Tango-seq: overlaying transcriptomics on connectomics to identify neurons downstream of Drosophila clock neurons.

Knowing how neural circuits change with neuronal plasticity and differ between individuals is important to fully understand behavior. Connectomes are typically assembled using electron microscopy, but this is low throughput and impractical for analyzing plasticity or mutations. Here, we modified the trans-Tango genetic circuit-tracing technique to identify neurons synaptically downstream of Drosophila s-LNv clock neurons, which show 24hr plasticity rhythms. s-LNv target neurons were labeled specifically in adult flies using a nuclear reporter gene, which facilitated their purification and then single cell sequencing. We call this Tango-seq, and it allows transcriptomic data - and thus cell identity - to be overlayed on top of anatomical data. We found that s-LNvs preferentially make synaptic connections with a subset of the CNMa+ DN1p clock neurons, and that these are likely plastic connections. We also identified synaptic connections between s-LNvs and mushroom body Kenyon cells. Tango-seq should be a useful addition to the connectomics toolkit.

Quaternary Ammonium Compounds and Contact Dermatitis: A Review and Considerations During the COVID-19 Pandemic.

The recent global pandemic has resulted in increased use of quaternary ammonium compounds (QACs). Currently, QACs are active ingredients in 292 disinfectants recommended by the US EPA for use against SARS-CoV-2. Among QACs, benzalkonium chloride (BAK), cetrimonium bromide (CTAB), cetrimonium chloride (CTAC), didecyldimethylammonium chloride (DDAC), cetrimide, quaternium-15, cetylpyridinium chloride (CPC), and benzethonium chloride (BEC) were all identified as potential culprits of skin sensitivity. Given their widespread utilization, additional research is needed to better classify their dermal effects and identify other cross-reactors. In this review, we aimed to expand our knowledge about these QACs to further dissect its potential allergic and irritant dermal effects on healthcare workers during COVID-19.

Improvement in Disease Activity in Refractory Juvenile Dermatomyositis Following Abatacept Therapy.

OBJECTIVE: This open-label, 24-week study was conducted to evaluate the safety and efficacy of abatacept in patients with refractory juvenile dermatomyositis (DM). METHODS: Ten patients ≥7 years of age with moderate disease activity were enrolled in a 24-week study to examine the safety of subcutaneous abatacept and patient responses to the treatment. The primary endpoint was the International Myositis Assessment and Clinical Studies (IMACS) group Definition Of Improvement (DOI). Secondary endpoints included safety, changes in the core set activity measures (CSMs) of the IMACS group and the Pediatric Rheumatology International Trials Organization, and improvements in disease activity based on the American College of Rheumatology (ACR)/EULAR response criteria for juvenile DM. Radiologists blinded with regard to participant data assessed magnetic resonance images (MRIs) of patient thigh muscles. Interferon (IFN)-regulated gene score was performed on whole-blood RNA samples using a NanoString assay, and cytokines were assessed using a Luminex assay. RESULTS: Five patients achieved DOI at week 12, and 9 patients achieved DOI at week 24, including 2 patients with minimal, 4 patients with moderate, and 3 patients with major improvement by the 2016 ACR/EULAR response criteria for juvenile DM when patients were assessed using the CSMs of the IMACS Group. Improvements from baseline were seen in all CSMs at weeks 12 and 24, except in muscle enzymes. Daily glucocorticoid doses decreased from a mean of 16.7 mg at baseline to 10.2 mg at week 24 (P = 0.002). Average MRI muscle edema scores decreased from a mean baseline score of 5.3 to 2.3 at week 24 (P = 0.01). Six patients had down-trending IFN-regulated gene scores and galectin-9 expression at week 24. Decreases in IFN-regulated gene scores and in levels of interferon-γ-inducible protein 10kDa, galectin-9, and interleukin-2 correlated with improvements in disease activity and in muscle edema shown on MRI. Eleven grade 2 or 3 treatment-emergent adverse events were observed. CONCLUSION: This open-label study demonstrated that abatacept may be beneficial for patients with treatment-refractory juvenile DM.

Systemic Contact Dermatitis: A review.

Systemic contact dermatitis (SCD) is a broad category of syndromes characterized by a variety of clinical presentations and offending agents. There exists general consensus that SCD and its subcategories are due to type IV (and less commonly type III) hypersensitivity reactions, in which a previously sensitized individual undergoes a cytotoxic CD8+ T-cell response upon systemic reexposure. There are various linked allergens, generally grouped into plants, foods, metals, and medications. Diagnosis is relatively successful through epicutaneous patch testing utilizing standard series and customized panels. Treatment consists of allergen avoidance diets as determined by clinical history and patch testing.

Patch Test Clinic Start-up: From Basics to Pearls.

Allergic contact dermatitis is a prevalent burdensome condition affecting millions of Americans. Patch testing, the criterion-standard allergic contact dermatitis diagnostic tool, is underused by US dermatologists. Incorporating patch testing into modern dermatology practices is achievable with utilization of accurate resources and sustainable support. This review focuses on the basics of patch testing and provides practical pearls to assist novice providers in establishing a contact dermatitis specialty practice.

Burning Mouth Syndrome and Contact Dermatitis.

: Burning mouth syndrome (BMS) is a condition that remains a diagnostic challenge and is frequently difficult to treat. Rather than being a singular entity, more recent research has suggested that the diagnosis of BMS encompasses a family of syndromes. Of this family, type 3 has been identified as being related to contact dermatitis. Although this subtype has been most commonly associated with dental allergens, several food, cosmetic, and pharmaceutical products have also been identified as allergens related to the onset of BMS. Failure to identify these allergens prevents timely diagnosis and initiation of treatment for patients with BMS related to contact dermatitis. This article identifies the allergens most relevant to this type 3 and describes the commercially available allergy panels needed to ensure that all relevant allergens are included during patch testing. This study also describes approaches to diagnosis of BMS and discusses approaches to treatment based on subtypes of the condition.

Emerging Nonsteroid-Based Procedural Therapies for Alopecia Areata: A Systematic Review.

BACKGROUND: Alopecia areata (AA) is a common form of patchy, nonscarring hair loss. Although intralesional steroid injections are currently the mainstay procedural therapy for AA, other nonsteroid-based procedural therapies, including platelet-rich plasma (PRP), ultraviolet radiation (UVR), and laser-based modalities, are emerging as practical options. OBJECTIVE: To systematically review nonsteroid-based procedural therapies for AA and recapitulate the available clinical data. MATERIALS AND METHODS: A systematic review of the literature was performed searching PubMed/MEDLINE databases identifying studies investigating PRP, UVR, and laser-based modalities for AA treatment. RESULTS: Literature search yielded 644 articles encompassing PRP, UVR, and laser treatment modalities for AA. Of the 644 articles, 46 met inclusion criteria. Although numerous reports demonstrate strong potential for PRP, UVR, and laser modalities in treating AA, high-quality evidence supporting their efficacy is still lacking. CONCLUSION: There is an abundance of evidence for nonsteroid-based procedural therapies in the treatment of AA. Randomized control trials comparing these treatment options head-to-head should be performed to better understand the true efficacy of these treatments.

Psychological Therapies in Management of Psoriatic Skin Disease: A Systematic Review.

BACKGROUND: Psoriasis is a chronic, immune-mediated skin disease shown to have a multifaceted relationship with psychological factors. Because these factors have been shown to both worsen and result from psoriasis, an increasing number of studies have sought to investigate the efficacy of various psychological interventions in psoriasis management. METHODS: A systematic review of PubMed® and Scopus® databases was performed for studies investigating psychological interventions in psoriasis management published from 1 January 1990 through 4 November 2018. Primary articles published in English and conveying physical treatment outcomes were included, whereas articles not describing clinical outcomes were excluded. Studies supporting intervention efficacy were graded with a level of evidence according to the Scottish Intercollegiate Guidelines Network levels of evidence. RESULTS: A total of 28 reports studying 27 unique sets of patients receiving psychological therapies in psoriasis management were identified, including three case reports and series and 24 clinical trials, investigating 1522 patients in total. Cognitive behavioral therapy and its variants, biofeedback, meditation and mindfulness-based therapies, hypnosis, music resonance therapy, motivational interviewing, emotional disclosure, and educational and multidisciplinary approaches have been studied in the treatment of psoriasis. Although 16 randomized controlled trials were included in this review, literature is limited by heterogeneity of methodology, analyses, and outcomes. Only 4 of 27 studies (three of which investigated cognitive behavioral therapy) were rated a level of evidence of 1+ or greater. Studies, overall, have sample sizes often < 50 patients, lack follow-up past 12 months, and have attrition rates > 20%. CONCLUSIONS: Based on assigned levels of evidence, the most promising methods of psychological intervention in psoriasis include cognitive behavioral therapy, mindfulness-based therapies, motivational interviewing, and educational and interdisciplinary interventions. Further study is needed to determine the efficacy, practicality, and economic feasibility of these treatment options for patients with psoriasis.

Retrospective review of insurance coverage for patch testing.

BACKGROUND: There is a paucity of data on the burden of insurance limitations for patients undergoing patch testing. OBJECTIVE: To characterize the burden of insurance limitations and its impact on differences in management and execution of patch testing. METHODS: A retrospective chart review was performed on patients with a diagnosis of contact dermatitis (International Classification of Disease [ICD], Ninth Edition, code ICD 692) who received patch testing (Current Procedural Terminology code 95044) at the George Washington Medical Faculty Associates Dermatology Clinic between January 1, 2015 and June 30, 2017. Variables including allergen limitations were compared between government-sponsored insurance and private insurance providers (eg, Insurers A, B, C, and D). RESULTS: A total of 371 records were identified. Government-sponsored insurance patients encountered allergen limitations more frequently than private insurance patients (86.8% vs 14.2%, P < .0001). Insurer C and D patients were least likely to encounter allergen limitations (1.2% vs 0%, P < .0001) and were tested to the most allergens (mean = 146 vs 152, P < .0001). Insurer A patients had the least allergens tested among those privately insured. CONCLUSION: Considering modification of insurance policies to allow patch testing with a larger number of allergens without restrictions is needed, with the goal of improving quality of life of these patients while saving costs from chronic use of topical corticosteroids.

Dermatologic Surgical Care for Transgender Individuals.

BACKGROUND: Transgender individuals experience common and unique dermatologic concerns from severe acne associated with testosterone therapy in transmen to complications due to illicit silicone injections in transwomen. Currently, 2 survey studies and 4 reviews have addressed the dermatologic care of transgender individuals. However, none of them provide a focus on the dermatologic surgeon. OBJECTIVE: To assess the dermatologic considerations in transgender individuals and the role of dermatologic surgeon in their care. METHODS: The PubMed and MEDLINE databases were reviewed in June 2018 using keywords, such as transgender, procedures, hair removal, laser, and hormone therapy. RESULTS: In total, 48 relevant publications addressing dermatologic care in transgender patients were reviewed. According to the literature, there are several critical dermatologic considerations in transgender patients, including hair growth and removal, acne vulgaris, facial procedures to masculinize and feminize the face, scar removal, and sexually transmitted infections. CONCLUSION: As dermatologic surgeons have the privilege to improve the health care of transgender patients, they must understand the common and unique concerns of transgender individuals. Given the considerable spectrum of physical goals expressed by transmen and transwomen, individual patient preference must ultimately guide his/her/their dermatologic care.

Features distinguishing clinically amyopathic juvenile dermatomyositis from juvenile dermatomyositis.

Objective: We examined features of clinically amyopathic JDM (CAJDM), in which patients have characteristic rashes with little to no evidence of muscle involvement, to determine whether this is a distinct phenotype from JDM. Methods: Demographic, clinical, laboratory and treatment data from 12 (9 hypomyopathic, 3 amyopathic) patients meeting modified Sontheimer criteria for CAJDM and from 60 matched JDM patients meeting Bohan and Peter criteria were examined. Differences were evaluated by Fisher's exact and Mann-Whitney tests, random forests and logistic regression analysis. Results: Nine (75%) CAJDM patients had anti-p155/140 (transcriptional intermediary factor 1), one (8.3%) anti-melanoma differentiation-associated gene 5 autoantibodies and two (16.7%) were myositis autoantibody negative. CAJDM patients were younger at diagnosis and frequently had mild disease at onset. CAJDM patients had less frequent myalgias, arthritis, contractures, calcinosis, dysphagia, abdominal pain and fatigue. The muscle, skeletal and overall clinical scores were lower in CAJDM. Serum muscle enzymes were less frequently increased in CAJDM, and peak values were lower. CAJDM patients received fewer medications compared with JDM patients. Only 50% of CAJDM patients received oral prednisone, but the maximum dose and treatment duration did not differ from JDM. At a median follow-up of 2.9 years, CAJDM patients had no documented functional disability, and none developed weakness, calcinosis, interstitial lung disease or lipodystrophy. Multivariable modelling revealed a lower skeletal score and less frequent myalgias as the most important factors in distinguishing CAJDM from JDM. Conclusion: CAJDM may be distinguished from JDM, in that they often have p155/140 (transcriptional intermediary factor 1) autoantibodies, have fewer systemic manifestations and receive less therapy.

A Case-control Study to Evaluate the Prevalence of Nonalcoholic Fatty Liver Disease Among Patients with Moderate-to-severe Psoriasis.

Objective: International case-control studies have demonstrated that psoriasis is associated with an increased prevalence of nonalcoholic fatty liver disease (NAFLD). The purpose of the present study was to establish an association of psoriasis and NAFLD in patients attending a dermatology clinic center in the United States. Design: This was an observational, case-control study. Setting: The study setting was an outpatient dermatology clinic of the George Washington Medical Faculty Associates in Washington DC. Participants: One hundred fifty-one adult patients with psoriasis and 51 control subjects were recruited. Measurements: NAFLD was diagnosed by ultrasonography after excluding secondary causes of liver disease. Regression analysis was used to assess the associations between: 1) NAFLD and psoriasis and 2) metabolic syndrome components and NAFLD among psoriasis patients. Results: NAFLD was more prevalent in patients with psoriasis (21.2% vs. 7.8%, p<0.04). However, psoriasis was not associated with NAFLD when matching for age, sex, and body mass index (BMI) (odds ratio: 2.63, 95% confidence interval [CI]: 0.51-13.6; p=0.25). As compared to patients with psoriasis but without NAFLD, those with NAFLD were more likely to have obesity (BMI: 34.9 vs. 27.2, 95% CI: 32.4-37.5 vs. 25.9-28.5; p<0.01). NAFLD in patients with psoriasis was also associated with select components of metabolic syndrome, including hyperglycemia and hyperlipidemia. Conclusion: Our findings show there is an association of psoriasis with NAFLD. Our findings also suggest an increased presence of metabolic syndrome components in patients with psoriasis and NAFLD. Trial registry: NCT00930384.

Genital Allergic Contact Dermatitis.

Genital allergic contact dermatitis (ACD) is an uncommon disorder, yet it severely impairs the quality of life for both men and women. Because of cultural taboos, many patients self-treat and delay proper diagnosis before presenting to a provider. Diagnosis is further confounded by irritant contact dermatitis and other genital dermatoses, which can predispose to skin barrier dysfunction and allergen penetration. Genital ACD can present acutely with erythematous erosions and pruritus or chronically with lichenification. Patch testing helps determine the diagnosis and provide relief for the patient. Topical medications, including local anesthetics and corticosteroids, are the most common genital allergens. Other typical allergens include fragrances, preservatives, adhesives, dyes, and rubber products. Less commonly considered allergens include herbs, spices, and topical vehicle components. Here, we review the most common allergens for both men and women, discuss important patch-testing panels, and recommend safe products for patients with genital ACD.

Profile of dupilumab and its potential in the treatment of inadequately controlled moderate-to-severe atopic dermatitis.

Atopic dermatitis (AD) is a common inflammatory skin disorder that manifests as eczematous lesions, often associated with allergic rhinitis and asthma. Historically, moderate-to-severe disease has been managed with systemic immunosuppression, such as oral corticosteroids, which result in relapse and limiting side effects. Due to recent advancements in the identification of interleukin (IL)-4 and IL-13 as key mediators in AD, new biological agents have been developed for treatment. Dupilumab is a recently approved monoclonal antibody that targets the alpha subunit of the IL-4 receptor and, thus, downregulates activity of IL-4 and IL-13. This review discusses the profile of dupilumab and its potential for efficacy and safety in treating moderate-to-severe AD by reviewing data from Phase I-III clinical trials. Results suggest that dupilumab shows great therapeutic promise for AD. Further studies investigating extended use of dupilumab and dupilumab in comparison to other agents are needed to establish long-term efficacy and safety.