A clinical investigation of early-onset alopecia areata in children: Onset earlier than 4 years of age might have a better short-term prognosis.

Alopecia areata (AA) is a non-scarring autoimmune hair loss of the scalp or body. While an early onset is considered a primary factor for poor prognosis, children with early-onset AA show varied responses to treatment. This study aimed to describe the clinical characteristics and assess the prognostic factors of early-onset AA in children. We performed a retrospective study of AA patients aged <10 years who visited our dermatologic clinic between January 2013 and December 2020, with a follow-up period >12 months. A clinical review of medical records, photographs, and telephonic interviews was performed. Treatment efficacy was assessed based on the degree of hair regrowth at a 12-month follow-up. Of 162 patients treated with topical corticosteroids, alone or in combination with other modalities, 57.4% showed >50% hair regrowth. On comparing the good and poor treatment response groups, no significant differences were observed in the presence of known prognostic factors, except for personal atopic history. In addition, patients aged <4 years at onset responded significantly better than older patients (p = 0.0127). There is a possibility that the patients with early-onset AA, especially those aged <4 years, demonstrate good treatment response. Further studies on long-term prognosis are required.

Serial Hydrolysis for the Simultaneous Analysis of Catecholamines and Steroids in the Urine of Patients with Alopecia Areata.

Catecholamines and steroids are well-known neurotransmitters and hormones that rapidly change the excitability of neurons. Alopecia areata is a disease for which the exact cause is unknown, but it is considered to be associated with stress, and so the simultaneous analysis of catecholamines and steroids is required for the diagnosis of alopecia areata. Thus, we herein report the simultaneous analysis of catecholamines and steroids bearing different functional groups for the first time, during which it was necessary to carry out a serial hydrolysis procedure. Following hydrolysis of the urine samples to produce the free forms from the urinary conjugates, ethyl acetate extractions were carried out, and chemical derivatization was performed using dansyl chloride to increase the sensitivity of the liquid chromatography-tandem mass spectrometry method. The matrix effects and recoveries of this analytical method were validated, giving values of 85.4-122.9% and 88.8-123.0%, respectively. In addition, the method accuracy and precision were assessed, giving values of 0.4-21.5% and 2.0-21.6% for the intra-day and inter-day precisions, respectively. This validated method was then applied to identify differences between patients with and without alopecia areata, wherein the metanephrine content was found to be significantly higher in the alopecia areata patient group. This quantitative profiling method can also be applied to steroid-dependent diseases, as well as catecholamine-related diseases.

Sex-related differences in urinary immune-related metabolic profiling of alopecia areata patients.

INTRODUCTION: Alopecia areata is a well-known autoimmune disease affecting humans. Polyamines are closely associated with proliferation and inflammation, and steroid hormones are involved in immune responses. Additionally, bile acids play roles in immune homeostasis by activating various signaling pathways; however, the roles of these substances and their metabolites in alopecia areata remain unclear. OBJECTIVES: In this study, we aimed to identify differences in metabolite levels in urine samples from patients with alopecia areata and healthy controls. METHODS: To assess polyamine, androgen, and bile acid concentrations, we performed high-performance liquid chromatography-tandem mass spectrometry. RESULTS: Our results showed that spermine and dehydroepiandrosterone levels differed significantly between male patients and controls, whereas ursodeoxycholic acid levels were significantly higher in female patients with alopecia areata than in controls. CONCLUSION: Our findings suggested different urinary polyamine, androgen, and bile acid concentrations between alopecia areata patients and normal controls. Additionally, levels of endogenous substances varied according to sex, and this should be considered when developing appropriate treatments and diagnostic techniques. Our findings improve our understanding of polyamine, androgen, and bile acid profiles in patients with alopecia areata and highlight the need to consider sex-related differences.

Distribution of polyamines may be altered in different scalp regions of patients with hair loss.

Hair loss, from the vertex or front of the head, generally occurs due to increased androgenic steroid levels. Androgenic steroids, particularly testosterone and dihydrotestosterone, are distributed differently across the vertex and occipital regions and are involved in inducing ornithine decarboxylase expression. Therefore, we hypothesized that the distribution of polyamines may be altered in different scalp regions. For the overall metabolic profiling of polyamines in patients with hair loss, a liquid chromatography-mass spectrometry was used. We investigated the differential polyamine levels in different regions of the hair of patients with male pattern baldness and those with female pattern hair loss. The levels of most polyamines were higher in the vertex region than in the occipital region, and N-acetyl polyamine levels differed significantly. We proposed to test our hypothesis by profiling polyamines in human hair fibre to evaluate the distribution of metabolites in various regions of the scalp.

Correction to: HiComet: a high-throughput comet analysis tool for large-scale DNA damage assessment.

After publication of the original article [1], it has been found that the author affiliations have been accidentally left out in the PDF. The full affiliations can be found in this correction.

HiComet: a high-throughput comet analysis tool for large-scale DNA damage assessment.

BACKGROUND: DNA damage causes aging, cancer, and other serious diseases. The comet assay can detect multiple types of DNA lesions with high sensitivity, and it has been widely applied. Although comet assay platforms have improved the limited throughput and reproducibility of traditional assays in recent times, analyzing large quantities of comet data often requires a tremendous human effort. To overcome this challenge, we proposed HiComet, a computational tool that can rapidly recognize and characterize a large number of comets, using little user intervention. RESULTS: We tested HiComet with real data from 35 high-throughput comet assay experiments, with over 700 comets in total. The proposed method provided unprecedented levels of performance as an automated comet recognition tool in terms of robustness (measured by precision and recall) and throughput. CONCLUSIONS: HiComet is an automated tool for high-throughput comet-assay analysis and could significantly facilitate characterization of individual comets by accelerating its most rate-limiting step. An online implementation of HiComet is freely available at https://github.com/taehoonlee/HiComet/ .

Clinical efficacy of oral administration of finasteride at a dose of 2.5 mg/day in women with female pattern hair loss.

Female pattern hair loss (FPHL) presents with diffuse thinning over the mid-frontal scalp, for which various treatment modalities have been tried. Although currently, oral 5 α-reductase inhibitors such as finasteride are being used, their clinical efficacy remains controversial. We retrospectively investigated 544 premenopausal or postmenopausal patients with FPHL who were prescribed finasteride at a dose of 2.5 mg/day. Our study excluded patients with a follow-up period of < 3 months and patients who were prescribed other FPHL treatment modalities including topical minoxidil. Finally, 112 patients were evaluated based on their medical records and clinical photographs. Based on assessment using the Ludwig scale at the time of their initial visit, among 112 patients studied, 59 patients were classified as belonging to grade I, 47 were grade II, and 6 were grade III. Using global photographs, we found that 33 (29.5%) of the 112 patients studied showed slight improvement, 73 (65.2%) showed significant improvement, whereas no change was recorded in 6 (5.4%). We could demonstrate efficacy of administration of finasteride at a dose of 2.5 mg/day for patients with FPHL and also found that finasteride has a better effect on hair growth when patients had a lower Ludwig score and an older age at onset.

A Case of Phacomatosis Pigmentokeratotica Associated With Multiple Basal Cell Carcinomas.

Phacomatosis pigmentokeratotica is a recently identified disease characterized by the coexistence of an epidermal nevus with sebaceous differentiation arranged along Blaschko lines and a speckled lentiginous nevus showing a checkerboard pattern, mostly in association with various extracutaneous defects. A 52-year-old man presented with asymptomatic ulcerative plaque on his left side of perioral area. A 2 × 2-cm-sized fleshy colored ulceration on his left perioral area was consistent with basal cell carcinoma with nevus sebaceous. Next to the ulceration, there was a light pinkish to fleshy colored papule on his left cheek that showed syringocystadenoma papilliferum. On his chin area, there was a 2 × 0.3-cm-sized skin colored papule that was consistent with trichilemmoma. Moreover, various sized light brownish macules and dark brownish papules were also located on his left side of the chest wall, back, and arm. Biopsy specimens from macules on the left side of the trunk confirmed the clinical diagnosis of speckled lentiginous nevus and multiple black papules beside that a speckled lentiginous nevus also revealed basal cell carcinomas. Herein, we present a rare case of a patient with phacomatosis pigmentokeratotica who had no extracutaneous abnormalities and who developed basal cell carcinoma, syringocystadenoma papilliferum, and trichilemmoma in nevus sebaceous on the face and speckled lentiginous nevus on the trunk. This syndrome needs adequate follow-up due to the possibility of malignant transformation.

A vector-free microfluidic platform for intracellular delivery.

Intracellular delivery of macromolecules is a challenge in research and therapeutic applications. Existing vector-based and physical methods have limitations, including their reliance on exogenous materials or electrical fields, which can lead to toxicity or off-target effects. We describe a microfluidic approach to delivery in which cells are mechanically deformed as they pass through a constriction 30-80% smaller than the cell diameter. The resulting controlled application of compression and shear forces results in the formation of transient holes that enable the diffusion of material from the surrounding buffer into the cytosol. The method has demonstrated the ability to deliver a range of material, such as carbon nanotubes, proteins, and siRNA, to 11 cell types, including embryonic stem cells and immune cells. When used for the delivery of transcription factors, the microfluidic devices produced a 10-fold improvement in colony formation relative to electroporation and cell-penetrating peptides. Indeed, its ability to deliver structurally diverse materials and its applicability to difficult-to-transfect primary cells indicate that this method could potentially enable many research and clinical applications.

Correction of pincer nail deformities using a modified double Z-plasty.

BACKGROUND: Pincer nail is a deformity characterized by excessive transverse curvature of the nail plate that increases distally for which many conservative and surgical corrective modalities have been recommended. OBJECTIVE: The purpose of this study is to investigate the outcomes and safety of modified double Z-plasty in the management of symptomatic pincer nail. MATERIALS AND METHODS: Modified double Z-plasty has been performed on 20 great toes in 12 patients from January 2008 to December 2013. The mean age of patients was 43 (range: 20-65) years. Three men and 9 women were enrolled. Visual analogue scale (VAS) score for pain, transverse angle, and width indices were investigated at the initial and the last follow-up. The average follow-up period was 2.4 years. RESULTS: All parameters showed significant improvement after surgery. Between the initial and last follow-up, the mean VAS score fell from 7.4 to 0.3, the mean transverse angle improved from 50 to 166°, and the mean width index improved from 65.4% to 97%. In all patients, the deformity was successfully eliminated with no recurrences. No complications were identified. CONCLUSION: Modified double Z-plasty provides a long-standing effective treatment for pincer nail deformity with an excellent esthetic result.

Association of HSPA1B SNP rs6457452 with Alopecia Areata in the Korean population.

The heat shock 70 kDa protein 1B (HSPA1B), which has been well-studied among the famous heat shock proteins HSPA1A/B/L, is related to autoimmune diseases, including Alopecia Areata (AA). In this study, the association of a 5'-untranslated region (5'UTR) SNP rs6457452 and a promoter SNP rs2763979 (-1140C > T) of HSPA1B with AA was investigated in 236 controls and 228 AA patients. Statistical analyses using the multiple logistic models were done, according to the onset and the clinical features of AA, including the age of onset, family history, type of AA lesion, nail involvement and body hair involvement. The results showed that rs6457452 was associated with the onset of AA (p < 0.002). In the analysis of clinical features of AA, rs6457452 was weakly related to the age of onset (p ≤ 0.04) and that rs2763979 was only weakly related to the type of AA lesion (p = 0.041). In conclusion, we suggest that the 5'UTR SNP rs6457452 of HSPA1B may be associated with the onset of AA and the T allele of rs6457452 may confer the reduced susceptibility to AA in the Korean population.

Long-term efficacy and safety of dutasteride 0.5 mg in Korean men with androgenetic alopecia: 5-year data demonstrating clinical improvement with sustained efficacy.

Dutasteride 0.5 mg is a dual inhibitor of 5α-reductase type I and II and was approved in Korea in 2009 for treating androgenetic alopecia (AGA) in men. We investigated the 5-year efficacy and safety of dutasteride 0.5 mg in Korean men with AGA using the basic and specific (BASP) classification. This retrospective analysis included 99 male AGA patients aged ≥18 years who were treated with dutasteride 0.5 mg for at least 5 years from October 2009 to December 2016 at Kyung Hee University Hospital in Gangdong. Patient photographs were scored using the BASP classification, and the Investigator Global Assessment (IGA) was performed using a seven-point scale. Patient improvement (IGA score ≥1) and prevention of disease progression (IGA score ≥0) were 89.9% (89/99) and 93.9% (93/99), respectively. According to the BASP classification, 52.5% (52/99) of the basic type, 75% (15/20) of the specific F type, and 82.2% (60/73) of the specific V type showed clinical improvement after 5 years of treatment. Dutasteride demonstrated long-term safety and efficacy in Korean male patients with AGA over a period of at least 5 years, with results comparable to those of other long-term efficacy studies of finasteride 1 mg in male patients with AGA.

Therapeutic maintenance effect of finasteride 1 mg every other month regimen in androgenetic alopecia and study on the difference in response to finasteride treatment: A prospective cohort study.

Finasteride is commonly used for androgenetic alopecia (AGA) treatment. The aim of this study was to assess the therapeutic maintenance effect of a finasteride every other month (EOM) regimen and analyze clinical and laboratory differences in patients with AGA according to their treatment response. One hundred males with AGA who received finasteride 1 mg daily treatment for a year were enrolled in the study. At 1 year follow-up, treatment responses of patients who completed the visit schedule were assessed using five scales. The patients were assigned to good or bad response groups according to their assessment. Further, they were randomly divided into two groups (daily vs. EOM) and treated with finasteride (1 mg) for 1 more year. At 2 years follow-up, treatment efficacy was assessed. At 1-year follow-up, 36 patients completed the schedule, including eight and three patients in the good and bad response groups, respectively. At the 2-year follow-up, 23 patients completed the schedule, with nine in the daily group and 14 in the EOM group. Changes in global photographic assessment in the second year were 1.33 and 1.29 for the daily and EOM groups, respectively. The daily group showed an elevated hair density and lower concentration of dihydrotestosterone (DHT) and the DHT to testosterone ratio (DHT/T). However, the EOM group showed decreased hair density and elevated DHT and DHT/T. Following treatment response assessment after 1 year of treatment, the good response group showed early onset which was associated with maternal AGA. Analysis of serum androgen hormone magnitude of DHT reduction was much greater (54.4% vs. 44.4%). DHT/T was higher in the bad response group (1.98 vs. 2.33). We concluded that the finasteride EOM regimen showed similar maintenance effects to the daily regimen.

Nonendocytic delivery of functional engineered nanoparticles into the cytoplasm of live cells using a novel, high-throughput microfluidic device.

The ability to straightforwardly deliver engineered nanoparticles into the cell cytosol with high viability will vastly expand the range of biological applications. Nanoparticles could potentially be used as delivery vehicles or as fluorescent sensors to probe the cell. In particular, quantum dots (QDs) may be used to illuminate cytosolic proteins for long-term microscopy studies. Whereas recent advances have been successful in specifically labeling proteins with QDs on the cell membrane, cytosolic delivery of QDs into live cells has remained challenging. In this report, we demonstrate high throughput delivery of QDs into live cell cytoplasm using an uncomplicated microfluidic device while maintaining cell viabilities of 80-90%. We verify that the nanoparticle surface interacts with the cytosolic environment and that the QDs remain nonaggregated so that single QDs can be observed.

Occurence of Cutaneous Marginal Zone B-Cell Lymphoma Post Breast Cancer Chemotherapy: A Case Report.

Primary cutaneous marginal zone B-cell lymphomas (PCMZLs) are classified as low-grade as they run an indolent course. They are histologically characterized through non-epidermotropic nodular or diffuse infiltrates consisting of small or medium heterogeneous atypical lymphoid cells. In the past few years, chemotherapy has increased the survival rate of breast cancer patients. However, the adverse effects of treatment, such as leukemia, have also been shown to emerge gradually. Additionally, cases of occurrence of non-Hodgkin lymphoma (NHL) post chemotherapy have also been reported. A 48-year-old female patient was presented with a violaceous nodule on her left thigh. Around 15 months ago, she completed breast cancer chemotherapy. Eight months later, a skin lesion appeared. Histological findings revealed dense and nodular lymphocyte infiltration. Immunohistochemical staining was positive for CD20 and BCL2. Clinical and histological examination of the lesions confirmed PCMZL. After systemic evaluation, lymphoma was found to be limited to the skin, and thus, she underwent complete excision of the lesion. At the first month follow-up, there was a recurrent lesion on the right wrist, which was excised successfully. However, recurrences occurred again in the calf and forearm in the following five and two months, respectively. These lesions were also confirmed with PCMZL using biopsy. We assume that this case is related to chemotherapy as it was presented and recurred abruptly post chemotherapy. Additionally, there are several reported cases of NHL post breast cancer chemotherapy. However, this is the first case report of PCMZL associated with chemotherapy.

A retrospective study on the clinical characteristics and prognosis of alopecia totalis and universalis: An update on prognosis.

Alopecia totalis (AT) and alopecia universalis (AU) is known to have a poor prognosis with high relapse rate, and treatment failure is observed in most patients, regardless of the type of therapy. Although treatment and the prognosis of AT and AU have improved in recent years, old data are routinely cited in recent review papers without questioning them. The authors aimed to study the clinical characteristics and prognosis of AT and AU to update and compare the results with those of previously reported studies. The authors retrospectively reviewed patients diagnosed with AT and AU from 2006 to 2017 in a single institution. Of the 419 patients, the mean age at first episode was 22.9 years, and 24.6% had early onset (≤13 years). During follow-up, 53.9% had more than 50% hair growth, and 19.6% of patients showed >90% hair growth. Among patients who showed >50% improvement, 36.7% had no recurrence. In early studies conducted in the 1950s and 1960s, the chance of full hair regrowth was reported to be <10%. In our study, patients with >90% improvement in AT and AU accounted for 19.6% of patients. The authors provide an update on data regarding the prognoses of AT and AU.