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Background: Oral antifungal drugs are the primary treatment for onychomycosis. However, there are few studies on the effectiveness and safety of oral combination therapy after laser treatment. Objective: We sought to contrast the efficacy and safety of laser and oral combination therapy with that of oral monotherapy for non-responders to laser treatment. Methods: We retrospectively evaluated the medical charts and photographs of 20 patients who received four sessions of Nd:YAG laser. Among these patients, 11 were "laser non-responders" and 9 were "laser partial responders". Afterward, 10 patients received oral drugs in addition to laser treatment (combination therapy) and the other 10 were completely altered to oral drugs, with no laser treatment (oral monotherapy). Clinical evaluation was conducted at baseline and 3 months after treatment. Recurrence was evaluated 3 months after the final evaluation. Results: Clinical evaluation revealed that combining or switching to oral antifungal drugs was substantially effective in the laser non-responder group (Z = -2.481, p = 0.013). Combination therapy was more effective than oral monotherapy (Z = -1.324, p = 0.247). Furthermore, positive baseline mycological results demonstrated a higher possibility of laser monotherapy failure (χ2 = -5.089, p = 0.024). There were two cases of recurrence in the oral monotherapy group and no adverse effect was discovered in any patient. Conclusion: This study highlighted that the combination of oral drugs with laser therapy could be beneficial regarding efficacy, recurrence, and safety in the treatment of patients who are refractory to laser therapy.

The acquisition of tamoxifen resistance is a major therapeutic problem in breast cancer. We developed a tamoxifen-resistant MCF-7 (TRM-7) cell line to elucidate the molecular mechanisms and factors associated with acquisition of such resistance. We showed that phosphorylation of STAT3 at tyrosine 705 (Y705) and RANTES expression are increased in response to tamoxifen in human breast cancer cells. On the basis of these results, we hypothesize that upregulated STAT3 phosphorylation and RANTES may be correlated with the development of drug resistance. Here, we showed that STAT3 and RANTES contribute to the maintenance of drug resistance. STAT3 phosphorylation is constitutively retained via a RANTES autocrine loop, which in turn upregulates anti-apoptotic signals in TRM-7 cells. STAT3–RANTES autocrine signaling affected expression of anti-apoptotic BCL-2 family genes and prevented TRM-7 cells from undergoing programmed cell death by inhibiting PARP and caspase-9 cleavage. Subsequently, blockade of STAT3 and RANTES in TRM-7 cells resulted in reduction of anti-apoptotic signals, which was rescued by exogenous RANTES treatment; drug resistance was also restored. Taken together, our results suggested that STAT3–RANTES autocrine signaling is essential for maintenance of drug resistance and inhibition of programmed cell death. These mechanisms of STAT3–RANTES autocrine signaling suggest a novel strategy for management of patients with tamoxifen-resistant tumors. Mol Cancer Res; 11(1); 31–42. ©2012 AACR.

Botulinum toxin type A is widely used to treat primary axillary hyperhidrosis and has proven to be an effective and safe approach. Onabotulinumtoxin A was approved by the FDA as a treatment for primary axillary hyperhidrosis. This study aimed to evaluate the efficacy and safety of Neu-BoNT/A in subjects diagnosed with primary axillary hyperhidrosis.The Hyperhidrosis Disease Severity Scale, gravimetric measurement of sweat, and Global Assessment Scale were analyzed at weeks 4, 8, 12, and 16 to determine the effect of treatment. Adverse events, physical examination, and vital signs were monitored.Subjects treated with Neu-BoNT/A showed statistically significant improvement by all 3 methods at weeks 4, 8, 12, and 16 (P value = 0.00). There were no severe adverse events or significant changes in vital signs, physical examination, or laboratory tests.Neu-BoNT/A can be effectively and safely used for primary axillary hyperhidrosis.This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Background Despite the invention of various non-invasive bioengineering tools, skin-type analysis has largely been based on subjective assessments. However, advancements in the functional cosmetic industry and artificial intelligence-assisted dermatology are creating a greater demand for an objective skin-type classification system. Objectives To propose an objective skin-type classification system solely based on non-invasive, bioengineering devices; provide reference values applicable to the Korean population; and compare our reference values with those of published studies. Methods Biophysical parameter measurements were obtained from the 2018 International Skin Characteristics Data Bank Project conducted by the Foundation of Korea Cosmetic Industry Institute. The participants were 434 healthy South Korean adults. Each participant was assessed using eight bioengineering devices (Tewameter® , pH-meter® , Corneometer® , Sebumeter® , Cutometer® , Spectrophotometer® , PRIMOS® lite, and Janus® ). The measurements were divided into tertiles to determine reference points. Results Our objective skin-type classification consists of five main categories (sensitivity, hydration, oiliness, elasticity, and skin tone) and five corresponding subcategories (erythema, roughness, pores, wrinkles, and pigmentation, respectively). Each skin type was assigned based on the reference point of the biophysical parameter, which was established as the tertile value associated with 'unfavourable' skin characteristics. Individuals were categorized as having sensitive skin when the TEWL scores were over 18.0 g/m2 /h or the pH was over 5.45; dehydrated skin when the corneometric value measured below 47.17 A.U.; oily skin when the sebumetric value exceeded 70 μg/cm2 ; and loose skin when the cutometric R2 value was below 0.68 E/mm. Conclusions This study is the first to provide a comprehensive skin-type classification system based solely on non-invasive biophysical parameters. As measurement data accumulate, the reference points will progress to become more accurate, and they will be subdivided according to gender, age, and ethnic group. Therefore, our classification system serves as a basis for artificial intelligence-based skin-type analysis.

Radiofrequency (RF) has been widely used as a noninvasive technique for skin tightening and rejuvenation. Moiré is a type of interference pattern corresponding to the shape of the face. We aimed to objectively evaluate the effect of RF on facial skin laxity using moiré. Ten subjects participated and were treated with a monopolar RF on the face. Clinical photographs and moiré images were obtained at the baseline and after treatment. The periorbital angle from the upper third of the face, zygomatic length ratio (L1/L2), angle from the middle third, perioral perpendicular length, and angle from the lower third were analyzed. After one session of RF treatment, the mean zygomatic length ratio (L1/L2) from the middle third of the face significantly increased in the 4th week (by 49.68%, P = .047). The L1/L2 ratio increased to nearly one, which were not significant after 8 weeks. The mean perioral perpendicular length decreased to 282.25 ± 84.069 pixels (px) after 4 weeks, and to 281.38 ± 76.03 px after 24 weeks; these differences were statistically significant. The parameters of zygomatic length ratio and perioral perpendicular length extracted from illuminated moiré images can be useful for objectively assessing various facial tightening treatments in clinical settings.

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.

An individual's first impression can be influenced by a number of esthetic factors, one of which is a natural hairline. The anterior hairline can be affected by various factors, such as race, age, forehead shape, and hair loss progression, similar to androgenetic alopecia. Information on the shape, hairline location on the forehead, and race are required to classify the anterior hairline. According to previous studies, the shape of the anterior hairline can be classified as round, M-shaped, rectangular, bell-shaped, or triangular. This study aimed to analyze the type of anterior hairline in Asian males without androgenetic alopecia. The subjects consisted of 461 males in China, Japan, Kazakhstan, Mongolia, the Philippines, South Korea, and Taiwan. We classified the shape of the anterior hairline into four types: M-shaped (M), rectangular (R), round (O), and wave-shaped (W). We classified the location of the anterior hairline into three types: high (H), middle (M) and low (L), according to the subjects' forehead ratio. Finally, we combined the shape and location types to devise a novel classification system for the anterior hairline type. The most common hairline types in our newly developed classification were MM (23.94%), RM (18.00%) and ML (11.04%). The least common types were OL (0.58%), OH (2.34%) and WH (2.74%). Our results will set standards for hairline shapes and locations, which will be helpful for evaluating hair loss treatment, establishing criteria and designs for reconstructive surgery, and developing camouflage makeups for the forehead hairline.

A model for evaluating theThe aim of this study was to analyze the healing process of fractionally induced microwounds using RCM.Eight healthy volunteers had a fractional carbon dioxide (CO₂) laser applied to the healthy skin of their inner arm in a single session. The wound healing of the skin at the stratum spinosum and stratum basale layers was examined using RCM. Two dermatologists evaluated the changes in the ablative zone using a grading system (ranging from completely recovered to slightly enlarged ablative zone) at four temporal time points: 3, 7, 14, and 28 days after laser application.The ablative zone in the epidermis was 75 percent of the baseline after seven days and 25 percent of the area after 14 days compared to the baseline. The expanded ablative zones in the epidermis were observed in some subjects resulting from contraction between Day 3 and Day 7. The ablative zone completely healed 28 days after laser application in both the spinous and basal layers of the epidermis.The healing process in the ablative zone of the fractional CO₂ laser-induced microwounds was observed over 2 to 4 weeks, revealing a regenerated epidermis of replaced keratinocytes from the basal layer through RCM.

Objectives To investigate the role of NF-κB in osteoblast lineage cells and periodontal ligament (PDL) fibroblasts during orthodontic tooth movement (OTM). Materials and Methods Transgenic mice that expressed a dominant negative mutant of the inhibitor of kB kinase (IKK-DN) with lineage specific expression in osteoblastic cells and PDL fibroblasts driven by a response element in the collagen1α1 promoter and matched wild-type (WT) mice were examined. A 10-12 g force was applied by a NiTi coil and maintained for 5 or 12 days. OTM distance, PDL width, and bone volume fraction were measured using micro computed tomography. Osteoclast numbers were counted in tartrate-resistant acid phosphatase-stained sections. Activation of nuclear factor kappa B (NF-kB) was assessed by nuclear localization of p65, and the receptor activator of nuclear factor-κB ligand (RANKL) was measured by immunofluorescence and compared to control specimens with no orthodontic force. Results OTM-induced NF-kB activation (p65 nuclear localization) in WT mice was largely blocked in transgenic (TG) mice. OTM was significantly reduced in the TG mice compared to WT mice along with reduced osteoclastogenesis, narrower PDL width, higher bone volume fraction, and reduced RANKL expression. Conclusions Osteoblast lineage cells and PDL fibroblasts are key contributors to alveolar bone remodeling in OTM through IKKβ dependent NF-κB activation.

Onychomycosis is a fungal infection of the nail unit. Compared to other superficial dermatophytoses of the skin and hair, onychomycosis is associated with a chronic course and frequent recurrence. Originally, structural characteristics of the nail, such as poor vascular supply and thick layers of hard keratin, were thought to be limiting factors for efficient drug delivery, resulting in prolonged treatment. However, recent research reveals the following crucial mechanisms contributing to the chronicity of nail dermatophytosis: innate characteristics of Trichophyton rubrum, formation of dormant spores called arthroconidia, physical and immunologic characteristics of the nail apparatus, and alteration of the defense system of the host. T. rubrum, the most common causative fungal pathogen for onychomycosis, acquires selective immune tolerance toward the host's defense system. Transformation into dormant phases, such as arthroconidia, creates greater resistance to antifungal medication and nonnutritive environments. The anatomical and biological structures of the nail allow immune evasion, increase infection susceptibility, and promote biofilm formation. Key regulators of the host's innate and adaptive immune systems are downregulated as infection persists, and age-associated immunomodulation aggravates the process.

Studies on facial hyperpigmentation across different facial units are limiting. We aimed to analyze melanin pigmentation images to observe facial pigmentary demarcation lines (FPDLs) and suggest facial hyperpigmentation types for normal individuals.3D facial melanin pigmentation images of 173 volunteers were obtained and analyzed for the presence of FPDLs. Pigmentation severity was assessed for each of the thirteen facial pigment units. The images were then grouped according to a pattern of hyperpigmentation to suggest three facial hyperpigmentation types-dark spot, photoaging and post-inflammatory hyperpigmentation.Four groups of FPDLs including a novel group I were observed. Nasal, frontal, auricular were the darkest pigmented facial pigment unit, and the anterior neck was the least pigmented. The dark spot type was the most common facial hyperpigmentation type. The photoaging type and the PIH type showed age-dependent distribution, as the photoaging type was more common among the subjects over 40s, and the PIH type was more common in younger subjects.Facial hyperpigmentation among healthy individuals with Fitzpatrick skin types II-IV is often accompanied by FPDLs and categorized into three types. Each type is modeled after the pattern of pigmentation associated with certain dermatological disorders. The practical implications of facial hyperpigmentation types can be resourceful in various fields including prevention and treatment of pigmentary disorders.

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

Introduction: Neuronox® has not yet been investigated for its efficacy and safety in the treatment of lateral canthal lines (LCL).Methods: This study was a randomized, double-blind, active drug con...

Mycobacterium avium-intracellulare complex (MAC) is one of the most prevalent pathogenic nontuberculous mycobacteria that cause chronic pulmonary disease. The prevalence of MAC infection has been rising globally in a wide range of hosts, including companion animals. MAC infection has been reported in dogs; however, little is known about interaction between MAC and dogs, especially in immune response. In this study, we investigated the host immune response driven by M. intracellulare using the co-culture system of canine T helper cells and autologous monocyte-derived macrophages (MDMs). Transcriptomic analysis revealed that canine MDMs differentiated into M1-like macrophages after M. intracellulare infection and the macrophages secreted molecules that induced Th1/Th17 cell polarization. Furthermore, canine lymphocytes co-cultured with M. intracellulare-infected macrophages induced the adaptive Th17 responses after 5 days. Taken together, our results indicate that M. intracellulare elicits a Th17 response through macrophage activation in this system. Those findings might help the understanding of the canine immune response to MAC infection and diminishing the potential zoonotic risk in One Health aspect.

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The role of vitamin D deficiency and vitamin D receptor (VDR) gene polymorphisms has been established in many autoimmune diseases, including vitiligo, but the result is still controversial.The aim of this study was to investigate the serum vitamin D levels in vitiligo patients and to compare the association of VDR gene polymorphisms in vitiligo patients and healthy controls.We collected the data of age, sex, serum 25-hydroxy vitamin D (25[OH]D) level, thyroid autoantibodies, disease duration, types of vitiligo, family history and the affected body surface area of vitiligo from 172 patients. And we analyzed the VDR gene polymorphisms in 130 vitiligo and 453 age-sex-matched control subjects.The mean serum level of 25(OH)D in 172 vitiligo patients was 18.75 ± 0.60 ng/mL, which had no significant difference with a mean serum value of 25(OH)D in the Korean population. However, there were significant differences according to the duration of the disease and family history. Also, there were no significant differences in the genotypic and allelic distributions of 37 examined SNPs of VDR gene between vitiligo patients and healthy controls.Serum level of 25(OH)D in vitiligo patients was not significantly different from the mean serum value of the Korean population. Also, there were no significant differences in the genotypic distributions of VDR gene between vitiligo patients and healthy controls.

Background Many ingredients used in cosmetics evoke a comedogenic response. The concept of ''acne cosmetica'' was developed to link the use of certain ingredients to comedone formation. Various clinical research methods have been suggested for the effective screening of an ingredient that can worsen acne or acneiform eruption and confirm its clinical relevance as to whether it is used as a non-comedogenic claim. Although comedogenicity assessment has not yet been established, attempts have been made to evaluate the comedogenicity of cosmetic ingredients and find the most appropriate method to evaluate comedogenicity in human skin. Materials and methods Total 6 participants were included in the study. Each participant received patches on the upper back containing cocoa butter. We used reflectance confocal microscopy (RCM) to count the number of microcomedones and follicles induced by cocoa butter. Results The mean value change of microcomedone/follicle by the comedogenic substance was significantly higher than that of the non-applied site for 2 weeks (p = 0.0419). The mean value changes of the microcomedone diameter caused by the comedogenic substance were significantly larger than those found at the non-applied site at 2 and 4 weeks (p = 0.0026 and p = 0.0038, respectively). Conclusions We recommend RCM as a non-invasive real-time method that is useful for evaluating comedogenicity and early detection of a microcomedone.

Nuclear receptor coactivator 6 (NCOA6) is a transcriptional coactivator of nuclear receptors and other transcription factors. A general

Background Acne scarring can be divided into 2 types: atrophic and hypertrophic scars. Papular acne scars are commonly encountered, skin-colored papules on the chin and back. Objective This study aimed to estimate the prevalence of each acne scar type and to investigate the clinical manifestations of papular acne scars. Methods This retrospective study included 416 patients with acne scars. Dermatologists classified the scars into 3 types (atrophic, papular, and keloid type) based on clinical photographs and analyzed the clinical and histologic features of papular acne scars. Results Among 416 patients with acne scars, 410 patients (98.56%) had atrophic scars, 53 patients (12.74%) had keloid scars, and 46 patients (11.06%) had papular acne scars. Twenty patients (4.81%) had both papular and keloid acne scars. Histologic analysis showed fibrotic tissue in both keloid and papular acne scars. Fibrosis of the papular scar was limited to the upper dermis. Conclusion Papular acne scars were significantly more prevalent in patients with keloid scars than in those without keloid scars. These results provide a basis for understanding papular acne scars, which have been under-recognized. The association between papular and keloid acne scars can suggest the decision for scar treatment.

Atopic dermatitis (AD) is associated with allergic comorbidities, such as asthma, allergic rhinitis (AR), and allergic contact dermatitis (ACD). The etiology of keloid is largely unknown; however, AD and keloid share inflammatory pathways characterized by T-helper cell 2 cytokines and increased dermal fibroblast activity. The prevalence of keloids is known to increase in patients with AD. This study aimed to estimate the prevalence of keloids in patients with AD, and compare it with the prevalence of other comorbidities of AD. We assessed the Korean National Health Information Database and medical records including coexisting asthma, AR, and ACD. Single and multiple logistic regression models were created for keloids and each allergic disease. The prevalence of keloids was higher in the AD group than in the control group. Among patients with AD, adolescents and adults had a higher prevalence of keloids than infants and children. The risk of keloids was high with AD alone, and coexisting asthma significantly increased the risk. Similarly, the risk of keloids was higher in AR associated with AD and ACD associated with AD than in AD alone. Thus, among Koreans, patients with AD have a higher risk of keloid development, with coexisting allergic diseases increasing the risk.