101 research outputs found

    Limited clinical utility of HLA-Cw6 genotyping for outcome prediction in psoriasis patients under ustekinumab therapy: a monocentric, retrospective analysis

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    Florian Anzengruber,1,2 Adhideb Ghosh,1–3 Julia-Tatjana Maul,1,2 Mathias Drach,1,2 Alexander A Navarini1–3 1Department of Dermatology, University Hospital Zurich, Zurich, Switzerland; 2Faculty of Medicine, University of Zurich, Zurich, Switzerland; 3Competence Center Personalized Medicine University of Zurich/Swiss Federal Institute of Technology (ETH) Zurich, Switzerland Purpose: Several studies have suggested that an HLA-Cw6+ allele can predict an improved outcome of treatment in psoriasis patients. The aim of the study was to assess whether the published association between HLA-Cw6 allele carriers and response to ustekinumab has the potential to impact treatment decisions. Patients and methods: Differences in Psoriasis Activity and Severity Index 50, 75, and 90; Nail Psoriasis Severity Index; and Dermatology Life Quality Index at 16 weeks were evaluated between HLA-Cw6 allele carriers vs. non-carriers. Thirty patients with moderate-to-severe psoriasis under treatment with ustekinumab were included in our study. Results: There was no difference between the two groups with respect to Psoriasis Activity and Severity Index 50, 75, and 90 or in terms of change in Nail Psoriasis Severity Index or Dermatology Life Quality Index. Conclusion: In our retrospectively analyzed cohort, we could not detect the previously reported better response in HLA-Cw6+ vs. HLA-Cw6− patients. Keywords: human leukocyte antigen, Cw6, genetic variations, HLA-Cw6, ustekinuma

    Classification of Matching Molecular Series on the Basis of SAR Phenotypes and Structural Relationships

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    <p>A database comprising a total of 13,236 pairs of MMS with different SAR characteristics is provided. For each pair the corresponding MMS-cores are provided  as SMILES. In addition, for each MMS-core the number of compounds and the SAR phenotype are given. ChEMBL target IDs (CHEMBLID_Target) designate target sets from which the MMS pairs originate.  </p&gt

    Wide range of age of onset and low referral rates to psychiatry in a large cohort of acne excoriée at a Swiss tertiary hospital

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    Repetitive skin manipulation is the key symptom in skin picking disorder (SPD) or acne excoriée des jeunes filles Brocq. The diagnostic and statistical manual of mental disorders (DSM-5) has recognized SPD as an independent disease, namely an obsessive-compulsive disorder. Thus, psychiatric treatment is indicated. Therefore, in a large cohort of SPD, we asked whether dermatologists' treatment strategy includes routine referrals to psychiatry. In addition, we describe epidemiological data, treatments and follow up.; We performed a retrospective study, searching in our hospital database between January 1 2011 and December 31 2016.; A total of 154 (141 female, 13 male) patients were included in our study. In less than 5% a referral to a psychologist or psychiatrist occurred. More than 90% of all patients received topical and almost 40% systemical anti-acne treatment. The loss of follow-up was very high.; Our study shows that dermatologists focus on treating acne-like lesions in SPD, but rarely refer to psychiatry. Possible reasons include considerations of patients' reactions who often reject the idea of a psychological origin of the disease. Our results suggest that new treatment strategies should be created to address SPD correctly, i.e. by combined consultations with psychiatrists or specific training of dermatologists in psychiatric therapy and diagnostics

    Limited clinical utility of HLA-Cw6 genotyping for outcome prediction in psoriasis patients under ustekinumab therapy: a monocentric, retrospective analysis

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    Purpose: Several studies have suggested that an HLA-Cw6+ allele can predict an improved outcome of treatment in psoriasis patients. The aim of the study was to assess whether the published association between HLA-Cw6 allele carriers and response to ustekinumab has the potential to impact treatment decisions. Patients and methods: Differences in Psoriasis Activity and Severity Index 50, 75, and 90; Nail Psoriasis Severity Index; and Dermatology Life Quality Index at 16 weeks were evaluated between HLA-Cw6 allele carriers vs. non-carriers. Thirty patients with moderate-to-severe psoriasis under treatment with ustekinumab were included in our study. Results: There was no difference between the two groups with respect to Psoriasis Activity and Severity Index 50, 75, and 90 or in terms of change in Nail Psoriasis Severity Index or Dermatology Life Quality Index. Conclusion: In our retrospectively analyzed cohort, we could not detect the previously reported better response in HLA-Cw6+ vs. HLA-Cw6- patients

    Transgene-free direct conversion of murine fibroblasts into functional muscle stem cells

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    Abstract Transcription factor-based cellular reprogramming provides an attractive approach to produce desired cell types for regenerative medicine purposes. Such cellular conversions are widely dependent on viral vectors to efficiently deliver and express defined factors in target cells. However, use of viral vectors is associated with unfavorable genomic integrations that can trigger deleterious molecular consequences, rendering this method a potential impediment to clinical applications. Here, we report on a highly efficient transgene-free approach to directly convert mouse fibroblasts into induced myogenic progenitor cells (iMPCs) by overexpression of synthetic MyoD-mRNA in concert with an enhanced small molecule cocktail. First, we performed a candidate compound screen and identified two molecules that enhance fibroblast reprogramming into iMPCs by suppression of the JNK and JAK/STAT pathways. Simultaneously, we developed an optimal transfection protocol to transiently overexpress synthetic MyoD-mRNA in fibroblasts. Combining these two techniques enabled robust and rapid reprogramming of fibroblasts into Pax7 positive iMPCs in as little as 10 days. Nascent transgene-free iMPCs proliferated extensively in vitro, expressed a suite of myogenic stem cell markers, and could differentiate into highly multinucleated and contractile myotubes. Furthermore, using global and single-cell transcriptome assays, we delineated gene expression changes associated with JNK and JAK/STAT pathway inhibition during reprogramming, and identified in iMPCs a Pax7 + stem cell subpopulation resembling satellite cells. Last, transgene-free iMPCs robustly engrafted skeletal muscles of a Duchenne muscular dystrophy mouse model, restoring dystrophin expression in hundreds of myofibers. In summary, this study reports on an improved and clinically safer approach to convert fibroblasts into myogenic stem cells that can efficiently contribute to muscle regeneration in vivo
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