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Background: Ankle valgus deformity secondary to proximal migration of the fibula following an Ilizarov tibial lengthening has not been discussed in detail in the literature. The purposes of this study were to determine the underlying mechanism of and to identify factors associated with proximal migration of the fibula that caused ankle valgus deformity after an Ilizarov tibial lengthening.Methods: We reviewed the outcome of seventy-four bilateral Ilizarov tibial lengthenings for short stature in thirty-seven patients. The mean age at the time of surgery was 21.7 years (range, thirteen to thirty-one years), and the mean duration of follow-up was forty-five months. Proximal migration of the fibula was assessed with changes in the malleolar tip distance. A valgus change of ≥ 5° in the tibiotalar angle was regarded as ankle valgus deformity following tibial lengthening.Results: The average length gain was 6.9 cm (range, 4.7 to 11.5 cm), and the average lengthening index was 1.5 mo/cm. Valgus deformity developed in six ankles (8%) and fibular nonunion developed in ten (14%). Proximal migration of the lateral malleolus of ≥ 5 mm was related to valgus talar tilting. Bifocal tibial lengthening, rapid distraction rate of the fibula (>1 mm per day), and development of a fibular nonunion were factors associated with proximal migration of the distal end of the fibula of ≥ 5 mm, which suggests that regenerated bone of poor quality in the distraction gap may cause proximal migration of the distal end of the fibula following tibial lengthening.Conclusions: Proximal migration of the distal end of the fibula following tibial lengthening may occur even with the use of an Ilizarov ring fixator. This migration seems to be caused by collapse of regenerated bone of poor quality or fibular nonunion. Proximal migration of ≥ 5 mm is associated with the risk of valgus talar tilting. Surgeons should consider earlier intervention with bone-grafting if there are conditions that compromise regenerated bone formation in the fibular distraction gap, such as can occur with extensive tibial lengthening by bifocal corticotomy. [ABSTRACT FROM AUTHOR]

In modern cloud environments, container orchestration tools are essential for effectively managing diverse workloads and services, and Kubernetes has become the de facto standard tool for automating the deployment, scaling, and operation of containerized applications. While Kubernetes plays an important role in optimizing and managing the deployment of diverse services and applications, its default scheduling approach, which is not optimized for all types of workloads, can often result in poor performance and wasted resources. This is particularly true in environments with complex interactions between services, such as microservice architectures. The traditional Kubernetes scheduler makes scheduling decisions based on CPU and memory usage, but the limitation of this arrangement is that it does not fully account for the performance and resource efficiency of the application. As a result, the communication latency between services increases, and the overall system performance suffers. Therefore, a more sophisticated and adaptive scheduling method is required. In this work, we propose an adaptive pod placement optimization technique using multi-tier inspection to address these issues. The proposed technique collects and analyzes multi-tier data to improve application performance and resource efficiency, which are overlooked by the default Kubernetes scheduler. It derives optimal placements based on the coupling and dependencies between pods, resulting in more efficient resource usage and better performance. To validate the performance of the proposed method, we configured a Kubernetes cluster in a virtualized environment and conducted experiments using a benchmark application with a microservice architecture. The experimental results show that the proposed method outperforms the existing Kubernetes scheduler, reducing the average response time by up to 11.5% and increasing the number of requests processed per second by up to 10.04%. This indicates that the proposed method minimizes the inter-pod communication delay and improves the system-wide resource utilization. This research aims to optimize application performance and increase resource efficiency in cloud-native environments, and the proposed technique can be applied to different cloud environments and workloads in the future to provide more generalized optimizations. This is expected to contribute to increasing the operational efficiency of cloud infrastructure and improving the quality of service.

Background: During the COVID-19 pandemic, in South Korea, several inpatient wards were converted to temporary negative pressure isolation (TNPI) wards by using portable high-efficiency particulate air filter units (PHUs). This study proposes improvements to the TNPI ward to prepare for airborne infections., Methods: Existing air-conditioning systems were investigated during the pandemic in 4 hospitals through a document review and field investigation with staff interviews. On-site experiments and measurements were conducted under vacant conditions. Differential pressure (∆P) between spaces was measured in all 4 hospitals, while tracer gas tests were carried out in 2 hospitals., Results: The investigation revealed that thermal discomfort caused the existing systems remaining perpetually active. Additionally, the noise generated by the PHU caused an unexpected shutdown of that equipment. Furthermore, the ∆P of over -2.5 Pa was measured as a result of the operating status of equipment. These situations can cause duct backflow and gas diffusion through unsealed diffusers. Moreover, low airtightness of existing facilities can affect indoor environment, pressure difference, and gas diffusion., Conclusions: When using existing facilities as TNPI wards, the airtightness and existing systems should be considered. We concluded that it is important to increase the airtightness and seal unused diffusers in order to prevent cross-infection by unpredictable airflow., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Recent evidence of gut microbiota dysbiosis in the context of psoriasis and the increased cooccurrence of inflammatory bowel disease and psoriasis suggest a close relationship between skin and gut immune responses. Using a mouse model of psoriasis induced by the Toll-like receptor (TLR) 7 ligand imiquimod, we found that psoriatic dermatitis was accompanied by inflammatory changes in the small intestine associated with eosinophil degranulation, which impaired intestinal barrier integrity. Inflammatory responses in the skin and small intestine were increased in mice prone to eosinophil degranulation. Caco-2 human intestinal epithelial cells were treated with media containing eosinophil granule proteins and exhibited signs of inflammation and damage. Imiquimod-induced skin and intestinal changes were attenuated in eosinophil-deficient mice, and this attenuation was counteracted by the transfer of eosinophils. Imiquimod levels and the distribution of eosinophils were positively correlated in the intestine. TLR7-deficient mice did not exhibit intestinal eosinophil degranulation but did exhibit attenuated inflammation in the skin and small intestine following imiquimod administration. These results suggest that TLR7-dependent bidirectional skin-to-gut communication occurs in psoriatic inflammation and that inflammatory changes in the intestine can accelerate psoriasis., (© 2024. The Author(s).)

The lateral cephalogram in orthodontics is a valuable screening tool on undetected obstructive sleep apnea (OSA), which can lead to consequences of severe systematic disease. We hypothesized that a deep learning-based classifier might be able to differentiate OSA as anatomical features in lateral cephalogram. Moreover, since the imaging devices used by each hospital could be different, there is a need to overcome modality difference of radiography. Therefore, we proposed a deep learning model with knowledge distillation to classify patients into OSA and non-OSA groups using the lateral cephalogram and to overcome modality differences simultaneously. Lateral cephalograms of 500 OSA patients and 498 non-OSA patients from two different devices were included. ResNet-50 and ResNet-50 with a feature-based knowledge distillation models were trained and their performances of classification were compared. Through the knowledge distillation, area under receiver operating characteristic curve analysis and gradient-weighted class activation mapping of knowledge distillation model exhibits high performance without being deceived by features caused by modality differences. By checking the probability values predicting OSA, an improvement in overcoming the modality differences was observed, which could be applied in the actual clinical situation., (© 2023. Springer Nature Limited.)

Background: There has been debate regarding whether patients with atopic dermatitis (AD) have an altered frequency of contact allergen sensitization. Increased exposure to topical medications and moisturizers as well as impaired skin barrier function increase the risk of contact sensitization, whereas the Th2-skewed inflammatory pathway of AD is associated with a reduced risk., Objective: This retrospective study was performed to determine the characteristics of contact sensitization in allergic contact dermatitis (ACD) patients with a current or past history of AD., Methods: A clinical record review was conducted for patients referred to Ewha Womans University Medical Center, for patch tests between March 2017 and March 2021. We compared the rates of contact sensitization between ACD patients with and without AD., Results: In total, 515 patch test results were reviewed and divided into the AD group (n=53) and non-AD group (n=462). The AD group showed decreased any-allergen positivity (1+, 2+, or 3+) (56.6%) compared to the non-AD group (72.9%) ( p =0.013). The positivity rate for budesonide was significantly higher in the AD group ( p =0.011), while the prevalence of a positive result for balsam of Peru was higher in the non-AD group ( p =0.036). Nickel sulfate, cobalt chloride, and potassium dichromate were the most common sensitized allergens in both groups., Conclusion: Our study shows a decreased prevalence of contact sensitization in AD patients compared to non-AD patients. Clinicians should be aware of the risk of corticosteroid allergies in ACD patients with history of AD., Competing Interests: The authors have nothing to disclose., (Copyright © The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)

Objectives: To evaluate the accuracy of fully automatic segmentation of pharyngeal volume of interests (VOIs) before and after orthognathic surgery in skeletal Class III patients using a convolutional neural network (CNN) model and to investigate the clinical applicability of artificial intelligence for quantitative evaluation of treatment changes in pharyngeal VOIs., Methods: 310 cone-beam computed tomography (CBCT) images were divided into a training set (n = 150), validation set (n = 40), and test set (n = 120). The test datasets comprised matched pairs of pre- and post-treatment images of 60 skeletal Class III patients (mean age 23.1 ± 5.0 years; ANB<-2⁰) who underwent bimaxillary orthognathic surgery with orthodontic treatment. A 3D U-Net CNNs model was applied for fully automatic segmentation and measurement of subregional pharyngeal volumes of pre-treatment (T0) and post-treatment (T1) scans. The model's accuracy was compared to semi-automatic segmentation outcomes by humans using the dice similarity coefficient (DSC) and volume similarity (VS). The correlation between surgical skeletal changes and model accuracy was obtained., Results: The proposed model achieved high performance of subregional pharyngeal segmentation on both T0 and T1 images, representing a significant T1-T0 difference of DSC only in the nasopharynx. Region-specific differences amongst pharyngeal VOIs, which were observed at T0, disappeared on the T1 images. The decreased DSC of nasopharyngeal segmentation after treatment was weakly correlated with the amount of maxillary advancement. There was no correlation between the mandibular setback amount and model accuracy., Conclusions: The proposed model offers fast and accurate subregional pharyngeal segmentation on both pre-treatment and post-treatment CBCT images in skeletal Class III patients., Clinical Significance: We elucidated the clinical applicability of the CNNs model to quantitatively evaluate subregional pharyngeal changes after surgical-orthodontic treatment, which offers a basis for developing a fully integrated multiclass CNNs model to predict pharyngeal responses after dentoskeletal treatments., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Acral melanoma (AM), a rare subtype of cutaneous melanoma, shows higher incidence in Asians, including Koreans, than in Caucasians. However, the genetic modification associated with AM in Koreans is not well known and has not been comprehensively investigated in terms of oncogenic signaling, and hallmarks of cancer. We performed whole-exome and RNA sequencing for Korean patients with AM and acquired the genetic alterations and gene expression profiles. KIT alterations (previously known to be recurrent alterations in AM) and CDK4/CCND1 copy number amplifications were identified in the patients. Genetic and transcriptomic alterations in patients with AM were functionally converge to the hallmarks of cancer and oncogenic pathways, including 'proliferative signal persistence', 'apoptotic resistance', and 'activation of invasion and metastasis', despite the heterogeneous somatic mutation profiles of Korean patients with AM. This study may provide a molecular understanding for therapeutic strategy for AM., Competing Interests: Declaration of competing interest KK is an employee of VUNO Inc., and all authors declare no potential conflicts., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Primary sclerosing cholangitis (PSC) is a rare autoimmune bile duct disease that is strongly associated with immune-mediated disorders. In this study, we implemented multitrait joint analyses to genome-wide association summary statistics of PSC and numerous clinical and epidemiological traits to estimate the genetic contribution of each trait and genetic correlations between traits and to identify new lead PSC risk-associated loci. We identified seven new loci that have not been previously reported and one new independent lead variant in the previously reported locus. Functional annotation and fine-mapping nominated several potential susceptibility genes such as MANBA and IRF5. Network-based in silico drug efficacy screening provided candidate agents for further study of pharmacological effect in PSC., (© 2023. The Author(s).)

Competing Interests: The authors have nothing to disclose.

Background: Data illustrating the impact of atopic dermatitis (AD) on lives of adults with AD in South Korea are limited., Objective: To assess the AD disease severity and its impact on quality of life (QoL) in patients with AD from South Korea., Methods: Patients with AD utilizing the specialist dermatology services of major hospitals in South Korea were assessed for disease severity using Eczema Area and Severity Index (EASI) score, for QoL using Dermatology Life Quality Index (DLQI) (for QoL), and for comorbidities and treatment experience via retrospective review of 12-month medical records. Clinical and sociodemographic characteristics were also measured., Results: Of the 1,163 patients, 695 (59.8%) were men (mean age [years]±standard deviation: 31.6±12.1). Overall, 52.9% (n=615) patients had moderate-to-severe disease (EASI>7). The QoL of 72.3% (n=840) patients was affected moderately-to-severely (DLQI score: 6~30). Systemic immunosuppressants were used ≥1 over past 12 months in 51.9% (n=603) patients, and the most commonly used were cyclosporines (45.7%, n=531) and systemic corticosteroids (40.5%, n=471). Approximately, 10.8% (n=126) patients consulted or received treatment for AD-related eye problem. Of these, 40% (n=50) patients reported poor, very poor, or completely blind status; approximately, 16.7% patients (n=192) reported having depression or anxiety; and 35.5% (n=410) reported suicidal ideation or suicidal attempt., Conclusion: A large proportion of patients had moderate-to-severe AD, a compromised QoL, and ocular or mental health comorbidities, indicating a high disease burden despite systemic treatment. These findings highlight the importance of a holistic approach for the evaluation and treatment of patients with AD., Competing Interests: Dr. TY Han was involved in honorarium from Sanofi-Genzyme. Dr. EH Choi was involved in Sanofi advisory board meeting and post marketing surveillance. Dr. HC Ko was involved in presentations and participation in advisory board for Sanofi. Dr. JY Roh was involved in advisory meeting and provision of study material, received clinical trial contract, expert consult fee, honorarium for lecture. Dr. S Lee is an employee of Sanofi. Rest of the authors have nothing to disclose., (Copyright © The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)

Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

Background: In psoriasis treatment, not all body regions improve simultaneously after clinical interventions., Objective: This study was aimed at evaluating clinical responses across body regions, which may differentially influence patient treatment plans., Methods: This prospective, observational, and multi-center study was conducted in Koreans who adhered to ustekinumab treatment based on criteria per local label and reimbursement guidelines. A total of 581 were included in this analysis., Results: The mean (±standard deviation) psoriasis area severity index (PASI) score at baseline, age, disease duration, and body surface area (%) were 18.9±9.69, 44.2±13.29 years, 11.3±9.65 years, and 27.8±17.83, respectively. Across the head and neck, upper extremities, trunk, and lower extremities, the correlation between the PASI sub-scores for the upper and lower extremities was the highest (r=0.680). The mean PASI sub-score for the lower extremities was the highest at baseline. PASI90 and PASI100 scores were the highest for the head and neck region, indicating the highest response rates, while those for the lower extremities were consistently low at all visits., Conclusion: We found differences in regional ustekinumab responses, with the lower extremities being the most difficult to treat. These findings should be considered in psoriasis treatment., Competing Interests: CONFLICTS OF INTEREST: Dr. Sang Wook Son has no conflict of interest to declare. Dae Young Yu, Youngdoe Kim, and Dr. YoungJa Lee are employees of Janssen Korea Ltd. Dr. Hyo Hyun Ahn performed phase II clinical trial sponsored by Regeneron, and phase III trial by Novartis, Pfizer, and Galderma. Dr. Yong Hyun Jang served as a speaker or consultant for AbbVie, Eli Lilly, GlaxoSmithKline, LEO Pharma, Janssen, Sanofi Genzyme, and Novartis also performed phase III clinical trials sponsored by Pfizer and Eli Lilly. Dr. Joo Young Roh served as a adviser or investigator for clinical trials for Novratis, Eli-Lilly, Janssen, Abbvie, BMS and Regeneron and Sanofi. Dr. Young Bok Lee served as a speaker for AbbVie, Janssen, Novartis and has engaged or been working as a principal investigator or sub-investigator in number of clinical trials sponsored by Janssen, Novartis, and Sanofi. Dr. Ji Yeoun Lee served as a speaker for Novartis. Dr. Myung Hwa Kim served as a speaker for Novartis and has engaged or been working as a principal investigator or sub-investigator in number of clinical trials sponsored by Eli-Lilly, Janssen, LEO Pharma, Novartis, Abbvie, and Sanofi. Dr. Gyeong-Hun Park and Dr. Hyun-Sun Yoon have no conflict of interest to declare. Dr. Sang Woong Youn served as a speaker for AbbVie, Eli Lilly, Janssen, and Novartis and also performed phase III clinical trials sponsored by AbbVie, BMS, Eli Lilly, Janssen, Novartis and UCB., (Copyright © The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)

Background: The phase 3 studies, VOYAGE 1 and 2, were conducted to assess guselkumab in the treatment of patients with moderate-to-severe psoriasis., Objectives: To investigate the efficacy and safety of guselkumab in Korean patients., Methods: The Korean sub-population of VOYAGE 1 and 2 study patients were included in this analysis. Efficacy and safety were evaluated through Weeks 24 and 28, respectively., Results: Of 126 randomized Korean patients, 30, 63, and 33 received placebo, guselkumab, and adalimumab, respectively. At Week 16, guselkumab was superior to placebo in achieving an Investigator's Global Assessment (IGA) score of 0 or 1 (cleared or minimal; 90.5 vs. 20.0%, p <.001) and a Psoriasis Area and Severity Index (PASI) 90 response (71.4 vs. 3.3%, p <.001). At week 24, a significantly higher proportion of guselkumab-treated patients achieved PASI 75 and IGA 0 (clear skin) responses compared to adalimumab-treated patients (PASI 75: 93.7 vs. 66.7%, p <.001; IGA 0: 52.4 vs. 21.2%, p =.004). Through Week 28, guselkumab and adalimumab showed comparable safety profiles., Conclusion: The efficacy and safety of guselkumab in Korean psoriasis patients through 28 weeks were consistent with findings for the overall VOYAGE 1 and 2 study population.

Background: One of coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused coronavirus disease 2019 (COVID-19) pandemic and threatened worldwide. However, therapy for COVID-19 has rarely been proven to possess specific efficacy. As the virus relies on host metabolism for its survival, several studies have reported metabolic intervention by SARS-CoV-2., Results: We investigated the coronavirus-metabolic hijacking using mouse hepatitis virus (MHV) as a surrogate for SARS-CoV-2. Based on the altered host metabolism by MHV infection, an increase of glycolysis with low mitochondrial metabolism, we tried to investigate possible therapeutic molecules which increase the TCA cycle. Endogenous metabolites and metabolic regulators were introduced to restrain viral replication by metabolic intervention. We observed that cells deprived of cellular energy nutrition with low glycolysis strongly suppress viral replication. Furthermore, viral replication was also significantly suppressed by electron transport chain inhibitors which exhaust cellular energy. Apart from glycolysis and ETC, pyruvate supplement suppressed viral replication by the TCA cycle induction. As the non-glucose metabolite, fatty acids supplement decreased viral replication via the TCA cycle. Additionally, as a highly possible therapeutic metabolite, nicotinamide riboside (NR) supplement, which activates the TCA cycle by supplying NAD+, substantially suppressed viral replication., Conclusions: This study suggests that metabolite-mediated TCA cycle activation suppresses replication of coronavirus and suggests that NR might play a role as a novel therapeutic metabolite for coronavirus., (© 2021. The Author(s).)

Background: In 2015, the Korean Atopic Dermatitis Association (KADA) working group published consensus guidelines for treating atopic dermatitis (AD)., Objective: We aimed to provide updated consensus recommendations for systemic treatment of AD in South Korea based on recent evidence and experience., Methods: We compiled a database of references from relevant systematic reviews and guidelines on the systemic management of AD. Evidence for each statement was graded and classified based on thestrength of the recommendation. Forty-two council members from the KADA participated in three rounds of voting to establish a consensus on expert recommendations., Results: We do not recommend long-term treatment with systemic steroids forpatients with moderate-to-severe AD due to the risk of adverse effects. We recommend treatment with cyclosporine or dupilumab and selective treatment with methotrexate or azathioprine for patients with moderate-to-severe AD. We suggest treatment with antihistamines as an option for alleviating clinical symptoms of AD. We recommend selective treatment with narrowband ultraviolet B for patients with chronic moderate-to-severe AD. We do not recommend treatment with oral antibiotics for patients with moderate-to-severe AD but who have no signs of infection. We did not reach a consensus on recommendations for treatment with allergen-specific immunotherapy, probiotics, evening primrose oil, orvitamin D for patients with moderate-to-severe AD. We also recommend educational interventions and counselling for patients with AD and caregivers to improve the treatment success rate., Conclusion: We look forward to implementing a new and updated consensus of systemic therapy in controlling patients with moderate-to-severe AD., Competing Interests: CONFLICTS OF INTEREST: Joo Young Roh is a clinical investigator for Novartis, Bristol-Myers Squibb, Sanofi-Aventis, AbbVie, Boehringer Ingelheim, and Regeneron., (Copyright © 2021 The Korean Dermatological Association and The Korean Society for Investigative Dermatology.)

Background: Cranial Electrotherapy Stimulation (CES) is a promising non-invasive brain stimulation technique with the potential to alleviate anxiety. We examined the effectiveness of home-based CES with novel, headphone-like, in-ear electrodes on anxiety-related symptoms and resting-state brain activity., Methods: This study spanned 3-weeks, with randomized, double blind, and active-controlled design. Nonclinical volunteers experiencing daily anxiety were randomly assigned to either the active or the sham groups. CES provides an alternating current (10 Hz frequency, 500 μA intensity), connected to smartphone recording treatment logs. Participants treated themselves with 20 trials of CES at home. We evaluated the effectiveness using State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), Wisconsin Card Sort Test (WCST), and resting-state electroencephalography (EEG)., Results: The active group showed a significant improvement in state-anxiety compared to sham, while there was a statistical trend in the WCST-Category Completed (p = .061) and no change in depression. In EEG analysis, the active group showed significantly increased relative power for theta in the left frontal region compared with the sham, and this significantly correlated with the changes in state-anxiety. The active group exhibited significantly increased high-beta source activity in cuneus and middle occipital gyrus after intervention compared with the baseline., Limitations: This study had a relatively short treatment period and small sample size., Conclusions: Our findings provide the first electrophysiological evidence for CES for novel in-ear electrodes to improve anxiety. The modulatory effects of CES on resting-state oscillations of EEG imply that CES could beneficially affect functional brain activity., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Psoriasis is a chronic inflammatory skin disease. Recently, lysophosphatidic acid (LPA)/LPAR5 signaling has been reported to be involved in both NLRP3 inflammasome activation in macrophages and keratinocyte activation to produce inflammatory cytokines, contributing to psoriasis pathogenesis. However, the effect and molecular mechanisms of LPA/LPAR signaling in keratinocyte proliferation in psoriasis remain unclear. In this study, we investigated the effects of LPAR1/3 inhibition on imiquimod (IMQ)-induced psoriasis-like mice. Treatment with the LPAR1/3 antagonist, ki16425, alleviated skin symptoms in IMQ-induced psoriasis-like mouse models and decreased keratinocyte proliferation in the lesion. It also decreased LPA-induced cell proliferation and cell cycle progression via increased cyclin A2, cyclin D1, cyclin-dependent kinase (CDK)2, and CDK4 expression and decreased p27 Kip1 expression in HaCaT cells. LPAR1 knockdown in HaCaT cells reduced LPA-induced proliferation, suppressed cyclin A2 and CDK2 expression, and restored p27 Kip1 expression. LPA increased Rho-associated protein kinase 2 (ROCK2) expression and PI3K/AKT activation; moreover, the pharmacological inhibition of ROCK2 and PI3K/AKT signaling suppressed LPA-induced cell cycle progression. In conclusion, we demonstrated that LPAR1/3 antagonist alleviates IMQ-induced psoriasis-like symptoms in mice, and in particular, LPAR1 signaling is involved in cell cycle progression via ROCK2/PI3K/AKT pathways in keratinocytes.

Background: Tissue resident memory T cells (TRMs) persist long-term in peripheral tissues without recirculation, triggering an immediate protective inflammatory state upon the re-recognition of the antigen. Despite evidence incriminating the dysregulation of TRMs in autoimmune diseases, few studies have examined their expression in cutaneous lupus erythematosus (CLE)., Objectives: We aimed to examine whether there are differences among TRM populations in CLE depending on different clinical conditions, such as the CLE subtype or association with systemic lupus erythematosus, and to determine the effect of type I interferon (IFN) on the development of TRMs in CLE., Methods: CLE disease activity was evaluated using the Cutaneous Lupus Erythematosus Disease Area and Severity Index. The expression of the TRM markers CD69 and CD103 in CLE lesions was evaluated by immunofluorescence. Flow cytometry was performed on peripheral blood mononuclear cells after IFNα treatment., Results: The number of TRMs expressing either CD69 or CD103 was significantly higher in CLE lesions than in control skin; however, it was not significantly different between discoid lupus erythematosus and subacute CLE, or dependent on the presence of concomitant systemic lupus. Lesional severity was not correlated with an increase in TRMs in CLE. IFNα treatment induced a conspicuous increase in CD69 expression in skin-homing T cells, more profoundly in CD4+ T cells than in CD8+ T cells., Conclusions: Skin TRMs, either CD69 or CD103-positive cells, showed increased levels in the lesional skin of CLE, and IFNα increased the expression of CD69 in T cells.

Background: Previous studies have reported numerous environmental factors for atopic dermatitis (AD), such as allergens and chemical stimulants. However, few studies have addressed the relationship between ambient air pollution and AD at a population level., Objective: To evaluate the effect of air pollutants on medical care visits for AD and to identify susceptible populations., Methods: In this time-series study conducted on 513,870 medical care visits for AD from 2012 to 2015 identified by reviewing national health insurance claim data in Incheon, Republic of Korea. Treating daily number of medical care visits for AD as a dependent variable, generalized additive models with Poisson distributions were constructed, which included air pollutant levels, ambient temperature, relative humidity, day of the week, national holiday, and season. Risks were expressed as relative risks (RR) with 95% confidence intervals (95% CIs) per interquartile range increase of each air pollutant., Results: Higher levels of particulate matter of diameter ≤10 μm (PM 10 ) (RR, 1.009; 95% CI, 1.007-1.012), ozone (1.028; 1.023-1.033), and sulfur dioxide (1.033; 1.030-1.037) were significantly associated with increased risk of medical care visits for AD on same days. In all age and sex groups, ozone was associated with a significantly higher risk of medical care visits, with the greatest risk among 13- to 18-year-old males (RR, 1.127; 95% CI, 1.095-1.159)., Conclusion: This study suggests relationships of ambient PM 10 , ozone, and sulfur dioxide levels with medical care visits for AD., (Copyright © 2020. Published by Elsevier Inc.)

Atopic dermatitis is a chronic skin inflammatory disease mediated by Th2-type immune responses. Although intestinal immune responses have been shown to play a critical role in the development or prevention of atopic dermatitis, the precise influence of intestinal immunity on atopic dermatitis is incompletely understood. We show here that orally tolerized mice are protected from experimental atopic dermatitis induced by sensitization and epicutaneous (EC) challenge to ovalbumin. Although the expression of Th2-type cytokines in the small intestine of orally tolerized and EC-challenged mice did not change significantly, these mice showed decreased inflammatory responses in the small intestine with restoration of microbial change elicited by the EC challenge. Interestingly, an increase in small intestinal eosinophils was observed with the EC challenge, which was also inhibited by oral tolerance. The role of small intestinal eosinophils and microbiota in the pathogenesis of experimental atopic dermatitis was further substantiated by decreased inflammatory mediators in the small intestine and attenuated Th2-type inflammation in the skin of eosinophil-deficient and microbiota-ablated mice with EC challenges. Based on these data, we propose that the bidirectional interaction between the skin and the intestine has a role in the pathogenesis of atopic dermatitis and that modulation of the intestinal microenvironments could be a therapeutic approach to atopic dermatitis.

Quite a few patients with chronic spontaneous urticaria (CSU) are refractory to H₁-antihistamines, even though the dose of H₁-antihistamines is increased up to 4-fold. CSU that is not controlled with H₁-antihistamines results in increased disease burden. Several immunomodulators have been used to manage these patients. The guidelines reported herein are connected to Part 1 of the KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children, and aimed to provide evidence-based recommendations for the management of H₁-antihistamine-refractory CSU. Part 2 focuses on the more commonly used additional treatment options for refractory CSU, including omalizumab, cyclosporine, leukotriene receptor antagonist, dapsone, methotrexate, and phototherapy. The evidence to support their efficacy, dosing, safety, and selection of these agents is systematically reviewed. To date, for patients with refractory CSU, the methodologically sound data to evaluate the use of omalizumab has been growing; however, the evidence of other immunomodulators and phototherapy is still insufficient. Therefore, an individualized stepwise approach with a goal of achieving complete symptom control and minimizing side effects can be recommended. Larger controlled studies are needed to elevate the level of evidence to select a rational therapeutic agent for patients with refractory CSU., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2020 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Aedes albopictus (Skuse, 1894) is a mosquito vector raising global health concerns owing to its transmission of dengue, Zika, and chikungunya viruses. This vector accounts for a large proportion of the Korean mosquito community; however, autochthonous clinical cases resulting from this species remain unreported in South Korea. This study aimed to examine the geographical genetic variations and sources of Ae. albopictus populations in South Korea exclusively on the basis of COI gene analysis from 292 samples collected from 37 localities in 2016-2018 and 290 reference sequences from GenBank. Thirty-eight haplotypes were identified among the 292 Ae. albopictus samples, with H1 (n = 190, 65.1%), H29 (n = 24, 8.22%), and H32 (n = 24, 8.22%) being the most common and widely distributed haplotypes in the mainland, southern coastal region, and Jeju Island, respectively. In general, high haplotype (≥0.5; 44.7%) and low nucleotide (≤0.00148 max.) diversity were observed in these populations. Based on eight regional groups, results of neutral tests and a mismatch analysis supported demographic expansions after bottlenecks. Furthermore, analysis of molecular variance, FST, and K2P distance showed that Gyeongsangnam-do, Jeju Island, and mainland groups were genetically differentiated. Haplotype network and phylogenetic analyses revealed that the sources of the main haplotypes are related to strains from other countries. The current findings need to be validated with additional sampling from heterogeneous habitats and different genetic markers. However, our results suggest that haplotype changes should be closely monitored for efficient vector surveillance and control., (© The Author(s) 2020. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2020 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease.)

The dissolution rate of a microneedle array patch (MAP) determines how long a MAP must remain attached to the skin (often called "wear time"). In this study, the dissolution rate of a MAP was increased, not by changing the drug formulation but by employing an infrared (IR) device that is widely used for hospital treatment and in-home therapy. A MAP with microneedles 480 μm in height was prepared using hyaluronic acid (HA). Changes in transepidermal water loss (TEWL), the surface temperature of the skin, and the dissolution rate of the MAP tips with IR irradiation were evaluated on human skin in vivo. Time for recovery from erythema that occurred after MAP attachment and IR irradiation was also evaluated. TEWL increased more than fourfold with IR irradiation. Water that evaporated as a result of IR irradiation was trapped in the skin layer by the patch, resulting in the increased dissolution rate of the MAP tips. After 10 min of IR irradiation, the height of the dissolving tips compared with their initial height increased from 41 to 56%, and the dissolved volume of the tips compared with their initial volume increased from 7 to 18%. During the 10 min of irradiation, the skin surface temperature rose from 32 to 40 °C. Erythema occurred in the early stage of treatment with IR irradiation and MAP attachment, but it abated within 2 h after removal of the MAP and cessation of IR irradiation. Through this study, it was possible to shorten the administration time of MAPs by using an IR device that could be easily accessed. This method can be applied to various types of MAPs in order to reduce the time that the MAPs must remain attached to the skin without changing the drug formulation. Graphical abstract The increase in dissolution rate of dissolving microneedle array patch (MAP) as a result of infrared radiation. a Water-soluble tips of MAP dissolved in water in skin without infrared irradiation. Dotted line indicates the initial dissolving microneedles. b Water in skin and subcutaneous layer evaporated actively with infrared irradiation and was stored under patch of MAP. Increased amount of water in skin induced faster dissolution of MAP tips.

Owing to global climate change, the global resurgence of vector-borne infectious diseases and their potential to inflict widespread casualties among human populations has emerged as a pivotal burden on public health systems. Tsutsugamushi disease (scrub typhus) in the Republic of Korea is steadily increasing and was designated as a legal communicable disease in 1994. The disease is a mite-borne acute febrile disease most commonly contracted from October to December. In this study, we tried to determine the prevalence of tsutsugamushi disease transmitted by chigger mites living on rodents and investigated their target vector diversity, abundance, and distribution to enable the mapping of hotspots for this disease in 2015. A total of 5 species belonging to 4 genera (109 mites): Leptotrombidium scutellare 60.6%, L. pallidum 28.4% Neotrombicula tamiyai 9.2%, Euschoengastia koreaensis/0.9%), and Neoschoengastia asakawa 0.9% were collected using chigger mite collecting traps mimicking human skin odor and sticky chigger traps from April to November 2015. Chigger mites causing tsutsugamushi disease in wild rodents were also collected in Hwaseong for the zoonotic surveillance of the vector. A total of 77 rodents belonging to 3 genera: Apodemus agrarius (93.5%), Crocidura lasiura (5.2%), and Micromys minutus (1.3%) were collected in April, October, and November 2015. The most common mite was L. pallidum (46.9%), followed by L. scutellare (18.6%), and L. orientale (18.0%). However, any of the chigger mite pools collected from rodent hosts was tested positive for Orientia tsutsugamushi, the pathogen of tsutsugamushi disease, in this survey.

Although lupus erythematosus is known to be more common among women of color, the study populations in previous reports were predominantly Caucasian and there is scarce information on Asian patients. Therefore, we performed a retrospective study using a nationwide population-based cohort in South Korea. The average annual incidence of cutaneous lupus was 4.36/100 000. Among 634 patients with cutaneous lupus, 20.8% had systemic disease: cutaneous lupus was diagnosed before systemic lupus in 4.26% and after systemic lupus in 8.52%. More female patients than male patients developed systemic lupus erythematosus. The average time to progression to systemic lupus was 1.53 ± 1.46 years., (© 2019 Japanese Dermatological Association.)

Japanese encephalitis virus (JEV) is a single stranded positive sense RNA virus of the genus Flavivirus that belongs to family Flaviviridae and emerged as one of the most pivotal form of viral encephalitis. The virus is transmitted to humans by mosquito vector and is an etiological agent of acute zoonotic infection. In this study, we investigated distribution and density over 3-year period in central regions of Korean peninsula. We selected two cities as mosquito-collecting locations and subdivided them into five collection sites; downtown Incheon Metropolitan City as a typical urban area, and the Hwaseong-si area as a rural area. A total of 35,445 female culicine mosquitoes were collected using black light traps or BG Sentinel™ traps from March to November 2016-2018. Aedes (Ae.) vexans nipponii was the most frequently collected specimens (48.91%), followed by Culex (Cx.) pipiens (32.05%), Ochlerotatus (Och.) dorsalis (13.58%), Och. koreicus (1.68%), and Cx. tritaeniorhynchus (1.49%). In the urban area, Cx. pipiens was the predominant species (92.21%) and the other species accounted for <5% of the total mosquitoes collected. However, in the rural area, Ae. vexans nipponii had the highest population (61.90%), followed by Och. dorsalis (17.10%), Cx. tritaeniorhynchus (1.84%) and Och, koreicus (1.78%). Culicine mosquitoes were identified at the species level, placed in pools of up to 30 mosquitoes each, and screened for flavivirus RNA using the SYBR Green-based RT-PCR. Three of the assayed 1092 pools were positive for Chaoyang virus from Ae. vexans nipponii and Japanese encephalitis virus from Cx. pipiens. The maximum likelihood estimations (the estimated number of virus-positive mosquitoes/1000 mosquitoes) for Ae. vexans nipponii positive for Chaoyang virus and Cx. pipiens for Japanese encephalitis virus were 3.095 and 0.20, respectively. The results of our study demonstrate that although mosquito-borne diseases were not detected in the potential vectors, enhanced monitoring and long-term surveillance of these vector viruses are of great public health importance., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interests., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background/aim: To evaluate whether topical use of a film-forming silicone gel (StrataXRT®) could reduce radiation dermatitis compared to a moisturizing cream (X-derm®) in patients receiving whole breast radiotherapy., Patients and Methods: A total of 56 patients with breast cancer were randomized to use StrataXRT or X-derm. The severity of radiation dermatitis was graded using physiological skin parameters, clinician-assessed visual rating scales and patient-reported symptoms. Changes in these parameters from baseline to 4 weeks post-radiotherapy were evaluated every two weeks., Results: Two-way repeated-measures ANOVA revealed different patterns of changes in the erythema index (F=3.609, p=0.008) and melanin index (F=3.475, p=0.015). The post hoc analysis demonstrated a significantly lower erythema index and melanin index in the patients allocated to the StrataXRT group., Conclusion: The use of StrataXRT can reduce radiation dermatitis with respect to objectively measured physiological skin parameters. The results of the present study will support the feasibility of conducting a larger randomized controlled trial., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The seasonal abundance of hard ticks that transmit severe fever with thrombocytopenia syndrome virus was monitored with a collection trap method every April to November during 2015-2018 and with a flagging method every July and August during 2015-2018 in Ganghwa-do (island) of Incheon Metropolitan City, Republic of Korea. This monitoring was performed in a copse, a short grass field, coniferous forest and broad-leaved forest. A total of 17,457 ticks (8,277 larvae, 4,137 nymphs, 3,389 females, and 1,654 males) of the ixodid ticks comprising 3 species (Haemaphysalis longicornis, H. flava, and Ixodes nipponensis) were collected with collection traps. Of the identified ticks, H. longicornis was the most frequently collected ticks (except larval ticks) (94.26%, 8,653/9,180 ticks (nymphs and adults)), followed by H. flava (5.71%, 524/9,180) and Ix. nipponensis (less than 0.04%, 3/9,180). The ticks collected with collecting traps were pooled and assayed for the presence of SFTS virus with negative results. In addition, for monitoring the prevalence of hard ticks, a total of 7,461 ticks (5,529 larvae, 1,272 nymphs, 469 females, and 191 males) of the ixodid ticks comprising 3 species (H. longicornis, H. flava, and Ix. nipponensis) were collected with flagging method. H. longicornis was the highest collected ticks (except larval ticks) (99.53%, 1,908/1,917 ticks (nymphs and adults)), followed by H. flava (1.15%, 22/1,917).

Objectives: Chigger mites are vectors for scrub typhus. This study evaluated the annual fluctuations in chigger mite populations and Orientia tsutsugamushi infections in South Korea., Methods: During 2006 and 2007, chigger mites were collected monthly from wild rodents in 4 scrub typhus endemic regions of South Korea. The chigger mites were classified based on morphological characteristics, and analyzed using nested PCR for the detection of Orientia tsutsugamushi ., Results: During the surveillance period, the overall trapping rate for wild rodents was 10.8%. In total, 17,457 chigger mites (representing 5 genera and 15 species) were collected, and the average chigger index (representing the number of chigger mites per rodent), was 31.7. The monthly chigger index was consistently high (> 30) in Spring (March to April) and Autumn (October to November). The mite species included Leptotrombidium pallidum (43.5%), L. orientale (18.9%), L. scutellare (18.1%), L. palpale (10.6%), and L. zetum (3.6%). L. scutellare and L. palpale populations, were relatively higher in Autumn. Monthly O. tsutsugamushi infection rates in wild rodents (average: 4.8%) and chigger mites (average: 0.7%) peaked in Spring and Autumn., Conclusion: The findings demonstrated a bimodal pattern of the incidence of O. tsutsugamushi infections. Higher infection rates were observed in both wild rodents and chigger mites, in Spring and Autumn. However, this did not reflect the unimodal incidence of scrub typhus in Autumn. Further studies are needed to identify factors, such as human behavior and harvesting in Autumn that may explain this discordance., Competing Interests: Conflicts of Interest The authors have no conflicts of interest to declare., (Copyright ©2019, Korea Centers for Disease Control and Prevention.)

The seasonal abundance of Haemaphysalis longicornis Neumann and H. flava Neumann (Acari: Ixodidae) was monitored from 2015 through 2017 in Gyeonggi-do, South Korea. The hard ticks were surveyed monthly using CO2 bait traps from April to November and flagging from July to September in a coniferous forest, a deciduous forest, shrubs, and a grassland vegetation types. Haemaphysalis longicornis and H. flava were most abundant in the grassland and shrubs, which yielded over 50% of the total number of ticks in all 3 yr. Furthermore, H. longicornis comprised up to 90% of the ticks collected. Generally, peaks of nymph, adult, and larva numbers were observed from April to June, from June to July, and from August to September, respectively. Half of the ticks were pooled and tested for the presence of the SFTS virus with negative results., (© The Author(s) 2019. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Exposure to certain chemicals such as disinfectants through inhalation is suspected to be involved in the development of pulmonary fibrosis, a lung disease in which lung tissue becomes damaged and scarred. Pulmonary fibrosis is known to be regulated by transforming growth factor β (TGF-β) and peroxisome proliferator-activated receptor gamma (PPARγ). Here, we developed an adverse outcome pathway (AOP) to better define the linkage of PPARγ antagonism to the adverse outcome of pulmonary fibrosis. We then conducted a systematic analysis to identify potential chemicals involved in this AOP, using the ToxCast database and deep learning artificial neural network models. We identified chemicals bearing a potential inhalation hazard and exposure hazards from the database that could be related to this AOP. For chemicals that were not present in the ToxCast database, multilayer perceptron models were developed based on the ToxCast assays related to the AOP. The reactivity of ToxCast untested chemicals was then predicted using these deep learning models. Both approaches identified a set of chemicals that could be used to validate the AOP. This study suggests that chemicals categorized using an existing database such as ToxCast can be used to validate an AOP and that deep learning approaches can be used to characterize a range of potential active chemicals for an AOP of interest.

The clinical characteristics of cutaneous lupus erythematosus (CLE) are well delineated in adults, but pediatric data, particularly in Asian populations, are limited. Therefore, we evaluated the characteristics of pediatric cases by retrospectively reviewing the medical records of children with CLE during a 15-year period in a tertiary care dermatology clinic in South Korea. The study included 21 children (8 males and 13 females), 4 of whom had neonatal lupus erythematosus (NLE). Among 17 patients with CLE, discoid lupus erythematosus (DLE) was most common (47.1%), followed by acute CLE (ACLE, 35.3%). All ACLE cases had systemic lupus erythematosus (SLE). Female predominance was conspicuous in ACLE/SLE (6/11 females versus 0/6 males), as was older age, whereas DLE and NLE showed near-equal sex distributions. The median age at the diagnosis of CLE was significantly higher in females than in males (15 years versus 4.5 years, p  = 0.02). All patients with ACLE/SLE simultaneously showed skin and systemic symptoms from onset. The kidney was the most commonly involved organ. This study revealed unique characteristics of pediatric CLE, further warranting a comprehensive review among various ethnicities to understand the wide spectrum of CLE in the pediatric population.

Blunt airway trauma is rare but life threatening. Injuries to other vital organs accompany this type of injury in most cases; therefore, conservative treatment may be considered first. In cases of delayed fibrotic airway stenosis after conservative treatment, surgical treatment or bronchoscopic intervention are therapeutic options. We herein report a case of delayed airway stenosis after a blunt traumatic airway injury that was successfully managed by silicone stenting.

Eosinophils are proinflammatory granulocytes that are involved in the pathogenesis of various inflammatory reactions. However, their roles in psoriasis remain largely unknown. In this study, by examining the inflammatory features of the eosinophilic cell line EoL-1 and an imiquimod-induced murine model of psoriasis, we show that eosinophils provide inflammatory signals that accelerate the pathogenesis of psoriasis. EoL-1 cells constitutively expressed TLR7, which mediates acute and rapidly developing psoriatic inflammation. The activation of TLR7 on EoL-1 cells using R837 resulted in the secretion of inflammatory mediators that support the migration, activation, and survival of neutrophils. The underlying pathologic role of eosinophils in psoriatic inflammation was further substantiated by markedly decreased psoriasiform inflammation in imiquimod-treated ΔdblGATA mice, which have a systemic eosinophil deficiency. While imiquimod-treated wild-type mice showed a significant increase in the eosinophils in their skin, neutrophils remarkably outnumbered the eosinophils in the skin, lymph nodes, and spleen in wild-type mice after imiquimod application. In addition, lesional skin samples from psoriasis patients also showed up-regulated eosinophil cytotoxic granules, accompanied by marked neutrophil infiltration. Based on these collective data, we propose that eosinophils accelerate psoriatic inflammation by supporting inflammatory microenvironments to favor the activation and infiltration of neutrophils., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Cholesterol clefts have rarely been described in cutaneous tumors other than lipid-rich tumors. However, they seem to be a relatively common phenomenon in basal cell carcinoma (BCC). This study was undertaken to determine the frequency of cholesterol cleft deposition in BCCs, and to identify associated histopathologic and clinical features. Twenty-eight of 249 BCC cases reviewed showed features of cholesterol cleft. Mean disease duration in those with cholesterol cleft was significantly longer than in those without cholesterol cleft (5.58 vs. 3.29 years, respectively; P = 0.013). Sex and age distributions, and average tumor longest diameter (11.6 vs. 9.41 mm) were no different for those with or without cholesterol clefts. The most common anatomical location was the nose in both those with and without cholesterol clefts. BCCs without cholesterol clefts more frequently involved the periauricular and perioral areas, and areas other than the head and neck, such as the trunk and lower extremities (P = 0.087). Histopathologic features of necrosis (26/28, 92.86%), keratinization (19/28, 67.86%), and pigment deposition (18/28, 64.29%) were found to be associated with cholesterol clefts. Cholesterol clefts were intratumorally located in 27/28 cases (96.43%), and stromally located in 2 cases (7.14%); intravascularly located cholesterol clefts were observed in no case. In conclusion, this study shows that cholesterol clefts are relatively common in BCC, and suggests that cholesterol crystal deposition could be associated with longer disease duration and microtrauma.

Accumulating data have indicated a fundamental role of eosinophils in regulating adipose tissue homeostasis. Here, we performed whole-genome RNA sequencing of the small intestinal tract, which suggested the presence of impaired lipid metabolism in eosinophil-deficient ΔdblGATA mice. ΔdblGATA mice fed a high-fat diet (HFD) showed reduced body fat mass, impaired enlargement of adipocytes, decreased expression of adipogenic genes, and developed glucose intolerance. HFD induced accumulation of eosinophils in the perigonadal white adipose tissue. Concordantly, adipocyte-differentiated 3T3-L1 cells promoted the migration of eosinophils through the expression of CCL11 (eotaxin-1) and likely promoted their survival through the expression of interleukin (IL)-3, IL-5, and granulocyte-macrophage colony-stimulating factor. HFD-fed ΔdblGATA mice showed increased infiltration of macrophages, CD4 + T-cells, and B-cells, increased expression of interferon-γ, and decreased expression of IL-4 and IL-13 in white adipose tissue. Interferon-γ treatment significantly decreased lipid deposition in adipocyte-differentiated 3T3-L1 cells, while IL-4 treatment promoted lipid accumulation. Notably, HFD-fed ΔdblGATA mice showed increased lipid storage in the liver as compared with wild-type mice. We propose that obesity promotes the infiltration of eosinophils into adipose tissue that subsequently contribute to the metabolic homeostasis by promoting adipocyte maturation.

Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

As part of a study to explore the long-term effects of the Hebei Spirit oil spill accident, transgenerational toxicity and associated epigenetic changes were investigated in the nematode Caenorhabditis elegans. Under experimental conditions, worms were exposed to Iranian heavy crude oil (IHC) under three different scenarios: partial early-life exposure (PE), partial late-life exposure (PL), and whole-life exposure (WE). Growth, reproduction, and histone methylation were monitored in the exposed parental worms (P0) and in three consecutive unexposed offspring generations (F 1-3 ). Reproductive potential in the exposed P0 generation in the WE treatment group was reduced; additionally, it was inhibited in the unexposed offspring generations of the P0 worms. This suggests that there was transgenerational inheritance of defective reproduction. Comparison of developmental periods of exposure showed that IHC-treated worms in the PL group had a greater reduction in reproductive capacity than those in the PE group. Decreased methylation of histone H3 (H3K9) was found in the IHC-exposed parental generation. A heritable reduction in reproductive capacity occurred in wildtype N2 but was not found in a H3K9 histone methyltransferase (HMT) mutant, met-2(n4256), suggesting a potential role for HMT in transgenerational toxicity. Our results suggest that the reproductive toxicity after IHC exposure could be heritable and that histone methylation is associated with the transmission of the inherited phenotype., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Topical tacrolimus is an effective anti-inflammatory therapy for acute and chronic states of atopic dermatitis (AD) in both adults and children. Topical tacrolimus has particular use at sensitive areas such as the face, anogenitals, and skin folds of neck and extremities. However, many AD patients also experience aggravated symptoms on trunk., Objective: The aim of this study was to investigate the efficacy and safety of topical tacrolimus for AD patients with truncal lesions., Methods: AD patients with truncal lesions who were aged ≥2 years were recruited from 20 centres in Korea. They received treatment with topical tacrolimus ointment twice daily during 4 weeks. The primary end point was change of the local eczema area and severity index (EASI) of the trunk from baseline to day 28. The secondary end points were changes in the patient global assessment (PGA) score and itch visual analogue scale (VAS) score of the trunk between baseline and day 28., Results: Two hundred and ninety-one patients were recruited, and 176 patients completed the full 4-week treatment course. By the end of the treatment, the mean local EASI of the trunk (2.2±4.71) was significantly decreased from that at baseline (4.71±4.03, p <0.001). PGA (1.71±1.15) and itch VAS score of the trunk (2.61±2.19) on day 28 were also profoundly decreased compared with the baseline (2.96±1.07 and 5.15±2.47, respectively). No serious adverse events were observed during the study period., Conclusion: Topical tacrolimus is an effective and safe therapy for truncal lesions in AD patients., Competing Interests: CONFLICTS OF INTEREST: The authors have nothing to disclose.

Defective gut immune reactions have been implicated in the development of atopic dermatitis (AD), whereas oral tolerance (OT), that is, the immune unresponsiveness induced by oral antigen administration, protects mice against AD. To investigate this protective role of OT, the transcriptomic profiles of skin were obtained by RNA sequencing from mice that were epicutaneously sensitized, orally tolerized prior to epicutaneous sensitization, or neither (control). Oral tolerance inhibited the upregulation of keratin- and allergic inflammation-associated genes that occurred in the epicutaneously sensitized group. Compared to the controls, mice that were orally tolerized and epicutaneously sensitized showed an upregulation of genes that regulate inflammation or keratinocyte differentiation. Knocking down two of those genes, SCGB1A1 and TSC22D3, upregulated Th2 inflammatory mediators and downregulated a cornified cell envelope-related gene. Based on our findings, OT may protect skin against allergic inflammation by promoting the expression of genes that regulate Th2 inflammatory responses and skin barrier function., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Oxidative stress was evaluated for anthracene (Ant) and alkyl-Ants (9-methylanthracene [9-MA] and 9,10-dimethylanthracene [9,10-DMA]) in Caenorhabditis elegans to compare changes in toxicity due to the degree of alkylation. Worms were exposed at 1) the same external exposure concentration and 2) the maximum water-soluble concentration. Formation of reactive oxygen species, superoxide dismutase activity, total glutathione concentration, and lipid peroxidation were determined under constant exposure conditions using passive dosing. The expression of oxidative stress-related genes ( daf-2, sir-2.1, daf-16, sod-1, sod-2, sod-3 and cytochrome 35A/C family genes) was also investigated to identify and compare changes in the genetic responses of C. elegans exposed to Ant and alkyl-Ant. At the same external concentration, 9,10-DMA induced the greatest oxidative stress, as evidenced by all indicators, except for lipid peroxidation, followed by 9-MA and Ant. Interestingly, 9,10-DMA led to greater oxidative stress than 9-MA and Ant when worms were exposed to the maximum water-soluble concentration, although the maximum water-soluble concentration of 9,10-DMA is the lowest. Increased oxidative stress by alkyl-Ants would be attributed to higher lipid-water partition coefficient and the π electron density in aromatic rings by alkyl substitution, although this supposition requires further confirmation.

Although atopic dermatitis (AD) is characterized by cytokine production predominantly mediated by T helper (Th) 2 cells, AD pathogenesis also involves innate immune and Th1 cells. To optimize the cytokine milieu required for accurate reproduction of AD-related gene expression profile in vitro , we evaluated the expression pattern of CCL22 , CCL17 , IL5 , IL13 , IL33 , IL25 , TSLP , FLG , and LOR in human lesional AD skin and cytokine-stimulated HaCaT cells. An increase in Th2 mediators ( IL5 , IL13 , CCL22 , CCL17, IL25 , IL33 , and TSLP ) and a decrease in genes related to cornified cell envelope (filaggrin and loricrin) were observed in human AD lesions. Innate (tumor necrosis factor-α) and/or Th1/Th2 adaptive cytokines (interferon-γ/IL-4) were required for inducing these inflammatory changes in HaCaT cells, implying that a complex network of innate, Th1, and Th2 cytokines drives AD-like changes. Therefore, stimulation with various combinations of cytokines, beyond Th2 polarization, is necessary when HaCaT cell line is used to study genetic changes implicated in AD pathogenesis., Competing Interests: Conflict of Interest: The authors have no conflict of interest to declare.