Immunohistochemical Profiling Reveals Distinct Inflammatory Landscape in Rosacea Subtypes / 대한피부과학회지

Background@#The immunological and histopathological understanding of rosacea subtypes remain unclear. This study aimed to characterize erythematotelangiectatic rosacea (ETR), papulopustular rosacea (PPR), and granulomatous rosacea (GR) immunologically through facial punch biopsy samples. @*Objective@#Our goal was to investigate the immunohistochemical profile of rosacea subtypes, providing insights into pathogenesis for targeted therapies. @*Methods@#Biopsy samples from 52 rosacea patients and 25 controls were stained for antibodies retrospectively. Statistical analyses identified expression differences. @*Results@#In the rosacea group (average age, 55.0; male-to-female ratio, 1:2.1), Langerhans cell count, p53, and vitamin D receptor expression showed no differences from controls or among subtypes. Claudin-1 and occludin expression decreased in rosacea compared to controls, with no variance among subtypes. Demodex mites were present in 40.4% of rosacea cases vs. 8.0% in controls (p=0.003), more frequently in PPR than GR, and absent in ETR. Neutrophil elastase expression mirrored the Demodex pattern. The CD4/CD8 ratio averaged 2.15 in rosacea without differences among subtypes. CD20 and CD68 expression increased in rosacea, escalating in the order of ETR, PPR, and GR, mirroring matrix metalloproteinase-2 (MMP-2). ETR exhibited insignificant CD20 and MMP-2 expression. @*Conclusion@#Our findings validate a CD4＋ T cell-driven response across all rosacea subtypes. Increased neutrophils, B cells, and macrophages, likely influenced by Demodex, were observed in PPR and GR. Demodex mites may recruit additional B cells and macrophages, potentially linked to MMP-2 expression. This comprehensive characterization offers additional insights into the immunopathogenesis of rosacea, paving the way for targeted interventions.

Investigating the Diagnostic Utility of Potassium Hydroxide (KOH) Smear Test and the Influence of Clinical and Practical Factors in Onychomycosis / 대한피부과학회지

Background@#Onychomycosis, a common fungal nail infection, particularly affects the elderly. The diagnostic accuracy of a potassium hydroxide (KOH) smear, a primary diagnostic method, can vary based on the examiner’s proficiency. @*Objective@#To evaluate the diagnostic utility of KOH smears in a real-world setting and the influence of clinical and practical factors on onychomycosis. @*Methods@#This study included 381 patients who underwent KOH smear and histopathological staining for nail diseases at Seoul National University Hospital between March 2020 and February 2023. The study evaluated the diagnostic utility of the KOH smear, including its sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic odds ratio. We investigated the influence of factors such as training duration of examiners, prior history of antifungal treatment, and lesion location on diagnostic utility. @*Results@#Of the 381 patients, 139 were male (36.5%) and 242 were female (63.5%). Onychomycosis was the most common diagnosis (59.3%), with 34.1% of patients reporting prior antifungal therapy within the past 6 months. The sensitivity of the monthly KOH smear varied from 16.7% to 70.0% with an annual sensitivity of 48.1%. The specificity ranged from 83.3% to 100.0%, with an annual specificity of 90.3%. While prior antifungal therapy decreased the sensitivity and specificity, no statistical significance was observed. Examiner's experience, measured by training duration, was not associated with sensitivity or specificity. Among patients with a history of antifungal treatment, an increasing number of KOH smear tests showed reduced sensitivity. @*Conclusion@#Variations in the diagnostic utility of the KOH smear test, influenced by various factors, highlight the necessity for cautious interpretation in clinical settings.

T Cell Microvilli: Finger-Shaped External Structures Linked to the Fate of T Cells

Microvilli are outer membrane organelles that contain cross-linked filamentous actin.Unlike well-characterized epithelial microvilli, T-cell microvilli are dynamic similar to those of filopodia, which grow and shrink intermittently via the alternate actin-assembly and -disassembly. T-cell microvilli are specialized for sensing Ags on the surface of Ag-presenting cells (APCs). Thus, these finger-shaped microprotrusions contain many signaling-related proteins and can serve as a signaling platforms that induce intracellular signals. However, they are not limited to sensing external information but can provide sites for parts of the cell-body to tear away from the cell. Cells are known to produce many types of extracellular vesicles (EVs), such as exosomes, microvesicles, and membrane particles. T cells also produce EVs, but little is known about under what conditions T cells generate EVs and which types of EVs are released. We discovered that T cells produce few exosomes but release large amounsts of microvilli-derived particles during physical interaction with APCs. Although much is unanswered as to why T cells use the same organelles to sense Ags or to produce EVs, these events can significantly affect T cell fate, including clonal expansion and death. Since TCRs are localized at microvilli tips, this membrane event also raises a new question regarding long-standing paradigm in T cell biology; i.e., surface TCR downmodulation following T cell activation. Since T-cell microvilli particles carry T-cell message to their cognate partner, these particles are termed T-cell immunological synaptosomes (TISs). We discuss the potential physiological role of TISs and their application to immunotherapies.

Increase in Potential Low-value Magnetic Resonance Imaging Utilization Due to Out-of-pocket Payment Reduction Across Income Groups in Korea: An Experimental Vignette Study / 예방의학회지

Objectives@#This study examined the effect of out-of-pocket (OOP) payment reduction on the potential utilization of low-value magnetic resonance imaging (MRI) across income groups. @*Methods@#We conducted an experimental vignette survey using a proportional quota-based sample of individuals in Korea (n=1229). In two hypothetical vignettes, participants were asked whether they would be willing to use MRI if they had uncomplicated headache and non-specific low back pain, each before and after OOP payment reduction. To account for the possible role of physician inducement, half of the participants were initially presented with vignettes that included a physician recommendation for low-value care. The predicted probability, slope index of inequality (SII), and relative index of inequality (RII) were calculated using logistic regression. @*Results@#Before OOP payment reduction, the lowest income quintile was least likely to use low-value MRI regardless of physician inducement (36.7-49.6% for low back pain; 30.5-39.3% for headache). After OOP payment reduction, almost all individuals in each income quintile were willing to use low-value MRI (89.8-98.0% for low back pain; 78.1-90.3% for headache). Absolute and relative inequalities concerning potential low-value MRI utilization decreased after OOP payments were reduced, even without physician inducement (SII: from 8.15 to 5.37%, RII: from 1.20 to 1.06 for low back pain; SII: from 6.99 to 0.83%, RII: from 1.20 to 1.01 for headache). @*Conclusions@#OOP payment reduction for MRI has the potential to increase low-value care utilization among all income groups while decreasing inequality in low-value care utilization.

Analysis of the Conjunctival Microbiome in Patients with Atopic Keratoconjunctivitis and Healthy Individuals

Background@#Atopic dermatitis (AD) has been clarified that imbalance of bacterial and fungal communities in the skin and gut play key roles in immunologic dysfunction. Atopic keratoconjunctivitis (AKC), one of severe ophthalmic manifestation of AD, could be related with dysbiosis as same as AD. @*Objective@#In this case-control study, the roles of conjunctival microbial communities in AKC were evaluated by a comparative analysis with healthy controls (HCs). @*Methods@#16S rRNA sequencing was used to construct libraries of compositional information for a total of 30 volunteers including 20 patients with AKC and 10 HCs. @*Results@#In the results, variation in the conjunctival taxonomic composition was higher in patients with AKC than in the HC group. In an analysis of relative abundance at the genus level, some taxa significantly differed between groups, including Ralstonia, Staphylococcus, Pseudomonas, Proteus, Haemophilus, and Bifidobacterium(p＜0.05). Beta diversity was significantly higher in patients with AKC than in HCs (PERMANOVA, p=0.004). @*Conclusion@#The results indicated that the diversity and composition of the microbiome differs between patients with AKC and HCs.

Public Preferences for Allocation Principles for Scarce Medical Resources in the COVID-19 Pandemic in Korea: Comparisons With Ethicists’ Recommendations / 예방의학회지

Objectives@#The purpose of this study was to investigate public preferences regarding allocation principles for scarce medical resources in the coronavirus disease 2019 (COVID-19) pandemic, particularly in comparison with the recommendations of ethicists. @*Methods@#An online survey was conducted with a nationally representative sample of 1509 adults residing in Korea, from November 2 to 5, 2020. The degree of agreement with resource allocation principles in the context of the medical resource constraints precipitated by the COVID-19 pandemic was examined. The results were then compared with ethicists’ recommendations. We also examined whether the perceived severity of COVID-19 explained differences in individual preferences, and by doing so, whether perceived severity helps explain discrepancies between public preferences and ethicists’ recommendations. @*Results@#Overall, the public of Korea agreed strongly with the principles of “save the most lives,” “Koreans first,” and “sickest first,” but less with “random selection,” in contrast to the recommendations of ethicists. “Save the most lives” was given the highest priority by both the public and ethicists. Higher perceived severity of the pandemic was associated with a greater likelihood of agreeing with allocation principles based on utilitarianism, as well as those promoting and rewarding social usefulness, in line with the opinions of expert ethicists. @*Conclusions@#The general public of Korea preferred rationing scarce medical resources in the COVID-19 pandemic predominantly based on utilitarianism, identity and prioritarianism, rather than egalitarianism. Further research is needed to explore the reasons for discrepancies between public preferences and ethicists’ recommendations.

Hepatitis B virus X Protein Promotes Liver Cancer Progression through Autophagy Induction in Response to TLR4 Stimulation

Hepatitis B virus X (HBx) protein has been reported as a key protein regulating the pathogenesis of HBV-induced hepatocellular carcinoma (HCC). Recent evidence has shown that HBx is implicated in the activation of autophagy in hepatic cells. Nevertheless, the precise molecular and cellular mechanism by which HBx induces autophagy is still controversial.Herein, we investigated the molecular and cellular mechanism by which HBx is involved in the TRAF6-BECN1-Bcl-2 signaling for the regulation of autophagy in response to TLR4 stimulation, therefore influencing the HCC progression. HBx interacts with BECN1 (Beclin 1) and inhibits the association of the BECN1-Bcl-2 complex, which is known to prevent the assembly of the pre-autophagosomal structure. Furthermore, HBx enhances the interaction between VPS34 and TRAF6-BECN1 complex, increases the ubiquitination of BECN1, and subsequently enhances autophagy induction in response to LPS stimulation. To verify the functional role of HBx in liver cancer progression, we utilized different HCC cell lines, HepG2, SK-Hep-1, and SNU-761. HBx-expressing HepG2 cells exhibited enhanced cell migration, invasion, and cell mobility in response to LPS stimulation compared to those of control HepG2 cells. These results were consistently observed in HBx-expressed SK-Hep-1 and HBx-expressed SNU-761 cells. Taken together, our findings suggest that HBx positively regulates the induction of autophagy through the inhibition of the BECN1-Bcl-2 complex and enhancement of the TRAF6-BECN1-VPS34 complex, leading to enhance liver cancer migration and invasion.

Clinical Differences of Androgenetic Alopecia between Adolescents and Adults / 대한피부과학회지

Background@#Androgenetic alopecia (AGA) is characterized by terminal hair miniaturization, which progressively decreases hair density and thickness. Genetic predisposition and the role of androgen in AGA have been widely accepted; however, its definite mechanism has not been clarified. AGA may also occur in adolescents, although its clinical characteristics including the disease prevalence have not yet been fully established. @*Objective@#To analyze the clinical differences of AGA between adolescents and adults. @*Methods@#Six-hundred fourteen patients with AGA were recruited and information about age, sex, and family history, comorbidities were collected. @*Results@#A total of 74.5% of adolescents and 66.4% of adults had family history of AGA, with “paternal only” as the most common pattern. A total of 27.3% of adolescents and 44.5% of adults had comorbidities, with seborrheic dermatitis being the most common. Other common comorbidities were acne, folliculitis, and atopic dermatitis in adolescents, dyslipidemia, hypertension, mood disorder, and diabetes mellitus in adults. A total of 12.7% and 15.0% of adolescents and adults, respectively, had abnormal serum testosterone levels, and 5.5% of adolescents and 7.5% of adults had abnormal serum dehydroepiandrosterone sulfate (DHEA-S) levels. Regardless of age, the proportion of patients with abnormal testosterone levels was higher in the female group than in the male group. @*Conclusion@#AGA showed paternal predominance in family history regardless of sex or age, suggesting paternal history as an important factor of AGA. Testosterone and DHEA-S abnormalities were found in patients with AGA, indicating a need for further studies on therapeutic effects associated with differences in hormonal profiles.

Public Preferences for Allocation Principles for Scarce Medical Resources in the COVID-19 Pandemic in Korea: Comparisons With Ethicists’ Recommendations / 예방의학회지

Objectives@#The purpose of this study was to investigate public preferences regarding allocation principles for scarce medical resources in the coronavirus disease 2019 (COVID-19) pandemic, particularly in comparison with the recommendations of ethicists. @*Methods@#An online survey was conducted with a nationally representative sample of 1509 adults residing in Korea, from November 2 to 5, 2020. The degree of agreement with resource allocation principles in the context of the medical resource constraints precipitated by the COVID-19 pandemic was examined. The results were then compared with ethicists’ recommendations. We also examined whether the perceived severity of COVID-19 explained differences in individual preferences, and by doing so, whether perceived severity helps explain discrepancies between public preferences and ethicists’ recommendations. @*Results@#Overall, the public of Korea agreed strongly with the principles of “save the most lives,” “Koreans first,” and “sickest first,” but less with “random selection,” in contrast to the recommendations of ethicists. “Save the most lives” was given the highest priority by both the public and ethicists. Higher perceived severity of the pandemic was associated with a greater likelihood of agreeing with allocation principles based on utilitarianism, as well as those promoting and rewarding social usefulness, in line with the opinions of expert ethicists. @*Conclusions@#The general public of Korea preferred rationing scarce medical resources in the COVID-19 pandemic predominantly based on utilitarianism, identity and prioritarianism, rather than egalitarianism. Further research is needed to explore the reasons for discrepancies between public preferences and ethicists’ recommendations.

Eccrine Syringofibroadenoma Associated with Bowen's Disease: A Case Report and Review of the Literature

Eccrine syringofibroadenoma (ESFA) is a rare, benign adnexal neoplasm which usually manifests as a solitary nodule on the extremities of elderly patients. Few case reports have described an association between ESFA and carcinomas including squamous cell carcinoma, porocarcinoma, and basal cell carcinoma. A 66-year-old male presented with a pruritic, erythematous brownish solitary plaque with crusted and verrucous surface on the extensor side of the right thigh. The lesion developed 6 to 7 years ago, and had been growing slowly. Biopsy revealed anastomosing epithelial strands which were composed of 2 areas: the upper area consisting of dysplastic cells with prominent nucleoli and abundant mitoses, and the lower area consisting of oval and round cells, and occasionally small luminal ducts. Dysplastic cells comprised almost the entire epidermis but did not invade into the dermis. Benign syringofibroadenomatous lesion surrounded the dysplastic cells in the lowermost portion of the epidermis. Although it is still unclear whether ESFA undergoes malignant transformation or it is a reactive change to carcinoma, complete excision should be performed to prevent malignant transformation with unknown risk.

pH-Dependent Expression, Stability, and Activity of Malassezia restricta MrLip5 Lipase

Background@#The lipophilic yeasts Malassezia spp. are normally resident on the surface of the human body, and often associated with various skin diseases. Of the 18 known Malassezia spp., Malassezia restricta is the most predominantly identified Malassezia sp. found on the human skin. Malassezia possesses a large number of genes encoding lipases to degrade human sebum triglycerides into fatty acids, which are required not only for their growth, but also trigger skin diseases. Previously, we have shown that MrLIP5 (MRET_0930), one of the 12 lipase genes in the genome of M. restricta, and is the most frequently expressed lipase gene in the scalp of patients with dandruff. @*Objective@#In this study, we aimed to analyze the activity, stability, and expression of MrLip5, with particular focus on pH. @*Methods@#We heterologously expressed MrLip5 in Escherichia coli, and purified and analyzed its activity and expression under different pH conditions. @*Results@#We found that MrLip5 was most active and stable and highly expressed under alkaline conditions, which is similar to that of the diseased skin surface. @*Conclusion@#Our results suggest that the activity and expression of MrLip5 are pH-dependent, and that this lipase may play an essential role at the M. restricta-host interface during disease progression.

Gene Therapy Options as New Treatment for Inherited Peripheral Neuropathy

Inherited peripheral neuropathy (IPN) is caused by heterogeneous genetic mutations in more than 100 genes. So far, several treatment options for IPN have been developed and clinically evaluated using small molecules. However, gene therapy-based therapeutic strategies have not been aggressively investigated, likely due to the complexities of inheritance in IPN. Indeed, because the majority of the causative mutations of IPN lead to gainof- function rather than loss-of-function, developing a therapeutic strategy is more difficult, especially considering gene therapy for genetic diseases began with the simple idea of replacing a defective gene with a functional copy. Recent advances in gene manipulation technology have brought novel approaches to gene therapy and its clinical application for IPN treatment. For example, in addition to the classically used gene replacement for mutant genes in recessively inherited IPN, other techniques including gene addition to modify the disease phenotype, modulations of target gene expression, and techniques to edit mutant genes have been developed and evaluated as potent therapeutic strategies for dominantly inherited IPN. In this review, the current status of gene therapy for IPN and future perspectives will be discussed.

A Case of Tender Calcinosis Cutis of an Infant Following a Single Heel Stick / 대한피부과학회지

No abstract available.

Hair Follicle Nevus Located on the Neck: Comparison with Accessory Tragus, Cervical Chondrocutaneous Branchial Remnants and Trichofolliculoma

Hair follicle nevus (HFN) is a rare, benign, follicular hamartoma that most frequently presents as a congenital nodule on the face. We experienced a rare case of HFN on the neck of a 14-year-old boy and performed a pilot immunohistochemical study with cytokeratin 19 (CK19) to compare the staining pattern of hair follicles in HFN and its differential diagnoses, accessory tragus, cervical chondrocutaneous branchial remnants (CCBR) and trichofolliculoma. With hematoxylin and eosin stain, HFN showed numerous tiny hair follicles in the dermis with several sebaceous and eccrine glands, and perifollicular fibrous thickening. With CK19 stain, some hair follicles in HFN and CCBR showed positive expression, a few hair follicles in accessory tragus showed weak expression, and no hair follicles in trichofolliculoma showed expression. The present report supports the view that HFN, accessory tragus and CCBR are within the same spectrum of hamartomas.

miR-381 Attenuates Peripheral Neuropathic Phenotype Caused by Overexpression of PMP22

Charcot-Marie Tooth disease type 1A (CMT1A), the major type of CMT, is caused by duplication of peripheral myelin protein 22 (PMP22) gene whose overexpression causes structural and functional abnormalities in myelination. We investigated whether miRNA-mediated regulation of PMP22 expression could reduce the expression level of PMP22, thereby alleviating the demyelinating neuropathic phenotype of CMT1A. We found that several miRNAs were down-regulated in C22 mouse, a CMT1A mouse model. Among them, miR-381 could target 3′ untranslated region (3′UTR) of PMP22 in vitro based on Western botting and quantitative Real Time-PCR (qRT-PCR) results. In vivo efficacy of miR-381 was assessed by administration of LV-miR-381, an miR-381 expressing lentiviral vector, into the sciatic nerve of C22 mice by a single injection at postnatal day 6 (p6). Administration of LV-miR-381 reduced expression level of PMP22 along with elevated level of miR-381 in the sciatic nerve. Rotarod performance analysis revealed that locomotor coordination of LV-miR-381 administered C22 mice was significantly enhanced from 8 weeks post administration. Electrophysiologically, increased motor nerve conduction velocity was observed in treated mice. Histologically, toluidine blue staining and electron microscopy revealed that structural abnormalities of myelination were improved in sciatic nerves of LV-miR-381 treated mice. Therefore, delivery of miR-381 ameliorated the phenotype of peripheral neuropathy in CMT1A mouse model by down-regulating PMP22 expression. These data suggest that miRNA can be used as a potent therapeutic strategy to control diseases with copy number variations such as CMT1A.

A Rare Case of Bilateral Frontal Linear Scleroderma (En Coup de Sabre) / 대한피부과학회지

No abstract available.

Eccrine Poroma with Rapid Growth during Pregnancy: A Case Report and Review of the Literature

Eccrine poroma is a benign solitary tumor with acrosyringeal differentiation that usually occurs on the sole or either side of the foot. Rapid growth of eccrine poroma during pregnancy has rarely been reported. We demonstrate a unique case of a 37-year-old pregnant woman who suffered from enlarged eccrine poroma on her left palm, which was tiny for 10 years but suddenly grew to a size of bean-sized reddish brown colored, pedunculated mass during pregnancy. The patient denied a previous history of trauma or infection to the lesion. Histopathologic findings with a shave biopsy were consistent with eccrine poroma. After the tumor was completely removed by the shave biopsy, no recurrence was noted for 5 months.

Concurrence of Circumscribed Morphea and Segmental Vitiligo: A Case Report

Although a few reports have noted the concurrent presentation of morphea and vitiligo at distinctly separate sites in the same patient, it is extremely rare that these two conditions occur at the same sites in a patient. We report the case of a 10-year-old Korean girl with morphea and vitiligo and those lesions occurred at the same sites and progressed simultaneously. An autoimmunity and a cutaneous mosaicism was considered to be involved in such an unique presentation as the pathogenesis is concerned.

Development of cell models for high-throughput screening system of Charcot-Marie-Tooth disease type 1

PURPOSE: Charcot-Marie-Tooth disease (CMT) is a peripheral neuropathy mainly divided into CMT type 1 (CMT1) and CMT2 according to the phenotype and genotype. Although molecular pathologies for each genetic causative have not been revealed in CMT2, the correlation between cell death and accumulation of misfolded proteins in the endoplasmic reticulum (ER) of Schwann cells is well documented in CMT1. Establishment of in vitro models of ER stress-mediated Schwann cell death might be useful in developing drug-screening systems for the treatment of CMT1. MATERIALS AND METHODS: To develop high-throughput screening (HTS) systems for CMT1, we generated cell models using transient expression of mutant proteins and chemical induction. RESULTS: Overexpression of wild type and mutant peripheral myelin protein 22 (PMP22) induced ER stress. Similar results were obtained from mutant myelin protein zero (MPZ) proteins. Protein localization revealed that expressed mutant PMP22 and MPZ proteins accumulated in the ER of Schwann cells. Overexpression of wild type and L16P mutant PMP22 also reduced cell viability, implying protein accumulation-mediated ER stress causes cell death. To develop more stable screening systems, we mimicked the ER stress-mediated cell death in Schwann cells using ER stress inducing chemicals. Thapsigargin treatment caused cell death via ER stress in a dose dependent manner, which was measured by expression of ER stress markers. CONCLUSION: We have developed genetically and chemically induced ER stress models using Schwann cells. Application of these models to HTS systems might facilitate the elucidation of molecular pathology and development of therapeutic options for CMT1.

Nutritional and Physicochemical Characteristics of the Antidementia Acetylcholinesterase-Inhibiting Methanol Extracts from Umbilicaria esculenta

To develop new antidementia nutraceuticals, a potent acetylcholinesterase (AChE)-inhibiting extract was screened from various extracts of nutritional mushrooms and lichens nutritional and its physicochemical properties were investigated. Among the several extracts tested, methanol extracts of Umbilicaria esculenta fruiting body showed the highest AChE inhibitory activity of 22.4%. U. esculenta AChE inhibitor was maximally extracted when fruiting bodies were treated with 80% methanol at 40degrees C for 18 h. The methanol extracts contained 18.9% crude lipid, 18.8% crude protein, and 11.6% total sugar. In addition, they contained 444 mg/g glutamic acid, 44 mg/g histidine, and 41 mg/g aspartic acid. The methanol extracts were soluble in a solution of methanol and 20% dimethylsulfoxide, insoluble in n-hexane, chloroform, and water, and were stable at 20~60degrees C and pH 1.0~5.0 for 1 h.