Development and validation of the K‐VSCOR for scoring Koebner's phenomenon in vitiligo/non‐segmental vitiligo

The relation of vitiligo/non‐segmental vitiligo (NSV) to Koebner's phenomenon is variably appreciated. Our objective was to develop and validate a simple clinical score for Koebner's phenomenon (KP) in patients with vitiligo/NSV. The study population was composed of 351 individuals in the development sample and 285 patients in the validation sample. Seven variables were independently associated with the presence of KP: disease duration of more than 3 yr, forehead + scalp areas, eyelids, wrists, genital + belt areas, knees and tibial crests. The score computed by the weighted sum of the rounded coefficients of these seven variables ranged from 0 to 56 (mean 38.39 ± 22.93). The probability of having KP was computed as follows: exp (?2.37 + 0.1*score)/exp [1 + (?2.37 + 0.1*score)]. When applying the score to each patient in the validation and the development sample, the score maintained adequate discrimination and calibration (AUC‐ROC = 0.78), arguing that KP can be adequately predicted using our score. Further studies should evaluate KP assessed by the K‐VSCOR in clinical practice with the aim to determine its association with clinical profile, course and treatment response of vitiligo.     

Increased circulating Th17 cells and elevated serum levels of TGF‐beta and IL‐21 are correlated with human non‐segmental vitiligo development

Although non‐segmental vitiligo (NSV) results from the autoimmune destruction of melanocytes, the detailed immune mechanisms have not yet been fully elucidated. Th17 cells have been identified to be implicated in human autoimmune diseases. In this study, the frequencies of peripheral blood Th17 cells and serum levels of IL‐17A and Th17 cell‐related cytokines were examined in 45 patients with active NSV compared to 45 race‐, gender‐, and age‐matched healthy controls. Our results showed increased circulating Th17 cell frequencies and elevated serum IL‐17A, TGF‐β1, and IL‐21 levels in patients with NSV. Meanwhile, the increased Th17 cell frequencies are positively correlated with serum TGF‐β1 level, and the body surface area of lesions is positively correlated with elevated TGF‐β1 and IL‐21 levels and Th17 cell frequencies. Furthermore, positive correlation was identified between Th17 and Th1 cell frequencies in patients with NSV. These results further indicate the potential involvement of Th17 cells and the collaborative contribution of Th17 and Th1 in NSV development, and suggest that the elevated serum TGF‐β1 and IL‐21 levels could contribute to enhanced Th17 cell differentiation in NSV.     

A review and a new hypothesis for non‐immunological pathogenetic mechanisms in vitiligo

Vitiligo is an acquired depigmenting disorder characterized by the loss of functioning epidermal melanocytes because of multifactorial and overlapping pathogenetic mechanisms. Besides the immunological approach, the study of the metabolic deregulations leading to toxic damage of the melanocytes appears to be more and more relevant. It was only last year that the first in vitro evidence supporting the link and the temporal sequence between the immune response and the cellular oxidative stress was provided, suggesting that the intrinsic damage of the melanocytes is primitive. What can be the guide line of the multiple altered metabolisms? A compromised membrane could render the cell sensitive to the external and internal agents differently, usually ineffective on the cell activity and survival. The primitive altered arrangement of the lipids may affect the transmembrane housing of proteins with enzymatic or receptorial activities, also conferring on them antigenic properties.     

On boundary solutions and identifiability in categorical regression with non‐ignorable non‐response

This paper considers the regression analysis of categorical variables when the response variable is incompletely observed and the non‐response mechanism is assumed to be non‐ignorable. Maximum likelihood estimation of the model parameters can lead to substantively implausible boundary solutions where the estimated proportion of non‐respondents taking certain values of the response variable is zero. A geometric explanation of why boundary solutions occur was given in a previous paper for a simple model. By extending this explanation, it is possible to define the sub‐class of non‐ignorable models whose parameters are identified, and to show all models not in this sub‐class are non‐identified. The conditions under which a model is a member of this class are easily established.     

Comparing the effects of GM and non‐GM soybean varieties on non‐target arthropods

In order to guarantee the safety of genetically modified (GM) soybean crops, it is important to assess the potential toxicity of their expressed insecticidal proteins to non‐target organisms. In the present study, the effects of the GM soybean Insulin‐like Growth Factor (IGF), which is tolerant to the herbicide glufosinate, on plant‐dwelling non‐target insects and arachnids were evaluated in soybean agroecosystems. For comparison, the non‐GM parental cultivar of soybean Gwangan‐kong was used as a control. Data were collected in 2016 and 2017 via surveying at Ochang and Jeonju, Korea. In total, 13,031 individual insects and arachnids, representing 64 families in 11 orders, were captured during the study. Firstly, the results indicate that the GM soybean IGF did not negatively affect plant‐dwelling non‐target insects and arachnids. However, the numbers of captured individuals on both IGF and Gwangan‐kong were higher at Ochang in 2017. The occurrence of insect pests, natural enemies, and other insects differed significantly according to region, region and survey year, and survey year, respectively. In addition, the dominance, diversity, evenness, and richness indices for the collected insects varied significantly among the regions and survey years regardless of soybean variety. The score from PROXSCAL multidimensional scaling using combined data showed that insects and arachnids in different natural environments were separated by their cultivation regions and years irrespective of soybean cultivars.     

The first transepidermal transplantation of non‐cultured epidermal suspension using a dermarolling system in vitiligo: A sequential histological and clinical study

The current methods for melanocyte delivery to depigmented skin are invasive and often require sophisticated approaches. Here, we describe a promising simple and minimally invasive technique based on the dermarolling system. The technique involves preparation of a keratinocyte/melanocyte suspension prepared by trypsinization from a non‐lesioned part of a patient's scalp skin and transepidermal delivery using a dermaroller equipped with 0.2‐mm needles. Dermarolling leads to epidermal microinjuries without, however, causing pain or inflammation. The technique was applied to facial depigmented areas of five patients with stable vitiligo that were resistant to conventional UV/tacrolimus treatment. The efficacy of cell delivery was analysed histologically on punch biopsies, and repigmentation was evaluated photographically and by clinical assessment. We found that the transplanted keratinocytes rapidly degenerated, leading to keratinization, but melanocytes survived and integrated appropriately into the basal layer of the epidermis, leading to excellent repigmentation after 6 months in three cases and mild repigmentation in two cases. Although based on a small number of patients, we anticipate this technique to become a valid addition to the arsenal of therapeutic approaches to repigmentation in depigmenting disorders.     

Raman spectroscopy for the non‐contact and non‐destructive monitoring of collagen damage within tissues

The non‐destructive and label‐free monitoring of extracellular matrix (ECM) remodeling and degradation processes is a great challenge. Raman spectroscopy is a non‐contact method that offers the possibility to analyze ECM in situ without the need for tissue processing. Here, we employed Raman spectroscopy for the detection of heart valve ECM, focusing on collagen fibers. We screened the leaflets of porcine aortic valves either directly after dissection or after treatment with collagenase. By comparing the fingerprint region of the Raman spectra of control and treated tissues (400–1800 cm^–1), we detected no significant differences based on Raman shifts; however, we found that increasing collagen degradation translated into decreasing Raman signal intensities. After these proof‐of‐principal experiments, we compared Raman spectra of native and cryopreserved valve tissues and revealed that the signal intensities of the frozen samples were significantly lower compared to those of native tissues, similar to the data seen in the enzymatically‐degraded tissues. In conclusion, our data demonstrate that Raman microscopy is a promising, non‐destructive and non‐contact tool to probe ECM state in situ. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Long non‐coding RNAs in non‐small cell lung cancer as biomarkers and therapeutic targets

Lung cancer‐associated mortality is the most common cause of cancer death worldwide. Non‐coding RNAs (ncRNAs), with no protein‐coding ability, have multiple biological roles. Long non‐coding RNAs (lncRNAs) are a recently characterized class of ncRNAs that are over 200 nucleotides in length. Many lncRNAs have the ability of facilitating or inhibiting the development and progression of tumours, including non‐small cell lung cancer (NSCLC). Because of their fundamental roles in regulating gene expression, along with their involvement in the biological mechanisms underlying tumourigenesis, they are a promising class of tissue‐ and/or blood‐based cancer biomarkers. In this review, we highlight the emerging roles of lncRNAs in NSCLC, and discuss their potential clinical applications as diagnostic and prognostic markers and as therapeutic targets.     

Landscape‐scale determinants of non‐native fish communities

Aim Predicting and preventing invasions depends on knowledge of the factors that make ecosystems susceptible to invasion. Current studies generally rely on non‐native species richness (NNSR) as the sole measure of ecosystem invasibility; however, species identity is a critical consideration, given that different ecosystems may have environmental characteristics suitable to different species. Our aim was to examine whether non‐native freshwater fish community composition was related to ecosystem characteristics at the landscape scale. Location United States. Methods We described spatial patterns in non‐native freshwater fish communities among watersheds in the Mid‐Atlantic region of the United States based on records of establishment in the U.S. Geological Survey’s Nonindigenous Aquatic Species Database. We described general relationships between non‐native species and ecosystem characteristics using canonical correspondence analysis. We clustered watersheds by non‐native fish community and described differences among clusters using indicator species analysis. We then assessed whether non‐native communities could be predicted from ecosystem characteristics using random forest analysis and predicted non‐native communities for uninvaded watersheds. We estimated which ecosystem characteristics were most important for predicting non‐native communities using conditional inference trees. Results We identified four non‐native fish communities, each with distinct indicator species. Non‐native communities were predicted based on ecosystem characteristics with an accuracy of 80.6%, with temperature as the most important variable. Relatively uninvaded watersheds were predicted to be invasible by the most diverse non‐native community. Main conclusions Non‐native species identity is an important consideration when assessing ecosystem invasibility. NNSR alone is an insufficient measure of invasibility because ecosystems with equal NNSR may not be equally invasible by the same species. Our findings can help improve predictions of future invasions and focus management and policy decisions on particular species in highly invasible ecosystems.     

Review ‐ Helicobacter pylori and non‐malignant upper gastro‐intestinal diseases

This review takes into account recent publications focusing on the relationship between Helicobacter pylori infection and non‐malignant diseases of the upper gastro‐intestinal tract. The authors have summarized current knowledge on associations between the H pylori infection and non‐malignant upper GI conditions including gastroesophageal reflux disease (GERD), Barrett's esophagus, eosinophilic esophagitis (EOE), peptic ulcer disease (PUD), H pylori gastritis, celiac disease and functional dyspepsia. In the field of GERD, current data focusing on different locations of H pylori infection detect significant differences between antrum‐ and corpus predominant gastritis explainable by different changes in acid secretion in different gastric niches. High volume studies from Sweden and Brazil underline the safety of H pylori eradication concerning the risk of Barret's esophagus or adenocarcinoma. The relationship betweenH pylori infection and EOE remains uncertain, but current data supports the concept of expected positive and protective effects of H pylori exposure reducing the risk of EOE. Analyzing biomarkers might be helpful to identify subjects under risk for the development of precancerous lesions after H pylori infection, where microRNAs, IL‐9 and IL‐4, and also Tc17/9 and Th17/9 and microbiota profiles showed promising results to identify subgroups under risk.     

Structural centrosome aberrations promote non‐cell‐autonomous invasiveness

Centrosomes are the main microtubule‐organizing centers of animal cells. Although centrosome aberrations are common in tumors, their consequences remain subject to debate. Here, we studied the impact of structural centrosome aberrations, induced by deregulated expression of ninein‐like protein (NLP), on epithelial spheres grown in Matrigel matrices. We demonstrate that NLP‐induced structural centrosome aberrations trigger the escape (“budding”) of living cells from epithelia. Remarkably, all cells disseminating into the matrix were undergoing mitosis. This invasive behavior reflects a novel mechanism that depends on the acquisition of two distinct properties. First, NLP‐induced centrosome aberrations trigger a re‐organization of the cytoskeleton, which stabilizes microtubules and weakens E‐cadherin junctions during mitosis. Second, atomic force microscopy reveals that cells harboring these centrosome aberrations display increased stiffness. As a consequence, mitotic cells are pushed out of mosaic epithelia, particularly if they lack centrosome aberrations. We conclude that centrosome aberrations can trigger cell dissemination through a novel, non‐cell‐autonomous mechanism, raising the prospect that centrosome aberrations contribute to the dissemination of metastatic cells harboring normal centrosomes.     

Acetylcholin als non‐neuronales Signalmolekül

The non‐neuronal cholinergic system Lately there was increasing evidence that acetylcholine plays an important role as a signalling molecule in non‐neuronal cells, besides its well known function as a neurotransmitter. The so‐called non‐neuronal cholinergic system (NNCS) was detected in many organs such as lung, skin and placenta, where it is involved in the regulation of diverse physiological processes. Additionally there is increasing evidence that the NNCS may be involved in the pathogenesis of diseases such as cystic fibrosis. Therefore detailed investigation of the NNCS is essential for a better understanding of human physiology and for developing improved therapies.