[Novel Findings in Follicular Lymphoma Pathogenesis and the Concepts of Targeted Therapy]. / Nové poznatky o patogenezi folikulárního lymfomu a koncepty cílené lécby.

The molecular pathogenesis of follicular lymphoma (FL) was partially revealed by the discovery of BCL2 translocations to the region encoding the immunoglobulin heavy chain, which accompany the vast majority of cases. This aberration leads to the ectopic and constitutive expression of anti-apoptotic BCL2 protein in B-cells. Nevertheless, the aberration alone is not sufficient for FL development, which suggests necessity of further genetic aberrations acquisition for neoplastic transformation to FL. Their discovery has been enabled by recent progress in the field of massive parallel sequencing (next generation sequencing), which revealed high number of genetic aberrations connected with onset and progression of FL. The occurrence of many of these aberrations in the early stages of the disease, and the fact that they are shared by the majority of patients with FL, fundamentally changed our former understanding of the disease onset. Furthermore, in a large fraction of patients, FL undergoes histological transformation to a more aggressive lymphoma, which is also associated with specific genetic alterations. In this review, we summarize the current knowledge of molecular pathways connected with FL biology and discuss their role in the context of normal B-cell development. Understanding of FL biology is essential for the development of new targeted therapies and the stratification of patients, and potentially also for the selection of treatment for specific patients who share the same genetic aberrations.Key words: follicular lymphoma - mutation - aberration - apoptosis - epigenetic regulators - microRNA This research was carried out under the project CEITEC 2020 (LQ1601) with financial support from the Ministry of Education, Youth and Sports of the Czech Republic under the National Sustain ability Programme II. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 28. 1. 2017Accepted: 5. 3. 2017.

[The Importance of MicroRNA Deregulation in the Molecular Pathogenesis and Histological Transformation of Follicular Lymphoma]. / Význam deregulace mikroRNA v molekulární patogenezi a histologické transformaci folikulárního lymfomu.

BACKGROUND: Molecular pathogenesis of follicular lymphoma (FL) is characterized by substantial dysregulation of epigenetic regulators. Many cases of FL are associated with the aberrant expression of non-coding regulatory RNAs, namely microRNAs (miRNA). Here we studied changes in miRNA expression and their association with histological transformation of FL to diffuse large B-cell lymphoma (DLBCL). MATERIAL AND METHODS: To identify changes in miRNA levels during FL transformation we performed a global expression analysis of 377 miRNAs in 16 samples (8 pairs) from FL patients vs. transformed FL (tFL) (TLDA miRNA cards; Thermo Fisher Scientific). The association of miRNA expression with clinical-biological characteristics and target proteins were further analyzed in a cohort of 89 FL patients. RESULTS: The miRNA expression profiling of paired FL-tFL samples revealed statistically significant changes in the expression of five miRNAs (p < 0.05). Four of them were down-regulated and one was up-regulated in tFL compared to FL. Lower levels of one of these miRNA were also associated with higher proliferation rate of FL cells (Ki-67 > 20%), higher FLIPI score ( 3) and shorter overall survival of FL patients. Furthermore, we found that this miRNA regulates the levels of FOXP1 protein in FL. The patients with high-level FOXP1 expression (> 70% positive cells) had significantly shorter overall survival in comparison to those with low-level FOXP1 expression (< 30% positive cells). Moreover, FOXP1 protein levels were higher in most tFL samples compared to FL before transformation. CONCLUSION: We found miRNAs associated with the transformation of FL to a more aggressive DLBCL, and described that one of them could serve as a prognostic marker. We found that reduced expression of this tFL-associated miRNA results in increased levels of FOXP1 protein and we assume that the increased activity of FOXP1 proto-oncogene contributes to the histological transformation of FL.Key words: follicular lymphoma - microRNA - histological transformation This work was supported by Czech Ministry of Health registration No. 16-29622A. All rights reserved. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 5. 3. 2017Accepted: 26. 3. 2017.

Lack of association between lactotransferrin polymorphism and dental caries.

OBJECTIVE: Dental caries is a complex, multifactorial disease and one of the most common illnesses worldwide. Its etiology is related to microbial, dietary and host factors. Recent evidence suggests a role of lactotransferrin (LTF) in caries. The purpose of this study was to determine the association between LTF gene polymorphism and dental caries. METHODS: In this case-control study, 637 unrelated children, aged 11-13 years, were enrolled. The subjects were divided into two groups, i.e. caries-free (decayed/missing/filled teeth = 0) and caries-affected children (decayed/missing/filled teeth ≥ 1). The LTF rs1126478 (140A/G in exon 2, Lys/Arg) genotypes were determined by PCR with restriction analysis using the EarI enzyme. RESULTS: Of 637 children, 155 (24.3%) were caries free. There were no statistically significant differences between caries levels and allele or genotype distributions in the total cohort. When the caries-affected group (n = 482) was stratified into low (decayed/missing/filled teeth = 1), moderate (2 ≤ decayed/missing/filled teeth ≤ 3) and high (decayed/missing/filled teeth ≥ 4) caries experience, allele and genotype frequencies were similar among all subgroups. CONCLUSIONS: The LTF 140A/G (exon 2, Lys/Arg) polymorphism was not associated with the susceptibility to or severity of dental caries in the Czech population.

Relationship between gingivitis severity, caries experience and orthodontic anomalies in 13-15 year-old adolescents in Brno, Czech Republic.

OBJECTIVES: The aim of the present cross-sectional study was to assess oral health in adolescents selected from the ELSPAC (European Longitudinal Study of Pregnancy and Childhood) Bmo group and complete thus the ELSPAC series of studies on child general health. MATERIAL AND METHODS: Randomly selected children from the ELSPAC group (n=780) were examined clinically for dental and periodontal status, dental plaque, dental calculus and orthodontic anomalies. The following clinical parameters were assessed: DMFT score and its components, gingival index (GI), plaque index (PI) and calculus index (CSI). GI, PI and CSI were recorded on selected teeth. The presence/absence of orthodontic anomalies and their severity were recorded. ANOVA test for quantitative and XZ2 test for qualitative parameters evaluation were used. RESULTS: Mean DMFT of the group was 2.82 (SE 0.36), share of caries-free children 25.4%. Mean GI index of the cohort was 0.204 (SE 0.011), grade 0 was found in 36.9% children, grade 1 in 43.0%, and grade 2 in 19.5%. Statistical significant associations (p < 0.05) were observed in GI and DMFT, GI and DT value, GI and severity of orthodontic anomaly; significant difference was found in GI of caries-free and treated children vs. treatment need and in PI value between children with gingivitis vs healthy ones. CONCLUSION: The results demonstrated a relatively high caries experience, low level of gingival inflammation and relation between GI and DMFT, particularly in D component, and between GI and orthodontic anomalies.

Peri-ictal bed leaving in temporal lobe epilepsy: incidence and lateralizing value.

We analyzed peri-ictal bed leaving (PBL) symptoms in 105 patients with temporal lobe epilepsy (TLE). All patients were classified as Engel I at the 2-year follow-up visit. Histopathological examination revealed hippocampal sclerosis (TLE-HS) in 64 patients and other lesions in 38 patients (TLE-other); 3 patients had no lesions. We reviewed 412 seizures. PBL was defined as lateralized leaving of the bed occurring during the seizure or up to 3 minutes after the end of the seizure. PBL was observed in 28 of 105 patients (26.7%), and in 45 of 412 seizures (10.9%). PBL occurred more frequently in patients with TLE-HS than in patients with TLE-other (32.8% vs 17.1%, P=0.058). PBL was ipsilateral to the seizure onset in 71.4% of patients and 71.2% of seizures (P=0.012 and P<0.001). In patients with TLE-HS, PBL was ipsilateral to seizure onset in 76.2% of patients and 81.2% of seizures (P=0.008 and P<0.001). In patients with TLE-other, PBL was ipsilateral to seizure onset in 42.8% of patients and 46.1% of seizures. There were no differences in the incidence and lateralizing value between patients with right-sided and those with left-sided TLE. PBL is a relatively frequent peri-ictal sign in patients with TLE. The side of PBL in patients with TLE-HS lateralizes the seizure onset to the ipsilateral temporal lobe.

Occurrence and lateralizing value of "rare" peri-ictal vegetative symptoms in temporal lobe epilepsy.

We retrospectively investigated rare peri-ictal vegetative symptoms (PIVS) in 380 seizures of 97 patients with temporal lobe epilepsy (TLE): 234 seizures of 60 patients with TLE with mesiotemporal sclerosis (TLE/MTS) and 146 seizures of 37 patients with TLE with other lesions (TLE/non-MTS) who were at least 2 years after epilepsy surgery and classified as Engel I. We assessed the following PIVS: peri-ictal cough (pC), peri-ictal water drinking (pWD), peri-ictal vomiting (pV), and peri-ictal spitting (pS). We observed pC in 24.7% of patients and 10% of seizures; pWD in 14.4% of patients and 5.9% of seizures; pV and pS occurred more rarely. Both pWD and pC occurred significantly more often in those with TLE of the non- language-dominant hemisphere. The limited occurrence of pV and pS made it impossible to perform statistical analysis for these symptoms. In patients with TLE, pC and pWD were quite frequent; we observed pV and pS less frequently. Both pC and pWD have a significant lateralizing value in TLE.

MicroRNAs in B-cell lymphomas: how a complex biology gets more complex.

MicroRNAs (miRNAs) represent important regulators of gene expression besides transcriptional control. miRNA regulation can be involved in the cell developmental fate decisions, but can also have more subtle roles in buffering stochastic fluctuations in gene expression. They participate in pathways fundamental to B-cell development like B-cell receptor (BCR) signalling, B-cell migration/adhesion, cell-cell interactions in immune niches, and the production and class-switching of immunoglobulins. miRNAs influence B-cell maturation, generation of pre-, marginal zone, follicular, B1, plasma and memory B cells. In this review, we discuss miRNAs with essential functions in malignant B-cell development (such as miR-150, miR-155, miR-21, miR-34a, miR-17-92 and miR-15-16). We also put these miRNAs in the context of normal B-cell differentiation, as this is intimately connected to neoplastic B-cell development. We review miRNAs' role in the most common B-cell malignancies, including chronic lymphocytic leukaemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and mantle cell lymphoma (MCL). We focus on miR-contribution to the regulation of important signalling pathways (such as NF-κB, PI3K/AKT and TGF-ß), BCR signalling and its modulators (such as PTEN, SHIP-1, ZAP-70, GAB1 and BTK), anti- and pro-apoptotic proteins (such as BCL2, MCL1, TCL1, BIM, p53 and SIRT1) and transcription factors (such as MYC, MYB, PU.1, FOXP1 and BCL6). We also discuss the association of miRNAs' expression levels with the patients' survival and response to therapy, summarizing their potential use as predictive and prognostic markers. Importantly, the targeting of miRNAs (like use of anti-miR-155 or miR-34a mimic) could provide a novel therapeutic approach as evidenced by tumour regression in xenograft mouse models and initial promising data from clinical trials.

[Initial experience with postgraduate specialization of nurses from orthopaedic departments.]. / První zkusenosti s pomaturitním specializacním studiem zdravotních sester z ortopedických oddelení

In the Institute for Postgraduate Training of Health Workers in Brno the first three-semester course of nurses working in orthopaedic departments was held in 1991-1993. Of 25 participants 19 nurses completed the course with honours. In the submitted article the syllabus of the course is given with emphasis on new views on nursing (in particular basic care and specialized nursing care, therapeutic care and psychosomatic care and management in the health services). Teaching calls for close interdisciplinary collaboration of doctors, teachers of nursing, psychologists, lawyers, and other specialists. Those who passed this course are candidates for leading posts in orthopaedic departments (ward sisters and matrons). Postgraduate training is essential for all groups of health workers. Key words: postgraduate training of nurses, nursing in orthopaedics, theory and practice in medicine.