Impact of climate change on atopic dermatitis: A review by the International Eczema Council.

Atopic dermatitis (AD), the most burdensome skin condition worldwide, is influenced by climatic factors and air pollution; however, the impact of increasing climatic hazards on AD remains poorly characterized. Leveraging an existing framework for 10 climatic hazards related to greenhouse gas emissions, we identified 18 studies with evidence for an impact on AD through a systematic search. Most climatic hazards had evidence for aggravation of AD the impact ranged from direct effects like particulate matter-induced AD exacerbations from wildfires to the potential for indirect effects like drought-induced food insecurity and migration. We then created maps comparing the past, present, and future projected burden of climatic hazards to global AD prevalence data. Data are lacking, especially from those regions most likely to experience more climatic hazards. We highlight gaps important for future research: understanding the synergistic impacts of climatic hazards on AD, long-term disease activity, the differential impact on vulnerable populations, and how basic mechanisms explain population-level trends.

Topical Management of Pediatric Psoriasis: A Review of New Developments and Existing Therapies.

Psoriasis is a chronic immune-mediated disorder that commonly affects adults and children. In recent years, pediatric psoriasis has increased in prevalence and the disease is often associated with various comorbidities and psychological distress. The conventional topical treatments for psoriasis, such as corticosteroids, calcineurin inhibitors, vitamin D analogs, anthralin, and coal tar, are often limited by their side effects, tolerability, and/or efficacy, particularly for use in children and on sensitive and intertriginous areas. Recently, the US Food and Drug Administration approved two new topical non-steroidal agents for treating psoriasis that target different pathogenic pathways than the conventional treatments. Roflumilast is a phosphodiesterase type 4 inhibitor approved for the treatment of plaque psoriasis in patients aged 12 years and older. Tapinarof is a novel aryl hydrocarbon receptor modulator approved for adult psoriasis and currently undergoing studies for pediatric psoriasis. Ongoing efforts are also being made to optimize conventional treatments, for instance, a new foam formulation of halobetasol propionate was recently approved for pediatric psoriasis. Clinical trials of various new drugs targeting one or multiple pathogenic pathways of psoriasis, such as Janus kinase inhibitors, different formulations of phosphodiesterase type 4 inhibitors, and aryl hydrocarbon receptor modulators have also been explored. The recent emergence of novel topical agents provides promising new options for managing pediatric psoriasis with the potential to improve clinical outcomes and quality of life. In this article, we review the mechanism of action, efficacy, and safety profile of novel topical agents and discuss their potential roles in the management of pediatric psoriasis.

Early Cutaneous Manifestations of COVID-19: A Systematic Review and Public Health Implications.

INTRODUCTION: Cutaneous manifestations before other symptoms have great potential for early COVID-19 diagnosis to prevent surge. METHODS: We conducted a search of PubMed and Embase databases through April 11, 2021 to include 39 studies reporting skin manifestations occurring prior to any other COVID-19 symptoms in laboratory-confirmed cases. RESULTS: Ninety-seven patients were included. Urticarial (24.7%) and maculopapular (22.7%) lesions were most common, followed by pernio (17.5%), vesicular (14.4%), papulosquamous (8.2%), and purpuric (5.1%) lesions. Cutaneous to systemic symptom latency ranged from 2 to 20 days in cases that reported it (26%), while skin lesions were the only presentation in 23 cases (23.7%). Skin lesions were the only COVID-19 manifestation in 58.8% of pernio, 40% of vesicular, 16.6% of urticarial, 18.2% of maculopapular, and 12.5% of papulosquamous presymptomatic cases. Although sample size is limited, all purpuric cases developed other symptom(s) later. CONCLUSIONS: Pernio and purpuric lesions have been well-associated with COVID-19, but papulosquamous, vesicular, mild maculopapular, and urticarial lesions can easily be dismissed as unrelated to COVID-19. Pernio lesions are thought to be related to strong immune response and low contagiousness, while purpuric and vesicular cases are speculated to be related to higher SARS-CoV2 viral load, severity, and contagiousness. All rashes, even without other symptoms, should necessitate high level of suspicion for isolation or contact tracing.

Symmetry breaking of tissue mechanics in wound induced hair follicle regeneration of laboratory and spiny mice.

Tissue regeneration is a process that recapitulates and restores organ structure and function. Although previous studies have demonstrated wound-induced hair neogenesis (WIHN) in laboratory mice (Mus), the regeneration is limited to the center of the wound unlike those observed in African spiny (Acomys) mice. Tissue mechanics have been implicated as an integral part of tissue morphogenesis. Here, we use the WIHN model to investigate the mechanical and molecular responses of laboratory and African spiny mice, and report these models demonstrate opposing trends in spatiotemporal morphogenetic field formation with association to wound stiffness landscapes. Transcriptome analysis and K14-Cre-Twist1 transgenic mice show the Twist1 pathway acts as a mediator for both epidermal-dermal interactions and a competence factor for periodic patterning, differing from those used in development. We propose a Turing model based on tissue stiffness that supports a two-scale tissue mechanics process: (1) establishing a morphogenetic field within the wound bed (mm scale) and (2) symmetry breaking of the epidermis and forming periodically arranged hair primordia within the morphogenetic field (µm scale). Thus, we delineate distinct chemo-mechanical events in building a Turing morphogenesis-competent field during WIHN of laboratory and African spiny mice and identify its evo-devo advantages with perspectives for regenerative medicine.

Tissue Mechanics in Haired Murine Skin: Potential Implications for Skin Aging.

During aging, the skin undergoes changes in architecture and composition. Skin aging phenotypes occur due to accumulated changes in the genome/epigenome, cytokine/cell adhesion, cell distribution/extracellular matrix (ECM), etc. Here we review data suggesting that tissue mechanics also plays a role in skin aging. While mouse and human skin share some similarities, their skin architectures differ in some respects. However, we use recent research in haired murine skin because of the available experimental data. Skin suffers from changes in both its appendages and inter-appendage regions. The elderly exhibit wrinkles and loose dermis and are more likely to suffer from wounds and superficial abrasions with poor healing. They also have a reduction in the number of skin appendages. While telogen is prolonged in aging murine skin, hair follicle stem cells can be rejuvenated to enter anagen if transplanted to a young skin environment. We highlight recent single-cell analyses performed on epidermis and aging human skin which identified new basal cell subpopulations that shift in response to wounding. This may be due to alterations of basement membrane stiffness which would change tissue mechanics in aging skin, leading to altered homeostatic dynamics. We propose that the extracellular matrix (ECM) may play a key role as a chemo-mechanical integrator of the multi-layered senescence-associated signaling pathways, dictating the tissue mechanical landscape of niche microenvironments in aging phenotypes. We show examples where failed chemo-mechanical signaling leads to deteriorating homeostasis during skin aging and suggest potential therapeutic strategies to guide future research to delay the aging processes.

Species richness and redundancy promote persistence of exploited mutualisms in yeast.

Mutualisms, or reciprocally beneficial interspecific interactions, constitute the foundation of many ecological communities and agricultural systems. Mutualisms come in different forms, from pairwise interactions to extremely diverse communities, and they are continually challenged with exploitation by nonmutualistic community members (exploiters). Thus, understanding how mutualisms persist remains an essential question in ecology. Theory suggests that high species richness and functional redundancy could promote mutualism persistence in complex mutualistic communities. Using a yeast system (Saccharomyces cerevisiae), we experimentally show that communities with the greatest mutualist richness and functional redundancy are nearly two times more likely to survive exploitation than are simple communities. Persistence increased because diverse communities were better able to mitigate the negative effects of competition with exploiters. Thus, large mutualistic networks may be inherently buffered from exploitation.

Different genetic basis for alcohol dehydrogenase activity and plasticity in a novel alcohol environment for Drosophila melanogaster.

Phenotypic plasticity is known to enhance population persistence, facilitate adaptive evolution and initiate novel phenotypes in novel environments. How plasticity can contribute or hinder adaptation to different environments hinges on its genetic architecture. Even though plasticity in many traits is genetically controlled, whether and how plasticity's genetic architecture might change in novel environments is still unclear. Because much of gene expression can be environmentally influenced, each environment may trigger different sets of genes that influence a trait. Using a quantitative trait loci (QTL) approach, we investigated the genetic basis of plasticity in a classic functional trait, alcohol dehydrogenase (ADH) activity in D. melanogaster, across both historical and novel alcohol environments. Previous research in D. melanogaster has also demonstrated that ADH activity is plastic in response to alcohol concentration in substrates used by both adult flies and larvae. We found that across all environments tested, ADH activity was largely influenced by a single QTL encompassing the Adh-coding gene and its known regulatory locus, delta-1. After controlling for the allelic variation of the Adh and delta-1 loci, we found additional but different minor QTLs in the 0 and 14% alcohol environments. In contrast, we discovered no major QTL for plasticity itself, including the Adh locus, regardless of the environmental gradients. This suggests that plasticity in ADH activity is likely influenced by many loci with small effects, and that the Adh locus is not environmentally sensitive to dietary alcohol.

Selection on structural allelic variation biases plasticity estimates.

Wang and Althoff (2019) explored the capacity of Drosophila melanogaster to exhibit adaptive plasticity in a novel environment. In a full-sib, half-sib design, they scored the activity of the enzyme alcohol dehydrogenase (ADH) and plastic responses, measured as changes in ADH activity across ethanol concentrations in the range of 0-10% (natural variation) and 16% (the novel environment). ADH activity increased with alcohol concentration, and there was a positive association between larval viability and ADH activity in the novel environment. They also reported that families exhibiting greater plasticity had higher larval survival in the novel environment, concluding that ADH plasticity is adaptive. However, the four authors now concur that, since the study estimated plasticity from phenotypic differences across environments using full-sib families, it is not possible to disentangle the contributions of allele frequency changes at the Adh locus from regulatory control at loci known to influence ADH activity. Selective changes in allele frequencies may thus conflate estimates of plasticity; any type of "plasticity" (adaptive, neutral, or maladaptive) could be inferred depending on allele frequencies. The problem of scoring sib-groups after selection should be considered in any plasticity study that cannot use replicated genotypes. Researchers should monitor changes in allele frequencies as one mechanism to deal with this issue.

Phenotypic plasticity facilitates initial colonization of a novel environment.

Phenotypic plasticity can allow organisms to respond to environmental changes by producing better matching phenotypes without any genetic change. Because of this, plasticity is predicted to be a major mechanism by which a population can survive the initial stage of colonizing a novel environment. We tested this prediction by challenging wild Drosophila melanogaster with increasingly extreme larval environments and then examining expression of alcohol dehydrogenase (ADH) and its relationship to larval survival in the first generation of encountering a novel environment. We found that most families responded in the adaptive direction of increased ADH activity in higher alcohol environments and families with higher plasticity were also more likely to survive in the highest alcohol environment. Thus, plasticity of ADH activity was positively selected in the most extreme environment and was a key trait influencing fitness. Furthermore, there was significant heritability of ADH plasticity that can allow plasticity to evolve in subsequent generations after initial colonization. The adaptive value of plasticity, however, was only evident in the most extreme environment and had little impact on fitness in less extreme environments. The results provide one of the first direct tests of the adaptive role of phenotypic plasticity in colonizing a novel environment.

Treatment of hereditary epidermolysis bullosa: updates and future prospects.

Epidermolysis bullosa (EB) represents a group of inherited blistering skin diseases, some forms of which are associated with considerable morbidity and increased mortality. Notably, in recessive dystrophic EB there can be extensive muco-cutaneous fragility and disease complications such as scars, contractures, anemia, malnutrition, and malignancy. Currently, there is no effective therapy or cure for EB. Over the last decade, however, a number of important advances have been made that are bringing new treatments closer to the clinic, including gene therapy, protein replacement therapy, cell therapies [allogeneic fibroblasts, mesenchymal stromal cells (MSCs), bone marrow stem cell transplantation, culturing/grafting revertant mosaic keratinocytes], gene editing/engineering, and clinical application of inducible pluripotent stem cells. Although a cure for EB still remains elusive, recent data on animal models and initial human clinical trials have raised the expectations of patients, clinicians, and researchers that disease modification and improved quality of life are feasible goals. Furthermore, the lessons learned in treating EB are likely to have significant implications for improving the management of other genetic diseases.