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Background:Natural moisturizing factor (NMF) is used as genotypic and phenotypic biomarker in diagnostics. This study is a side-to-side comparison of two different methods to determine NMF in atopic dermatitis patients: Raman microspectroscopy and stratum corneum tape stripping followed by HPLC. Results:Measured NMF values were significantly correlated (R2 = .61;p < .0001), both methods demonstrated a concentration-depth dependence of NMF and reduced NMF levels in the carriers of filaggrin null mutations. Good agreement between measurements of left and right arms indicated robustness and good reproducibility of both methods. Conclusions:Both methods showed comparable performance, choice of method will rather be influenced by practical consideration. [ABSTRACT FROM PUBLISHER]

Reports on the results of a case study which showed the potential of the bacterium acidophilus as a treatment for drug-induced diarrhea. Sources of acidophilus; Description of diarrhea patients' condition.

Radiotherapy in the head-and-neck area is one of the main curative treatment options. However, this comes at the cost of varying levels of normal tissue toxicity, affecting up to 80% of patients. Mucositis can cause pain, weight loss and treatment delays, leading to worse outcomes and a decreased quality of life. Therefore, there is an urgent need for an approach to predicting normal mucosal responses in patients prior to treatment. We here describe an assay to detect irradiation responses in healthy oral mucosa tissue. Mucosa specimens from the oral cavity were obtained after surgical resection, cut into thin slices, irradiated and cultured for three days. Seven samples were irradiated with X-ray, and three additional samples were irradiated with both X-ray and protons. Healthy oral mucosa tissue slices maintained normal morphology and viability for three days. We measured a dose-dependent response to X-ray irradiation and compared X-ray and proton irradiation in the same mucosa sample using standardized automated image analysis. Furthermore, increased levels of inflammation-inducing factors-major drivers of mucositis development-could be detected after irradiation. This model can be utilized for investigating mechanistic aspects of mucositis development and can be developed into an assay to predict radiation-induced toxicity in normal mucosa.

Abundant corneocyte surface protrusions, observed in patients with atopic dermatitis with filaggrin loss-of-function mutations, are inversely associated with levels of natural moisturizing factors (NMFs) in the stratum corneum. To dissect the etiological role of NMFs and filaggrin deficiency in surface texture alterations, we examined mouse models with genetic deficiencies in the synthesis or degradation of filaggrin monomers for NMFs, cell stiffness (elastic modulus) and corneocyte surface protrusion density (dermal texture index). Five neonatal and adult mouse models carrying inactivating mutations of SASPase (Sasp -/- ), filaggrin (Flg ft/ft and Flg -/- ), filaggrin-hornerin (FlgHrnr -/- ), and bleomycin hydrolase (Blmh -/- ) were investigated. Sasp -/- and Flg -/- were on the hairless mouse background. Atomic force microscopy was used to determine elastic modulus and dermal texture index. Corneocytes of each neonatal as well as hairless adult knockout mouse exhibited an increased number of protrusions and decreased elastic modulus. In these mice, NMFs were reduced except for Sasp -/- . Dermal texture index was inversely correlated with NMFs and elastic modulus. Our findings demonstrate that any filaggrin-NMF axis deficiency can affect corneocyte mechanical properties in mice and likely in humans. Differences in NMFs and corneocyte surface texture between neonatal and adult as well as hairless and hairy mice emphasize the need for carefully selecting the most appropriate animal models for studies., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: In rodents, we reported that short pulse-width (PW) neuromodulation might provide more efficient therapy delivery than traditional 0.21 msec PW. Using fully implanted, commercialized systems in the sheep, the goal of this study was to characterize the relationship of electromyographic (EMG) responses of the external anal sphincter (EAS) to different PWs of sacral neuromodulation (SNM)., Materials and Methods: In seven sheep, InterStim® quadripolar tined leads were implanted adjacent to the S3 nerve root bilaterally to deliver SNM and two pairs of intramuscular leads were placed on either side of the EAS for EMG sensing. The EMG responses to SNM with different PWs were examined using variable intensities in both anesthetized and conscious conditions., Results: The EMG responses from ipsilateral EAS (I EAS ) and contralateral EAS (C EAS ) were compared. The area under the curve of EMG responses from I EAS were significantly stronger than that from C EAS. The late component EMGs were more sensitive to nerve stimulation with a higher response amplitude in awake sheep. The response threshold-PW relationship from the I EAS as ascertained visually and with EMG in anesthetized and awake sheep were fitted with a monoexponential nonlinear regression; the resulting chronaxies were of 0.05 msec (n = 6), and 0.04 msec (n = 6), and 0.04 msec (n = 8), respectively., Conclusions: In both anesthetized and awake conditions, a similar motor response may be evoked in the EAS at PWs much shorter (0.04-0.05 msec) than the 0.21 msec typically used with SNM. Potential battery savings manifested by shorter PW would provide more efficient therapy delivery and increased longevity of the stimulator., (© 2018 International Neuromodulation Society.)

Theoretically embedded in the migration/social policy nexus, this paper investigates cooperation with return (CWR) as a policy tool to remove practical deportation barriers for third-country nationals pending removal. Based on legal and policy documents and expert interviews with stakeholders in Austria and the Netherlands, the paper asks how CWR is implemented and what influence it has, both on migration control aims and on access to social rights. We argue that the politicization of the issue and diverging interests between policy networks of welfare and migration affect the regulation and implementation of the tool. By comparing the use of CWR within two country contexts, the analysis presented here adds valuable insights on features of governmental instruments in response to the "deportation gap". The paper further adds to the literature on sanction-oriented, personalized migration policies., Competing Interests: Sieglinde Rosenberger carries an MA (Mag.rer.soc.oec.) in Economics and Political Science as well as a PhD in Political Science from the University of Innsbruck. Since 1998 Sieglinde Rosenberger is Full Professor at the Department of Political Science at University of Vienna, since then she took up several research fellowships at renowned Universities like Harvard (2003/04) and the EUI in Florence (2007). Her main research interests are Democracy and Differences/Diversity in Europe, Migration and asylum policies and politics, Political Protest in Asylum and Migration, Political Participation. Rosenberger coordinates the FWF funded research project “Inside the Deportation Gap: Social Membership of non-deported Migrants” (2015–2018). Sabine Koppes was born in 1990 in the Netherlands. She carries an MA in Conflict Studies and Human Rights from the University of Utrecht. Since 2012, she has been working with migrants in limbo in the Netherlands. Sabine Koppes was involved as a research fellow in the project ‘Inside the deportation gap: Social membership for non-deported persons’ at the Department of Political Science at the University of Vienna, where she was responsible for the collection and analysis of data in the Netherlands. Currently, she is program officer at the Dutch section of Amnesty International where she works on the subject of human rights for migrants without residency status in the Netherlands.The authors declare no competing interests with respect to the research, authorship and publication of this article.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Background: Recent studies have demonstrated allergen-specific differences in the gene expression of inflammatory mediators in patch tested skin., Objectives: To determine levels of various inflammatory mediators in the stratum corneum (SC) after patch testing with common contact allergens and the skin irritant sodium lauryl sulfate (SLS)., Methods: In total, 27 individuals who had previously patch tested positive to nickel, chromium, methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) or para-phenylenediamine were retested and then patch tested with SLS and petrolatum, with petrolatum serving as the patch test control. At 72 h, the test sites were clinically graded and the SC samples collected on adhesive tape., Results: The levels of 18 of the 32 quantified mediators differed significantly from that of the control patches for at least one of the tested substances. SLS and MCI/MI induced the largest number of immunomediators. Interleukin (IL)-16 levels were significantly higher in patch test reactions in all allergens than they were in the controls, while no significant difference was detected for SLS. Furthermore, a strong negative correlation was found between strength of patch test reaction and IL-1α levels., Conclusions: Cytokine profiles in the SC of patch tested skin did not show a distinct allergen-specific pattern. However, MCI/MI induced a larger and wider immune response than the other allergens, perhaps due to its potency as an irritant. The levels of IL-16 were significantly increased in patch test reactions to allergens but not to SLS; thus, they may help clinicians to differentiate between allergic contact dermatitis and irritant contact dermatitis., (© 2016 British Association of Dermatologists.)

Contributions of mechanical signals to airway remodeling during asthma are poorly understood. Transient receptor potential vanilloid 4 (TRPV4), a mechanosensitive ion channel, has been implicated in cardiac and pulmonary fibrosis; however, its role in asthma remains elusive. Employing a Dermatophagoides farinae -induced asthma model, we report here that TRPV4-knockout mice were protected from D. farinae -induced airway remodeling. Furthermore, lung fibroblasts that were isolated from TRPV4-knockout mice showed diminished differentiation potential compared with wild-type mice. Fibroblasts from asthmatic lung exhibited increased TRPV4 activity and enhanced differentiation potential compared with normal human lung fibroblasts. Of interest, TGF-β1 treatment enhanced TRPV4 activation in a PI3K-dependent manner in normal human lung fibroblasts in vitro Mechanistically, TRPV4 modulated matrix remodeling in the lung via 2 distinct but dependent pathways: one enhances matrix deposition by fibrotic gene activation, whereas the other slows down matrix degradation by increased plasminogen activator inhibitor 1. Of importance, both pathways are regulated by Rho/myocardin-related transcription factor-A and contribute to fibroblast differentiation and matrix remodeling in the lung. Thus, our results support a unique role for TRPV4 in D. farinae -induced airway remodeling and warrant further studies in humans for it to be used as a novel therapeutic target in the treatment of asthma.-Gombedza, F., Kondeti, V., Al-Azzam, N., Koppes, S., Duah, E., Patil, P., Hexter, M., Phillips, D., Thodeti, C. K., Paruchuri, S. Mechanosensitive transient receptor potential vanilloid 4 regulates Dermatophagoides farinae -induced airway remodeling via 2 distinct pathways modulating matrix synthesis and degradation., (© FASEB.)