Dexamethasone acetate loaded poly(ε-caprolactone) nanofibers for rat corneal chemical burn treatment.

Topical eye drop approaches to treat ocular inflammation in dry eyes often face limitations such as low efficiency and short duration of drug delivery. Nanofibers serve to overcome the limitation of the short duration of action of topical eye drops used against ocular inflammation in dry eyes. Several attempts to develop suitable nanofibers have been made; however, there is no ideal solution. Here, we developed polycaprolactone (PCL) nanofibers loaded with dexamethasone acetate (DEX), prepared by electrospinning, as a potential ocular drug delivery platform for corneal injury treatment. Thirty-nine Sprague Dawley rats (7 weeks old males) were divided into four treatment groups after alkaline burns of the cornea; negative control (no treatment group); dexamethasone eyedrops (DEX group); PCL fiber (PCL group); dexamethasone loaded PCL (PCL + DEX group). We evaluated therapeutic efficacy of PCL + DEX by examining the epithelial wound healing effect, the extent of corneal opacity and neovascularization. Additionally, various inflammatory factors, including IL-1ß, were investigated through immunochemistry, western blot analysis, and quantitative real-time RT-PCR (qRT-PCR). PCL + DEX group showed histologically alleviated signs of corneal inflammation compared with DEX group, which showed a decrease in IL-1ß and MMP9 in the corneal stroma. The quantitative expression on day 1 after alkaline burn of pro-inflammatory markers, including IL-1ß and IL-6, in the PCL + DEX group was significantly lower than that in the DEX group. Notably, PCL + DEX treatment significantly suppressed neovascularization, and enhanced the anti-inflammatory function of DEX during the acute phase of ocular inflammation. Collectively, these findings suggest that PCL + DEX may be a promising approach to effective drug delivery in corneal burn injuries.

Efficient data labeling strategies for automated muscle segmentation in lower leg MRIs of Charcot-Marie-Tooth disease patients.

We aimed to develop efficient data labeling strategies for ground truth segmentation in lower-leg magnetic resonance imaging (MRI) of patients with Charcot-Marie-Tooth disease (CMT) and to develop an automated muscle segmentation model using different labeling approaches. The impact of using unlabeled data on model performance was further examined. Using axial T1-weighted MRIs of 120 patients with CMT (60 each with mild and severe intramuscular fat infiltration), we compared the performance of segmentation models obtained using several different labeling strategies. The effect of leveraging unlabeled data on segmentation performance was evaluated by comparing the performances of few-supervised, semi-supervised (mean teacher model), and fully-supervised learning models. We employed a 2D U-Net architecture and assessed its performance by comparing the average Dice coefficients (ADC) using paired t-tests with Bonferroni correction. Among few-supervised models utilizing 10% labeled data, labeling three slices (the uppermost, central, and lowermost slices) per subject exhibited a significantly higher ADC (90.84±3.46%) compared with other strategies using a single image slice per subject (uppermost, 87.79±4.41%; central, 89.42±4.07%; lowermost, 89.29±4.71%, p < 0.0001) or all slices per subject (85.97±9.82%, p < 0.0001). Moreover, semi-supervised learning significantly enhanced the segmentation performance. The semi-supervised model using the three-slices strategy showed the highest segmentation performance (91.03±3.67%) among 10% labeled set models. Fully-supervised model showed an ADC of 91.39±3.76. A three-slice-based labeling strategy for ground truth segmentation is the most efficient method for developing automated muscle segmentation models of CMT lower leg MRI. Additionally, semi-supervised learning with unlabeled data significantly enhances segmentation performance.

Epidemiologic characteristics and risk factors of Clostridioides difficile infection in patients with active tuberculosis in the Republic of Korea: A nationwide population-based study.

BACKGROUND: The relationship between anti-tuberculosis (TB) agents and Clostridioides difficile infection (CDI) remains unclear. This study aimed to investigate the epidemiological characteristics and risk factors for CDI in patients with TB. METHODS: This nationwide, population-based cohort study was conducted in the Republic of Korea (ROK) between January 2018 and December 2022. Data were extracted from the National Health Insurance Service (NHIS) National Health Information Database. The risk factors for CDI in patients with TB were identified through multivariate logistic regression analysis using a 1:4 greedy matching method based on age and sex. RESULTS: During the study period, CDI developed in 2,901 of the 131,950 patients with TB who were prescribed anti-TB agents. The incidence of CDI in patients with TB has increased annually in the ROK from 12.31/1000 in 2018 to 33.51/1000 in 2022. Oral metronidazole (81.94%) was the most common first-line treatment for CDI. The in-hospital mortality rate of patients with concomitant CDI and tuberculosis was 9.9% compared with 6.9% in those with TB alone (P<0.0001). Multivariate logistic regression analysis found intensive care unit admission, Charlson Comorbidity Index ≥3, antibiotics exposure, standard regimen, multidrug resistant TB, and extrapulmonary TB as significant risk factors for development of CDI in patients with TB. CONCLUSION: CDI is uncommon in patients with TB, but it results in a significantly increased mortality rate. Patients being treated for TB should be carefully monitored for the development of CDI. Further clinical research is warranted to identify effective interventions for preventing and controlling CDI during TB treatment.

Non-equilibrium formation and relaxation of magnetic flux ropes at kinetic scales.

Magnetic flux ropes are pivotal structures and building blocks in astrophysical and laboratory plasmas, and various equilibrium models have thus been studied in the past. However, flux ropes in general form at non-equilibrium, and their pathway from formation to relaxation is a crucial process that determines their eventual properties. Here we show that any localized current parallel to a background magnetic field will evolve into a flux rope via non-equilibrium processes. The detailed kinetic dynamics are exhaustively explained through single-particle and Vlasov analyses and verified through particle-in-cell simulations. This process is consistent with many proposed mechanisms of flux rope generation such as magnetic reconnection. A spacecraft observation of an example flux rope is also presented; by invoking the non-equilibrium process, its structure and properties can be explicated down to all six components of the temperature tensor.

Metabolic phenotyping combined with transcriptomics metadata fortifies the diagnosis of early-stage Hepatocellular carcinoma.

INTRODUCTION: The low sensitivity of alpha-fetoprotein (AFP) renders it unsuitable as a stand-alone marker for early hepatocellular carcinoma (eHCC) surveillance. Therefore, additional blood-based biomarkers with enhanced sensitivities are required. OBJECTIVES: In light of the metabolic changes that are distinctive to eHCC development, the current study presents a panel of serum metabolites that may serve as noninvasive diagnostic indicators for patients with eHCC. METHODS: Serum samples obtained from normal control (NC), cirrhosis, and eHCC patients were analyzed by four different metabolomic platforms. A meta-analysis of very early-stage HCC transcriptomic datasets retrieved from public sources supports the integrated interpretation with metabolic changes. RESULTS: A total of 94 metabolites were significantly correlated with a progressive disease status. Integrated analysis of the significant metabolites and differentially expressed genes from meta-analysis emphasized metabolic pathways including bile acid biosynthesis, phenylalanine and tyrosine metabolism, and butanoate metabolism. The 11 metabolites associated with these pathways were compiled into a metabolite panel for use as diagnostic signatures. With an accuracy of 81.8%, compared with 45.4% for a model trained solely on AFP, the model enhanced its ability to differentiate between the three groups by incorporating a metabolite panel and AFP. Upon examining the trained models using receiver operating characteristic curves, the AFP and metabolite panel combined model exhibited greater area under the curve values in comparisons between NC and eHCC (1.000 versus 0.810) and cirrhosis and eHCC (0.926 versus 0.556). The result was consistent in an independent validation cohort. CONCLUSION: This study emphasizes the role of circulating metabolite markers in the diagnosis of eHCC.

Clinical significance and outcomes of adult living donor liver transplantation for acute liver failure: a retrospective cohort study based on 15-year single-center experience.

Purpose: This study aimed to describe adult living donor liver transplantation (LDLT) for acute liver failure and evaluate its clinical significance by comparing its surgical and survival outcomes with those of deceased donor liver transplantation (DDLT). Methods: We retrospectively reviewed the medical records of 267 consecutive patients (161 LDLT recipients and 106 DDLT recipients) aged 18 years or older who underwent liver transplantation between January 2006 and December 2020. Results: The mean periods from hepatic encephalopathy to liver transplantation were 5.85 days and 8.35 days for LDLT and DDLT, respectively (P = 0.091). Among these patients, 121 (45.3%) had grade III or IV hepatic encephalopathy (living, 34.8% vs. deceased, 61.3%; P < 0.001), and 38 (14.2%) had brain edema (living, 16.1% vs. deceased, 11.3%; P = 0.269) before liver transplantation. There were no significant differences in in-hospital mortality (living, 11.8% vs. deceased, 15.1%; P = 0.435), 10-year overall survival (living, 90.8% vs. deceased, 84.0%; P = 0.096), and graft survival (living, 83.5% vs. deceased, 71.3%; P = 0.051). However, postoperatively, the mean intensive care unit stay was shorter in the LDLT group (5.0 days vs. 9.5 days, P < 0.001). In-hospital mortality was associated with vasopressor use (odds ratio [OR], 3.40; 95% confidence interval [CI], 1.45-7.96; P = 0.005) and brain edema (OR, 2.75; 95% CI, 1.16-6.52; P = 0.022) of recipient at the time of transplantation. However, LDLT (OR, 1.26; 95% CI, 0.59-2.66; P = 0.553) was not independently associated with in-hospital mortality. Conclusion: LDLT is feasible for acute liver failure when organs from deceased donors are not available.

In Vivo Optical Clearing of Mammalian Brain.

Established methods for imaging the living mammalian brain have, to date, taken optical properties of the tissue as fixed; we here demonstrate that it is possible to modify the optical properties of the brain itself to significantly enhance at-depth imaging while preserving native physiology. Using a small amount of any of several biocompatible materials to raise the refractive index of solutions superfusing the brain prior to imaging, we could increase several-fold the signals from the deepest cells normally visible and, under both one-photon and two-photon imaging, visualize cells previously too dim to see. The enhancement was observed for both anatomical and functional fluorescent reporters across a broad range of emission wavelengths. Importantly, visual tuning properties of cortical neurons in awake mice, and electrophysiological properties of neurons assessed ex vivo, were not altered by this procedure.

Single center experience with hourglass-like constriction neuropathy of suprascapular nerve.

INTRODUCTION/AIMS: Hourglass-like constriction (HGC) may occur in several peripheral nerves. However, data on the prognosis of motor weakness in patients with HGC of the suprascapular nerve (SSN) are limited compared with other nerves. Here, we aimed to describe the clinical and imaging features of HGC of the SSN. METHODS: We retrospectively reviewed patients diagnosed with suprascapular neuropathy using magnetic resonance imaging (MRI) or electrodiagnostic studies over 16 years. After excluding extrinsic causes, patients with HGC of the SSN detected using MRI were included. RESULTS: Fourteen patients with HGC of the SSN were identified. MRI revealed that all HGCs were located between the origin of the SSN from the upper trunk of the brachial plexus and the suprascapular notch. Seven patients exhibited HGC precisely at the origin of the SSN from the brachial plexus. Four patients showed T2 hyperintensity of the SSN extending to the upper trunk of the brachial plexus or the extraforaminal cervical root. The initial treatments included observation (n = 1), steroid therapy (n = 12), suprascapular notch release (n = 1). Of the 12 patients with a sufficient follow-up period, nine fully recovered from motor weakness of the SSN with non-operative treatments. Six of the nine patients who recovered fully experienced their first clinical improvement more than 6 months after onset. DISCUSSION: Treatment strategies for HGC differ depending on the affected nerve. For HGC of the SSN, due to the high spontaneous recovery rate observed in our study, conservative management for at least 6 months should be initially considered.

Generation of Directly Reprogrammed Human Endothelial Cells.

Direct reprogramming provides a novel breakthrough for generating functional endothelial cells (ECs) without the need for intermediate stem or progenitor states, offering a promising resource for cardiovascular research and treatment. ETV2 is a key transcription factor that has been identified as a pioneering factor for specifying endothelial lineage. Achieving precise ETV2 induction is essential for effective endothelial reprogramming, and maintaining the reprogrammed cellular phenotype relies on a specific combination of growth factors and small molecules. Thus, we hereby provide a straightforward and comprehensive protocol for generating two distinct types of reprogrammed ECs (rECs) from human dermal fibroblasts (HDFs). Early rECs demonstrate a robust neovascularization property but lack the mature EC phenotype, while late rECs exhibit phenotypical similarity to human postnatal ECs and have a neovascularization capacity similar to early rECs. Both cell types can be derived from human somatic source cells, making them suitable for personalized disease investigations, drug discovery, and disease therapy.

Fabrication of granular three-dimensional graphene oxide/UiO-66 adsorbent for high uranium adsorption: Density functional theory and fixed bed column studies.

This study presents a thorough investigation of the novel application of graphene oxide (GO) modified with melamine formaldehyde to fabricate granular three-dimensional GO (3D-GO), followed by the introduction of UiO-66 doping (3D-GO/U) for high uranium (U) adsorption. The U(VI) adsorption isotherms revealed that 3D-GO/U-10 with 10 % UiO-66 incorporation exhibited an impressive adsorption capacity of 375.5 mg g-1 and remained high U(VI) sorption performance in wide pH range. The introduction of UiO-66 to 3D-GO (3D-GO/U-10) led to the deagglomeration of the UiO-66 particles. The in situ surface-enhanced-Raman-spectroscopy-analysis and density-functional-theory simulations showed the symmetric metal center site Zr-O2 on UiO-66 was discovered to exhibit the highest adsorption energy (-3.21 eV) for U(VI) species due to the electrons transfer from the oxygen atom to U(VI) drives the covalent bonding between the symmetric metal center sites Zr-O2 and U(VI) on 3D-GO/U-10. The 3D-GO/U-10 was regenerated using a 0.1 M Na2CO3/0.01 M H2O2 solution and achieved up to 89.7 % U(VI) removal in the 5th cycle. The continuous flow column experiments results revealed 3D-GO/U-10 can regenerate and maintain a U(VI) removal capacity of ∼76 % for up to 4 cycles column experiments. Therefore, 3D-GO/U-10 exhibits great potential for removing U(VI) from water bodies.

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.

Short- and medium-term exposure to ambient air pollution and periodontal status.

We investigated the association between ambient air pollutant exposure and periodontal health using data from 17,271 adults in the Korea National Health and Nutrition Examination Survey (2012-2015). Participants' periodontal status was categorized based on their community periodontal index (CPI) scores. Using multiple logistic regression models, we examined the relationship between air pollutant levels and poor periodontal status at various lag periods. After adjusting for potential confounders, PM10 exposure was associated with a poor periodontal status (short-term: 0-1 and 0-2 lag days; medium-term: 0-1 and 0-2 lag months). SO2 exposure showed similar associations (short-term, 0-2 to 0-7 lag days; medium-term, 0-4 to 0-6 lag months). Only increased medium-term O3 exposure (0-2 to 0-6 lag months) was associated with a poor periodontal status. NO2 exposure was inversely associated with poor periodontal status for both short- and medium-term durations.

Perspectives on advance care planning and related end-of-life care in people with heart failure: A Q methodology study.

Negative perspectives around advance care planning (ACP) prevent people with heart failure (HF) from preparing their end-of-life (EOL) effectively. A Q methodology study was conducted to identify types of ACP perspectives in Koreans with HF. The Q sample (31 statements representing ACP perspectives) was constructed through an extensive literature review and in-depth qualitative interview. The P sample (individuals with HF) completed each grid with a statement on the Q sorting table. The data were analyzed using the PQ program. Individuals with HF have both different and common perspectives on ACP. Three types of perspectives were identified: "positive acceptance," "contemplative support," and "hesitancy in acceptance." Common perspectives across types indicated that people with HF had positive attitudes toward ACP and emphasized their autonomy in EOL decisions. Clinicians need to consider these different and common perspectives on ACP to facilitate patients' engagement and provide relevant support.

Seasonal dynamics of airborne biomolecules influence the size distribution of Arctic aerosols.

Organic matter is crucial in aerosol-climate interactions, yet the physicochemical properties and origins of organic aerosols remain poorly understood. Here we show the seasonal characteristics of submicron organic aerosols in Arctic Svalbard during spring and summer, emphasizing their connection to transport patterns and particle size distribution. Microbial-derived organic matter (MOM) and terrestrial-derived organic matter (TOM) accounted for over 90% of the total organic mass in Arctic aerosols during these seasons, comprising carbohydrate/protein-like and lignin/tannin-like compounds, respectively. In spring, aerosols showed high TOM and low MOM intensities due to biomass-burning influx in the central Arctic. In contrast, summer exhibited elevated MOM intensity, attributed to the shift in predominant atmospheric transport from the central Arctic to the biologically active Greenland Sea. MOM and TOM were associated with Aitken mode particles (<100 nm diameter) and accumulation mode particles (>100 nm diameter), respectively. This association is linked to the molecular size of biomolecules, impacting the number concentrations of corresponding aerosol classes. These findings highlight the importance of considering seasonal atmospheric transport patterns and organic source-dependent particle size distributions in assessing aerosol properties in the changing Arctic.

Contrast-Enhanced T1-Weighted Magnetic Resonance Cholangiography Using Gadoxetate Disodium in Potential Living Liver Donors: Qualitative and Quantitative Improvement with 3-hour Delayed Imaging.

BACKGROUND: Contrast-enhanced T1-weighted magnetic resonance cholangiography (CE-T1-MRC) after gadoxetate disodium administration can be used for preoperative evaluation of the bile ducts in live liver donors. This study aimed to determine whether CE-T1-MRC with 3-hour delayed imaging improves bile duct visualization both qualitatively and quantitatively compared with 20-minute delayed imaging in potential living liver donors. METHODS: We retrospectively identified 33 potential living liver donors (mean age, 30.1 years; 18 men and 15 women) who underwent preoperative CE-T1-MRC with both 20-minute delayed and 3-hour delayed imaging in a single session. The radiologist scored biliary visualization for right and left hepatic ducts (RHD and LHD), their secondary confluences and segmental bile ducts, common hepatic duct (CHD), and cystic duct (CD), and measured relative contrast ratio (rC) and relative signal intensity (rS) for RHD, LHD, and CHD. The data were analyzed using Wilcoxon's signed-rank test and paired t-test. RESULTS: In qualitative analysis, duct visualization scores for RHD and LHD, their secondary confluences and segmental bile ducts, CHD, and CD were significantly higher on CE-T1-MRC with 3-hour delayed imaging than with 20-minute delayed imaging (all, P ≤ .046). In quantitative analysis, both rC and rS of RHD, LHD, and CHD were significantly higher on CE-T1-MRC with 3-hour delayed imaging than with 20-minute delayed imaging (all, P < .001). CONCLUSIONS: CE-T1-MRC with 3-hour delay imaging improves bile duct visualization both qualitatively and quantitatively in potential living liver donors.

Double-Cannula Maneuver for the Double-Roll Configuration of Donor Descemet Membrane Outside Recipient Anterior Chamber During Descemet Membrane Endothelial Keratoplasty.

PURPOSE: The purpose of this study was to present a new surgical technique to convert a single roll of Descemet membrane (DM) into a double roll using 2 cannulas in a balanced salt solution-filled Petri dish during DM endothelial keratoplasty. METHODS: A single DM roll stained with trypan blue was placed in a balanced salt solution-filled Petri dish. Two cannulas (28G) were introduced from opposite ends of the single roll, inserted into the roll, and slowly spread apart to change the single roll into a double roll. The DM was aspirated into the modified Jones tube and loaded, maintaining a double-roll configuration with endothelium-down orientation in a bevel-up position. The modified Jones tube with the bevel down was inserted into the recipient anterior chamber through the main wound. The modified Jones tube was rotated to the bevel-up orientation. After checking the graft orientation, the DM was inserted into the recipient anterior chamber. The double-roll DM was easily unfolded by tapping the center of the cornea using a cannula. A 28G cannula was inserted under the DM, and the anterior chamber was filled with air. RESULTS: Three months after surgery, the patient's corrected visual acuity in the right eye was 6/7.5 and the endothelial cell count was 1095/mm2. The corneal thickness was 533 µm, and the cornea was clear. CONCLUSIONS: The double-cannula maneuver mechanically changes the single roll of the donor DM to a double roll outside the recipient anterior chamber, making DM unfolding easier and minimizing the risk of upside-down apposition of the donor DM.