Juxtaglomerular cell tumor (JxGCT) is a rare type of renal neoplasm demonstrating morphologic overlap with some mesenchymal tumors such as glomus tumor (GT) and solitary fibrous tumor (SFT). Its oncogenic drivers remain elusive, and only a few cases have been analyzed with modern molecular techniques. In prior studies, loss of chromosomes 9 and 11 appeared to be recurrent. Recently, whole-genome analysis identified alterations involving genes of MAPK-RAS pathway in a subset, but no major pathogenic alterations have been discovered in prior whole transcriptome analyses. Considering the limited understanding of the molecular features of JxGCTs, we sought to assess a collaborative series with a multiomic approach to further define the molecular characteristics of this entity. Fifteen tumors morphologically compatible with JxGCTs were evaluated using immunohistochemistry for renin, single-nucleotide polymorphism array (SNP), low-pass whole-genome sequencing, and RNA sequencing (fusion assay). In addition, methylation analysis comparing JxGCT, GT, and SFT was performed. All cases tested with renin (n=11) showed positive staining. Multiple chromosomal abnormalities were identified in all cases analyzed (n=8), with gains of chromosomes 1p, 10, 17, and 19 and losses of chromosomes 9, 11, and 21 being recurrent. A pathogenic HRAS mutation was identified in one case as part of the SNP array analysis. Thirteen tumors were analyzed by RNA sequencing, with 2 revealing in-frame gene fusions: TFG::GPR128 (interpreted as stochastic) and NAB2::STAT6 . The latter, originally diagnosed as JxGCT, was reclassified as SFT and excluded from the series. No fusions were detected in the remaining 11 cases; of note, no case harbored NOTCH fusions previously described in GT. Genomic methylation analysis showed that JxGCT, GT, and SFT form separate clusters, confirming that JxGCT represents a distinct entity (ie, different from GT). The results of our study show that JxGCTs are a distinct tumor type with a recurrent pattern of chromosomal imbalances that may play a role in oncogenesis, with MAPK-RAS pathway activation being likely a driver in a relatively small subset.

• MeSH
• dospělí MeSH
• epigeneze genetická MeSH
• epigenomika MeSH
• fúze genů * MeSH
• genetická predispozice k nemoci MeSH
• genomika MeSH
• imunohistochemie MeSH
• jednonukleotidový polymorfismus MeSH
• juxtaglomerulární aparát patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metylace DNA MeSH
• nádorové biomarkery * genetika   MeSH
• nádory ledvin * genetika   patologie   chemie   MeSH
• sekvenování celého genomu MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Prostate cancer (PCa) poses a significant global health threat, with high incidence and mortality rates. In 2022, the Council of the European Union (EU) updated its screening recommendations, prioritizing PCa screening. This signals a crucial step towards establishing new early detection programmes in EU member states. This study investigates the role of policy makers and governance in cancer screening to inform the development of PCa screening. We had a mixed-method study design. First, a rapid review was conducted on policy making and governance in EU-funded cancer screening initiatives. Second, a focus group discussion reviewed study concepts and methods. Third, a systematic literature review was performed and, fourth, a series of in-depth interviews with actors involved in PCa screening pilots was conducted. Data were analysed thematically and the findings are used to propose 10 recommendations for policy makers. The results of the rapid review and focus group discussion framed the study in the context of existing cancer screening programmes across the EU, and highlighted what already exists in terms of governance tools and methodology. The literature review and in-depth interviews presented key learnings from the literature and real-life settings. These findings are reported using a pre-existing conceptional framework for effective health system governance. The study underscores the critical importance of governance in effective cancer screening programmes. Ten recommendations are proposed, including: defining cancer screening governance, allocating budgets and defining common approaches and key performance indicators for evaluation, establishing methods to enhance citizen participation, and reinforcing network governance.

• MeSH
• časná detekce nádoru * metody   MeSH
• Evropská unie MeSH
• lidé MeSH
• nádory prostaty * diagnóza   MeSH
• plošný screening * organizace a řízení   MeSH
• správní úředníci * MeSH
• vytváření politiky * MeSH
• zdravotní politika * MeSH
• zjišťování skupinových postojů MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• systematický přehled MeSH

Sepsa je život ohrozujúci stav s orgánovou dysfunkciou a dysregulovanou odpoveďou organizmu na infekčné agens. Incidencia v Európe je 3,4 milióna prípadov každý rok. Mortalita je vysoká a má 2 vrcholy – u detí vo veku do 5 rokov a u seniorov. Analyzovali sme 65-ročných a starších pacientov so sepsou (n = 32). Zamerali sme sa na vzájomný vzťah kardiálnych (NT-proBNP a troponín) a renálnych (urea a kreatinín) ukazovateľov v časovom rámci prvých 72 hodín od stanovenia diagnózy sepsy. Vychádzali sme z predpokladu, že srdce a obličky nie sú dve oddelené nádoby, ale sú skôr dva kodominantné permanentne prepojené elementy. Súvislosti sme sledovali v 2 rovinách a to v rámci kardiorenálnych interakcií a pri kardiorenoinflamatórnom komplexe. Preukázal sa pozitívny vzťah medzi markermi v oboch týchto rovinách, avšak ich prepojenie nebolo fixné, ale dynamicky sa meniace, pričom ako rozhodujúci časový rámec vyšiel horizont prvých 24 hodín. To podporuje koncept kardiorenálneho syndrómu (KRS) 5. typu ako dynamického ochorenia. Hoci pribúdajú údaje o stúpajúcej incidencii latentného chronického postihnutia srdca aj obličiek, ostáva otvorená otázka, či KRS 5. typu je samostatnou nozologickou jednotkou, alebo je subtypom KRS 1. či 3. typu.

Sepsis is a life-threatening condition with organ dysfunction and dysregulated body response to infectious agents. The incidence in Europe is 3.4 million cases each year. Mortality is high and has 2 peaks – in children under the age of 5 and in the elderly. We analyzed a set of 65-years old and older pacients with sepsis (n = 32). We focused on the relationship between cardiac (NT-proBNP and troponin) and renal (urea and creatinine) indicators within the time frame of the first 72 hours after diagnosis of sepsis. We started from the assumption that the heart and kidneys are not two separate vessels, but rather two codominant permanently connected elements. We monitored relationships in 2 levels, within the cardio-renal interactions and in the cardio-reno-inflammatory complex. A positive relationship between markers in both levels was demonstrated, but their connection was not fixed, but dynamically changing, with the first 24 hours being the decisive time frame. This supports the concept of cardio-renal syndrome(KRS) type 5 as a dynamic disease. Due to the increasing data on the rising incidence of latent chronic involvement of the heart and kidneys, the question is whether CRS type 5 is a separate nosological unit or is a subtype of CRS type 1 or 3.

• MeSH
• analýza rozptylu MeSH
• biologické markery krev   MeSH
• časové faktory MeSH
• kardiorenální syndrom diagnóza   krev   MeSH
• klinické laboratorní techniky metody   přístrojové vybavení   MeSH
• lidé MeSH
• renální insuficience diagnóza   krev   MeSH
• senioři MeSH
• sepse * komplikace   MeSH
• srdeční selhání * diagnóza   krev   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• klinická studie MeSH

Antisense transcripts play an important role in generating regulatory non-coding RNAs but whether these transcripts are also translated to generate functional peptides remains poorly understood. In this study, RNA sequencing and six-frame database generation were combined with mass spectrometry analysis of peptides isolated from polysomes to identify Nascent Pioneer Translation Products (Na-PTPs) originating from alternative reading frames of bi-directional transcripts. Two Na-PTP originating peptides derived from antisense strands stimulated CD8+ T cell proliferation when presented to peripheral blood mononuclear cells (PBMCs) from nine healthy donors. Importantly, an antigenic peptide derived from the reverse strand of two cDNA constructs was presented on MHC-I molecules and induced CD8+ T cell activation. The results demonstrate that three-frame translation of bi-directional transcripts generates antigenic peptide substrates for the immune system. This discovery holds significance for understanding the origin of self-discriminating peptide substrates for the major histocompatibility class I (MHC-I) pathway and for enhancing immune-based therapies against infected or transformed cells.

• MeSH
• aktivace lymfocytů imunologie   MeSH
• antisense RNA * genetika   imunologie   MeSH
• CD8-pozitivní T-lymfocyty * imunologie   MeSH
• leukocyty mononukleární imunologie   MeSH
• lidé MeSH
• MHC antigeny I. třídy * imunologie   genetika   MeSH
• peptidy * imunologie   genetika   MeSH
• prezentace antigenu MeSH
• proteosyntéza * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

This paper describes a compact video-ophthalmoscope (VO) designed for capturing retinal video sequences of the optic nerve head (ONH) under flicker light stimulation. The device uses an OLED display and a fiber optic-coupled LED light source, enabling high-frame-rate video at low illumination intensity (12 μW/cm2). Retinal responses were recorded in 10 healthy subjects during flicker light exposure with a pupil irradiance of 2 μW/cm2. Following 20 s of stimulation, all subjects displayed changes in retinal reflectance and pulsation attenuation, linked to blood flow and volume variations. These findings suggest that increased blood volume leads to decreased retinal reflectance. Temporal analysis confirmed the ability to capture flicker-induced retinal reflectance changes, indicating its potential for spatial and temporal analysis. Overall, this device offers a portable approach for investigating dynamic retinal responses to light stimuli, which can aid the diagnosis of retinal diseases like diabetic retinopathy, glaucoma, or neurodegenerative diseases affecting retinal blood circulation.

• MeSH
• audiovizuální záznam * přístrojové vybavení   MeSH
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• oftalmoskopy * MeSH
• retina * účinky záření   fyziologie   MeSH
• světelná stimulace * MeSH
• světlo * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Autosomal dominant craniometaphyseal dysplasia (AD-CMD) is a rare condition defined by the occurrence of progressive diffuse hyperostosis of cranial bones and abnormal metaphyseal widening of the tubular bones. ANKH is known to be the only gene associated with AD-CMD. We present a case of a toddler boy with macrodolichocephaly, asymmetry of the skull, wide bulging forehead, gingival hypertrophy and irregular teeth. Physical examination, X-ray and DNA analysis were performed. All exons and flanking intron regions of ANKH were amplified by PCR and directly sequenced using the Sanger method. X-ray images showed diffuse osteosclerosis in the area of facial skeleton and skull base. Limbs exhibited club-shaped enlargement of the distal metaphysis of the femur and the proximal metaphysis of the tibia were described. The DNA analysis showed that the patient is a heterozygous carrier of the known pathogenic in-frame deletion (rs121908406; ANKH:c.1122-4delCTC, p.Ser375del), which has already been described in patients with AD-CMD.

• MeSH
• hyperostóza MeSH
• hypertelorismus MeSH
• kojenec MeSH
• kraniofaciální abnormality genetika   diagnostické zobrazování   MeSH
• lidé MeSH
• proteiny přenášející fosfát * genetika   MeSH
• radiografie MeSH
• vývojové onemocnění kostí genetika   diagnostické zobrazování   diagnóza   MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

BACKGROUND AND OBJECTIVE: Stone size has traditionally been measured in one dimension. This is reflected in most of the literature and in the EAU guidelines. However, recent studies have shown that multidimensional measures provide better prediction of outcomes. METHODS: We performed a systematic review and meta-analysis of the prognostic accuracy of measures of stone size (PROSPERO reference CRD42022346967). We considered all studies reporting prognostic accuracy statistics on any intervention for kidney stones (extracorporeal shockwave lithotripsy [ESWL], ureterorenoscopy [URS], or percutaneous nephrolithotomy [PCNL]; Population) using multiplane measurements of stone burden (area in mm2 or volume in mm3; Intervention) in comparison to single-plane measurements of stone burden (size in mm; Intervention) for the study-defined stone-free rate (Outcome) in a PICO-framed question. We also assessed complication rates (overall and by Clavien-Dindo grade) and the operative time as secondary outcomes. Searches were made between 1970 and August 2023. We used the DeLong method to compare receiver operating characteristic (ROC) curves. KEY FINDINGS AND LIMITATIONS: Of 24 studies included in the review, 12 were eligible for comparative analysis with the DeLong test following meta-analysis of prognostic accuracy. For prediction of stone-free status, the area under the ROC curve (AUC) was significantly higher for stone volume than for stone size (0.71 vs 0.67; p < 0.001). Subanalyses confirmed this for ESWL and URS, but not for PCNL. For URS, the AUC was also significantly higher for stone area than for stone size (0.79 vs 0.77; p < 0.001). Throughout all analyses, there was no difference in AUC between stone area and stone volume. There was high risk of bias for all analyses apart from the URS subanalyses. CONCLUSIONS AND CLINICAL IMPLICATIONS: According to the limited data currently available, stone-free rates are predicted with significantly higher accuracy using multidimensional measures of stone burden in comparison to a single linear measurement. PATIENT SUMMARY: We reviewed different ways of measuring the size of stones in the kidney or urinary tract and compared their accuracy in predicting stone-free rates after treatment. We found that measurement of the stone area (2 dimensions) or stone volume (3 dimensions) is better than stone diameter (1 dimension) in predicting stone-free status after treatment.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Bisphenol A (BPA), a synthetic chemical widely used in the production of polycarbonate plastic and epoxy resins, has been associated with a variety of adverse effects in humans including metabolic, immunological, reproductive, and neurodevelopmental effects, raising concern about its health impact. In the EU, it has been classified as toxic to reproduction and as an endocrine disruptor and was thus included in the candidate list of substances of very high concern (SVHC). On this basis, its use has been banned or restricted in some products. As a consequence, industries turned to bisphenol alternatives, such as bisphenol S (BPS) and bisphenol F (BPF), which are now found in various consumer products, as well as in human matrices at a global scale. However, due to their toxicity, these two bisphenols are in the process of being regulated. Other BPA alternatives, whose potential toxicity remains largely unknown due to a knowledge gap, have also started to be used in manufacturing processes. The gradual restriction of the use of BPA underscores the importance of understanding the potential risks associated with its alternatives to avoid regrettable substitutions. This review aims to summarize the current knowledge on the potential hazards related to BPA alternatives prioritized by European Regulatory Agencies based on their regulatory relevance and selected to be studied under the European Partnership for the Assessment of Risks from Chemicals (PARC): BPE, BPAP, BPP, BPZ, BPS-MAE, and TCBPA. The focus is on data related to toxicokinetic, endocrine disruption, immunotoxicity, developmental neurotoxicity, and genotoxicity/carcinogenicity, which were considered the most relevant endpoints to assess the hazard related to those substances. The goal here is to identify the data gaps in BPA alternatives toxicology and hence formulate the future directions that will be taken in the frame of the PARC project, which seeks also to enhance chemical risk assessment methodologies using new approach methodologies (NAMs).

• MeSH
• benzhydrylové sloučeniny * chemie   toxicita   MeSH
• endokrinní disruptory * chemie   toxicita   MeSH
• hodnocení rizik metody   MeSH
• lidé MeSH
• sulfony toxicita   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Genetic factors are involved in the pathogenesis of familial and sporadic amyotrophic lateral sclerosis (ALS) and constitute a link to its association with frontotemporal dementia (FTD). Gene-targeted therapies for some forms of ALS (C9orf72, SOD1) have recently gained momentum. Genetic architecture in Czech ALS patients has not been comprehensively assessed so far. OBJECTIVE: We aimed to deliver pilot data on the genetic landscape of ALS in our country. METHODS: A cohort of patients with ALS (n = 88), recruited from two Czech Neuromuscular Centers, was assessed for hexanucleotide repeat expansion (HRE) in C9orf72 and also for genetic variations in other 36 ALS-linked genes via next-generation sequencing (NGS). Nine patients (10.1%) had a familial ALS. Further, we analyzed two subgroups of sporadic patients - with concomitant FTD (n = 7) and with young-onset of the disease (n = 22). RESULTS: We detected the pathogenic HRE in C9orf72 in 12 patients (13.5%) and three other pathogenic variants in FUS, TARDBP and TBK1, each in one patient. Additional 7 novel and 9 rare known variants with uncertain causal significance have been detected in 15 patients. Three sporadic patients with FTD (42.9%) were harbouring a pathogenic variant (all HRE in C9orf72). Surprisingly, none of the young-onset sporadic patients harboured a pathogenic variant and we detected no pathogenic SOD1 variant in our cohort. CONCLUSION: Our findings resemble those from other European populations, with the highest prevalence of HRE in the C9orf72 gene. Further, our findings suggest a possibility of a missing genetic variability among young-onset patients.

• MeSH
• amyotrofická laterální skleróza * genetika   MeSH
• DNA vazebné proteiny genetika   MeSH
• dospělí MeSH
• expanze repetic DNA * MeSH
• frontotemporální demence * genetika   MeSH
• genetická predispozice k nemoci MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• protein C9orf72 * genetika   MeSH
• protein FUS vázající RNA genetika   MeSH
• protein-serin-threoninkinasy genetika   MeSH
• senioři MeSH
• věk při počátku nemoci MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Policy development and implementation are key to improving access to Assistive Technology (AT). In this paper, we describe a strength-based framework for doing this at national level. We used an action research approach, with the United Nations Conventions on the Rights of Persons with Disability (UNCRPD) as the primary frame of reference. Primary data were collected using the World Health Organisation's rapid Assistive Technology Assessment (rATA). We describe the process of applying our emergent framework and how our findings support it. We identified seven guiding principles for effective policy process: Participatory, Resource aware, Outcomes focused, Collaborative, Evidence-informed, supporting good practices, and System strengthening - which can be summarized by the acronym PROCESS. Five crucial building blocks for effective AT policy development emerged: Identification of the assistive technology ecosystem, Demography of disability and AT use, Evaluation of inclusion and participation in existing policy, Alignment with UNCRPD and Sustainable Development Goals (SDGs), and Locality of implementation - which can be summarized with the acronym IDEAL. The IDEAL PROCESS incorporates key content building blocks and core process principles, constituting a systematic framework for guiding the development of context sensitive AT policy and a strength-based pathway to improving access AT.

• MeSH
• lidé MeSH
• pomůcky pro sebeobsluhu * MeSH
• postižení * rehabilitace   MeSH
• vytváření politiky MeSH
• zdravotní politika MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH