Direct oral anticoagulants for oral anticoagulants-naïve Asian patients with atrial fibrillation and end-stage renal disease undergoing dialysis.

In Asian patients with atrial fibrillation (AF) and end-stage renal disease (ESRD) undergoing dialysis, the use of direct oral anticoagulants (DOACs) remains debatable. From the national health insurance claims data in South Korea, we included 425 new users of OAC among patients with non-valvular AF and ESRD undergoing dialysis between 2013 and 2020. Patients were categorized into DOAC (n = 106) and warfarin group (n = 319). Clinical outcomes, including ischemic stroke, myocardial infarction (MI), intracranial hemorrhage (ICH), and gastrointestinal (GI) bleeding, were compared between the two groups using inverse probability of treatment weighting (IPTW) analysis. During the median follow-up of 3.2 years, the incidence of ischemic stroke was significantly reduced in the DOAC compared to the warfarin group [Hazard ratio (HR) 0.07; P = 0.001]. However, the incidence of MI (HR 1.32; P = 0.41) and GI bleeding (HR 1.78; P = 0.06) were not significantly different between the two groups. No ICH events occurred in the DOAC group, although the incidence rate did not differ significantly between the two groups (P = 0.17). In Asian patients with AF and ESRD undergoing dialysis, DOACs may be associated with a reduced risk of ischemic stroke compared with warfarin. The MI, ICH, and GI bleeding rates may be comparable between DOACs and warfarin.

Relation between change of effective lens position and toric IOL rotation after toric IOL implantation.

OBJECTIVE: To evaluate the relationship between change of effective lens position (ELP) and toric intraocular lens (IOL) rotation in patients with increasing postoperative refractive astigmatism after successful toric IOL implantation. METHODS: The subjects include 61 people (61 eyes) with increasing residual astigmatism >0.5 D 3 months after successful toric IOL implantation. Clinical measurements included preoperative, 1-week, and 1-, 2-, and 3-month postoperative visual acuity; refraction; keratometer; anterior and posterior corneal astigmatism; ELP by Scheimpflug camera imaging; and IOL axis by slit-lamp biomicroscopic photograph with pupil dilation. RESULTS: Residual astigmatism in postoperative month 3 (0.81 ± 0.50 D) is higher than that at postoperative week 1 (0.41 ± 0.38 D; p < 0.05). ELP decreased by 264.44 ± 163.25 µm, and the IOL rotated by 2.91 ± 1.44 degrees from week 1 to month 3 (p < 0.05). The ELP change had a positive correlation with IOL rotation (R2 = 0.383; p = 0.006), and the postoperative refractive astigmatic change had a positive correlation with ELP change (R2 = 0.272; p = 0.027) and IOL rotation (R2 = 0.272; p = 0.0001) from week 1 to month 3. CONCLUSION: ELP change can influence toric IOL rotation and increase residual astigmatism after toric IOL implantation.

Evaluation of Droplet Digital PCR for the Detection of BRAF V600E in Fine-Needle Aspiration Specimens of Thyroid Nodules.

Background: Droplet digital (dd)PCR is a new-generation PCR technique with high precision and sensitivity; however, the positive and negative droplets are not always effectively separated because of the "rain" phenomenon. We aimed to develop a practical optimization and evaluation process for the ddPCR assay and to apply it to the detection of BRAF V600E in fine-needle aspiration (FNA) specimens of thyroid nodules, as an example. Methods: We optimized seven ddPCR parameters that can affect "rain." Analytical and clinical performance were analyzed based on histological diagnosis after thyroidectomy using a consecutive prospective series of 242 FNA specimens. Results: The annealing time and temperature, number of PCR cycles, and primer and probe concentrations were found to be more important considerations for assay optimization than the denaturation time and ramp rate. The limit of blank and 95% limit of detection were 0% and 0.027%, respectively. The sensitivity of ddPCR for histological papillary thyroid carcinoma (PTC) was 82.4% (95% confidence interval [CI], 73.6%-89.2%). The pooled sensitivity of BRAF V600E in FNA specimens for histological PTC was 78.6% (95% CI, 75.9%-81.2%, I2=60.6%). Conclusions: We present a practical approach for optimizing ddPCR parameters that affect the separation of positive and negative droplets to reduce rain. Our approach to optimizing ddPCR parameters can be expanded to general ddPCR assays for specific mutations in clinical laboratories. The highly sensitive ddPCR can compensate for uncertainty in cytological diagnosis by detecting low levels of BRAF V600E.

The combined effect of epidermal growth factor and keratinocyte growth factor delivered by hyaluronic acid hydrogel on corneal wound healing.

This study strategically incorporates epidermal growth factor (EGF) and keratinocyte growth factor (KGF) within a hyaluronic acid (HA) hydrogel to enhance corneal wound healing. The controlled release of EGF and KGF from the HA hydrogel is engineered to promote the regeneration of both the epithelial and stromal layers. Specifically, EGF plays a pivotal role in the regeneration of the epithelial layer, while KGF exhibits efficacy in the regeneration of the stromal layer. The combination of these growth factors facilitates efficient regeneration of each layer and demonstrates the capability to modulate each other's regenerative effects. The interplay between EGF and KGF provides an understanding of their cooperative influence on the dynamics of corneal wound healing. The results of this study contribute to the development of advanced strategies for corneal wound management and offer insights into the complex process of corneal regeneration.

Modeling of solar UV-induced photodamage on the hair follicles in human skin organoids.

Solar ultraviolet (sUV) exposure is known to cause skin damage. However, the pathological mechanisms of sUV on hair follicles have not been extensively explored. Here, we established a model of sUV-exposed skin and its appendages using human induced pluripotent stem cell-derived skin organoids with planar morphology containing hair follicles. Our model closely recapitulated several symptoms of photodamage, including skin barrier disruption, extracellular matrix degradation, and inflammatory response. Specifically, sUV induced structural damage and catagenic transition in hair follicles. As a potential therapeutic agent for hair follicles, we applied exosomes isolated from human umbilical cord blood-derived mesenchymal stem cells to sUV-exposed organoids. As a result, exosomes effectively alleviated inflammatory responses by inhibiting NF-κB activation, thereby suppressing structural damage and promoting hair follicle regeneration. Ultimately, our model provided a valuable platform to mimic skin diseases, particularly those involving hair follicles, and to evaluate the efficacy and underlying mechanisms of potential therapeutics.

In Vivo Human Lacrimal Gland Imaging Using an Ultrasound Biomicroscopy.

PURPOSE: In the present study, we introduce human lacrimal gland imaging using an ultrasound biomicroscopy (UBM) with a soft cover and show their findings. METHODS: The representative UBM findings of palpebral lobes in seven subjects (four with non-Sjögren dry eye syndrome, one with Sjögren syndrome, and two healthy subjects) were described in this study. To prolapse the palpebral lobe, the examiner pulled the temporal part of the upper eyelid in the superotemporal direction and directed the subject to look in the inferonasal direction. We scanned the palpebral lobes longitudinally and transversely using UBM. We used an Aviso UBM with a 50 MHz linear probe and ClearScan. RESULTS: In UBM of two healthy subjects, the echogenicity of the lacrimal gland was lower than that of the sclera and homogeneous. But the parenchyma of a patient with Sjögren dry eye syndrome was quite inhomogeneous compared to the healthy subjects. In two patients with dry eye syndrome, we were able to observe some lobules in the parenchyma. We could find excretory ducts running parallel at the surface of the longitudinal section in some subjects. In the longitudinal UBM scan of a subject, we observed a tubular structure at a depth of 1,500 µm that was considered a blood vessel. It ran from the superonasal to the inferotemporal direction. In a subject, we observed a large cyst beneath the conjunctiva. CONCLUSIONS: Lacrimal gland imaging using UBM has both advantages of optical coherence tomography and sonography, and could be useful for evaluating dry eye syndrome.

Potential biological functions and future perspectives of sialylated milk oligosaccharides.

Sialyllactoses (SLs) primarily include sialylated human milk oligosaccharides (HMOs) and bovine milk oligosaccharides (BMOs). First, the safety assessment of 3'-sialyllactose (3'-SL) and 6'-sialyllactose (6'-SL) revealed low toxicity in various animal models and human participants. SLs constitute a unique milk component, highlighting the essential nutrients and bioactive components crucial for infant development, along with numerous associated health benefits for various diseases. This review explores the safety, biosynthesis, and potential biological effects of SLs, with a specific focus on their influence across various physiological systems, including the gastrointestinal system, immune disorders, rare genetic disorders (such as GNE myopathy), cancers, neurological disorders, cardiovascular diseases, diverse cancers, and viral infections, thus indicating their therapeutic potential.

Effect of complicated, untreated and uncontrolled diabetes and pre-diabetes on treatment outcome among patients with pulmonary tuberculosis.

BACKGROUND AND OBJECTIVE: Patients with tuberculosis and diabetes have a higher risk of unfavourable anti-tuberculosis treatment outcomes. In the present study, we aimed to evaluate the effects of various diabetes statuses on the outcomes of patients with pulmonary tuberculosis. METHODS: Among the patients with pulmonary tuberculosis enrolled in the Korea Tuberculosis Cohort (KTBC) registry and the multicentre prospective cohort study of pulmonary tuberculosis (COSMOTB), those with diabetes and complicated diabetes were identified. The primary and secondary outcomes were unfavourable outcomes and mortality, respectively. The effect of diabetes and complicated diabetes on the outcomes was assessed using multivariable logistic regression analysis. Using COSMOTB, subgroup analyses were performed to assess the association between various diabetes statuses and outcomes. RESULTS: In the KTBC, diabetes (adjusted odds ratio [aOR] = 1.93, 95% CI = 1.64-2.26) and complicated diabetes (aOR = 1.96, 95% CI = 1.67-2.30) were significantly associated with unfavourable outcomes, consistent with the COSMOTB data analysis. Based on subgroup analysis, untreated diabetes at baseline was an independent risk factor for unfavourable outcomes (aOR = 2.72, 95% CI = 1.26-5.61). Prediabetes and uncontrolled diabetes increased unfavourable outcomes and mortality without statistical significance. CONCLUSION: Untreated and complicated diabetes at the time of tuberculosis diagnosis increases the risk of unfavourable outcomes and mortality.

Inverse chirality-induced spin selectivity effect in chiral assemblies of π-conjugated polymers.

Coupling of spin and charge currents to structural chirality in non-magnetic materials, known as chirality-induced spin selectivity, is promising for application in spintronic devices at room temperature. Although the chirality-induced spin selectivity effect has been identified in various chiral materials, its Onsager reciprocal process, the inverse chirality-induced spin selectivity effect, remains unexplored. Here we report the observation of the inverse chirality-induced spin selectivity effect in chiral assemblies of π-conjugated polymers. Using spin-pumping techniques, the inverse chirality-induced spin selectivity effect enables quantification of the magnitude of the longitudinal spin-to-charge conversion driven by chirality-induced spin selectivity in different chiral polymers. By widely tuning conductivities and supramolecular chiral structures via a printing method, we found a very long spin relaxation time of up to several nanoseconds parallel to the chiral axis. Our demonstration of the inverse chirality-induced spin selectivity effect suggests possibilities for elucidating the puzzling interplay between spin and chirality, and opens a route for spintronic applications using printable chiral assemblies.

CD19 CAR-expressing iPSC-derived NK cells effectively enhance migration and cytotoxicity into glioblastoma by targeting to the pericytes in tumor microenvironment.

In cancer immunotherapy, chimeric antigen receptors (CARs) targeting specific antigens have become a powerful tool for cell-based therapy. CAR-natural killer (NK) cells offer selective anticancer lysis with reduced off-tumor toxicity compared to CAR-T cells, which is beneficial in the heterogeneous milieu of solid tumors. In the tumor microenvironment (TME) of glioblastoma (GBM), pericytes not only support tumor growth but also contribute to immune evasion, underscoring their potential as therapeutic targets in GBM treatment. Given this context, our study aimed to target the GBM TME, with a special focus on pericytes expressing CD19, to evaluate the potential effectiveness of CD19 CAR-iNK cells against GBM. We performed CD19 CAR transduction in induced pluripotent stem cell-derived NK (iNK) cells. To determine whether CD19 CAR targets the TME pericytes in GBM, we developed GBM-blood vessel assembloids (GBVA) by fusing GBM spheroids with blood vessel organoids. When co-cultured with GBVA, CD19 CAR-iNK cells migrated towards the pericytes surrounding the GBM. Using a microfluidic chip, we demonstrated CD19 CAR-iNK cells' targeted action and cytotoxic effects in a perfusion-like environment. GBVA xenografts recapitulated the TME including human CD19-positive pericytes, thereby enabling the application of an in vivo model for validating the efficacy of CD19 CAR-iNK cells against GBM. Compared to GBM spheroids, the presence of pericytes significantly enhanced CD19 CAR-iNK cell migration towards GBM and reduced proliferation. These results underline the efficacy of CD19 CAR-iNK cells in targeting pericytes within the GBM TME, suggesting their potential therapeutic value for GBM treatment.

Current status of contact lenses usage in Korea: A population-based cohort study 2021.

PURPOSE: To investigate trends in contact lens usage in a nationally representative sample of the Korean population in 2021. METHODS: For this retrospective study, we analyzed data of 3,601 Korean participants aged 10-59 years, from the Korea National Health and Nutrition Examination Survey (KNHANES 2021 version), who underwent eye examination, of whom 1,136 individuals (274 men and 862 women) were contact lens users. The demographic trend among Korean contact lens wearers was examined using statistical analyses to investigate the changes in their contact lens-wearing experience, duration of lens use, type of lens used, location of purchase, presence of an Eye Care Practitioner(ECP)'s prescription, lens-related ophthalmic complications, and type of lenses worn at the time of complications, according to sex. Multivariable logistic regression analysis was conducted to examine the association of each variable with the rate of complications and use of soft lenses. RESULTS: The average age of the contact lens users was 33.42±0.33 years, with 70.36% (weighted percentage) of users being women who used contact lenses for significantly longer periods than men (p<0.001). Additionally, only wearing of cosmetic lenses was significantly correlated with the occurrence of complications (p = 0.006), and 6.76% of users purchased lenses without a prescription. Multivariate analysis among the contact lens users revealed a significant relationship between the complication rate and female sex (p = 0.002), pre-existing eye disease diagnosed by ECPs (p = 0.0288), and duration of contact lens use (p<0.0001). CONCLUSION: We identified sex differences in contact lens usage trends in Korea. The main changes observed were an increase in middle-aged lens users and a decrease in female users compared to that in the early 2000s. In addition, contact lens complications were significantly associated with sex and pre-existing eye disease. Therefore, those wearing contact lenses for extended periods should exercise caution and consult eye care specialists in the presence of any symptoms.

Analysis of the perceptions, competencies, and educational needs for global health among Korean medical students.

PURPOSE: The purpose of this study was to examine perceptions of global health education (GHE) among medical students and their involvement in global health activities and identify priorities of educational needs for developing GHE programs. METHODS: This study was cross-sectional and conducted through an online survey for medical students. The participants were students attending medical schools nationwide, and the final analysis target was 678. The survey developed questionnaires necessary for research purposes regarding global health-related experiences and perceptions, level of awareness of global health competencies (GHC), and needs assessments. The data were analyzed using the frequency analysis, chi-square test, independent t-test, Borich Needs Assessment Model, and the Locus for Focus Model. RESULTS: In total, 60.6% (411/678) agreed on the need for GHE, whereas 12.1% (82/678) agreed on the appropriateness of GHE in the current medical school curriculum, indicating a perception gap between the necessity and the status. At the current level of awareness of global health and GHC, we identified statistically significant differences according to gender, participation in global health activities, and GHE. In the analysis of the educational needs of GHC, all items of GHC had statistically significant differences between the importance level and the current level, and priorities were derived. The competency with the highest priority was domain A (Global Burden of Disease). CONCLUSION: We expect the findings of this study to be used in Korean medical education as fundamental data to prepare a hereafter research foundation for GHE and discuss systematic GHE based on GHC.

Ocular parameters associated with visual performance of enhanced monofocal intraocular lens.

BACKGROUND: An enhanced monofocal intraocular lenses (IOLs) (Tecnis Eyhance ICB00 and Tecnis Eyhance Toric DIU) has been developed to enhance intermediate vision while avoiding the disadvantages of multifocal IOLs. Although many studies have demonstrated the improvement of intermediate visual acuity with enhanced monofocal IOLs, it is not known specifically for which patients these IOLs should be recommended or avoided. In this study, we aim to find out which ocular parameters affect vision performance and photic phenomenon of ICB00 or DIU at different distances. METHODS: Patients who underwent cataract surgery with ICB00 or DIU, performed by a single surgeon, were included. Before surgery, the patients' age, gender, axial length, anterior chamber depth, spherical aberration Z (4,0), vertical coma, horizontal coma, angle kappa (κ), angle alpha (α), and other ocular parameters were investigated. One month after surgery, uncorrected near visual acuity (UNVA at 40 cm), uncorrected intermediate visual acuity (UIVA at 66 cm), uncorrected distance logMAR visual acuity (UDVA), IOL decentration, and quality of vision (QoV) questionnaires were conducted. RESULTS: A total of 43 patients (58 eyes) were included. The results of the univariate linear regression analyses showed a negative correlation between spherical aberration and logMAR UNVA and UIVA (p = 0.003, ß=-0.51 and p = 0.018, ß=-0.23, respectively) and a positive correlation between angle α and logMAR UIVA (p = 0.036, ß = 0.19). Deeper anterior chamber depth (ACD) was associated with poorer total QoV (p = 0.018, ß = 14.43), particularly in glare, halo, blur, and fluctuation perception. A higher degree of IOL decentration tended to decrease UNVA and UIVA (Pearson correlation coefficient, r = 0.336 and r = 0.221, respectively); however, no significant effect was observed on UDVA (Pearson correlation coefficient, r = 0.042). CONCLUSIONS: In enhanced monofocal IOLs, a higher level of spherical aberration is associated with better performance in UNVA and UIVA, whereas a larger angle α has a negative impact. A deeper ACD negatively affects the QoV.

Retrospective Analysis of a New Intrastromal Dissection Technique Using the Retinal Reflex for Deep Anterior Lamellar Keratoplasty.

PURPOSE: The purpose of this study was to describe a new surgical technique for deep anterior lamellar keratoplasty. METHODS: All pupils in the recipient eyes were dilated preoperatively. Vertical grooving was performed using a crescent blade with a width of 5 mm and a depth of one-third to half corneal thickness on the temporal side of the limbus. Stromal dissection was performed as close as possible to Descemet membrane by observing the gap between the gold line by retinal reflex and the front edge of the crescent blade. Lamellar dissection was performed along the lamellar plane using corneal dissectors. The ophthalmic viscoelastic device was injected into the intrastromal pocket to separate the anterior and posterior stroma and an anterior corneal lamella was excised. A donor cornea was sutured into the recipient bed. RESULTS: In 18 eyes, none of the patients had Descemet membrane rupture during surgery. The mean postoperative residual stromal thickness was 80 ± 31 µm. The mean central corneal thickness after surgery was 660 ± 69 µm. At the last follow-up, the cornea was cleared in all 18 eyes on slit-lamp examination. CONCLUSIONS: We estimated the residual stromal thickness based on the gap between the gold line by the retinal reflex and crescent blade, and intrastromal lamellar dissection was performed using a smooth corneal dissector. Consequently, the surface of stromal dissection was smooth, and the residual stromal thickness was even.

3'-Sialyllactose protects against LPS-induced endothelial dysfunction by inhibiting superoxide-mediated ERK1/2/STAT1 activation and HMGB1/RAGE axis.

AIM: Endothelial hyperpermeability is an early stage of endothelial dysfunction associated with the progression and development of atherosclerosis. 3'-Sialyllactose (3'-SL) is the most abundant compound in human milk oligosaccharides, and it has the potential to regulate endothelial dysfunction. This study investigated the beneficial effects of 3'-SL on lipopolysaccharide (LPS)-induced endothelial dysfunction in vitro and in vivo. MAIN METHODS: We established LPS-induced endothelial dysfunction models in both cultured bovine aortic endothelial cells (BAECs) and mouse models to determine the effects of 3'-SL. Western blotting, qRT-PCR analysis, immunofluorescence staining, and en face staining were employed to clarify underlying mechanisms. Superoxide production was measured by 2',7'-dichlorofluorescin diacetate, and dihydroethidium staining. KEY FINDINGS: LPS significantly decreased cell viability, whereas 3'-SL treatment mitigated these effects via inhibiting ERK1/2 activation. Mechanistically, 3'-SL ameliorated LPS-induced ROS accumulation leading to ERK1/2 activation-mediated STAT1 phosphorylation and subsequent inhibition of downstream transcriptional target genes, including VCAM-1, TNF-α, IL-1ß, and MCP-1. Interestingly, LPS-induced ERK1/2/STAT1 activation leads to the HMGB1 release from the nucleus into the extracellular space, where it binds to RAGE, while 3'-SL suppressed EC hyperpermeability by suppressing the HMGB1/RAGE axis. This interaction also led to VE-cadherin endothelial junction disassembly and endothelial cell monolayer disruption through ERK1/2/STAT1 modulation. In mouse endothelium, en face staining revealed that 3'-SL abolished LPS-stimulated ROS production and VCAM-1 overexpression. SIGNIFICANCE: Our findings suggest that 3'-SL inhibits LPS-induced endothelial hyperpermeability by suppressing superoxide-mediated ERK1/2/STAT1 activation and HMGB1/RAGE axis. Therefore, 3'-SL may be a potential therapeutic agent for preventing the progression of atherosclerosis.

Evaluation of ergonomic risks for work-related musculoskeletal disorders of nursing tasks in Korea.

Among all industrial accident-induced diseases, musculoskeletal disorders (MSDs) are most prominently observed among nurses. The physical load of everyday tasks involved in nursing work was assessed in this study using a developed risk index, whereby the physical burden was evaluated using the exposure duration and work intensity levels. This survey targeted nine small, medium and large-sized hospitals in South Korea and categorized representative nursing tasks into six groups. The subtasks within these six categories (evaluated as high risk) included changing a patient's posture and assisting with walkers or wheelchairs, transporting/handling drug carts, bathing patients, replacing bedding, traction therapy, cardiopulmonary resuscitation and artificial manual breathing unit, and computer work. The risk index ratio was significantly different by task type for each task. We demonstrated that the risk index developed in this study can be used to evaluate MSDs in hospitals.

Research trends in ergonomics, industrial safety and health: semantic network and topic analyses.

We evaluated the research trends in ergonomics, industrial safety and health from the 1980s to the present. In the ergonomics area, keywords and abstracts from five journals were analyzed. For industrial safety and health, six journal databases were evaluated. A frequency analysis, a semantic network of keywords and a topic network of abstracts were conducted. The results of ergonomics showed that 'macro-ergonomics' and 'manual material handling' were the most popular topics, and 'ergonomic' and 'electromyography' were the most cited keywords. 'Posture' and 'biomechanics' were the most frequently used with high centrality. The results of industrial safety and health showed that 'job stress' and 'organizational safety' were the most popular topics, and 'occupational exposure' and 'occupational health' were the most cited keywords. 'Dust' and 'exposure' were frequently used with high centrality. The results would be helpful in understanding the trends of research efforts and foreseeing trends of future research.

Categorization of Meibomian Gland Dysfunction Using Lipid Layer Thickness and Meibomian Gland Dropout in Dry Eye Patients: A Retrospective Study.

PURPOSE: In the present study, we determined the prevalence of obstructive meibomian gland dysfunction (MGD), hyposecretory MGD, grossly normal MG, and hypersecretory MGD in patients with dry eye syndrome using lipid layer thickness (LLT) and MG dropout. METHODS: Eighty-eight patients with dry eye syndrome were included in the study. Patients were categorized into four groups according to the LLT and weighted total meiboscore. The proportion of patients in each group was calculated. The age, sex, Ocular Surface Disease Index, LLT, Schirmer, tear film breakup time, cornea stain, weighted total meiboscore, expressibility, and quality of meibum were compared between the four groups. RESULTS: Fifteen eyes (17.0%) had obstructive MGD, two eyes (2.3%) had hyposecretory MGD, 40 eyes (45.5%) had grossly normal MG, and 17 eyes (19.3%) had hypersecretory MGD. The obstructive MGD group was younger than the grossly normal MG group. In obstructive MGD, the ratio of men to women was higher than that of the other groups. However, Ocular Surface Disease Index, Schirmer, tear film breakup time, and corneal stain did not show statistically significant differences between the four groups. The meibum expressibility of the hyposecretoy MGD group was worse than those of the other groups. The meibum expressibility of the hyposecretoy MGD group was poor than those of the obstructive and hypersecretory MGD group. CONCLUSIONS: This categorization was expected to help determine the best treatment method for dry eye syndrome, according to the MG status.