Tocotrienol-Rich Fraction as a Protective Agent against Blue Light Induced Oxidative Stress and Melanogenesis in B16-F1 Melanocytes (preprint)

Our skin is constantly exposed to blue light (BL), which is abundant in sunlight and emitted by digital devices. Prolonged exposure to BL can lead to oxidative stress-induced damages and skin hyperpigmentation. In this study, we investigated the protective effects of tocotrienol-rich fraction (TRF) on BL-induced oxidative stress and hyperpigmentation in B16-F1 melanocytes. Alpha-tocopherol (αTP) was used as a comparator. Our results showed that TRF effectively suppressed the formation of reactive oxygen species, and preserved the mitochondrial membrane potential. Additionally, TRF exhibited anti-apoptotic properties by reducing the activation of p38 mitogen-activated protein kinase molecule and downregulating the expression of cleaved caspase-3. Moreover, TRF modulated tyrosinase activity, resulting in a lowered rate of melanogenesis and reduced melanin production. In contrast, αTP did not exhibit the significant protective effects against skin damages and pigmentation in BL-induced B16-F1 cells. Therefore, this study indicates that TRF may offer superior protective effects over αTP against the effects of BL on melanocytes. These findings demonstrate the potential of TRF as a protective natural active against BL-induced skin damages and hyperpigmentation via its antioxidative and anti-melanogenic properties.

Generalized Rash in Severe Hospitalized COVID Patients: Correlation between Histological Examination, Drug Intake, Blood Interleukins Profileand Long-Term Follow-Up (preprint)

Background: There have been few reports of cutaneous skin lesions in severe COVID-19 hospitalized patients which exhibit different behavior compared to outpatients. Furthermore, a notable lack of rigorous studies exits. In this study we included patients with generalized rash during the first wave of the pandemic for characterization.Methods: Hospitalized patients with severe confirmed pulmonary COVID-19 infection and a generalized cutaneous rash during the first wave in March-May 2020 were included. The study received approval from the ethics committee. Clinical presentation, histo-logical examination, blood test, and complete blood interleukin profile were assessed. Special immunohistochemical investigations were conducted. Long term follow-up of the patient was performed throuhg a phone call 24 months later. Results: A total 28 patients were studied and classified by histological examination into three groups: G1: perivascular dermatitis (18/28, 64%); G2: Drug reaction (7/28, 25%); and G3: Generalized exanthema and chilblain (3/28, 11%). The virus was not detected in the skin, by PCR and by immunohistochemical analysis, and the interleukin expression in the skin were undetectable results. Vascular cell adhesion molecule 1 (VCAM1), E-selectine, and IT Galpha 5 were unspecific. G1 exhibited the least inflammation, G2 the most in-flammatory, and G3 had previous inflammation. Discussion: Our data suggest that generalized exanthemas during severe SARS-Cov-2 infection exhibit unspecific finding and are similar to other rashes caused by inflammation. Drug reaction should be considered, as they accounted for 25% of the rashes. Further studies including higher number of patients are necessary.

A Negative Emotion Recognition System with IoT-Based Multimodal Biosignal Data (preprint)

Previous studies to recognize negative emotions (e.g. disgust, fear, sadness) for mental health care have used heavy equipment directly attaching electroencephalogram (EEG) electrodes to the head, making it difficult to use in daily life, and they have proposed binary classification methods to determine whether negative emotion or not. To tackle this problem, we propose a negative emotion recognition system to collect multimodal biosignal data such as five EEG signals in an EEG headset and heart rate, galvanic skin response, and skin temperature in a smart band for classifying multiple negative emotions. It consists of android Internet of Things (IoT) application, an oneM2M-compliant IoT server, and a machine learning server. The android IoT application upload the biosignal data to the IoT server. By using the biosignal data stored in the IoT server, the machine learning server recognizes the negative emotions of disgust, fear, and sadness using a multi-class support vector machine (SVM) model with a radial basis function kernel (RBF). The experimental results showed that the multi-class SVM model achieved 93% accuracy when considering all the multimodal biosignal data. Moreover, when considering only data in the smart band, it could achieve 98% accuracy by optimizing the hyper-parameter of the RBF kernel.

Zoon’s Balanitis as a Separate Type of Balanitis with the Characteristic Pattern of Pro-Inflammatory Cytokines Expression (preprint)

Zoon balanitis (ZB) is a mild and chronic inflammatory dermatosis that mostly affects uncircumcised men of middle and old age. The etiology of this disease remains unknown. Moreover, some authors have questioned the presence of this type of balanitis. Our study aimed to assess the expression of proinflammatory cytokines in ZB and demonstrate the presence of a characteristic expression pattern, different from that reported in the literature for penile lichen sclerosus(LS) and penile cancer. Skin biopsies from four foreskins affected by Zoon’s balanitis with surrounding morphologically unchanged skin and 13 from nonlesional foreskins (healthy control adult males undergoing circumcision) were obtained. RNA was extracted from each biopsy, followed by quantitative assessment of the gene expression of interleukin 1-A(IL-1A), interleukin 1-B(IL-1B),interleukin 1 receptor antagonist(IL-1RN),interleukin 6(IL-6), transforming growth factor β1(TGF-β1), and interferon-gamma(INF-γ). The decreased level of IL-1A mRNA was observed in Zoon’s balanitis in both inflamed and healthy skin compared to control samples. There were no statistically significant differences in other investigated cytokines gene expression between Zoon’s balanitis and the control group. In conclusion, the expression of proinflammatory cytokines was not related to the course of zoon balanitis. Moreover, in the case of IL-1A, we observed the suppression of the immune response.

Classification of Skin Lesion Images Using Artificial Intelligence Methodologies through Radial FourierMellin, Hilbert Transforms Signatures (preprint)

Eight lesions were analyzed using some algorithms of Intelligence Artificial: basal cell carcinoma (BCC), squamous cell carcinoma (SCC), melanoma (MEL), actinic keratosis (AK), benign keratosis (BKL), dermatofibromas (DF), melanocytic nevi (NV), and vascular lesions (VASC). This manuscript presents the possibility of using concatenated signatures (instead of images) obtained from different integral transforms, such as Fourier, Mellin, and Hilbert, to classify skin lesions. Eleven other Artificial Intelligence models were applied so that eight skin lesions could be classified by analyzing the particular signatures of each lesion. The database was randomly divided into 80%–20% for the training and test datasets images, respectively. The metrics that are being reported are accuracy, sensitivity, specificity, and precision. Each case was repeated 30 times to avoid bias, according to the central limit theorem in this work, and the average and ±standard deviation were reported. Although all the results were very satisfactory, the best average mark for the eight lesions analyzed was obtained using the Subspace KNN model, where the metrics for the test were 99.98% accuracy, 99.96% sensitivity, 99.99% specificity, and 99.95% precision.

IL-31—Pruritus Interleukin: Serum Values and Clinical Impact in Chronic Spontaneous Urticaria —A Romanian Retrospective Study (preprint)

(1) Background: This study aimed to evaluate the implications of IL-31 in the pathogenesis of chronic spontaneous urticaria (CSU) and to assess the differences that occur between its serum values compared to controls. Additionally, the serum IL-31 levels were measured alongside other clinical and paraclinical parameters identified in the patients to understand its immunological importance in this skin disease and to determine if it could potentially serve as a therapeutic target in CSU in the future. (2) Methods: The serum levels of IL-31 were estimated in 50 patients diagnosed with CSU according to the international guidelines. Additionally, 38 controls who had not experienced any episodes of urticaria during their lifetime were included. (3) Results: Our data have shown higher serum levels of IL-31 in CSU patients compared to controls. A correlation between the serum level of IL-31 and other inflammatory markers, such as ERS, CRP, or serum eosinophils and total IgE was not identified. On the other hand, statistically significant differences were found in IL-31 serum values in UCS patients depending on the severity of the disease, its impact on the patients' quality of life, the severity of itching, and the response to H1 antihistamines. (4) Conclusions: In the present study, IL-31 did not change directly with non-specific inflammation, nor with eosinophilic inflammation or atopy. However, its expression was modified in CSU depending on major characteristics of the disease: severity, pruritus, and response to H1 antihistamines. The focus on the pathogenesis of CSU is of indisputable significance since any additional information in understanding the mechanisms of this disease can open doors to new therapeutic targets. This is particularly important considering that the available therapies are deficient, incomplete, and the remaining symptoms are uncontrolled in many cases.

Occupational dermatoses in health care personnel using PPE during the COVID pandemic. (preprint)

Background: A sudden surge of occupation-associated dermatoses among the healthcare workers (HCWs) serving COVID-19 patients have been witnessed recently due to increased usage of PPE (PPE) kits and increased frequency of hygiene practices, with a significant impact on their quality of life and compromised efficacy at work. Hence, this study was conducted to measure the prevalence of occupational dermatoses among HCWs serving Covid-19 patients using PPE kits and hygiene practices and their impact on quality of life. Methods: HCWs of all cadres were screened for occupation-associated dermatoses. Cases with occupational dermatosis were evaluated further regarding the use of a PPE kit, and DLQI was calculated. Results: 19% of HCWs had dermatoses associated with PPE and hygiene practices. Hands were most affected, followed by the face, nasal bridge, and facial skin in contact with goggles. 48% had Mathias score >/= 4. Most cases had reported some impact on their quality of life. A significant association could be established between frequency of hand washing >/= 10 times/day with hand dermatitis (p=0.000). Conclusion: The use of PPE has significantly raised cases of occupational dermatosis among HCWs. Repeated hand washing and hand sanitizer use has increased the incidence of hand dermatitis.

Value of the Lymphocyte Transformation Test for the Diagnosis of Drug-Induced Hypersensitivity Reactions in Severe Hospitalized COVID-19 Patients (preprint)

In the first wave of COVID-19, up to 20% of patients had skin lesions with variable characteristics. There is no clear evidence of the involvement of the SARS-CoV-2 virus in all the cases; some of these lesions may be secondary to drug hypersensitivity. To analyze the possible cause of the skin lesions, we performed a complete allergology study on 11 patients. One year after recovery from COVID-19, we performed a lymphocyte transformation test (LTT) and Th1/Th2 cytokine secretion assays of PBMC. We included 5 nonallergic patients treated with the same drugs without lesions. Except for one patient who had an immediate reaction to azithromycin, all patients had a positive LTT to at least one of the drugs tested (azithromycin, clavulanic acid, hydroxychloroquine, lopinavir, and ritonavir). None of the nonallergic patients had a positive LTT. We found mixed Th1/Th2 cytokine secretion (IL-4, IL-5, IL-13, and IFN-γ) in patients with skin lesions corresponding to mixed drug hypersensitivity type IVa and IVb. In all cases, we identified a candidate drug as the culprit for skin lesions during SARS-CoV-2 infection, although only three patients had a positive drug challenge. Therefore, it would be reasonable to recommend avoiding the drug in question in all cases.

Skin Diseases Associated With COVID-19: A Narrative Review.

COVID-19 is an infectious disease caused by SARS-CoV-2, which emerged in China in 2019 and rapidly spread worldwide to become a pandemic in March 2020. Although the most severe manifestations concern the lower respiratory tract, COVID-19 is a multiorgan disease that also affects the skin. Several types of skin lesions have been reported to be associated with SARS-CoV-2 infection, though their causal relationship with the virus has not yet been well documented. In addition to the cutaneous manifestations that develop in patients with COVID-19-thought to be caused by the virus-other findings associated with the pandemic in a broader sense include dermatoses triggered or aggravated by the infection, the adverse cutaneous effects due to the drugs and protective devices used to prevent or fight the infection, and the adverse cutaneous effects of COVID-19 vaccines. We provide an overview of these dermatoses associated with the COVID-19 pandemic.

Change of dermatological practice after the COVID-19 outbreak resolves.

AIM: Dermatological care has already been deeply impacted by the coronavirus disease-2019 (COVID-19) epidemic. The consequences may continue long after the epidemic resolves. In this study, we aimed to evaluate the change of dermatological practice since the COVID-19 outbreak is almost controlled in mainland China. MATERIAL AND METHODS: Patients requesting a dermatology outpatient visit from January to May in 2019 and 2020 were retrospectively investigated. RESULTS: The number of patients decreased significantly shortly after the COVID-19 outbreak, and it started to increase after the spread of coronavirus was gradually controlled at the end of February in China. The three most common diseases were atopic dermatitis (11.0%), acne (10.2%), and warts (7.2%) in 2019, while acne (8.9%), warts (5.8%), and acute urticaria (5.6%) in 2020. The most statistically significant increased reasons for requesting an outpatient visit from March to May in 2020 was pet-related dermatophytoses, followed by cosmetic consultation and irritated contact dermatitis, an increase of 88.2%, 84.7%, and 58.8%, respectively, over the same period of 2019. CONCLUSION: Understanding the trends and impacts of dermatologic diseases on patients and health systems during this epidemic will allow for better preparation of dermatologists in the future.

Age-dependent NK cell dysfunctions in severe COVID-19 patients.

Natural Killer (NK) cells are key innate effectors of antiviral immune response, and their activity changes in ageing and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we investigated the age-related changes of NK cell phenotype and function during SARS-CoV-2 infection, by comparing adult and elderly patients both requiring mechanical ventilation. Adult patients had a reduced number of total NK cells, while elderly showed a peculiar skewing of NK cell subsets towards the CD56lowCD16high and CD56neg phenotypes, expressing activation markers and check-point inhibitory receptors. Although NK cell degranulation ability is significantly compromised in both cohorts, IFN-γ production is impaired only in adult patients in a TGF-ß-dependent manner. This inhibitory effect was associated with a shorter hospitalization time of adult patients suggesting a role for TGF-ß in preventing an excessive NK cell activation and systemic inflammation. Our data highlight an age-dependent role of NK cells in shaping SARS-CoV-2 infection toward a pathophysiological evolution.

Cutaneous Manifestation in COVID-19: A Lesson Over 2 Years Into the Pandemic.

Cutaneous manifestations related to Coronavirus Disease-19 (COVID-19) have been reported over 2 years since the pandemic began. This research aimed to review articles published in English that describe cutaneous manifestations related to COVID-19/SARS-CoV-2. A data search for case reports, original studies, and review articles from the onset of the current COVID-19 pandemic to December 31, 2022, was performed using PUBMED, Cochrane Library, ResearchGate, and Google search engines. Keywords were "coronavirus", "novel coronavirus 2019", "COVID-19", "SARS-CoV-2", and "2019-nCoV" in combination with "cutaneous", "skin" and "dermatology" The extracted data included authors, region, sex, age, number of participants with skin signs, cutaneous signs, its location, symptoms, extracutaneous/associated symptoms, suspected or confirmed status for COVID-19, timeline, and healing duration. Six authors independently reviewed the abstracts and full-texts to identify publications providing these details concerning cutaneous manifestations related to COVID-19. A total of 139 publications with full text (122 case reports, 10 case series, and 7 review articles) that reported cutaneous manifestations were identified, and reviewed from 5 continents. The most common cutaneous manifestations of COVID-19 were maculopapular, followed by chilblain-like lesion, urticarial, livedoid/necrotic, vesicular, and other/non-descript rashes/skin lesions. After 2 years into the COVID-19 pandemic, we can conclude that there is no pathognomonic cutaneous manifestation of COVID-19, since it can be also found in other viral infections.

Prevention of skin lesions caused by the use of protective face masks by an innovative gelatin-based hydrogel patch: Design and in vitro studies.

The recent Covid-19 pandemics led to the increased use of facial masks, which can cause skin lesions due to continuous pressure, tension and friction forces on the skin. A preventive approach is the inclusion of dressings between the face and the mask. However, there are still uncertainties about the protective effect of dressings and whether their use compromises the efficiency of masks. The current study aimed to develop and test the efficacy of a gelatin-based hydrogel patch to be placed between the mask and the facial area. Design of Experiment with a Quality by Design approach tools were used in the patch development and in vitro characterization was performed through rheological evaluation, ATR-FTIR and molecular docking studies. Furthermore, tribology studies were performed to test the patch performance. The results showed that the addition of excipients enhanced gelation temperature, elasticity and adhesiveness parameters. The interactions between excipients were confirmed by ATR-FTIR and molecular docking. The tribology assay revealed similar friction values at room and physiological temperature, and when testing different skin types. In conclusion, the physical properties and the performance evaluation reported in this study indicate that this innovative film-forming system can be used to prevent skin lesions caused by the continuous use of protective masks.

Prevalence of phalangeal bone marrow edema on MRI before and during the COVID-19 pandemic and correlation with chilblain skin lesions.

OBJECTIVE: The purpose of this study is to establish the prevalence bone marrow edema of the phalanges of the feet and hands before and during the COVID-19 pandemic on MRI studies and correlate with clinically chilblain skin lesions and epidemiological data. METHODS: This observational retrospective study. In patients with confirmed bone marrow edema of the phalanges, epidemiological data and clinical findings were collected, including the history of current or remote COVID-19 infection and vaccination status. The two-proportion test was used to compare the frequency of bone marrow edema in the phalanges before and during the pandemic, and the comparison between the categories variables was performed using the one-proportion test. RESULTS: Of the total of 7215 patients, only 20 presented isolated bone marrow edema of the digits in MRI studies; 2 (0.05%) were found two years before the pandemic's beginning, and 18 (0.64%) after the pandemic's onset, demonstrating an increase of 13-fold in this period. 16 were women with a mean age of 40.3 years and 4 were men with a mean age of 53.5 years. The most frequently reported clinical symptoms by the patients were pain (85.0%), and erythema of the skin (45.0%). Of the 18 patients found after the pandemic's onset, only 27.8% had COVID-19 infections confirmed by RT-PCR before the imaging study, and all cases were mild. CONCLUSION: This study demonstrated a significant increase in the prevalence of bone marrow edema of the phalanges after the onset of the COVID-19 pandemic, particularly in middle-aged and younger women.

Monkeypox detection from skin lesion images using an amalgamation of CNN models aided with Beta function-based normalization scheme.

We have recently been witnessing that our society is starting to heal from the impacts of COVID-19. The economic, social and cultural impacts of a pandemic cannot be ignored and we should be properly equipped to deal with similar situations in future. Recently, Monkeypox has been concerning the international health community with its lethal impacts for a probable pandemic. In such situations, having appropriate protocols and methodologies to deal with the outbreak efficiently is of paramount interest to the world. Early diagnosis and treatment stand as the only viable option to tackle such problems. To this end, in this paper, we propose an ensemble learning-based framework to detect the presence of the Monkeypox virus from skin lesion images. We first consider three pre-trained base learners, namely Inception V3, Xception and DenseNet169 to fine-tune on a target Monkeypox dataset. Further, we extract probabilities from these deep models to feed into the ensemble framework. To combine the outcomes, we propose a Beta function-based normalization scheme of probabilities to learn an efficient aggregation of complementary information obtained from the base learners followed by the sum rule-based ensemble. The framework is extensively evaluated on a publicly available Monkeypox skin lesion dataset using a five-fold cross-validation setup to evaluate its effectiveness. The model achieves an average of 93.39%, 88.91%, 96.78% and 92.35% accuracy, precision, recall and F1 scores, respectively. The supporting source codes are presented in https://github.com/BihanBanerjee/MonkeyPox.