Synergistic Renoprotective Effects of Green Tea Extract and Gemigliptin against Tacrolimus-Induced Nephrotoxicity in Mice

SUMMARY: Although tacrolimus (TAC) significantly reduces allograft rejection incidence in solid-organ transplantation, its long-term use is associated with an increased risk of TAC-induced nephrotoxicity. In this study, we investigated the renoprotective effects of green tea extract (GTE) with or without the dipeptidyl peptidase 4 inhibitor, gemigliptin, by assessing serum creatinine levels, the amount of proteinuria, and histopathology in TAC-induced nephrotoxicity. TAC-induced nephrotoxicity was induced by intraperitoneal TAC injection, GTE was administered via subcutaneous injection, and gemigliptin was administered orally. Mice with TAC-induced nephrotoxicity exhibited a significant increase in both serum creatinine levels and 24-hour urine protein. However, when treated with GTE via subcutaneous injection, mice showed a decrease in serum creatinine levels and the amount of proteinuria. When GTE was combined with gemigliptin, further renoprotective effects were observed in biochemical assessments, consistent with the attenuation of TAC-induced nephrotoxicity in histopathology. The expression of p53 protein was lower in the mice treated with the combination of GTE and gemigliptin compared to mice with TAC-induced nephrotoxicity. Our results demonstrate that the combination of GTE and gemigliptin treatment reveals synergistic renoprotective effects by decreasing the expression of p53 protein. These findings suggest that the combination of GTE and gemigliptin could potentially be used as a prophylactic or therapeutic strategy for TAC-induced nephrotoxicity.

Aunque tacrolimus (TAC) reduce significativamente la incidencia de rechazo de aloinjertos en trasplantes de órganos sólidos, su uso a largo plazo se asocia con un mayor riesgo de nefrotoxicidad inducida por TAC. En este estudio, investigamos los efectos renoprotectores del extracto de té verde (GTE) con o sin el inhibidor de la dipeptidil peptidasa 4, gemigliptina, mediante la evaluación de los niveles de creatinina sérica, la cantidad de proteinuria y la histopatología en la nefrotoxicidad inducida por TAC. La nefrotoxicidad inducida por TAC se indujo mediante inyección intraperitoneal de TAC, el GTE se administró mediante inyección subcutánea y la gemigliptina se administró por vía oral. Los ratones con nefrotoxicidad inducida por TAC mostraron un aumento significativo tanto en los niveles de creatinina sérica como en la proteína en orina de 24 horas. Sin embargo, cuando se trataron con GTE mediante inyección subcutánea, los ratones mostraron una disminución en los niveles de creatinina sérica y en la cantidad de proteinuria. Cuando se combinó GTE con gemigliptina, se observaron efectos renoprotectores adicionales en las evaluaciones bioquímicas, lo que concuerda con la atenuación de la nefrotoxicidad inducida por TAC en histopatología. La expresión de la proteína p53 fue menor en los ratones tratados con la combinación de GTE y gemigliptina en comparación con los ratones con nefrotoxicidad inducida por TAC. Nuestros resultados demuestran que la combinación de tratamiento con GTE y gemigliptina revela efectos renoprotectores sinérgicos al disminuir la expresión de la proteína p53. Estos hallazgos sugieren que la combinación de GTE y gemigliptina podría usarse potencialmente como estrategia profiláctica o terapéutica para la nefrotoxicidad inducida por TAC.

Factors affecting good prognosis for out-of-hospital cardiac arrest patients in interhospital helicopter transport in rural area

Objective@#Out-of-hospital cardiac arrest (OHCA) is a common cause of death and serious neurological morbidity. Efforts to reduce the mortality due to OHCA focus on the “chain of survival.” The survival rates of OHCA patients are known to be related to prehospital conditions. @*Methods@#Helicopter emergency medical services (HEMS) provide a variety of procedures, such as cardiopulmonary resuscitation (CPR) and other advanced interventions that may improve the prognosis of OHCA patients. HEMS can respond quickly to long-distance or difficult-to-access places. This study attempted to investigate the characteristics of OHCA patients who had utilized inter-hospital air transport. The study was an observational cohort study using prospective data from a single suburban tertiary care hospital over a period of 7 years. The study data were analyzed using the SPSS version 28 software. @*Results@#In the survival group, the cause was more cardiac-related than in the death group (54% vs. 23.4%; P<0.001). CPR by bystanders and defibrillation by the emergency medical technicians were more frequent than in the death group. Also, the initial rhythm of the survivors was mainly VT or VF (48.0% vs. 14.9%; P<0.003). @*Conclusion@#In the HEMS mission with OHCA arrest, the patients with a cardiac origin, witnessed arrest, those with a shockable rhythm and shorter CPR time had a trend towards better survival and neurological outcomes in this study.

Effects of Analgesics and Sedatives before Silicone-tube Intubation on Patients’ Pain with Nasolacrimal Duct Stenosis

Purpose@#We investigated the effect of preoperative administration of analgesics and sedatives on pain levels during silicone tube intubation conducted under local anesthesia in patients with acquired nasolacrimal duct stenosis. @*Methods@#We retrospectively reviewed the medical records from 121 patients at the ophthalmology department of our hospital from July 2016 to May 2022. In total, 71 patients were administered acetaminophen and diazepam orally, while the remaining 50 were not. Postoperative pain (measured using the visual analogue scale [VAS] score [0 = no pain, 10 = severe pain] immediately after operation), operative duration, and improvement in epiphora symptoms were compared between the two groups. @*Results@#The premedication group had significantly lower VAS scores than the non-premedication group (5.23 ± 2.75 vs. 6.34 ± 2.33, p = 0.02). It also had a notably shorter (p < 0.01) operation duration and higher subjective improvement rate of epiphora symptoms. However, premedication did not influence the tube retention period post-surgery (p = 0.86). @*Conclusions@#The administration of analgesics and sedatives prior to silicone tube intubation effectively mitigates operative pain and reduces operation duration. Furthermore, it may help improve postoperative epiphora symptoms.

Validation and Reliability of the Cataract-related Visual Function Questionnaire (CVFQ)

Purpose@#To evaluate the reliability and validity of the Cataract-related Visual Function Questionnaire (CVFQ). @*Methods@#A prospective cross-sectional study of 141 cataract patients was conducted from March 2022 to June 2022. The questionnaire was created based on a literature review and advice from an expert panel. This study determined its construct validity, criterion validity, internal consistency, and test-retest reliability. @*Results@#The CVFQ consists of 15 items distributed among five categories: overall visual quality, overall visual function, distance vision, near vision, and glare. In the exploratory factor analysis of validity, the first three principal components explained 77.8% of the variance. The p-values in the Spearman correlation test comparing the pre- and postoperative total CVFQ score and best-corrected visual acuity (BCVA) were 0.006 and 0.004, respectively. In the reliability analysis, Cronbach’s alpha was > 0.9 for internal consistency and the p-values of each subcategory were all significant in the analysis of test-retest reliability. @*Conclusions@#Our results indicate that the CVFQ is useful for measuring the visual quality and visual function of cataract patients in Korea.

Senescent tumor cells in colorectal cancer are characterized by elevated enzymatic activity of complexes 1 and 2 in oxidative phosphorylation

Background@#Cellular senescence is defined as an irreversible cell cycle arrest caused by various internal and external insults. While the metabolic dysfunction of senescent cells in normal tissue is relatively well-established, there is a lack of information regarding the metabolic features of senescent tumor cells. @*Methods@#Publicly available single-cell RNA-sequencing data from the GSE166555 and GSE178341 datasets were utilized to investigate the metabolic features of senescent tumor cells. To validate the single-cell RNA-sequencing data, we performed senescence-associated β-galactosidase (SA-β-Gal) staining to identify senescent tumor cells in fresh frozen colorectal cancer tissue. We also evaluated nicotinamide adenine dinucleotide dehydrogenase–tetrazolium reductase (NADH-TR) and succinate dehydrogenase (SDH) activity using enzyme histochemical methods and compared the staining with SA-β-Gal staining. MTT assay was performed to reveal the complex 1 activity of the respiratory chain in in-vitro senescence model. @*Results@#Single-cell RNA-sequencing data revealed an upregulation in the activity of complexes 1 and 2 in oxidative phosphorylation, despite overall mitochondrial dysfunction in senescent tumor cells. Both SA-β-Gal and enzyme histochemical staining using fresh frozen colorectal cancer tissues indicated a high correlation between SA-β-Gal positivity and NADH-TR/SDH staining positivity. MTT assay showed that senescent colorectal cancer cells exhibit higher absorbance in 600 nm wavelength. @*Conclusions@#Senescent tumor cells exhibit distinct metabolic features, characterized by upregulation of complexes 1 and 2 in the oxidative phosphorylation pathway. NADH-TR and SDH staining represent efficient methods for detecting senescent tumor cells in colorectal cancer.

A Study on the Mental Health and Burnout of Medical Staff Responding to the Coronavirus Disease 2019 / 신경정신의학

Objectives@#This study was conducted to identify the level of mental health and burnout of medical staff at hospitals and public health centers, which responded to the coronavirus disease 2019 (COVID-19) in South Korea and to suggest appropriate management plans. @*Methods@#The mental health and burnout levels of medical staff responding to COVID-19 were evaluated through an online survey conducted during the period July 1–14, 2021. To analyze the mental health status of the participants according to their demographic characteristics, the chisquare test, t-test, and an analysis of variance were conducted, followed by Scheffe post-hoc tests for pairwise comparisons. @*Results@#A total of 773 participants were included in the study. An analysis of the clinically significant symptoms of the group showed that 29.5% had posttraumatic stress symptoms, 30.6% had depression, 15.8% had anxiety, 39.8% had somatic symptoms, and 4.5% were seen to be at risk of suicide. The average scores for burnout were as follows: 3.55±1.75 for emotional exhaustion, 2.68±1.73 for depersonalization, and 3.89±1.40 for personal accomplishment. Mental health problems and burnout were found to be high in women, those in the 20–39-year age bracket, those with less than 5 years of work experience, and public health center workers. @*Conclusion@#The medical staff responding to COVID-19 were observed to experience high levels of mental health and burnout problems. Work-related characteristics, such as younger age, lower work experience, and employment at a public health center, may have a negative impact on mental health and cause burnout. Therefore, individualized and systemic support for mental health and to prevent the burnout of medical staff responding to cases of COVID-19 is needed.

Clinical Characteristics of Gynecologic Problems During Childhood in the Korean Population

Background@#This study analyzed common gynecologic problems among Korean patients younger than ten years. @*Methods@#We performed a retrospective analysis of medical records of patients younger than ten years who visited the Pediatric and Adolescent Gynecology Clinic at Samsung Medical Center between 1995 and 2020. @*Results@#Among the 6,605 patients who visited the Pediatric and Adolescent Gynecology Clinic, data from 642 patients younger than ten years were analyzed in this study. The most common chief complaint was genital anomalies, followed by increased vaginal discharge and abnormal findings on clinical examinations. The most common disease entity was agglutination of the labia minora, which was commonly discovered incidentally during routine screenings. Vulvovaginitis, the second most common disease, was identified by symptoms of vaginal discharge, pruritus, and vaginal spotting. Neoplasm, issues with vaginal bleeding, and “other causes” were additional categories of gynecologic problems.245 patients (38.2%) were referred from primary care sources, 175 patients (27.4%) sought care directly at the clinic, 169 patients (26.3%) were referrals from the institution’s pediatric department, and the remainder were referrals from other departments. @*Conclusion@#This study provides information about the gynecologic problems most frequently encountered in pediatric patients. The study provides helpful insight for primary care physicians into the proper management and timing of referrals for these gynecologic problems of pediatric patients.

Risk of Ischemic Heart Disease in Chronic Obstructive Pulmonary Disease: A Nationwide Cohort Study

Background@#Subjects with chronic obstructive pulmonary disease (COPD) have a higher risk of ischemic heart disease (IHD) than individuals without COPD; however, longitudinal evidence is lacking. Therefore, we aimed to estimate the risk of IHD between COPD and control cohorts using a longitudinal nationwide database. @*Methods@#We used 2009–2017 data from the Korean National Health Insurance Service National Sample Cohort (NHIS-NSC). Adult participants at least 20 years of age who underwent health examinations and without a history of COPD or IHD were included (n = 540,976). Participants were followed from January 1, 2009, until death, development of IHD, or December 31, 2019, whichever came first. @*Results@#At baseline, there were 3,421 participants with incident COPD and 537,555 participants without COPD. During a median of 8.0 years (5.3–9.1 years) of follow-up, 2.51% of the participants with COPD (n = 86) and 0.77% of the participants without COPD (n = 4,128) developed IHD, with an incidence of 52.24 and 10.91 per 10,000 person-years, respectively. Participants with COPD had a higher risk of IHD (adjusted hazard ratio, 1.55;95% confidence interval, 1.25–1.93) than subjects without COPD. Demographics such as age, sex, body mass index, and personal health behaviors including smoking status and physical activity did not show significant interaction with the relationship between COPD and IHD (P for interaction > 0.05 for all). @*Conclusion@#The results indicate that COPD is associated with the development of IHD independent of demographic characteristics and health-related behaviors. Based on these results, clinicians should closely monitor the onset of IHD in subjects with COPD.

Visual Aura in Non-Migraine Headaches: A Population Study

Background@#Visual aura (VA) occurs mostly in migraine with aura (MA), but some case studies have reported aura in non-migraine headaches. Thus, information of VA in nonmigraine headaches is scarce. Aim of this study was to investigate the prevalence and impact of VA in non-migraine headache and compare it with that of migraine headache. @*Methods@#This study was a nationwide population-based study. We used an internet-based headache diagnosis questionnaire to diagnose headache, and various modules to evaluate clinical features and comorbidities of participants with headache. We defined migraine headache as migraine and probable migraine (PM), whereas non-migraine headache was defined as a headache but not migraine or PM. VA was defined as a self-reporting VA rating scale score ≥ 3. @*Results@#Of the 3,030 participants, 1,431 (47.2%) and 507 (16.7%) had non-migraine headache and migraine headache, respectively. VA prevalence was much lower in the non-migraine headache group than in the migraine headache group (14.5% [207/1,431] vs. 26.0% [132/507], P < 0.001). In subjects with non-migraine headache, those with VA had a markedly higher number of headache days per 30 days (median [25th –75th percentiles]: 2.0 [1.0–5.0] vs. 2.0 [1.0–3.0], P < 0.001), and headache-related disability (6.0 [3.0–16.0] vs. 2.0 [0.0–7.0], P < 0.001) than those without VA. VA prevalence did not differ significantly according to age and sex. @*Conclusion@#Non-migraine headache with VA patients had more severe symptoms than those without VA. These findings may improve the understanding of VA and the management of individuals with non-migraine headache.

Association Between Oral Health and Airflow Limitation: Analysis Using a Nationwide Survey in Korea

Background@#Although poor oral health is a common comorbidity in individuals with airflow limitation (AFL), few studies have comprehensively evaluated this association. Furthermore, the association between oral health and the severity of AFL has not been well elucidated. @*Methods@#Using a population-based nationwide survey, we classified individuals according to the presence or absence of AFL defined as pre-bronchodilator forced expiratory volume in 1 second/forced vital capacity < 0.7. Using multivariable logistic regression analyses, we evaluated the association between AFL severity and the number of remaining teeth; the presence of periodontitis; the Decayed, Missing, and Filled Teeth (DMFT) index; and denture wearing. @*Results@#Among the 31,839 participants, 14% had AFL. Compared with the control group, the AFL group had a higher proportion of periodontitis (88.8% vs. 79.4%), complete denture (6.2% vs. 1.6%), and high DMFT index (37.3% vs. 27.8%) (P < 0.001 for all). In multivariable analyses, denture status: removable partial denture (adjusted odds ratio [aOR], 1.12; 95% confidence interval [95% CI], 1.04–1.20) and complete denture (aOR, 1.52; 95% CI, 1.01– 2.05), high DMFT index (aOR, 1.13; 95% CI, 1.02–1.24), and fewer permanent teeth (0–19;aOR, 1.32; 95% CI, 1.12–1.52) were significantly associated with AFL. Furthermore, those with severe to very severe AFL had a significantly higher proportion of complete denture (aOR, 2.41; 95% CI, 1.11–3.71) and fewer remaining teeth (0–19; aOR, 2.29; 95% CI, 1.57–3.01). @*Conclusion@#Denture wearing, high DMFT index, and fewer permanent teeth are significantly associated with AFL. Furthermore, a reduced number of permanent teeth (0–19) was significantly related to the severity of AFL. Therefore, physicians should pay attention to oral health in managing patients with AFL, such as chronic obstructive pulmonary disease.

Internal Structure of the Health-Related Quality of Life Instrument with 8-Items in a Nationally Representative Population

Purpose@#This study evaluated the internal structure (structural validity, internal consistency, and measurement invariance) of the Health-Related Quality of Life Instrument with Eight Items (HINT-8), developed to measure Korean people’s health-related quality of life. @*Methods@#A secondary analysis was conducted using data from the Korea National Health and Nutrition Examination Survey, involving 6,167 adults aged over 18 years. The structural validity of the HINT-8 was assessed using exploratory graph analysis and confirmatory factoranalysis. Internal consistency and measurement invariance were analyzed using McDonald’s omega (ω) and multigroup confirmatory factor analysis, respectively. @*Results@#The HINT-8 had a single dimension and good internal consistency (ω = .804). The one-dimension HINT-8 ex-hibited matric invariance but not scalar invariance across sociodemographic groups (sex, age, education, and marital status). Further, it exhibited scalar or partial scalar invariance across medical condition groups (hypertension, diabetes, depressive symptoms, and cancer). @*Conclusion@#The study finds that the HINT-8 demonstrated satisfactory structural validity and internal consistency, indicating its suitability for practice and research. However, the HINT-8 scores cannot be compared across different groups regarding sex, age, education, and marital status, as the interpretation varies within each sociodemographic category. Conversely, interpretation of the HINT-8 is consistent for individuals with and without hypertension, diabetes, depressive symptom, and cancer.

A Nomogram for Predicting Extraperigastric Lymph Node Metastasis in Patients With Early Gastric Cancer

Background@#There are no clear guidelines to determine whether to perform D1 or D1+ lymph node dissection in early gastric cancer (EGC). This study aimed to develop a nomogram for estimating the risk of extraperigastric lymph node metastasis (LNM). @*Materials and Methods@#Between 2009 and 2019, a total of 4,482 patients with pathologically confirmed T1 disease at 6 affiliated hospitals were included in this study. The basic clinicopathological characteristics of the positive and negative extraperigastric LNM groups were compared. The possible risk factors were evaluated using univariate and multivariate analyses. Based on these results, a risk prediction model was developed. A nomogram predicting extraperigastric LNM was used for internal validation. @*Results@#Multivariate analyses showed that tumor size (cut-off value 3.0 cm, odds ratio [OR]=1.886, P=0.030), tumor depth (OR=1.853 for tumors with sm2 and sm3 invasion, P=0.010), cross-sectional location (OR=0.490 for tumors located on the greater curvature, P=0.0303), differentiation (OR=0.584 for differentiated tumors, P=0.0070), and lymphovascular invasion (OR=11.125, P<0.001) are possible risk factors for extraperigastric LNM. An equation for estimating the risk of extraperigastric LNM was derived from these risk factors. The equation was internally validated by comparing the actual metastatic rate with the predicted rate, which showed good agreement. @*Conclusions@#A nomogram for estimating the risk of extraperigastric LNM in EGC was successfully developed. Although there are some limitations to applying this model because it was developed based on pathological data, it can be optimally adapted for patients who require curative gastrectomy after endoscopic submucosal dissection.

Association between ischemic stroke and pyogenic spondylitis in Korea: Nationwide longitudinal cohort study

Objective@#The purpose of this nationwide age- and sex- matched longitudinal study was to determine the pyogenic spondylitis (PS) increases the incidence of ischemic stroke (IS) in Korea. @*Methods@#From the National Health Insurance Service (NHIS), we collected the patient data for the period from January 1, 2004 to December 31, 2015. PS was classified according to the International Classification of Disease codes M46.2-M46.8, M49.2, and M49.3. By using a 1:5 age- and sex- stratified matching, a total of 628 patients and 3140 control subjects were included in the study. The IS incidence rates in PS and control group was calculated by using the Kaplan-Meier method. The outcome of hazard ratio of IS was estimated by Cox proportional hazards regression analyses. This study did not exclude PS as a result of postoperative complications. @*Results@#According to the study, 51 patients (8.12%) in the PS group and 201 patients (6.4%) in the control group experienced IS. The adjusted hazard ratio of IS in the PS group was 3.419 (95% CI: 2.473-4.729) after adjusting individual medical condition and demographics. Following the results of subgroup analysis, the risk ratio of IS was greater in most of the subgroup categories (male, female, age 65, non-diabetic, hypertensive, non-hypertensive, dyslipidemic and non-dyslipidemic subgroup). However, the risk of IS did not differ significantly in diabetic subgroup (95% CI: 0.953-4.360). @*Conclusions@#The risk rate of IS increased in patient with pyogenic spondylitis.

Spinal Sagittal Imbalance is Associated with Vertebral Fracture without a Definite History of Falls: Cross-Sectional, Comparative Study of Cohort with and without a Distal Radius Fracture

Background@#Treating osteoporosis in patients with a distal radius fracture (DRF) became paramount at the Fracture Liaison Service. Spinal sagittal imbalance emerged as a risk factor for subsequent fractures. Therefore, here we investigated the spinal profile of patients with DRF to investigate its association with a history of falls and prevalent vertebral fractures. @*Methods@#We reviewed the cases of 162 women presenting with DRF and 162 age-matched women without fracture who underwent an osteoporosis evaluation including bone mineral density (BMD) and lateral spine imaging. We compared the incidence of prevalent vertebral fracture and sagittal vertical axis (SVA) to measure spinal sagittal imbalance. We also performed a regression analysis of the risks of prevalent vertebral fracture, such as age, body mass index (BMI), BMD, and SVA. @*Results@#The SVA was significantly smaller (indicating more stable sagittal balance) in patients with a DRF versus controls (16 mm vs. 34 mm, respectively; p<0.001). The incidence of a prevalent vertebral fracture was similar between groups (12% vs. 15%, respectively; p=0.332). In both groups, the SVA was significantly greater in those with versus without a vertebral fracture. The vertebral fracture was significantly associated with age and SVA but not BMI or spinal BMD. @*Conclusions@#Spinal sagittal balance was superior in DRF patients, yet the frequency of prevalent vertebral fractures was similar. The identification of this unique spinal profile in patients with DRF may increase our understanding of osteoporotic fractures.

Transcriptional Signature of Valproic Acid-Induced Neural Tube Defects in Human Spinal Cord Organoids

In vertebrates, the entire central nervous system is derived from the neural tube, which is formed through a conserved early developmental morphogenetic process called neurulation. Although the perturbations in neurulation caused by genetic or environmental factors lead to neural tube defects (NTDs), the most common congenital malformation and the precise molecular pathological cascades mediating NTDs are not well understood. Recently, we have developed human spinal cord organoids (hSCOs) that recapitulate some aspects of human neurulation and observed that valproic acid (VPA) could cause neurulation defects in an organoid model. In this study, we identified and verified the significant changes in cell–cell junctional genes/proteins in VPA-treated organoids using transcriptomic and immunostaining analysis. Furthermore, VPA-treated mouse embryos exhibited impaired gene expression and NTD phenotypes, similar to those observed in the hSCO model. Collectively, our data demonstrate that hSCOs provide a valuable biological resource for dissecting the molecular pathways underlying the currently unknown human neurulation process using destructive biological analysis tools.

The Essential Function of miR-5739 in Embryonic Muscle Development

Background and Objectives@#Embryologically, mesodermal development is closely related to the development of various organs such as muscles, blood vessels, and hearts, which are the main organs that make up the body. However, treatment for mesoderm developmental disorders caused by congenital or acquired factors has so far relied on surgery and drug treatment for symptom relief, and more fundamentally, treatment for mesoderm developmental disorders is needed. @*Methods@#and Results: In our study, microRNA (miRNA), which plays an important role in the mesoderm development process, was identified and the developmental function was evaluated. miRNAs consist of small nucleotides, which act as transcription factors that bind to the 3’ untranslated region and suppressed target gene expression. We constructed the human embryonic stem cell (hESC) knockout cell line and analyzed the function and characteristics of miR-5739, which plays an important role in mesoderm lineage. miR-5739 acts as a transcription factor targeting SMA, Brachyury T, Hand1, which controls muscle proliferation and differentiation, and KDR gene, which regulates vessel formation in vitro. In vivo results suggest a role in regulating muscle proliferation and differentiation. Gene ontology analysis confirmed that the miR-5739 is closely related to genes that regulate muscle and vessel proliferation and differentiation. Importantly, abnormal expression of miR-5739 was detected in somatic cells derived from patients with congenital muscle disease. @*Conclusions@#Our study demonstrate that miR-5739 gene function significantly affects transcriptional circuits that regu-late muscle and vascular differentiation during embryonic development.

Development and Verification of Time-Series Deep Learning for Drug-Induced Liver Injury Detection in Patients Taking Angiotensin II Receptor Blockers: A Multicenter Distributed Research Network Approach / 대한의료정보학회지

Objectives@#The objective of this study was to develop and validate a multicenter-based, multi-model, time-series deep learning model for predicting drug-induced liver injury (DILI) in patients taking angiotensin receptor blockers (ARBs). The study leveraged a national-level multicenter approach, utilizing electronic health records (EHRs) from six hospitals in Korea. @*Methods@#A retrospective cohort analysis was conducted using EHRs from six hospitals in Korea, comprising a total of 10,852 patients whose data were converted to the Common Data Model. The study assessed the incidence rate of DILI among patients taking ARBs and compared it to a control group. Temporal patterns of important variables were analyzed using an interpretable timeseries model. @*Results@#The overall incidence rate of DILI among patients taking ARBs was found to be 1.09%. The incidence rates varied for each specific ARB drug and institution, with valsartan having the highest rate (1.24%) and olmesartan having the lowest rate (0.83%). The DILI prediction models showed varying performance, measured by the average area under the receiver operating characteristic curve, with telmisartan (0.93), losartan (0.92), and irbesartan (0.90) exhibiting higher classification performance. The aggregated attention scores from the models highlighted the importance of variables such as hematocrit, albumin, prothrombin time, and lymphocytes in predicting DILI. @*Conclusions@#Implementing a multicenter-based timeseries classification model provided evidence that could be valuable to clinicians regarding temporal patterns associated with DILI in ARB users. This information supports informed decisions regarding appropriate drug use and treatment strategies.

Intramuscular Neural Distribution of Adductor Pollicis Muscle Spasticity in Cadaver Model Regarding Botulinum Neurotoxin Treatment

Purpose@#The adductor pollicis muscle is frequently targeted for botulinum neurotoxin injective treatment for spasticity. However, there are no injective guidelines for delivering injection to the muscle. @*Materials and Methods@#A method known as the modified Sihler’s method was used to stain the adductor pollicis muscle in 16 specimens to reveal intramuscular neural distribution of the muscle. @*Results@#The most intramuscular neural distribution was located on 1/5 to 3/5 of the muscle regarding midline of 3rd metacarpal bone (0) to the base of the 1st proximal phalanx (5/5). The nerve entry point was mostly located on 0 to 1/5 of the muscle. @*Conclusion@#The result suggests that botulinum neurotoxin should be delivered at the middle of second metacarpal bone via deep injection.

Intramuscular Neural Distribution of the Gastrocnemius for Botulinum Neurotoxin Injection:Application to Cosmetic Calf Shaping

Purpose@#Anatomical landmarks can provide vital information on the distribution of nerves in the gastrocnemius muscle. We aimed to provide an anatomical perspective on appropriate locations for botulinum neurotoxin (BoNT) injections in the medial and lateral parts of the gastrocnemius for calf shaping. @*Materials and Methods@#A modified Sihler’s method was applied to both the medial and lateral parts of the gastrocnemius muscles (16 specimens). Intramuscular neural distributions were revealed by dissecting along a transverse line crossing the fibular head and superior margin of the calcaneal tuberosity. @*Results@#The intramuscular neural distribution for the medial and lateral parts of the gastrocnemius had the greatest arborized patterns in the 7/10–8/10 section of the medial head and 7.5/10–8.5/10 section of the lateral part of the gastrocnemius. @*Conclusion@#We propose that BoNT injections should be directed to the 7/10–8/10 section of the medial head and the 7.5/10– 8.5/10 section of the lateral part of the gastrocnemius. Following our guidelines, clinicians can ensure satisfactory results with the use of minimal doses to limit adverse effects, such as gait disturbance, antibody production, and bruising, due to multiple injections. The results can also be altered and applied to electromyography.

Development of Hetero-Cell Type Spheroids Via Core–Shell Strategy for Enhanced Wound Healing Effect of Human AdiposeDerived Stem Cells

BACKGROUND@#Stem cell-based therapies have been developed to treat various types of wounds. Human adiposederived stem cells (hADSCs) are used to treat skin wounds owing to their outstanding angiogenic potential. Although recent studies have suggested that stem cell spheroids may help wound healing, their cell viability and retention rate in the wound area require improvement to enhance their therapeutic efficacy. @*METHODS@#We developed a core–shell structured spheroid with hADSCs in the core and human dermal fibroblasts (hDFs) in the outer part of the spheroid. The core–shell structure was formed by continuous centrifugation and spheroid incubation. After optimizing the method for inducing uniform-sized core–shell spheroids, cell viability, cell proliferation, migration, and therapeutic efficacy were evaluated and compared to those of conventional spheroids. @*RESULTS@#Cell proliferation, migration, and involucrin expression were evaluated in keratinocytes. Tubular assays in human umbilical vein endothelial cells were used to confirm the improved skin regeneration and angiogenic efficacy of core–shell spheroids. Core–shell spheroids exhibited exceptional cell viability under hypoxic cell culture conditions that mimicked the microenvironment of the wound area. @*CONCLUSION@#The improvement in retention rate, survival rate, and angiogenic growth factors secretion from core– shell spheroids may contribute to the increased therapeutic efficacy of stem cell treatment for skin wounds.