Impact of Respiratory Phase during Pleural Puncture on Complications in CT-Guided Percutaneous Lung Biopsy.

Purpose: This study investigated whether the respiratory phase during pleural puncture in CT-guided percutaneous transthoracic needle biopsy (PTNB) affects complications. Materials and Methods: We conducted a retrospective review of 477 lung biopsy CT scans performed during free breathing. The respiratory phases during pleural puncture were determined based on the table position of the targeted nodule using CT scans obtained during free breathing. We compared the rates of complications among the inspiratory, mid-, and expiratory respiratory phases. Logistic regression analysis was performed to control confounding factors associated with pneumothorax. Results: Among the 477 procedures, pleural puncture was performed during the expiratory phase in 227 (47.6%), during the mid-phase in 108 (22.6%), and during the inspiratory phase in 142 (29.8%). The incidence of pneumothorax was significantly lower in the expiratory puncture group (40/227, 17.6%; p = 0.035) and significantly higher in the mid-phase puncture group (31/108, 28.7%; p = 0.048). After controlling for confounding factors, expiratory-phase puncture was found to be an independent protective factor against pneumothorax (odds ratio = 0.571; 95% confidence interval = 0.360-0.906; p = 0.017). Conclusion: Our findings suggest that pleural puncture during the expiratory phase may reduce the risk of pneumothorax during image guided PTNB.

Assessing Radiation Exposure and Contrast Agent Utilization: A Comparative Analysis of the Woven EndoBridge Device and Stent-Assisted Coil Embolization for Managing Unruptured Wide-Neck Bifurcation Aneurysms.

PURPOSE: In this study, we determined whether there were significant differences in procedure time, radiation dose, fluoroscopy time, and total contrast media dose when unruptured wideneck bifurcation aneurysms (WNBAs) were treated with the Woven EndoBridge (WEB) device and stent-assisted coil (SAC) embolization. MATERIALS AND METHODS: The WEB device and SAC embolization (14:17) were used to treat 31 cases of internal carotid artery bifurcation, anterior communicating artery, middle cerebral artery bifurcation, and basilar bifurcation aneurysms between August 2021 and December 2022. The procedure time, radiation dose, fluoroscopy time, and total contrast medium dose between the 2 treatment groups were compared and analyzed. In the WEB device group, the results between operators were compared, and the follow-up radiologic outcomes were investigated. RESULTS: The procedure and fluoroscopy times were significantly shorter in the WEB device group. Radiation and total contrast media dose were also significantly smaller in the WEB device, but there was no significant difference in results between operators. The follow-up radiological outcome showed adequate occlusion in 83.3% (10/12) of cases. CONCLUSION: The WEB device can be used as an alternative treatment method among the available endovascular treatment methods for WNBAs to reduce radiation exposure and the dose of contrast media when used adequately with appropriate indications.

Tuberculous Pericarditis Mimicking a Malignant Pericardial Tumor: A Case Report.

Tuberculous pericarditis is an extrapulmonary manifestation of tuberculosis that is most commonly associated with pericardial thickening, effusion, and calcification. We present a case of tuberculous pericarditis mimicking a malignant pericardial tumor in a 77-year-old male. CT revealed an irregular and nodular pericardial thickening. MRI revealed high signal intensity on T1-weighted fat-suppressed images and peripheral rim enhancement after gadolinium administration. MRI can be helpful in determining the differential diagnoses in cases of tuberculous pericarditis with nonspecific imaging findings.

A Case of Idiopathic Orbital Inflammation With Elevated Anti-Mumps Immunoglobulin M Antibody.

A 21-year-old female presented with periocular swelling, diplopia, and painful ophthalmoplegia in the OS. Orbital magnetic resonance imaging revealed an enhanced soft tissue mass involving the left medial rectus muscle. Laboratory test results revealed leukocytosis, elevated reactive C-reactive protein, and positive serum levels of anti-mumps immunoglobulin M (IgM) antibody without systemic manifestations of mumps infection. The clinical course was refractory, and the patient showed a poor response to high-dose steroids. An incisional biopsy revealed stromal fibrosis with focal lymphoid aggregates, indicating sclerosing inflammation. Myopathy of the medial rectus progressed to superior, inferior, and lateral recti involvement of the left orbit. Immunosuppressive agents, including steroids, were administered for 22 months after disease onset. The mumps IgM antibody level was positive for over 5 months and became negative upon testing performed 1 year after the first visit.

Effects of Melatonin, GM-CSF, IGF-1, and LIF in Culture Media on Embryonic Development: Potential Benefits of Individualization.

The implantation of good-quality embryos to the receptive endometrium is essential for successful live birth through in vitro fertilization (IVF). The higher the quality of embryos, the higher the live birth rate per cycle, and so efforts have been made to obtain as many high-quality embryos as possible after fertilization. In addition to an effective controlled ovarian stimulation process to obtain high-quality embryos, the composition of the embryo culture medium in direct contact with embryos in vitro is also important. During embryonic development, under the control of female sex hormones, the fallopian tubes and endometrium create a microenvironment that supplies the nutrients and substances necessary for embryos at each stage. During this process, the development of the embryo is finely regulated by signaling molecules, such as growth factors and cytokines secreted from the epithelial cells of the fallopian tube and uterine endometrium. The development of embryo culture media has continued since the first successful human birth through IVF in 1978. However, there are still limitations to mimicking a microenvironment similar to the reproductive organs of women suitable for embryo development in vitro. Efforts have been made to overcome the harsh in vitro culture environment and obtain high-quality embryos by adding various supplements, such as antioxidants and growth factors, to the embryo culture medium. Recently, there has been an increase in the number of studies on the effect of supplementation in different clinical situations such as old age, recurrent implantation failure (RIF), and unexplained infertility; in addition, anticipation of the potential benefits from individuation is rising. This article reviews the effects of representative supplements in culture media on embryo development.

Transarterial Chemoembolization Using Idarubicin Versus Doxorubicin Chemoemulsion in Patients with Hepatocellular Carcinoma (IDADOX): Protocol for a Randomized, Non-inferiority, Double-Blind Trial.

PURPOSE: This study aims to test the hypothesis that idarubicin-based transarterial chemoembolization (IDA-TACE), using one of the most potent chemotherapeutic agents, could yield oncologic outcomes equivalent to or marginally improved over doxorubicin-based TACE (DOX-TACE). MATERIALS AND METHODS: This single-center, prospective, phase II, randomized controlled, non-inferiority, double-blind trial will enroll 128 treatment-naïve patients with HCC (≤ 5 tumors, 1-5 cm in diameter) for conventional TACE. Participants will be randomly assigned (1:1) to either IDA-TACE or DOX-TACE, with stratification by Child-Pugh class. Superselective conventional TACE will be performed using cone-beam CT and small-bore microcatheters. Patient evaluations, including dynamic imaging and blood tests, will occur at 1, 3, and 6 months post-initial treatment. The primary outcome measure is the objective response rate (ORR) according to mRECIST at 6 months. Secondary outcomes include 3-month and 6-month tumor responses, time-to-progression, the incidence of treatment-related serious adverse events within 30 days, and the incidence and severity of any adverse events. STATISTICS: Non-inferiority will be claimed if the upper limit of a one-sided 97.5% confidence interval for the proportion difference (i.e., "6-month ORR of DOX-TACE" - "6-month ORR of IDA-TACE") falls below 0.15 in both intention-to-treat and per-protocol analyses. The proportion difference and its confidence interval will be calculated by the Cochran-Mantel-Haenszel method to obtain a weighted average of stratum-specific proportion differences. EXPECTED GAIN OF KNOWLEDGE: If IDA-TACE demonstrates outcomes comparable to DOX-TACE, this study could provide compelling evidence that various cytotoxic agents yield similar contributions in TACE, considering the minor role of chemotherapeutic agents in TACE. TRIAL REGISTRATION: ClinicalTrials.gov ( https://clinicaltrials.gov/ ). Identifier: NCT06114082. World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) ( https://trialsearch.who.int/Default.aspx ). Identifier: KCT0008166.

Coordination chemistry of mitochondrial copper metalloenzymes: exploring implications for copper dyshomeostasis in cell death.

Mitochondria, fundamental cellular organelles that govern energy metabolism, hold a pivotal role in cellular vitality. While consuming dioxygen to produce adenosine triphosphate (ATP), the electron transfer process within mitochondria can engender the formation of reactive oxygen species that exert dual roles in endothelial homeostatic signaling and oxidative stress. In the context of the intricate electron transfer process, several metal ions that include copper, iron, zinc, and manganese serve as crucial cofactors in mitochondrial metalloenzymes to mediate the synthesis of ATP and antioxidant defense. In this mini review, we provide a comprehensive understanding of the coordination chemistry of mitochondrial cuproenzymes. In detail, cytochrome c oxidase (CcO) reduces dioxygen to water coupled with proton pumping to generate an electrochemical gradient, while superoxide dismutase 1 (SOD1) functions in detoxifying superoxide into hydrogen peroxide. With an emphasis on the catalytic reactions of the copper metalloenzymes and insights into their ligand environment, we also outline the metalation process of these enzymes throughout the copper trafficking system. The impairment of copper homeostasis can trigger mitochondrial dysfunction, and potentially lead to the development of copper-related disorders. We describe the current knowledge regarding copper-mediated toxicity mechanisms, thereby shedding light on prospective therapeutic strategies for pathologies intertwined with copper dyshomeostasis. [BMB Reports 2023; 56(11): 575-583].

Copper trafficking systems in cells: insights into coordination chemistry and toxicity.

Transition metal ions, such as copper, are indispensable components in the biological system. Copper ions which primarily exist in two major oxidation states Cu(I) and Cu(II) play crucial roles in various cellular processes including antioxidant defense, biosynthesis of neurotransmitters, and energy metabolism, owing to their inherent redox activity. The disturbance in copper homeostasis can contribute to the development of copper metabolism disorders, cancer, and neurodegenerative diseases, highlighting the significance of understanding the copper trafficking system in cellular environments. This review aims to offer a comprehensive overview of copper homeostatic machinery, with an emphasis on the coordination chemistry of copper transporters and trafficking proteins. While copper chaperones and the corresponding metalloenzymes are thoroughly discussed, we also explore the potential existence of low-molecular-mass metal complexes within cellular systems. Furthermore, we summarize the toxicity mechanisms originating from copper deficiency or accumulation, which include the dysregulation of oxidative stress, signaling pathways, signal transduction, and amyloidosis. This perspective review delves into the current knowledge regarding the intricate aspects of the copper trafficking system, providing valuable insights into potential treatment strategies from the standpoint of bioinorganic chemistry.

Prolapsed Uterine Smooth Muscle Tumor of Uncertain Malignant Potential: A Case Report and Review of Radiologic Findings.

INTRODUCTION: Uterine smooth muscle tumor of uncertain malignant potential (STUMP) is a rare tumor that arises in the myometrium of the uterus. It is regarded as an intermediate malignant tumor according to the recent World Health Organization classification. Few studies have reported the radiologic findings of STUMP, and the differentiation of STUMP from leiomyoma remains controversial. CASE DESCRIPTION: A 42-year-old nulliparous female presented at our institution with massive vaginal bleeding. Radiological studies, including ultrasonography, computed tomography (CT), and magnetic resonance imaging, revealed an oval-shaped mass with well-defined margins in the uterus protruding into the vagina. The patient underwent a total abdominal hysterectomy, and the final pathology was confirmed as STUMP. CONCLUSION: Distinguishing STUMP from leiomyomas based solely on radiological findings can be challenging. However, if the uterine mass appears as a single mass lacking acoustic shadowing on ultrasound and demonstrates diffusion restriction with high T2 signal intensity on magnetic resonance imaging, consideration of STUMP may be necessary for proper patient management, given the poor prognosis associated with this tumor.

Huge Primary Clear Cell Hepatocellular Carcinoma: a Case Report and Review of Radiologic Findings.

INTRODUCTION: Clear cell hepatocellular carcinoma (HCC) is a rare subtype of HCC. Histologically, clear cell HCC is characterized by the cytoplasmic accumulation of glycogen with a clear cell appearance, constituting > 80% of tumor cells. Radiologically, clear cell HCC demonstrates early enhancement and washout similar to conventional HCC. Occasionally, enhancing capsule and intratumoral fat are accompanied by clear cell HCC. CASE DESCRIPTION: A 57-year-old male presented to our hospital with right upper quadrant abdominal pain. Ultrasonography, computed tomography, and magnetic resonance imaging revealed a large mass with a well-defined margin in the right hemiliver. The patient underwent a right hemihepatectomy, and the final histopathology revealed clear cell-type HCC. CONCLUSION: Distinguishing clear cell types from other types of HCC solely based on radiological findings is challenging. If hepatic tumors exhibit encapsulated margins, enhancing rims, intratumoral fat, and arterial phase hyperenhancement/washout pattern despite their large size, consideration of clear cell subtypes in the differential diagnosis list will aid patient management, implying better prognosis than not-otherwise-specified HCC.

Effect of the respiratory motion of pulmonary nodules on CT-guided percutaneous transthoracic needle biopsy.

BACKGROUND: Computed tomography (CT)-guided percutaneous transthoracic needle biopsy (PTNB) is highly affected by respiratory motion; however, respiratory motion of target nodule during the PTNB and its effect on CT-guided lung biopsy have not been studied. PURPOSE: To investigate the effect of the respiratory motion of pulmonary nodules on CT-guided PTNB. MATERIAL AND METHODS: We retrospectively reviewed the procedural CT scans of 426 pulmonary nodules that underwent PTNB during quiet breathing. Maximal and average respiratory motions were measured using the difference of table position of the targeted nodule between multiple procedural scans. Diagnostic performance, complications, and technical factors of PTNB in nodules with large motion (maximal motion >1 cm) were compared with those in nodules with small motion (≤1 cm). RESULTS: The mean maximal and average respiratory motions between tidal volume breathing were 5.4 ± 4.4 and 2.7 ± 2.6 mm, respectively. Sensitivity and accuracy were 93.1% and 96.1% in nodules with large motion, compared with 94.7% and 95.9% in nodules with small motion, respectively. Respiratory targeting (P < 0.001), needle modulation (P < 0.001), motion artifact of target (P < 0.001), target disappearance from scans (P < 0.001), and number of performed CT scans (P < 0.001) were significantly higher in the large motion group, with no significant difference in radiation dose and complications between the groups. CONCLUSION: The respiratory motion of pulmonary nodules during CT-guided PTNB may cause technical difficulties but does not affect diagnostic performance nor complications associated with PTNB.

Transbronchial Lung Cryobiopsy for Diagnosing Interstitial Lung Disease: A Retrospective Single-Center Experience.

BACKGROUND: An accurate diagnosis in patients with interstitial lung diseases (ILDs) by multidisciplinary discussion (MDD) based on histopathologic information is essential for optimal treatment. Transbronchial lung cryobiopsy (TBLC) has increasingly been used as a diagnostic alternative to surgical lung biopsy. This study aimed to evaluate the appropriate methods of TBLC in patients with ILD in Korea. METHODS: A total of 27 patients who underwent TBLC were included. TBLC procedure details and clinical MDD diagnosis using TBLC histopathologic information were retrospectively analyzed. RESULTS: All procedures were performed under general anesthesia with the fluoroscopic guidance in the operation room using flexible bronchoscopy and endobronchial balloon blocker. The median procedure duration was less than 30 minutes, and the median number of biopsies per participant was 2. Most of the bleeding after TBLC was not severe, and the rate of pneumothorax was 25.9%. The most common histopathologic pattern was alternative (48.2%), followed by indeterminate (33.3%) and usual interstitial pneumonia (UIP)/probable UIP (18.5%). In the MDD after TBLC, the most common diagnosis was idiopathic pulmonary fibrosis (33.3%), followed by smoking-related ILD (25.9%), nonspecific interstitial pneumonia (18.6%), unclassifiable-ILD (14.8%), and others (7.4%). CONCLUSION: This first single-center experience showed that TBLC using a flexible bronchoscopy and endobronchial balloon blocker with the fluoroscopic guidance under general anesthesia may be a safe and adequate diagnostic method for ILD patients in Korea. The diagnostic yield of MDD was 85.2%. Further studies are needed to evaluate the diagnostic yield and confidence of TBLC.

Time delays and risk factors in the management of patients with active pulmonary tuberculosis: nationwide cohort study.

Estimating the time delay and identifying associated factors is essential for effective tuberculosis control. We systemically analysed data obtained from the Korea Tuberculosis Cohort in 2019 by classifying delays as presentation and healthcare delays of pulmonary tuberculosis (PTB). Of 6593 patients with active PTB, presentation and healthcare delays were recorded in 4151 and 5571 patients, respectively. The median presentation delay was 16.0 (5.0-40.0) days. Multivariable logistic regression analysis showed that longer presentation delays were associated with neuropsychiatric disease [adjusted odds ratio (OR) 2.098; 95% confidence interval (CI) 1.639-2.687; p < 0.001] and heavy alcohol intake (adjusted OR 1.505; 95% CI 1.187-1.907; p < 0.001). The median healthcare delay was 5.0 (1.0-14.0) days. A longer healthcare delay was associated with malignancy (adjusted OR 1.351; 95% CI 1.069-1.709; p = 0.012), autoimmune disease (adjusted OR 2.445; 95% CI 1.295-4.617; p = 0.006), and low bacterial burden manifested as an acid-fast bacillus smear-negative and tuberculosis polymerase chain reaction-negative status (adjusted OR 1.316; 95% CI 1.104-1.569; p = 0.002). Active case-finding programmes need to focus on patients with heavy alcoholism or neuropsychiatric diseases. To ensure early PTB detection, healthcare providers must carefully monitor patients with malignancy, autoimmune disease, or a high index of suspicion for PTB.

Clinical outcomes of hyperprogression based on volumetry in non-small cell lung cancer after immune checkpoint inhibitor treatment.

BACKGROUND: Hyperprogressive disease (HPD) is a novel pattern of the treatment course after immune checkpoint inhibitor (ICI) therapy in patients with non-small cell lung cancer (NSCLC). This study aimed to investigate the clinical characteristics, outcomes, and associated factors of HPD using a semiautomatic volume measurement. METHODS: This retrospective study enrolled patients with recurrent and/or metastatic NSCLC treated with ICIs between January 2015 and August 2019 at eight tertiary centers in Korea. HPD was defined according to the tumor growth kinetics and time to treatment failure. Tumor volume was measured using a semiautomatic software. RESULTS: A total of 219 NSCLC patients with 35 HPD by volumetric measurement (HPDv) (15.9%) were enrolled. The median duration of overall survival (OS) and OS after ICI treatment (ICI-OS) were 34.5 and 18.4 months, respectively. HPDv patients had significantly worse progression-free survival (PFS) than progressive disease patients without HPDv (1.16 vs. 1.82 months, p-value <0.001). ICI-OS did not significantly differ between patients with HPDv and those without HPDv (2.66 vs. 5.4 months, p = 0.105). PD-L1 expression lower than 50%, more than three metastatic sites, neutrophil-to-lymphocyte ratio equal to or higher than 3.3, and hemoglobin level lower than 10 were found to be associated with HPDv. CONCLUSIONS: There is no standardized definition of HPD. However, defining HPD in NSCLC patients treated with ICI using a semiautomatic volume measurement software is feasible.

Is Free Breathing Possible During Computed Tomography-Guided Percutaneous Transthoracic Lung Biopsy? The Clinical Experience in 585 Cases.

OBJECTIVE: The aim of the study was to retrospectively evaluate the safety and accuracy of computed tomography (CT)-guided percutaneous transthoracic needle biopsy (PTNB) of lung lesions during quiet breathing. METHODS: We investigated the diagnostic performance and complication rate of 585 procedures in 563 patients (357 men; mean age, 67.7 years), who underwent CT-guided PTNBs during quiet breathing, aided by a respiratory targeting technique from May 2017 to July 2019. Differences between the cases with and without respiratory targeting were analyzed. Logistic regression analyses were performed to examine the development of pneumothorax and hemoptysis. RESULTS: Percutaneous transthoracic needle biopsy samples were successfully obtained in 574 of 585 procedures (98.1%). Final diagnoses included: 410 malignant cases, 119 benign cases, and 45 indeterminate cases. The sensitivity, specificity, and accuracy of diagnosis were 94.4%, 100%, and 95.7%, respectively. Use of respiratory targeting was associated with younger age (P = 0.004), smaller lesion size (P < 0.001), peripheral location (P = 0.003), shorter distance from the diaphragm (P < 0.001), lower lobe location (P < 0.001), prone position (P = 0.004), and visible motion artifact (P < 0.001). Pneumothorax and hemoptysis rates were 22.9% and 7.9%, respectively. Upon multivariate analysis, emphysema (P = 0.002) was the only independent risk factor for pneumothorax, whereas distance from the pleura greater than 2 cm (P < 0.001), tissue sampling 3 times or more (P = 0.003), and a less experienced operator (P < 0.001) were risk factors for hemoptysis. CONCLUSIONS: Computed tomography-guided PTNB during quiet breathing with respiratory targeting yielded high diagnostic performance with a slightly higher rate of complications. Free-breathing PTNB can be applied in clinical practice, based on lesion location and risk factors for complications.

Uterine Angiolipoleiomyoma with US, CT, and MRI Findings: A Case Report.

INTRODUCTION: Angiolipoleiomyoma (ALLM) is a rare hamartomatous tumor of mesenchymal origin composed of smooth muscle, mature adipose tissue, and blood vessels in various proportions. Because of its histologic similarity to renal Angiomyolipoma (AML), it is also called uterine angiomyolipoma. Preoperative diagnosis of uterine ALLM is very challenging due to its uncommon incidence and absence of established characteristic imaging findings. CASE PRESENTATION: A 50-year-old multiparous female patient visited our institution for gynecologic screening. Transvaginal Sonography (TVS), Abdominopelvic Computed Tomography (CT), and pelvic Magnetic Resonance Imaging (MRI) revealed large well-defined masses involving the posterior uterine wall with rectal indentation. The patient underwent a total abdominal hysterectomy for this tumor and the histopathological diagnosis was uterine ALLM. CONCLUSION: This report would contribute to understanding and establishing the radiologic findings of the uterine ALLM. Considering the benign characteristics and favorable prognosis of this rare tumor, familiarity with its imaging findings by radiologists will guide clinicians in better patient management and prevention of unnecessary radical surgery.

Detection of pericardial flow in black blood-prepared T2 HASTE sequence imaging: Differentiation between pericardial diverticulum and cyst.

Pericardial diverticulum is a focal herniation of the pericardium. It is differentiated from a pericardial cyst by the presence of communication with the pericardial cavity. Radiological differentiation between the diverticulum and cyst via computed tomography is difficult unless changes in size are identified with different body positions in additional scans. Herein we describe a case of pericardial diverticulum that was successfully diagnosed via the detection of internal pericardial flow in black blood-prepared T2 half-Fourier acquisition single-shot turbo spin-echo magnetic resonance imaging. Detection of a flow void in the pericardial sac may be a definitive magnetic resonance imaging finding in the diagnosis of pericardial diverticulum.

Gangliocytic Paraganglioma of the Gastrointestinal Tract: A Case Report of Cecal Origin.

INTRODUCTION: Gangliocytic paraganglioma is an extremely rare tumor that is composed of epithelioid, ganglion, and spindle cells. It has a predilection site in the duodenum, especially the periampullary region. The clinical course is usually benign, but a few cases of metastasis to lymph nodes or distant sites have been noted. Several case reports or small series reviews of gangliocytic paraganglioma have been published, but so far, cecal gangliocytic paraganglioma has not been described. CASE DESCRIPTION: A 61-year-old man underwent an abdominal Computed Tomography (CT) scan for known GB stones, which revealed an incidental cecal mass. The patient underwent wedge resection of the cecum for diagnostic and therapeutic purposes. Histopathological examination of the cecal mass identified a gangliocytic paraganglioma. There was no evidence of metastasis in the dissected regional lymph nodes. No additional treatment, such as adjuvant chemotherapy or radiotherapy, was administered, and the patient underwent regular follow-up without any complications. CONCLUSION: The most common radiologic finding in gangliocytic paraganglioma is a circumscribed, enhancing subepithelial mass. Herein, we report an uncommon case of cecal-origin gangliocytic paraganglioma. With knowledge of the radiologic and histologic characteristics of gangliocytic paraganglioma, appropriate management can be provided without unnecessary radical resection.

Efficacy of ethyl ascorbyl ether-containing cosmetic cream on blue light-induced skin changes.

BACKGROUND: Office workers are consistently exposed to blue light, mainly from sunlight and digital device. Recent studies report that blue light has various harmful effects, including cellular changes via reactive oxygen species. Studies on blue light-induced skin changes have only been conducted in vitro and have not been clinically confirmed. OBJECTIVE: We provide novel methods to evaluate the effect of the product on the recovery of skin changed by blue light. METHODS: Internet surveys were conducted for workers in their 20s and 40s regarding exposure time to blue light in various environments. To study the effects of long-term exposure to blue light (456 nm) on the skin, we designed three light intensity conditions, and various skin characteristics were observed. After blue light irradiation, various skin characteristics were analyzed before and after applying ethyl ascorbyl ether (EAE)-containing cosmetic cream for 2 weeks. RESULTS: When exposed to strong blue light for approximately 16 days, the L* value, skin hydration, transparency, and elasticity decreased, and the melanin index, erythema index, a* value, and b* value increased. Furthermore, after short-term blue light irradiation (dose, 269 J/cm2 , the equivalent of blue light exposure for approximately 38 days in daily life), the L* value and elasticity decreased, and the melanin index and erythema index increased. However, when EAE cream was applied on skin for 1-2 weeks, the skin recovered. CONCLUSION: This study clinically confirms the skin changes caused by blue light and the effect of EAE in relieving such changes.

Elucidating molecular mechanisms of acquired resistance to BRAF inhibitors in melanoma using a microfluidic device and deep sequencing.

BRAF inhibitors (e.g., vemurafenib) are widely used to treat metastatic melanoma with the BRAF V600E mutation. The initial response is often dramatic, but treatment resistance leads to disease progression in the majority of cases. Although secondary mutations in the mitogen-activated protein kinase signaling pathway are known to be responsible for this phenomenon, the molecular mechanisms governing acquired resistance are not known in more than half of patients. Here we report a genome- and transcriptome-wide study investigating the molecular mechanisms of acquired resistance to BRAF inhibitors. A microfluidic chip with a concentration gradient of vemurafenib was utilized to rapidly obtain therapy-resistant clones from two melanoma cell lines with the BRAF V600E mutation (A375 and SK-MEL-28). Exome and transcriptome data were produced from 13 resistant clones and analyzed to identify secondary mutations and gene expression changes. Various mechanisms, including phenotype switching and metabolic reprogramming, have been determined to contribute to resistance development differently for each clone. The roles of microphthalmia-associated transcription factor, the master transcription factor in melanocyte differentiation/dedifferentiation, were highlighted in terms of phenotype switching. Our study provides an omics-based comprehensive overview of the molecular mechanisms governing acquired resistance to BRAF inhibitor therapy.