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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.

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.

Lespedeza bicolor (L. bicolor) is used for medicinal purposes because of its various biological and pharmacological activities. In this study, the effects of L. bicolor ethanol extract on the treatment of vitiligo were investigated. The determination of melanin content in melanocytes was measured using B16 melanoma cells and C57BL/6J Ler-vit/vit mice. Finally, the quercetin content in L. bicolor were qualitatively analyzed using HPLC. The results obviously indicated that the L. bicolor extract enhanced melanogenesis and increased tyrosinase activity in cultured melanoma cells and C57BL/6J Ler-vit/vit mice. Treatment with L. bicolor extract led to a higher content of melanin and eumelanin in C57BL/6J Ler-vit/vit mice hair than in control (untreated) mice, which demonstrated the therapeutic effect of hair-graying associated with vitiligo. There was a notable increase in melanocytes in the skin of C57BL/6J Ler-vit/vit mice treated with L. bicolor extract compared with the control. L. bicolor extract was a potent tyrosinase and melanin synthesis activator in B16 melanoma cells. C57BL/6J Ler-vit/vit mice treated with L. bicolor extract had significantly higher melanin content in hair than the untreated control. The results suggest that L. bicolor extract is a potential alternative treatment for improvement of vitiligo.

Coagulase-negative staphylococci (CNS) are one of the most common bovine mastitis pathogens found worldwide. In this study, we investigated the prevalence and distribution of CNS species in mastitis milk samples and further characterized the methicillin-resistant (MR) CNS. A total of 311 CNS were isolated from 3,692 quarter milk samples from 1,373 dairy cattle at 81 farms between 2013 and 2017. Further evaluation of the CNS isolates revealed 14 CNS species among the samples and 3 predominant species-namely, Staphylococcus chromogenes, Staphylococcus simulans, and Staphylococcus epidermidis. Resistance was higher in S. epidermidis than in other CNS species except for resistance against oxacillin in Staphylococcus sciuri. Resistance to β-lactams was the most common in all CNS species (8.4% in ampicillin, 21.2% in oxacillin, and 13.5% in penicillin). Conversely, only minimal resistance to cephalothin, ceftiofur, and pirlimycin/novobiocin was found. Twenty-one isolates from 4 species were mecA-carrying MRCNS strains, including 18 S. epidermidis and 1 each of S. sciuri, Staphylococcus equorum, and Staphylococcus hominis. The majority of the mecA-carrying MRCNS isolates were produced in the biofilm. Furthermore, multidrug-resistant sequence type 179 isolate produced the strongest biofilm. Seven genotypes were detected in the 18 MR S. epidermidis strains, the most predominant of which persisted on a farm for 2 yr. Our findings for the antimicrobial susceptibility profiles and genotypic characterization of the MRCNS isolates could provide valuable information for controlling the spread of resistance and the selection of appropriate antimicrobial therapies for mastitis in the future. Further, strategic antibiotic use for mastitis treatment and hygienic management practices aimed at the prevention of the growth of resistant bacteria are urgently needed on dairy farms.

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.

Alzheimer’s disease (AD) is the most predominant age-related neurodegenerative disease, pathologically characterized by the accumulation of aggregates of amyloid beta Aβ1–42 and tau hyperphosphorylation in the brain. It is considered to be the primary cause of cognitive dysfunction. The aggregation of Aβ1–42 leads to neuronal inflammation and apoptosis. Since vitamins are basic dietary nutrients that organisms need for their growth, survival, and other metabolic functions, in this study, the underlying neuroprotective mechanism of nicotinamide (NAM) Vitamin B3 against Aβ1–42 -induced neurotoxicity was investigated in mouse brains. Intracerebroventricular (i.c.v.) Aβ1–42 injection elicited neuronal dysfunctions that led to memory impairment and neurodegeneration in mouse brains. After 24 h after Aβ1–42 injection, the mice were treated with NAM (250 mg/kg intraperitoneally) for 1 week. For biochemical and Western blot studies, the mice were directly sacrificed, while for confocal and “immunohistochemical staining”, mice were perfused transcardially with 4% paraformaldehyde. Our biochemical, immunofluorescence, and immunohistochemical results showed that NAM can ameliorate neuronal inflammation and apoptosis by reducing oxidative stress through lowering malondialdehyde and 2,7-dichlorofluorescein levels in an Aβ1–42-injected mouse brains, where the regulation of p-JNK further regulated inflammatory marker proteins (TNF-α, IL-1β, transcription factor NF-kB) and apoptotic marker proteins (Bax, caspase 3, PARP1). Furthermore, NAM + Aβ treatment for 1 week increased the amount of survival neurons and reduced neuronal cell death in Nissl staining. We also analyzed memory dysfunction via behavioral studies and the analysis showed that NAM could prevent Aβ1–42 -induced memory deficits. Collectively, the results of this study suggest that NAM may be a potential preventive and therapeutic candidate for Aβ1–42 -induced reactive oxygen species (ROS)-mediated neuroinflammation, neurodegeneration, and neurotoxicity in an adult mouse model.

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.

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.

An endogenous metabolite of 17β-estradiol, 2-methoxyestradiol (2-ME), has affinity for estrogen receptors. This compound was reported to be a promising antitumor drug due to its anti-proliferative effects on a wide range of tumor cell types. Numerous previous studies have been performed to evaluate the cytotoxic effects of 2-ME on tumor cell lines in following the induction of G2/M cell cycle arrest and subsequent apoptosis. Uterine leiomyosarcoma (ULMS) is a relatively rare malignant smooth muscle cell tumor that develops in the uterus muscle layer. The aim of the present study was to examine the in vitro anti-proliferative effects of 2-ME on SK-LMS-1 human leiomyosarcoma cells. An MTT assay, terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling assay, immunocytochemistry and western blotting were performed. A high concentration (10-5 M) of 2-ME was identified to have an anti-proliferative effect on SK-LMS-1 cells. Additionally, expression of the apoptosis markers was upregulated in the presence of 10-5 M 2-ME, according to western blot analysis. Furthermore, the expression level of an autophagic marker, light chain 3, was increased by 2-ME treatment in a dose-dependent manner. This was associated with cell death induced by the upregulation of phosphorylated extracellular-signal-regulated kinase 1/2 signaling pathway. The results of the present study demonstrated that 2-ME, which is used as a therapeutic agent for treating solid tumors, exhibits apoptotic and anti-proliferative effects depending on the dose. Therefore, 2-ME may be a potential therapeutic reagent for human ULMS, but the appropriate dose of this compound should be carefully selected.

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.

Standardized methodologies for describing and classifying vitiligo and for assessing the effect of treatments are needed to be developed. Currently, there are many noninvasive techniques available for diagnosis and assessment of vitiligo. Objective measurements of vitiligo area using digital image analysis are available. Noninvasive instruments such as reflectance spectroscopy or dermoscopy are methods to characterize and study vitiligo lesion. The Vitiligo European Task Force (VETF) recommends Wood’s light examination as a diagnostic tool in evaluating vitiligo to assess staging and spreading in a selected area. More reliable and quantitative measures to augment clinical judgment of vitiligo assessment include image analysis of digital photographs. The digital image analysis system can overcome the inevitable differences between observers, which are intrinsic to a visual grading method, and is advisable for clinical trials on vitiligo to objectively assess repigmentation in limited lesions (Linthorst Homan MW et al. J Eur Acad Dermatol Venereol 27(2):e235–238, 2013). However, this technique needs to be properly validated.

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.

Background: The differential diagnosis of psoriasis and seborrheic dermatitis can be difficult when both conditions are localized to the scalp without the involvement of other skin sites. Objective: We aimed to evaluate the histopathological differences between psoriasis and seborrheic dermatitis on the scalp and identify favorable criteria for their differential diagnosis. Methods: We evaluated 15 cases of psoriasis and 20 cases of seborrheic dermatitis of the scalp that had been clinicopathologically diagnosed. Skin biopsy sections stained with H&E were examined. Additional immunohistochemistry was performed, including Ki-67, keratin 10, caspase- 5, and GLUT-1. Results: On histopathological examination, mounds of parakeratosis with neutrophils, spongiform micropustules of Kogoj, and clubbed and evenly elongated rete ridges were significantly more frequently observed in psoriasis. Follicular plugging, shoulder parakeratosis and prominent lymphocytic exocytosis were significantly more common in seborrheic dermatitis. Moreover, significantly higher mitotic figures were observed in psoriatic lesions than in seborrheic dermatitis. Immunohistochemistry did not show any difference between psoriasis and seborrheic dermatitis. Conclusion: Histopathological features favoring psoriasis include mounds of parakeratosis with neutrophils, spongiform micropustules of Kogoj, clubbed and evenly elongated rete ridges, and increased mitotic figures (≥ 6/high-powered field). Features indicating seborrheic dermatitis are follicular plugging, shoulder parakeratosis and prominent lymphocytic exocytosis. Immunohistochemistry was not helpful in differentiating psoriasis from seborrheic dermatitis. (Ann Dermatol 28(4) 427∼432, 2016)

Humans are at daily risk by simultaneous exposures to a broad spectrum of man-made chemicals in the commercial products. Several classes of chemicals have been shown to alter follicle development and reduce fertility, leading to premature ovarian failure (POF) in mammals. We investigate the synergistic effects of 4-vinylcyclohexene diepoxide (VCD) and phthalate, including di(2-ethylhexyl) phthalate (DEHP), butyl benzyl phthalate (BBP) and di-n-butyl phthalate (DBP) on POF. Combination exposure with VCD and phthalate significantly reduced the numbers of primary follicles. The expressions of Amh and Sohlh2 were significantly decreased in the combination groups. Serum Amh levels were significantly lower in the combination groups. Additionally, serum levels of follicle-stimulating hormone were significantly increased in combination groups. Taken together, exposure to phthalates promotes the depletion of follicular follicles and consequently increases the risk of premature menopause, and combined exposure of phthalates and VCD to early menopausal women is likely to aggravate the POF syndrome.

Melasma is a common acquired hyperpigmentary disorder of the face mostly in women with darker skin types. Chronic sun exposure, genetic influences, and female sex hormones have been addressed as major etiological factors. The pathogenesis of melasma is not fully understood, but current studies suggest that endogenous or exogenous stimuli may stimulate the microenvironment, leading to the release of various mediators that activate melanocytes in the development of melasma. In melasma skin, not only melanocytes but other actors, especially dermal components such as photoaged fibroblasts or vasculature, most likely play a key role in the development and in relapses of melasma. Treatment of melasma is difficult because it is recalcitrant to therapy and frequently recurs, even after successful clearance. There are various treatment options, usually in combination with topical depigmenting agents, laser or light therapies, as well as systemic tranexamic acid.

Background Confluent and reticulated papillomatosis (CRP) is an uncommon dermatosis with a reticular pattern. As differentiation between CRP and benign acanthosis nigricans (AN) can be challenging because of their similar clinicopathological features, we aimed to distinguish the two diseases. Methods We retrospectively reviewed the clinical characteristics of 60 CRP and 30 AN patients. Histological examinations were conducted on 33 CRP and 30 AN lesions. Results While CRP was concentrated on the trunk, AN mostly appeared in the axilla. In the AN group, the number of obese patients was higher, and acanthosis and papillomatosis were more evident. In both group, increases in Ki-67 and keratin 16 expression were similar. Bacterial infection was detected at a higher rate in CRP lesions than in AN lesions.AN lesions had greater pigmentation because of a high number of melanocytes than CRP lesions. Conclusions The location of skin lesions and body mass index are the main clinical factors that enable differentiation between CRP and AN. The epidermal histological changes in CRP are milder than those in AN. AN lesions also showed a greater degree of pigmentation and melanocytic proliferation.

Cortisol is a steroid hormone essential to the maintenance of homeostasis that is released in response to stress and low blood glucose concentration. Cortisol is converted from cortisone by 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1). It has been reported that too much cortisol or overexpression of HSD11B1 induces obesity and the insulin resistance that accompanies metabolic syndrome in rodent adipose tissue. In our previous study, HSD11B1-transgenic (TG) fibroblasts were established, and a porcine model was generated by SCNT using those fibroblasts. Hepatocytes overexpressing HSD11B1 were obtained from livers of this porcine model and cultured in vitro. However, the primary hepatocytes were found to have a short life span or low proliferation rate. To overcome these problems, the SV40 large T antigen was transduced into primary HSD11B1-TG hepatocytes, and those cells were immortalized. Immortalized HSD11B1-TG hepatocytes showed restored morphology, more rapid proliferation rate, and more expression of HSD11B1 than primary hepatocytes. As well, these cells kept the hepatic characteristics such as gluconeogenic response to cortisone and increased expression of hepatic makers. The immortalized HSD11B1-TG hepatocytes may be useful for studying traits and potential therapeutic drugs for treatment of metabolic disorders induced by overexpression of HSD11B1.

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.

Parabens are widely used preservatives in basic necessities such as cosmetic and pharmaceutical products. In previous studies, xenoestrogenic actions of parabens were reported in an immature rat model and a rat pituitary cell line (GH3 cells). The relationship between parabens and ovarian failure has not been described. In the present study, the influence of parabens on ovarian folliculogenesis and steroidogenesis was investigated. A disruptor of ovarian small pre-antral follicles, 4-vinylcyclohexene diepoxide (VCD, 40 mg/kg), was used to induce premature ovarian failure (POF). Methylparaben (MP, 100 mg/kg), propylparaben (PP, 100 mg/kg), and butylparaben (BP, 100 mg/kg) dissolved in corn oil were treated in female 8-week-old Sprague-Dawley rat for 5 weeks. Estrus cycle status was checked daily by vaginal smear test. Ovarian follicle development and steroid synthesis were investigated through real-time PCR and histological analyses. Diestrus phases in the VCD, PP, and BP groups were longer than that in the vehicle group. VCD significantly decreased mRNA level of folliculogenesis-related genes (Foxl2, Kitl and Amh). All parabens significantly increased the Amh mRNA level but unchanged Foxl2 and Kitlg acting in primordial follicles. VCD and MP slightly increased Star and Cyp11a1 levels, which are related to an initial step in steroidogenesis. VCD and parabens induced an increase in FSH levels in serum and significantly decreased the total number of follicles. Increased FSH implies impairment in ovarian function due to VCD or parabens. These results suggest that VCD may suppress both formation and development of follicles. In particular, combined administration of VCD and parabens accelerated inhibition of the follicle-developmental process through elevated AMH level in small antral follicles.

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.

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.

The purpose of this study was to develop a scenario suited for our clinical situations and evaluate the application possibility by evaluating students` problem solving ability and learning satisfaction in simulation learning. This study consisted of contents which could be applied for varied situations such as complications and symptoms related to liver cirrhosis, looking into hyperkalemia symptoms of patients with liver cirrhosis in emergency unit. The stage of developing scenario was organized in the order of setting simulation learning objectives and situations of scenario, making algorithm, writing checklists of clinical performance appraisal, and debriefing. The scenario was constructed with monitor setting(actions), patient/mannequin(actions), expected interventions(events), and cues in chronological order, according to the scenario progression outline of Jeffries (2007). The scenario was used in 2011, consisting of 4-5 people per group of 53 senior nursing students who registered for `clinical performance appraisal` course. The problem solving ability improved from a score of 4.05 before simulation learning to a score of 4.30 after simulation learning (t

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.

Purpose: This study was done to evaluate the effects of dementia education program on knowledge and attitude toward dementia among nursing students. Methods: A non-equivalent control group pre-post test design with an experimental group (n

Resume Dans les populations asiatiques, les anomalies pigmentaires sont une composante du vieillissement cutane beaucoup plus importante que les rides. Parmi les hyperpigmentations faciales, le melasma est tres frequent chez les Asiatiques. Les anomalies du derme et les alterations de la membrane basale jouent probablement un role dans le developpement de l’hyperpigmentation epidermique du melasma. Les pigmentations de nature dermique sont assez frequentes chez les Asiatiques. La melanose bilaterale du cou est une maladie particuliere, de localisation dermique, qu’on observe sur la nuque chez les femmes autour de la menopause. Elle est caracterisee par une accumulation importante de pigment melanique dans le derme, associe a un infiltrat inflammatoire lymphocytaire perivasculaire. Cette maladie pourrait appartenir au spectre de la melanose de Riehl. Des traumatismes mineurs ou de nature inflammatoire pourraient etre en cause dans ce type de pigmentation.

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.

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.

Dear Editor: Lymphedema is a common sequelae after cancer surgery with lymph node dissection1. A lymphedematous limb, which is prone to the development of infections or tumors, suggests an alteration in regional immune competence2. Neutrophilic dermatosis on postmastectomy lymphedema (NDPL) is a newly suggested disease by Demitsu and Tadaki3 It is also referred to as localized Sweet's syndrome (SS) because of the histological similarities between the two conditions4. Herein, we report additional cases of neutrophilic dermatosis confined within a lymphedematous site and a review of the disease entity. All three cases involved female patients, two of whom were breast cancer patients who underwent modified radical mastectomy with axillary lymph node dissections (Table 1). The third patient had undergone radical hysterectomy with pelvic lymph node dissection for cervical cancer. Lymphedema was confined to the lymphnode-dissected limb developed in all three patients after the surgery. All of them rapidly developed erythematous rashes on their lymphedematous limb (Fig. 1A, B). Skin biopsy revealed marked papillary dermal edema and dense dermal neutrophil infiltrates, consistent with the histopathologic features of SS (Fig. 1C, D). The laboratory findings, including white blood cell count, percentage of neutrophils, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), were within the normal ranges, except in case 3 (ESR: 35 mm/h; CRP: 4.09 mg/dl). Each case was treated with topical or oral corticosteroid, or oral antibiotics. In case 3, the lesion recurred rapidly after initially being treated with oral antibiotics. After the administration of oral corticosteroid, the lesion rapidly resolved within 1 week. On the basis of the characteristic distribution of the lesion and the histopathologic features, a diagnosis of 'neutrophilic dermatosis on the lymphedematous area' was made. Fig. 1 (A) Case 1. Multiple variable-sized erythematous papules, vesicles, and plaques localized on the right lymphedematous arm. (B) Case 3. Multiple erythematous papules and patches confined on the left lymphedematous leg. (C, D) Histopathological findings. ... Table 1 Clinical characteristics of the three cases Neutrophilic dermatosis or SS localized on the area of lymphedema is rare, and only 11 cases have been reported1,3,4. The clinical presentations of previously reported cases were erythematous papules, plaques, and vesicles on the lymphedematous arm after a mastectomy, which are consistent with our cases1,3,4. The pathomechanism cannot be fully demonstrated; however, the vulnerability of the lymphedematous area seems to be the main factor1,2,5. The stasis of protein-rich lymphatic fluid contains numerous cytokines that might attract neutrophils and also result in the impairment of immune surveillance2,5. Because this dermatosis shows typical clinicohistopathological findings of SS, they are considered a localized variant of SS4. However, other systemic presentations, such as leukocytosis, neutrophilia, or fever, were less frequent than in typical SS. Therefore, several other reports suggested the use of the new term NDPL1,3. Other clinical differential diagnosis included cellulitis or erysipelas. Contrary to cellulitis or erysipelas, the lesion was confined only to the lymphedematous area and was well treated with oral or topical corticosteroid1,4. Although the 11 reports to date were cases of a lesion on a lymphedematous arm after a mastectomy, our report includes one case of a lesion that had developed on the lymphedematous leg after a hysterectomy for cervical cancer. Consequently, our cases suggest a novel point that a lesion could develop on any lymphedematous limb after lymph node dissection. Therefore, we suggest the term 'neutrophilic dermatosis on the lymphedematous area' rather than NDPL.

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.

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.

Melasma is a frequent pigmentary disorder caused by abnormal melanin deposits in the skin. In vivo reflectance confocal microscopy (RCM) is a repetitive imaging tool that provides real-time images of the skin at nearly histological resolution. As melanin is the strongest endogenous contrast in human skin, pigmentary disorders are the most suitable candidates for RCM examination but RCM features of melasma have never been reported. This study investigates the pilot use of RCM in melasma to provide a set of well-described morphological criteria with histological correlations. RCM images were acquired from melasma skin and compared to adjacent control skin in 26 patients. Skin biopsies were obtained from eight patients. In the epidermis, RCM showed in all patients a significant increase in hyperrefractile cobblestoning cells. These cells corresponded to hyperpigmented basal keratinocytes in histology. In six patients, dendritic cells corresponding to activated melanocytes were also found in the epidermis. In the dermis, RCM identified in nine patients plump bright cells corresponding to melanophages. Interestingly, for a given patient, the topographic distribution of melanophages in melasma lesions was very heterogeneous. RCM also showed a significant increase in solar elastosis and blood vessels in the dermis. RCM is a non-invasive technique that detects pigmentary changes in melasma at a cellular level resolution. Therefore, RCM provides an innovative way to classify melasma by pigment changes.

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.

Photodynamic therapy (PDT) has been reported to be useful in treating non-melanoma skin cancers and a variety of benign skin conditions including psoriasis. However, only two reports of palmoplantar pustular psoriasis (PPP) treated with PDT have been reported. We treated three intractable cases of PPP with PDT, using 20% 5-aminolaevulinic acid and a 630 ± 50 nm light-emitting diode device. The power density was 30 mW/cm 2 and the fluence was 15 J/cm 2 . After treatment, all cases showed mild to marked improvement. Topical PDT may be an alternative therapy in the treatment of PPP, but further study is necessary to confirm the effectiveness of topical PDT in PPP.

SummaryBackground Tranexamic acid (TA) has been suggested as an effective treatment for melasma. Aim To investigate the effects and mechanism of action of topical TA in the treatment of melasma. Methods In this study, 23 participants with melasma applied a 2% TA formulation to the whole face for 12 weeks. Clinical effects were evaluated using the modified Melasma Area and Severity Index (mMASI) and a chromameter. Skin biopsies were obtained from 10 participants to evaluate pigmentation, vascularity and the expression levels of possible paracrine factors contributing to the effect of TA. Results Most of the participants had mild melasma, with mMASI of < 5. The mMASI scores significantly improved in 22 of 23 participants after application. The L* values were increased and the a* values were decreased in both lesional and perilesional normal skin. Fontana–Masson staining showed a significant decrease in melanin content in the epidermis. The number of CD31-positive vessels and the expression of the vascular endothelial growth factor both tended to decrease. Endothelin (ET)-1 was found to be downregulated with TA. Conclusions Topical TA is effective for melasma. This immunohistochemical study found that suppression of ET-1 could be one of the mechanisms of action of TA on melasma.