BACKGROUND: X-linked nephrogenic diabetes insipidus (NDI) is a rare genetic renal disease caused by pathogenic variants in the AVPR2 gene. Single nucleotide variants and small insertions/deletions in AVPR2 are reliably detected by routine clinical sequencing. Nevertheless, structural variants involving AVPR2 are challenging to identify accurately by conventional genetic testing. Here, we report a novel deletion of AVPR2 in a Czech family identified for the first time by targeted long-read sequencing (T-LRS). METHODS: A male proband with X-linked NDI underwent clinical sequencing of the AVPR2 gene that failed and thus indicated possible whole-gene deletion. Therefore, PCR mapping and subsequent targeted long-read sequencing (T-LRS) using a Pacific Biosciences sequencer were applied to search for the suspected deletion. To validate the deletion breakpoints and prove variant segregation in the family with X-linked NDI, Sanger sequencing of the deletion junction was performed. Quantitative real-time PCR was further carried out to confirm the carrier status of heterozygous females. RESULTS: By T-LRS, a novel 7.5 kb deletion of AVPR2 causing X-linked NDI in the proband was precisely identified. Sanger sequencing of the deletion junction confirmed the variant breakpoints and detected the deletion in the probands ́ mother, maternal aunt, and maternal cousin with X-linked NDI. The carrier status in heterozygous females was further validated by quantitative real-time PCR. CONCLUSIONS: Identifying the 7.5 kb deletion gave a precise molecular diagnosis for the proband, enabled genetic counselling and genetic testing for the family, and further expanded the spectrum of structural variants causing X-linked NDI. Our results also show that T-LRS has significant potential for accurately identifying putative structural variants.

• MeSH
• delece genu MeSH
• diabetes mellitus * MeSH
• genetické testování MeSH
• heterozygot MeSH
• ledviny MeSH
• lidé MeSH
• nefrogenní diabetes insipidus * genetika   MeSH
• vzácné nemoci MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

PURPOSE: To describe the genotype-phenotype correlation and serial observations in a five-generation Czech family with X-linked retinitis pigmentosa (XLRP) associated with severe visual impairment in women. METHODS: Comprehensive ophthalmological examination including spectral domain optical coherence tomography (SD-OCT) was performed. Based on the pedigree structure and women being severely affected, autosomal dominant inheritance was suspected, and screening for known mutations by genotyping microarray was performed. Subsequently, direct sequencing of ORF15 RPGR was undertaken. RESULTS: Eighteen family members (nine women and nine men) were examined. A pathogenic variant, c.2543del in ORF15 of RPGR, was found to segregate with disease. The oldest woman and her two sisters had no perception of light in their sixth decade. Four women and five men had signs and symptoms of typical XLRP, including moderate to high myopia. Three other women also had moderate to high myopia and myopic astigmatism but without the presence of bone spicule-like formation. Severe disruption of macular architecture on SD-OCT was equally common in both sexes. Only one 32-year-old female carrier had clinically normal findings. Subfoveal choroidal thickness was decreased in all affected men and in all female carriers, except the only carrier with a normal fundus examination. CONCLUSIONS: The c.2543del mutation in ORF15 of RPGR is associated with a severe phenotype in the women in this family. The presence of a significant myopic refractive error, in the absence of male-to-male transmission, may be indicative of X-linked inheritance. Measurements of choroidal thickness may help in clinically identifying carrier status.

• MeSH
• choroidea metabolismus   patologie   MeSH
• dítě MeSH
• dominantní geny MeSH
• dospělí MeSH
• geny vázané na chromozom X * MeSH
• heterozygot MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• molekulární sekvence - údaje MeSH
• oční proteiny genetika   MeSH
• optická koherentní tomografie MeSH
• otevřené čtecí rámce MeSH
• retina metabolismus   patologie   MeSH
• retinopathia pigmentosa genetika   patologie   MeSH
• rodokmen MeSH
• sekvence nukleotidů * MeSH
• sekvenční delece * MeSH
• senioři MeSH
• sexuální faktory MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disorder categorized into 3 phenotypic variants: infantile, juvenile, and adult. Four recent reports have linked NIID to CGG expansions in the NOTCH2NLC gene in adult NIID (aNIID) and several juvenile patients. Infantile NIID (iNIID) is an extremely rare neuropediatric condition. We present a 7-year-old male patient with severe progressive neurodegenerative disease that included cerebellar symptoms with cerebellar atrophy on brain MRI, psychomotor developmental regression, pseudobulbar syndrome, and polyneuropathy. The diagnosis of iNIID was established through a postmortem neuropathology work-up. We performed long-read sequencing of the critical NOTCH2NLC repeat motif and found no expansion in the patient. We also re-evaluated an antemortem skin biopsy that was collected when the patient was 2 years and 8 months old and did not identify the intranuclear inclusions. In our report, we highlight that the 2 methods (skin biopsy and CGG expansion testing in NOTCH2NLC) used to identify aNIID patients may provide negative results in iNIID patients.

• MeSH
• biopsie MeSH
• dítě MeSH
• intranukleární inkluzní tělíska genetika   patologie   MeSH
• kojenec MeSH
• kůže patologie   MeSH
• lidé MeSH
• mícha patologie   MeSH
• mozek patologie   MeSH
• neurodegenerativní nemoci diagnóza   genetika   patologie   MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• receptor Notch2 genetika   MeSH
• trinukleotidové repetice genetika   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH

The Leishmania donovani species complex consists of all L. donovani and L. infantum strains mainly responsible for visceral leishmaniasis (VL). It was suggested that genome rearrangements in Leishmania spp. occur very often, thus enabling parasites to adapt to the different environmental conditions. Some of these rearrangements may be directly linked to the virulence or explain the reduced efficacy of antimonial drugs in some isolates. In the current study, we focused on a large-scale analysis of putative gene conversion events using publicly available datasets. Previous population study of L. donovani suggested that population variability of L. donovani is relatively low, however the authors used masking procedures and strict read selection criteria. We decided to re-analyze DNA-seq data without masking sequences, because we were interested in the most dynamic fraction of the genome. The majority of samples have an excess of putative gene conversion/recombination events in the noncoding regions, however we found an overall excess of putative intrachromosomal gene conversion/recombination in the protein coding genes, compared to putative interchromosomal gene conversion/recombination events.

• Publikační typ
• časopisecké články MeSH

Carbapenem-resistant Acinetobacter baumannii (CRAB) is an important opportunistic pathogen linked to a variety of nosocomial infections and hospital outbreaks worldwide. This study aimed at investigating and characterizing a CRAB outbreak at a large tertiary hospital in Lebanon. A total of 41 isolates were collected and analyzed using pulsed-field gel electrophoresis (PFGE). Whole-genome sequencing (WGS) was performed on all the isolates, and long-read PacBio sequencing was used to generate reference genomes. The multilocus sequence types (MLST), repertoire of resistance genes, and virulence factors were determined from the sequencing data. The plasmid content was analyzed both in silico and using the A. baumannii PCR-based replicon typing (AB-PBRT) method. Genome analysis initially revealed two clones, one carrying blaOXA-23 on Tn2006 (ST-1305, ST-195, and ST-218) and another carrying blaOXA-72 on pMAL-1 (ST-502 and ST-2059, a new ST), with the latter having two subclones, as revealed using the Bayesian transmission network. All isolates were extensively drug resistant (XDR). WGS analysis revealed the transmission pathways and demonstrated the diversity of CRAB isolates and mobile genetic elements in this health care setting. Outbreak detection using WGS and immediate implementation of infection control measures contribute to restraining the spread and decreasing mortality.IMPORTANCE Carbapenem-resistant Acinetobacter baumannii (CRAB) has been implicated in hospital outbreaks worldwide. Here, we present a whole-genome-based investigation of an extensively drug-resistant CRAB outbreak rapidly spreading and causing high incidences of mortality at numerous wards of a large tertiary hospital in Lebanon. This is the first study of its kind in the region. Two circulating clones were identified using a combination of molecular typing approaches, short- and long-read sequencing and Bayesian transmission network analysis. One clone carried blaOXA-23 on Tn2006 (ST-1305, ST-195, and ST-218), and another carried blaOXA-72 on a pMAL-1 plasmid (ST-502 and ST-2059, a new ST). A pMAL-2 plasmid was circulating between the two clones. The approaches implemented in this study and the obtained findings facilitate the tracking of outbreak scenarios in Lebanon and the region at large.

• MeSH
• Acinetobacter baumannii klasifikace   účinky léků   MeSH
• antibakteriální látky farmakologie   MeSH
• Bayesova věta MeSH
• centra terciární péče MeSH
• dospělí MeSH
• epidemický výskyt choroby * MeSH
• genom bakteriální * MeSH
• infekce bakteriemi rodu Acinetobacter mikrobiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• mnohočetná bakteriální léková rezistence genetika   MeSH
• multilokusová sekvenční typizace MeSH
• pulzní gelová elektroforéza MeSH
• rozptýlené repetitivní sekvence MeSH
• sekvenování celého genomu MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• techniky typizace bakterií MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Libanon MeSH

A highly effective way to improve the prognosis of viral infectious diseases is early detection of antibodies to various viral pathogens in biological fluids. Among a wide range of viral pathogens, tick-borne encephalitis virus (TBEV) attracts a special attention. This work reports a comparison between two bioanalytical methods (enzyme‑linked immunosorbent assay (ELISA) and voltammetric immunoassay) to determine antibodies to TBEV in a human blood serum. In these assays, the detected mo­lecule binds to the conjugate which is labelled with enzyme (in ELISA) or silver nanoparticles (in voltammetric immunoassay). In the ELISA, the signal corresponding to a colour-producing substrate (3,3',5,5'-tetramethylbenzidine) through an enzymatic reaction is detected using a spectrophotometer at a wavelength of 450 nm. In the electrochemical immunoassay, the signal is read by the linear sweep anodic stripping voltammetry (LSASV) of silver ions (through the electrochemical stripping of accumulated elemental silver) on a graphite composite electrode. The results of both measurements demonstrated that signals increased with the increasing concentration of the target antibodies to TBEV within the range from 100 to 1600 IU mL–1. Detection limits for ELISA and voltammetric assay were 30 and 90 IU mL–1, respectively. The practical application of both immunoanalytical approaches has been verified by determining the amount of antibodies to TBEV in the human blood serum. The obtained results clearly showed an excellent agreement between the detected concentration values of antibodies to TBEV obtained by the electrochemical method and by the standard ELISA method.

Autori uvádzajú kazuistiku 46-ročnej pacientky s adultnou formou Stillovej choroby, u ktorej v klinickom obraze dominovala masívna exudatívna polyserozitída. Diagnóza Stillovej choroby sa stanovila na základe diagnostických kritérií Yamaguchiho, Cusha a Fautrela po vylúčení infekčných, onkologických a iných chorôb prebiehajúcich pod podobným klinickým obrazom. Polyserozitída, prítomná v úvode choroby, si vyžadovala opakované evakuačné pleurálne punkcie a fenestráciu perikardu. Klinické prejavy ustúpili po zahájení liečby kortikoidmi, ktorých detrakcia bola opakovane spojená s klinickým relapsom, ale bez manifestácie serozitídy, ku ktorým sa pridružil prchavý makulopapulózny exantém. Po pridaní metotrexátu bola pacientka niekoľko mesiacov v klinickej remisii, keď po infekcii dýchacích ciest došlo znovu k relapsu s obrazom obojstranného pleulárneho výpotku. Pri zvýšení dávky kortikoidov a pridaní cyklosporínu, masívny pleurálny výpotok pretrvával, aj napriek ústupu ostatných klinických a laboratórnych prejavov. Z podobným prípadom sme sa doteraz v literatúre nestretli. Kazuistika si zasluhuje pozornosť vzhľadom na ojedinelý výskyt tejto choroby bez prítomnosti výraznej hyperferitinémie, ktorá sa považuje za patognomonickú pre túto chorobu, a rezistenciu pleuritídy na štandardnú imunosupresívnu liečbu. Zvláštnosťou prípadu je aj nález atypickej populácie buniek v kostnej dreni.

The authors present a case report of a 46-year-old female patient with adult Still´s disease with predominant mass exudative polyserositis in clinical picture. Diagnosis of Still´s disease was determined on basis of Yamaguchi, Cush and Fautrel criteria after eliminating infectious, oncological and other diseases with similar clinical picture. Polyserositis present at the onset of the disease needed repeated evacuated pleural punctions and pericardial fenestration. Clinical manifestations receded after corticoid therapy detraction of which was recurrently linked with clinical relapse without manifestation of serositis but with subtle maculopapulous exanthema. After added metotrexate the patient was in clinical remission for several months. After infection of respiratory tract, relapse developed again, with the picture of bilateral pleural exudates. After increasing dose of corticosteroids and adding cyclosporine the mass pleural exudates persisted though other clinical and lab manifestations retreated. We have never read about the similar case. The case report deserves attention due to uniqueness of the disease without significant hyperferitinemia that is considered pathognomonic for this disease and resistance of pleuritis to standard immunosuppressive therapy. Uniqueness of the disease is also in atypical cells population in the bone marrow.

Úvod: Pro veřejnost představují tištěná média nejdůležitější zdroj informací o duševních onemocněních. Je známo, že média značně přispívají ke stigmatizaci lidí s duševními poruchami. Tato mezinárodní komparativní studie popisuje obsahy mediálních sdělení o duševních onemocněních ve vztahu ke stigmatizaci ve třech středoevropských státech. Metodika: Výzkumný soubor tvořily články týkající se tématu duševního zdraví publikované během pěti týdnů v roce 2007 v šesti nejčtenějších denících a týdenících v každém státě. Celkem bylo nalezeno 450 článků pojednávajících o duševních poruchách (203 článků v České republice, 172 na Slovensku a 75 v Chorvatsku). Mediální sdělení byla zpracována metodou obsahové analýzy za účelem dosažení kvantitativních i kvalitativních cílů. Výsledky: Statisticky významné rozdíly byly nalezeny mezi třemi státy v distribuci článků podle umístění článku v periodiku, podle typu zmíněné diagnózy a podle agresivního aktu uváděného v souvislosti s psychiatrickým pacientem. Negativní postoje vůči osobám s duševním onemocněním byly nalezeny v 37% článků publikovaných v České republice, v 38% článků na Slovensku a ve 40 % článků v Chorvatsku. Analyzované články ukázaly, že lidé s duševním onemocněním jsou častěji zobrazováni v roli pachatele trestné činnosti (29%) než v roli její oběti (9 %). Závěr: Výsledky naznačují, že stupeň stigmatizace lidí s duševními poruchami je relativně vysoký. Dochází k posilování negativních stereotypů, jelikož lidé s duševními poruchami jsou zobrazováni jako násilní jedinci. Na základě těchto zjištění mohou být praktická doporučení pro novináře vypracována zvlášť pro každou zemi.

Objectives: Media are considered to be the publics primary source of information regarding mental illness. Its known that media significantly contribute to the stigmatisation of mental disorders, as well as the people with such ailments. This international comparative study describes the content of media messages about mental health in terms of stigma in three central European countries. Methods: The study sample comprises articles pertaining to the topic of mental health collected during five week-long periods in 2007 chosen from the six most widely read newspapers and magazines in each country. A total of 450 articles with mental illness as main content were found (203 articles from Czech Republic, 172 from Slovak Republic, 75 from Croatia). Content analysis methods were used to achieve quantitative as well as qualitative objectives. Results: Statistically significant differences were found among three countries in the distribution of articles associated with the position of articles, type of mental disorder and aggressive acts linked to psychiatric patients. Negative global impression of the text was found in the 37% articles from Czech Republic, 38% articles from Slovakia and 40% articles from Croatia. Analyzed articles showed dominance in portrayal of the mentally ill persons as perpetrators in crime related stories (29%) contrary to very low occurence of those portrayed as victims (9%). Conclusion: The results suggest that the degree of stigma of persons with mental disorders in all three countries is relatively high. Negative stereotypes are further strengthened as the persons with mental illness are depicted as violent individuals. Based on the findings, practical recommendations for journalists can be tailored specifically for each country.

• Klíčová slova
• obsahová analýza, stigma, tištěná média,
• MeSH
• duševně nemocní MeSH
• duševní zdraví MeSH
• financování organizované MeSH
• lidé MeSH
• odmítání (psychologie) MeSH
• psychologický odstup MeSH
• sociální žádoucnost MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• novinové články MeSH
• zprávy MeSH
• Geografické názvy
• Česká republika MeSH
• Chorvatsko MeSH
• Slovenská republika MeSH

BACKGROUND: Autosomal-dominant mutations in the Park8 gene encoding Leucine-rich repeat kinase 2 (LRRK2) have been identified to cause up to 40% of the genetic forms of Parkinson's disease. However, the function and molecular pathways regulated by LRRK2 are largely unknown. It has been shown that LRRK2 serves as a scaffold during activation of WNT/β-catenin signaling via its interaction with the β-catenin destruction complex, DVL1-3 and LRP6. In this study, we examine whether LRRK2 also interacts with signaling components of the WNT/Planar Cell Polarity (WNT/PCP) pathway, which controls the maturation of substantia nigra dopaminergic neurons, the main cell type lost in Parkinson's disease patients. METHODS: Co-immunoprecipitation and tandem mass spectrometry was performed in a mouse substantia nigra cell line (SN4741) and human HEK293T cell line in order to identify novel LRRK2 binding partners. Inhibition of the WNT/β-catenin reporter, TOPFlash, was used as a read-out of WNT/PCP pathway activation. The capacity of LRRK2 to regulate WNT/PCP signaling in vivo was tested in Xenopus laevis' early development. RESULTS: Our proteomic analysis identified that LRRK2 interacts with proteins involved in WNT/PCP signaling such as the PDZ domain-containing protein GIPC1 and Integrin-linked kinase (ILK) in dopaminergic cells in vitro and in the mouse ventral midbrain in vivo. Moreover, co-immunoprecipitation analysis revealed that LRRK2 binds to two core components of the WNT/PCP signaling pathway, PRICKLE1 and CELSR1, as well as to FLOTILLIN-2 and CULLIN-3, which regulate WNT secretion and inhibit WNT/β-catenin signaling, respectively. We also found that PRICKLE1 and LRRK2 localize in signalosomes and act as dual regulators of WNT/PCP and β-catenin signaling. Accordingly, analysis of the function of LRRK2 in vivo, in X. laevis revelaed that LRKK2 not only inhibits WNT/β-catenin pathway, but induces a classical WNT/PCP phenotype in vivo. CONCLUSIONS: Our study shows for the first time that LRRK2 activates the WNT/PCP signaling pathway through its interaction to multiple WNT/PCP components. We suggest that LRRK2 regulates the balance between WNT/β-catenin and WNT/PCP signaling, depending on the binding partners. Since this balance is crucial for homeostasis of midbrain dopaminergic neurons, we hypothesize that its alteration may contribute to the pathophysiology of Parkinson's disease.

• MeSH
• beta-katenin metabolismus   MeSH
• dopaminergní neurony metabolismus   MeSH
• kadheriny metabolismus   MeSH
• lidé MeSH
• LRRK2 genetika   metabolismus   MeSH
• mutace genetika   MeSH
• polarita buněk fyziologie   MeSH
• protein-serin-threoninkinasy metabolismus   MeSH
• proteomika metody   MeSH
• signální dráha Wnt fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

"Diagnostic Imaging: Pediatric Neuroradiology, Second Edition is a useful tool for all health professionals involved in ordering, performing, or interpreting imaging studies of the child's brain, head, neck, spinal column, and spinal cord. The book consists of diagnoses of all common disorders of the pediatric nervous system and many that are not common. For each diagnosis, information is included concerning the clinical presentation(s) of affected patients, the best sequences to perform for imaging analysis, what each imaging sequence is expected to show (in both common and uncommon presentations), and examples of images showing the key features. In addition, information is included concerning the pathophysiology and pathology of the disorders being discussed, and some basic information concerning the causative genes (when appropriate). In addition to the diagnoses, the book contains introductory chapters in multiple sections that give background on basic embryology, anatomy, and physiology as well as typical imaging features of normal structures in areas being imaged. Put together, the contents of the book make it useful for readers of many different backgrounds and at nearly all stages of training as well as practicing health professionals. This beautiful second edition comes with Amirsys eBook Advantage, an online and searchable version of the book with linked references. In classic Amirsys style, both print and electronic content is viewable in easy-to-read bulleted lists supported by clearly described images. With a comprehensive overhaul, Diagnostic Imaging: Pediatric Neuroradiology, Second Edition promises to become another classic."--Provided by publisher.

• MeSH
• dítě MeSH
• hlava radiografie   MeSH
• krk radiografie   MeSH
• nemoci centrálního nervového systému * radiografie   MeSH
• neuroradiografie metody   MeSH
• páteř radiografie   MeSH
• Check Tag
• dítě MeSH
• Publikační typ
• atlasy MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• radiologie, nukleární medicína a zobrazovací metody
• neurologie
• pediatrie