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Abstract Thus far, attempts to develop drugs that target corticotropin-releasing hormone receptor 1 (CRF1R), a drug target in stress-related therapy, have been unsuccessful. Studies have focused on using high-resolution G protein-coupled receptor (GPCR) structures to develop drugs. X-ray free-electron lasers (XFELs), which prevent radiation damage and provide access to high-resolution compositions, have helped accelerate GPCR structural studies. We elucidated the crystal structure of CRF1R complexed with a BMK-I-152 antagonist at 2.75 Å using fixed-target serial femtosecond crystallography. The results revealed that two unique hydrogen bonds are present in the hydrogen bond network, the stalk region forms an alpha helix and the hydrophobic network contains an antagonist binding site. We then developed two antagonists—BMK-C203 and BMK-C205—and determined the CRF1R/BMK-C203 and CRF1R/BMK-C205 complex structures at 2.6 and 2.2 Å, respectively. BMK-C205 exerted significant antidepressant effects in mice and, thus, may be utilized to effectively identify structure-based drugs against CRF1R.

Background and Objectives: Lateral ankle injuries are commonly encountered injuries, and the open modified Broström operation (OMBO) is the primary treatment option. Recently, an arthroscopic modification of the Broström operation (AMBO) was developed; many studies have shown that there are no significant differences in clinical and radiological outcomes between the two surgical methods. However, no studies have been conducted comparing the two surgical methods in terms of return to play (RTP) time. This study assesses the time to RTP and the functional clinical outcomes. Materials and Methods: Sixty patients were enrolled from January 2012 to July 2014. They were segregated into two cohorts: the AMBO group comprised 30 patients, while the OMBO group comprised another 30 patients. Each participant underwent standardized treatment and rehabilitation regimens and RTP time was measured using seven questions that explored the times to return of painless walking, running, jumping, squatting, climbing stairs, and rising up on the heels and toes. We compared the time intervals from the onset of instability to the date of surgery. Clinical outcomes were evaluated before the surgery, 6 weeks after surgery, and 6 months after surgery. The assessments included the American Orthopedic Foot & Ankle Society (AOFAS) ankle–hindfoot score, the pain visual analog scale (VAS) score, subjective satisfaction with rehabilitation, and activity level. Results: In terms of RTP, AMBO was associated with a shorter interval to walking without pain (7.07 ± 2.96 weeks) relative to OMBO (11.03 ± 8.58 weeks). No disparities were observed in the time to return to play (RTP) between OMBO and AMBO. While there were no discrepancies in the 6-month postoperative AOFAS or VAS scores, the 6-week postoperative VAS score was notably lower in the AMBO group compared to the OMBO group. AMBO provided a faster RTP in terms of two of the seven questions in a group exhibiting high-level physical activity. The rate of subjective satisfaction with rehabilitation was higher for AMBO than for OMBO. Conclusions: Aside from walking, the duration to return to play and the clinical outcomes were similar between AMBO and OMBO treatments for lateral ankle instability. AMBO is a good treatment option and should be carefully considered for athletes with lateral ankle instability. AMBO demonstrated positive outcomes in a group with higher activity levels compared to others, particularly in terms of time to RTP, subjective satisfaction, and postoperative pain.

Background: Patients who require initial venoarterial extracorporeal membrane oxygenation (VA ECMO) support may need to undergo veno-arteriovenous ECMO (VAV ECMO) conversion. However, there are no definitive criteria for conversion to VAV ECMO. We report 9 cases of VAV ECMO at Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine. Methods: Of 158 patients who received ECMO support between January 2017 and June 2019, 82 were supported by initial VA ECMO. We retrospectively reviewed the medical records of 9 patients (7 men and 2 women; age, 53.1±19.4 years) who had differential hypoxia and required VAV ECMO support. Percutaneous transaortic catheter venting was used to detect the differential hypoxia. Results: Among the 82 patients who received VA ECMO support, 9 (10.9%) had differential hypoxia and required conversion to VAV ECMO support. The mean time from VA ECMO support to VAV ECMO support and the mean duration of the VAV support were 2.1±2.2 days and 1.9±1.5 days, respectively. The average peak inspiratory pressure before and after VAV ECMO application was 23.89±3.95 cmH2O and 20.67±5.72 cmH2O, respectively, decreasing by an average of 3.2±3.5 cmH2O (p=0.040). The PaO2/FiO2 ratio was kept below 100 mm Hg in survivors and non-survivors for 116±65.4 and 250±124.9 minutes, respectively (p=0.016). Six patients underwent extracorporeal cardiopulmonary resuscitation, of whom 4 survived (67%). The overall survival rate of patients who underwent conversion from VA ECMO to VAV ECMO was approximately 56%. Conclusion: Rapid detection of differential hypoxia is required when VA ECMO is applied, and efficient conversion to VAV ECMO may be critical for patient survival.

Background and objectives: Diabetic foot stands out as one of the most consequential and devastating complications of diabetes. Many factors, including VIPS (Vascular management, Infection management, Pressure relief, and Source of healing), influence the prognosis and treatment of diabetic foot patients. There are many studies on VIPS, but relatively few studies on “sources of healing”. Nutrients that affect wound healing are known, but objective data in diabetic foot patients are insufficient. We hypothesized that “sources of healing” would have many effects on wound healing. The purpose of this study is to know the affecting factors related to the source of healing for diabetic foot patients. Materials and Methods: A retrospective review identified 46 consecutive patients who were admitted for diabetic foot management from July 2019 to April 2021 at our department. Several laboratory tests were performed for influencing factor evaluation. We checked serum levels of total protein, albumin, vitamin B, iron, zinc, magnesium, copper, Hb, HbA1c, HDL cholesterol, and LDL cholesterol. These values of diabetic foot patients were compared with normal values. Patients were divided into two groups based on wound healing rate, age, length of hospital stay, and sex, and the test values between the groups were compared. Results: Levels of albumin (37%) and Hb (89%) were low in the diabetic foot patients. As for trace elements, levels of iron (97%) and zinc (95%) were low in the patients, but levels of magnesium and copper were usually normal or high. There were no differences in demographic characteristics based on wound healing rate. However, when compared to normal adult values, diabetic foot patients in our data exhibited significantly lower levels of hemoglobin, total protein, albumin, iron, zinc, copper, and HDL cholesterol. When compared based on age and length of hospital stay, hemoglobin levels were significantly lower in both the older age group and the group with longer hospital stays. Conclusions: Serum levels of albumin, Hb, iron, and zinc were very low in most diabetic foot patients. These low values may have a negative relationship with wound healing. Nutrient replacements are necessary for wound healing in diabetic foot patients.

Soft tissue calcifications frequently appear on imaging studies, representing a prevalent but non-specific discovery, varying from a local reaction without clear cause to suggesting an underlying systemic condition. Because calcifications like these can arise from various causes, an accurate differential diagnosis is crucial. Differential diagnosis entails a methodical assessment of the patient, encompassing clinical presentation, medical history, radiological and pathological findings, and other pertinent factors. Through scrutiny of the patient’s medical and trauma history, we can refine potential causes of calcification to vascular, metabolic, autoimmune, neoplastic, or traumatic origins. Furthermore, routine laboratory assessments, including serum levels of calcium, phosphorus, ionized calcium, vitamin D metabolites, and parathyroid hormone (PTH), aid in identifying metabolic etiologies. We describe a rare occurrence of osteoma cutis in a 15-year-old female patient with a history of pseudohypoparathyroidism (PHP) and Albright’s hereditary osteodystrophy (AHO). The patient presented with a painful mass on the lateral side of her left foot. The diagnosis was based on medical history, laboratory tests, and imaging, leading to an excisional biopsy and complete pain relief post-surgery. Understanding such rare occurrences and related conditions is crucial for accurate diagnosis and management.

Introduction: Distal tibial fractures make up approximately 3% to 10% of all tibial fractures or about 1% of lower extremity fractures. MIPO is an appropriate procedure and method to achieve stable metal plate fixation and osseointegration by minimizing soft tissue damage and vascular integrity at the fracture site. MIPO to the medial tibia during distal tibial fractures induces skin irritation due to the thickness of the metal plate, which causes discomfort and pain on the medial side of the distal leg, and if severe, complications such as infection and skin defect may occur. The reverse sural flap is a well-researched approach for covering defects in the lower third of the leg, ankle, and foot. Materials and Methods: Among 151 patients with distal tibia fractures who underwent minimally invasive metal plate fixation, soft tissue was injured due to postoperative complications. We treated 13 cases with necrosis and exposed metal plates by retrograde nasogastric artery flap surgery. For these patients, we collected obligatory patient records, radiological data, and wound photographs of the treatment results and complications of reconstructive surgery. Results: In all the cases, flap survival was confirmed at the final outpatient follow-up. The exposed area of the metal plate was well coated, and there was no plate failure due to complete necrosis. Three out of four women complained of aesthetic dissatisfaction because the volume of the tunnel through which the skin mirror passed and the skin plate itself were thick. In two cases, defatting was performed to reduce the thickness of the plate while removing the metal plate. Conclusions: Metal plate exposure after distal tibial fractures have been treated with minimally invasive metal plate fusion and can be successfully treated with retrograde nasogastric artery flaps, and several surgical techniques are used during flap surgery.

Extensor hallucis longus tendon injury is relatively rare and is principally caused by a laceration when a sharp object is dropped on the instep. Primary suturing is possible if the injury is acute, but if the tear is chronic, tendon contracture causes the space between the edges of the tear to widen, disrupting the end-to-end connection. In particular, a claw toe or checkrein foot deformity may develop over time due to adhesion of the lower leg tendons near the fracture site or scar. We report on a 44-year-old man who visited our outpatient clinic complaining of pain in the right foot and a hindered ability to extend his great toe. He had enjoyed playing soccer during his schooldays; since that time, the extension of that toe had become somewhat difficult. T2-weighted sagittal magnetic resonance imaging revealed that the continuity of the extensor hallucis longus tendon had been lost at the distal phalangeal base attachment site, and that the region of the proximal tendon was retracted to level of the middle shaft of the proximal phalanx. The findings allowed us to diagnose extensor hallucis longus tendon rupture accompanying osteoarthritic changes in the joint and soft tissues. We performed surgical tenorrhaphy and adhesiolysis. This is a rare case of extensor hallucis longus tendon rupture caused by minor trauma. Arthritis that developed at a young age caused the adhesions. If patients with foot and ankle arthritis show tendon adhesion at the arthritic site, tendon rupture can develop even after minor trauma or intense stretching.

Background: The arthroscopic Broström procedure is a promising treatment for chronic ankle instability. However, little is known regarding the location of the intermediate superficial peroneal nerve at the level of the inferior extensor retinaculum; knowledge about this location is important for procedural safety. The purpose of this cadaveric study was to clarify the anatomical relationship between the intermediate superficial peroneal nerve and the sural nerve at the level of the inferior extensor retinaculum. Methods: Eleven dissections of cadaveric lower extremities were performed. The origin of the experimental three-dimensional axis was defined as the location of the anterolateral portal during ankle arthroscopy. The distances from the standard anterolateral portal to the inferior extensor retinaculum, sural nerve, and intermediate superficial peroneal nerve were measured using an electronic digital caliper. The location of inferior extensor retinaculum, the tract of sural nerve, and intermediate superficial peroneal nerve were checked using average and standard deviations. For the statistical analyses, data are presented as average ± standard deviation, and then they are reported as means and standard deviations. Fisher’s exact test was used to identify statistically significant differences. Results: At the level of the inferior extensor retinaculum, the mean distances from the anterolateral portal to the proximal and distal intermediate superficial peroneal nerve were 15.9 ± 4.1 (range, 11.3–23.0) mm and 30.1 ± 5.5 (range, 20.8–37.9) mm, respectively. The mean distances from the anterolateral portal to the proximal and distal sural nerve were 47.6 ± 5.7 (range, 37.4–57.2) mm and 47.2 ± 4.1 (range, 41.0–51.8) mm), respectively. Conclusions: During the arthroscopic Broström procedure, the intermediate superficial peroneal nerve may be damaged by the anterolateral portal; the proximal and distal parts of the intermediate superficial peroneal nerve were located within 15.9 and 30.1 mm, respectively, at the level of the inferior extensor retinaculum in cadavers. These areas should be considered danger zones during the arthroscopic Broström procedure.

Abstract Background Smoking‐ and nonsmoking‐associated lung cancers have different mechanisms of carcinogenesis. We divided non‐small cell lung cancer (NSCLC) patients into nonsmoking and smoking groups with the aim of trying to understand the utility of brain‐specific angiogenesis inhibitor 1 (BAI1) expression in the separate groups. Methods Clinicopathological data were obtained from 148 patients who had undergone surgery for NSCLC of the lung. Tissue microarray blocks were made of samples from NSCLC patients. Two pathologists graded the intensity of BAI1 expression as high or low expression in the cancer cells of patients in the smoking and nonsmoking groups. Results NSCLC nonsmokers with higher BAI1 nuclear expression had poor disease‐specific survival (DSS) (hazard ratio: 2.679; 95% confidence interval [CI]:1.022–7.022, p = 0.045). The Kaplan–Meier survival curve confirmed that higher BAI1 expression was significantly associated with poor DSS (p = 0.034) in the nonsmoking group. Conclusions We divided NSCLC patients into nonsmoking and smoking groups and found that nuclear BAI1 expression was related to patient survival in nonsmoking NSCLC patients. We suggest BAI1 expression as a predictive marker of nonsmoking‐associated NSCLC and recommend that it be evaluated as an AJCC staging criterion in the future.

Abstract Background Nurses are presumably the first to see an in-hospital cardiac arrest patient. This study proposed measuring nursing students’ knowledge, self-efficacy, and skills performance in advanced life support (ALS), 6 months after training, by sending videos taken during their final skills test after the ALS training. Methods This is an experimental study using a randomised control group design. This study was conducted from June to December 2018, and the subjects of the study were 4th year students, recruited through a bulletin board at a nursing university. The participants’ knowledge, self-efficacy, and skill performance in ALS were evaluated immediately after the training, and participants were videotaped during the final skills test. Thereafter, the videos were sent to the experimental group through a mobile phone messenger application, once a month, from the third month after training. Approximately six months after training day, a follow-up test was conducted for the measured variables using a blinded method. The paired t-test and Wilcoxon signed-rank test were used to compare the two groups pre-and post-intervention. The statistical significance level was set at p

Background and Objectives: Hallux valgus is one of the most common chronic foot complaints, with prevalences of over 23% in adults and up to 35.7% in older adults. However, the prevalence is only 3.5% in adolescents. The pathological causes and pathophysiology of hallux valgus are well-known in various studies and reports. A change in the position of the sesamoid bone under the metatarsal bone of the first toe is known to be the cause of the initial pathophysiology. Purpose: The relationships between the changes in the location of the sesamoid bone and each radiologically measured angle and joint congruency in the hallux valgus remain as yet unknown. Therefore, this study investigated the relationships of sesamoid bone subluxation with the hallux valgus angle, intermetatarsal angle, and metatarsophalangeal joint congruency in hallux valgus patients. The goal is to know the hallux valgus angle, the intermetatarsal angle, and metatarsophalangeal joint congruency’s correlation with hallux valgus severity and prognosis by revealing the relationship between each measured value and sesamoid bone subluxation. Materials and Methods: We reviewed 205 hallux valgus patients who underwent radiographic evaluation and subsequent hallux valgus correction surgery in our orthopedic clinic between March 2015 and February 2020. Sesamoid subluxation was assessed using a new five-grade scale on foot radiographs, and other radiologic measurements were assessed, such as hallux valgus angle, the intermetatarsal angle, distal metatarsal articular angle, joint congruency, etc. Conclusions: Measurements of the hallux valgus angle, interphalangeal angle, and joint congruency exhibited high interobserver and intraobserver reliabilities in this study. They also showed correlations with sesamoid subluxation grade.

(1) Background: Achilles tendon rupture is a common sports injury that may result in severe disability. The overall incidence of Achilles tendon rupture is increasing as a result of growing sports participation. However, cases of spontaneous bilateral Achilles tendon rupture with no underlying disease or risk factors, such as systemic inflammatory disease, steroid or (fluoro)quinolone antibiotics use, are rare. (2) Objective: Here, we report a case of a Taekwondo athlete’s bilateral Achilles tendon rupture after kicking and landing. By sharing the experience of treatment and the patient’s course, we suggest one of the possible treatment options and the need to establish a treatment method. (3) Procedure: A 23-year-old male Taekwondo athlete visited the hospital, presenting foot plantar flexion failure and severe pain in both tarsal joints, which had occurred upon kicking and landing on both feet earlier that day. During surgery, no degenerative changes or denaturation were observed in the ruptured areas of the Achilles tendons. Bilateral surgery was performed using the modified Bunnel method on the right side and minimum-section suturing on the left side was performed using the Achillon system, followed by lower limb casting. (4) Result: Good outcomes were observed on both sides at 19 months postoperatively. (5) Conclusion: The possibility of bilateral Achilles tendon rupture during exercise in young subjects with no risk factors should be acknowledged, especially in association with landing. In addition, in athletes, even if there is a possibility of complications, surgical treatment should be considered for functional recovery.

Abstract Background Research on diagnosing recurrent non‐small cell lung cancer (NSCLC) and applying target gene treatment using exosomes in a less invasive way is very important. Recently, however, it has been argued that exosomes do not contain double‐stranded DNA (dsDNA) or histones. In this study, we describe the expression of extracellular vesicle (EV) markers in specimens from squamous cell carcinoma (SCC) of the lung and analyze their relationship with the prognosis of patients. Methods Clinical and pathological data were obtained from 96 patients who had undergone surgery for SCC of the lung. Tissue microarray blocks were made using representative paraffin blocks of samples from patients with SCC of the lung. Two pathologists graded the intensity of CD63, CD9, LC3A/B, P62, and ANXA1 expression as high or low expression. In addition, the authors designated the combined expression of these five independent markers as “positive EV expression” in this article. Results SCCs with low CD63 and SCCs with low EV expression showed unfavorable disease‐free survival (DFS) (P‐value = 0.037 and 0.006, respectively) in the survival analysis. The Kaplan‐Meier survival curve confirmed that the low EV expression showed a statistically significant relationship with unfavorable DFS (P‐value = 0.004). There were no statistically significant differences in DFS and disease‐specific survival in each low and high expression group for CD9, LC3A/B, ANXA1, and P62 in the Cox regression analysis. Conclusions As EV expression was related to the prognosis of lung SCC patients, a broader approach using different extracellular vesicles rather than a conventional exosome‐dependent one is needed.

Background and Objectives: Even though low-molecular-weight heparin (LMWH), including dalteparin, has a critical role in portal vein thrombosis (PVT) treatment in liver cirrhosis (LC) patients, the predictive factors and the proper dose of dalteparin for PVT treatment and relapse have not yet been investigated. Materials and Methods: This retrospective study evaluated the records of LC patients receiving dalteparin from July 2013 to June 2019. The odds ratio (OR) and adjusted OR were calculated from univariate and multivariable analyses, respectively. Results: Among data from 121 patients, the overall recanalization rate of all patients was 66.1% (80 patients). No history of variceal bleeding (OR 4.6, 95% CI: 1.88–11.43) and the case of newly developed thrombus before dalteparin treatment (OR 3.2, 95% CI: 1.24–8.08) were predictive factors associated with increased treatment response. Relapse of PVT occurred in 32 out of 80 patients (40%) who showed a recanalization. The risk of relapse was 3.1–3.9 times higher in those who took more than three months or more than six months from the diagnosis of PVT to dalteparin treatment compared to those who took less than these durations, respectively. In the dosing regimen, patients with the kg-based dosing regimen showed 2.6 times better response than those with the fixed dosing regimen. However, no difference in bleeding complications was observed. Conclusion: In the dosing regimen, the kg-based regimen that was the same as the venous thromboembolism regimen was a better option for the efficacy and safety of dalteparin therapy. Additionally, when treating PVT in LC patients, careful monitoring is recommended for patients with predictive factors for treatment response and relapse of PVT.

Charcot neuropathic arthropathy is a relatively rare, chronic disease that leads to joint destruction and reduced quality of life of patients. Early diagnosis of Charcot arthropathy is essential for a good outcome. However, the diagnosis is often based on the clinical course and longitudinal follow-up of patients is required. Charcot arthropathy is suspected in patients with suggestive symptoms and an underlying etiology. Failed spinal surgery is not a known cause of Charcot arthropathy. Herein we report a patient with ankle Charcot neuropathic arthropathy that developed after failed spinal surgery. A 58-year-old man presented to the emergency room due to painful swelling of the left ankle for 2 weeks that developed spontaneously. He underwent spinal surgery 8 years ago that was associated with nerve damage, which led to weakness of great toe extension and ankle dorsiflexion, and sensory loss below the knee. CT and T2-weighted sagittal MRI showed a fine erosive lesion, subluxation, sclerosis, fragmentation, and large bone defects. Based on the patient’s history and radiological findings, Charcot arthropathy was diagnosed. However, the abnormal blood parameters, positive blood cultures, and severe pain despite the decreased sensation suggested a diagnosis of septic arthritis. Therefore, diagnostic arthroscopy was performed. The ankle joint exhibited continued destruction after the initial surgery. Consequently, several repeat surgeries were performed over the next 2 years. Despite the early diagnosis and treatment of Charcot arthropathy, the destruction of the ankle joint continued. Given the chronic disease course and poor prognosis of Charcot arthropathy, it is essential to consider this diagnosis in patients with neuropathy.

Abstract Background Acute type A aortic dissection complicated by malperfusion is a life – threatening emergency. The optimal management strategy for malperfusion remains controversial. Case presentation A 46-year-old man presented to another institution with acute type A aortic dissection with abdominal aorta occlusion. Motor and sensory grade of both lower extremities were zero. Immediate antegrade distal perfusion of both lower extremities was achieved, and total arch replacement with left axillo-bifemoral bypass was performed. At the time of discharge, motor and sensory grades of both lower extremities were 2 and 3, respectively. Conclusion This case demonstrates many of the techniques in the management of acute type A aortic dissection with abdominal aorta occlusion. In this case, direct antegrade perfusion of both lower extremities and axillo-bifemoral bypass may be helpful for patients presenting with severe malperfusion of both lower extremities with acute type A aortic dissection.

Chest computed tomography demonstrated a suspected primary tumor in the upper sternal body of a 48‐year‐old woman who presented with sternal pain. After being diagnosed with chondrosarcoma, she underwent sternal resection. Subsequent chest wall reconstruction was performed after careful planning using a bone cement block made of polypropylene mesh and polymethylmethacrylate. The block was fixed to the manubrium and ribs using the SternaLock System. She was discharged following an uneventful postoperative recovery, and is currently undergoing follow‐up.

Background Pulmonary emphysema is a major component of chronic obstructive pulmonary disease and lung cancer. However the prognostic significance of quantitative emphysema severity in patients with lung cancer is unclear. We analyzed whether numerical emphysema value is a prognostic factor for recurrence in patients with surgically resected non‐small cell lung cancer. Methods We quantified emphysema severity of the whole lung and regional lobes in 45 patients (mean age 68.0 years) using an automated chest computed tomography‐based program. Predictive factors for recurrence were investigated using a Cox proportional hazards model. Recurrence‐free and overall survival was compared after dichotomization of patients according to whole lung emphysema severity. Results The mean percentage emphysema ratio of the whole lung was 1.21 ± 2.04. Regional lobar emphysema severity was highest in the right middle lobe (1.93 ± 0.36), followed by right upper (1.35 ± 2.50), left upper (1.34 ± 2.12), left lower (1.05 ± 2.52), and right lower (0.78 ± 2.28) lobes. The low severity group showed significantly longer overall survival compared to the high severity group (log‐rank test, P = 0.018). Quantitative emphysema severity of the whole lung (hazard ratio 1.36; 95% confidence interval 1.0–1.73) and stage III (hazard ratio 6.17; 95% confidence interval 1.52–25.0) were independent predictors of recurrence after adjusting for age, gender, smoking status, and forced expiratory volume in one second. Conclusion The severity of whole lung emphysema was independently associated with recurrence. Patients with non‐small cell lung cancer and marginal pulmonary emphysema at lower severity survive longer after curative‐intent surgery.

This paper proposes a new high-performance light-emitting diode (LED) converter with separation of the AC and DC driving parts for a T8 LED tube. The proposed LED converter is mounted at the end of the LED tube in G13 base and G13 base dummy. The separation of the AC and DC driving parts enhances the light uniformity of the LED tube by securing the optical distance between the optic cover and light source. The AC driving part was designed to be inserted in a G13 base and was connected with the DC driving part through an LED module. The proposed LED converter is based on single-stage buck-boost topology and was designed for the operation at 19 W for a 1200 mm T8 LED tube. The proposed LED converter is very small and has fewer parts than other LED converters but still has high performance. The measurement results of the proposed LED converter show that the line regulation of the LED output current is less than 3.4% at 100-240 VAC and achieves high circuit efficiency (>89%), high power factor (>0.93), and low total harmonic distortion (

Mitochondrial NADP+-dependent isocitrate dehydrogenase 2 (IDH2) is a major NADPH-producing enzyme which is essential for maintaining the mitochondrial redox balance in cells. We sought to determine whether IDH2 deficiency induces mitochondrial dysfunction and modulates auditory function, and investigated the protective potential of an antioxidant agent against reactive oxygen species (ROS)-induced cochlear damage in Idh2 knockout (Idh2−/−) mice. Idh2 deficiency leads to damages to hair cells and spiral ganglion neurons (SGNs) in the cochlea and ultimately to apoptotic cell death and progressive sensorineural hearing loss in Idh2−/− mice. Loss of IDH2 activity led to decreased levels of NADPH and glutathione causing abnormal ROS accumulation and oxidative damage, which might trigger apoptosis signal in hair cells and SGNs in Idh2−/− mice. We performed ex vivo experiments to determine whether administration of mitochondria-targeted antioxidants might protect or induce recovery of cells from ROS-induced apoptosis in Idh2-deficient mouse cochlea. MitoQ almost completely neutralized the H2O2-induced ototoxicity, as the survival rate of Idh2−/− hair cells were restored to normal levels. In addition, the lack of IDH2 led to the accumulation of mitochondrial ROS and the depolarization of ΔΨm, resulting in hair cell loss. In the present study, we identified that IDH2 is indispensable for the functional maintenance and survival of hair cells and SGNs. Moreover, the hair cell degeneration caused by IDH2 deficiency can be prevented by MitoQ, which suggests that Idh2−/− mice could be a valuable animal model for evaluating the therapeutic effects of various antioxidant candidates to overcome ROS-induced hearing loss. Keywords: Idh2, NADP+, ROS, Hearing loss, Antioxidant, MitoQ

Background S100A8 and S100A9 have been gaining recognition for modulating tumor growthand metastasis. This study aimed at evaluating the clinical significance of S100A8 and S100A9 innon-small cell lung cancer (NSCLC). Methods We analyzed the relationship between S100A8and S100A9 expressions, clinicopathological characteristics, and prognostic significance in tumorcells and peritumoral inflammatory cells. Results The positive staining of S100A8 in tumorcells was significantly increased in male (p < .001), smoker (p = .034), surgical method other thanlobectomy (p = .024), squamous cell carcinoma (SQCC) (p < .001) and higher TNM stage (p = .022)compared with female, non-smoker, lobectomy, adenocarcinoma (ADC), and lower stage. Theproportion of tumor cells stained for S100A8 was related to histologic type (p < .001) and patientsex (p = .027). The proportion of inflammatory cells stained for S100A8 was correlated with patientage (p = .022), whereas the proportion of inflammatory cells stained for S100A9 was correlatedwith patient sex (p < .001) and smoking history (p = .031). Moreover, positive staining in tumorcells, more than 50% of the tumor cells stained and less than 30% of the inflammatory cellsstained for S100A8 and S100A9 suggested a tendency towards increased survivability in SQCCbut towards decreased survivability in ADC. Conclusions S100A8 and S100A9 expressions might be potential prognostic markers in patients with NSCLC.

Abstract Background The pseudoaneurysms of sinus of Valsalva is an uncommon and serious complication of an infection, trauma, or after cardiac surgery or procedure. Pseudoaneurysms of sinus of Valsalva from left is rare. We describe a case of pseudoaneurysm of the left coronary sinus of Valsalva invaded into the left ventricle (LV) diagnosed by transthoracic echocardiography (TTE), transesophageal ecoccardiography (TEE), and multiple detector computed tomography (MDCT). Case presentation A 44-year-old male patient had New York Heart Association (NYHA) class II / III dyspnea during 4 months. He underwent surgery including aortic valve replacement using mechanical prosthesis, and he was discharged well without significant complications on follow – up TTE and chest computed tomography (CT) post-operative 7 days. Conclusions We report this rare case in which a ruptured pseudoaneurysm of sinus of Valsalva into LV with severe AR due to perforation of LCC was successfully-treated.

A conventional two-switch buck-boost (TSBB) converter can operate in buck, boost, and buck-boost modes. This paper introduces a new topology for a two-switch buck-boost converter with the same operation modes. However, the proposed TSBB converter has fewer conductions and switching components than the conventional TSBB converter, which reduces the power losses.

We report the case of a patient with penetrating chest trauma (right chest) who had undergone a left pneumonectomy due to pulmonary tuberculosis 24 years ago. We performed an emergent thoracotomy, finding an opening of the penetrating wound in a lower-lobe basal segment of the right lung. A stapled tractotomy was performed along the tract. Bleeding control and air-leakage control was done easily and rapidly. The patient was discharged without any complications on the seventh day of admission. Tractotomy can be a good option for treating penetrating lung injuries in patients with limited lung function who need emergent surgery.

Background: Ventilator-associated pneumonia (VAP) is a common disease that may contribute to morbidity and mortality among trauma patients in the intensive care unit (ICU). This study evaluated the associations between trauma factors and the development of VAP in ventilated patients with multiple rib fractures. Methods: We retrospectively and consecutively evaluated 101 patients with multiple rib fractures who were ventilated and managed at our hospital between January 2010 and December 2015, analyzing the associations between VAP and trauma factors in these patients. Trauma factors included sternal fracture, flail chest, diaphragm injury, traumatic aortic dissection, combined cardiac injury, pulmonary contusion, pneumothorax, hemothorax, hemopneumothorax, abbreviated injury scale score, thoracic trauma severity score, and injury severity score. Results: Forty-six patients (45.5%) had at least 1 episode of VAP, 10 (21.7%) of whom died in the ICU. Of the 55 (54.5%) patients who did not have pneumonia, 9 (16.4%) died in the ICU. Using logistic regression analysis, we found that VAP was associated with severe lung contusion (odds ratio, 3.07; 95% confidence interval, 1.12 to 8.39; p=0.029). Conclusion: Severe pulmonary contusion (pulmonary lung contusion score 6–12) is an independent risk factor for VAP in ventilated trauma patients with multiple rib fractures.

Inflammatory bowel disease (IBD) is a group of chronic, relapsing, immunological, inflammatory disorders of the gastrointestinal tract including ulcerative colitis (UC) and Crohn's disease (CD). It has been reported that UC, which is studied using a dextran sodium sulfate (DSS)-induced colitis model, is associated with the production of reactive oxygen species (ROS) and the apoptosis of intestine epithelial cells (IEC). Mitochondrial NADP+-dependent isocitrate dehydrogenase (IDH2) has been reported as an essential enzyme in the mitochondrial antioxidant system via generation of NADPH. Therefore, we evaluated the role of IDH2 in DSS-induced colitis using IDH2-deficient (IDH2-/-) mice. We observed that DSS-induced colitis in IDH2-/- mice was more severe than that in wild-type IDH2+/+ mice. Our results also suggest that IDH2 deficiency exacerbates PUMA-mediated apoptosis, resulting from NF-κB activation regulated by histone deacetylase (HDAC) activity. In addition, DSS-induced colitis is ameliorated by an antioxidant N-acetylcysteine (NAC) through attenuation of oxidative stress, resulting from deficiency of the IDH2 gene. In conclusion, deficiency of IDH2 leads to increased mitochondrial ROS levels, which inhibits HDAC activity, and the activation of NF-κB via acetylation is enhanced by attenuated HDAC activity, which causes PUMA-mediated apoptosis of IEC in DSS-induced colitis. The present study supported the rationale for targeting IDH2 as an important cancer chemoprevention strategy, particularly in the prevention of colorectal cancer.

Purpose: Ruptured abdominal aortic aneurysm (RAAA) is a rare, extremely dangerous condition. Previous studies have published preoperative, intraoperative, and postoperative data; however, there are not enough studies on the preoperative factors alone. Here we studied the preoperative predictors of 30-day mortality in patients with RAAA. Materials and Methods: We conducted a retrospective, consecutive review of the medical records of 57 patients who received management for RAAA between February 2005 and December 2016. We analyzed the association between preoperative predictors and 30-day mortality in patients with RAAA. The initial systolic blood pressure (SBP) and hemoglobin level (HbL), which were proven as significant predictors by multivariate logistic regression analysis, were compared using receiver operating characteristic curves.Results : Overall, early mortality was 29.8%. Results: of logistic regression analysis found that 30-day mortality in patients with RAAA was associated with the initial SBP (odds ratio [OR], 0.922; 95% confidence interval [CI], 0.874–0.973; P=0.003) and initial HbL (OR, 0.513; 95% CI, 0.289–0.91; P=0.023). Area under the curves were 0.89 for the initial SBP and 0.78 for the initial HbL. The initial SBP with a cut-off value of 90 mmHg had a sensitivity of 85% and specificity of 88.2%. At a cut-off of 10.5, the sensitivity and specificity of HbL for death were 75% and 70.6%, respectively. Conclusion: The initial SBP and HbL are independent preoperative predictors of early mortality in patients with RAAA.

In the embryo, the thymus originates from the third and fourth pharyngeal pouches and migrates from the superior neck to the mediastinum. Ectopic cervical thymoma (ECT) is an extremely rare tumor that originates from ectopic tissue, and is caused by the aberrant migration of the embryonic thymus. Our patient was a 30-year-old woman who had a nodular lesion in the neck for several years. Ultrasonography and computed tomography were performed. She underwent surgery, and a histological examination resulted in a diagnosis of type AB thymoma. Herein, we report a case of ECT that was resected through a transcervical approach.

Background Initial evaluation of injury severity in trauma patients is an important and challenging task. We aimed to assess whether easily measurable biochemical parameters (hemoglobin, pH, and prothrombin time/international normalized ratio [PT/INR]) can predict in-hospital mortality in patients with severe trauma. Methods This retrospective study involved review of the medical records of 315 patients with severe trauma and an injury severity score >15 who were managed at Gyeongsang National University Hospital between January 2005 and December 2015. We extracted the following data: in-hospital mortality, injury severity score, and initial hemoglobin level, pH, and PT/INR. The predictive values of these variables were compared using receiver operation characteristic curves. Results Of the 315 patients, 72 (22.9%) died. The in-hospital mortality rates of patients with hemoglobin levels

Two-switch buck-boost (TSBB) is one of the non-isolated dc-to-dc converters that can change its mode from among buck, boost, and buck-boost modes. Changing its mode is possible by controlling gate signals. This paper presents a novel modified topology of TSBB converter. Even if the proposed converter has the same number of components as a conventional TSBB converter, the proposed converter has fewer conduction components and switching semiconductors than a conventional TSBB. This results in reduced power loss. Moreover, source terminals of metal-oxide-semiconductor field-effect transistor in the proposed converter are directly connected to ground. This configuration has an advantage in selecting gate driver integrated circuit (IC), since the IC does not necessarily need to provide high-side gate signals. A printed circuit board was designed to evaluate the improvement of the proposed converter.

Background: Blunt traumatic cardiac rupture is rare. However, such cardiac ruptures carry a high mortality rate. This study reviews our experience treating blunt traumatic cardiac rupture. Methods: This retrospective study included 21 patients who experienced blunt traumatic cardiac rupture from 1999 to 2015. Every patient underwent surgery. Several variables were compared between survivors and fatalities. Results: Sixteen of the 21 patients survived, and 5 (24%) died. No instances of intraoperative mortality occurred. The most common cause of injury was a traffic accident (81%). The right atrium was the most common location of injury (43%). Ten of the 21 patients were suspected to have cardiac tamponade. Significant differences were found in preoperative creatine kinase–myocardial band (CK-MB) levels (p=0.042) and platelet counts (p= 0.004) between the survivors and fatalities. The patients who died had higher preoperative Glasgow Coma Scale scores (p=0.007), worse Trauma and Injury Severity Scores (p=0.007), and higher Injury Severity Scores (p=0.004) than those who survived. Conclusion: We found that elevated CK-MB levels, a low platelet count, and multi-organ traumatic injury were prognostic factors predicting poor outcomes of blunt cardiac rupture. If a patient with blunt traumatic cardiac rupture has these factors, clinicians should be especially attentive and respond promptly in order to save the patient’s life.

Clinical and experimental observations indicate a critical role for vascular endothelial growth factor (VEGF), secreted by the retinal pigment epithelium (RPE), in pathological angiogenesis and the development of choroidal neovascularization (CNV) in age-related macular degeneration (AMD). RPE-mediated VEGF expression, leading to angiogenesis, is a major signaling mechanism underlying ocular neovascular disease. Inhibiting this signaling pathway with a therapeutic molecule is a promising anti-angiogenic strategy to treat this disease with potentially fewer side effects. Oxalomalate (OMA) is a competitive inhibitor of NADP+-dependent isocitrate dehydrogenase (IDH), which plays an important role in cellular signaling pathways regulated by reactive oxygen species (ROS). Here, we have investigated the inhibitory effect of OMA on the expression of VEGF, and the associated underlying mechanism of action, using in vitro and in vivo RPE cell models of AMD. We found that OMA reduced the expression and secretion of VEGF in RPE cells, and consequently inhibited CNV formation. This function of OMA was linked to its capacity to activate the pVHL-mediated HIF-1α degradation in these cells, partly via a ROS-dependent ATM signaling axis, through inhibition of IDH enzymes. These findings reveal a novel role for OMA in inhibiting RPE-derived VEGF expression and angiogenesis, and suggest unique therapeutic strategies for treating pathological angiogenesis and AMD development.

Patients with cardiopulmonary failure may not be fully supported with typical configurations of extracorporeal membrane oxygenation (ECMO), either veno-arterial (VA) or veno-venous (VV). Veno-arterial-venous (VAV)-ECMO is a technique used to support the cardiopulmonary systems during periods of inadequate gas exchange and perfusion. In the severe case of coronavirus disease 2019 (COVID-19), which simultaneously affects the heart and lung, VAV-ECMO may improve a patient’s recovery potential. We report the case of a 72-year-old woman with acute respiratory distress syndrome and circulatory failure following COVID-19, who was treated with VAV-ECMO.

Austenitic Fe-base alloys, SS 316H and Alloy 800HT, were diffusion bonded for use in compact-type heat exchangers in supercritical-carbon dioxide (S-CO2) Brayton cycles. For diffusion bonded 316H, grain boundary migration across the bond-line was observed despite the formation of some Cr-rich carbide, and its tensile properties were similar to those of as-received 316H. However, diffusion bonded Alloy 800HT exhibited severely degraded elongation compared to as-received 800HT due to the formation of continuous Ti-rich carbides along the bond-line. Post-bond heat treatment (PBHT) was found to improve elongation at fracture for diffusion bonded alloys. However, a subsequent corrosion test in S-CO2 at 600 °C (20 MPa) for 1000 h resulted in a loss of elongation. This was much more severe for PBHT-ed 800HT due to the formation of Cr-rich carbides at the bond-line. Meanwhile, it was found that the effect of ageing on loss of elongation during high temperature exposure was greater than that of S-CO2 environment.

BACKGROUND:A wider angle between the left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCX) has been suggested to induce plaque formation in the arterial system via changes in shear stress. However, the relationship between the left main coronary artery (LM)-LAD angle and LAD stenosis has not been investigated. Therefore, we aimed to evaluate the associations between the LM-LAD and LAD-LCX angles and LAD stenosis. METHODS:Coronary computed tomography angiographies (CTAs) of 201 patients with suspected coronary artery disease were analyzed. Angle measurements were performed twice by experts using CTA images, and the values were averaged. The patients were divided into two groups, based on the presence of significant LAD stenosis (luminal diameter narrowing ≥50%) on CTA. RESULTS:The mean LM-LAD and LAD-LCX angles were 37.46° and 63.04°, respectively. The LM-LAD and LAD-LCX angles of the group with significant LAD stenosis were significantly wider than that of the group with nonsignificant LAD stenosis (P

PurposeThis study investigates Korean speech sound development, including articulatory error patterns, among the Japanese-Korean children whose mothers are Japanese immigrants to Korea.MethodsThe subjects were 28 Japanese-Korean children with normal development born to Japanese women immigrants who lived in Jeonbuk province, Korea. They were assessed through Computerized Speech Lab 4500. The control group consisted of 15 Korean children who lived in the same area.ResultsThe values of the voice onset time of consonants /ph/, /t/, /th/, and /k*/ among the children were prolonged. The children replaced the lenis sounds with aspirated or fortis sounds rather than replacing the fortis sounds with lenis or aspirated sounds, which are typical among Japanese immigrants. The children showed numerous articulatory errors for /c/ and /l/ sounds (similar to Koreans) rather than errors on /p/ sounds, which are more frequent among Japanese immigrants. The vowel formants of the children showed a significantly prolonged vowel /o/ as compared to that of Korean children (P

To date, four main mechanisms mediating inhibition of influenza infection by anti-hemagglutinin antibodies have been reported. Anti-globular-head-domain antibodies block either influenza virus receptor binding to the host cell or progeny virion release from the host cell. Anti-stem region antibodies hinder the membrane fusion process or induce antibody-dependent cytotoxicity to infected cells. In this study we identified a human monoclonal IgG1 antibody (CT302), which does not inhibit both the receptor binding and the membrane fusion process but efficiently reduced the nucleus entry of viral nucleoprotein suggesting a novel inhibition mechanism of viral infection by antibody. This antibody binds to the subtype-H3 hemagglutinin globular head domain of group-2 influenza viruses circulating throughout the population between 1997 and 2007.

Mediastinitis is a life-threatening disease, and effective drainage is needed to treat mediastinitis with abscess formation. We recommend an alternative drainage method using chest tube binding with a Silastic Penrose drainage tube. The use of a Silastic Penrose drainage tube may help to manage mediastinitis with abscess formation. This method facilitates effective draining and prevents tissue adhesion.

Introduction: Video head-impulse tests (video-HITs) often fail to detect anterior inferior cerebellar artery (AICA) infarction due to peripheral and central vestibular system involvement. Anecdotal studies suggest that video-HITs may reveal bilateral impairment in AICA infarction. However, the diagnostic utility of videoHITs has not been established, particularly when compared to labyrinthitis, which accounts for the majority of acute audiovestibular syndrome (AAVS) cases. Methods: We reviewed the medical records of consecutive patients presenting with new-onset acute hearing loss and spontaneous vertigo (i.e., AAVS) between March 2018 and July 2023 at a tertiary hospital in South Korea. Video-HIT patterns were categorized as follows: (1) ipsilaterally positive, (2) contralaterally positive, (3) bilaterally normal, and (4) bilaterally positive. Results: Twenty-eight patients with AICA infarction (mean age±standard deviation  =  67±15  years; 14 men) and 51 with labyrinthitis (63±17  years, 26 men) were included in the analyses. Among the 28 patients with AICA infarction, 15 presented with AAVS in isolation, without other co-morbid neurologic deficits (15/28, 54%). The vestibulo-ocular reflex (VOR) gains of ipsilesional horizontal canals (HCs) ranged from 0.21 to 1.22 (median  =  0.81, interquartile range [IQR]  =  0.50–0.89). However, those for contralateral HC gain ranged from 0.57 to 1.19 (median  =  0.89 [IQR  =  0.73–0.97]). Collectively, HITs were bilaterally positive in 13 patients (including 12 patients with bilaterally positive HITs for the horizontal canal), normal in eight, ipsilesionally positive in six, and contralesionally positive in one patient with AICA infarction. The VOR gains were typically decreased ipsilaterally in 28 (28/51, 55%), normal in 17 (17/51, 33%), and decreased bilaterally in six patients with labyrinthitis (6/51, 12%). Logistic regression analysis revealed that bilaterally positive HITs (p  =  0.004) and multiple vascular risk factors (p  =  0.043) were more frequently associated with AICA infarction than labyrinthitis. Discussion: Among patients presenting with AAVS, bilaterally positive HITs can be indicative of AICA infarction in patients with multiple vascular risk factors. [ABSTRACT FROM AUTHOR]