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ImportanceIndividuals with allergic contact dermatitis to one topical corticosteroid may also react to other corticosteroids. Corticosteroid classification models have been proposed to predict such copositivity, recommend representative screening corticosteroids, and guide allergen avoidance.ObjectiveTo use patient data to determine copositivity patterns between corticosteroids and evaluate against previous corticosteroid classification models.Design, Setting, and ParticipantsThis qualitative study included a retrospective analysis of the Mayo Clinic Contact Dermatitis Group corticosteroid patch test data from 2010 to 2019. Among patients undergoing patch testing with the Mayo Clinic’s standard or steroid series who consented to research participation, 5637 patients were included in the analysis. Copositivity rates were determined between corticosteroids and analyzed by hierarchical clustering for comparison to previous classification models.Main Outcomes and MeasuresThe frequency of patch test positivity to each of the analyzed corticosteroids was noted and compared with previously published patch test positivity rates. Copositivity rates between each pair of corticosteroids were determined, and overall copositivity patterns were analyzed and evaluated against known steroid classes.ResultsA total of 49 472 individual patches were applied to 5637 patients, testing 18 corticosteroids. Patch test positivity rates ranged between 0.3% and 4.7%. The fluocinonide positivity rate corresponded to the highest copositivity rate with other corticosteroids (mean [SD], 50.7% [26.1%]). Tixocortol-21-pivalate, 0.1%, and tixocortol-21-pivalate, 1%, positivity rates corresponded to the lowest copositivity rates (mean [SD], 4.1% [1.7%] and 3.6% [1.4%], respectively). Hierarchical clustering elucidated patterns that did not support previous corticosteroid classification models.Conclusions and RelevanceIn this qualitative study, copositivity rates were variable between corticosteroids, and overall patch test positivity for allergy to topical corticosteroids was rare. Previously published corticosteroid classifications are not supported by real patient-derived data and may not be accurate in predicting corticosteroid copositivity.

This cohort study examines factors that may contribute to whether patients address physicians differently through electronic messaging

Background Granuloma annulare (GA) and the related annular elastolytic giant cell granuloma (AEGCG) and interstitial granulomatous dermatitis (IGD) are idiopathic histiocytic inflammatory disorders, which are frequently recalcitrant to treatment. Objectives Evaluate the efficacy of sulphasalazine in treating GA, AEGCG and IGD. Methods Sixteen patients were identified with granulomatous disease who were treated with sulphasalazine between September 2015 and September 2019. Outcomes were based on patients' and providers' subjective evaluations. Results Sixteen patients were included in the study (ages 56-89, four male and twelve female). Previous treatments were attempted in fifteen patients. Clinical improvement was seen in fourteen patients (87.5%). Initial improvement was noted within a mean (SD) of 66.4 (35.1) days after starting therapy, with increasing benefits over time. Ten patients (62.5%) reported complete or near-complete clearance, three patients (18.8%) reported significant improvement, and one (6.3%) reported partial improvement. Twelve patients elected to stop or reduce therapy, resulting in relapse or worsening in five patients. Conclusions Sulphasalazine may be considered as treatment for GA and GA-related conditions.

Background Knowledge regarding the use of xenografts in cutaneous surgery is limited. Objective We sought to better understand the utility, outcomes, and complications of porcine xenograft applications in cutaneous surgery. Methods and materials A single center, retrospective study of patients with porcine xenograft applications was completed. Characteristics of tumors, surgical procedures, resulting wound beds, follow-up care, and final length of follow-up were determined, and statistical analysis was conducted. Results Of 225 porcine xenograft placements in 220 patients, the majority of tumors were nonmelanoma skin cancers (89%) and similarly divided between the head (excepting nose/ear), nose, ear, and extremities. Both Mohs and standard excision resulted in a 5.7 cm mean area of surgical defect, with the majority closed by porcine xenograft only (84.1%), and healing by secondary intention (97.3%). The area of surgical defect and topical antibiotics contributed to increased length of time to final follow-up. Conclusion The data represent the largest series of biologic dressings in cutaneous surgery and demonstrate the applicability and safety of porcine xenografts. We recommend consideration of porcine xenografts in the appropriate clinical context, to augment secondary intention.

Trichothiodystrophy is a rare autosomal recessive disorder resulting in a broad range of systemic abnormalities. Polarizing microscopy of the hair reveals the pathognomic “tiger tail” of alternating light and dark bands, but the need for a microscope prevents rapid bedside diagnosis. We describe a new technique for the bedside diagnosis of trichothiodystrophy using a handheld polarizing dermatoscope, precluding the need for microscopic examination.

SummaryLong noncoding RNAs (lncRNAs) are increasingly appreciated as regulators of cell-specific gene expression. Here, an enhancer-like lncRNA termed NeST (nettoie Salmonella pas Theiler’s [cleanup Salmonella not Theiler’s]) is shown to be causal for all phenotypes conferred by murine viral susceptibility locus Tmevp3. This locus was defined by crosses between SJL/J and B10.S mice and contains several candidate genes, including NeST. The SJL/J-derived locus confers higher lncRNA expression, increased interferon-γ (IFN-γ) abundance in activated CD8+ T cells, increased Theiler’s virus persistence, and decreased Salmonella enterica pathogenesis. Transgenic expression of NeST lncRNA alone was sufficient to confer all phenotypes of the SJL/J locus. NeST RNA was found to bind WDR5, a component of the histone H3 lysine 4 methyltransferase complex, and to alter histone 3 methylation at the IFN-γ locus. Thus, this lncRNA regulates epigenetic marking of IFN-γ-encoding chromatin, expression of IFN-γ, and susceptibility to a viral and a bacterial pathogen.

Populations are at risk of extinction when unsuitable or when sink habitat exceeds a threshold frequency in the environment. Sinks that present cues associated with high-quality habitats, termed ecological traps, have especially detrimental effects on net population growth at metapopulation scales. Ecological traps for viruses arise naturally, or can be engineered, via the expression of viral-binding sites on cells that preclude viral reproduction. We present a model for virus population growth in a heterogeneous host community, parameterized with data from populations of the RNA bacteriophage Phi6 presented with mixtures of suitable host bacteria and either neutral or trap cells. We demonstrate that viruses can sustain high rates of population growth in the presence of neutral non-hosts as long as some host cells are present, whereas trap cells dramatically reduce viral fitness. In addition, we demonstrate that the efficacy of traps for viral elimination is frequency dependent in spatially structured environments such that population viability is a nonlinear function of habitat loss in dispersal-limited virus populations. We conclude that the ecological concepts applied to species conservation in altered landscapes can also contribute to the development of trap cell therapies for infectious human viruses.

Gene expression profiling in E 11 mouse embryos identified high expression of the long noncoding RNA (lncRNA), LNCRNA-HIT in the undifferentiated limb mesenchyme, gut, and developing genital tubercle. In the limb mesenchyme, LncRNA-HIT was found to be retained in the nucleus, forming a complex with p100 and CBP. Analysis of the genome-wide distribution of LncRNA-HIT-p100/CBP complexes by ChIRP-seq revealed LncRNA-HIT associated peaks at multiple loci in the murine genome. Ontological analysis of the genes contacted by LncRNA-HIT-p100/CBP complexes indicate a primary role for these loci in chondrogenic differentiation. Functional analysis using siRNA-mediated reductions in LncRNA-HIT or p100 transcripts revealed a significant decrease in expression of many of the LncRNA-HIT-associated loci. LncRNA-HIT siRNA treatments also impacted the ability of the limb mesenchyme to form cartilage, reducing mesenchymal cell condensation and the formation of cartilage nodules. Mechanistically the LncRNA-HIT siRNA treatments impacted pro-chondrogenic gene expression by reducing H3K27ac or p100 activity, confirming that LncRNA-HIT is essential for chondrogenic differentiation in the limb mesenchyme. Taken together, these findings reveal a fundamental epigenetic mechanism functioning during early limb development, using LncRNA-HIT and its associated proteins to promote the expression of multiple genes whose products are necessary for the formation of cartilage., Author Summary A fundamental problem studied by skeletal biologists is the development of regenerative therapies to replace cartilage tissues impacted by injury or disease, which for individuals affected by osteoarthritis represents nearly half of all of all adults over the age of sixty five. To date, no therapies exist to promote sustained cartilage regeneration, as we have not been able to recapitulate the programming events necessary to instruct cells to form articular cartilage without these cells continuing to differentiate into bone. Our analysis of the early programming events occurring during cartilage formation led to the identification of LncRNA-HIT a long noncoding RNA that is essential for the differentiation of the embryonic limb mesenchyme into cartilage. A genome wide analysis of LncRNA-HIT’s distribution in the mesenchyme revealed strong association between LncRNA-HIT and numerous genes whose products facilitate cartilage formation. In the absence of LncRNA-HIT, the expression of these chondrogenic genes is severely reduced, impacting the differentiation of these cells into cartilage. Mechanistically, LncRNA-HIT regulates these pro-chondrogenic genes by recruiting p100 and CBP to these loci, facilitating H3K27ac and transcriptional activation. LncRNA-HIT also appears to be present in most vertebrate species, suggesting that the epigenetic program regulated by this lncRNA may represent a fundamental mechanism used by many species to promote cartilage formation.

A major question in developmental biology is how functionally related groups of genes are switched on at the right time and in the right place. Long intergenic non-coding RNAs (lincRNAs) have been implicated in both gene silencing and activation, and could be a means of long-range control of gene expression. A lincRNA termed HOTTIP that coordinates the activation of multiple 5' HOXA regulatory genes has now been identified at the 5' tip of the HOXA locus. Chromosomal looping brings HOTTIP close its target genes, where it facilitates histone H3 lysine 4 trimethylation and gene transcription. Long intergenic non-coding RNAs (lincRNAs) have been implicated in both gene silencing and activation, and could be a means for long-range control of gene expression. Here a lincRNA termed HOTTIP is identified at the 5′ tip of the HOXA locus that coordinates the activation of multiple 5′ HOXA genes. Chromosomal looping brings HOTTIP into the proximity of its target genes, where it seems to be required to facilitate histone H3 lysine 4 trimethylation and gene transcription. The genome is extensively transcribed into long intergenic noncoding RNAs (lincRNAs), many of which are implicated in gene silencing1,2. Potential roles of lincRNAs in gene activation are much less understood3,4,5. Development and homeostasis require coordinate regulation of neighbouring genes through a process termed locus control6. Some locus control elements and enhancers transcribe lincRNAs7,8,9,10, hinting at possible roles in long-range control. In vertebrates, 39 Hox genes, encoding homeodomain transcription factors critical for positional identity, are clustered in four chromosomal loci; the Hox genes are expressed in nested anterior-posterior and proximal-distal patterns colinear with their genomic position from 3′ to 5′of the cluster11. Here we identify HOTTIP, a lincRNA transcribed from the 5′ tip of the HOXA locus that coordinates the activation of several 5′ HOXA genes in vivo. Chromosomal looping brings HOTTIP into close proximity to its target genes. HOTTIP RNA binds the adaptor protein WDR5 directly and targets WDR5/MLL complexes across HOXA, driving histone H3 lysine 4 trimethylation and gene transcription. Induced proximity is necessary and sufficient for HOTTIP RNA activation of its target genes. Thus, by serving as key intermediates that transmit information from higher order chromosomal looping into chromatin modifications, lincRNAs may organize chromatin domains to coordinate long-range gene activation.

Pathogens vectored by nematodes pose serious agricultural, economic, and health threats; however, little is known of the ecological and evolutionary aspects of pathogen transmission by nematodes. Here we describe a novel model system with two trophic levels, bacteriophages and nematodes, each of which competes for bacteria. We demonstrate for the first time that nematodes are capable of transmitting phages between spatially distinct patches of bacteria. This model system has considerable advantages, including the ease of maintenance and manipulation at the laboratory bench, the ability to observe many generations in short periods, and the capacity to freeze evolved strains for later comparison to their ancestors. More generally, experimental studies of complex multispecies interactions, host-pathogen coevolution, disease dynamics, and the evolution of virulence may benefit from this model system because current models (e.g., chickens, mosquitoes, and malaria parasites) are costly to maintain, are difficult to manipulate, and require considerable space. Our initial explorations centered on independently assessing the impacts of nematode, bacterium, and phage population densities on virus migration between host patches. Our results indicated that virus transmission increases with worm density and host bacterial abundance; however, transmission decreases with initial phage abundance, perhaps because viruses eliminate available hosts before migration can occur. We discuss the microbial growth dynamics that underlie these results, suggest mechanistic explanations for nematode transmission of phages, and propose intriguing possibilities for future research.