Dermatologic Manifestations of Mitochondrial Dysfunction: A Review of the Literature.

Mitochondria are eukaryotic cellular organelles that function in energy metabolism, ROS production, and programmed cell death. Cutaneous epithelial and hair follicle dermal papilla cells are energy-rich cells that thereby may be affected by mitochondrial dysfunction and DNA mutation accumulation. In this review, we aimed to summarize the medical literature assessing dermatologic conditions and outcomes associated with mitochondrial dysfunction. A search of PubMed and Embase was performed with subsequent handsearching to retrieve additional relevant articles. Mitochondrial DNA (mtDNA) deletions, mutation accumulation, and damage are associated with phenotypic signs of cutaneous aging, hair loss, and impaired wound healing. In addition, several dermatologic conditions are associated with aberrant mitochondrial activity, such as systemic lupus erythematosus, psoriasis, vitiligo, and atopic dermatitis. Mouse model studies have better established causality between mitochondrial damage and dermatologic outcomes, with some depicting reversibility upon restoration of mitochondrial function. Mitochondrial function mediates a variety of dermatologic conditions, and mitochondrial components may be a promising target for therapeutic strategies.

Bacteriophages and the Microbiome in Dermatology: The Role of the Phageome and a Potential Therapeutic Strategy.

Bacteriophages, also known as phages, are viruses that selectively target and infect bacteria. In addition to bacterial dysbiosis, dermatologic conditions such as acne, psoriasis, and atopic dermatitis are characterized by a relative reduction in the abundance of phages and the overgrowth of the corresponding bacteria. Phages often exhibit high specificity for their targeted bacteria, making phage-replacement therapy a promising therapeutic strategy for the control of pathogenic bacteria in dermatologic disease. Novel therapeutic strategies regulating pathogenic bacteria are especially necessary in light of growing antibiotic resistance. In this review, we aimed to review the medical literature assessing phage dysbiosis and therapeutic trials in dermatology. Ultimately, studies have depicted promising results for the treatment of acne, psoriasis, and atopic dermatitis but are limited by low sample sizes and the omission of control groups in some trials. Additional work is necessary to validate the efficacy depicted in proof-of-concept trials and to further determine optimal treatment vehicles, administration mechanisms, and dosing schedules. This review provides the necessary framework for the assessment of phage efficacy in future trials.

Sneddon-Wilkinson disease following COVID-19 vaccination.

Sneddon-Wilkinson disease, also known as subcorneal pustular dermatosis (SPD), is a rare disease characterized by vesicles or pustules that may rapidly expand and coalesce. Idiopathic in nature, SPD's clinical presentation of "half-half" blisters, with half of each blister containing pus and half containing clear fluid, is characteristic of this disease. We describe a previously healthy 21-year-old man who developed acute pustular vesicular eruptions consistent with SPD eight days following the Moderna COVID-19 vaccination.

Non-invasive diagnostic potential of microRNA-203 in liquid biopsy of urothelial carcinoma of bladder.

Increased CD44 antigen activity has been reported in recurrent cases of UBC. To date, no reliable biomarker is available with high significance and specificity for non-invasive detection of UBC. This study aimed to identify a CD44-linked microRNAs (miRNAs) (miR-9, miR-34a, miR-203) for non-invasive diagnosis of bladder cancer from other urinary tract malignancies. The expression of CD44-linked miRNAs was examined in serum, urine, and tissue specimens of Indian UBC patients (N = 25). For this purpose, healthy subjects (N = 25) and benign prostatic hyperplasia (BPH) (N = 10) patients were taken as controls. The relative expression of miRNAs was analyzed in serum, urine, and tissue samples using real-time quantitative reverse transcription PCR (qRT-PCR). The diagnostic potential of these miRNAs was accessed by plotting ROC curve. Increased miR-9 expression was observed in serum of UBC patients than healthy and BPH controls. In UBC patients, miR-34a expression was lower than healthy controls but non-significant as compared to BPH. miR-203 expression was considerably higher in serum of UBC patients but non-significant as compared to BPH controls. miR-203 was found to be considerably higher in urine samples from UBC patients as compared to BPH and healthy controls. The diagnostic potential of these miRNAs was evaluated using the ROC curve. Higher miR-203 levels in the urine of Indian UBC patients demonstrate its non-invasive diagnostic ability out of the three miRNAs studied. Our results characterize the non-invasive diagnostic potential of CD44-linked miR-203 in the urine of Indian UBC patients, which could be utilized in clinical settings in future after validation in larger patient cohort.

DFT study of hydrogen interaction with transition metal doped graphene for efficient hydrogen storage: effect of d-orbital occupancy and Kubas interaction.

Hydrogen adsorption on pristine graphene (PG), graphene with defect (GD), and transition metal (TM) (Ag, Au, Cu, and Fe) doped graphene is systematically investigated for potential hydrogen storage using density functional theory. The stability of the TM atom doped graphene has been analysed by studying the binding energy and the electron density distribution. The TM atom-doped GD shows better binding energy and electron density overlap than PG; therefore, the TM/GD system has been considered and analysed for hydrogen adsorption. The hydrogen adsorption property is studied by examining the adsorption energy, mode of H2, density of states (DOS), charge density difference, and Löwdin charges before and after adsorption to find a better TM/GD system for hydrogen storage. The Fe/GD system shows higher hydrogen adsorption energy and hydrogen in its stable Kubas mode. Furthermore, two to five H2 molecule adsorption and desorption is studied. The increase in the number of H2, which changes the DOS at the Fermi level, suggests that one can predict H2 concentration by measuring conductivity changes. The present work is focused on studying the interaction between H2 and TM/GD systems, which will help understand the basic adsorption mechanism for practical hydrogen storage.

The effect of synthetic acetylhexapeptide-8 (AH8) on sebaceous function.

OBJECTIVE: This study aims to evaluate the in vitro and clinical effects of topical acetylhexapeptide-8 (AH8) on the appearance of oily skin. METHOD: In vitro SEB-1 human sebocyte cell lines were exposed to different concentrations of AH8, then the lipid content of the sebocytes was measured. For the randomized, controlled, split-face clinical study, participants received AH8 10% lotion formulated in Cetaphil Moisturizing Facial Lotion on one side of their face and the control vehicle lotion on the other side of their face. Facial oiliness was assessed by a trained physician using a three-point grading system, high-resolution digital photographs, and a sebumeter (SM815). Participants also filled out self-assessments of their skin oiliness. RESULTS: The in vitro experiments showed that sebocyte lipid content significantly decreased after AH8 treatment (p < 0.05 at 0.00005% AH8, p = 0.09 at 0.0005% AH8, p < 0.05 at 0.005% AH8, and p < 0.001 at 0.025% AH8). In the clinical study, participants trended towards a 10% reduction (p = 0.16) in sebum production after AH8 treatment in comparison to the vehicle treatment. CONCLUSION: AH8 inhibits the accumulation of lipids in sebocytes in vitro without altering cell proliferation or SREBP-1 expression. Topical AH8 trended towards decreased sebum production in human participants. The use of AH8 may serve as a promising agent to reduce sebocyte lipid production and the appearance of oily skin. RÉSUMÉ: Objectif Cette étude vise à évaluer les effets in vitro et cliniques de l'acétylhexapeptide-8 (AH8) topique sur l'aspect de la peau grasse. Méthode Des lignées cellulaires de sébocytes humains SEB-1 in vitro ont été exposées à différentes concentrations d'AH8, à la suite de quoi la teneur en lipides des sébocytes a été mesurée. Pour l'étude clinique randomisée, contrôlée, en hémi-visage, les participants ont reçu une lotion AH8 10 % formulée dans la lotion hydratante pour le visage Cetaphil d'un côté de leur visage et la lotion témoin de l'autre côté de leur visage. Le sébum du visage a été évalué par un médecin formé à l'aide d'un système de classification à trois points, de photographies numériques à haute résolution et d'un sébumètre (SM815). Les participants ont également rempli des auto-évaluations du sébum de leur peau. Résultats Les expériences in vitro ont montré que la teneur en lipides des sébocytes diminuait significativement après le traitement par AH8 (p < 0.05 à 0.00005 % AH8, p = 0.09 à 0.0005 % AH8, p < 0.001 à 0.025 % AH8). Dans l'étude clinique, les participants avaient tendance à voir leur production de sébum diminuer de 10 % (p = 0.16) après le traitement par AH8, par rapport au traitement par excipient. Conclusion L'AH8 inhibe l'accumulation de lipides dans les sébocytes in vitro sans altérer la prolifération cellulaire ou l'expression de SREBP-1. L'AH8 topique tendait à diminuer la production de sébum chez les participants humains. L'utilisation d'AH8 peut servir d'agent prometteur pour réduire la production de lipides sébocytaires et l'apparence de peau grasse.

Peptide-Based Antiviral Drugs.

Three types of chemical entities, namely, small organic molecules (organics), peptides, and biologics, are mainly used as drug candidates for the treatment of various diseases. Even though the peptide drugs are known since 1920 in association with the clinical use of insulin, only a limited number of peptides are currently used for therapeutics due to various disadvantages associated with them such as limited serum and blood stability, oral bioavailability, and permeability. Since, through chemical modifications and structure tuning, many of these limitations can be overcome, peptide-based drugs are gaining attention in pharmaceutical research. As of today, there are more than 60 peptide-based drugs approved by FDA, and over 150 peptides are in the advanced clinical studies. In this book chapter, the peptide-based lead compounds and drugs available for treating various viral diseases and their advantages and disadvantages when compared to small molecules drugs are discussed.

Health insurance relationship to sun protection practices and beliefs.

PURPOSE: Lower socioeconomic status is associated with decreased sun protection practices. This survey study investigated practices and beliefs surrounding sun protection based on health insurance. METHODS: 401 surveys were administered May to June 2019 at two dermatology clinics in Sacramento, California. 384 surveys by private insurance, Medi-Cal (California's Medicaid), and Medicare coverage were analyzed. RESULTS: Patients with Medi-Cal are twice as likely to rarely or never use sunscreen (OR=2.37; 95% CI 1.45-3.87; P<0.001) compared to those with private insurance. Patients with Medi-Cal or Medicare are less likely to use sunscreen (P<0.001), protective clothing (P=0.025), and sun avoidance (P=0.028). Medi-Cal patients more often used tanning beds (OR=4.90; 95% CI 1.30-18.50; P=0.019). Over half of patients with Medi-Cal agreed it is worth getting burned for a tan (54.6%, OR=2.54; 95% CI 1.41-4.62; P=0.0021). There were no significant differences in opinion that sunscreen is a hassle to apply or expensive. Groups did not differ significantly in ethnicities or skin type. CONCLUSION: Those with Medi-Cal are less likely to use all forms of sun protection and more likely to value tanning. Negative opinions of sunscreen and perceived knowledge and concern for skin cancer were similar, pointing to additional factors influencing these disparities.

Papulopustular rosacea during nivolumab therapy of metastatic squamous cell esophageal carcinoma.

We present a 76-year old man who developed papulopustular rosacea after receiving nivolumab treatment for his esophageal carcinoma, metastatic to the lungs. Nivolumab is an emerging cancer therapy whose immune-related adverse events are still not fully recognized and likely underreported. The treatment has been reported to cause a myriad of cutaneous immune-related adverse events. However, nivolumab-induced-papulopustular rosacea has been scarcely reported. Thus, this case presents a clinically important finding that physicians should be aware of when seeing patients on nivolumab therapy.

Anti-MDA-5 negative, anti-Ku positive clinically amyopathic dermatomyositis.

We present a patient with anti-MDA5 negative, anti-Ku positive clinically amyopathic dermatomyositis (CADM). A 61-year-old woman presented with a chief complaint of a 20-year history of a pruritic rash that was active on her face, chest, hands, legs, and back. A mildly scaly, erythematous, photo-distributed eruption along with slightly violaceous, scaly papules accentuated on the wrist, metacarpophalangeal joints, proximal interphalangeal and distal interphalangeal joints. Antibody profile was significant for positive ANA and anti-dsDNA, elevated anti-TIF-1gamma (RDL)/p155, and weakly positive anti Ku. Biopsy was consistent with dermatomyositis. Melanoma differentiation-associated gene 5 antibody (anti-MDA-5) has been identified as the most commonly associated autoantibody found in CADM and is associated with poor prognosis and a biomarker for the diagnosis of rapidly progressive interstitial lung disease. To our knowledge, our patient is the first case of negative anti-MDA-5 and anti-Ku positive CADM.

Lichen planopilaris with significant post-inflammatory pigmentary alteration.

Lichen planopilaris is an uncommon dermatological manifestation of lichen planus of the scalp and results in cicatricial alopecia. We present a patient with lichen planopilaris and significant post-inflammatory pigmentary alteration, confirmed by histopathology. The patient's case represents a clinically important variation from an expected typical pattern of dyschromia at periphery of alopecic zones in lichen planopilaris.

Directing Group Assisted Unsymmetrical Multiple Functionalization of Arene C-H Bonds.

Multiple C-H bond functionalizations promptly install diverse groups on the molecular framework and consequently fabricate complex molecular entities. This review briefly surveys the conceptual development of directing group assisted unsymmetrical multiple functionalization of arene C(sp2 )-H bonds, which is exceedingly appealing and highly important.

Sulfoximine-Assisted Unsymmetrical Twofold C-H Functionalization of Arenes.

An unprecedented ruthenium (Ru)-catalyzed twofold unsymmetrical annulation of 3-O/N-allyl benzoic acid derivatives with isocyanates for the construction of dihydro-furan/indole-fused phthalimide scaffolds is discussed. This double-unsymmetrical functionalization of both o,o'-C-H bonds of arene moiety is explicitly viable under the influence of methylphenyl sulfoximine directing group constructing three different [C-C/C-C(O)/N-C(O)] bonds under a single catalytic system. A broad scope with all six-carbon-substituted arene motifs, control experiments, and gram-scale synthesis make the synthetic model viable and significant.

Comparison of 2-Octylcyanoacrylate Versus 5-0 Fast-Absorbing Gut During Linear Wound Closures and the Effect on Wound Cosmesis.

BACKGROUND: Although the use of 2-octylcyanoacrylate (OCA) in cutaneous surgery offers increased efficiency, there is scant data comparing scar outcomes achieved with OCA versus 5-0 fast-absorbing gut suture (FG). OBJECTIVE: To compare scar cosmesis achieved with OCA versus FG for surgical wound closure. MATERIALS AND METHODS: A total of 44 patients with postoperative defects of at least 3 cm were included. Half of each wound was randomized to receive closure with either OCA or FG. At 3 months, patients and 2 blinded observers evaluated each scar using the Patient and Observer Scar Assessment Scale (POSAS). RESULTS: The total observer POSAS score (mean [SD]) for the side repaired with OCA (12.3 [4.72]) and the side that received FG (11.6 [4.36]) did not differ significantly (p = .40). There was no significant difference in the total patient POSAS scores between closure with OCA (14.9 [8.67]) and FG (14.6 [8.90]) (p = .70). Based on observer POSAS scores, scar pigmentation was significantly worse on the scar half repaired with OCA (1.98 [0.91]) compared with FG (1.79 [0.80]) (p = .05). CONCLUSION: With the exception of inferior scar pigmentation with OCA, there was no statistically significant difference in wound cosmesis after linear wound closure with OCA versus FG.

Medullary Compression Due to Ectatic Vertebral Artery-Case Report and Review of Literature.

Medullary compression syndrome due to anomalous course of blood vessels is a rare disease most commonly seen in the adult population. The offending vessels causing this syndrome are mostly posterior inferior cerebellar artery or the vertebral artery. The symptoms of this syndrome vary from most common hypertension to various other neurologic deficits like hemiplegia, dysesthesia, and dysarthria. Intractable dizziness is a rare symptom of this disease. The definite management plan for this disease is microvascular decompression. We present our case of medullary compression syndrome which manifested as intractable dizziness. We describe our experience in the management of this patient as well as present a review of literature of this rare disease.

The Outcome of Medical Management of Chronic Subdural Hematoma with Tranexamic Acid - A Prospective Observational Study.

INTRODUCTION: The conservative management of Chronic subdural hematoma (CSDH) is controversial. Many drugs have been tried in the conservative management of CSDH. Tranexamic acid (Txa) is one such drug in the armamentarium for conservative management of CSDH. We conducted a prospective observational study about treatment of CSDH with Txa. MATERIAL AND METHODS: The study was conducted over three years. The clinical grading was assessed by the Markwalder grading system. All patients who were relatively and mildly symptomatic and willing for conservative management were recruited for the study. All patients were given Txa in the dosage of 750 mg/day in divided doses. The patients were followed up in the neurosurgery out-patient department. RESULTS: There were 27 patients with 30 CSDH during this period who were treated with Txa. There were 20 cases of primary CSDHs and 7 cases of recurrent CSDHs following surgery that were enrolled in the Txa group. The mean volume of treated CSDH was 135.62 ± 92.90 SD. The mean thickness of CSDH enrolled in the study was 14.31 ± 5.47 SD. The mean number of days the patients treated with Txa was 64.83 ± 24.8 SD. There were no complications in any of the patients. All patients had good resolution of the hematomas, and none of the hematomas progressed during conservative treatment. CONCLUSION: The conservative management of CSDH with Txa is both a safe and effective alternative in the absence of life-threatening symptoms.

The role of hypothalamus-pituitary-adrenal (HPA)-like axis in inflammatory pilosebaceous disorders.

Skin is the largest peripheral endocrine organ and functions as a hormone target and endocrine gland. A cutaneous hypothalamus-pituitary-adrenal (HPA)-like axis enables the skin to respond to stress and regulates its steroidogenic activity. The pilosebaceous unit is a site for production and metabolism of a number of steroid hormones, including stress and sex hormones. This is an overview of the important role that the cutaneous HPA-like-axis plays in the pathogenesis and treatment of inflammatory pilosebaceous disorders, including acne, rosacea, seborrheic dermatitis, and hidradenitis suppurativa.

Use of 5-0 Fast Absorbing Gut versus 6-0 Fast Absorbing Gut during cutaneous wound closure on the head and neck: A randomized evaluator-blinded split-wound comparative effectiveness trial.

BACKGROUND: Absorbable suture material (Fast Absorbing Gut [FG], Ethicon, Somerville NJ) is often used for patient convenience; however, the optimal diameter of FG sutures is debatable. OBJECTIVE: To determine whether the use of 6-0 FG during repair of linear cutaneous surgery wounds on the head and neck improves scar cosmesis compared with the use of 5-0 FG. METHODS: This was a prospective, randomized, split-scar intervention in patients undergoing repair of linear cutaneous wounds on the head and neck. The scar was assessed 3 months after surgery via the Physician Observer Scar Assessment Scale (POSAS), a validated instrument. RESULTS: The difference in the sum of the POSAS component scores for 6-0 FG (12.03) compared with that for 5-0 FG (13.11) was not statistically significant (P = .26). Observer overall opinion was similar for both interventions, at 2.49 for 6-0 FG vs 2.64 for 5-0 FG (P = .54). The difference in the number of complications in the 5-0 FG group (15) vs the 6-0 FG group (10) was not statistically significant (P = .40). LIMITATIONS: Single-center study with wounds limited to the head and neck in white individuals, with a predominance of men. CONCLUSION: For linear repair of cutaneous wounds, 6-0 FG was not statistically different for cosmetic outcomes, scar width, and complications compared with 5-0 FG.

Dermal suture only versus layered closure: A randomized, split wound comparative effectiveness trial.

BACKGROUND: Layered closure of cutaneous wounds is a commonly used surgical practice. However, there are studies that suggest the additional layer of epidermal sutures might not be necessary. OBJECTIVE: To compare scar outcomes between the single-layer deep-dermal suture technique and the conventional layered suture technique for primary closure of cutaneous wounds. METHODS: A total of 49 patients were enrolled in a prospective, randomized, evaluator-blinded, split scar study to compare the conventional bilayered closure technique with the single-layer deep-dermal suturing technique for primary closure of wounds. The primary outcome measure was mean sum Patient and Observer Scar Assessment Scale (POSAS) score at 3 and 12 months. RESULTS: At the 3-month follow-up, there was a statistically significant difference in the mean total POSAS scores for both the blinded observer and patients, indicating a preference for the side with the standard layered closure. However, at the 12-month follow-up, this difference was lost, with the exception of scar color, which was significantly more noticeable on the wound side closed with only dermal sutures. LIMITATION: Single-center study. CONCLUSION: Three months after surgery, the layered closure technique resulted in a slightly better scar outcome than the single-layered closure containing only dermal sutures. At 12-months' follow-up, this difference diminished, with scars for both sides appearing similar.

Noninvasive profiling of sweat-derived lipid mediators for cutaneous research.

BACKGROUND AND OBJECTIVE: Recent increases in the use of noninvasive matrices for biomedical analysis has led to interest in the evaluation of sweat for both clinical and research applications. However, despite being one of the two main cutaneous secretions, until very recently, only one study actually analyzed sweat in the context of cutaneous disease. This review attempts to make the case for increased use of sweat in cutaneous research, and discusses lipid mediators as potential analytical targets in sweat. METHODS: Sweat composition and its relationship with the skin and systemic circulation are discussed, as are practical considerations for sweat sampling and analysis. Previous analyses of lipid mediators in skin biopsies are provided to show that lipid mediators can regulate cutaneous processes and disease pathways. Summaries of recent studies involving the analysis of sweat lipid mediators are provided to demonstrate the utility of sweat lipid mediator testing to support future cutaneous research studies. RESULTS: Sweat has the potential to reflect both local and systemic biochemical changes in response to disease or intervention, and two recent studies of sweat lipid mediators confirm this ability. Additionally, sweat lipid mediators appear to be temporally stable with individual variability comparable to other matrices, suggesting that these analytes could be useful biomarkers. CONCLUSIONS: Sweat metabolites may be capable of reporting changes in cutaneous biochemical pathways, thereby providing insight into the immunomodulatory biochemistry of the skin. Lipid mediator analysis of sweat appears to be a non invasive approach that could enhance existing cutaneous research and diagnostic methodologies.