Association Between Natural Hair Color, Race, and Alopecia.

INTRODUCTION: Limited epidemiologic data has suggested direct associations between hair pigment, race, and incidence of alopecia areata (AA). Here, we examine the relationship between natural hair color, race, and the lifetime risk alopecia. METHODS: In this case-control study, we included UK Biobank patients of all races and self-reported hair color with diagnoses of AA, androgenetic alopecia (AGA), or scarring alopecia (SA). Multivariable logistic regression was used to detect differences in lifetime risk. RESULTS: Findings reveal a significantly increased risk of AA among individuals with black hair compared to dark brown hair (OR 1.71 [95% CI 1.22-2.38], p < 0.001). Those with red or blonde hair showed a decreased risk of AA (0.74 [0.56-0.97]; 0.62 [0.41-0.95], p < 0.05). No racial differences in AA prevalence were observed among individuals with black hair. CONCLUSIONS: Darker hair colors may be associated with a higher risk of AA, lighter hair colors with a lower risk, and differences in hair color could contribute to previously noted racial variations in AA incidence, potentially influencing dermatologists' perspectives on the disease's epidemiology.

Exploring the Relationship Between Immune Cells and Non-Scarring Hair Loss: A Mendelian Randomization Study.

Background: Non-scarring hair loss (NSHL) is a global health concern with increasing prevalence due to lifestyle changes and an aging population. It can cause psychological distress and affect quality of life. Objective: This study aimed to identify the associations between NSHL and immune cell phenotypes using a two-sample Mendelian randomization (MR) analysis, offering insights for future immune-based therapies for NSHL. Methods: We obtained immunocyte data from the IEU Open GWAS Project and NSHL data from the same database and used MR analysis to evaluate the causal association between each immunophenotype and NSHL. Three statistical methods were employed: the MR-Egger regression, weighted median estimation, and inverse variance weighting (IVW). Results: The MR resonance imaging identified 31 immunocyte phenotypes associated with NSHL. Among these, 19 immunocyte phenotypes were negatively associated with NSHL, indicating their protective effects. The remaining 12 immunocyte phenotypes were positive association. Sensitivity analyses suggested the robustness of all MR findings. Conclusion: These findings highlight a clear correlation between NSHL and immunity, demonstrating the significant role of certain immune cell phenotypes. This study offers a new direction for immune-based therapies in the treatment of NSHL.

Platelet Rich plasma injection of the vocal folds in benign vocal pathologies.

PURPOSE: There are few options for treatment of dysphonia secondary to vocal pathology related to lamina propria scar, atrophy, sulcus, or inflammatory disorders. Platelet rich plasma (PRP) may provide anti-inflammatory and regenerative properties seen with other tissue engineering therapies without the risks associated with these treatments. We evaluated vocal fold (VF) injection of PRP for feasibility, phonatory effects, patient satisfaction and durability. METHODS: Patients with dysphonia secondary to vocal fold scar, atrophy, sulcus and inflammatory lesions were included. PRP injections were administered in office, to bilateral vocal folds. Patients were followed up at 1 week, 1 month, 3 months and 6 months to assess outcomes (GRBAS scale, maximum phonation time, vocal fatigue index (VFI), voice handicap index (VHI-10) and stroboscopy). RESULTS: 75 intracordal PRP injections were administered to 48 patients. All injections were completed, and no adverse reactions were experienced. Improvements in VHI-10 scores at 1,3,6 months were seen (mean VHI 21.73 at baseline, 15.62 at six months, p < 0.001). 72.3% rated improvement at 7 or above on Likert scale. 95.7% of patients would consider a future PRP injection. Secondary outcomes VFI, MPT, and GRBAS also demonstrated significant improvements over time. Patients receiving a single PRP injection (n = 26) still demonstrated significant VHI-10 improvements at 1,3 and 6 months. CONCLUSIONS: VF office PRP injections are feasible and safe and can provide phonatory benefit and reduce vocal effort in benign VF disorders. A single PRP injection is sufficient to provide sustained benefit in some cases. LEVEL OF EVIDENCE: Level III: prospective cohort study.

A Prospective Study of Patients Presenting With Pre-sternal Keloids.

INTRODUCTION: Keloid represents a pathological form of scarring. They are very common in the anterior chest area; nearly 50% of all keloids occur in this location. One of the reasons for this is that folliculitis and acne, known for triggering the development of keloids, are common on the anterior chest. The other reason is the tension load in this area due to the frequent movements of the upper limbs and the respiratory movements. These movements stretch the skin of the anterior chest horizontally. When this cyclical tension is imposed on the anterior chest wounds, there is an exacerbation and prolongation of the inflammation in the reticular dermis of the wound. These stresses induce the growth of keloids along the prevailing lines of skin tension. MATERIALS AND METHODS: We performed a prospective study in which patients were recruited over a period of one year. Patients presenting with symptomatic pre-sternal keloids and requesting treatment but were unwilling to undergo surgical intervention were included in this study. Patients with a history of previous thoracic surgery were excluded. Baseline assessment and documentation of the lesion were performed. The study patients received three sessions of intralesional injections of a combination of triamcinolone acetonide and hyaluronidase at four weekly intervals. The final assessment was performed four weeks after the third session. RESULTS: The study included 47 lesions in 47 patients with ages of the patients ranging from 16 to 70 years. Pre-sternal keloids were found to be more common among males than females, with a male-to-female ratio of 2.35:1. Patients presented with pre-sternal keloids that had been present for varying periods ranging from three to 81 months. All of our 47 patients completed the three sessions of the treatment. Following the treatment, there was an improvement in the patient's symptoms, as evidenced by the reduction in the mean pruritis scores and pain scores. There was an overall reduction in the size of the lesion. The decrease in the height of the lesions was more evident than the reduction in the craniocaudal or transverse dimensions of the lesions. There were improvements in Vancouver Scar Scale (VSS) vascularity scores and pliability scores following the treatment. CONCLUSION: We conclude that pre-sternal keloids should be considered as a distinct clinico-pathological entity. There are differences with regard to pathogenesis, clinical presentation, and management when compared to keloids elsewhere. Treatment with intralesional injections of a combination of triamcinolone acetonide and hyaluronidase effectively relieves the symptoms and may be considered in patients not willing to undergo surgical intervention. Recurrences can occur and need further treatments.

Laser tattoo removal strategies: Part II: A review of the methods, techniques, and complications involved in tattoo removal.

The rising global popularity of cosmetic and corrective tattoos has concurrently led to an increased demand for their removal. While in the past, methods like surgical excision, chemical destruction, and dermabrasion were employed, lasers have emerged as a reliable and effective tool for tattoo removal. Increasing technological options and combination treatment strategies have raised the importance of understanding the various approaches to laser tattoo removal along with their respective clinical impact. This CME aims to describe the multifaceted aspects of laser tattoo removal, including the method selection, application principles, and safety considerations. Furthermore, it addresses the factors considered when selecting the most suitable laser to achieve optimal treatment outcomes.

A Case Series on a Rare Clinical Presentation of Lichen Planopilaris Restricted to the Face.

Lichen planopilaris (LPP) restricted to the face is extremely rare. This case series includes five unique LPP cases that presented with a varied degree of pigmentation and scarring alopecia restricted to the face. We herein describe the clinical characteristics, dermoscopy, and treatment of these histopathologically confirmed facial LPP cases. None of them had lesions anywhere else on the body.

Performing Suction Blister Skin Biopsies.

Traditional skin sampling methods include punch or shave biopsies to produce a solid tissue sample for analysis. These biopsy procedures are painful, require anesthesia, and leave permanent scars. This unit describes a suction blister skin biopsy method that can be used in place of traditional biopsy methodologies as a minimally invasive, non-scarring skin sampling technique. The induction of suction blisters uses an instrument with a chamber that applies negative pressure and gentle heat to the skin. Blister formation occurs within 1 hr, producing up to five blisters, each 10 mm in diameter per biopsy site. Blister fluid can be extracted and centrifuged to retrieve cells from the epidermis and upper dermis for flow cytometry, single-cell RNA sequencing, cell culture, and more without the need for digestion protocols. In addition, the blister fluid can be used to measure soluble proteins and metabolites. This unit describes the preparation of supplies and subjects, the suction blister biopsy procedure and blister formation, fluid extraction, and post-blistering care. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Preparation of supplies and subject Basic Protocol 2: Suction blister biopsy procedure and formation Basic Protocol 3: Blister fluid extraction Basic Protocol 4: Post-blister care and clean up.

AT2R Activation Improves Wound Healing in a Preclinical Mouse Model.

Abnormal skin healing resulting in chronic wounds or hypertrophic scarring remains a major healthcare burden. Here, the antifibrotic angiotensin II type 2 receptor (AT2R) signaling pathway was modulated to determine its impact on cutaneous wound healing. Balb/c mice received two splinted full-thickness wounds. Topical treatments with the selective AT2R agonist compound 21 (C21) and/or selective antagonist PD123319 or saline vehicle were administered until sacrifice on post-wounding days 7 or 10. The rate of wound re-epithelialization was accelerated by PD123319 and combination treatments. In vitro, C21 significantly reduced human fibroblast migration. C21 increased both collagen and vascular densities at days 7 and 10 post-wounding and collagen I:III ratio at day 10, while PD123319 and combination treatments decreased them. Genes associated with regeneration and repair were upregulated by C21, while PD123319 treatment increased the expression of genes associated with inflammation and immune cell chemotaxis. C21 treatment reduced wound total leukocyte and neutrophil staining densities, while PD123319 increased these and macrophage densities. Overall, AT2R activation with C21 yields wounds that mature more quickly with structural, cellular, and gene expression profiles more closely approximating unwounded skin. These findings support AT2R signal modulation as a potential therapeutic target to improve skin quality during wound healing.

Development and validation of novel keloid-derived immortalized fibroblast cell lines.

Keloids are a common connective tissue disorder with an ill-understood etiopathogenesis and no effective treatment. This is exacerbated because of the absence of an animal model. Patient-derived primary keloid cells are insufficient as they age through passaging and have a limited supply. Therefore, there is an unmet need for development of a cellular model that can consistently and faithfully represent keloid's pathognomic features. In view of this, we developed keloid-derived immortalized fibroblast (KDIF) cell lines from primary keloid fibroblasts (PKF) by transfecting the human telomerase reverse transcriptase (hTERT) gene. The TERT gene encodes the catalytic subunit of the telomerase enzyme, which is responsible for maintaining the cellular replicative potential (cellular immortalization). Primary fibroblasts from keloid-specific lesional (peripheral, middle, and top) as well as extralesional sites were isolated and evaluated for cell line development and comparative cellular characteristics by employing qRT-PCR and immunofluorescence staining. Moreover, the immortalized behavior of KDIF cell lines was evaluated by comparing with cutaneous fibrosarcoma and dermatofibrosarcoma protuberans cell lines. Stable KDIF cell lines with elevated expression of hTERT exhibited the cellular characteristics of site-specific keloid fibroblasts. Histochemical staining for ß-galactosidase revealed a significantly lower number of ß-gal-positive cells in all three KDIF cell lines compared with that in PKFs. The cell growth curve pattern was studied over 10 passages for all three KDIF cell lines and was compared with the control groups. The results showed that all three KDIF cell lines grew significantly faster and obtained a fast growing characteristic as compared to primary keloid and normal fibroblasts. Phenotypic behavior in growth potential is an indication of hTERT-mediated immortalized transformation. Cell migration analysis revealed that the top and middle KDIF cell lines exhibited similar migration trend as site-specific PKFs. Notably, peripheral KDIF cell line showed significantly enhanced cell migration in comparison to the primary peripheral fibroblasts. All KDIF cell lines expressed Collagen I protein as a keloid-associated fibrotic marker. Functional testing with triamcinolone inhibited cell migration in KDIF. ATCC short tandem repeat profiling validated the KDIF as keloid representative cell line. In summary, we provide the first novel KDIF cell lines. These cell lines overcome the limitations related to primary cell passaging and tissue supply due to immortalized features and present an accessible and consistent experimental model for keloid research.

Evaluation of the Efficacy of Platelet-Rich Plasma Injections With and Without Microneedling for Managing Atrophic Facial Acne Scars: A Prospective Comparative Study.

Background and aim The majority of acne has the potential to transform into facial scars, which have a physical and psychological effect on the individual. There are plenty of treatment options to manage such scars. The aim of this study is to assess the comparative effect of the injection of platelet-rich plasma (PRP) alone, with that of the injection of PRP with microneedling, in the reduction of atrophic facial acne scars.  Methods A total of 30 participants were included in this study, divided into two groups (n = 15). Patients in Group I received intradermal injection of PRP only, and Group II included patients receiving intradermal injection of PRP with microneedling. The scar appearance was evaluated at baseline, after one, two, and three months using Goodman Baron's scar scale. The statistics were analysed using the Chi-square and Student's t-tests.  Results Patients in the PRP with microneedling group had lower acne scar scores on the Goodman Baron scale compared to those who received only PRP. The acne scores were statistically significant (p-value < 0.05) in the second and third months of treatment in Group II.  Conclusion The addition of microneedling to PRP has proven to be effective in the reduction of facial acne scars. However, different types of scars require different modalities of treatment, and the final decision lies in the hands of the operator and the requirements of the patients.

Corrigendum: Trickle infection with Heligmosomoides polygyrus results in decreased worm burdens but increased intestinal inflammation and scarring.

[This corrects the article DOI: 10.3389/fimmu.2022.1020056.].

Treatment of Atrophic Acne Scarring with Fractional Microplasma Radiofrequency: A Multicentric Experience.

Background: Atrophic scarring is a severe form-disfiguring sequela of acne, which can lead to negative effect on patients' life. Fractional microplasma radiofrequency (RF) has emerged as a promising modality, leveraging dermal fibroblast remodeling to enhance aesthetic results for scars and hyperpigmentation. This study evaluates the efficacy and safety of high-power fractional microplasma RF for atrophic acne scars, considering patient tolerance to procedural discomfort. Methods: In this prospective study, 95 Chinese patients with atrophic facial acne scars underwent three sessions of fractional microplasma RF treatment, with assessments at 1, 3, and 6 months post-treatment. Patients were categorized based on treatment power: Group A (50-70 W) and Group B (70-85 W). Efficacy was determined by three independent dermatologists using digital photographs and Echelle d'Evaluation Clinique des Cicatrices d'Acné (ECCA) scores, and patient-reported outcomes gauged satisfaction levels. Results: Eighty-six patients completed the study. Significant improvements were observed, with a reduction in ECCA scores from 107.21 to 42.27 (P<0.05), demonstrating notable scar amelioration across both groups, albeit with a superior outcome in Group B. All patients experienced transient side effects such as pain, erythema, and edema, deemed tolerable with no long-term adverse effects reported. The treatment was well-received, with high satisfaction rates, underscoring its efficacy and acceptable safety profile. Conclusion: Fractional microplasma RF therapy, particularly at higher power settings, is an effective and safe option for treating atrophic acne scars, offering significant aesthetic improvement with manageable discomfort. This modality presents a valuable addition to acne scar management strategies, especially for patients with darker skin tones seeking minimal downtime and reduced risk of hyperpigmentation.

Growing or declining penalties? A cross-temporal analysis of unemployment scars in the German labor market.

We know that unemployment leaves scars. Unemployment scars are the penalties in terms of employment outcomes that workers experience due to past unemployment. To date we lack a long-term longitudinal account which examines how unemployment scarring has developed over time. The aim of this article is to fill this gap. We draw on longitudinal data from the German Socio-Economic Panel spanning a period of more than 30 years, from 1985 to 2020, and investigate long-term time trends of unemployment scarring. The German labor market has experienced profound structural and institutional change over the past decades. These changes have been associated with increased inequalities in the labor market. We examine whether the substantial transformation of the German labor market also had repercussions for the extent of post-unemployment penalties. We focus on employment probabilities and wages, and consider both short-term (two years after the unemployment incidence) and mid-term outcomes (four years after the unemployment incidence). Changes in the amount of unemployment scarring over time can also occur due to changes in the composition of the unemployed. Our analyses therefore do not only investigate how macro-economic and institutional change are associated with varying amounts of unemployment scarring, but also control for and examine the role of compositional change.

The influence of endurance exercise training on myocardial fibrosis and arrhythmogenesis in a coxsackievirus B3 myocarditis mouse model.

Nonischaemic myocardial fibrosis is associated with cardiac dysfunction, malignant arrhythmias and sudden cardiac death. In the absence of a specific aetiology, its finding as late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging is often attributed to preceding viral myocarditis. Athletes presenting with ventricular arrhythmias often have nonischaemic LGE. Previous studies have demonstrated an adverse effect of exercise on the course of acute viral myocarditis. In this study, we have investigated, for the first time, the impact of endurance training on longer-term outcomes such as myocardial fibrosis and arrhythmogenicity in a murine coxsackievirus B3 (CVB)-induced myocarditis model. Male C57BL/6J mice (n = 72) were randomly assigned to 8 weeks of forced treadmill running (EEX) or no exercise (SED). Myocarditis was induced 2 weeks later by a single intraperitoneal injection with CVB, versus vehicle in the controls (PBS). In a separate study, mice (n = 30) were subjected to pretraining for 13 weeks (preEEX), without continuation of exercise during myocarditis. Overall, continuation of exercise resulted in a milder clinical course of viral disease, with less weight loss and better preserved running capacity. CVB-EEX and preEEX-CVB mice tended to have a lower mortality rate. At sacrifice (i.e. 6 weeks after inoculation), the majority of virus was cleared from the heart. Histological assessment demonstrated prominent myocardial inflammatory infiltration and cardiomyocyte loss in both CVB groups. Inflammatory lesions in the CVB-EEX group contained higher numbers of pro-inflammatory cells (iNOS-reactive macrophages and CD8+ T lymphocytes) compared to these in CVB-SED. Treadmill running during myocarditis increased interstitial fibrosis [82.4% (CVB-EEX) vs. 56.3% (CVB-SED); P = 0.049]. Additionally, perivascular and/or interstitial fibrosis with extensive distribution was more likely to occur with exercise [64.7% and 64.7% (CVB-EEX) vs. 50% and 31.3% (CVB-SED); P = 0.048]. There was a numerical, but not significant, increase in the number of scars per cross-section (1.9 vs. 1.2; P = 0.195), with similar scar distribution and histological appearance in CVB-EEX and CVB-SED. In vivo electrophysiology studies did not induce sustained monomorphic ventricular tachycardia, only nonsustained (usually polymorphic) runs. Their cumulative beat count and duration paralleled the increased fibrosis between CVB-EEX and CVB-SED, but the difference was not significant (P = 0.084 for each). Interestingly, in mice that were subjected to pretraining only without continuation of exercise during myocarditis, no differences between pretrained and sedentary mice were observed at sacrifice (i.e. 6 weeks after inoculation and training cessation) with regard to myocardial inflammation, fibrosis, and ventricular arrhythmogenicity. In conclusion, endurance exercise during viral myocarditis modulates the inflammatory process with more pro-inflammatory cells and enhances perivascular and interstitial fibrosis development. The impact on ventricular arrhythmogenesis requires further exploration.

Enhanced bioenergetic cellular activity with metabolic switch to aerobic glycolysis in Keloid and Folliculitis Keloidalis Nuchae.

Keloid scars and folliculitis keloidalis nuchae (FKN) are benign fibroproliferative dermal lesions of unknown aetiology and ill-defined treatment, which typically present in genetically susceptible individuals. Their pathognomonic hallmarks include local aggressive invasive behaviour plus high recurrence post-therapy. In view of this, we investigated proliferative and key parameters of bioenergetic cellular characteristics of site-specific keloid-derived fibroblasts (intra(centre)- and peri(margin)-lesional) and FKN compared to normal skin and normal flat non-hypertrophic scar fibroblasts as negative controls.The results showed statistically significant (P < 0.01) and variable growth dynamics with increased proliferation and migration in keloid fibroblasts, while FKN fibroblasts showed a significant (P < 0.001) increase in proliferation but similar migration profile to controls. A statistically significant metabolic switch towards aerobic glycolysis in the fibroblasts from the disease conditions was noted. Furthermore, an increase in basal glycolysis with a concomitant increase in the cellular maximum glycolytic capacity was also demonstrated in perilesional keloid and FKN fibroblasts (P < 0.05). Mitochondrial function parameters showed increased oxidative phosphorylation in the disease conditions (P < 0.05) indicating functional mitochondria. These findings further suggest that Keloids and FKN demonstrate a switch to a metabolic phenotype of aerobic glycolysis. Increased glycolytic flux inhibition is a potential mechanistic basis for future therapy.

Inhibition and reversal of a TGF-ß1 induced myofibroblast phenotype by adipose tissue-derived paracrine factors.

BACKGROUND: Hypertrophic scarring results from myofibroblast differentiation and persistence during wound healing. Currently no effective treatment for hypertrophic scarring exists however, autologous fat grafting has been shown to improve scar elasticity, appearance, and function. The aim of this study was to understand how paracrine factors from adipose tissues and adipose-derived stromal cells (ADSC) affect fibroblast to myofibroblast differentiation. METHODS: The transforming growth factor-ß1 (TGF-ß1) induced model of myofibroblast differentiation was used to test the effect of conditioned media from adipose tissue, ADSC or lipid on the proportion of fibroblasts and myofibroblasts. RESULTS: Adipose tissue conditioned media inhibited the differentiation of fibroblasts to myofibroblasts but this inhibition was not observed following treatment with ADSC or lipid conditioned media. Hepatocyte growth factor (HGF) was readily detected in the conditioned medium from adipose tissue but not ADSC. Cells treated with HGF, or fortinib to block HGF, demonstrated that HGF was not responsible for the inhibition of myofibroblast differentiation. Conditioned media from adipose tissue was shown to reduce the proportion of myofibroblasts when added to fibroblasts previously treated with TGF-ß1, however, conditioned media treatment was unable to significantly reduce the proportion of myofibroblasts in cell populations isolated from scar tissue. CONCLUSIONS: Cultured ADSC or adipocytes have been the focus of most studies, however, this work highlights the importance of considering whole adipose tissue to further our understanding of fat grafting. This study supports the use of autologous fat grafts for scar treatment and highlights the need for further investigation to determine the mechanism.

Corneal injury repair and the potential involvement of ZEB1.

The cornea, consisting of three cellular and two non-cellular layers, is the outermost part of the eyeball and frequently injured by external physical, chemical, and microbial insults. The epithelial-to-mesenchymal transition (EMT) plays a crucial role in the repair of corneal injuries. Zinc finger E-box binding homeobox 1 (ZEB1), an important transcription factor involved in EMT, is expressed in the corneal tissues. It regulates cell activities like migration, transformation, and proliferation, and thereby affects tissue inflammation, fibrosis, tumor metastasis, and necrosis by mediating various major signaling pathways, including transforming growth factor (TGF)-ß. Dysfunction of ZEB1 would impair corneal tissue repair leading to epithelial healing delay, interstitial fibrosis, neovascularization, and squamous cell metaplasia. Understanding the mechanism underlying ZEB1 regulation of corneal injury repair will help us to formulate a therapeutic approach to enhance corneal injury repair.