Changes in MicroRNA Expression during Rabbit Hemorrhagic Disease Virus (RHDV) Infection.

Current knowledge on the role of microRNAs (miRNAs) in rabbit hemorrhagic disease virus (RHDV) infection and the pathogenesis of rabbit hemorrhagic disease (RHD) is still limited. RHDV replicates in the liver, causing hepatic necrosis and liver failure. MiRNAs are a class of short RNA molecules, and their expression profiles vary over the course of diseases, both in the tissue environment and in the bloodstream. This paper evaluates the expression of miRNAs in the liver tissue (ocu-miR-122-5p, ocu-miR-155-5p, and ocu-miR-16b-5p) and serum (ocu-miR-122-5p) of rabbits experimentally infected with RHDV. The expression levels of ocu-miR-122-5p, ocu-miR-155-5p, and ocu-miR-16b-5p in liver tissue were determined using reverse transcription quantitative real-time PCR (RT-qPCR), and the expression level of circulating ocu-miR-122-5p was established using droplet digital PCR (ddPCR). The expression levels of ocu-miR-155-5p and ocu-miR-16b-5p were significantly higher in the infected rabbits compared to the healthy rabbits (a fold-change of 5.8 and 2.5, respectively). The expression of ocu-miR-122-5p was not significantly di�erent in the liver tissue from the infected rabbits compared to the healthy rabbits (p = 0.990), while the absolute expression level of the circulating ocu-miR-122-5p was significantly higher in the infected rabbits than in the healthy rabbits (p < 0.0001). Furthermore, a functional analysis showed that ocu-miR-155-5p, ocu-miR-16b-5p, and ocu-miR-122-5p can regulate the expression of genes involved in processes correlated with acute liver failure (ALF) in rabbits. Search tool for the retrieval of interacting genes/proteins (STRING) analysis showed that the potential target genes of the three selected miRNAs may interact with each other in di�erent pathways. The results indicate the roles of these miRNAs in RHDV infection and over the course of RHD and may reflect hepatic inflammation and impairment/dysfunction in RHD

Hereditary xerocytosis - spectrum and clinical manifestations of variants in the PIEZO1 gene, including co-occurrence with a novel β-globin mutation

Hereditary xerocytosis (HX) is a rare, autosomal dominant congenital hemolytic anemia (CHA) characterized by erythrocyte dehydration with presentation of various degrees of hemolytic anemia. HX is often misdiagnosed as hereditary spherocytosis or other CHA. Here we report three cases of suspected HX and one case of HX associated with β-thalassemia. Sanger method was used for sequencing cDNA of the PIEZO1 gene. Variants were evaluated for potential pathogenicity by MutationTaster, PROVEAN, PolyPhen-2 and M-CAP software, and by molecular modeling. Four different variants in the PIEZO1 gene were found, including three substitutions (p.D669H, p.D1566G, p.T1732 M) and one deletion (p.745delQ). In addition, in the patient with the p.T1732 M variant we detected a 12-nucleotide deletion in the β-globin gene leading to a deletion of amino acids 62AHGK65. The joint presence of mutations in two different genes connected with erythrocytes markedly aggravated the presentation of the disease. Bioinformatic analysis and molecular modeling strongly indicated likely deleterious effects of all four PIEZO1 variants, but co-segregation analysis showed that the p.D1566G substitution is in fact non-pathogenic. Identification of causative mutations should improve the diagnosis and management of HX and provide a new insight into the molecular basis of this complex red blood cell abnormality

Serum microRNA in patients undergoing atrial fibrillation ablation.

MicroRNAs mediate posttranscriptional gene regulation. The aim of the study was to find a microRNA predictor of successful atrial fibrillation (AF) ablation. A total of 109 patients undergoing first-time AF ablation were included. Nineteen patients were selected to undergo serum microRNA sequencing (study group). The sequencing data were used to select several microRNAs that correlated with 12-month recurrences after AF ablation. Those microRNAs were validated by digital droplet PCR in samples from remaining 90 patients. All patients underwent pulmonary vein isolation (RF ablation, contact force catheter, electroanatomical system). The endpoint of the study was the 12-month AF recurrence rate; the overall recurrence rate was 42.5%. In total, levels of 34 miRNAs were significantly different in sera from patients with AF recurrence compared to patients without AF recurrence. Six microRNAs (miR-183-5p, miR-182-5p, miR-32-5p, miR-107, miR-574-3p, and miR-144-3p) were validated in the whole group. Data from the validation group did not confirm the observations from the study group, as no significant differences were found between miRNAs serum levels in patients with and without recurrences 12 months after AF ablation

A Family Affected by a Life-Threatening Erythrocyte Defect Caused by Pyruvate Kinase Deficiency With Normal Iron Status: A Case Report

Background: Red cell pyruvate kinase deficiency (PKD) is a defect of glycolysis causing congenital non-spherocytic hemolytic anemia. PKD is transmitted as an autosomal recessive trait. The clinical features of PKD are highly variable, from mild to life-threatening anemia which can lead to death in the neonatal period. Most patients with PKD must receive regular transfusions in early childhood and as a consequence suffer from iron overloading. Patient: Here, we report a Polish family with life-threatening hemolytic anemia of unknown etiology. Whole exome sequencing identified two heterozygous mutations, c.1529 G > A (p.R510Q) and c.1495 T > C (p.S499P) in the PKLR gene. Molecular modeling showed that the both PKLR mutations are responsible for major disturbance of the protein structure and functioning. Despite frequent transfusions the patients do not show any signs of iron overload and hepcidin, a major regulator of iron uptake, is undetectable in their serum. The patients were homozygous for the rs855791 variant of the TMPRSS6 gene which has earlier been shown to down-regulate iron absorption and accumulation. Conclusion: The lack of iron overload despite a reduced level of hepcidin in two transfusion-dependent PKD patients suggests the existence of a hepcidin-independent mechanism of iron regulation preventing iron overloading

Expression of versican mRNA transcript to predict cardiac remodelling after myocardial infarction

Background: Adverse left-ventricular remodelling (LVR) is defined as an increase in end-diastolic left-ventricular volume by 20% 6 months after acute myocardial infarction (AMI). LVR is associated with cardiac dysfunction, therefore deteriorating the prognosis. Aims: We aimed to compare the concentrations of messenger RNA transcripts in the peripheral blood of patients with and without LVR at 6 months. Methods: The study included 75 patients with first ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention. Whole blood concentrations of 6 transcripts were determined 24 hours after AMI using droplet digital polymerase chain reaction. The correlations between mRNA transcript expression and left ventricular ejection fraction (LVEF) and N-terminal-pro B type natriuretic peptide (NT-proBNP) concentration were evaluated. Results: Among 75 patients, 4 were lost to follow-up and 71 were included in the analysis. Seventeen (24%) patients developed LVR at 6 months. Versican (VCAN) mRNA expression was lower in patients who developed LVR, compared to those who did not (P = 0.02), and discriminated between these patients (area under the ROC curve 67%; P = 0.04). Expression of VCAN transcript < 75.3 normalized units predicted LVR with 71% sensitivity and 67% specificity. In a multivariable regression analysis, VCAN expression remained the only independent predictor of LVR (OR 3.475; 95% CI, 1.000-12.075; P = 0.04). Conclusions: Dysregulation of VCAN expression in the acute phase of AMI may contribute to LVR at 6 months. Whether decreased expression of VCAN might be a useful tool to predict LVR in clinical practice remains to be established

Preferencje nauczycieli i uczniów w zakresie korekcji błędów językowych w krótkich wypowiedziach ustnych na lekcjach języka angielskiego

Błędy wydają się być nieodłączną i naturalną częścią procesu nauki języka obcego. W literaturze znane są różne definicje zarówno błędów, jak i ich kategorii. Ponadto, istnieje szeroki wachlarz nurtów specjalizujących się w nauczaniu języka, a każdy z nich reprezentuje inne podejście do pomyłek językowych. Co więcej, jest również duża różnorodność technik, które mogą być użyte podczas ustnej poprawy uczniów. Niniejsza praca magisterska skupia się na sposobie postrzegania błędów przez nauczycieli i uczniów, ich preferencjach oraz postawie wobec otrzymywanych informacji zwrotnych podczas krótkich wypowiedzi ustnych. Część teoretyczna pracy analizuje naturę błędu, sposoby poprawy oraz jego różne kategorii. Część praktyczna przedstawia i omawia wyniki badania, które miało na celu znalezienie odpowiedzi na następujące pytania: Jakie są preferencje nauczycieli co do ustnej poprawy błędów? Jakie są preferencje uczniów podczas ustnej poprawy błędów? Czy techniki stosowane przez nauczycieli wzmacniają motywację uczniów by a) uczestniczyć w klasowych ćwiczeniach b) uczyć się języka angielskiego? W celu triangulacji pozyskiwania potrzebnych danych zostały użyte następujące narzędzia badawcze: arkusze obserwacji lekcji, kwestionariusze dla uczniów oraz wywiady z nauczycielami. Wyżej wymienione badanie zostało przeprowadzone pośród polskich uczniów i nauczycieli ze szkoły średniej. Uzyskane wyniki wykazały, że ogólnie rzecz biorąc preferencje uczniów i nauczycieli pokrywają się, jednakże używane przez nauczycieli techniki poprawiania błędów wydają się być ograniczone. Co więcej, uczniowie wykazują dużą świadomość potrzeby i konieczności poprawiania błędów. Odpowiedzi młodzieży sugerują również, że otrzymywanie informacji o pojawiających się błędach w żadnym stopniu nie obniża ich motywacji do nauki języka obcego.Errors seem to be an inseparable and natural part of learning a foreign language. There are different definitions of an error and its categories. What is more, various pedagogical trends in language learning recommend different approaches to error treatment. Finally, there is a wide variety of techniques that can be used by teachers while providing learners with oral corrective feedback. This MA thesis focuses on the teachers’ and learners’ perceptions of oral error correction and the attitudes towards corrective feedback received while performing short speaking activities. The theoretical part of the thesis scrutinizes the nature of error, corrective feedback, and various categories of oral error correction. The empirical part of the dissertation presents and analyzes the results of the research that aimed to obtain the answers to the following questions: What are the teachers’ preferences for oral error correction? What are the learners’ preferences for oral error correction? Do the techniques used by the teachers enhance the students’ motivation to a) participate in classroom activities? b) learn English in general? In order to triangulate the data collection there were three research instruments used, namely lesson observation sheets, students’ questionnaires, and interviews with the teachers. The study was administered among the Polish high school students and teachers. The results of the research showed that in general the students’ and the teachers’ preferences correspond with each other; however, the techniques used by the teachers seem to be limited. Moreover, the students are aware that error correction is necessary and important in second language learning, and corrective feedback does not contribute to the loss of motivation in mastering a foreign tongue

Expression of versican mRNA transcript to predict cardiac remodelling after myocardial infarction

Background: Adverse left-ventricular remodelling (LVR) is defined as an increase in end-diastolic left-ventricular volume by 20% 6 months after acute myocardial infarction (AMI). LVR is associated with cardiac dysfunction, therefore deteriorating the prognosis. Aims: We aimed to compare the concentrations of messenger RNA transcripts in the peripheral blood of patients with and without LVR at 6 months. Methods: The study included 75 patients with first ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention. Whole blood concentrations of 6 transcripts were determined 24 hours after AMI using droplet digital polymerase chain reaction. The correlations between mRNA transcript expression and left ventricular ejection fraction (LVEF) and N-terminal-pro B type natriuretic peptide (NT-proBNP) concentration were evaluated. Results: Among 75 patients, 4 were lost to follow-up and 71 were included in the analysis. Seventeen (24%) patients developed LVR at 6 months. Versican (VCAN) mRNA expression was lower in patients who developed LVR, compared to those who did not (P = 0.02), and discriminated between these patients (area under the ROC curve 67%; P = 0.04). Expression of VCAN transcript &lt; 75.3 normalized units predicted LVR with 71% sensitivity and 67% specificity. In a multivariable regression analysis, VCAN expression remained the only independent predictor of LVR (OR 3.475; 95% CI, 1.000–12.075; P = 0.04). Conclusions: Dysregulation of VCAN expression in the acute phase of AMI may contribute to LVR at 6 months. Whether decreased expression of VCAN might be a useful tool to predict LVR in clinical practice remains to be established

Research on BNCT in Poland and in the world

Przy Reaktorze MARIA w Narodowym Centrum Badań Jądrowych (NCBJ) powstaje stanowisko do badań nad terapią borowo-neutronową (BNCT). Terapia polega na napromienianiu nowotworu wiązką neutronów o odpowiednich parametrach po uprzednim podaniu pacjentowi związku boru, który w wyniku określonych mechanizmów gromadzi się głównie w komórkach rakowych. W wyniku reakcji 10B(n,α)7Li emitowane są cząstki jonizujące powodujące zniszczenie tylko tych komórek, w których zgromadzony jest bor [1]. Badania kliniczne prowadzone na świecie potwierdzają skuteczność metody, otwierając nowe perspektywy dla jej zastosowania w terapii konwencjonalnej.The stand for research on Boron Neutron Capture Therapy (BNCT) at the MARIA Reactor at the National Centre for Nuclear Research is being created. The therapy consists of irradiation of the tumour with a neutron beam with specific parameters after prior administration of the boron compound to the patient, which accumulates mainly in cancer cells as a result of specific mechanisms. As a result of 10B(n,α)7Li reaction, ionising particles are emitted and destroy only those cells, in which boron is accumulated. Clinical trials conducted in the world show relatively high efficiency of BNCT, opening new perspectives for its use in conventional therapy