Diagnostic markers of allergic bronchopulmonary aspergillosis in patients with severe asthma.

INTRODUCTION: Allergic bronchopulmonary aspergillosis (ABPA) is a lung disease in patients with asthma or cystic fibrosis (CF) caused by chronic allergic inflammation to Aspergillus spp. antigens. The role of different immunological mediators in the formation of chronic allergic inflammation in patients with ABPA is not sufficiently explored. OBJECTIVES: This study aimed to investigate serum levels of thymic stromal lymphopoietin (TSLP), thymus and activated chemokine (TARC) as well as IL-8 in patients with ABPA, and to evaluate their diagnostic and monitoring value in the disease. PATIENTS/METHODS: Prospective study included 21 patients with ABPA, 25 patients with severe asthma with fungal sensitisation (SAFS), 37 patients with severe asthma without fungal sensitisation (SAwFS), and 16 healthy people. In patients with ABPA, the serum levels of biomarkers were determined at baseline and after 12 weeks of itraconazole therapy. Serum levels of total IgE, Aspergillus-fumigatus-specific IgE, TSLP, TARC, IL-8 were analysed by enzyme-linked immunosorbent assay. RESULTS: In patients with ABPA we established significantly higher serum levels of TARC, IL-8, total IgE, Aspergillus-fumigatus-specific IgE and peripheral blood eosinophil counts, compared to patients with SAwFS. There were no differences in TSLP levels between the examined groups of patients. Serum TARC levels were positively correlated to serum total IgE levels, A fumigatus-specific IgE levels and peripheral blood eosinophil counts and also negatively correlated to lung function (FEV1 ). Longitudinally, serum levels TARC, total IgE and peripheral blood eosinophil counts significant decreased after treatment of ABPA. CONCLUSION: Thymus and activated chemokine is a useful test in diagnosing and monitoring response to the antifungal treatment of patients with ABPA.

Aberrant alternative splicing of HTR2A exon II in peripheral blood lymphocytes of drug-naïve schizophrenic patients.

The aim of the study was to characterize the pattern of transcript isoforms of HTR2A exon II in lymphocytes of the blood as peripheral biomarkers of schizophrenia development and the effectiveness of antipsychotic therapy. We primarily observed an increase in mRNA levels and elevation of alternative variants in a sample of drug-naïve schizophrenic patients compared to the control group. There was no association of the expression level of HTR2A transcript isoforms with the effectiveness of the antipsychotic therapy. Antipsychotic-induced akathisia was associated with a significant reduction in the mRNA levels of the studied isoforms. In summary, our results suggest that levels of HTR2A exon II transcript isoforms are upregulated in patients with schizophrenia, but at the same time, elevated expression level of the studied HTR2A transcripts is associated with fewer side effects of the therapy.

Links of gut microbiota composition with alcohol dependence syndrome and alcoholic liver disease.

BACKGROUND: Alcohol abuse has deleterious effects on human health by disrupting the functions of many organs and systems. Gut microbiota has been implicated in the pathogenesis of alcohol-related liver diseases, with its composition manifesting expressed dysbiosis in patients suffering from alcoholic dependence. Due to its inherent plasticity, gut microbiota is an important target for prevention and treatment of these diseases. Identification of the impact of alcohol abuse with associated psychiatric symptoms on the gut community structure is confounded by the liver dysfunction. In order to differentiate the effects of these two factors, we conducted a comparative "shotgun" metagenomic survey of 99 patients with the alcohol dependence syndrome represented by two cohorts-with and without liver cirrhosis. The taxonomic and functional composition of the gut microbiota was subjected to a multifactor analysis including comparison with the external control group. RESULTS: Alcoholic dependence and liver cirrhosis were associated with profound shifts in gut community structures and metabolic potential across the patients. The specific effects on species-level community composition were remarkably different between cohorts with and without liver cirrhosis. In both cases, the commensal microbiota was found to be depleted. Alcoholic dependence was inversely associated with the levels of butyrate-producing species from the Clostridiales order, while the cirrhosis-with multiple members of the Bacteroidales order. The opportunist pathogens linked to alcoholic dependence included pro-inflammatory Enterobacteriaceae, while the hallmarks of cirrhosis included an increase of oral microbes in the gut and more frequent occurrence of abnormal community structures. Interestingly, each of the two factors was associated with the expressed enrichment in many Bifidobacterium and Lactobacillus-but the exact set of the species was different between alcoholic dependence and liver cirrhosis. At the level of functional potential, the patients showed different patterns of increase in functions related to alcohol metabolism and virulence factors, as well as pathways related to inflammation. CONCLUSIONS: Multiple shifts in the community structure and metabolic potential suggest strong negative influence of alcohol dependence and associated liver dysfunction on gut microbiota. The identified differences in patterns of impact between these two factors are important for planning of personalized treatment and prevention of these pathologies via microbiota modulation. Particularly, the expansion of Bifidobacterium and Lactobacillus suggests that probiotic interventions for patients with alcohol-related disorders using representatives of the same taxa should be considered with caution. Taxonomic and functional analysis shows an increased propensity of the gut microbiota to synthesis of the toxic acetaldehyde, suggesting higher risk of colorectal cancer and other pathologies in alcoholics.

Data on gut metagenomes of the patients with alcoholic dependence syndrome and alcoholic liver cirrhosis.

Alcoholism is associated with significant changes in gut microbiota composition. Metagenomic sequencing allows to assess the altered abundance levels of bacterial taxa and genes in a culture-independent way. We collected 99 stool samples from the patients with alcoholic dependence syndrome (n=72) and alcoholic liver cirrhosis (n=27). Each of the samples was surveyed using "shotgun" (whole-genome) sequencing on SOLiD platform. The reads are deposited in the ENA (project ID: PRJEB18041).