Dysbiosis of skin microbiota with increased fungal diversity is associated with severity of disease in atopic dermatitis

Background: Atopic dermatitis (AD) is a multifactorial inflammatory skin disease and an altered skin microbiota with an increase of Staphylococcus aureus has been reported. However, the role of fungi remains poorly investigated. Objectives: We aimed to improve the understanding of the fungal skin microbiota, the mycobiota, in AD in relation to the bacterial colonization. Methods: Skin swabs of 16 AD patients and 16 healthy controls (HC) from four different skin sites, that is antecubital crease, dorsal neck, glabella and vertex from multiple time points were analysed by DNA sequencing of the internal transcribed spacer region 1 (ITS1) and 16S rRNA gene for fungi and bacteria, respectively. Results: Malassezia spp. were the predominant fungi in all subjects but with a decreased dominance in severe AD patients in favour of non-Malassezia fungi, for example Candida spp. For bacteria, a decrease of Cutibacterium spp. in AD patients in favour of Staphylococcus spp., particularly S. aureus, was observed. Further, both bacterial and fungal community compositions of severe AD patients significantly differed from mild-to-moderate AD patients and HC with the latter two having overall similar microbiota showing some distinctions in bacterial communities. Conclusions: We conclude that severe AD is associated with a pronounced dysbiosis of the microbiota with increased fungal diversity. Potentially infectious agents, for example Staphylococcus and Candida, were increased in severe AD. Keywords: atopic dermatitis; bacteria; disease severity; fungi; skin microbiot

Increased fibrosis in a mouse model of anti-laminin 332 mucous membrane pemphigoid remains unaltered by inhibition of aldehyde dehydrogenase

Mucous membrane pemphigoid (MMP) is an autoimmune blistering disease characterized by autoantibodies against the basal membrane zone of skin and surface-close epithelia and predominant mucosal lesions. The oral cavity and conjunctivae are most frequently affected, albeit clinical manifestations can also occur on the skin. MMP-associated lesions outside the oral cavity typically lead to scarring. Mechanisms underlying scarring are largely unknown in MMP and effective treatment options are limited. Herein, we assessed the collagen architecture in tissue samples of an antibody-transfer mouse model of anti-laminin-332 MMP. In MMP mice, increased collagen fibril density was observed in skin and conjunctival lesions compared to mice injected with normal rabbit IgG. The extracellular matrix of MMP skin samples also showed altered post-translational collagen cross-linking with increased levels of both lysine- and hydroxylysine-derived collagen crosslinks supporting the fibrotic phenotype in experimental MMP compared to control animals. In addition, we evaluated a potential anti-fibrotic therapy in experimental anti-laminin-332 MMP using disulfiram, an inhibitor of the aldehyde dehydrogenase (ALDH), which has been implicated in immune-mediated mucosal scarring. In addition, disulfiram also acts as a copper chelator that was shown to block lysyl oxidase activity, an enzyme involved in formation of collagen crosslinks. Topical use of disulfiram (300 μM in 2 [w/v] methocel) did not improve ocular lesions in experimental MMP over the 12-day treatment period in disulfiram-treated mice compared to vehicle-treated mice (n=8/group). Furthermore, C57BL6/J mice (n=8/group) were treated prophylactically with 200 mg/kg p.o. disulfiram or the solvent once daily over a period of 12 days. Systemic treatment did not show any reduction in the severity of oral and ocular lesions in MMP mice, albeit some improvement in skin lesions was observed in disulfiram- vs. vehicle-treated mice (p=0.052). No reduction in fibrosis was seen, as assessed by immunohistochemistry. Whilst blocking of ALDH failed to significantly ameliorate disease activity, our data provide new insight into fibrotic processes highlighting changes in the collagenous matrix and cross-linking patterns in IgG-mediated MMP

Surveillance and Outbreak Response Management System (SORMAS) to support the control of the Ebola virus disease outbreak in West Africa

In the context of controlling the current outbreak of Ebola virus disease (EVD), the World Health Organization claimed that ‘critical determinant of epidemic size appears to be the speed of implementation of rigorous control measures’, i.e. immediate follow-up of contact persons during 21 days after exposure, isolation and treatment of cases, decontamination, and safe burials. We developed the Surveillance and Outbreak Response Management System (SORMAS) to improve efficiency and timeliness of these measures. We used the Design Thinking methodology to systematically analyse experiences from field workers and the Ebola Emergency Operations Centre (EOC) after successful control of the EVD outbreak in Nigeria. We developed a process model with seven personas representing the procedures of EVD outbreak control. The SORMAS system architecture combines latest In-Memory Database (IMDB) technology via SAP HANA (in-memory, relational database management system), enabling interactive data analyses, and established SAP cloud tools, such as SAP Afaria (a mobile device management software). The user interface consists of specific front-ends for smartphones and tablet devices, which are independent from physical configurations. SORMAS allows real-time, bidirectional information exchange between field workers and the EOC, ensures supervision of contact follow-up, automated status reports, and GPS tracking. SORMAS may become a platform for outbreak management and improved routine surveillance of any infectious disease. Furthermore, the SORMAS process model may serve as framework for EVD outbreak modelling

Polymorphisms in the Mitochondrial Genome Are Associated With Bullous Pemphigoid in Germans

Bullous pemphigoid (BP) is the most prevalent autoimmune skin blistering disease and is characterized by the generation of autoantibodies against the hemidesmosomal proteins BP180 (type XVII collagen) and BP230. Most intriguingly, BP is distinct from other autoimmune diseases because it predominantly affects elderly individuals above the age of 75 years, raising the question why autoantibodies and the clinical lesions of BP emerges mostly in this later stage of life, even in individuals harboring known putative BP-associated germline gene variants. The mitochondrial genome (mtDNA) is a potential candidate to provide additional insights into the BP etiology; however, the mtDNA has not been extensively explored to date. Therefore, we sequenced the whole mtDNA of German BP patients (n = 180) and age- and sex-matched healthy controls (n = 188) using next generation sequencing (NGS) technology, followed by the replication study using Sanger sequencing of an additional independent BP (n = 89) and control cohort (n = 104). While the BP and control groups showed comparable mitochondrial haplogroup distributions, the haplogroup T exhibited a tendency of higher frequency in BP patients suffering from neurodegenerative diseases (ND) compared to BP patients without ND (50%; 3 in 6 BP with haplogroup T). A total of four single nucleotide polymorphisms (SNPs) in the mtDNA, namely, m.16263T>C, m.16051A>G, and m.16162A>G in the D-loop region of the mtDNA, and m.11914G>A in the mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 4 gene (MT-ND4), were found to be significantly associated with BP based on the meta-analysis of our NGS data and the Sanger sequencing data (p = 0.0017, p = 0.0129, p = 0.0076, and p = 0.0132, respectively, Peto's test). More specifically, the three SNPs in the D-loop region were negatively, and the SNP in the MT-ND4 gene was positively associated with BP. Our study is the first to interrogate the whole mtDNA in BP patients and controls and to implicate multiple novel mtDNA variants in disease susceptibility. Studies using larger cohorts and more diverse populations are warranted to explore the functional consequences of the mtDNA variants identified in this study on immune and skin cells to understand their contributions to BP pathology

Hephaistos. A multimodal help assistant for the home environment

The TIDE 1004 HEPHAISTOS project (Home Environment Private Help AssISTant fOr elderly and diSabled) aims to develop a remote control unit for a broad range of home electronic devices. The multimodal user interface of the HEPHAISTOS remote control unit is based on a coloured high resolution touch screen extended with speech input/output. On the bases of first results of the HEPHAISTOS user trials the practical implication of the design for all philosophy for user interface design is discussed in this paper