The mRNA expression of pro- and anti-inflammatory cytokines in T regulatory cells in children with type 1 diabetes.

Type 1 diabetes mellitus (T1DM) is caused by the autoimmune-mediated destruction of insulin-producing beta cells in the pancreas. T regulatory cells (Tregs) represent an active mechanism of suppressing autoreactive T cells that escape central tolerance. The aim of our study was to test the hypothesis that T regulatory cells express pro- and anti-inflammatory cytokines, elements of cytotoxicity and OX40/4-1BB molecules. The examined group consisted of 50 children with T1DM. Fifty two healthy individuals (control group) were enrolled into the study. A flow cytometric analysis of T-cell subpopulations was performed using the following markers: anti-CD3, anti-CD4, anti-CD25, anti-CD127, anti-CD134 and anti-CD137. Concurrently with the flow cytometric assessment of Tregs we separated CD4+CD25+CD127dim/- cells for further mRNA analysis. mRNA levels for transcription factor FoxP3, pro- and anti-inflammatory cytokines (interferon gamma, interleukin-2, interleukin-4, interleukin-10, transforming growth factor beta1 and tumor necrosis factor alpha), activatory molecules (OX40, 4-1BB) and elements of cytotoxicity (granzyme B, perforin 1) were determined by real-time PCR technique. We found no alterations in the frequency of CD4+CD25highCD127low cells between diabetic and control children. Treg cells expressed mRNA for pro- and anti-inflammatory cytokines. Lower OX40 and higher 4-1BB mRNA but not protein levels in Treg cells in diabetic patients compared to the healthy children were noted. Our observations confirm the presence of mRNA for pro- and anti-inflammatory cytokines in CD4+CD25+CD127dim/- cells in the peripheral blood of children with T1DM. Further studies with the goal of developing new strategies to potentiate Treg function in autoimmune diseases are warranted

Clinical complexity and impact of the ABC (Atrial fibrillation Better Care) pathway in patients with atrial fibrillation: a report from the ESC-EHRA EURObservational Research Programme in AF General Long-Term Registry

Background: Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The ‘Atrial fibrillation Better Care’ (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We aim to determine the impact of ABC pathway in a contemporary cohort of clinically complex AF patients. Methods: From the ESC-EHRA EORP-AF General Long-Term Registry, we analysed clinically complex AF patients, defined as the presence of frailty, multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on major outcomes was analysed through Cox-regression analyses and delay of event (DoE) analyses. Results: Among 9966 AF patients included, 8289 (83.1%) were clinically complex. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.72, 95%CI 0.58–0.91), major adverse cardiovascular events (MACEs; aHR: 0.68, 95%CI 0.52–0.87) and composite outcome (aHR: 0.70, 95%CI: 0.58–0.85). Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.74, 95%CI 0.56–0.98) and composite outcome (aHR: 0.76, 95%CI 0.60–0.96) also in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all the outcomes investigated in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the number needed to treat for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. Conclusions: An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes among clinically complex AF patients

Impact of renal impairment on atrial fibrillation: ESC-EHRA EORP-AF Long-Term General Registry

Background: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. Methods: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. Results: A total of 9306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment, p <.001. Over 24 months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07 [95% CI, 1.01–1.14] per 10 ml/min/1.73 m2 decrease), that was most notable in patients with eGFR <30 ml/min/1.73 m2 (HR 2.21 [95% CI, 1.23–3.99] compared to eGFR ≥90 ml/min/1.73 m2). Conclusion: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P <.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Some etiological factors and consequences of alcoholism

Temat mojej pracy jest charakterystyka wybranych czynników etiologicznych oraz konsekwencji w chorobie alkoholowej. Głównym celem pracy było przedstawienie czynników psychologicznych oraz konsekwencji psychiatrycznych w przebiegu choroby alkoholowej i wskazanie na prawdopodobne powiązania przyczynowo-skutkowe między nimi.Coraz więcej ludzi sięga po alkohol, a ze względu na jego dostępność robią to coraz młodsi. Jest wiele czynników predysponujących do powstania uzależnienia od alkoholu, a jedną z grup takich czynników są te o charakterze psychologicznym. Niedojrzałość emocjonalna, zaburzenia osobowości czy depresje choć są czynnikami wpływającymi pozytywnie na rozwój uzależnienia mogą także stanowić konsekwencje nadmiernego spożywania alkoholu. Choroba alkoholowa niesie ze sobą wiele poważnych konsekwencji. W sferze psychicznej prowadzi do poważnych zaburzeń psychiatrycznych tj: psychozy alkoholowe, otępienie czy depresje alkoholowe.Uzależnienie od alkoholu to choroba która degraduje życie człowieka na wszystkich jego płaszczyznach: fizycznej, psychicznej, duchowej oraz społecznej.About my work is the characterization of selected etiological factors and the consequences of the disease of alcoholism. The main objective of this study was to provide psychological factors and the effects of psychiatric disease and indication alcohol likely causal relationship between them. More and more people reach for alcohol, and because of its accessibility make it increasingly younger. There are many factors that predispose to the formation of alcohol dependence, and one of the groups of such agents are those of a psychological nature. Emotional immaturity, personality disorders and depression although there are positive factors in the development of addiction may also be the consequences of excessive alcohol consumption. Alcoholism has many serious consequences. In the mental sphere leads to serious psychiatric disorders, such as: alcoholic psychosis, dementia and depression alcohol.Alcohol dependence is a disease that degrades human life on all levels: physical, mental, spiritual and social

The incidence and causes exacerbations of bronchial asthma in adults.

Wprowadzenie: Praca ma charakter badawczy i napisana została na podstawie analizy najnowszego piśmiennictwa i prowadzonych badań. W tym celu stworzony został własny kwestionariusz ankiety. W pierwszej części pracy zostały ukazane podstawy kliniczne schorzenia, ze szczególnym naciskiem na przyczyny zaostrzeń i możliwość ich minimalizacji oraz leczenie.Cel pracy: Zidentyfikowanie grupy osób u których astma nie jest kontrolowana, ukazanie przyczyn i częstości zaostrzeń w przebiegu astmy oskrzelowej.Materiał i metody: Badaniem objęto 83 osoby ze stwierdzoną astmą oskrzelową. Badania przeprowadzono na oddziale Pulmonologii oraz w przychodni Szpitala Uniwersyteckiego przy ul. Skawińskiej 8. Podczas przeprowadzania badań przestrzegano zasady etyki i zachowanie anonimowości uczestników badań. Pacjenci wyrażali dobrowolną zgodę na wypełnienie kwestionariusza ankiety. Istotnym warunkiem wzięcia udziału w badaniach była potwierdzona klinicznie astma oskrzelowa. Jako metodę zastosowano sondaż diagnostyczny; narzędziem badawczym był kwestionariusz własnej konstrukcji oraz standaryzowane narzędzia badawcze Inwentarz Zachowań Zdrowotnych (IZZ) oraz Skala Akceptacji Choroby (AIS) autorstwa Z. Juczyńskiego. Wyniki badań opracowana przy użyciu programu EXCEL. Występowanie zależności statystycznych poddano testowi chi kwadrat dla przyjętego poziomu istotności p≤ 0,05. Wyniki: Przeprowadzone badania wskazały że 36 % osób z grupy badanej nie uzyskało kontroli nad astmą. Ankietowani wskazują jako najczęstszy czynnik wywoływania zaostrzenia infekcje dróg oddechowych w 24 % infekcje bakteryjne i w 20 % infekcje wirusowe. Zgodnie z danymi średnia częstość zaostrzeń wyniosła 2,7+/-3,7 w ciągu roku. Wnioski: Przeprowadzone badania wyłoniły grupę osób u których astma nie jest kontrolowana. Respondenci wskazali wiele przyczyn które wywołują zaostrzenia. Zwrócić należy jednak uwagę na złą kontrolę schorzenia wynikającą zarówno ze źle dostosowanego leczenia i braku właściwej edukacji ze strony lekarza, jak i z nieodpowiedniego podejścia pacjentów, niestosowania się do zaleceń, nie prawidłowej inhalacji leków, nie zgłaszaniu się na wizytę kontrolną i wykonywaniu podstawowych badań kontrolujących schorzenie.Work is a research and was written based on an analysis of current literature and research. For this purpose has been created its own questionnaire. In the first part of this work we have been shown the base of clinical disease, with particular emphasis on the cause of exacerbations and the possibility of their minimization and treatment.Target: Identify a group of people whose asthma is not controlled, to show the causes and exacerbations of bronchial asthma.Making and method: The study involved 83 people with diagnosed asthma. The study was conducted at the department of Pulmonology and the clinic of the University Hospital at Skawinska 8. During testing complied with the rules of ethics and anonymity of study participants. Patients expressed their voluntary consent to fill out a questionnaire. An essential condition for participation in the study was clinically proven asthma. As a diagnostic survey method was used; research tool was a questionnaire of our own design and standardized research tools Healthy Behaviour Inventory (IZZ) and the Acceptance of Illness Scale (AIS) by Z. Juczyńskiego. The results developed using Excel. The presence of statistical relationships were subjected to the chi-square test for the adopted level of significance p≤ 0.05.Results: The study showed that 36% of people in the study group did not obtain control of asthma. Respondents indicate is the most common factor causing exacerbation of respiratory infections, bacterial infections, 24% and 20% of viral infections. According to the data, the average frequency of exacerbations was 2.7 +/- 3.7 during the year.Conclusions: The study emerged from a group of people whose asthma is not controlled. Respondents indicated a number of reasons that cause exacerbation. One should, however, attention to the poor control of the disease resulting from both poorly adapted treatment and lack of proper education on the part of the doctor, as well as with the wrong approach patients, failure to follow without proper inhaler, not to raise up visit and perform basic research controlling the disease

Qualidade na interação familiar e estresse parental e suas relações com o autoconceito, habilidades sociais e problemas de comportamento dos filhos

Diverse academic research about child education and its relationships with children’s psychological development has been conducted ever since the last century. The object of this study was to analyze quality in family interaction and parental stress of fathers and mothers whose children who are in the phase of transition to the first year of primary education and the relationships of these factors with these children’s self-concept, social skills and behavior problems. The participants were 39 children (5.9 years), their mothers (n=39) and their fathers (n=25) who answered the Family Interaction Quality Scales, the Parental Stress Index, the Preschool and Kindergarten Behavior Skills and the Child Self-Concept Perception Scales. The results indicated several significant correlations/relationships and lead to three models of multiple linear regression, whereby the predictive value of the variable relating to the children’s social skills stood out. Quality in family interaction can therefore be both a decisive source of security and well-being and also an environment propitious to externalizing behaviors which hinders children’s formation of positive self-concept and an adequate repertoire of social skills.Desde o século passado, diversas pesquisas acadêmicas sobre educação de filhos e suas relações com o desenvolvimento psicológico infantil são realizadas. O objetivo da presente pesquisa foi analisar a qualidade na interação familiar e o estresse parental de pais e mães de crianças que estão na fase de transição para o primeiro ano do ensino fundamental e suas relações com autoconceito, habilidades sociais e problemas de comportamento dessas crianças. Os participantes foram 39 crianças (5,9 anos), suas mães (n=39) e seus pais (n=25) que responderam as Escalas de Qualidade na Interação Familiar, Inventário de Estresse Parental, Escala de Comportamento Social para Pré-Escolares e Escala de Percepção do Autoconceito Infantil. Os resultados apontaram para várias correlações/relações significativas e estabeleceram três modelos de regressão linear múltipla, tendo a variável habilidades sociais das crianças um valor preditivo em destaque. Portanto, a qualidade na interação familiar pode ser tanto uma fonte decisiva de segurança e bem estar, quanto um ambiente que propicia comportamentos externalizantes e dificulta as construções de um autoconceito positivo e repertório adequado de habilidades sociais de crianças.Desde el siglo pasado, diversas investigaciones académicas sobre educación de hijos y sus relaciones con el desarrollo sicológico infantil se lleva a cabo. El objetivo de la presente investigación ha sido lo de analizar la calidad de las interacciones familiares y el estrés parental, de padres y madres de niños que están en la fase de transición para el primer año de la escuela primaria y su relación con el autoconcepto, habilidades sociales y problemas de conducta de esos niños. Los participantes han sido de 39 niños (5, 9 años), sus madres (n=39) y sus padres (n=25) que han contestado a la Escala de Calidad en la Interacción Familiar, Inventario de Estrés Parental, Escala de Comportamiento Social para Preescolar y Escala de Percepción del Autoconcepto Infantil. Los resultados han apuntado para varias correlaciones/relaciones significativas y han establecido tres patrones de regresión lineal múltiple, y las habilidades sociales de los niños el valor predictivo variable resaltada. Por lo tanto, la calidad de las interacciones familiares puede ser una fuente decisiva de la seguridad y el bienestar, como un ambiente que promueva um comportamiento llamativo y dificulta la construcción de un autoconcepto positivo y las habilidades sociales adecuadas de los niños

Przekształcenie konwencjonalnych limfocytów T w komórki T−regulatorowe u dzieci z zespołem metabolicznym

Background: Much research has been done in the recent years to establish an association between obesity, metabolic syndrome and the immune system. Numerous data suggest that the decreased number and/or function of regulatory T cells (Treg cells) can lead to chronic minimal inflammation present in patients with obesity and trigger formation of atherosclerotic plaque. Aim: To generate Treg cells from the peripheral blood in children meeting the diagnostic criteria of metabolic syndrome. Methods: A total of 25 children with metabolic syndrome and 25 controls were enrolled in the study. Peripheral blood was collected, CD4+/CD25– cells were separated and cultured for 4 weeks in the presence of a Treg expander (CD3/CD28) and interleukin-2. The expression of the transcription factor FoxP3 as a Treg marker was assessed before and after culture using reverse transcriptase polymerase chain reaction (RT-PCR) and flow cytometry. Results: Before the culture we observed a slightly lower percentage of Treg cells in children with metabolic syndrome vs controls. After the culture we noted a significant increase in mRNA expression and in the percentage of FoxP3-positive cells. We observed no differences in the results between the children with metabolic syndrome and the controls. Conclusions: Our study shows that it is possible to generate Treg cells from peripheral blood of children with metabolic syndrome. In future, these findings could be used to develop a model of immunotherapeutic intervention for patients at risk of cardiovascular disease. Kardiol Pol 2011; 69, 12: 1221–1226Wstęp: W ostatnich latach poszukuje się związków między otyłością i zespołem metabolicznym a układem immunologicznym. Wiele danych wskazuje, że niedobór i/lub dysfunkcja jednej z subpopulacji limfocytów, tj. komórek T-regulatorowych, może przyczyniać się do przewlekłego, minimalnego stanu zapalnego obecnego u pacjentów z otyłością, w konsekwencji prowadzącego do powstania blaszek miażdżycowych. Cel: Celem pracy była próba generacji limfocytów T-regulatorowych z krwi obwodowej dzieci spełniających kryteria rozpoznania zespołu metabolicznego. Metody: Do badania włączono 25 dzieci z zespołem metabolicznym i 25 dzieci z grupy kontrolnej. Materiał do badań stanowiła krew obwodowa, z której wyizolowano limfocyty o fenotypie CD4+/CD25–, aby następnie umieścić je w 4-tygodniowej hodowli z odczynnikiem Treg-expander (CD3/CD28) oraz interleukiną 2. Ekspresję czynnika transkrypcyjnego FoxP3 jako markera limfocytów T-regulatorowych oceniano przed hodowlą i po jej zakończeniu za pomocą łańcuchowej reakcji polimerazy (na poziomie mRNA) oraz cytometrii przepływowej. Wyniki: Przed hodowlą zanotowano nieznacznie niższe odsetki limfocytów T-regulatorowych u dzieci z zespołem metabolicznym w porównaniu z dziećmi z grupy kontrolnej. Po hodowli wykazano istotny statystycznie wzrost ekspresji mRNA dla FoxP3 i wzrost odsetka komórek FoxP3-dodatnich. Nie obserwowano różnic między hodowlami z krwi dzieci z zespołem metabolicznym a hodowlami limfocytów dzieci z grupy kontrolnej. Wnioski: Uzyskane wyniki świadczą o możliwości generacji limfocytów T-regulatorowych z krwi dzieci z rozpoznaniem zespołu metabolicznego i powinny być wykorzystane w przyszłości do konstruowania modeli interwencji immunoterapeutycznej w grupie pacjentów z obecnymi czynnikami ryzyka rozwoju chorób układu sercowo-naczyniowego. Kardiol Pol 2011; 69, 12: 1221–122