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In this study, we examined the effect of C. japonicum flower extract (CFE) on melanogenesis and its mechanism in vitro and ex vivo.The effect of CFE on melanogenesis was investigated with lightly (HEMn-LP) and moderately (HEMn-MP) pigmented normal human melanocytes, reconstituted three-dimensional skin (3D skin) model and ex vivo human hair follicles. The melanogenesis-inducing effect of CFE was evaluated using melanin content and intracellular tyrosinase activity assay. The amount and type of eumelanin and pheomelanin were analysed by using HPLC method. The mechanism involved in the effect of CFE on hyperpigmentation was explored by cyclic adenosine monophosphate (cAMP) immunoassay and western blot analysis for tyrosinase, microphthalmia-associated transcription factor (MITF) and phosphorylated CRE-binding protein (pCREB) expression. The degree of pigmentation in 3D skin and L-values were measured using a CR-300 chroma meter. The amount of dissolved melanin was measured using a spectrophotometer. The content of melanin in the hair follicles was evaluated by Fontana Masson staining.C. japonicum flower extract significantly increased the melanin content and cellular tyrosinase activity in both HEMn-LP and HEMn-MP cells. The markers of pheomelanin and eumelanin in HEMn-LP and HEMn-MP were also increased by CFE. We observed that CFE treatment on melanocytes increased intracellular cAMP with inducing pCREB and up-regulating the protein levels of TYR and MITF. Furthermore, CFE considerably increased the melanin content in a 3D skin model and ex vivo human hair follicles.These results suggest that CFE exerts hyperpigmentation activity through cAMP signalling in human melanocytes that it can improve follicular depigmentation and vitiligo by stimulating the melanin synthesis.Dans cette étude, nous avons examiné l'effet de l'extrait de fleur de C. japonicum (EFC) sur la mélanogenèse et son mécanisme in vitro et ex vivo. MÉTHODES: L'effet du EFC sur la mélanogenèse a été étudié avec des mélanocytes humains normaux légèrement (HEMn-LP) et modérément (HEMn-MP) pigmentés, un modèle de peau reconstituée en 3 dimensions (peau 3D) et des follicules pileux ex vivo. L'effet inducteur de la mélanogénèse de la EFC a été évalué en utilisant la teneur en mélanine et le dosage de l'activité de la tyrosinase intracellulaire. La quantité et le type d'eumélanine et de phéomélanine ont été analysés en utilisant la méthode HPLC. Le mécanisme impliqué dans l'effet de la EFC sur l'hyperpigmentation a été exploré par immunoessai à l'adénosine monophosphate cyclique (AMPc) et Western blot pour l'expression de la tyrosinase, du facteur de transcription associé à la microphtalmie (MITF) et l’expression de la protéine CREB phosphorylée. Le degré de pigmentation de la peau 3D, les valeurs L ont été mesurées à l'aide d'un chromamètre CR-300. La quantité de mélanine dissoute a été mesurée à l'aide d'un spectrophotomètre. La teneur en mélanine des follicules pileux a été évaluée par coloration Fontana Masson. RÉSULTATS: EFC a augmenté de manière significative la teneur en mélanine et l'activité de la tyrosinase cellulaire dans les cellules HEMn-LP et HEMn-MP. Les marqueurs de phéomélanine et d'eumélanine dans HEMn-LP et HEMn-MP ont également été augmentés par EFC. Nous avons observé que le traitement EFC sur les mélanocytes augmentait l'AMPc intracellulaire en induisant pCREB et en régulant à la hausse les niveaux de protéines de TYR et MITF. De plus, le EFC a considérablement augmenté la teneur en mélanine dans un modèle de peau 3D et dans les follicules pileux humains ex vivo.Ces résultats suggèrent que la EFC exerce une activité d'hyperpigmentation via la signalisation de l'AMPc dans les mélanocytes humains qu'elle peut améliorer la dépigmentation folliculaire et le vitiligo en stimulant la synthèse de mélanine.

Human skin aging is a natural phenomenon that results from continuous exposure to intrinsic (time, genetic factors, hormones) as well as extrinsic factors (UV exposure, pollution, tobacco). In areas that are frequently exposed to the sun, photoaging blends with the process of intrinsic aging, resulting in an increased senescent cells number and consequently accelerating the aging process. The severity of photodamage depends on constitutional factors, including skin phototype (skin color, tanning capacity), intensity, and duration of sunlight/UV exposure. Aging affects nearly every aspect of cutaneous biology, including pigmentation. Clinically, the phenotype of age pigmented skin has a mottled, uneven color, primarily due to age spots, with or without hypopigmentation. Uneven pigmentation might be attributed to the hyperactivation of melanocytes, altered distribution of pigment, and turnover. In addition to direct damage to pigment-producing cells, photodamage alters the physiological crosstalk between keratinocytes, fibroblasts, endothelial cells, and melanocytes responsible for natural pigmentation homeostasis. Interestingly, age-independent diffuse expression of senescence-associated markers in the dermal and epidermal compartment is also associated with vitiligo, suggesting that premature senescence plays an important role in the pathology.

Background Topical calcineurin inhibitors have been used to treat vitiligo, either alone or in combination with phototherapy; however, the long-term safety of these agents remains controversial. Objective To investigate the risk of lymphoma and skin cancer in vitiligo patients who received topical calcineurin inhibitors or phototherapy. Methods A multicenter retrospective cohort study of 25,694 vitiligo patients who received topical calcineurin inhibitors or phototherapy for 6 weeks or more between 2001 and 2019 was performed. Cumulative doses of topical calcineurin inhibitors and total phototherapy sessions were determined. Outcomes were the development of lymphoma or skin cancer after enrollment, confirmed through chart review and pathology reports. Results During 95,203 person-years, 13 cases of lymphoma, 22 of actinic keratosis, 15 of nonmelanoma skin cancer, and 5 of melanoma were observed. The risk of lymphoma and skin cancer was not significantly increased by topical calcineurin inhibitor dose or phototherapy sessions. The interaction between the topical calcineurin inhibitors and phototherapy was not associated with an increased risk of skin cancer. Limitations Retrospective study, individual follow-up duration less than 4 years, and no adjustment for comorbidities and medication history. Not generalizable to other races. Conclusion The long-term risk of skin cancer or lymphoma was not associated with the use of topical calcineurin inhibitors, phototherapy, and both treatments in combination in patients with vitiligo.

BackgroundA flipped classroom with team-based learning is a blended educational strategy that guides active learning inside and outside the classroom. This study aimed to verify the effects of this innovative blended educational strategy on knowledge, problem-solving ability, and learning satisfaction of undergraduate nursing students undergoing public healthcare education.MethodsThe subjects were undergraduate nursing students enrolled in H University in South Korea. The experiment was conducted over a period of 8 weeks in the public healthcare course. Two groups, blended learning (A flipped classroom with team-based learning) which was the experimental group and traditional lecture-based classroom group, the control group, were assessed. In the blended learning group, the students had pre-class, in-class (including team-based learning elements), and post-class learning elements. The two groups were compared on the following learning outcomes: knowledge, problem-solving ability, and learning satisfaction.ResultsResults showed that the blended learning instructional methods, in comparison with traditional lectures, enhanced the students’ knowledge, problem-solving ability, and learning satisfaction in the public healthcare course.ConclusionsThis study supports the feasibility of the flipped classroom with team-based learning as a blended learning strategy, able to produce improvements in nursing students’ learning outcomes. Blended learning approaches may be an effective alternative to conventional approaches in nursing education.

Background/purpose Vitiligo remains a major challenge in dermatology. However, much of the treatment remains unclear, because little evidence is available. We sought to answer some critical questions pertaining to management of vitiligo patients. Methods A modified Delphi process among 31 vitiligo experts was conducted. A total of 12 clinical vitiligo treatment questions without clear answers were collected via a vote. To address each question, two members performed systematic literature reviews and prepared draft statements along with the levels of evidence and strength of recommendation. After reviewing the draft, all expressed their extent of agreement from 1 (strong disagreement) to 9 (strong agreement) for each item. The drafts were revised to reflect suggested comments. Discussion continued until all members agreed with the ultimate decision. Results The consensus process was completed after five rounds. We identified the best answers to 12 key questions, including issues on long-term phototherapy, systemic and topical corticosteroids, topical calcineurin inhibitors, immunosuppressants, excimer laser treatment, and surgical interventions. Conclusion This consensus would complement current guidelines and aid both physician and patient decision-making in the treatment of vitiligo.

Dasatinib, a second-generation tyrosine kinase inhibitor, is indicated for the therapy of imatinib-resistant leukemia and also for the treatment of solid cancers. Here, we report a novel effect of dasatinib of inducing differentiation in normal human melanocytes. Treatment with dasatinib significantly increased the melanin content and tyrosinase activity through the up-regulation of MITF and tyrosinase expressions. Consistently, dasatinib had clear stimulatory action in the pigmentation of ex vivo cultured skin. The molecular mechanism underlying the melanogenic effect of dasatinib was associated with the ERK-dependent phosphorylation of CREB. The ERK inhibitor PD98059 not only inhibited the phosphorylation of CREB but also abrogated dasatinib-induced melanocyte differentiation. These results demonstrate for the first time the capacity of dasatinib to induce differentiation in normal human melanocytes depending on the activation of ERK-CREB-MITF-tyrosinase signaling cascades.

Ponatinib, an oral third-generation tyrosine kinase inhibitor, is indicated for the treatment of imatinib-resistant leukemia. We experienced a case of ponatinib-induced eruptive nevi, and the biologic effects of ponatinib on melanocytes were investigated. Treatment with ponatinib significantly increased the proliferation of normal human melanocyte or melanoma cells through the upregulation of the extracellular signal-regulated kinase and protein kinase B signaling pathways. The downstream molecules of cyclin B1 and D1 were significantly increased in ponatinib-treated melanocytes. These results demonstrate the capacity of ponatinib to induce the proliferation and tumorigenesis of melanocytes.

The Korean Triage and Acuity Scale is a tool developed to classify severity and urgency of emergency department patients, focusing on their symptoms. Considering the importance of the Korean Triage and Acuity Scale, learning for emergency department nurses who perform the Korean Triage and Acuity Scale must be structured to ensure that the knowledge they gain can be applied to various clinical situations of the emergency department. Moreover, Web-based learning is considered appropriate in this situation. This is a methodological research study that was conducted to develop a Web-based Korean Triage and Acuity Scale learning program for emergency department nurses. The learning program was developed using each of the five phases of the "analysis, design, development, implementation, and evaluation" model, that is, analysis, design, development, implementation, and evaluation. The learning program was composed of 22 cases of emergency situations based on the Korean Triage and Acuity Scale teaching material with an approval from the Korean Triage and Acuity Scale committee in the Korean Society of Emergency Medicine. The developed program was delivered in 4-hour sessions over 4 weeks. Emergency department nurses who were given the Web-based Korean Triage and Acuity Scale learning program showed improvement in work-site transfer and reported satisfactory learning. The findings indicate that the Web-based learning program for nurses can be used as an effective tool that is easily accessible and provides multiple learning opportunities.

Skin aging is induced and sustained by chronological aging and photoaging. Aging skin pigmentation such as mottled pigmentation (senile lentigo) and melasma are typical signs of photoaging. The skin, like other human organs, undergoes cellular senescence, and senescent cells in the skin increase with age. The crosstalk between melanocytes as pigmentary cells and other adjacent types of aged skin cells such as senescent fibroblasts play a role in skin-aging pigmentation. In this review, we provide an overview of cellular senescence during the skin-aging process. The discussion also includes cellular senescence related to skin-aging pigmentation and the therapeutic potential of regulating the senescence process.

It has been proposed that melasma is a photoageing skin disorder. The photoaged fibroblasts have been suggested as an important source of melanogenic factors which are involved in the regulation of pigmentation. To investigate whether melasma includes senescent cells, lesional and perilesional normal skin from 38 melasma patients was assessed using a cell senescence marker, p16INK4A . The results showed that lesional dermal skin had more p16INK4A -positive senescent cells than perilesional skin. The impact of senescent fibroblasts was further investigated in a pilot study using radiofrequency (RF) intervention for melasma. It showed that the RF therapy decreased the number of senescent cells with increased expression of procollagen-1, which were associated with reduced epidermal pigmentation. This leads us to the speculation that senescent fibroblasts may contribute to drive melasma and might be considered as a potential therapeutic target.

OBJECTIVE The purpose of this study was to examine the effects of an educational program on disaster nursing competency among Korean nursing students. DESIGN AND SAMPLE A quasi-experimental design with a nonequivalent control group was used. We randomly assigned 60 junior nursing students from two nursing colleges in Korea to an experimental group (n = 30) and a control group (n = 30). MEASURES A disaster educational program for nursing students was developed based on the International Council of Nurses framework of disaster nursing competencies. The program sought to teach nursing activities by stage of disaster (i.e., prevention/mitigation, preparedness, response, and recovery/rehabilitation). Disaster nursing knowledge, disaster triage, and disaster readiness were measured as dependent variables. RESULTS Compared with the control group, the experimental group showed a significant increase in disaster nursing knowledge (t = 14.37, p

IMPORTANCE: Narrowband UV-B (NBUVB) phototherapy has been the mainstay in the treatment of vitiligo, but its long-term safety in terms of photocarcinogenesis has not been established. OBJECTIVES: To investigate the risks of skin cancer and precancerous lesions among patients with vitiligo undergoing NBUVB phototherapy, based on the number of NBUVB phototherapy sessions. DESIGN, SETTING, AND PARTICIPANTS: This nationwide population-based retrospective cohort study enrolled 60 321 patients with vitiligo 20 years or older between January 1, 2007, and December 31, 2017. Patients and outcomes were identified through nationwide cohort data from the Korean national health insurance claims database, and frequency matching by age and sex was performed. EXPOSURES: The number of phototherapy sessions each patient received between 2008 and 2017. Patients were classified into 5 groups according to the number of phototherapy sessions (0 sessions, 20 105 patients; 1-49 sessions, 20 106 patients; 50-99 sessions, 9702 patients; 100-199 sessions, 6226 patients; and ≥200 sessions, 4182 patients). We also identifed patients who underwent at least 500 phototherapy sessions (717 patients). MAIN OUTCOMES AND MEASURES: Primary outcomes were the development of actinic keratosis, Bowen disease, nonmelanoma skin cancer, or melanoma after enrollment. RESULTS: Among the 60 321 patients with vitiligo in this study (33 617 women; mean [SD] age, 50.2 [14.9] years), the risks of Bowen disease (

Ashy dermatosis (AD), lichen planus pigmentosus (LPP), erythema dyschromicum perstans (EDP), and idiopathic eruptive macular pigmentation are several acquired macular hyperpigmentation disorders of uncertain etiology described in literature. Most of the published studies on these disorders are not exactly comparable, as there are no clear definitions and different regions in the world describe similar conditions under different names. A consensus on the terminology of various morphologies of acquired macular pigmentation of uncertain etiology was a long-felt need. Several meetings of pigmentary disorders experts were held to address this problem. A consensus was reached after several meetings and collation of e-mailed questionnaire responses and e-mail communications among the authors of publications on the above conditions. This was achieved by a global consensus forum on AD, LPP, and EDP, established after the 22nd International Pigment Cell Conference held in Singapore in 2014. Thirty-nine experts representing 18 countries participated in the deliberations. The main focus of the deliberations was terminology of the conditions; as such, we present here the consensus statement of the forum and briefly review the available literature on the subject. We have not attempted to discuss treatment modalities in detail.

Since localized treatment for vitiligo is as essential as systemic treatment, a reliable instrument for target evaluation is needed besides those for whole body evaluation. We developed the Vitiligo Extent Score for a Target Area (VESTA) using reference images of both marginal and perifollicular repigmentation to measure the repigmentation rate (%) in a target lesion. In the validation study, a total of 65 dermatologists in 10 institutes evaluated 17 pairs of vitiligo images (pre- and post-treatment) using both a rough estimate and the VESTA. The VESTA (concordance correlation coefficient: 0.949, 95% confidence interval [CI] 0.942-0.955) was significantly more accurate than the rough estimate (0.896, 95% CI: 0.883-0.908). It was also associated with better inter-rater reliability over the rough estimate, albeit not significant. The VESTA can afford intuitive, convenient, and reliable assessment of the treatment response in a target area, and would be useful in clinical practice as well as retrospective studies.

Cutaneous ageing is an important extrinsic process that modifies the pigmentary system. Because cellular senescence is a fundamental ageing mechanism, we examined the role of senescent cells in ageing pigmentation. Methods: Biopsies obtained from senile lentigo and perilesional normal skin were assayed for a marker of cellular senescence, p16INK4A. To determine the secretory phenotypes of senescent fibroblasts, we performed microarray, RNA sequencing and methylation array analyses in senile lentigo and senescent fibroblasts. To further investigate the impact of senescent cells on ageing-related pigmentation, an intervention that targeted senescent cells using radiofrequency was performed. Results: In vivo, senescent fibroblasts accumulated at the sites of age-related pigmentation. Phenotype switching of the cells resulted in the repression of stromal-derived factor 1 (SDF1) by promoter methylation. SDF1 induced melanocyte differentiation via stromal-epithelial interactions, ultimately driving skin pigmentation. Furthermore, the elimination of senescent fibroblasts from pigmented skin using radiofrequency was accompanied by skin lightening, rendering it a potential target for treatment. Conclusion: Aged pigmented skin contains an increasing proportion of senescent fibroblasts. Cells with phenotype switching exhibited a loss of SDF1, which stimulates the melanogenic process and thereby contributes to aging pigmentation. These data may promote the development of new therapeutic paradigms, such as a stroma-targeting therapy for pigmentary disorders.

OBJECTIVE(S) The objective of the study was to explore and describe the health-seeking experience of North Korean women defectors settled in South Korea. DESIGN AND SAMPLE A qualitative study was conducted using Colaizzi's phenomenological method. Participants were 10 North Korean women defectors. MEASURES Data were collected through in-depth, unstructured interviews with individual participants. RESULTS A total of 24 themes, eight theme clusters, and four categories emerged. The structure of the health-seeking experience for them was identified as 'having new opportunities to better understand my own body and protecting my own health while adapting to the health care system of the South'. The four categories were: finding out about my own body, confusion regarding the medical treatment, enjoying the health care benefits, and protecting my own health. CONCLUSIONS The findings of this study will help improve the understanding of the health-seeking experience of North Korean women defectors and provide valuable resources to assist in caring for their health needs. This will contribute to preparing the groundwork to enhance the quality of their remaining life in South Korea.

Urinary tract infections (UTIs) are one of the most common types of bacterial infection in humans in various parts of the world and are caused mainly by uropathogenic Escherichia coli (UPEC). A total of 58 UPEC isolates from urine were characterized by serotyping and pulsed-field gel electrophoresis (PFGE). The majority of the UPEC strains belonged to serogroups O2 and O6. The UPEC strains were grouped under different pulsotypes and majority of them belonged to serogroups O2 and O6. Among the 14 virulence factors considered, 13 were present in various serogroups. The virulence genes fimH and sfa were present in all the isolates while none of the isolates carried lt-1. The strains exhibited 36 different virulence patterns, of which 11, referred to as UP (UPEC pattern) 1 to UP 11 were most common. Antibiotic resistance profiling of the UPEC isolates revealed that the serogroups O2 and O6 contain the highest number of resistant strains. The data from the current study depicting the distribution of UPEC strains among various serogroups and pulsotypes, and the occurrence of virulence genes and antibiotics resistance offer useful information on the epidemiological features of UPEC in Korea for the enhanced surveillance of potential emergence of UPEC.

This study aims to investigate the effects of meridian acupressure massage on body composition, edema, stress, and fatigue in postpartum women.A quasi-experimental design with a nonequivalent control group was utilized.The Postpartum Care Center of Women's Hospital in Gwangju City, Republic of Korea.The study group consisted of 39 postpartum women, 19 in the experimental group and 20 in the control group, recruited from the postpartum care center of Women's Hospital in Gwangju city, South Korea.The experimental group was provided with meridian acupressure massage for 90 min daily over 5 days as an experimental therapy.Body composition (body weight, BMI, total body water, ECW ratio, LBM, and body fat) Edema (subjective edema, average girth of the upper limbs, and average girth of the lower limbs), Stress (psychological stress and physical stress), and Fatigue.The experimental group demonstrated a significantly larger decrease compared with the control group in measures of body composition, edema, total subjective stress, psychological stress, and subjective fatigue.Meridian acupressure massage can hasten the return to original body composition after childbirth.

Solar lentigo (SL) is a hallmark of ultraviolet (UV)-induced photoaged skin and growing evidence implicates blood vessels in UV-associated pigmentation. In this study, we investigated whether the vasculatures are modified in SL. Twenty-five women with facial SL were enrolled and colorimetric and blood flow studies were performed. There was a significant increase in erythema which was associated with increased blood flow in the lesional skin compared with perilesional normal skin. Immunohistochemical studies with 24 facial SL biopsies consistently revealed a significant increase in vessel density accompanied by increased levels of vascular endothelial growth factor expression. CD68 immunoreactivity was significantly higher in lesional skin suggesting increased macrophage infiltration in SL. In conclusion, SL is characterized by increased blood flow and vasculature. These findings suggest the possible influence of the characteristics of vasculature on development of SL.

Background Clinical photography is an important component of the initial assessment and follow-up of patients with vitiligo in clinical practice and research settings. Standardization of this photographic process is essential to achieve useful, high-quality, and comparable photographs over time. Objective The aim is to develop an international consensus for a core set of recommendations for standardized vitiligo clinical photography. Methods Based an international meeting of vitiligo experts, a standard operating procedure was developed for vitiligo photography in daily practice and research settings. This protocol was subsequently reviewed by 20 vitiligo experts until agreement was reached. Results The resulting protocol includes a set of 10 and 15 photographs for clinical practice and research purposes, respectively. The photographic series are based on anatomic units included in the Vitiligo Extent Score. Furthermore, graphic representations of standardized positioning and suggestions for guidelines to standardize the process (background color, lighting, position marking, scales, materials, instruments) for both color and ultraviolet photographs are described. Conclusions This consensus-based protocol for vitiligo photography will harmonize imaging for both clinical practice, translational research, and clinical trials. It can improve outcome assessment, foster multicenter collaboration, and promote better communication with patients regarding outcomes of treatment.

Background: Over the course of repetitive and long-term chemotherapy treatment, multiple myeloma (MM) patients experience physical and psychological problems and side effects. Objectives: The objective of this study was to investigate the levels of pain, uncertainty, social support, anxiety, depression, and quality of life (QOL) receiving chemotherapy for MM patients and to identify psychosocial factors influencing their QOL. Methods: A cross-sectional descriptive design was used. A total of 110 MM patients receiving chemotherapy were recruited into the study. The data were collected by personal interviews using questionnaires and were analyzed using descriptive statistics, t-test, one-way ANOVA, Pearson's correlation, and hierachial multiple regression analysis. Findings: Global health status QOL was explained by uncertainty, anxiety, and depression. Functional QOL was explained by age, uncertainty, and anxiety. Symptom QOL was explained by pain, and depression. Uncertainty, anxiety and depression were the strongest predictive factors. To improve QOL of patients with MM, nurses should focus on the factors identified in this study when doing nursing care. Impact statement: This study confirmed psychological difficulties such as uncertainty, anxiety and depression affecting quality of life of MM patients receiving chemotherapy.

Debriefing, based on reflection, is imperative in simulation. Mezirow's transformative learning theory (TLT) uses critical reflection in providing care to patients, which involves clinical judgment in nursing. The aim of this study was to compare the effects of TLT-versus a non-TLT–based debriefing protocol on knowledge, problem-solving process, critical thinking disposition, and clinical judgment in nursing students. A randomized controlled trial was performed. Fifty-six junior nursing students were assigned to the TLT (n = 26) and the control (n = 30) groups in South Korea. Debriefing protocols based on Mezirow's TLT for the experimental group and gather-analyze-summarize–based debriefing for the control group were used for four weeks. Scores of the TLT group were significantly higher than those of the control group in the problem-solving process, critical thinking disposition, and clinical judgment of reflection. We identified the main effects of group, time, and time-by-group interaction for clinical judgment (noticing, interpreting, and responding), except for knowledge between the two groups. The TLT debriefing approach in simulation can be tailored to improve problem-solving, critical thinking, and clinical judgment outcomes, which are vital to nursing education related to the provision of care to patients.

Cutaneous vasculature systems play a role in regulating skin pigmentation. We analysed RNA sequencing data to identify novel antimelanogenic factors secreted from endothelial cells and found that one of the secreted factors, clusterin, is highly expressed by HDMECs. To investigate the paracrine effect of clusterin from HDMECs on the regulation of melanogenesis, HDMECs were infected with clusterin or sh-clusterin lentivirus and the HDMEC-derived conditioned media were used to treat normal human melanocytes. It was found that HDMEC-derived clusterin inhibits melanogenesis through MITF/tyrosinase downregulation. The findings here suggest that HDMECs secrete copious amounts of clusterin and that the clusterin is a factor contributing to the inhibitory effect of endothelial cells on melanogenesis via paracrine crosstalk between endothelial cells and melanocytes.

A 308-nm excimer laser (EL) has been widely used to treat patients with localized vitiligo. However, data are rare on the influence of EL treatment on the risks of skin cancer. To evaluate the skin cancer risks after long-term EL treatment, we performed a nationwide population-based retrospective cohort study using the Korean National Health Insurance Claims Database. A total of 5,052 patients with vitiligo were classified into three groups according to the EL treatment sessions between 2009 and 2016: no, 50-99, and 100 or more EL treatments after 2-year washout period (2007 and 2008). Using multivariable Cox proportional hazard models, we found that the risks of actinic keratosis, non-melanoma skin cancers, and melanoma did not significantly differ among the groups, respectively. In conclusion, EL treatment would not increase the risks of premalignant skin lesions and skin cancers in patients with vitiligo. Based on our results, EL is likely to be a safe treatment option for patients with localized vitiligo.

Staphylococcus aureus is among the most common zoonotic pathogens that cause foodborne illnesses worldwide. The main objectives of the current study were therefore to determine the antimicrobial susceptibility profiles of S. aureus isolated from goats in Korea and to investigate the molecular characteristics of identified methicillin-resistant S. aureus (MRSA). In the study, 481 S. aureus isolates (431 from the nasal cavity and 50 from carcass) were recovered from 1146 carcasses and nasal swabs between July 2018 and January 2019. Approximately 82% and 72.6% of nasal and carcass isolates, respectively, were resistant to at least one antimicrobial agent, with the highest rate of resistance to penicillin, followed by resistance to chloramphenicol and tetracycline. Relatively small proportions of the isolates were resistant to cefoxitin, clindamycin, and erythromycin. However, all S. aureus isolates were sensitive to linezolid, rifampin, and vancomycin. Six MRSA isolates were obtained, three each from the nasal cavity and carcass. MRSA isolates were of two sequence types (ST) (ST72 and ST398), three spa types (t664, t324, and t571), and two SCCmec types (IV and V). The ST72 MRSA isolates had identical PFGE profiles. In addition, ST72 MRSA-SCCmec IV isolates carried at least six staphylococcal leukotoxin- and enterotoxin-encoding genes (lukED, seg, sei, sem, sen, seo, and seq). The remaining ST398 isolate carried only the lukED gene and was additionally resistant to eight non–β-lactam antibiotics. To the best of our knowledge, this is the first report of MRSA from goats in Korea. There is a possibility of transmission of MRSA from goat to human or contamination of food products. Therefore, regular microbiological investigation in goats, farms, and slaughterhouses is critical to determine the existence of virulent and multi-drug resistant (MDR) S. aureus and to implement preventive strategies.

Food-producing animals are considered a leading source of human Salmonella infections in Korea. However, there is a lack of comprehensive and up-to-date data regarding the diversity and resistance profiles of Salmonella serotypes in these animals. Therefore, this study aimed to determine the distribution and antimicrobial resistance profiles of Salmonella serotypes isolated from cattle, pigs, and chickens in Korea between 2010 and 2018. A total of 3018 Salmonella isolates were obtained from 16 laboratories/centers participating in the Korean Veterinary Antimicrobial Resistance Monitoring System. Salmonella serotypes were identified from the following isolates: 179 cattle (17 serotypes), 959 pig (45 serotypes), and 1880 chicken (64 serotypes). The most frequent serotypes in cattle (Typhimurium, Salmonella 4,[5],12:i:-, and Schwarzengrund), pigs (Typhimurium, Rissen, and S. 4,[5],12:i:-), and chickens (Enteritidis, Albany, Virchow, and Montevideo) accounted for more than 50% of the total serotypes in the respective animal species. To the best of our knowledge, Salmonella 4,[5],12:i:- has not been identified in cattle in Korea to date. More than 80% of the isolates demonstrated resistance to at least one antimicrobial agent. Multidrug-resistance was found in almost half of the serotypes; the highest proportion in cattle (59.2%), followed by pigs (53.4%), and chickens (45.7%). Significant proportions of the serotypes were resistant to ampicillin, streptomycin, and tetracycline. Ceftiofur and ciprofloxacin resistance rates were the highest in Salmonella isolated from chickens (17.1% and 4.1%, respectively) and cattle (10.1% and 3.9%, respectively) compared to that in pigs. Among the frequent serotypes, Albany demonstrated the highest resistance rate (>90%) to five different antimicrobials. Alarmingly, some Salmonella serotypes that are frequently associated with human infections demonstrated a trend of increasing resistance to critically important antibiotics, including 3rd generation cephalosporins and quinolones. Collectively, the presence of antibiotic-resistant Salmonella in food-producing animals poses a potential risk to public health.

Senescent fibroblasts play a role in aging pigmentation. In this study, we found that GDF15 expression levels are increased in UV-irradiated senescent fibroblasts and photoaged hyperpigmented skin. To investigate the effects of GDF15 on melanogenesis, normal human melanocytes were cocultured with fibroblasts infected with the GDF15 lentivirus or GDF15 short hairpin RNA. It was found that GDF15 stimulates melanogenesis in melanocytes through MITF/tyrosinase upregulation via β-catenin signaling. The stimulatory action of GDF15 during pigmentation was further confirmed in ex vivo cultured skin and in a reconstituted human skin sample. These results suggest that senescent fibroblast-derived GDF15 stimulates skin pigmentation and may play a role in aging-associated pigmentation.

In this study, we found that secreted frizzled-related protein 2 (sFRP2) is overexpressed in the hyperpigmentary skin of melasma and solar lentigo and in acutely UV-irradiated skin. To investigate the effect of sFRP2 on melanogenesis, normal human melanocytes were infected with sFRP2-lentivirus or sh-sFRP2. It was found that sFRP2 stimulates melanogenesis through microphthalmia-associated transcription factor and/or tyrosinase upregulation via β-catenin signaling. The stimulatory action of sFRP2 in pigmentation was further confirmed in melanocytes cocultured with fibroblasts and in ex vivo cultured skin. The findings suggest that sFRP2 functions as a melanogenic stimulator and that it plays a role in the development of UV-induced hyperpigmentary disorders.

Ultraviolet (UV)-associated hyperpigmented skins are characterized with increased vasculature underlying pigmentation, suggestive of the possible biological role of endothelial cells in the regulation of skin pigmentation during UV irradiation. In this study, we showed that UV-irradiated endothelial cells significantly increased the pigmentation of melanocytes through epithelial-mesenchymal crosstalk. The stimulatory effect of endothelial cells was further demonstrated using ex vivo human skin. RNA sequence analysis and enzyme-linked immunosorbent assay showed that endothelial cells secrete more stem cell factor (SCF) upon UV irradiation than non-irradiated cells. The increased pigmentation elicited by endothelial cells was abrogated following inhibition of SCF/c-KIT signaling. Together these results suggest that endothelial cells are activated upon UV exposure to release melanogenic factors such as SCF, which contributes to the development of skin hyperpigmentation during chronic sun exposure.

Recent progress in the understanding non-thermal plasma (NTP) properties prompted its application in the treatment of various diseases. However, therapeutic effect of NTP on keloid cells has not been reported previously. We sought to investigate the effect of NTP treatment on keloid by comparing cell migration and collagen production of keloid (KFs) and normal fibroblasts (NFs) and determined the regulatory pathways involved. We assessed NTP effects on cell migration in KFs and NFs by the wound healing assay and measured the expression of the epidermal growth factor receptor (EGFR), signal transducer and activator of transcription-3 (STAT3), and collagen by western blot. Expression of the transforming growth factor-β and Type I collagen following NTP treatment was determined by reverse transcription-polymerase chain reaction, immunofluorescence staining, and the Sircol collagen assay. NTP treatment increased cell migration and collagen production of NFs. However, it reduced these parameters in KFs. NTP reduced the expression of EGFR, STAT3, and Type I collagen in KFs but increased their levels in NFs. We revealed that NTP suppressed KF cell migration via down-regulation of EGFR and STAT3 and reduced collagen production via supressing transforming growth factor-β. Our data suggest that NTP may be a new therapeutic strategy for keloids.

This study aimed to identify the factors influencing Korean mothers' intentions to vaccinate their daughters against human papillomavirus (HPV). In Korea, a mother's will is a key determinant for daughters receiving the cervical cancer vaccine. The factors influencing mothers' intentions to vaccinate their daughters against HPV were the perceived benefits of the vaccine, having acquaintances with cervical cancer experiences, awareness of the cervical cancer vaccine, believing that one's daughter needs regular Pap smears, and occupation; these variables explained 32% of the variance. The perceived benefits of the vaccine were the strongest predictor of mothers' intentions. The findings of the current study suggested that mothers' perceived benefits about the HPV vaccine play an important role in their choice to vaccinate their daughters.

In this study, we aimed to assess trends in antimicrobial resistance and to investigate the characteristics of extended-spectrum β-lactamase (ESBL)-producing isolates from bovine mastitic milk from 2012 to 2015. A total of 374 Escherichia coli isolates were analyzed (154 in 2012, 113 in 2013, 76 in 2014, and 31 in 2015). No consistent trends in antimicrobial resistance of E. coli isolates occurred during the 4-yr period. The most frequently observed resistance was tetracycline (23.3%), followed by streptomycin (17.1%), ampicillin (16.6%), neomycin (11.8%), and trimethoprim/sulfamethoxazole (11.2%). Multidrug resistance was observed in 15.5% of isolates. Among these isolates, 15 (4.0%) carried one or more blaCTX-M and AmpC ESBL genes from 11 different farms, including blaCTX-M-15 at 4 farms, blaCTX-M-3 at 2 farms, blaCTX-M-1 at 3 farms, and blaCMY-2 at 3 farms. This study is the first report of blaCTX-M-3-producing E. coli in dairy milk. Transfer of ESBL was observed in 3 blaCTX-M-3-producing isolates, 1 blaCTX-M-1-producing isolate, and all 3 blaCMY-2-producing isolates. Almost all blaCTX-M-15 and blaCTX-M-1 genes possessed an insertion sequence, ISECP1, upstream of the blaCTX-M gene. Identical pulsed-field gel electrophoresis profiles were also observed in blaCTX-M-producing E. coli from the same farm. These results suggested that ESBL might spread by both clonal and horizontal spread in dairy farms in South Korea. Although no significant changes occurred in the antimicrobial resistance of E. coli during the 4-yr study period, the resistance rates and presence of ESBL were high compared with those in other countries. Thus, these findings suggest the importance of control measures for E. coli, particularly ESBL-producing bacteria, on dairy farms to reduce treatment failure and transmission to humans.

Background Magnetic resonance imaging (MRI) is a useful tool to predict the diagnosis and progression of Alzheimer's disease (AD), especially for primary physicians. However, the correlation between baseline MRI findings and AD progression has not been fully established. Objective To investigate the correlation between hippocampal atrophy (HA) and white matter hyperintensities (WMH) on initial brain MRI images and the degree of cognitive decline and functional changes over 1 year. Methods In this prospective, 12-month observational study, dementia outpatients were recruited from 29 centers across South Korea. Baseline assessments of HA and WMH on baseline brain MRI were derived as well as cognitive function, dementia severity, activities of daily living, and acetylcholinesterase inhibitor (AChEI) use. Follow-up assessments were conducted at 6 and 12 months. Results Among 899 enrolled dementia patients, 748 were diagnosed with AD of whom 654 (87%) were taking AChEIs. Baseline WMH showed significant correlations with age, current alcohol consumption, and Clinical Dementia Rating score; baseline HA was correlated with age, family history, physical exercise, and the results of cognitive assessments. Among the AChEI group, changes in the Korean version of the Instrumental Activities of Daily Living (K-IADL) were correlated with the severity of HA on baseline brain MRI, but not with the baseline severity of WMH. In the no AChEI group, changes in K-IADL were correlated with the severity of WMH and HA at baseline. Conclusion Baseline MRI findings could be a useful tool for predicting future clinical outcomes by primary physicians, especially in relation to patients' functional status.

Purpose The Korean Triage and Acuity Scale (KTAS) is a tool used to classify the severity and urgency of emergency department (ED) patients, focusing on their symptoms. In consideration of the importance of the KTAS, a web-based learning program has emerged as a new mode of education; it enables ED triage nurses to access it anytime and anywhere, and according to their own learning abilities. This study aimed to develop a web-based KTAS learning program and evaluate its effects on self-efficacy and triage performance ability in ED nurses. Methods A quasi-experimental design with a non-equivalent control group pretest-posttest was used. The conceptual framework was Bandura's self-efficacy theory. There were 30 participants in the experimental group and 29 in the control group. The experimental group attended an orientation and 4 sessions of a web-based KTAS learning program. The learning program lasted 280 minutes over five weeks, consisting of 40 minutes of orientation and four 60-minute sessions. Results The scores of self-efficacy, triage performance ability in KTAS level, and chief complaints significantly increased in the experimental group compared to the control group. In addition, the numbers of under-triage in KTAS significantly decreased in the experimental group in comparison to the control group. Conclusion The results suggest that the learning program was effective in improving ED nurses' level of self-efficacy and triage performance ability (KTAS level and KTAS chief complaint). Accordingly, the web-based KTAS learning program can be applied as an education intervention to improve ED nurses' triage skill.

Inflammatory cytokines are closely related to pigmentary changes. In this study, the effects of IFN-γ on melanogenesis were investigated. IFN-γ inhibits basal and α-MSH-induced melanogenesis in B16 melanoma cells and normal human melanocytes. MITF mRNA and protein expressions were significantly inhibited in response to IFN-γ. IFN-γ inhibited CREB binding to the MITF promoter but did not affect CREB phosphorylation. Instead, IFN-γ inhibited the association of CBP and CREB through the increased association between CREB binding protein (CBP) and STAT1. These findings suggest that IFN-γ inhibits both basal and α-MSH-induced melanogenesis by inhibiting MITF expression. The inhibitory action of IFN-γ in α-MSH-induced melanogenesis is likely to be associated with the sequestration of CBP via the association between CBP and STAT1. These data suggest that IFN-γ plays a role in controlling inflammation- or UV-induced pigmentary changes.

Wnt signaling plays a role in the differentiation as well as the development of melanocytes. Using a microarray analysis, hyperpigmentary skin of melasma expressed high levels of Wnt inhibitory factor-1 (WIF-1) compared with perilesional normal skin. In this study, the expression and functional roles of WIF-1 on melanocytes were investigated. WIF-1 was expressed both in the melanocytes of normal human skin and in cultured melanocytes. The upregulation of WIF-1 on cultured normal human melanocytes significantly induced expressions of MITF and tyrosinase, which were associated with increased melanin content and tyrosinase activity. Consistent with the stimulatory effect of WIF-1, WIF-1 siRNA reduced melanogenesis in the cells. Moreover, WIF-1 increases pigmentation in melanocytes co-cultured with WIF-1-overexpressed fibroblasts and of organ-cultured human skin. These findings suggest that melanocytes express WIF-1 constitutively in vivo and in vitro and that WIF-1 promotes melanogenesis in normal human melanocytes.

Background Patients with infantile nephropathic cystinosis have progressive accumulation of cystine in tissues leading to delayed extrarenal complications. No simple tool is available to evaluate the level of body cystine accumulation. Objective We sought to determine the value of in vivo reflectance confocal microscopy of the skin in patients with infantile nephrogenic cystinosis. Methods Nine patients and control subjects were recruited for this study. Images were acquired by means of a near-infrared reflectance confocal laser scanning microscope. Results Scattered bright particles within the papillary dermis were observed in all patients but not in control subjects. The density of particles ranged from numerous (+++) to very few (+/–) and their distribution was heterogeneous. Electron microscopy confirmed that these particles corresponded to cystine crystal deposits within dermal fibroblasts. The density of cystine crystals within the dermis was greater in older patients, in patients with a high leukocyte cystine concentration, and with delayed cysteamine therapy. There was no correlation between the density of cystine deposits and renal disease or hypopigmentation but high levels of deposition occurred in association with extrarenal manifestations. Limitations This is a preliminary study on a small sample of patients. Repeated examination and longer follow-up is necessary. Conclusion In vivo reflectance confocal microscopy of the skin appears to be a noninvasive means of assessing body cystine accumulation in infantile cystinosis and could be used as a complementary marker of treatment response in addition to leukocyte cystine measurement.

Aquarobics, a combination of the words aqua and aerobics, is based on the idea that much more energy is consumed during exercise when resisting water rather than air. The aquarobic exercise program is composed of patient education and aquarobic exercise. The program was effective in enhancing self-efficacy, decreasing pain, and improving depression levels, body weight, and blood lipid levels in patients with osteoarthritis. Therefore, this program can be widely used in a community setting for the management of osteoarthritis.

Interferon α (IFN-α) is a cytokine, produced predominantly in immune cells in response to pathogens, which interferes with viral replication in host cells. Another cytokine hormone, erythropoietin (EPO), is synthesized in interstitial fibroblasts of the kidney and acts as a stimulator for the production of red blood cells. Importantly, the two cytokines have been used in the treatment of certain hematological malignancies, including renal anemia. In the production of recombinant proteins, a transgenic expression system in bovine species is an efficient strategy for pharmaceutical production. In the present study, recombinant constructs capable of producing recombinant human IFN-α and EPO proteins were established and were generated containing the mammary gland-specific αS1-casein promoter region (between -175 and + 796 nt), as this promoter was revealed to have the highest level of activity in a previous promoter study. In order to minimize developmental toxicity by constitutive exogenous expression, a doxycycline (dox)-inducible system was introduced to the IFN-α/EPO-expressing constructs. Therefore, a unitary tetracycline (tet)-on the IFN-α/EPO vector was established, which combined a tet-on activator cassette controlled by the αS1-casein promoter, with a responder cassette encoding the IFN-α/EPO gene, controlled by the tetracycline response element (TRE) promoter. In these systems, the tet-controlled transactivator is affected by mammary gland-specific αS1-casein promoter, and binding of the transcriptional activator to the TRE results in transcription of the downstream IFN-α/EPO genes in the presence of dox. To assess this, the unitary tet-on IFN-α/EPO vector was introduced into a bovine mammary gland cell line (MAC-T), and the cells were then treated with 0.1-1 µg/ml dox. A marked increase was observed in the expression levels of IFN-α/EPO. In addition, bovine transgenic fibroblasts containing a mammary gland-specific and dox-inducible IFN-α/EPO construct were generated. These transgenic fibroblasts may provide a source for somatic cell nuclear transfer for the generation of transgenic cattle producing recombinant human IFN-α/EPO protein during lactation.

Melasma is a commonly acquired hyperpigmentary disorder of the face, but its pathogenesis is poorly understood and its treatment remains challenging. We conducted a comparative histological study on lesional and perilesional normal skin to clarify the histological nature of melasma. Significantly, higher amounts of melanin and of melanogenesis-associated proteins were observed in the epidermis of lesional skin, and the mRNA level of tyrosinase-related protein 1 was higher in lesional skin, indicating regulation at the mRNA level. However, melanocyte numbers were comparable between lesional and perilesional skin. A transcriptomic study was undertaken to identify genes involved in the pathology of melasma. A total of 279 genes were found to be differentially expressed in lesional and perilesional skin. As was expected, the mRNA levels of a number of known melanogenesis-associated genes, such as tyrosinase, were found to be elevated in lesional skin. Bioinformatics analysis revealed that the most lipid metabolism-associated genes were downregulated in lesional skin, and this finding was supported by an impaired barrier function in melasma. Interestingly, a subset of Wnt signaling modulators, including Wnt inhibitory factor 1, secreted frizzled-related protein 2, and Wnt5a, were also found to be upregulated in lesional skin. Immunohistochemistry confirmed the higher expression of these factors in melasma lesions.

Background The histological findings associated with idiopathic guttate hypomelanosis (IGH) are hyperkeratosis, an atrophic epidermis, and flattened rete ridges. In addition, a decreased melanin content and reduced numbers of melanocytes are reported features. However, there are few recent studies that have been published on the histopathology of IGH and no comparative studies are available on the skin lesions and perilesional skin of patients with IGH. Objectives The goals of this study were to identify the clinical and histopathological features of IGH and determine their correlation. We evaluated the clinical features and the histopathological differences between the skin lesions and the perilesional skin in patients with IGH. Methods A clinical survey was carried out on 47 patients with IGH. Specimens from skin lesions and perilesional skin were stained with hematoxylin-eosin, Fontana–Masson, MART-1, and NKI/beteb. We also studied the ultrastructure of four cases. Results About 30% of the patients had their initial lesions prior to 20 years of age. The arm was the most commonly affected site (53%). Histologically, we found hyperkeratosis in 18 cases (38.3%), but epidermal atrophy was present in only five cases (10.6%), and flattened rete ridges in seven cases (14.9%) compared to the normal skin. Epidermal atrophy was more frequently found at nonsun-exposed areas. The IGH lesions demonstrated decreased melanin pigment and reduced numbers of melanocytes by NKI/beteb and MART-1. The ultrastructural evaluation showed degenerative melanocytes and decreased melanosomes. One specimen had normal melanocytes with decreased melanosomes. Conclusions Idiopathic guttate hypomelanosis is a disorder with multifactorial etiology; its pathogenesis may depend on various factors such as patient age and sun-exposure. Histopathologically, hyperkeratosis was frequently found; however, the other characteristic findings such as epidermal atrophy and flattened rete ridges were relatively rare.

TMPRSS4 is a novel type II transmembrane serine protease that is highly expressed on the cell surface in pancreatic, thyroid and other cancer tissues, although its oncogenic significance and molecular mechanisms are unknown. Previously, we have shown that TMPRSS4 promotes invasion, migration and metastasis of human tumor cells by facilitating an epithelial-mesenchymal transition (EMT). In this study, we explored the molecular basis underlying TMPRSS4-mediated effects. We show that multiple downstream signaling pathways, including focal adhesion kinase (FAK), extracellular signal-regulated kinase (ERK), Akt, Src and Rac1, are activated by TMPRSS4 expression and that FAK signaling and ERK activation are required for TMPRSS4-induced invasiveness and EMT, including cadherin switch. Inhibition of PI3K or Src reduced invasiveness and actin rearrangement mediated by TMPRSS4 without restoring E-cadherin expression. Downregulation of E-cadherin was required for TMPRSS4-mediated effects but was not sufficient to induce EMT and invasion. TMPRSS4 induced integrin alpha5 expression and its signal transduction, leading to invasiveness and EMT accompanied by downregulation of E-cadherin. Functional blocking confirmed that integrin alpha5beta1 is a critical signaling molecule that is sufficient to induce TMPRSS4-mediated effects. Immunohistochemical analysis showed that TMPRSS4 expression was significantly higher in human colorectal cancer tissues from advanced stages than in that of early stage. Furthermore, upregulation of TMPRSS4 was correlated with enhanced integrin alpha5 expression. These observations implicate integrin alpha5 upregulation as a molecular mechanism by which TMPRSS4 induces invasion and contributes to cancer progression.

Development of vitiligo-like hypopigmentary lesions associated with topical imiquimod has been reported. We hypothesized that mode of action of imiquimod in melanocytes may include triggering of apoptosis resulted in loss of cells, which may be a possible mechanism of imiquimod-induced hypopigmentary lesions. Therefore, we investigated whether imiquimod induces apoptosis of human melanocytes and also whether it modulates expression of apoptosis-related molecules in human melanocytes. Imiquimod treatment induced apoptosis of melanocytes, which was observed by TUNEL assay and Hoechst 33258 staining. Imiquimod-induced apoptosis was further shown by measuring mitochondrial membrane potential in melanocytes. The apoptotic activity of imiquimod was associated with caspase-3, Bcl-2 and mitogen-activated protein kinase expression in melanocytes. These results indicated that imiquimod induces apoptosis of melanocytes. These findings may provide a clue to understand pathogenesis of imiquimod-induced vitiligo-like hypopigmentary lesions.

Summary Background. Pityriasis alba (PA) is a skin disorder characterized by asymptomatic, variably hypopigmented, slightly scaling patches with indistinct margins. It is sometimes difficult to clinically differentiate PA from other hypopigmented disorders such as naevus depigmentosus. Aim. To examine the clinical and histopathological characteristics of PA that are important in differentiating PA from other hypopigmenting disorders. Methods. A clinical survey was carried out on 56 patients with PA. Histopathological features were investigated with immunostains for NKI/beteb antibody, melanoma antigen recognized by T cells (MART)-1 and S-100 protein, and by haematoxylin and eosin and Fontana–Masson stains. Results. Of the 56 PA patients, 10 (18%) had a previous history of atopic dermatitis and 9 (16%) had a solitary lesion. Histopathological study revealed markedly reduced pigment in the epidermis of lesional skin, but no significant difference in melanocyte count was found between lesional and normal skin. Ultrastructurally, degenerative changes in melanocytes and a reduced number of melanosomes within keratinocytes were seen. Conclusion. No significant difference in the number of melanocytes between lesional and normal skin was seen. These findings should be considered when diagnosing and differentiating PA from other hypopigmentary disorders.

In this study, we identified extended-spectrum beta-lactamase (ESBL) and plasmid-mediated AmpC beta-lactamase which were associated with 16S rRNA methylase gene on the conjugative plasmid. Among 82 clinical isolates of Enterobacteriaceae that carry 16S rRNA methylase gene (64 strains, armA, and 18 strains, rmtB), bla(SHV-12) was detected either alone or combined with bla(DHA-1), bla(CTX-M-3), and bla(CTX-M-14) in 30 strains carrying armA and 6 strains carrying rmtB. The bla(CTX-M-3) was detected in 13 of 64 strains carrying armA but no strains carrying rmtB. Whereas bla(CTX-M-14) was detected in 15 of 18 strains carrying rmtB but only 2 of 64 strains carrying armA. Overall, bla(SHV-12) and bla(CTX-M-14) was the most common ESBL gene which was associated with armA and rmtB, respectively. In addition, we found that bla(CTX-M-3) localized with armA on the same IncL/M plasmid and bla(CTX-M-14) localized with rmtB on the same IncA/C plasmid. Restriction fragment length polymorphism of conjugative plasmids and pulsed-field gel electrophoresis of genomic DNAs revealed that intercellular horizontal transfer of conjugative plasmid and clonal transmission have been occurred at the same time.

Cholesterol has been suggested to regulate cell differentiation. In this study, we have examined the effects of cholesterol modulation on pigmentation of skin using a treatment with methyl-beta-cyclodextrin (MbetaCD), a specific cholesterol-binding agent. Treatment with MbetaCD reduced pigmentation in human melanocyte and cultured skin. This decrease in pigmentation was related to the inhibition of the expression of tyrosinase and microphthalmia-associated transcription factor of melanocytes. Stimulation of melanocytes with MbetaCD led to the time-dependent phosphorylation of extracellular signal-regulated kinase (ERK). Furthermore, ERK functionally regulated the MbetaCD-induced melanin formation in melanocytes; a ERK inhibitor, PD98059, almost completely attenuated the MbetaCD-mediated inhibition of melanin synthesis and down-regulation of MITF and tyrosinase expression. These results suggest that cholesterol reduction by MbetaCD inhibit melanin synthesis via ERK activation and subsequent MITF downregulation.