The New Frontier of JAK Inhibitors: Significant Therapeutic Response to Tofacitinib in a Patient With Granulomatous Reaction to Filler in the Buttocks.

BACKGROUND: Recent research has demonstrated that Janus Kinase (JAK) inhibitors can be effective in treating refractory granulomatous diseases. CASE PRESENTATION: We report the case of a 50-year-old woman who developed a granulomatous reaction following a filler injection in her buttocks. MANAGEMENT: The patient was treated with tofacitinib, and after 1 year of therapy, the stiffness and swelling resolved without any side effects. CONCLUSION: Tofacitinib appears to be a viable option for the treatment of granulomatous reactions to fillers.

Fractional CO2 Laser Versus Microneedling Combined with Narrowband Ultraviolet and Topical Steroid for Treating Non-Segmental Vitiligo in Treatment-Resistant Localizations: A Comparative Randomized Clinical Trial Study.

Introduction: Vitiligo poses a significant challenge, particularly in treatment-resistant areas such as acral regions. This study aimed to evaluate the effectiveness and safety of combining fractional CO2 laser and microneedling with conventional therapies for non-segmental vitiligo in resistant areas. Methods: A randomized clinical trial with a paired design was conducted on 84 individuals with non-segmental vitiligo and treatment-resistant lesions. Participants in two separate groups received various combinations of interventions, including narrowband ultraviolet B (NB-UVB) and topical steroid (Clobetasol ointment) as conventional treatments, with fractional CO2 laser or microneedling as add-ons for four symmetrical treatment-resistant lesions. The treatment duration was 16 weeks, followed by observation until six months post-intervention for each patient, and it focused on assessing the percentage of repigmentation, safety, patient satisfaction, and potential adverse effects. Results: The results of the study revealed a significant difference in average efficacy, with treatments involving fractional CO2 laser and microneedling compared with other interventions without them showing a higher percentage of repigmentation. No notable distinction in repigmentation patterns was observed, except for slightly higher marginal repigmentation with microneedling. Side effects, including pain, burning sensation, and erythema, were more frequent, with no significant difference between the groups. Itching and crusting had a significant difference in the two groups. Patient satisfaction levels were comparable, with the first group slightly more than the second. Conclusion: In conclusion, combining NB-UVB and topical steroid therapies with the fractional CO2 laser or microneedling seems to be effective for vitiligo treatment in resistant areas. Attention to variations in patients' characteristics and specific body locations is necessary when applying these modalities. This study provides valuable insights into novel approaches for managing vitiligo and highlights the potential benefits of these innovative treatments in combination with conventional therapy.

The safety and efficacy of adipose tissue-derived exosomes in treating mild to moderate plaque psoriasis: A clinical study.

AIM: This study evaluates the safety and efficacy of autologous adipose-derived mesenchymal stem cell-derived exosomes as a treatment for Psoriasis, a chronic immune-related skin and joint disorder, compared to current treatments like topicals, phototherapy, and systemic. MATERIALS AND METHODS: The study isolated exosomes from Mesenchymal Stem Cells(MSCs) of healthy adipose tissue using ultracentrifugation. 12 patients with plaque psoriasis were divided into three groups and given single doses of exosomes. Tissue samples were collected pre- and post-treatment and examined for inflammatory(TNFα, IL23, IL17, IFNγ, CD3) and anti-inflammatory (FOXP3, IL10) markers. The severity of the lesion was also evaluated. KEY FINDINGS: In this study, it was found that erythema and induration (P < 0.05) decreased significantly in patients receiving 200 µg. Still, this reduction in scaling was not significant, the thickness was significantly reduced in patients receiving 100 and 200 µg doses (P < 0.05). H&E evaluation showed that the decreasing trend in these patients was not significant (P > 0.05). IHC evaluation in patients receiving doses of 100 and 200 µg showed a decrease in the presence of IL17 (P < 0.05, <0.001) & CD3(P < 0.001, <0.05) and a considerable increase in FOXP3(P ≤ 0.001), in the tissue samples of the patients. Examining the expression of inflammatory factors also shows that dose 200 µg decreased the expression of IL17(P > 0.05), IFNγ(P > 0.05), IL23(P < 0.05), & TNFα(P ≤ 0.05) and increased the expression of the anti-inflammatory factor IL10(P < 0.05). SIGNIFICANCE: The study indicates that a 200 µg dose is optimal for patients, but a larger patient population is needed for more reliable results. Additionally, higher doses or multiple injections with specific intervals can increase confidence.

Evaluation of the effects of carboxytherapy in the treatment of periorbital dark circles.

BACKGROUND: Dark eye circle (DEC) is one of the most common cosmetic problems. It has a great impact on the patients' quality of life. Carboxytherapy is a cosmetic technique using pure carbon dioxide for different uses in different areas of the body. The goal of this study is to evaluate the efficacy and tolerability of carboxytherapy in the cosmetic correction of DECs. METHODS: This study was conducted on 27 patients requesting the correction of DEC. The treatment was performed using a carboxy device in medical grade. The gas injection was performed intradermal after local anesthesia, with a pressure of one tenth bar and a speed of 20 cc/min, 1 cc in each upper and lower eyelid. The treatment sessions were done every 2 weeks for four sessions. RESULTS: The mean physicians' score of DECs before and after treatment was 8.7 ± 0.81 and 4.6 ± 1.1, respectively. The mean patients' score before and after treatment was 9.2 ± 0.5 versus 5.41 ± 1.37. The mean scores showed a significant reduction of skin discoloration without major side effects (p < 0.00001). CONCLUSION: Carboxytherapy seems to be an effective treatment option for dark circles around the eyes with a good safety profile and patient satisfaction.

Successful Treatment of Erosive Lichen Planus With Tofacitinib: A Case Series and Review of the Literature.

Lichen planus (LP) is an inflammatory disease that affects the skin, hair, nails and mucous membranes. Erosive LP is a chronic and difficult-to-treat subtype of lichen planus, characterized by lesions on mucosal surfaces, particularly in the oral and genital areas. The prevalence of erosive LP has not been determined. To date, treatment has consisted of surgical intervention, photodynamic therapy, laser therapy, and systemic or topical drugs, including steroids and immunomodulatory agents. LP usually need longer periods of treatment and are known as precancerous lesions with a 0.4% to 12% conversion rate. In addition, nearly 25% of patients who develop erosive LP of the vulva are resistant to topical corticosteroids, which are the first choice of treatment. This study reports 6 cases with a mean age of 3.33 years, who were diagnosed with erosive LP lesions and previously failed in treatment with local, intralesional, and systemic steroids, and hydroxychloroquine. These patients were then treated with 10 mg of tofacitinib per day. Interestingly, with the new treatment, the patients' mean overall satisfaction score was 9.16 out of 10 (range: 8-10), the mean pain relief score was 9.16 out of 10 (range: 9-10) and patients' symptom improvement also began an average of 1.33 months after starting treatment (range: 1-2.5 months).

DNA repair-related heritable photosensitivity syndromes: Mutation landscape in a multiethnic cohort of 17 multigenerational families with high degree of consanguinity.

Inherited photosensitivity syndromes are a heterogeneous group of genetic skin disorders with tremendous phenotypic variability, characterized by photosensitivity and defective DNA repair, especially nucleotide excision repair. A cohort of 17 Iranian families with heritable photosensitivity syndromes was evaluated to identify their genetic defect. The patients' DNA was analyzed with either whole-exome sequencing or RNA sequencing (RNA-Seq). The interpretations of the genomic results were guided by genome-wide homozygosity mapping. Haplotype analysis was performed for cases with recurrent mutations. RNA-Seq, in addition to mutation detection, was also utilized to confirm the pathogenicity. Thirteen sequence variants, including six previously unreported pathogenic variants, were disclosed in 17 Iranian families, with XPC as the most common mutated gene in 10 families (59%). In one patient, RNA-Seq, as a first-tier diagnostic approach, revealed a non-canonical homozygous germline variant: XPC:c.413-9 T > A. The Sashimi plot showed skipping of exon 4 with dramatic XPC down-expression. Haplotype analysis of XPC:c.2251-1 G>C and XPC:1243 C>T in four families showed common haplotypes of 1.7 Mb and 2.6 Mb, respectively, denoting a founder effect. Lastly, two extremely rare cases were presented in this report: a homozygous UVSSA:c .1990 C>T was disclosed, and ERCC2-related cerebro-oculo-facio-skeletal (COFS) syndrome with an early childhood death. A direct comparison of our data with the results of previously reported cohorts demonstrates the international mutation landscape of DNA repair-related photosensitivity disorders, although population-specific differences were observed.

The Combined Application of Bleomycin and Triamcinolone for Treating Refractory Keloids.

BACKGROUND: Triamcinolone acetate injections are considered the first treatment option for keloids, but quite high proportions of keloids either do not respond to triamcinolone or develop recurrence. Beneficial effects of intralesional bleomycin have been recently shown in the treatment of keloids and hypertrophic scars. However, the efficacy of combination therapy using intralesional triamcinolone and bleomycin remains undetermined. OBJECTIVE: The purpose of this study was to evaluate the efficacy of using bleomycin and triamcinolone mixture to treat refractory keloids. MATERIALS AND METHODS: In total, 33 patients with resistant keloids (including 8 men and 25 women) and a mean age of 36.52 years (age range of 18-65 years) were enrolled in this study. A mixture of bleomycin (1 u/cc) with triamcinolone acetonide (13.3 mg/cc) was injected intralesionally into the keloids every 4 to 6 weeks for a maximum of 6 cycles. The clinical improvement was evaluated using the Japan Scar Scale (JSS) and the physician's global assessment of the flattening of the lesions. Side effects were also noted and recorded. RESULTS: In all patients, the total JSS scores decreased significantly after treatment (2.33 ± 1.05), compared with baseline (11.61 ± 2.59), ( p < .001); 26 keloids (78.8%) showed an excellent response (75%-100% flattening), 7 keloids (21.2%) showed a fair response (25%-75% flattening), and 0 keloids (0%) showed a poor response (<25% flattening). Observed side effects were ulceration (33.3%), hyperpigmentation (33.3%), hypopigmentation (15.15%), secondary infection (33.3%), and telangiectasis (15.15%). CONCLUSION: The combined use of bleomycin and triamcinolone offers a promising treatment option for individuals who have not responded well to traditional therapies.

Non-thermal CO2 Laser Therapy (NTCLT): A Novel Photobiomodulative Approach for Immediate Pain Relief of Patchy Oral Mucositis Due to Chemotherapy of Solid Tumors.

Introduction: Chemotherapy-induced oral mucositis (COM) is a prominent complication of chemotherapy (CT). Non-thermal CO2 laser therapy (NTCLT) has been demonstrated as an innovative and safe photobiomodulative approach in some kinds of painful oral lesions. The purpose of this study was to evaluate the palliative effects of one session of NTCLT on COM lesions. Methods: Patients with painful COM (WHO grade:≥2) were included in this before-after clinical trial based on the eligibility criteria. The oral lesions were irradiated with a CO2 laser (power: 1 W, scanning the lesions with the rapid circular motion of the defocused handpiece) through a thick layer (3-4 mm) of a transparent gel containing a high-water content. The severity of pain in the lesions was self-assessed using a 0-to-10 visual analogue scale (VAS) for 7 consecutive days. The evaluating physician visited the patients on the 3rd and 7th days in search of any kind of complications. Results: Seventeen adult patients with 35 patches of OM due to chemotherapy of solid tumors completed the trial. Immediately after NTCLT, the mean for non-contact VAS pain scores of the lesions significantly declined from 4.91±2.356 to 0.29±0.622 (P<0.001) and the mean for contact VAS pain scores from 7.77±1.57 to 1.31±1.18 (P<0.001). The mean VAS pain scores of the lesions showed statistically significant differences between the follow-up periods compared to the baseline (P<0.001). The process was completely pain-free and required no anesthesia. After NTCLT, no kind of thermal adverse effects such as irritation, destruction, aggravation and even erythema were observed. Conclusion: Based on the results of this before-after clinical trial, NTCLT has the potential to be considered as a non-invasive and safe palliative option for the pain management of patchy OM due to chemotherapy of solid tumors.

Exploring the Efficacy of Fractional Carbon Dioxide Laser as an Add-on Combination to Conventional Therapies for Treatment-Resistant Vitiligo (A Review Article).

Introduction: Vitiligo, a dermatological disorder that leads to depigmented skin patches, presents a significant challenge, particularly in resistant areas such as acral regions. Fractional CO2 laser therapy holds promise as an adjunct to conventional treatment, enhancing repigmentation. This review comprehensively explores its efficacy and safety in resistant-to-treatment vitiligo. Methods: We conducted extensive database searches in PubMed, Embase, and Cochrane, focusing on English-language literature published between 2012 and 2023. We included comparative studies that met the following criteria: (1) Participants had non-segmental vitiligo, with resistant-to-treatment localization engagement; (2) The treatment involved the use of fractional CO2 laser in combination with conventional therapies; and (3) Outcomes were assessed based on the repigmentation ratio or significant difference. We excluded studies from which data from published results could not be extracted. Results: After extensive screening of 52 articles, we finally selected five studies. The results showed that fractional CO2 laser therapy, when combined with other treatments, often shows promise in vitiligo treatment in refractory cases. Although individual responses varied, overall efficacy and safety were promising, with minimal adverse effects and no severe complications. Conclusion: The fractional CO2 laser, when used in conjunction with conventional therapies, emerges as a promising option for treating refractory vitiligo. Large-scale randomized trials and a deeper understanding of the underlying mechanisms are vital for future progress in optimizing treatment protocols, case selection, and safety.

Effect of the 1064 nm Nd: YAG Laser on the MICs of Antifungals Used in Clinical Practice for the Treatment of Fungal Nail Infections.

Introduction: The fungal nail infection (onychomycosis) involves 18%-40% of all nail disorders, which, although not fatal, can cause mechanical, aesthetic, occupational, and economic problems. Drug treatments due to prolonged treatment periods, drug interactions, adverse effects, and slow progression may associate with numerous negative outcomes. This study aimed to evaluate the long-pulsed 1064-nm Nd: YAG laser effect on fungal colonies and subsequently possible change in the minimum inhibitory concentrations (MICs) of common antifungals compared with the same non-lasered colonies as a novel way to investigate laser and antifungal interaction. Methods: Sixty onychomycosis samples consisting of saprophyte (n=20), dermatophyte (n=20), and yeast (n=20) duplicate colonies were isolated. A series was treated by a long-pulsed 1064-nm Nd: YAG laser. Afterward, the MIC (CLSI-M38-A2 and CLSI-M27-A3) of two series against common antifungals were compared. Results: After 1064-nm Nd: YAG laser irradiation in all 20 tested saprophytes, the MICs of terbinafine (P value<0.035) were changed, and in all 20 tested dermatophytes, the MICs of voriconazole (P value<0.021) were changed. Also, in all 20 tested yeasts, the MICs of caspofungin (P value<0.037) were changed. Moreover, in saprophytes, dermatophytes, and yeasts, significant changes in the MICs of itraconazole (P value<0.032), terbinafine (P value<0.025), and caspofungin (P value<0.037) were detected. Our result showed the GM MICs of the 1064-nm Nd: YAG laser in all saprophyte, dermatophyte, and yeast groups were lower than in the control group. Conclusion: The present study indicated that the long-pulsed 1064-nm Nd: YAG laser significantly changes the MICs of antifungals in onychomycosis clinical samples.

Treatment of superficial and deep partial width second degree burn's wound with allogeneic cord blood platelet gel.

BACKGROUND: Burns are caused by a variety of mechanisms, including flames, hot liquids, metallurgy, chemicals, electric current, and ionizing and non-ionizing radiation. The most significant burn wound management involves complete repair and regeneration as soon as possible while minimizing infection, contraction, and scarring in the damaged tissue area. Some factors such as delivery of nutrients, growth factors, and oxygen are essential to promote and stimulate the wound healing progress in the burns area. When these factors are not provided, the burn wound undergoes a physiological crisis. The use of growth factors is a promising approach to overcoming this limitation. Umbilical cord blood platelet concentrates are a rich natural source of growth factors. METHODS: This clinical trial used growth factors released from the lysis of umbilical cord blood platelet concentrates that have a key role in promoting re-epithelization and regeneration of damaged tissues by forming a fibrin network. This study evaluated the effectiveness of allogeneic cord blood platelet gel topical dressing in a group of patients diagnosed with superficial and deep partial thickness (second-degree) burn wounds. Clinical outcomes were compared between the intervention group and a control group of patients with superficial second-degree burn wounds who received the standard routine treatment including paraffin gauze wound dressing and silver sulfadiazine ointment. RESULTS: The study's results showed that the increased rate of recovery and tissue granulation completely promoted to wound healing and burn wound closure, decreased the recovery time, and reduced inflammation and scars caused by burn injuries. However, the use of cord blood platelet gel topical dressing is not currently a routine treatment method in patients suffering from burn wounds. However, the study's results showed that allogenic cord blood platelet gel could be used to treat superficial and deep second-degree burns as a routine treatment. It was also shown that allogenic cord blood platelet gel topical dressing could be a candidate for autograft or after autograft skin transplantation surgery (in donor and recipient sites) instead of skin surgery in some patients. CONCLUSION: Allogeneic topical wound dressing provides an effective treatment that offers a faster rate of epithelialization and healing of wounds and also decreases patients' scar and inflammation level as well as the length of recovery time. This, finally, leads to better burn wound management and the improved quality of burn wound treatment.

BCL11B Is Involved in Stress-Induced Differentiation of Keratinocytes and Has A Potential Role in Psoriasis Pathogenesis.

OBJECTIVE: Psoriasis is a common, auto-immune skin disease characterized by abnormal proliferation and differentiation of keratinocytes. Studies revealed the role of stress stimulators in the pathogenesis of psoriasis. Oxidative stress and heat shock are two important stress factors tuning differentiation and proliferation of keratinocytes, regarding to psoriasis disease. BCL11B is a transcription factor with critical role in embryonic keratinocyte differentiation and proliferation. Given this, in keratinocytes we have investigated potential role of BCL11B in stress-induced differentiation. Furthermore, we searched for a potential intercommunication between BCL11B expression and psoriasis-related keratinocyte stress factors. MATERIALS AND METHODS: In this experimental study, data sets of psoriatic and healthy skin samples were downloaded in silico and BCL11B was chosen as a potential transcription factor to analyze. Next, a synchronized in vitro model was designed for keratinocyte proliferation and differentiation. Oxidative stress and heat shock treatments were employed on HaCaT keratinocytes in culture, and BCL11B expression level was measured. Cell proliferation rate and differentiation were analyzed by synchronized procedure test. Flow cytometry was done to analyze cell cycle alterations due to the oxidative stress. RESULTS: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) data revealed a significant upregulation of BCL11B expression in keratinocytes, by 24 hours after initiating differentiation. However, it was followed by a significant down-regulation in almost all the experiments, including the synchronized model. Flow cytometer data demonstrated a G1 cell cycle arrest in the treated cells. CONCLUSION: Results indicated a remarkable role of BCL11B in differentiation and proliferation of HaCaT keratinocytes. This data along with the results of flow cytometer suggested a probable role for BCL11B in stress-induced differentiation, which is similar to what is happening during initiation and progression of normal differentiation.

Whole transcriptome-based skin virome profiling in typical epidermodysplasia verruciformis reveals α-, ß-, and γ-HPV infections.

HPVs are DNA viruses include approximately 450 types that are classified into 5 genera (α-, ß-, γ-, µ-, and ν-HPV). The γ- and ß-HPVs are present in low copy numbers in healthy individuals; however, in patients with an inborn error of immunity, certain species of ß-HPVs can cause epidermodysplasia verruciformis (EV), manifesting as recalcitrant cutaneous warts and skin cancer. EV presents as either typical or atypical. Manifestations of typical EV are limited to the skin and are caused by abnormal keratinocyte-intrinsic immunity to ß-HPVs due to pathogenic sequence variants in TMC6, TMC8, or CIB1. We applied a transcriptome-based computational pipeline, VirPy, to RNA extracted from normal-appearing skin and wart samples of patients with typical EV to explore the viral and human genetic determinants. In 26 patients, 9 distinct biallelic mutations were detected in TMC6, TMC8, and CIB1, 7 of which are previously unreported to our knowledge. Additionally, 20 different HPV species, including 3 α-HPVs, 16 ß-HPVs, and 1 γ-HPV, were detected, 8 of which are reported here for the first time to our knowledge in patients with EV (ß-HPV-37, -47, -80, -151, and -159; α-HPV-2 and -57; and γ-HPV-128). This study expands the TMC6, TMC8, and CIB1 sequence variant spectrum and implicates new HPV subtypes in the pathogenesis of typical EV.

Efficacy of oral tofacitinib in refractory chronic spontaneous urticaria and urticarial vasculitis.

The treatment of chronic urticaria (CU) is difficult, currently, antihistamines (AH) are the mainstay of treatment, however, up to 40% of patients do not respond to even high (four-fold) daily doses of AH. Tofacitinib is, a small-molecule that blocks JAK1/3 and inhibits intracellular signaling of multiple key cytokines involved in the inflammatory cascade and its beneficial effects were reported in patients with mast cell activation disease but there is no report in patients with urticaria. Here, we present four cases of refractory CU and one case of urticarial vasculitis (UV) that were managed with tofacitinib. Despite the long-term unresponsiveness of various treatments in our patients, the addition of tofacitinib significantly improved the urticarial activity and ultimately led to tapering and discontinuation of cyclosporine or AH. In conclusion, tofacitinib appears to downregulate inflammatory phenomena associated with mast cells and might be a new therapeutic option for patients with refractory CU or UV.

Optimizing parameters of the Pulsed Dye Laser (PDL, 585-nm) for hemangioma treatment using diffuse reflectance spectroscopy.

INTRODUCTION: The lack of objectivity options for a specific individualized therapy might cause challenges in laser treatment. In other words, we need optimally determined laser parameters for less side effects. Generally, laser treatment procedures seem to be subjective. Then, the final evaluation of the patient needs for optimized better response with less laser sections and less side effects. Therefore, employing a reliable objective technique seems to be essential for better response with less laser treatment sessions and also less side effects. METHOD: In this research, UV-visible diffused reflection spectra from normal skin and a lesion were taken. We obtained the differences in absorption intensity at 575 nm, the wavelength corresponds to the absorption peak of blood oxyhemoglobin for normal skin and hemangioma. To calibrate the measurements, after using pulsed dye laser (PDL at 585 nm), the PDL treatment response of the patients were graded as "good (>50%), moderate(25%-50%), and poor (0%-25%)," by a specialist. Finally, patients were categorized based on the energy of the laser for the best treatment response to propose the recommended laser parameters. RESULTS: Based on the differences in the absorption peak hemangioma compare with normal skin, the energy density of PDL for a good treatment response of hemangioma was obtained at peak wavelength 575 nm. CONCLUSION: The analysis of optical reflection spectroscopy can assess the correlation of absorption peak differences of vascular lesions and normal skin. According to this data, it seems to be effective in optimizing lasers parameters for the hemangioma treatment.

Evaluation of Efficacy and Safety of Low-Fluence Q-Switched 1064-nm Laser in Infra-orbital Hyperpigmentation Based on Biometric Parameters.

Introduction: Dark circles and wrinkles under the eyes are common cosmetic problems, caused by various conditions, especially aging and overproduction of melanin in the epidermis or dermis of the skin. Iin addition to the application of topical lightening agents, different types of lasers, especially the Q-Switched ND:YAG laser, have been used for the treatment of cutaneous hyperpigmentation. Because of a high prevalence of idiopathic eye dark circles (EDCs) or periorbital melanosis and a poor response to available therapies, we decided to evaluate the efficacy and safety of the Fractional QS 1064 nm ND:YAG Laser through a before-after trial. Methods: 18-65-year-old patients with skin Fitzpatrick phototype of I-V and without any usage of a topical or systemic therapeutic regimen (2-4 weeks before the trial) were enrolled in the study. Each patient was treated with 6 sessions of the Fractional QS 1064 nm ND:YAG Laser at 2-week intervals and assessed for response and possible side effects or recurrences through 4 outcome measures, including Visoface-based color and erythema, melanin index and lightness (Before the fourth and sixth sessions of the therapy; also 1 week and 3 months after finishing the trial). Results: The changes of Visoface-based color and erythema, the melanin pigment amount by the Mexameter (melanin index) and the degree of lightness by the Colorimeter of patients after 6 months of intervention were statistically significant (P < 0.001). Conclusion: The fractional QS 1,064 nm ND:YAG Laser is an effective and safe therapy in EDCs since objective outcomes like the reduction of the melanin index and improving lightness and subjective ones like the reduction of darkness and erythema were confirmed.

Biophysical evaluation of treating adipose tissue-derived stem cells using non-thermal atmospheric pressure plasma.

Non-thermal atmospheric pressure plasma (NTAPP) is a partially ionized gas containing fast electrons and relatively slow ions. This study aims to investigate the influences of NTAPP on human adipose tissue-derived stem cells (ADSCs) and examine the feasibility of using optical spectroscopy as a non-destructive method for cell analysis. A plasma jet is used as the source of low-temperature plasma in which pure helium gas is ionized by a high voltage (8 kV) and frequency (6 kHz). ADSCs were exposed to the NTAPP for 30 s, 60 s, 90 s, and 120 s. The efficiency of the plasma treatment was investigated using flow cytometry and optical spectroscopy methods. This study compared surface markers of NTAPP treated and untreated ADSCs using CD90 and CD105 as positive markers. The result proved that NTAPP-exposed ADSCs maintain their stemming. Measuring ADSCS apoptosis by labeling Annexin V-Propidium Iodide showed that the plasma at short exposure time is relatively non-toxic. However, a longer exposure time can lead to apoptosis and necrosis. Moreover, Cell cycle analysis revealed that NTAPP accelerates the cell cycle in very low doses and can cause proliferation. In this experiment, flow cytometry measurements have been used to determine oxidative stress. The results showed that with increasing plasma dose, intracellular ROS levels reduced. This data also suggests that intracellular ROS are not responsible for the cells' viability. Furthermore, we used reflectance spectroscopy as a non-destructive method for evaluating treatment response and comparing this method with cell analysis techniques. The results indicate spectroscopy's efficiency as a method of cell analysis. This study suggests that NTAPP would be an efficient tool to improve ADSCs culture's efficiency in vitro; thus, we support the potential applications of NTAPP in the field of stem cell therapy and regenerative medicine.

Mutation update: The spectra of PLEC sequence variants and related plectinopathies.

Plectin, encoded by PLEC, is a cytoskeletal linker of intermediate filaments expressed in many cell types. Plectin consists of three main domains that determine its functionality: the N-terminal domain, the Rod domain, and the C-terminal domain. Molecular defects of PLEC correlating with the functional aspects lead to a group of rare heritable disorders, plectinopathies. These multisystem disorders include an autosomal dominant form of epidermolysis bullosa simplex (EBS-Ogna), limb-girdle muscular dystrophy (LGMD), aplasia cutis congenita (ACC), and an autosomal recessive form of EBS, which may associate with muscular dystrophy (EBS-MD), pyloric atresia (EBS-PA), and/or congenital myasthenic syndrome (EBS-MyS). In this study, genotyping of over 600 Iranian patients with epidermolysis bullosa by next-generation sequencing identified 15 patients with disease-causing PLEC variants. This mutation update analyzes the clinical spectrum of PLEC in our cohort and in the literature and demonstrates the relationship between PLEC genotype and phenotypic manifestations. This study has integrated our seven novel PLEC variants and phenotypic findings with previously published data totaling 116 variants to provide the most complete overview of pathogenic PLEC variants and related disorders.

The epidemiology and etiology of onychomycosis in 2 laboratory centers affiliated to Tehran university of medical sciences during 2019-2020.

Background and Objectives: Onychomycosis is caused by dermatophyte species, non-dermatophyte moulds (NDMs), and accounts for roughly 50% of all nail diseases. As the prevalence of onychomycosis is increasing, new epidemiologic documents may help with treatment and prevention. The present investigation aims to determine the epidemiological profile of onychomycosis in 2 mycology laboratories. Materials and Methods: A cross-sectional study conducted during eight months (2019-2020) on 169 patients with positive nail mycology tests referred to two mycological laboratory centers affiliated with Tehran University of Medical Science. The nail clippings were examined by direct smear and culture. Also, molecular assays were performed if needed. Results: 10% of nail lesions referred to Razi Hospital (RH), and 30% of nail lesions referred to TUMS mycology laboratory were positive. Middle age (40-60) suffer more from onychomycosis. Aspergillus flavus, Trichophyton mentagrophytes, and Candida albicans were the most common etiologic agents in each of the three main classes of fungi causing onychomycosis. Females were more infected. NDMs were the predominant etiologic agents, and toenails were the most common site of onychomycosis. Conclusion: The pattern of etiologic agents and clinical signs of onychomycosis differs according to geographical region and age, so repeated epidemiological surveys of onychomycosis seem to be fundamental.