MULTINUKLEARNE ORIJAŠKE STANICE EKSTRAVILOZNOG TROFOBLASTA U DECIDUI POSTELJICA IZ TRUDNOĆA S PREEKLAMPSIJOM

Objectives: To compare the number of Multinucleated Giant Cells (MGC) in the decidua basalis of placentas complicated with preeclampsia (PE) and placentas from normal pregnancies. Subject and Method: Fifteen placental samples from pregnancies complicated with PE and the same number of placental samples from normal pregnancies were taken. For each placental sample the number of MGC, extravillous trophoblast (EVTB) and decidual cells (DC) was counted in the decidua basalis. Immunohistochemistry with primary antibody CK7 was used to distinguish EVTB and MGC from DC. The MGC/DC ratio and MGC/EVTB ratio was also determined. Results: MGC number was significantly higher in placentas complicated with PE. Likewise MGC/DC ratio was found to be significantly higher in the studied group. There was no statistically significant difference in EVTB and DC number as well as MGC/EVTB ratio. Conclusion: Increased MGC number in the decidua basalis could be a morphological sign of PE and hypoxic conditions in the placenta.Ciljevi: Usporediti broj multinuklearnih orijaških stanica (MOS) u decidui basalis posteljica iz trudnoća s preeklampsijom (PE) i posteljica iz normalnih trudnoća. Materijali i metode: U ispitivanu skupinu je uključeno petnaest uzoraka posteljica iz trudnoća s PE. Isti broj uzoraka posteljica iz normalnih trudnoća je činio kontrolnu skupinu. U svakom uzorku je određen broj MOSa, stanica ekstraviloznog trofoblasta (EVTB) i decidualnih stanica (DS) u decidui basalis. Za razlikovanje stanica EVTB i MOSa od DSa korišteno je imunohistokemijsko bojanje s primarnim protutijelom CK7. Određen je i odnos MOS/DS i MOS/EVTB. Rezultati: Broj MOS je bio značajno veći u ispitivanoj skupini posteljica u odnosu na kontrolnu skupinu. Odnos MOS/DS je također bio značajno veći u ispitivanoj skupini posteljica. Nije bilo statistički značajne razlike u broju stanica EVTB, DS kao i u odnosu MOS/EVTB između dvije skupine. Zaključak: Povišeni broj MOSa u decidui basalis jedan je od morfoloških znakova koji mogu ukazivati da se radi o posteljici trudnoće s PE, to jest o postojanju hipoksičnih uvjeta

Etablierung eines NGS-basierten Verfahrens zur Bestimmung minimaler Resterkrankung bei B-Zell-Lymphomen anhand zellfreier DNA

Bei Follikulären Lymphomen ist die Bestimmung der minimalen Resterkrankung (MRD) im Therapieverlauf ein wesentlicher prognostischer Faktor. Allerdings sind der bisher angewandten Standardmethode der RQ-PCR zum Nachweis einer tumorspezifischen Rekombination des Immunglobulinschwerkettengens Limitationen gesetzt. Neben der arbeitsaufwändigen Etablierung patientenspezifischer Assays bleibt die RQ-PCR eine relative Quantifizierungsmethode mit einer begrenzten Sensitivität. Zellfreie DNA beschreibt kurze DNA Fragmente von 160-180 Basenpaaren, die von gesunden Zellen und von Tumorzellen in den Blutstrom freigesetzt und aus Plasma isoliert werden können. Sie stellt eine potenzielle alternative Quelle für die Bestimmung von molekularen Veränderungen des Tumors und minimaler Resterkrankung dar. In dieser Arbeit wurden standardisierte Verfahrensweisen zur Handhabung der zellfreien DNA für die MRD Diagnostik etabliert, die als Grundlage für eine prospektive MRD-Bestimmung im Plasma im Rahmen zukünftiger Studien dienen können. Der hohe Stellenwert einer NGS-basierten MRD-Diagnostik für die Analyse von zellfreier DNA in Follikulären Lymphomen konnte in dieser Arbeit belegt und die Anwendbarkeit durch ein standardisiertes Vorgehen verbessert werden. Neben der RQ-PCR und der hier als gleichwertig belegten ddPCR kann die zellfreie DNA zuverlässig und hochsensitiv mit NGS-basierten Assays untersucht werden. Dies bietet die Möglichkeit, die MRD Diagnostik im Plasma in zukünftigen Studien auch prospektiv in größeren Patientenkollektiven anzuwenden

MULTINUKLEARNE ORIJAŠKE STANICE EKSTRAVILOZNOG TROFOBLASTA U DECIDUI POSTELJICA IZ TRUDNOĆA S PREEKLAMPSIJOM

Objectives: To compare the number of Multinucleated Giant Cells (MGC) in the decidua basalis of placentas complicated with preeclampsia (PE) and placentas from normal pregnancies. Subject and Method: Fifteen placental samples from pregnancies complicated with PE and the same number of placental samples from normal pregnancies were taken. For each placental sample the number of MGC, extravillous trophoblast (EVTB) and decidual cells (DC) was counted in the decidua basalis. Immunohistochemistry with primary antibody CK7 was used to distinguish EVTB and MGC from DC. The MGC/DC ratio and MGC/EVTB ratio was also determined. Results: MGC number was significantly higher in placentas complicated with PE. Likewise MGC/DC ratio was found to be significantly higher in the studied group. There was no statistically significant difference in EVTB and DC number as well as MGC/EVTB ratio. Conclusion: Increased MGC number in the decidua basalis could be a morphological sign of PE and hypoxic conditions in the placenta.Ciljevi: Usporediti broj multinuklearnih orijaških stanica (MOS) u decidui basalis posteljica iz trudnoća s preeklampsijom (PE) i posteljica iz normalnih trudnoća. Materijali i metode: U ispitivanu skupinu je uključeno petnaest uzoraka posteljica iz trudnoća s PE. Isti broj uzoraka posteljica iz normalnih trudnoća je činio kontrolnu skupinu. U svakom uzorku je određen broj MOSa, stanica ekstraviloznog trofoblasta (EVTB) i decidualnih stanica (DS) u decidui basalis. Za razlikovanje stanica EVTB i MOSa od DSa korišteno je imunohistokemijsko bojanje s primarnim protutijelom CK7. Određen je i odnos MOS/DS i MOS/EVTB. Rezultati: Broj MOS je bio značajno veći u ispitivanoj skupini posteljica u odnosu na kontrolnu skupinu. Odnos MOS/DS je također bio značajno veći u ispitivanoj skupini posteljica. Nije bilo statistički značajne razlike u broju stanica EVTB, DS kao i u odnosu MOS/EVTB između dvije skupine. Zaključak: Povišeni broj MOSa u decidui basalis jedan je od morfoloških znakova koji mogu ukazivati da se radi o posteljici trudnoće s PE, to jest o postojanju hipoksičnih uvjeta

Improving Readability of Medical Data by Using Decision Rules

As medical journal abstracts have become more and more difficult to read, there is a burning issue for doctors to get relevant medical information in order to solve a problem in a fast and efficient way. The paper deals with the synthesis of sentences of spoken language from tabular historical data that relate to a specific medical sub domain. In this case Systematic Syntax Classification of\ud Objects or SSCO algorithm was used in order to generate decision rules which were consequently transformed to natural language and delivered to the user by a machine text reader. The system is “hands–free”, reliable, and enables communication by natural language. The experiments were conducted on data sample consisting of patient’s conditions after hip surgery procedure and originating from General hospital “Djordje Joanovic”, Zrenjanin, Serbia

Intestinal-cell kinase and juvenile myoclonic epilepsy

No abstract available

Performance characterisation of a new photo-microsensor based sensing head for displacement measurement

This paper presents a robust displacement sensor with nanometre-scale resolution over a micrometre range. It is composed of low cost commercially available slotted photo-microsensors (SPMs). The displacement sensor is designed with a particular arrangement of a compact array of SPMs with specially designed shutter assembly and signal processing to significantly reduce sensitivity to ambient light, input voltage variation, circuit electronics drift, etc. The sensor principle and the characterisation results are described in this paper. The proposed prototype sensor has a linear measurement range of 20 μm and resolution of 21 nm. This kind of sensor has several potential applications, including mechanical structural deformation monitoring system

Genetic determinants of common epilepsies: a meta-analysis of genome-wide association studies

published_or_final_versio

Optimizing genomic medicine in epilepsy through a gene-customized approach to missense variant interpretation

Gene panel and exome sequencing have revealed a high rate of molecular diagnoses among diseases where the genetic architecture has proven suitable for sequencing approaches, with a large number of distinct and highly penetrant causal variants identified among a growing list of disease genes. The challenge is, given the DNA sequence of a new patient, to distinguish disease-causing from benign variants. Large samples of human standing variation data highlight regional variation in the tolerance to missense variation within the protein-coding sequence of genes. This information is not well captured by existing bioinformatic tools, but is effective in improving variant interpretation. To address this limitation in existing tools, we introduce the missense tolerance ratio (MTR), which summarizes available human standing variation data within genes to encapsulate population level genetic variation. We find that patient-ascertained pathogenic variants preferentially cluster in low MTR regions (P < 0.005) of well-informed genes. By evaluating 20 publicly available predictive tools across genes linked to epilepsy, we also highlight the importance of understanding the empirical null distribution of existing prediction tools, as these vary across genes. Subsequently integrating the MTR with the empirically selected bioinformatic tools in a gene-specific approach demonstrates a clear improvement in the ability to predict pathogenic missense variants from background missense variation in disease genes. Among an independent test sample of case and control missense variants, case variants (0.83 median score) consistently achieve higher pathogenicity prediction probabilities than control variants (0.02 median score; Mann-Whitney U test, P < 1 × 10(-16)). We focus on the application to epilepsy genes; however, the framework is applicable to disease genes beyond epilepsy

De novo SCN1A mutations in Dravet syndrome and related epileptic encephalopathies are largely of paternal origin

Background: Dravet syndrome is a severe infantile epileptic encephalopathy caused in approximately 80% of cases by mutations in the voltage gated sodium channel subunit gene SCN1A. The majority of these mutations are de novo. The parental origin of de novo mutations varies widely among genetic disorders and the aim of this study was to determine this for Dravet syndrome. Methods: 91 patients with de novo SCN1A mutations and their parents were genotyped for single nucleotide polymorphisms (SNPs) in the region surrounding their mutation. Allele specific polymerase chain reaction (PCR) based on informative SNPs was used to separately amplify and sequence the paternal and maternal alleles to determine in which parental chromosome the mutation arose. Results: The parental origin of SCN1A mutations was established in 44 patients for whom both parents were available and SNPs were informative. The mutations were of paternal origin in 33 cases and of maternal origin in the remaining 11 cases. De novo mutation of SCN1A most commonly, but not exclusively, originates from the paternal chromosome. The average age of parents originating mutations did not differ from that of the general population. Conclusions: The greater frequency of paternally derived mutations in SCN1A is likely to be due to the greater chance of mutational events during the increased number of mitoses which occur during spermatogenesis compared to oogenesis, and the greater susceptibility to mutagenesis of the methylated DNA characteristic of sperm cells.Sarah E. Heron, Ingrid E. Scheffer, Xenia Iona, Sameer M. Zuberi, Rachael Birch, Jacinta M. McMahon, Carla M. Bruce, Samuel F. Berkovic, John C. Mulle