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1.
Epidemiol Infect ; 147: e240, 2019 01.
Article in English | MEDLINE | ID: mdl-31364577

ABSTRACT

Hendra virus (HeV) continues to cause fatal infection in horses and threaten infection in close-contact humans in eastern Australia. Species of Pteropus bats (flying-foxes) are the natural reservoir of the virus. We caught and sampled flying-foxes from a multispecies roost in southeast Queensland, Australia on eight occasions between June 2013 and June 2014. The effects of sample date, species, sex, age class, body condition score (BCS), pregnancy and lactation on HeV antibody prevalence, log-transformed median fluorescent intensity (lnMFI) values and HeV RNA status were assessed using unbalanced generalised linear models. A total of 1968 flying-foxes were sampled, comprising 1012 Pteropus alecto, 742 P. poliocephalus and 214 P. scapulatus. Sample date, species and age class were each statistically associated with HeV RNA status, antibody status and lnMFI values; BCS was statistically associated with HeV RNA status and antibody status. The findings support immunologically naïve sub-adult P. alecto playing an important role in maintaining HeV infection at a population level. The biological significance of the association between BCS and HeV RNA status, and BCS and HeV antibody status, is less clear and warrants further investigation. Contrary to previous studies, we found no direct association between HeV infection and pregnancy or lactation. The findings in P. poliocephalus suggest that HeV exposure in this species may not result in systemic infection and virus excretion, or alternatively, may reflect assay cross-reactivity with another (unidentified) henipavirus.


Subject(s)
Chiroptera/virology , Disease Outbreaks/statistics & numerical data , Disease Transmission, Infectious/statistics & numerical data , Hendra Virus/isolation & purification , Henipavirus Infections/epidemiology , Horse Diseases/epidemiology , Age Factors , Animals , Antibodies, Viral/blood , Australia/epidemiology , Body Composition , Female , Horses , Humans , Pregnancy , Prevalence , Queensland/epidemiology , RNA, Viral/analysis , Real-Time Polymerase Chain Reaction/methods , Risk Assessment , Seasons
2.
J Eur Acad Dermatol Venereol ; 33(2): 367-375, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30357932

ABSTRACT

BACKGROUND: Janus kinase (JAK) inhibition may be a promising new treatment modality for inflammatory (skin) diseases. However, little is known about direct effects of kinase inhibitors on keratinocyte differentiation and function as well as skin barrier formation. OBJECTIVE: Our aim was to address the direct impact of kinase inhibition of the JAK1/3 pathways by tofacitinib on keratinocyte immune function and barrier formation in atopic dermatitis (AD) and psoriasis. METHODS: 3D skin equivalents of both diseases were developed and concurrently pretreated with tofacitinib. To induce AD, 3D skin equivalents were stimulated with recombinant human IL-4 and IL-13. Psoriasis-like conditions were induced by incubation with IL-17A, IL-22 and tumour necrosis factor α (TNFα). The activation of signal transducer and activator of transcription (STAT)1, STAT3 and STAT6 was assessed by Western blot analysis. Microarray analysis and quantitative real-time PCR were used for gene expression analysis. RESULTS: Tofacitinib pretreatment preserved epidermal morphology and reduced STAT3 and STAT6 phosphorylation of AD-like and STAT3 phosphorylation of psoriasis-like culture conditions in 3D skin models compared to sham-controls. Filaggrin expression was fully maintained in the AD-like models, but only partially in psoriasis-like conditions after pretreatment with tofacitinib. In addition, tofacitinib upregulated DSC1, FLG and KRT1. Using gene expression analysis, downregulation of POSTN and IL24 was observed in AD-like conditions, whereas downregulation of IL20 and IL1B was observed in psoriasis-like conditions. CONCLUSION: JAK1/3 inhibition counteracted cytokine-induced AD- and psoriasis-like epidermal morphology and enhanced keratinocyte differentiation in 3D skin models. This effect was more pronounced in the AD-like models compared to the psoriasis-like 3D skin models.


Subject(s)
Dermatitis, Atopic/pathology , Imaging, Three-Dimensional , Intermediate Filament Proteins/pharmacology , Janus Kinase 1/drug effects , Piperidines/pharmacology , Psoriasis/pathology , Pyrimidines/pharmacology , Pyrroles/pharmacology , Cell Proliferation/drug effects , Computer Simulation , Dermatitis, Atopic/drug therapy , Filaggrin Proteins , Humans , Keratinocytes/cytology , Keratinocytes/drug effects , Psoriasis/drug therapy , STAT6 Transcription Factor/drug effects , Sensitivity and Specificity
3.
Lasers Med Sci ; 33(4): 765-772, 2018 May.
Article in English | MEDLINE | ID: mdl-29218493

ABSTRACT

Molecular effects of various ablative and non-ablative laser treatments on human skin cells-especially primary effects on epidermal keratinocytes and dermal fibroblasts-are not yet fully understood. We present the first study addressing molecular effects of fractional non-sequential ultrapulsed CO2 laser treatment using a 3D skin model that allows standardized investigations of time-dependent molecular changes ex vivo. While histological examination was performed to assess morphological changes, we utilized gene expression profiling using microarray and qRT-PCR analyses to identify molecular effects of laser treatment. Irradiated models exhibited dose-dependent morphological changes resulting in an almost complete recovery of the epidermis 5 days after irradiation. On day 5 after laser injury with a laser fluence of 100 mJ/cm2, gene array analysis identified an upregulation of genes associated with tissue remodeling and wound healing (e.g., COL12A1 and FGF7), genes that are involved in the immune response (e.g., CXCL12 and CCL8) as well as members of the heat shock protein family (e.g., HSPB3). On the other hand, we detected a downregulation of matrix metalloproteinases (e.g., MMP3), differentiation markers (e.g., LOR and S100A7), and the pro-inflammatory cytokine IL1α.Overall, our findings substantiate the understanding of time-dependent molecular changes after CO2 laser treatment. The utilized 3D skin model system proved to be a reliable, accurate, and reproducible tool to explore the effects of various laser settings both on skin morphology and gene expression during wound healing.


Subject(s)
Fibroblasts/radiation effects , Keratinocytes/radiation effects , Lasers, Gas/therapeutic use , Models, Biological , Skin/radiation effects , Chemokine CXCL12/metabolism , Child , Fluorescent Antibody Technique , Gene Expression Profiling , Humans , Male , Real-Time Polymerase Chain Reaction , Wound Healing/radiation effects
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