ЩОДО ДІЄВОСТІ ІНФОРМАЦІЙНИХ МЕТОДИЧНИХ МАТЕРІАЛІВ В НАВЧАЛЬНОМУ ПРОЦЕСІ НА КАФЕДРІ МІКРОБІОЛОГІЇ, ВІРУСОЛОГІЇ ТА ІМУНОЛОГІЇ

The aim of the study – to improve the mastery of the topic "Salmonella. Microbiological diagnosis of typhoid fever" in the educational process at the Department of Microbiology, Virology and Immunology.Materials and Methods. Development by the Department of Microbiology, Virology and Immunology a table which identified a correlation between clinical course, peculiarities of pathogenesis and clinical material, and development schemes of microbiological diagnosis of typhoid and paratyphoid.Results and Discussion. Students get training and methodological support such as convenient tables and diagrams of microbiological diagnosis of typhoid and paratyphoid for efficient acquisition of theoretical knowledge and practical skills.Conclusions. The table that introduces the principles of microbiological diagnostics of infectious diseases according to the pathogenesis and clinical disease for students can be used by teacher at a practical class on the topic “Salmonella. Microbiological diagnosis of typhoid and paratyphoid fever”. Such teaching at the present stage will facilitate the development of these topics at the Department of Infectious Diseases and orient future doctors in choosing appropriate methods of microbiological diagnostics in the making of the final clinical diagnosis. Thus, students get one more training and methodological support for qualitative acquisition of theoretical knowledge and practical skills.Мета дослідження – поліпшення опанування теми «Сальмонели. Мікробіологічна діагностика черевного тифу» в навчальному процесі на кафедрі мікробіології, вірусології та імунології.Матеріали та методи дослідження. Розробка кафедрою мікробіології, вірусології та імунології таблиці, в якій визначена кореляція між клінічним перебігом, особливостями патогенезу і видом клінічного матеріалу, та розробка схеми мікробіологічної діагностики черевного тифу і паратифів.Результати й обговорення.Студенти отримують навчально-методичну підтримку у вигляді зручної таблиці і схеми мікробіологічної діагностики черевного тифу та паратифів для якісного набуття теоретичних знань і практичних навичок.Висновки. Під час розгляду теми «Сальмонели. Мікробіологічна діагностика черевного тифу та паратифів» на практичному занятті викладачем може бути використана таблиця, яка ознайомить студентів із принципами мікробіологічної діагностики інфекційних захворювань, що залежать від патогенезу та клінічної картини захворювання. Таке викладання матеріалу на сучасному етапі буде сприяти опануванню цих тем на кафедрі інфекційних хвороб та орієнтує майбутніх лікарів в обранні адекватних методів мікробіологічної діагностики при постановці кінцевого клінічного діагнозу. Таким чином, студенти отримують ще одну навчально-методичну підтримку для якісного набуття теоретичних знань і практичних навичок

Information on effectiveness of teaching materials in educational process at the department of microbiology, virology and immunology

Мета дослідження – поліпшення опанування теми “Сальмонели. Мікробіологічна діагностика черевного тифу” в навчаль- ному процесі на кафедрі мікробіології, вірусології та імунології. Матеріали та методи дослідження. Розробка кафедрою мікробіології, вірусології та імунології таблиці, в якій визначена кореляція між клінічним перебігом, особливостями патогенезу і видом клінічного матеріалу, та розробка схеми мікробіологічної діагностики черевного тифу і паратифів. Результати й обговорення. Студенти отримують навчально-методичну підтримку у вигляді зручної таблиці і схеми мікро- біологічної діагностики черевного тифу та паратифів для якісного набуття теоретичних знань і практичних навичок. Висновки. Під час розгляду теми “Сальмонели. Мікробіологічна діагностика черевного тифу та паратифів” на практичному занятті викладачем може бути використана таблиця, яка ознайомить студентів із принципами мікробіологічної діагностики інфекційних захворювань, що залежать від патогенезу та клінічної картини захворювання. Таке викладання матеріалу на сучас- ному етапі буде сприяти опануванню цих тем на кафедрі інфекційних хвороб та орієнтує майбутніх лікарів в обранні адекватних методів мікробіологічної діагностики при постановці кінцевого клінічного діагнозу. Таким чином, студенти отримують ще одну навчально-методичну підтримку для якісного набуття теоретичних знань і практичних навичок; The aim of the study – to improve the mastery of the topic “Salmonella. Microbiological diagnosis of typhoid fever” in the educational process at the Department of Microbiology, Virology and Immunology. Materials and Methods. Development by the Department of Microbiology, Virology and Immunology a table which identified a correlation between clinical course, peculiarities of pathogenesis and clinical material, and development schemes of microbiological diagnosis of typhoid and paratyphoid. Results and Discussion. Students get training and methodological support such as convenient tables and diagrams of microbiological diagnosis of typhoid and paratyphoid for efficient acquisition of theoretical knowledge and practical skills. Conclusions. The table that introduces the principles of microbiological diagnostics of infectious diseases according to the pathogenesis and clinical disease for students can be used by teacher at a practical class on the topic “Salmonella. Microbiological diagnosis of typhoid and paratyphoid fever”. Such teaching at the present stage will facilitate the development of these topics at the Department of Infectious Diseases and orient future doctors in choosing appropriate methods of microbiological diagnostics in the making of the final clinical diagnosis. Thus, students get one more training and methodological support for qualitative acquisition of theoretical knowledge and practical skills

Helicobacter species in cancers of the gallbladder and extrahepatic biliary tract

Helicobacter species have been found in human bile and biliary tract (BT) tissue and are suspected to cause BT diseases, including gallbladder and extrahepatic cancers, collectively referred to in this work as BT cancers. We conducted a literature review of the epidemiological evidence linking the presence of Helicobacter species in bile or BT biopsies to BT cancers and benign diseases. Reports showed great variability with respect to study methods. Nine studies of BT cancers were identified, all with 30 or fewer BT cancers; eight included cancer-free control subjects and used polymerase chain reaction (PCR) as a means of Helicobacter species detection. In four of these studies, Helicobacter species were detected in patients with BT cancer significantly more frequently than in controls, at least when controls without BT diseases were used. In two studies, no Helicobacter species were detected in either cases or controls. Helicobacter species were also often detected in benign BT diseases such as gallstone disease or chronic cholecystitis. As our current knowledge relies on a few small studies that showed substantial differences, larger studies and more standardised protocols for detecting DNA and antibodies against Helicobacter species are needed to investigate a potential association with BT cancer

Update of EULAR recommendations for the treatment of systemic sclerosis

The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc

Digital ulcers predict a worse disease course in patients with systemic sclerosis

Objective: Systemic sclerosis (SSc) is a systemic autoimmune disease with high morbidity and significant mortality. There is a great need of predictors that would allow risk stratification of patients with SSc and ultimately initiation of treatment early enough to ensure optimal clinical results. In this study, we evaluated whether a history of digital ulcers (HDU) at presentation may be a predictor of vascular outcomes and of overall clinical worsening and death in patients with SSc. Methods: Patients from the EULAR Scleroderma Trials and Research (EUSTAR) database, satisfying at inclusion the 1980 American College of Rheumatology classification criteria for SSc, who had a follow-up of at least 3 years since baseline or who have died, were included in the analysis. HDU at presentation as a predictor of disease worsening or death was evaluated by Cox proportional hazards regression analysis. Results :3196 patients matched the inclusion criteria (male sex 13.2%, 33.4% diffuse subset). At presentation, 1092/3196 patients had an HDU (34.1%). In multivariable analysis adjusting for age, gender and all parameters considered potentially significant, HDU was predictive for the presence of active digital ulcers (DUs) at prospective visits (HR (95% CI)): 2.41(1.91 to 3.03), p<0.001, for an elevated systolic pulmonary arterial pressure on heart ultrasound (US-PAPs):1.36 (1.03 to 1.80), p=0.032, for any cardiovascular event (new DUs, elevated US-PAPs or LV failure):3.56 (2.26 to 5.62), p<0.001, and for death (1.53 (1.16 to 2.02), p=0.003). Conclusions :In patients with SSc, HDU at presentation predicts the occurrence of DUs at follow-up and is associated with cardiovascular worsening and decreased survival

Shared genetic variants suggest common pathways in allergy and autoimmune diseases.

BACKGROUND: The relationship between allergy and autoimmune disorders is complex and poorly understood. OBJECTIVE: To investigate commonalities in genetic loci and pathways between allergy and autoimmune diseases to elucidate shared disease mechanisms. METHODS: We meta-analyzed two GWAS on self-reported allergy and sensitization comprising a total of 62,330 individuals. These results were used to calculate enrichment for SNPs previously associated with autoimmune diseases. Furthermore, we probed for enrichment within genetic pathways and of transcription factor binding sites, and characterized commonalities in the variant burden on tissue-specific regulatory sites by calculating the enrichment of allergy SNPs falling in gene regulatory regions in various cells using Encode Roadmap DHS data, and compared the allergy data with all known diseases. RESULTS: Among 290 loci previously associated with 16 autoimmune diseases, we found a significant enrichment of loci also associated with allergy (p=1.4e-17) encompassing 29 loci at a false discovery rate<0.05. Such enrichment seemed to be a general characteristic for all autoimmune diseases. Among the common loci, 48% had the same direction of effect for allergy and autoimmune diseases. Additionally, we observed an enrichment of allergy SNPs falling within immune pathways and regions of chromatin accessible in immune cells that was also represented in autoimmune diseases, but not in other diseases. CONCLUSION: We identified shared susceptibility loci and commonalities in pathways between allergy and autoimmune diseases, suggesting shared diseases mechanisms. Further studies of these shared genetic mechanisms might help understanding the complex relationship between these diseases, including the parallel increase in disease prevalence

The regulation of IL-10 expression

Interleukin (IL)-10 is an important immunoregulatory cytokine and an understanding of how IL-10 expression is controlled is critical in the design of immune intervention strategies. IL-10 is produced by almost all cell types within the innate (including macrophages, monocytes, dendritic cells (DCs), mast cells, neutrophils, eosinophils and natural killer cells) and adaptive (including CD4(+) T cells, CD8(+) T cells and B cells) immune systems. The mechanisms of IL-10 regulation operate at several stages including chromatin remodelling at the Il10 locus, transcriptional regulation of Il10 expression and post-transcriptional regulation of Il10 mRNA. In addition, whereas some aspects of Il10 gene regulation are conserved between different immune cell types, several are cell type- or stimulus-specific. Here, we outline the complexity of IL-10 production by discussing what is known about its regulation in macrophages, monocytes, DCs and CD4(+) T helper cells

Dimethyl fumarate blocks pro-inflammatory cytokine production via inhibition of TLR induced M1 and K63 ubiquitin chain formation

Dimethyl fumarate (DMF) possesses anti-inflammatory properties and is approved for the treatment of psoriasis and multiple sclerosis. While clinically effective, its molecular target has remained elusive - although it is known to activate anti-oxidant pathways. We find that DMF inhibits pro-inflammatory cytokine production in response to TLR agonists independently of the Nrf2-Keap1 anti-oxidant pathway. Instead we show that DMF can inhibit the E2 conjugating enzymes involved in K63 and M1 polyubiquitin chain formation both in vitro and in cells. The formation of K63 and M1 chains is required to link TLR activation to downstream signaling, and consistent with the block in K63 and/or M1 chain formation, DMF inhibits NFκB and ERK1/2 activation, resulting in a loss of pro-inflammatory cytokine production. Together these results reveal a new molecular target for DMF and show that a clinically approved drug inhibits M1 and K63 chain formation in TLR induced signaling complexes. Selective targeting of E2s may therefore be a viable strategy for autoimmunity

BCAT1 controls metabolic reprogramming in activated human macrophages and is associated with inflammatory diseases

This work was supported by the Medical Research Council (MR/M004716/1 and MR/N01121X/1 to J.B.) and by Kidney Research UK (RP9/2013 to J.B.). D.C. is supported by the Institute Pasteur, Fondazione Cenci Bolognetti. C.M. is supported by the British Hearth Foundation Fellowship (FS/12/3829640)

Effectiveness and safety of tocilizumab in patients with systemic sclerosis: a propensity score matched controlled observational study of the EUSTAR cohort

Objectives Tocilizumab showed trends for improving skin fibrosis and prevented progression of lung fibrosis in systemic sclerosis (SSc) in randomised controlled clinical trials. We aimed to assess safety and effectiveness of tocilizumab in a real-life setting using the European Scleroderma Trial and Research (EUSTAR) database. Methods Patients with SSc fulfilling the American College of Rheumatology (ACR)/EULAR 2013 classification criteria, with baseline and follow-up visits at 12±3 months, receiving tocilizumab or standard of care as the control group, were selected. Propensity score matching was applied. Primary endpoints were the modified Rodnan skin score (mRSS) and FVC at 12±3 months compared between the groups. Secondary endpoints were the percentage of progressive/regressive patients for skin and lung at 12±3 months. Results Ninety-three patients with SSc treated with tocilizumab and 3180 patients with SSc with standard of care fulfilled the inclusion criteria. Comparison between groups did not show significant differences, but favoured tocilizumab across all predefined primary and secondary endpoints: mRSS was lower in the tocilizumab group (difference −1.0, 95% CI −3.7 to 1.8, p=0.48). Similarly, FVC % predicted was higher in the tocilizumab group (difference 1.5 (−6.1 to 9.1), p=0.70). The percentage of progressive/regressive patients favoured tocilizumab over controls. These results were robust regarding the sensitivity analyses. Safety analysis confirmed previously reported adverse event profiles. Conclusion Although this large, observational, controlled, real-life EUSTAR study did not show significant effectiveness of tocilizumab on skin and lung fibrosis, the consistency of direction of all predefined endpoints generates hypothesis for potential effectiveness in a broader SSc population