Background: We aimed to clarify the safety and efficacy of simultaneous skin exposure to blue, red, and infrared light. The purpose of this study was to confirm the mechanism by which multiple wavelengths increase hair development both in vivo and in vitro. Methods: Cultured human dermal papilla cells (hDPCs) were exposed to a 470/655/850 nm light-emitting diode (LED) array with a fixed energy density of 3.0 mW/cm 2 . We analyzed alkaline phosphatase (ALP) staining and activity. The relative expressions of ALP, VEGF, Shh, and OPN3 were examined using reverse transcriptasepolymerase chain reaction arrays 48 hours post-exposure and the protein levels related to extracellular signalregulated kinase (ERK)/protein kinase B (AKT)/glycogen synthase kinase 3 (GSK3)β signaling were assessed by western blotting. Next, we used H&E staining, hair growth scoring, skin thickness measurement, and the immunohistochemical analysis of the dorsal skin of C57BL/6 mice to investigate the effects of the mono- or combined-photobiomodulation (PBM) groups. Results: According to our findings, simultaneous irradiation with multi-wavelength LEDs at 470/655/850 nm increased the proliferation of hDPCs. Also, compared to the control group, the red wavelength and combined PBM groups had significantly improved skin thickness measurements. Overall, we concluded that the combined PBM therapy successfully induced the early onset of anagen and stimulated hair growth. Conclusion These results suggest that PBM therapy regulates hair growth by activating the ERK/AKT/GSK3βsignaling pathway. Thus, multiple-wavelength radiation from devices combining radiation emitted by lowpower lasers and LEDs could be a new approach for promoting PBM-induced beneficial effects.

Purpose: Since the introduction of robotic surgery, robots for colorectal cancer have replaced laparoscopic surgery, and a single-port robot (SPR) platform has been launched and is being used to treat patients. We analyzed the learning curve and initial complications of using an SPR platform in colorectal cancer surgery. Methods: We reviewed 39 patients who underwent SPR colectomy from April to October 2019. All surgeries were performed by the same surgeon using an SPR device. A learning curve was generated using the cumulative sum methodology to assess changes in total operation time, docking time, and surgeon console time. We grouped the patients into 3 groups according to the time period: the first 11 were phase 1, the next 11 were phase 2, and the last 17 were phase 3. Results: The mean age of the patients was 61.28±13.03 years, and they had a mean body mass index of 23.79±2.86 kg/m2. Among the patients, 23 (59.0%) were male, and 16 (41.0%) were female. The average operation time was 186.59±51.30 minutes, the average surgeon console time was 95.49±35.33 minutes, and the average docking time (time from skin incision to robot docking) was 14.87±10.38 minutes. The surgeon console time differed significantly among the different phases (P<0.001). Complications occurred in 8 patients: 2 ileus, 2 postoperation hemoglobin changes, 3 urinary retentions, and 1 complicated fluid collection. Conclusion In our experience, the learning curve for SPR colectomy was achieved after the 18th case.

OBJECTIVES: This study examined changes in socioeconomic inequalities in mortality in Korea before and after the outbreak of coronavirus disease 2019 (COVID-19). METHODS: From 2017 to 2020, age-standardized mortality rates were calculated for all-cause deaths, avoidable deaths (preventable deaths, treatable deaths), and unavoidable deaths using National Health Insurance claims data and Statistics Korea’s cause of death data. In addition, the slope index of inequality (SII) and the relative index of inequality (RII) by six income levels (Medical Aid beneficiary group and quintile of health insurance premiums) were computed to analyze the magnitude and change of mortality inequalities. RESULTS: All-cause and avoidable mortality rates decreased steadily between 2017 and 2020, whereas unavoidable mortality remained relatively stable. In the case of mortality inequalities, the disparity in all-cause mortality between income classes was exacerbated in 2020 compared to 2019, with the SII increasing from 185.44 to 189.22 and the RII increasing from 3.99 to 4.29. In particular, the preventable and unavoidable mortality rates showed an apparent increase in inequality, as both the SII (preventable: 91.31 to 92.01, unavoidable: 69.99 to 75.38) and RII (preventable: 3.42 to 3.66, unavoidable: 5.02 to 5.89) increased. CONCLUSIONS In the first year of the COVID-19 pandemic, mortality inequality continued to increase, although there was no sign of exacerbation. It is necessary to continuously evaluate mortality inequalities, particularly for preventable and unavoidable deaths.

Background/Aims: We aimed to define an optimal target population and drug-specific biomarkers that may predict dipeptidyl peptidase (DPP)-4 inhibitor responses in non-alcoholic fatty liver disease (NAFLD). Methods: An exploration study (study I) was performed using three different NAFLD models (basket study design; high-fat diet [HFD], methionine choline-deficient diet [MCD], and high-cholesterol Western diet [WD] models). RNA transcriptome analysis was performed on pre-studied liver tissues to identify biomarkers that could predict the response to DPP-4 inhibitors. In the validation study (study II), the HFD-induced NAFLD model was divided into high and low hepatic insulin-like growth factor binding protein 1 (Igfbp-1) groups based on the pre-study liver biopsy. Results: DPP-4 inhibitor attenuated the NAFLD activity score and fibrosis stage in the HFD model but not in the WD and MCD models. The overall response rate was 19% across the modified basket NAFLD trial and 42%, 25%, and 0% in the HFD, WD, and MCD models. Hepatic Igfbp-1 expression was higher in the responder group than in the non-responder group in pre-study biopsy samples. In contrast, hepatic Igfbp-1 expression was lower in the responder group than in the non-responder group in the end-study biopsy samples. DPP-4 inhibitor response rates were 83% and 17% in the baseline hepatic high Igfbp-1 and low Igfbp-1 groups, respectively. Hepatic messenger RNA Igfbp-1 expression was positively correlated with serum IGFBP-1 levels. Conclusions The DPP-4 inhibitor response was higher in the HFD phenotype and pre-treatment levels of hepatic or serum IGFBP-1 were high.

Background: Excessive proliferation and migration of vascular smooth muscle cells (VSMCs), which contributes to the development of occlusive vascular diseases, requires elevated mitochondrial oxidative phosphorylation to meet the increased requirements for energy and anabolic precursors. Therefore, therapeutic strategies based on blockade of mitochondrial oxidative phosphorylation are considered promising for treatment of occlusive vascular diseases. Here, we investigated whether DN200434, an orally available estrogen receptor-related gamma inverse agonist, inhibits proliferation and migration of VSMCs and neointima formation by suppressing mitochondrial oxidative phosphorylation. Methods: VSMCs were isolated from the thoracic aortas of 4-week-old Sprague-Dawley rats. Oxidative phosphorylation and the cell cycle were analyzed in fetal bovine serum (FBS)- or platelet-derived growth factor (PDGF)-stimulated VSMCs using a Seahorse XF-24 analyzer and flow cytometry, respectively. A model of neointimal hyperplasia was generated by ligating the left common carotid artery in male C57BL/6J mice. Results: DN200434 inhibited mitochondrial respiration and mammalian target of rapamycin complex 1 activity and consequently suppressed FBS- or PDGF-stimulated proliferation and migration of VSMCs and cell cycle progression. Furthermore, DN200434 reduced carotid artery ligation-induced neointima formation in mice. Conclusion Our data suggest that DN200434 is a therapeutic option to prevent the progression of atherosclerosis.

Central serous chorioretinopathy may induce poor eyesight and serous retinal detachment. However, its exact cause has not been well established thus far. It can be associated with systemic high-dose corticosteroid treatment mainly for young and middle-aged men and may spontaneously regress or recur after withdrawal from corticosteroid. After corticosteroid administration for Behcet's disease, it is necessary to identify any ocular symptoms. Behcet's disease can lead to the development of ocular complications, such as uveitis, hypopyon, retinal vasculitis, optic neuritis, angiogenesis, secondary cataract, and glaucoma. It is possible to diagnose any of these complications via optical coherence tomography and digital indocyanine green angiography. It is easy to neglect an ocular symptom that may appear after a low-dose corticosteroid treatment as an ocular complication in patients with Behcet's disease. Thus, we report on a case concerning high-dose corticosteroid treatment with a literature review.
Angiography ; Behcet Syndrome ; Capsule Opacification ; Central Serous Chorioretinopathy* ; Glaucoma ; Humans ; Indocyanine Green ; Male ; Optic Neuritis ; Retinal Detachment ; Retinal Vasculitis ; Tomography, Optical Coherence ; Uveitis

Central serous chorioretinopathy may induce poor eyesight and serous retinal detachment. However, its exact cause has not been well established thus far. It can be associated with systemic high-dose corticosteroid treatment mainly for young and middle-aged men and may spontaneously regress or recur after withdrawal from corticosteroid. After corticosteroid administration for Behcet's disease, it is necessary to identify any ocular symptoms. Behcet's disease can lead to the development of ocular complications, such as uveitis, hypopyon, retinal vasculitis, optic neuritis, angiogenesis, secondary cataract, and glaucoma. It is possible to diagnose any of these complications via optical coherence tomography and digital indocyanine green angiography. It is easy to neglect an ocular symptom that may appear after a low-dose corticosteroid treatment as an ocular complication in patients with Behcet's disease. Thus, we report on a case concerning high-dose corticosteroid treatment with a literature review.
Angiography ; Behcet Syndrome ; Capsule Opacification ; Central Serous Chorioretinopathy ; Glaucoma ; Humans ; Indocyanine Green ; Male ; Optic Neuritis ; Retinal Detachment ; Retinal Vasculitis ; Tomography, Optical Coherence ; Uveitis

Migration of cells along the right direction is of paramount importance in a number of in vivo circumstances such as immune response, embryonic developments, morphogenesis, and healing of wounds and scars. While it has been known for a while that spatial gradients in chemical cues guide the direction of cell migration, the significance of the gradient in mechanical cues, such as stiffness of extracellular matrices (ECMs), in directed migration of cells has only recently emerged. With advances in synthetic chemistry, micro-fabrication techniques, and methods to characterize mechanical properties at a length scale even smaller than a single cell, synthetic ECMs with spatially controlled stiffness have been created with variations in design parameters. Since then, the synthetic ECMs have served as platforms to study the migratory behaviors of cells in the presence of the stiffness gradient of ECM and also as scaffolds for the regeneration of tissues. In this review, we highlight recent studies in cell migration directed by the stiffness gradient, called durotaxis, and discuss the mechanisms of durotaxis. We also summarize general methods and design principles to create synthetic ECMs with the stiffness gradients and, finally, conclude by discussing current limitations and future directions of synthetic ECMs for the study of durotaxis and the scaffold for tissue engineering.
Artificial Cells ; Cell Movement ; Chemistry ; Cicatrix ; Cues ; Embryonic Development ; Extracellular Matrix ; Female ; Hydrogel* ; Hydrogels* ; Morphogenesis ; Pregnancy ; Regeneration ; Tissue Engineering* ; Wounds and Injuries

Hemorrhage into the esophagus due to aortoesophageal communication is very rare but life-threatening with high morbidity and mortality. Because of this, most cases of aortoesophageal fistula are confirmed by autopsy. However, we report herein a case of a 62-year-old male with an aortoesophageal fistula who was successfully treated with endovascular stent-grafting. The patient had undergone esophageal stent insertion due to esophageal cancer and experienced hematemesis and hemodynamic shock due to an aortoesophageal fistula. Emergency endoscopy was unable to identify the source of the hemorrhage due to massive bleeding. Computed tomography of the chest revealed a focal pseudoaneurysm at the descending aorta and diffuse thinning of the esophageal wall, which were treated with endovascular stent-grafting. Although aortoesophageal fistulas are usually fatal, implantation of a covered stent into the esophagus may help prevent massive bleeding, providing valuable time to treat the patient.
Aneurysm, False ; Aorta, Thoracic ; Autopsy ; Blood Vessel Prosthesis* ; Emergencies ; Endoscopy ; Esophageal Neoplasms* ; Esophagus ; Fistula* ; Hematemesis ; Hemodynamics ; Hemorrhage ; Humans ; Male ; Middle Aged ; Mortality ; Shock ; Stents ; Thorax

This study examined the dosimetric influence of implanted gold markers in proton therapy and the effects of their positions in the spread-out Bragg peak (SOBP) proton beam. The implanted cylindrical gold markers were 3 mm long and 1.2 mm in diameter. The dosimetric influence of the gold markers was determined with markers at various locations in a proton-beam field. Spatial dose distributions were measured using a three-dimensional moving water phantom and a stereotactic diode detector with an effective diameter of 0.5 mm. Also, a film dosimetry was performed using Gafchromic External Beam Treatment (EBT) film. The GEANT4 simulation toolkit was used for Monte-Carlo simulations to confirm the measurements and to construct the dose-volume histogram with implanting markers. Motion data were obtained from the portal images of 10 patients to investigate the effect of organ motions on the dosimetric influence of markers in the presence of a rectal balloon. The underdosed volume due to a single gold marker, in which the dose was less than 95% of a prescribed amount, was 0.15 cc. The underdosed volume due to the presence of a gold marker is much smaller than the target volume. However, the underdosed volume is inside the gross tumor volume and is not smeared out due to translational prostate motions. The positions of gold markers and the conditions of the proton-beam field give different impacts on the dose distribution of a target with implanted gold markers, and should be considered in all clinical proton-based therapies.
Film Dosimetry ; Humans ; Prostate ; Prostatic Neoplasms ; Proton Therapy ; Protons ; Tumor Burden ; Water