratory system, offer an innovative solution for comprehensive air purification of hermetic spaces. Circulatory/respiratory-inspired air purification system (CAPS) ensure both continuous removal of PM and exchange of gas species between indoor and outdoor environments to maintain homeostasis. The effectiveness of this system is also supported by animal behavior experiments with and without CAPS, showing an effect of reducing CO2 concentration by 30% and increasing mice locomotor activity by 53%. CAPS is expected to evolve into robust and comprehensive air purification schemes through the networked integration of plural internal and external environments.

Effect of Cost-Exemption Policy on Treatment Interruption in Patients With Newly Diagnosed Pulmonary Tuberculosis in South Korea.

BACKGROUND: In 2021, South Korea had the highest incidence rate (49 per 100 000 population) and the third highest mortality rate (3.8 per 100 000 population) due to pulmonary tuberculosis (TB) among Organization for Economic Co-operation and Development countries. Notably, premature interruption of TB treatment interferes with TB control efforts. Therefore, we examined the effect of the co-payment waiver on treatment interruption and mortality among patients with pulmonary TB in South Korea. METHODS: Patients who had newly treated TB in South Korea from 2013 to 2019 were selected from the nationwide data of the entire Korean National Health Insurance Service (NHIS) population. The effects of policy implementation on treatment adherence and mortality rates depending on treatment interruption history were evaluated. RESULTS: In total, 73 116 and 1673 patients with drug-susceptible (DS) and multidrug-resistant (MDR) pulmonary TB, respectively, were included in the final study population. After implementing the cost-exemption policy, the treatment interruption rate tended to decrease in the continuation phase in the DS-TB group (slope change: -0.097, P=.011). However, it increased in the intensive phase in the MDR-TB group (slope change: 0.733, P=.001). MDR-TB patients were likely to experience an interruption of TB treatment (adjusted odds ratio [aOR], 6.04; 95% CI, 5.43-6.71), and treatment interruption history was a significant risk factor for 1-year and overall mortality rates (adjusted hazard ratios [aHRs]: 2.01, 95% CI, 1.86-2.18 and 1.77, 95% CI, 1.70-1.84, respectively) in the DS-TB group. CONCLUSION: Implementing the cost-exemption policy effectively reduced the treatment interruption rate among patients with DS pulmonary TB.

Clinical data on treatment regimen and use of medication among patients with hemophilia B in Korea.

BACKGROUND: To investigate the clinical treatment status, such as treatment regimen, bleeding events, and drug dose, in patients with hemophilia B in South Korea. METHODS: In this retrospective chart review, data of patients with hemophilia B from eight university hospitals were collected. Demographic and clinical data, treatment data, such as regimen and number of injections, dose of factor IX concentrate, and bleeding data were reviewed. Descriptive analyses were performed with annual data for 2019, 2020, and 2021, as well as the three years consecutively. RESULTS: The medical records of 150 patients with hemophilia B between January 1, 2019, and December 31, 2021, were collected. Among these, 72 (48.0%) were severe, 47 (31.3%) were moderate, and 28 (18.7%) were mild. The results showed approximately two times more patients receiving prophylaxis as those receiving on-demand therapy, with 66.1% of patients receiving prophylaxis in 2019, 64.9% in 2020, and 72.1% in 2021. Annualized bleeding rates were 2.2% (± 3.1) in 2019, 1.8% (± 3.0) in 2020, and 1.8% (± 2.9) in 2021 among patients receiving prophylaxis. For the doses of factor IX concentrate, patients receiving prophylaxis received an average of 41.6 (± 11.9) IU/Kg/Injection in 2019, 45.7 (± 12.9) IU/Kg/Injection in 2020, and 60.1 (± 24.0) IU/Kg/Injection in 2021. CONCLUSIONS: Clinically, prophylaxis is more prevalent than reported. Based on insights gained from current clinical evidence, it is expected that the unmet medical needs of patients can be identified, and physicians can evaluate the status of patients and actively manage hemophilia B using more effective treatment strategies.

Nano-anticoagulant based on carrier-free low molecular weight heparin and octadecylamine with an albumin shuttling effect.

Low-molecular-weight heparin (LMWH), derived from unfractionated heparin (UFH), has enhanced anticoagulant efficacy, long duration of action, and extended half-life. Patients receiving LMWH for preventive therapies would strongly benefit from its long-term effects, however, achieving this is challenging. Here, we design and evaluate a nanoengineered LMWH and octadecylamine conjugate (LMHO) that can act for a long time while maintaining close to 97 ± 3% of LMWH activity via end-specific conjugation of the reducing end of LMWH. LMHO can self-assemble into nanoparticles with an average size of 105 ± 1.7 nm in water without any nanocarrier and can be combined with serum albumin, resulting in a lipid-based albumin shuttling effect. Such molecules can circulate in the bloodstream for 4-5 days. We corroborate the self-assembly capability of LMHO and its interaction with albumin through molecular dynamics (MD) simulations and transmission electron microscopy (TEM) analysis. This innovative approach to carrier-free polysaccharide delivery, enhanced by nanoengineered albumin shuttling, represents a promising platform to address limitations in conventional therapies.

Association of baseline muscle mass with functional outcomes in intensive care unit survivors: A single-center retrospective cohort study in Korea.

In critical care settings, ultrasound (US) of the quadriceps muscle and Bioelectrical Impedance Analysis (BIA) are noninvasive and widely available tools to evaluate muscle mass. We studied whether baseline muscle mass affects physical function in intensive care unit (ICU) survivors after discharge. This retrospective review of a prospective cohort enrolled 30 patients admitted to the medical ICU between April 2016 and June 2018. On ICU admission, quadriceps muscle thickness and skeletal muscle mass were measured using US and BIA, respectively. Muscle strength and physical function were measured using handgrip dynamometry, the 6-min walk test, and the Barthel index questionnaire survey during every clinic visit at 1, 3, 6, and 12 months after hospital discharge. Skeletal muscle mass at ICU admission was statistically correlated with the 6-min walk distance (6MWD) and Barthel index score. The segmental lean mass of the right arm was also positively correlated with handgrip muscle strength at 6 months after discharge. Likewise, the correlation between quadriceps muscle thickness at ICU admission and 6MWD at 6 months after discharge was positive and statistically significant. Multivariate regression analysis showed that skeletal muscle mass was associated with a reduced 6MWD, but the length of ICU stay was not. The segmental lean mass of the right arm also showed a significant association with handgrip strength after discharge. Low muscle mass on ICU admission is associated with reduced muscle strength, causing impaired physical function after hospital discharge in ICU survivors.