LIN28A loss of function is associated with Parkinson's disease pathogenesis.

Parkinson's disease (PD) is neurodegenerative movement disorder characterized by degeneration of midbrain-type dopamine (mDA) neurons in the substantia nigra (SN). The RNA-binding protein Lin28 plays a role in neuronal stem cell development and neuronal differentiation. In this study, we reveal that Lin28 conditional knockout (cKO) mice show degeneration of mDA neurons in the SN, as well as PD-related behavioral deficits. We identify a loss-of-function variant of LIN28A (R192G substitution) in two early-onset PD patients. Using an isogenic human embryonic stem cell (hESC)/human induced pluripotent stem cell (hiPSC)-based disease model, we find that the Lin28 R192G variant leads to developmental defects and PD-related phenotypes in mDA neuronal cells that can be rescued by expression of wild-type Lin28A. Cell transplantation experiments in PD model rats show that correction of the LIN28A variant in the donor patient (pt)-hiPSCs leads to improved behavioral phenotypes. Our data link LIN28A to PD pathogenesis and suggest future personalized medicine targeting this variant in patients.

Dermatofibroma-like dermal non-neural granular cell tumor.

Non-neural granular cell tumor (NNGCT) is a rare tumor with uncertain lineage. It presents as an asymptomatic polypoid or plaque-like lesion, especially on trunk. Because the granular cells are usually strongly reactive with S-100 stain, conventional granular cell tumors (GCTs) are regarded as those of neural or Schwann cell origin. Unlike GCTs, NNGCT is not reactive for S-100 protein and is thought to derive elsewhere, presumably from mesenchymal stem cells. A 20-year-old woman presented with a solitary, dermatofibroma-like, brownish nodule on her right arm. The lesion developed 3 months before presentation without subjective symptoms. Histopathologic examination revealed a grenz zone overlying a poorly circumscribed tumor extending through the reticular dermis. The tumor cells were large and polygonal, and they had numerous eosinophilic small granules in the cytoplasm. Immunohistochemical stains were positive for CD68, vimentin, factor XIIIa, CD10, and cyclin D1. Stains for S-100 protein, neuron-specific enolase, and CD34 were negative. Based on these findings, the lesion was diagnosed as dermal NNGCT.

Pigmented contact dermatitis and hair dyes: A retrospective case-control multicentre study in Korea.

BACKGROUND: Pigmented contact dermatitis (PCD), a rare variant of non-eczematous contact dermatitis, is clinically characterized by sudden-onset brown or grey pigmentation on the face and neck. It is hypothesized to be caused by repeated contact with low levels of allergens. OBJECTIVES: This study evaluated the risk of using hair dyes in patients with PCD in Korea. METHODS: A total of 1033 PCD patients and 1366 controls from 31 university hospitals were retrospectively recruited. We collected and analysed the data from the patient group, diagnosed through typical clinical findings of PCD and the control group, which comprised age/sex-matched patients who visited the participating hospitals with pre-existing skin diseases other than current allergic disease or PCD. RESULTS: Melasma and photosensitivity were significantly more common in the control group, and a history of contact dermatitis was more common in the PCD group. There were significantly more Fitzpatrick skin type V participants in the PCD group than in the control group. There was no significant difference in sunscreen use between the groups. Using dermatologic medical history, Fitzpatrick skin type and sunscreen use as covariates, we showed that hair dye use carried a higher PCD risk (odds ratio [OR] before adjustment: 2.06, confidence interval [CI]: 1.60-2.65; OR after adjustment: 2.74, CI: 1.88-4.00). Moreover, henna users had a higher risk of PCD (OR before adjustment: 5.51, CI: 4.07-7.47; OR after adjustment: 7.02, CI: 4.59-10.74), indicating a significant increase in the risk of PCD with henna dye use. Contact dermatitis history was more prevalent in henna users than in those using other hair dyes in the PCD group (17.23% vs. 11.55%). CONCLUSION: Hair dye use is a risk factor for PCD. The risk significantly increased when henna hair dye was used by those with a history of contact dermatitis.

Cryolipolysis for abdominal subcutaneous fat reduction: A prospective, multicenter, single arm, clinical study.

Various treatment methods are used for noninvasive body contouring. To evaluate the efficacy and safety of a newly designed cryolipolysis device using a three-dimensional cooling method for abdominal fat reduction. Twenty-five participants with clinically apparent abdominal fat tissue participated in the study. The thickness of fat tissue below the umbilicus level was measured using a caliper at baseline and 12 weeks after the first treatment. The height of abdominal subcutaneous fat tissue on ultrasonography and participant satisfaction were assessed at every visit for 16 weeks. All adverse events (AEs) during the study period were recorded. p values <0.05 were considered statistically significant. Twenty-four participants completed this study; the mean BMI of participants was 29.34 ± 2.36 kg/m2 . The mean thickness of abdominal subcutaneous fat was significantly lower at 12 weeks (40.4 ± 6.8 mm, p < 0.001) than at baseline (49.3 ± 8.5 mm). Differences in the height of abdominal subcutaneous fat compared to that at baseline were 1.02 ± 0.41 cm (12 weeks, p < 0.001) and 1.13 ± 0.44 cm (16 weeks, p < 0.001). Rates of abdominal subcutaneous fat reduction at 12 and 16 weeks compared to that at baseline were 28.45% and 31.13%, respectively. The ratio of abdominal circumference to hip circumference at 12 and 16 weeks was significantly decreased compared to that at baseline. Most participants (95.8%) reported improvement in satisfaction scores at 16 weeks. There were no serious AEs during the entire study period. The study demonstrated the efficacy of a noninvasive cryolipolysis device using a three-dimensional cooling method for reducing abdominal subcutaneous fat.

A split-face comparative trial of photopneumatic therapy versus intense pulsed light for the treatment of acne vulgaris.

A novel photopneumatic (PPX) technology, combining blue light-emitting diode (LED) and broadband intense pulsed light (IPL) with vacuum pressure, was developed for the treatment of acne vulgaris (AV). In this study, we enrolled 50 patients with mild to moderate AV. Five successive treatments were performed on one side of the face with a combined PPX device, and the opposite side was treated with only IPL with the same fluences at 2-week intervals. Clinical improvement was evaluated by inflammatory and non-inflammatory acne lesion counts. Additionally, patient self-assessment scores were assessed. The results showed that inflammatory and non-inflammatory acne lesion counts were significantly improved on both sides of the face after treatment (p < .001, p = .001, respectively). Both inflammatory and non-inflammatory lesion counts were significantly reduced on the side treated with PPX when compared to the side treated with IPL alone (p = .008, p = .045, respectively). Thirty-eight of 44 patients reported slight to moderate improvement on the patient self-assessment score. No significant side effect was observed during the study periods.In conclusion, PPX therapy is an effective and safe modality to treat mild to moderate AV. This study shows that PPX therapy has superior efficacy for the treatment of AV compared to IPL monotherapy.

"New classification of late and delayed complications after dermal filler: Localized or Generalized?"

Background: As filler injections have become very common procedures worldwide, the number of complications has increased. However, there is a lack of systematized studies and precise classification of late and delayed complications. This study aimed to suggest new and reliable classifications and to characterize the clinical manifestations of late and delayed complications after filler injections.Methods: This retrospective study analyzed patients and suggested a new classification of delayed adverse effects related to filler injection. Several demographic and clinical findings were analyzed. Patients were classified into two types according to their clinical presentation: Type I (Localized) or Type II (Generalized).Results: Twenty-five patients were evaluated during a clinically active adverse event suspected to be related to fillers. The most common injected filler substance was hyaluronic acid (HA, 68.8%). 76% of the patients were classified with Localized complications. In the Generalized complications group, systemic symptoms were more common (p=0.002), the treatment response was poor (p=0.010), and fewer patients showed complete remission (p=0.007) than in the Localized complications group.Conclusions: We propose a simple new classification method for late and delayed complications after dermal filler: Localized and Generalized. We expect that this new classification could help provide appropriate treatment and predict patient prognosis.

Protein tyrosine phosphatase conjugated with a novel transdermal delivery peptide, astrotactin 1-derived peptide recombinant protein tyrosine phosphatase (AP-rPTP), alleviates both atopic dermatitis-like and psoriasis-like dermatitis.

BACKGROUND: Atopic dermatitis (AD) and psoriasis are the 2 most common chronic inflammatory skin diseases. There is an unmet medical need to overcome limitations for transcutaneous drug development posed by the skin barrier. OBJECTIVE: We aimed to identify a novel transdermal delivery peptide and to develop a transcutaneously applicable immunomodulatory protein for treating AD and psoriasis. METHODS: We identified and generated reporter proteins conjugated to astrotactin 1-derived peptide (AP), a novel transdermal delivery peptide of human origin, and analyzed the intracellular delivery efficiency of these proteins in mouse and human skin cells and tissues using multiphoton confocal microscopy. We also generated a recombinant therapeutic protein, AP-recombinant protein tyrosine phosphatase (rPTP), consisting of the phosphatase domain of the T-cell protein tyrosine phosphatase conjugated to AP. The immunomodulatory function of AP-rPTP was confirmed in splenocytes on cytokine stimulation and T-cell receptor stimulation. Finally, we confirmed the in vivo efficacy of AP-rPTP transdermal delivery in patients with oxazolone-induced contact hypersensitivity, ovalbumin-induced AD-like, and imiquimod-induced psoriasis-like skin inflammation models. RESULTS: AP-conjugated reporter proteins exhibited significant intracellular transduction efficacy in keratinocytes, fibroblasts, and immune cells. In addition, transcutaneous administration of AP-dTomato resulted in significant localization into the dermis and epidermis in both mouse and human skin. AP-rPTP inhibited phosphorylated signal transducer and activator of transcription (STAT) 1, STAT3, and STAT6 in splenocytes and also regulated T-cell activation and proliferation. Transcutaneous administration of AP-rPTP through the paper-patch technique significantly ameliorated skin tissue thickening, inflammation, and cytokine expression in both AD-like and psoriasis-like dermatitis models. CONCLUSION: We identified a 9-amino-acid novel transdermal delivery peptide, AP, and demonstrated its feasibility for transcutaneous biologic drug development. Moreover, AP-rPTP is a novel immunomodulatory drug candidate for human dermatitis.

Comparative study of ablative fractional photothermolysis versus topical retinoid cream in the treatment of idiopathic guttate hypomelanosis.

Background: Despite various treatments attempts, no prospective studies have compared the different therapeutic modalities for treatment of idiopathic guttate hypomelanosis (IGH). This study aimed to compare the efficacy of CO2 fractional laser (CO2FL), Er:YAG fractional laser (EYFL), and 0.025% topical tretinoin for treating IGH. Materials and Methods: A total of 122 lesions were analyzed from 18 patients (mean age, 70.00 ± 20.00 years). Treatment outcome evaluations included the visual analog scale (VAS) to assess lesion severity, investigator's global assessment (IGA) to assess the extent of improvement, and patient's satisfaction score (PSS). Results: Among the 122 lesions, 42, 40, and 40 were assigned to the CO2FL, EYFL, and topical tretinoin treatment groups, respectively. The VAS score was significantly improved after the second treatment. CO2FL and EYFL therapy had superior treatment efficacy compared to topical tretinoin (p < 0.01 in VAS, IGA, and PSS). There was no significant difference between the two types of fractional lasers. Conclusions: Ablative fractional laser (AFL) was an effective treatment with a relatively short treatment time without serious adverse events. We recommended AFL to treat IGH as an active treatment strategy.

A Case of Cutaneous Myiasis Caused by Cordylobia anthropophaga Larvae in a Korean Traveler Returning from Central Africa.

The cutaneous myiasis has been rarely reported in the Republic of Korea. We intended to describe here a case of furuncular cutaneous myiasis caused by Cordylobia anthropophaga larvae in a Korean traveler returned from Central Africa. A patient, 55-year-old man, had traveled to Equatorial Guinea, in Central Africa for a month and just returned to Korea. Physical examinations showed 2 tender erythematous nodules with small central ulceration on the left buttock and thigh. During skin biopsy, 2 larvae came out from the lesion. C. anthropophaga was identified by paired mouth hooks (toothed, spade-like, oral hooklets) and 2 posterior spiracles, which lack a distinct chitinous rim. Although rarely described in Korea until now, cutaneous myiasis may be encountered more frequently with increasing international travel and exchange workers to tropical areas.

Importance of concomitant topical therapy in moderate-to-severe atopic dermatitis treated with cyclosporine.

Cyclosporine (CS) is widely used in patients with refractory atopic dermatitis (AD). During CS treatment, many patients have a tendency to decrease their adherence to topical agents as their disease improves. Our aim was to compare the efficacy and relapse rate of CS treatment combined with topical therapy and CS monotherapy. This prospective, randomized, 6 month study involved 60 patients with moderate-to-severe AD who were randomly assigned to two groups, one receiving CS and topical agents and the other, CS only. Clinical outcomes were based on investigators' global assessment (IGA) scores, eczema areas and severity index scores, and trans-epidermal water loss. If a patient achieved treatment success (IGA score ≤2) during the study period, CS was stopped. Relapse rate and time to relapse were evaluated during the 3 months after discontinuation of CS. The treatment success rate was significantly higher in the combination group (p = 0.028). The combination group had a shorter median time to response (p = 0.040), a lower cumulative dose (p = 0.041), and a longer time to relapse (p < 0.01) than the monotherapy group. Although CS monotherapy is effective against AD, topical agents should be used concomitantly.

A Digital Squamous Cell Carcinoma Mimicking a Diabetic Foot Ulcer, With Early Inguinal Metastasis and Cancer-Related Lymphedema.

Although squamous cell carcinoma (SCC) is the second most common nonmelanoma skin cancer, clinicians have difficulty diagnosing SCC of the toe because its clinical features can mimic other less serious diseases. Clinicians are especially prone to misdiagnose SCC of the toe as diabetic foot ulcer in patients with diabetes mellitus because of the clinical similarity of the 2 ailments. SCC of the toe is generally considered to have a low risk of metastasis. Locoregional or distant metastases without bone or tendon involvement are particularly rare. The authors report here an interesting case of rapidly spreading SCC of the toe with metastasis to multiple lymph nodes and cancer-related lymphedema. Physicians should be aware of the possibility of malignancy when they encounter chronic and recalcitrant ulcerative lesions of the digits.

Lower face lifting and contouring with a novel internal real-time thermosensing monopolar radiofrequency.

As demand for a youthful appearance has increased, various techniques for face lifting and contouring have been used to reduce excess fat deposition and improve skin laxity. Recently, radiofrequency (RF)-assisted lipolysis and liposuction (RFAL) has been introduced for body and face contouring. This study aimed to evaluate the clinical improvement and safety of a new RFAL device for face lifting and contouring. A prospective study was conducted in 20 Korean patients who underwent an internal real-time thermosensing monopolar RFAL procedure. Prior to treatment and 12 and 24 weeks after treatment, digital photographs were taken, and the degree of improvement as measured by investigators and patients was recorded. Skin elasticity was measured using a Cutometer (CT575, Courage and Khazaka®, Cologne, Germany). Safety profiles were also evaluated at each visit. Results showed favorable improvement in skin laxity and fat deposition. Both investigators' evaluations and patients' evaluation showed significant improvement between 12 and 24 weeks. Although the changes in skin elasticity measured by the Cutometer were not statistically significant, all three treated regions showed a trend toward improvement. No major side effects such as infection or burn were observed. The internal, real-time thermosensing monopolar RFAL device showed clinical efficacy and safety. After further studies with more patients and longer follow-up periods, internal real-time thermosensing monopolar RF devices might become one of the popular treatment options for face lifting and contouring.

A clinicopathologic study of morphea in Korean patients.

BACKGROUND: The exact pathogenesis of morphea is poorly understood, and only a few clinical or histopathological studies have been conducted in Asian patients. OBJECTIVE: The aim of this study was to identify the clinical and histopathological characteristics of morphea in Korean patients. METHODS: We retrospectively reviewed the medical records of 101 patients whose clinicopathologic findings were compatible with morphea and analyzed demographic characteristics, number of lesions, disease subtype and histopathological findings. RESULTS: Overall, circumscribed morphea (52.5%) was the most common clinical type, followed by linear (28.7%), mixed (13.9%) and generalized (5.0%) type. Disease duration was positively correlated with increased thickness of the skin in 54 patients (p < 0.001). Inflammatory cell infiltration was absent in 54, mild in 30 and moderate in 14 patients. There was no significant difference in the mean ratio of lesional to normal skin thickness (L/N ratio) among four types of morphea. Disease duration was not correlated with the density of inflammatory cell infiltration (p = 0.68). There were statistically significant differences in the duration of disease according to plasma cell counts (p < 0.05). CONCLUSIONS: A positive correlation was found between skin thickness and disease duration, but mean L/N ratio was not significantly different among various types of morphea.

Hair zinc levels and the efficacy of oral zinc supplementation in patients with atopic dermatitis.

Zinc deficiency in patients with atopic dermatitis (AD) and the use of zinc supplementation is still controversial. We measured hair zinc levels in 58 children with AD and 43 controls (age range 2-14 years). We also investigated the efficacy of oral zinc supplementation in AD patients with low hair zinc levels by comparing eczema assessment severity index (EASI), transepidermal water loss (TEWL), and visual analogue scales for pruritus and sleep disturbance in patients receiving zinc supplementation (Group A) and others not receiving supplementation (Group B). At baseline, the mean zinc level was significantly reduced in AD patients (113.1 µg/g vs. 130.9 µg/g, p = 0.012). After 8 weeks of supplement, hair zinc level increased significantly in Group A (p < 0.001), and EASI scores, TEWL, and visual analogue scales for pruritus improved more in Group A than in Group B (p = 0.044, 0.015 and < 0.001, respectively). Thus, oral zinc supplementation may be effective in AD patients with low hair zinc levels.

The safe delivery of fractional ablative carbon dioxide laser treatment for acne scars in Asian patients receiving oral isotretinoin.

BACKGROUND: Because acne scarring is associated with substantially reduced quality of life, early initiation of effective treatment is desirable. In previous reports, isotretinoin treatment was associated with increased scarring after cosmetic procedures, such as laser treatment, dermabrasion, and chemical peeling. OBJECTIVE: To evaluate wound healing after ablative carbon dioxide (CO2) fractional resurfacing for acne scarring conducted during and/or within 1 to 3 months of oral isotretinoin treatment. MATERIALS AND METHODS: The records of 20 patients with facial acne scars were included in this retrospective study. All patients were receiving isotretinoin treatment or had completed it within the previous 1 to 3 months. All patients received full-face fractional ablative CO2 laser treatment. Follow-up was for at least 6 months to evaluate side effects. RESULTS: All patients showed normal reepithelialization and were satisfied with the results of the laser treatments. All adverse events were minor, and there were no hypertrophic scars or keloids. CONCLUSION: Ablative CO2 fractional laser treatment for acne scarring seems to be safe regardless of isotretinoin use (10-60 mg/d). The authors' findings contribute to the discussion of whether oral isotretinoin treatment impairs wound healing after ablative laser treatment.

Objective evaluation of the clinical efficacy of fractional radiofrequency treatment for acne scars and enlarged pores in Asian skin.

BACKGROUND: Ablative fractional lasers can effectively treat acne scars and enlarged pores, but cause considerable pain and downtime for patients, as well as potentially causing postinflammatory hyperpigmentation (PIH), especially in Asian skin. OBJECTIVE: To evaluate the efficacy of a novel bipolar radiofrequency (RF)-based fractional device to treat acne scars and enlarged pores in Asians with objective measurements and histologic assessments. METHODS: Thirty-one Korean patients with acne scars and enlarged pores received 4 consecutive fractional RF treatments at 3-week intervals. Outcome assessments included photography, global evaluation by investigators in a blind manner, patient assessment, objective biophysical measurements of elasticity and color, and histological changes compared with untreated lesions. RESULTS: Follow-up assessments by physicians 3 months after the last treatment revealed that patients showed clinical improvement. Patient self-assessments paralleled physicians' assessments. Objective biophysical measurements showed significant improvements in elasticity (R2, R5, and R7) and the melanin/erythema index, together with increases in the levels of procollagen Types I and III, as well as elastin. There were no cases of PIH, and adverse events were limited to mild ones. CONCLUSION: Fractional bipolar RF provides clinical efficacy with safety in acne scars and enlarged pores through dermal matrix remodeling combined with tolerable epidermal ablation.

A pilot study of a novel dual--pulsed 1064 nm Q-switched Nd: YAG laser to treat Riehl's melanosis.

The treatment of Riehl's melanosis is difficult and challenging. Recently, a low-fluence 1064-nm quality (Q)-switched neodymium: yttrium-aluminum-garnet (Nd: YAG) laser method, referred to as 'laser toning', has been used in the treatment of melasma in Asian countries. We present here a series of cases of Riehl's melanosis that were treated effectively with a novel Q-switched Nd: YAG laser that was operated as a dual-pulse at half-fluence and 140-µs intervals.

Treatment of onychomycosis with a 1,064-nm long-pulsed Nd:YAG laser.

BACKGROUND: There are various treatment modalities of onychomycosis. Of these, however, oral antifungal therapies are complicated by potential drug interactions and systemic effects, and the surgical treatment can result in prolonged pain. Therefore, a new, safe and effective therapy is needed that can improve the aesthetic appearance of the nails. OBJECTIVE: The purpose of this study was to evaluate the effect of treatment of onychomycosis with a 1,064-nm long-pulsed Nd:YAG laser. METHODS: 13 patients (31 toenails, 12 fingernails) received five treatment sessions at 4-week intervals with a 1,064-nm long-pulsed Nd:YAG laser. Parameters for each treatment were 6 mm spot size, 5 J/cm(2) fluence, 0.3 ms pulse duration and 5 Hz pulse rate. RESULTS: Of the 13 patients, 8 (61.5%) were women and 5 were men. The mean age of the patients was 62. Of the 43 nails, 4 (9.3%) achieved a complete cure (9.3%), 8 had excellent treatment outcomes (18.6%) and 31 had good treatment outcomes (72%). None of the 13 patients experienced any discomfort except for a mild burning sensation and there were no adverse effects. CONCLUSIONS: Our results demonstrate that the 1,064-nm long-pulsed Nd:YAG laser could be a safe and effective treatment modality in the management of patients with onychomycosis.

Facial Dermatoses Associated With Mask-Wearing in the COVID-19 Era: A Nationwide, Cross-Sectional, Multicenter, Questionnaire-based Study.

BACKGROUND: Daily usage of facial masks during coronavirus disease 2019 pandemic influenced on facial dermatoses. OBJECTIVE: This study investigated the impact of mask-wearing habits on facial dermatoses. METHODS: A nationwide, observational, questionnaire-based survey was conducted from July through August 2021, involving 20 hospitals in Korea. RESULTS: Among 1,958 facial dermatoses, 75.9% of patients experienced aggravation or development of new-onset facial dermatoses after wearing masks. In aggravated or newly developed acne patients (543 out of 743), associated factors were healthcare provider, female gender, and a long duration of mask-wearing. Irritating symptoms, xerosis, and hyperpigmentation were more frequently observed in this group. Aggravated or newly developed rosacea patients (515 out of 660) were likely to be female, young, and have a long duration of mask-wearing per day. Seborrheic dermatitis patients who experienced aggravation or de novo development (132 out of 184) were younger, and they more frequently involved the chin and jaw in addition to the nasolabial folds and both cheeks. Contact dermatitis patients (132 out of 147) with aggravation or de novo development tended to be female, involve both cheeks, and complain of pruritus. Aggravated or newly developed atopic dermatitis patients (165 out of 224) were more likely to be female, and had a higher baseline investigator global assessment score before mask-wearing. CONCLUSION: Clinical features and factors related to aggravation were different according to the types of facial dermatoses.