IQGAP proteins mediate many processes important for the development of hyperproliferative skin diseases, namely the EGF signaling, WNT and MAPK kinase cascades, they are required for cell adhesion and migration processes, tight junction and zonula occludens formation, cell cycle regulation. However, the possible contribution of the IQGAP3 in the development of hyperproliferative psoriatic plaques is unknown. We have shown earlier that IQGAP3 is overexpressed in the lesional skin of patients with...
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Iron is an essential nutrient for all living organisms and functions as a cofactor for cellular enzymatic processes. Multiple organ systems are affected by inappropriate levels of circulating iron levels, including the bone marrow, central nervous system, and skin. Cutaneous conditions associated with high and low iron include telogen effluvium, angular cheilitis, koilonychia, ichtyosis-like changes, atrophy, and changes in pigmentation. Iron homeostasis mechanisms exist to maintain total body iron...
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Mammalian epidermis positioned at the interface with the environment, protecting underlying tissues from external challenges such as pollutants. Diesel exhaust particles (DEPs) are a major contaminator of air pollution particles, and emerging evidences indicate that polycyclic aromatic hydrocarbons (PAHs), a main component of DEPs, cause skin irritation and inflammation through aryl hydrocarbon receptor (AhR)-dependent signaling pathways. In particular, prior studies revealed that an AhR activation...
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Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear hormone receptors. In skin, PPARs modulate inflammation, lipid synthesis, keratinocyte differentiation and proliferation. These properties underscore the importance of PPARs in skin barrier homeostasis. Accordingly, PPAR expression is altered in various skin conditions that entail skin barrier impairment i.e. atopic dermatitis (AD) and psoriasis. In this study, we aim to elucidate the role of Pparα in models of skin barrier...
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Melanoma risk is increased in fairer-skinned individuals. Interestingly, melanomas in patients with oculocutaneous albinism (OCA) are reported less frequently than one would expect given their extremely fair skin. To date, fewer than 70 instances of malignant melanoma in OCA patients have been reported. We present the case of a 50-year old African American female with OCA and a medical history of systemic lupus erythematosus, idiopathic thrombocytopenic purpura and deep vein thromboses, who presented...
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Desmoglein 1 (Dsg1) is a key component of desmosomes and corneodesmosomes. While desmosomes play a critical role in maintaining intercellular adhesion between keratinocytes in the epidermis, corneodesmosomes are essential for intercellular adhesion between corneocytes. BP180 (collagen XVII) is a transmembrane protein in the hemidesmosome that functions in attaching the epidermis to the underlying dermis. We have recently generated a BP180-dysfunctional mouse strain by knocking out a key domain of...
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High levels of Ultra-Violet Radiation (UVR) are known to induce important biological effects on the skin, including the delayed pigmentation observed with tanning. p53 is a major transcription factor highly expressed in keratinocytes after UVR that is known to induce melanogenesis through expression of SCF (Stem Cell Factor), POMC (Pro-Opiomelanocortin), and other paracrine factors. In UV-irradiated human skin, melanocyte numbers increase accompanying tanning, yet the role of keratinocyte p53 in...
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LB1080 Effect of microclimate change on skin inflammation, barrier integrity and microbial diversity
The skin in the diapered region is constantly exposed to microclimate changes that can impact its barrier function and microbial homeostasis, leading to dermatitis. In this work, we aimed to understand the impact that prolonged occlusion and over-hydration have on immune response, skin barrier integrity and its microbiota. For this, adult back skin (female aged 18-40, n=26) was exposed, daily, to a dry or wet occlusive patch with or without absorbent material for 10 days. Skin biophysical parameters...
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Many dermatology societies have instituted a call to action for increased diversity in the field. One solution is to offer a dermatology information session targeted toward underrepresented minority undergraduate students (UMUS). Providing students with a venue to learn about dermatology and offering the opportunity to shadow and perform research may increase UMUS’ interest in dermatology. Undergraduate students were recruited to attend the event through premedical and minority student group listservs.
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Tight junction (TJ) is a cell-cell junction composed of numerous molecules, including claudin. It plays indispensable roles in skin homeostasis as demonstrated by lethal phenotypes of the claudin-deficient mice and ichthyosis-sclerosing cholangitis syndrome in humans, which is caused by mutations in the claudin-1 gene. To further elucidate its functions and significance in skin diseases, a detailed understanding of its overall structure is necessary. Some authors have suggested that epidermal TJ...
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It is known that the main bioenergetic pathway in skin is the anaerobic glycolysis. Thus, glucose consumption and a high production of lactate are a proof of an active metabolism in skin. This has never been demonstrated in an ex vivo human skin model before. NativeSkin® is an ex vivo human skin model, composed of the two upper skin layers. The skin explant is embedded in a proprietary gel-like matrix with epidermal surface left in direct contact with the air. The system is mounted into cell culture...
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SNPs in human OVOL1, which encodes a transcriptional repressor, are known to be associated with skin inflammatory diseases such as atopic dermatitis. Mouse Ovol1 is expressed in multiple epithelial tissues including the skin epidermis and hair follicles. Previously, our lab showed that Ovol1 regulates the growth arrest of embryonic epidermal progenitor cells, and its deletion (Ovol1-/- mice) leads to epidermal hyperproliferation and a transient delay in permeability barrier formation. However, it...
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Generalized pustular psoriasis (GPP) is a rare, life-threatening disease, characterized by recurrent flares of pustular, erythematous rashes, with a strong genetic linkage to the IL-36 pathway. The efficacy and safety of a single, open-label, intravenous dose of BI 655130 (10 mg/kg), an anti-IL-36R monoclonal antibody, was assessed in a Phase I trial (NCT02978690) in 7 patients presenting with a moderate-to-severe GPP flare. To characterize the response to BI 655130 at a molecular level, biomarkers...
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Skin hydration is one of the major factors that determine human skin quality, integrity and health. The epidermis plays a critical role in regulating skin hydration, since interstitial fluid, supplied from dermis, is irrigated through paracellular tracks up to the Stratum Corneum (SC). The epidermis has molecular and structural mechanisms to minimize water loss by tight junctions (TJs) at the stratum granulosum (SG) and natural moisturizing factor (NMF) production in SC. Although skin barrier function...
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Papulopustular rosacea (PPR) is a chronic inflammatory skin disease which manifests as red, inflammatory papules or pustules predominantly on the facial region. Although the pathogenesis of PPR is not well understood, an over-reactive inflammatory response plays a role, resulting in altered vasculature and skin sensitivity. Although previous studies have assessed RNA expression or immunohistochemistry staining in tissue, to our knowledge this is the first-time quantitative protein analysis of PPR...
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Cutaneous neurofibromas (cNF) are complex tumors of the skin in individuals with neurofibromatosis type 1 (NF1), a syndrome affecting approximately 1:3,000 persons worldwide. There are no drug therapies for these tumors, and current treatment is limited to various procedure-based approaches. A critical need in conducting meaningful translational studies of these tumors is to have high quality tissue samples representing the diversity of human cutaneous tumors. Multiple challenges exist, including...
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To assess the impact of disease severity on racial and ethnic differences in healthcare utilization for pediatric atopic dermatitis (AD), Wan and colleagues performed a longitudinal study involving 7,522 white, black, and Hispanic children from the United States. Black and Hispanic children were more likely than white children to visit a medical provider for AD, and these increased odds were similar across all levels of disease control and independent of sociodemographic factors. Specifically, black...
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The epidermal differentiation complex (EDC) includes over fifty genes encoding proteins involved in keratinocyte development. These belong to three gene families: the cornified envelope precursor family, the S100 protein family and the S100 fused type protein (SFTP). Of these fifty genes, filaggrin (FLG) located on chromosome 1 q21, a member of the SFTP family, is the most studied in the context of skin barrier dysfunction. We investigated the frequency and effect of rare loss-of-function (LOF) variants...
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XPD, coded by ERCC2, is a helicase component of the basal transcription factor, TFIIH, involved in both DNA repair and transcription. Mutations in XPD that cause xeroderma pigmentosum (XP) may be predominately associated with repair-affecting mutations while transcription-affecting XPD mutations may be predominately associated with trichothiodystrophy (TTD). XP is characterized by extreme sensitivity to sun damage, sun-induced cancers and neurodegeneration in some patients. The diagnostic symptom...
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Abstract Objective The aim of this study was to evaluate the effect of three different macrodesigns and two different insertion devices on the accuracy of static computer‐assisted implant surgery (sCAIS). Materials and Methods Ninety implant replicas with three different macrodesigns: Soft tissue level (TL), bone level (BL), and bone level tapered (BLT) were placed in 30 dental models with two implant insertion devices: Guided adapter and guided screwed‐in mount. Preoperative and postoperative...
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Atopic dermatitis (AD) is reported to be an allergic dermatitis characterized by eczematous lesions and pruritus. Qing-Re Chu-Shi Decoction (QRCSD) is the herbal formula long used as a complementary and alternative therapy for inflammatory skin diseases in China. However, the role and mechanism of action for QRCSD in AD remained poorly understood. The study was designed to explore the underlying effects of the formula and identify the components accounting for the therapeutic effects in2,4-Dinitrochlorobenzene(DNCB)-induced...
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Objective: The variant (c.445G > A; p. G149R) in IL-23 receptor (IL23R) was found to be associated with leprosy. However, the biological effect of this variant has not been determined in the pathogenesis of leprosy. Methods: We performed the functional investigation of the IL23R Arg381Gln gene variant in leprosy. Firstly, PBMC samples, isolated from six health individuals, were infected by Mycobacterium marine. QPCR and ELISA assay were then conducted to determine Th17 cell relative cytokines...
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The maintenance of psoriasis as a skin-confined chronic inflammatory condition requires the abnormal interplay between hyperproliferative epidermal keratinocytes and self-reactive immune cells. In this context, targeting metabolism of keratinocytes is recently reported to be an approach for treating psoriasis, however whether and how the metabolic adaptations of keratinocytes introduce inflammatory cues are unknown. We report that in psoriatic lesions, Protein Phosphatase 6 (PP6) is diminished in...
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When dengue vectors bite the human body, the virus released by the mosquito salivary glands first contacts the various cell types of dermis, which indicates that the physiological responses of skin dermal cells may be critical for dengue virus (DENV) replication in human. However, the role of dermal cells in dengue infection remains unclear. In this study, the mechanism of DENV infection in the dermal cells was explored. We established an in vitro DENV infection model in both human dermal fibroblasts...
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Research Techniques Made Simple: Forward Genetic Screening to Uncover Genes Involved in Skin Biology
The primary goals of modern genetics are to identify disease-causing mutations and to define the functions of genes in biological processes. Two complementary approaches, reverse and forward genetics, can be used to achieve this goal. Reverse genetics is a gene-driven approach that comprises specific gene targeting followed by phenotypic assessment. Conversely, forward genetics is a phenotype-driven approach that involves the phenotypic screening of organisms with randomly induced mutations followed...
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Drying dermo-cosmetic product is indicated for drying fragile and irritated skin prone to maceration. Here, we evaluated the antibacterial activity of a common antiseptic product (chlorhexidine gluconate-based solution) in presence or absence of drying products. We chose to evaluate products in the worst condition by applying drying products prior to the antiseptic whereas the recommendations of use are to apply drying product after antiseptic. First, we performed in tubo assay to assess the antibacterial...
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Mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma, has a dismal prognosis in advanced stages. The success of immune checkpoint inhibitors (ICI) in treating advanced malignancies has not extended to MF. There is an urgent need to identify predictive biomarkers, and to advance immunotherapies in MF. Neoantigens are ‘new’ peptides, generated by somatic mutations in tumour cells, that evoke an immune response. As tumour-specific markers, neoantigens are an attractive immunotherapeutic...
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Brentuximab vedotin is a monoclonal anti-CD30 antibody-drug conjugate that has been used to treat a variety of CD30+ neoplasms. The phenomenon of antigen loss has been observed in patients treated with the anti-CD20 antibody rituximab. This study seeks to assess for antigen loss in the setting of recurrent CD30+ neoplasms treated with brentuximab vedotin. We report 9 cases of persistent/recurrent cutaneous CD30+ lymphoid neoplasms that demonstrated variable CD30 expression after treatment with brentuximab...
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Discoid lupus erythematosus (DLE) is a severely disfiguring and difficult to treat autoimmune skin disease for which no new therapies have been FDA-approved in over 60 years. One potential therapeutic target is cutaneous B cells. Though rare in healthy skin, B cells are prevalent in DLE lesions, comprising 10-20% of the robust lymphocytic infiltrate. However, the phenotype and function of this expanded B cell population have not been evaluated in detail and it is unknown whether cutaneous B cells...
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Actinic damage increases the risk for non-melanoma skin cancer (NMSC). Topical imiquimod and 5-fluorouracil (5-FU) are effective for actinic keratoses (AK), but their role in preventing NMSC is not yet clear. Retrospective chart review of patients seen at a private dermatology practice from 2008-2016 was performed. Patients who completed field therapy (FT), (30 treatments of topical tretinoin, 5-FU and imiquimod plus cryotherapy every two weeks to the most keratotic lesions) with follow-up of at...
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An association between rosacea and cancer, especially as it may relate to sex-specific differences, has not been well-delineated. We sought to determine if an association exists, and if sex-specific differences are evident utilizing a large patient population. A medical record data repository (>6 million patients) was searched (using ICD-9-10 codes) for data from dermatology patients with a rosacea diagnosis vs. patients without rosacea as a control population (follow-up ≥1 year; 01/2001-11/2018)...
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There is a significant unmet need of safe and effective therapies for severe papulopustular rosacea (PPR). In this study, the baseline mean inflammatory lesion count in all enrolled subjects was 50.8 and all were rated as “severe” in the 5-point Investigator’s Global Assessment (IGA) scale, which represents significantly more severe disease compared to the previous pivotal trials conducted for existing FDA-approved products for PPR. Objective: To evaluate the safety and efficacy of once-daily topical...
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Psoriasis is a chronic immune-mediated skin disorder with high cost for therapies often complicated with serious adverse effects, thus there is a need to develop cheaper, safe and effective mechanism and target-based agents for its treatment. Natural agents that can rescind molecular defects associated with psoriasis could be developed as agents for its management. We examined the associated mechanism of fisetin-induced anti-proliferative and anti-inflammatory responses in 2D normal human epidermal...
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OBJECTIVE: The purpose of this study is to further characterize the population that is hospitalized for a severe cutaneous drug reaction or developed one during their hospitalization, including the most common manifestations of severe drug reactions, demographic susceptibility to developing a severe adverse drug reaction, as well as implicated drugs and treatment outcomes. METHODS: We conducted a chart review of patients seen by a dermatologist at a level 1 trauma center for the diagnosis of DRESS.
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Backgroud: Photodynamic therapy (PDT) is a new option for tumor treatment. The effect of PDT is largely dependent on its ability to induce cell death. During PDT, photo-sensitizers can induce reactive oxygen species (ROS) production after exposure to appropriated light source. ROS has been proven to be able to induce autophagy, which has been shown to have significant effect on apoptosis and necrosis. To improve the efficacy of PDT, it is important to understand the feature and mechanism of the interaction...
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Tele-dermatology generally involves Doctors taking images of patients. However, patients increasingly want to own or have easy access to their health data. Myskinselfie (http://myskinselfie.com) is a mobile phone application designed to improve the quality, consistency and accessibility of patient-held photos, and was developed to give patients the ability to generate and hold their own skin images to help guide their skin care. This study assessed the usability of this application in a cohort of...
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The standard of care for a melanoma in-situ (MIS) is surgical excision. However, residual MIS at the margins is not uncommon. For patients with residual MIS after excision who are reluctant to undergo additional surgical procedures, treatment with imiquimod 5% cream, an immunomodulatory agent, has been explored as an off-label treatment option. We present a case series of 34 patients who had positive surgical margins after excision of melanoma and melanoma in-situ, who underwent adjuvant treatment...
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Introduction: Demand for cosmetic procedures has increased among varying patient demographic groups in recent years, although motivations underlying this trend have not been well-defined. The purpose of this study is to assess whether cosmetic motives are correlated with demographic factors. Methods: Over 500 patients presenting for cosmetic consultation at 13 dermatology centers in the United States were surveyed. Similar motivations were organized into domains by qualitative analysis. Linear regression...
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BACKGROUND: Facial skin coloration, affected by both intrinsic and extrinsic factors, has substantial individual variations. Previous studies on facial skin coloration mostly focused on its correlation with age, but little was done to evaluate the associated environmental and genetic factors. OBJECTIVES: To identify the environmental and genetic factors associated with facial skin coloration. METHODS: We cropped facial cheek images from 11,699 Han Chinese subjects aged between 18 and 87 (54% men;...
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Introduction: There is no approved topical prescription medicine to treat molluscum contagiosum (MC). SB206 is an investigational topical product that consists of 2 components; a gel containing berdazimer sodium that releases nitric oxide (NO) when co-administered with a hydrogel. NO, an endogenous small molecule, is known to be an immune modulator as well as an antimicrobial agent. Objective: A Phase 2, 12-week, randomized, vehicle-controlled ascending dose trial was conducted in patients with MC...
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Immunotherapies have made significant strides in their development and use in advanced cancers by blocking immune checkpoints and interfering with normal functioning of the immune system. By deregulating the immune system, these treatments can cause cutaneous adverse events (AEs) such as maculopapular rash, pruritus and more. The onset of these AEs can cause delays in treatments and considerably impact quality of life (QoL); therefore compromising the survival of the patient. It is imperative to...
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The purpose of this study is to determine if patients with psoriasis are at an increased risk of developing appendicitis, cholecystitis, or diverticulitis compared to the general population. A retrospective, population-based, cohort study was performed utilizing data from the Kaiser Permanente Southern California (KPSC) health network during the study period January 1, 2004 through December 31, 2016. Of 1,690,214 KPSC patients eligible for our study, 10,307 met our diagnostic and inclusion criteria...
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The therapeutic strategies outlined within our study represent the first acne treatment recommendations in patients who have pre-existing lupus; this patient population requires a highly individualized treatment approach, as their disease state makes them particularly vulnerable to adverse effects from medications. Surprisingly, there have been no prior studies investigating which medications can and cannot be safely used to treat acne in patients who also have lupus. We sought to systematically...
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Introduction: The purpose of this study was to assess whether the improvements in itch seen with placebo are due to the use of minimum itch scores as an entry criterion. Methods: A systematic literature review was performed using MEDLINE to find studies that reported the effect of placebo on itch. We then characterized these studies based on whether or not itch was an entry criterion. Itch outcome in placebo arms of studies, quantified using visual analog scale (VAS), was gathered and compared to...
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Hair follicle stem cells (HFSCs) cycle through periods of growth (anagen) and rest (telogen). HFSCs located in the stem cell-containing compartment called the bulge have been shown to be the cells responsible for growing hair shafts de novo, contributing to wound healing, and are the cells of origin for squamous cell carcinoma (SCC). Our lab previously showed that HFSC quiescence is a tumor suppressor mechanism; the initiation of SCC by HFSCs requires active hair cycling. We are therefore exploring...
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Introduction: The purpose of this study was to assess the relationship between improvements in alopecia seen with placebo and the method of hair count analysis used to assess the response. Methods: A systematic literature review was performed using MEDLINE to find studies that reported the effect of placebo on alopecia. We then characterized these studies based on the method of hair count analysis. Hair counts in placebo arms of studies, quantified as mean change from baseline in total hair or nonvellus...
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Advanced age and ultraviolet light exposure are two important epidemiologic risk factors for the development of cutaneous malignancy. Ultraviolet light is a known mutagen, and while multiple reports describe the clonal expansion of tumor-associated mutations in clinically normal skin, how these cells switch to malignancy is unclear and may involve epigenetic mechanisms. Multiple reports describe genomic regions of DNA hypomethylation related to increased age and sun exposure in the epidermis of human...
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“Healthy Skin for Everyone”, or “Piel Saludable Para Todos”, is a community-based initiative to address rising rates of skin cancer in minority populations accompanied by higher mortality and lack of evidence-based interventions. We previously enrolled 114 Spanish-speaking adults from a non-profit clinic to participate in a 45-minute workshop on skin cancer prevention led by trained community health workers followed by a 12-week text-messaging program. These are the results of a one-year follow up...
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Abnormal angiogenesis and dysfunction of macrophage polarization in diabetic skin ulcers leads to non-healing wound. Huiyang Shengji Extract (HSE)is a traditional Chinese medicine prescribed for the treatment of chronic wounds. This study aims to investigate the effect and molecular mechanism of HSE on wound healing of diabetic mice. Diabetic db/db mice were operated with full-thickness excision, with wound treated externally by HSE. The results showed that HSE reduces the wound area on days 7 and...
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Atopic dermatitis (AD) and bullous pemphigoid (BP) are inflammatory skin diseases in which patients often report intense pruritus and significant quality of life (QOL) impact. Although they have differences in classical presentation (eczematous eruption versus urticaria and blisters) and population characteristics (young-to middle aged persons vs. elderly), early stages of BP can appear similar to AD clinically and histologically. We wanted to explore whether there were significant similarities or...
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CD8+ cutaneous lymphomas include a variety of rare cutaneous T-cell lymphomas (CTCL) and lymphoproliferative disorders (LPD) with distinctly different prognoses, clinicopathological overlap, and resistance to current therapeutic strategies. Improved diagnostic tools and therapeutic options are needed. To evaluate C-C chemokine receptor 4 (CCR4) expression in CD8+ CTCL/LPDs as a diagnostic and potential therapeutic biomarker we performed CCR4 immunohistochemistry (IHC) on formalin-fixed paraffin-embedded...
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Background: Hidradenitis suppurativa (HS) negatively impacts quality of life. Objective: To find how HS Hurley and Severity Assessment of Hidradenitis Suppurativa (SAHS) relate to scores on Dermatology Quality of Life Index (DQLI) and Beck Depression Inventory (BDI). Methods: Cross-sectional study run Oct. 2018-Feb. 2019. Eligibility: age 12+ and a clinical visit for HS. Exclusions: declined involvement; English or French illiteracy; known depression or mental health disorder as defined by DSM-5...
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We previously reported that the expression of CX3CL1 and its receptor, CX3CR1 was increased in patients with systemic sclerosis (SSc). In this study, we assessed the preclinical efficacy of an anti-CX3CL1 monoclonal antibody (mAb) in SSc. Cultured human dermal fibroblasts were used to evaluate the direct effect of anti-CX3CL1mAb on fibroblasts. In addition, bleomycin and growth factor-induced SSc models were used to investigate the effect of anti-CX3CL1mAb on leukocyte infiltration, collagen deposition,...
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We assessed the rate of isotretinoin therapy interruptions and terminations due to lipid, liver function, and hematologic lab abnormalities in patients with acne who had hypercholesterolemia (HC), hypertriglyceridemia (TG), elevated alanine aminotransferase (ALT), leukopenia, or thrombocytopenia prior to initiating isotretinoin, a drug associated with these abnormalities. We reviewed records for patients with acne and baseline HC, TG, elevated ALT, leukopenia, or thrombocytopenia who started isotretinoin...
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Skin resident memory T cells (TRMs) are a sessile population of cells implicated in various autoimmune inflammatory diseases including psoriasis (PSO). Long-lived CD8+ TRMs (CD103+) that produce IL-17A in psoriatic skin are thought to be responsible for the localized relapsing nature of the disease. Knowledge of the relative contribution of subsets of TRMs and other effector T cells to the pathogenesis of psoriasis remains limited. Here, we used immunophenotyping by multiparameter flow cytometry...
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LB1104 Histologic features of GVHD-associated angiomatosis: Insights into pathogenesis and treatment
Graft-versus-host disease-associated angiomatosis (GVHD-AA) is characterized by benign vascular growths often observed on sclerotic skin from chronic GVHD. These lesions can ulcerate, bleed with minor trauma, and cause pain, leading to significant morbidity. Although many treatments have been tried, no standard of care exists. To obtain insights into disease biology and inform treatment, we conducted a retrospective study analyzing clinical data and histologic and immunohistochemical features of...
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Editorial note: Welcome to the Journal of Investigative Dermatology (JID) Snapshot Dx Quiz. In this monthly online-only quiz, the first question (“What is your diagnosis?”) relates to the clinical image shown, while additional questions concern the findings reported in the JID article by Murer et al (2019) (https://doi.org/10.1016/j.jid.2018.11.028).
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Hidradenitis suppurativa is a chronic inflammatory skin disorder characterized by acute and chronic recurrent nodules, abscesses, and dermal tracts. We report a new morphologic variant of hidradenitis suppurativa manifest as hypergranulating wounds. Three female patients, ages 16, 18, and 44, with hidradenitis suppurativa symptoms spanning from 6 to 20 years, presented with red, fleshy, exophytic tissue, indistinguishable from pyogenic granuloma. These lesions were unresponsive to topical silver...
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Dermatology is an interdisciplinary specialty that requires incorporation of expertise from multiple backgrounds, including pathology, immunology, genetics, cell and developmental biology, biomedical engineering, and cancer biology, to better understand the mechanisms underlying conditions arising in our patients. It is critically important for dermatology training programs to reflect this broad and ever-expanding array of topics to prepare the next generation of clinicians and basic scientists for...
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Background: Recent analyses of rosacea skin biopsies implicated IL-17A in rosacea pathogenesis. Current rosacea treatment options are limited and no cure exists. Objective: Assess the potential benefit of secukinumab in patients with moderate-to-severe papulopustular rosacea. Methods: After IRB approval and written informed consent, a total of 23 participants received secukinumab at 300 mg weekly for five weeks then monthly for two months. Papule count, erythema, global severity, and adverse events...
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The skin employs multiple immune defense strategies, including the production of antimicrobial peptides, to manage interactions with skin microbiota and prevent infection. These interactions are governed by not only the microbiota and environmental factors but also by dietary intake, as vitamin A deficiency is associated with increased susceptibility to skin infection. Harris and colleagues recently reported that resistin-like molecule α (RELMα) is an antibacterial protein that is expressed in the...
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Introduction: Non-Melanoma Skin Cancer(NMSC) is generally treated in dermatology offices using invasive techniques. Objective: We evaluate the feasibility, tolerance, effectiveness and cosmesis using an office-based non-invasive modality for NMSC. Materials and Methods: Between April 2017 and August 2018, 87 patients with 123 pathologically confirmed early stage NMSC lesions treated with Image Guided Superficial Radiotherapy (IGSRT) were analysed. All lesions received twenty fractions of 50 or 70...
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The purpose of this study was to give dermatologists important information on the association of isotretinoin with aplastic anemia and therefore change their approach for monitoring patients taking isotretinoin. We reviewed FDA reports and most recent literature on the association of isotretinoin with bone marrow suppression. We then applied this information to the clinical course of a patient who had been on isotretinoin for a year and then presented six months later in septic shock with AA and...
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Bullous pemphigoid (BP) is a rare but often treatment-altering complication of immune checkpoint inhibitors (ICIs). This multicenter, retrospective case-control study aims to identify diagnostic and therapeutic differences between ICI-induced BP (ICI-BP) and idiopathic BP (iBP) using 15 ICI-BP cases and 30 age- and sex-matched iBP controls. ICI-BP cases were all from PD-1 blockade and occurred after a median of 11 cycles and 8.9 months of ICI treatment. Compared to controls, cases had a significantly...
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Psoriasis, a chronic, immune-mediated disease dependent upon the interleukin (IL)-23/Th17 pathway, is thought to be initiated through plasmacytoid dendritic cell activation and induction of Type I interferons (IFNs). BMS-986165 is a novel oral, selective tyrosine kinase 2 (TYK2) inhibitor that blocks signal transduction of IL-23, IL-12, and Type I IFNs in cellular assays. Its selectivity for TYK2 over Janus kinases 1–3 is driven by binding to the pseudokinase domain, rather than the conserved kinase...
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Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterized by recurrent nodules and abscesses that may progress to purulent dermal tracts and scarring. Although prior studies have reported improvement of HS with infliximab (IFX) 5 mg/kg, no reports have examined the efficacy of high-dose IFX, ranging from 7.5 mg/kg to 10 mg/kg. A retrospective chart review of 60 patients with moderate-to-severe HS receiving high-dose IFX, 7.5–10 mg/kg, was conducted at the Albert Einstein/Montefiore...
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Anti-p19 treatments, such as tildrakizumab, distinguish themselves from existing biological treatments by their capability of inducing long-term remission in psoriasis. The magnitude and particularly the prolonged clinical response seen with tildrakizumab indicates a fundamentally different mechanism of action than other biological treatments, including anti-TNF, anti-IL-17, and anti-p40 treatments. To explore these mechanisms, we utilized a method for isolation and ex vivo culture of skin-resident...
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Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterized by painful nodules, abscesses, and dermal tracts that severely impact patient quality of life (QOL). Intralesional triamcinolone (ILTAC) has been utilized for inflammatory lesions in HS, but the optimal dose has yet to be determined. Having observed the efficacy of high-dose ILTAC (20-40 mg/mL) for inflammatory nodules and draining fistulas in HS, we conducted a retrospective chart review and telephone interviews...
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Background: Psoriasis is an inflammatory disease associated with aberrant crosstalk between the epidermis and immune system. However, the role of Langerhans cells (LCs) in psoriasis remains controversial. Objectives: To elucidate whether LCs are functionally involved in the development of psoriasis using a mouse model. Methods: Two lines of transgenic mice were used and crossed. They included K5.Stat3C, the psoriasis-model mouse and langerin DTR knock-in (KI) mouse. We performed immunofluorescence...
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The impact of psoriatic inflammation on the eye is not fully understood. In this pilot study we investigated if peripheral vascular leakage (PVL), a feature of retinopathy, was evident in patients with psoriasis using Ultra-Wide-Field Fluorescein Angiography (UWFFA). We performed a pilot cross-sectional, IRB-approved, prospective study comparing UWFFA in patients with psoriasis to healthy age-matched controls. Subjects with active or history of moderate to severe plaque psoriasis underwent a complete...
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Abstract The differences in the growth performance between invasive species and native species might paly a key role in the effective invasion. The extensive use of silver nanoparticles (AgNPs) has created the concern of their release into environment. Thus, the possible effects of AgNPs on the growth performance of invading agents are critical to better illustrate the underlying mechanisms for effective invasion. This study aimed to assess the impacts of AgNPs with different concentrations...
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Viruses, Vol. 11, Pages 768: Discovery and Characterization of Novel RNA Viruses in Aquatic North American Wild Birds Viruses doi: 10.3390/v11090768 Authors: Marta Canuti Ashley N. K. Kroyer Davor Ojkic Hugh G. Whitney Gregory J. Robertson Andrew S. Lang Wild birds are recognized viral reservoirs but our understanding about avian viral diversity is limited. We describe here three novel RNA viruses that we identified in oropharyngeal/cloacal swabs collected from wild birds....
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Viruses, Vol. 11, Pages 767: Glycoprotein YKL-40 Is Elevated and Predicts Disease Severity in Puumala Hantavirus Infection Viruses doi: 10.3390/v11090767 Authors: Tuula K. Outinen Paula Mantula Pia Jaatinen Mari Hämäläinen Eeva Moilanen Antti Vaheri Heini Huhtala Satu Mäkelä Jukka Mustonen Most cases of hemorrhagic fever with renal syndrome (HFRS) in Europe are caused by the Puumala hantavirus (PUUV). Typical features of the disease are increased vascular permeability,...
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Viruses, Vol. 11, Pages 766: Inhibition of Influenza A Virus by Human Infant Saliva Viruses doi: 10.3390/v11080766 Authors: Brad Gilbertson Kathryn Edenborough Jodie McVernon Lorena E. Brown Innate antiviral factors in saliva play a role in protection against respiratory infections. We tested the anti-influenza virus activities of saliva samples taken from human infants, 1–12 months old, with no history of prior exposure to influenza. In contrast to the inhibitory...
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Viruses, Vol. 11, Pages 765: Measles Elimination: Identifying Susceptible Sub-Populations to Tailor Immunization Strategies Viruses doi: 10.3390/v11080765 Authors: Peter Kreidl David Ammerer Reinhard Würzner Anita Luckner Hornischer Dorothee von Laer Wegene Borena Measles elimination has been identified as a public health priority in Europe for a long time but has not yet been achieved. The World Health Organization (WHO) recommends identification of susceptible sub-populations...
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Given a tree network with vertices where each edge has an independent operational probability, we are interested in finding the optimal location of a reliable service provider facility in a shape of subtree with exactly leaves and with a diameter of at most which maximizes the expected number of nodes that are reachable from the selected subtree by operational paths. Demand requests for service originate at perfectly reliable nodes. So, the major concern of this paper is to find a location of...
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Deep learning is the crucial technology in intelligent question answering research tasks. Nowadays, extensive studies on question answering have been conducted by adopting the methods of deep learning. The challenge is that it not only requires an effective semantic understanding model to generate a textual representation but also needs the consideration of semantic interaction between questions and answers simultaneously. In this paper, we propose a stacked Bidirectional Long Short-Term Memory (BiLSTM)...
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Network embedding (NE), which maps nodes into a low-dimensional latent Euclidean space to represent effective features of each node in the network, has obtained considerable attention in recent years. Many popular NE methods, such as DeepWalk, Node2vec, and LINE, are capable of handling homogeneous networks. However, nodes are always fully accompanied by heterogeneous information (e.g., text descriptions, node properties, and hashtags) in the real-world network, which remains a great challenge to...
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We study the electromagnetic (EM) duality from derivative theory with homogeneous disorder. We find that, with the change of the sign of the coupling parameter of the derivative theory, the particle-vortex duality with homogeneous disorder holds better than that without homogeneous disorder. The properties of quasinormal modes (QNMs) of this system are also explored. When the homogeneous disorder is introduced, some modes emerge at the imaginary frequency axis for negative but not for positive...
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This paper presents a fuzzy regression analysis method based on a general quadrilateral interval type-2 fuzzy numbers, regarding the data outlier detection. The Euclidean distance for the general quadrilateral interval type-2 fuzzy numbers is provided. In the sense of Euclidean distance, some parameter estimation laws of the type-2 fuzzy linear regression model are designed. Then, the data outlier detection-oriented parameter estimation method is proposed using the data deletion-based type-2 fuzzy...
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A mathematical model is developed to examine the behaviors of a peristalsis flow with nanoparticles in a symmetric channel under the magnetic environment. Here, the nanofluid is electrically conducted through an external magnetic field. Thermal radiation and Joule heating effects are also retained in the present analysis. Under the lubrication approach, the reduced nonlinear systems are obtained. Then, they are solved very efficiently by means of a homotopy analysis method-based package BVPh 2.0....
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The concentration dependence of a microwave frequency radiation from a solution of a functioning enzyme system (ES) (with the example of cytochrome P450 BM3 (CYP102A1) system during lauric acid (LA) hydroxylation) has been studied with a radiothermometric sensor. Registration of the radiation from the enzyme solution has been performed in the frequency range from 3.4 to 4.2 GHz at the enzyme concentrations from 10−10 М to 10−6 М. It has been demonstrated that the catalysis of LA hydroxylation in...
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Triggering WORM/SRAM Memory Conversion by Composite Oxadiazole in Polymer Resistive Switching Device
Electrical characterization indicates that the nonvolatile write once read many (WORM) times/volatile static random access memory (SRAM) conversion was triggered by the composite of the oxadiazole small molecule. FTO/PMMA/Ag device possesses nonvolatile WORM memory behavior, while the FTO/PMMA+oxadiazole/Ag device shows vastly different volatile SRAM feature. The FTO/PMMA/Ag and FTO/PMMA+oxadiazole/Ag memory devices both exhibit high ON/OFF ratio nearly 104. The additive oxadiazole small molecule...
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The aim of the study is to explore the protective effect of new gelatin (NG, Xin’ejiao in China) on hematopoietic injury caused by chemotherapy. Zebrafish, at 48 hours post fertilization (hpf), was treated with different chemotherapeutic drugs to establish the zebrafish hematopoietic damage model with reduced thrombocytes and erythrocytes. The protecting effects of NG on the thrombocytes and erythrocytes were observed, respectively, on zebrafish models. Then, the RT-PCR method was used to detect...
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Dihydropyrimidine dehydrogenase (DPD) is the major enzyme in the catabolism of 5-Fluorouracil (5-FU) and its prodrug capecitabine. We report a 65-year-old female with rectal adenocarcinoma who experienced severe toxicities secondary to standard dose 5-FU based chemotherapy. She was found to be heterozygous for rs371313778, c.2434G>A. This finding prompted restarting 5-FU at 50% dose reduction with further titration in subsequent cycles. We herein report the first case of rs371313778, c.2434G>A...
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Multicomponent cyclocondensation of hydrazine derivatives, ethyl acetoacetate, aromatic aldehydes, and 4-hydroxycoumarin has been reported. The optimization details of the developed novel protocol are recorded. The novel procedure features short reaction time, moderate yields, and simple workup. In addition, BMIM[triflate] was chosen as a green solvent. The structures of the obtained benzylpyrazolyl coumarins were determined and confirmed by 1H NMR, 13C NMR, IR, and elemental analysis. The MIC values...
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A terrorist attack on a long-span spatial structure would cause horrible results. Therefore, it is important to determine the characteristics of blast pressure fields to protect such structures. In this study, fully confined blast loading tests were conducted using a rigid curved shell model, which had an inner space similar to that of a reticulated dome. Four different scenarios were carried out to record the blast loading on five typical positions. The blast pressure-time data were compared and...
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The papilionoid legume genus Ormosia comprises approximately 130 species, which are distributed mostly in the Neotropics, with some species in eastern Asia and northeastern Australia. The taxonomy and evolutionary history remain unclear due to the lack of a robust species-level phylogeny. Chloroplast genomes can provide important information for phylogenetic and population genetic studies. In this study, we determined the complete chloroplast genome sequences of five Ormosia species by Illumina sequencing....
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Objective. The Bayesian model plays an important role in diagnostic test evaluation in the absence of the gold standard, which used the external prior distribution of a parameter combined with sample data to yield the posterior distribution of the test characteristics. However, the correlation between diagnostic tests has always been a problem that cannot be ignored in the Bayesian model evaluation. This study will discuss how different Bayesian model, correlation scenarios, and prior distribution...
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The durability of lightweight cellular concrete (LCC) and the corresponding assessment method are studied in this paper to improve the utilization of LCC in subgrade construction engineering. The durability assessment method is established by combining the analytic hierarchy process (AHP) with fuzzy comprehensive evaluation (FCE). The main assessment processes are as follows. Firstly, based on the physical and mechanical properties of LCC, the influencing factors are selected in terms of preliminary...
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Background. Epidemiological studies have shown that exposure to PM induces oxidative stress, leading to a variety of health problems. In particular, PM2.5 contains a lot of substances harmful to the human body and penetrates into the lungs to induce lung injury. At the same time, there is increasing evidence that oxidative stress also affects the severity of lung injury. However, there is still no good way to reduce or eliminate these hazards. In the future, more experimental research is needed to...
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Cement structures are major capital investments globally. However, exposure of cement-based materials to aggressive media such as chloride- and sulphate-laden environments such as coastal areas affects their performance. Ordinary Portland cement (OPC) is the main cement used in buildings and civil structures such as dams and bridges. This paper reports the findings of an experimental investigation on the effect of ingress of Cl− and SO42− on compressive strength development and the ions’ diffusivity...
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The integrals evaluated are the products of multivariable Aleph-functions with algebraic functions, Jacobi polynomials, Legendre functions, Bessel-Maitland functions, and general class of polynomials. The main results of our paper are quite general in nature and competent at yielding a very large number of integrals involving polynomials and various special functions occurring in the problem of mathematical analysis and mathematical physics.
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Protein-protein interactions (PPIs) play a crucial role in various biological processes. To better comprehend the pathogenesis and treatments of various diseases, it is necessary to learn the detail of these interactions. However, the current experimental method still has many false-positive and false-negative problems. Computational prediction of protein-protein interaction has become a more important prediction method which can overcome the obstacles of the experimental method. In this work, we...
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The influence of irradiation on mechanical properties of nickel is studied using molecular dynamics (MD) simulation. The single crystal nickel is irradiated with the primary knocked-on atom (PKA) energies of 5 keV, 10 keV, 20 keV, and 30 keV at 300 K, and then the tensile test is performed. The simulation results reveal that the yield strain and yield stress of irradiated nickel decrease with the irradiation energy increasing, while the elastic modulus has no obvious change at various irradiation...
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Tunnel liner is conventionally designed according to the deterministic design methods. However, the loads transmitted from the surrounding ground to the liner are very uncertain. In other words, the tunnel liner is subjected to nonuniform loading conditions which may affect its performance. This is mainly due to the inherent randomness and spatial variability of ground properties. In addition, since borehole drillings are usually carried out before tunnel excavation, the measured borehole data should...
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Roadway floor rock burst is an important manifestation of rock bursts in deeply buried mines. With the increase of mining depth and mining intensity, rock burst disasters in the roadway floor such as floor heaves are becoming more serious. The article investigated the roadway floor severe heave caused by floor rock burst during excavation of the No. 3401 working face, which was controlled by an anticlinal structure and deep mining in Shandong Mine, China. Firstly, by analyzing geological conditions...
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Periodontal disease (PD) is a common infectious and inflammatory disease characterised by inflammation of tissues surrounding and supporting the teeth and destruction of the associated alveolar bone, eventually resulting in tooth loss. This disease is caused by periodontopathic bacteria in plaque biofilm and resultant innate and adaptive immune responses in periodontal tissues. Calprotectin (CLP) is a calcium-binding protein of the S-100 protein family and is found to be induced by activated granulocytes,...
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With the continuous construction of 500 m concrete-filled steel-tube (CFST) arch bridges such as the Bosideng Yangtze River Bridge and the Hejiang Changjiang Highway Bridge, the deviation between the dead pressure line and the arch axis produced by extant arch axis optimization methods increases. Therefore, an arch axis optimization method for long-span CFST arch bridges with a truss section must be designed. Following the optimization of the truss arch axis, this study develops the minimum section...
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A weakly compressible smoothed particle hydrodynamics (WCSPH) method was developed to model open-channel flow over rough bed. An improved boundary treatment is proposed to quantitatively characterize bed roughness based on the ghost boundary particles (GBPs). In this model, the velocities of GBPs are explicitly calculated by using evolutionary polynomial regression with a multiobjective genetic algorithm. The simulation results show that the proposed boundary treatment can well reflect the influence...
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Gut Flora: Novel Therapeutic Target of Chinese Medicine for the Treatment of Cardiovascular Diseases
Cardiovascular disease (CVD) is one of the three major threats to human health identified by WHO. Dyslipidemia, hypertension, diabetes, and obesity are well established as common CVD risk factors. However, controversies exist on the effects of gut flora on cardiovascular disease (CVD). Current evidence suggests that gut microbiota is a double-edged sword for CVD risk, and its effects are largely determined by the metabolites of the gut microbiota. Trimethylamine N-oxide (TMAO), as one of the metabolites...
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The actual burden and future burden of the small-for-gestational-age (SGA) babies turn their screening in pregnancy a question of major concern for clinicians and policymakers. Half of stillbirths are due to growth restriction in utero, and possibly, a quarter of livebirths of low- and middle-income countries are SGA. Growing body of evidence shows their higher risk of adverse outcomes at any period of life, including increased rates of neurologic delay, noncommunicable chronic diseases (central...
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In this work, we studied the effect of TiO2 sensitization with dry biomass extracted of cyanobacteria on the degradation of methylene blue dye (AM). Cyanobacterial cultures isolated from water samples were collected from the swamp of Malambo in Colombia; two main genera of cyanobacteria were identified, and they were cultivated with BG-11 culture medium. The concentrations of chlorophyll a in the exponential and stationary phases of growth were measured; the phycobilin content was quantified by spectrophotometry....
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There seems to be a correlation between soluble amyloid beta protein (Aβ) accumulation in the main olfactory bulb (OB) and smell deterioration in both Alzheimer’s disease (AD) patients and animal models. Moreover, this loss of smell appears to be related to alterations in neural network activity in several olfactory-related circuits, including the OB, as has been observed in anesthetized animals and brain slices. It is possible that there is a correlation between these two pathological phenomena,...
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Objective. To explore the effect of Tripterygium wilfordii polycoride (TWP) on the NADPH oxidases (NOXs)-reactive oxygen species (ROS)-NOD-like receptor protein 3 (NLRP3) inflammasome signaling pathway and the possibility of using TWP to treat ulcerative colitis (UC). Methods. BALB/c mice were randomly divided into five groups: model control, low TWP, middle TWP, high TWP, and normal control groups. A UC model was established with dextran sulfate sodium. The determination of ROS was carried out by...
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The dysfunction and decreased number of islet β cells are central to the main pathogenesis of diabetes. Improving islet β cell function and increasing the number of β cells are effective approaches to treat diabetes and constitute the main direction of diabetes drug development. The role of Chinese medicine in the treatment of diabetes began to be recognized. In recent years, Chinese medicine monomers have been found to increase insulin synthesis and secretion, reduce β cell-apoptosis, and protect...
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The mortise and tenon joints are the main connection forms used in ancient timber buildings, and damaged joints have a critical effect on the safety of a timber structure. There are three main damaged cases of dovetail joints which are pulling, contraction, and mixing damages. In this study, using a theoretical analysis of the stress distribution in a mortise and tenon joint resulted from the pullout damage, a theoretical equation for the resisting moment of the joint was proposed. A finite element...
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Background. Colony-stimulating factor-1 (CSF-1) is a homodimeric glycoprotein. The main role of CSF-1 is as a hematopoietic growth factor that modulates proliferation, differentiation, and survival of macrophages. Moreover, CSF-1 has also been reported to be aberrantly expressed in several human cancers. However, the precise role of CSF-1 in upper tract urothelial carcinomas (UTUC) has not been studied. In this research, we examined the clinical significance of CSF-1 expression in UTUC. Materials...
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The problem of artificial potential function (APF) safety and obstacle avoidance guidance for autonomous rendezvous and docking of chaser spacecraft with noncooperative spacecraft is studied. The relative motion equation of the chaser and the target is established based on the line-of-sight coordinate system, the reference state is designed, and the corresponding state error is deduced. The attitude motion equation of the noncooperative target spacecraft in space is established. The safety and obstacle...
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