Cytokines in Inflamed Mucosa of IBD Patients

Cells of the innate and the adaptive immune system have been identified as the key players in inflammatory bowel disease (IBD) pathogenesis, and the cytokines are central components of the inflammatory pathways that take place in the gut mucosa during the active and chronic phases of IBD. The effector cell response is largely determined by the type of cytokines that predominate in the intestinal mucosa. Here we describe the main cytokine players in intestinal inflammation during IBD—related to innate immune responses (tumor necrosis factor α—TNFα), TNF-like cytokine 1A, IL-8), and related to adaptive immune responses—Th1 (IL-1β, IL-18, IFNγ, IL-12), Th2 (IL-4, IL-5, IL-13, IL-11, IL-33), Th17 (IL-17A, IL-17F, IL-21, IL-22, IL-25, IL-27), cytokines required for Th17 development (IL-6, TGFβ, IL-23), anti-inflammatory cytokine IL-10 and Tregs along with IL-2. Recently described innate lymphoid cells (ILCs) could also be potential sources of IFN-γ, TNF, IL-5, IL-13, IL-17, and IL-22. The effects of cytokines in the gut are described in conjunction with the clinical implication and available biologic therapy. The data in the literature and our own results make us believe that in order to achieve immune homeostasis in the gut, pro-inflammatory and anti-inflammatory responses that define the mucosal cell immunophenotype should achieve balance

Експлетивно отрицание в подчинени изречения, въведени с ‘докато (не)’: джудезмо в балкански контекст

Expulsive negation in subordinate clauses introduced by‚ while (not) / until (not)’: Iudeo-Español in the Balkan context The paper approaches the temporal limitative subordinate clauses headed by asta/fin ke (no), the Judeo-Spanish equivalent to ‘while (not)/until (not)’ clauses. Having joined the Balkan linguistic area, Judeo-Spanish adopted the Balkan areal pattern of increased use of the expletive negation and indicative, unlike the Spanish pattern of subjunctive and positive verbs in the regarded clauses. In conative situations (mainly verbs expressing effort, try and attempt) the presence or omission of expletive negation in the subordinate clause allows for showing bias towards the proposition (presenting it as the desired goal or risk to be avoided). Furthermore, the expletive negation is found to be highly transmittable in situations of language contact and areal change.   Ekspletywna negacja w zdaniach podrzędnych wprowadzanych przez ‘póki (nie)/ zanim (nie)’: Iudeo-español w kontekście bałkańskim Artykuł dotyczy zdań podrzędnych czasowych ograniczających, wprowadzanych przez asta / fin ke (no) (judeo-hiszpański odpowiednik wyrażeń ‘póki (nie)’, zanim (nie)’). Znalazłszy się na bałkańskim obszarze językowym judeo-hiszpański zaadaptował bałkański uzus zwiększonego użycia negacji ekspletywnej i indykatywnej, w przeciwieństwie do hiszpańskiego uzusu, który w rozpatrywanym typie zdań subjunktywnych preferuje użycie czasowników niezaprzeczonych. W sytuacjach konatywnych (sygnalizowanych głównie czasownikami wyrażającymi wysiłek, usiłowanie, próbowanie) obecność lub brak wyrażenia negacji w zdaniu podrzędnym umożliwia sformułowanie tendencji w zakresie wyrażania omawianej modalności (przedstawiając ją jako pożądany cel lub ryzyko, którego należy unikać). Ponadto stwierdzono, że wyrażanie negacji jest szczególnie wrażliwe na konwergencję w sytuacji kontaktu językowego

Developing auditory comprehension subtests of the Russian Aphasia Test

There is a lack of modern quantitative language assessment tests in Russian, integrating neuropsychological and psychometric traditions, and allowing to specify the type and severity of linguistic deficits in individuals with different aphasia profiles. In response to these clinical and research needs, a novel standardized aphasia test – the Russian Aphasia Test (RAT) – is currently being developed. The principal novelty of this test is that each subtest corresponds to a specific level of linguistic processing in one of the four language domains: auditory comprehension, oral production, reading, and writing. In selection of specific tasks for each level of processing we took into account the structure and materials of contemporary standardized aphasia tests in other languages (e.g., Comprehension Aphasia Test, Howard et al., 2010; Psycholinguistic Assessment of Language Processing in Aphasia, Kay et al., 1996), as well as modern (psycho)linguistics theories, and the structural and phonetic specifics of the Russian language. Here we present data on preliminary standardization of auditory comprehension subtests that included the following tasks: • Phonemic – judgment of minimal pairs of nonwords (n=100) and words (n=72). The following factors were taken into account in the design of the subtest: phoneme manner and place of articulation, syllabic structure and position, frequency and imageability (for words). • Lexical – lexical decision (n=120). Lexical frequency, word length, and the degree of similarity of non-words to real words were taken into account. • Lexical-semantic processing – word to picture matching for objects (n=67) and actions (n=68). Items were selected based on naming and image agreement. • Syntactic – sentence to picture matching for various syntactic constructions (n=68), including reversible passives, subject and object clefts, and prepositional phrases. • Discourse – comprehension of orally presented stories of varying lexical-semantic and syntactic difficulty indexed by response accuracy to a set of 16 yes-no questions on explicit and implicit content of the stories. Each subtest was completed by at least 20 individuals with aphasia and 20 healthy age-matched controls. To maximize validity and reliability of the subtests, “poor” items were removed according to the following principles. First, items that were answered erroneously by two or more healthy participants were eliminated. Second, based on item difficulty and corrected-item-total correlation derived for the aphasia group, most sensitive and valid items were retained. Also, it was ensured that each influential psychometric property was represented in the refined set by a wide range of values. Thus, a final smaller set of items for each subtest was selected for further norming and standardization. We will discuss in detail the various conceptual and psychometric considerations that went into the design of the subtests and affected item selection. This project is supported by Russian Scientific Foundation for Humanities, grant №14-04-00596

Russian CliPS: a Corpus of Narratives by Brain-Damaged Individuals

Abstract In this paper we present a multimedia corpus of Pear film retellings by people with aphasia (PWA), right hemisphere damage (RHD), and healthy speakers of Russian. Discourse abilities of brain-damaged individuals are still under discussion, and Russian CliPS (Clinical Pear Stories) corpus was created for the thorough analysis of micro-and macro-linguistic levels of narratives by PWA and RHD. The current version of Russian СliPS contains 39 narratives by people with various forms of aphasia due to left hemisphere damage, 5 narratives by people with right hemisphere damage and no aphasia, and 22 narratives by neurologically healthy adults. The annotation scheme of Russian CliPS 1.0 includes the following tiers: quasiphonetic, lexical, lemma, part of speech tags, grammatical properties, errors, laughter, segmentation into clauses and utterances. Also analysis of such measures as informativeness, local and global coherence, anaphora, and macrostructure is planned as a next stage of the corpus development

Celiac-Related Autoantibodies and IL-17A in Bulgarian Patients with Dermatitis Herpetiformis: A Cross-Sectional Study

Background and objectives: Dermatitis herpetiformis (DH) is a blistering dermatosis, which shares common immunologic features with celiac disease (CD). The aim of the present study was to explore the performance of a panel of CD-related antibodies and IL-17A in Bulgarian patients with DH. Materials and Methods: Serum samples from 26 DH patients at mean age 53 ± 15 years and 20 healthy controls were assessed for anti-tissue transglutaminase (anti-tTG), anti-deamidated gliadin peptides (anti-DGP), anti-actin antibodies (AAA), and IL-17A by enzyme linked immuno-sorbent assay (ELISA), as well as anti-tTG, anti-gliadin (AGA), and anti-Saccharomyces cerevisiae antibodies (ASCA) using immunoblot. Results: The average serum levels of anti-tTG, anti-DGP, AGA, AAA, and the cytokine IL-17A were at significantly higher levels in patients with DH compared to the average levels in healthy persons which stayed below the cut-off value (p < 0.05). Anti-DGP and anti-tTG antibodies showed the highest diagnostic sensitivity and specificity, as well as acceptable positive and negative predictive value. None of the healthy individuals was found positive for the tested antibodies, as well as for ASCA within the DH group. All tests showed good to excellent correlations (r = 0.5 ÷ 0.9, p < 0.01). Conclusions: Although the diagnosis of DH relies on skin biopsy for histology and DIF, serologic testing of a panel of celiac-related antibodies could be employed with advantages in the diagnosing process of DH patients. Furthermore, DH patients who are positive for the investigated serologic parameters could have routine monitoring for gastrointestinal complications typical for the gluten-sensitive enteropathy

Conditioned Medium from Adipose Tissue-Derived Mesenchymal Stem Cells Induces CD4+FOXP3+ Cells and Increases IL-10 Secretion

Mesenchymal stem cells (MSCs) are a new and promising tool for therapy of autoimmune disorders. In recent years their possibility to take part in the modulation of the immune response is discussed. The exact mechanisms for immunoregulation realized by MSCs are not clear yet, but interactions with other immunoregulatory cells may be involved in this process. The investigation of the influence of MSCs on the expression of FoxP3 and cytokine secretion by T helper cells was the aim of this study. T helper cells were isolated from PBMCs by magnetic separation and MSCs were isolated from human adipose tissue, and CD4+ T cells were cultured with conditional medium of MSCs. The methods which were used include flow cytometry, ELISA, and Human Proteome profiler kits. The results demonstrated that secretory factors in MSCs conditional medium lead to increased expression of FoxP3 and increased secretion of IL-10 by T helpers. The obtained results give us opportunity to discuss the interaction between two kinds of immunoregulatory cells: MSCs and FoxP3+ T helpers. We suppose that this interaction leads to increased number of immunosuppressive helpers which secrete IL-10. MSCs provide some of their immunosuppressive functions acting on T regulatory cells, and we believe that IL-6 secreted by MSCs is involved in this process

The Russian Aphasia Test: The first comprehensive, quantitative, standardized, and computerized aphasia language battery in Russian

The lack of standardized language assessment tools in Russian impedes clinical work, evidence- based practice, and research in Russian-speaking clinical populations. To address this gap in assessment of neurogenic language disorders, we developed and standardized a new comprehensive assessment instrument-the Russian Aphasia Test (RAT). The principal novelty of the RAT is that each subtest corresponds to a specific level of linguistic processing (phonological, lexical-semantic, syntactic, and discourse) in different domains: Auditory comprehension, repetition, and oral production. In designing the test, we took into consideration various (psycho)linguistic factors known to influence language performance, as well as specific properties of Russian. The current paper describes the development of the RAT and reports its psychometric properties. A tablet-based version of the RAT was administered to 85 patients with different types and severity of aphasia and to 106 agematched neurologically healthy controls. We established cutoff values for each subtest indicating deficit in a given task and cutoff values for aphasia based on the Receiver Operating Characteristic curve analysis of the composite score. The RAT showed very high sensitivity (> .93) and specificity (> .96), substantiating its validity for determining presence of aphasia. The test's high construct validity was evidenced by strong correlations between subtests measuring similar linguistic processes. The concurrent validity of the test was also strong as demonstrated by a high correlation with an existing aphasia battery. Overall high internal, inter-rater, and test-retest reliability were obtained. The RAT is the first comprehensive aphasia language battery in Russian with properly established psychometric properties. It is sensitive to a wide range of language deficits in aphasia and can reliably characterize individual profiles of language impairments. Notably, the RAT is the first comprehensive aphasia test in any language to be fully automatized for administration on a tablet, maximizing further standardization of presentation and scoring procedures