Publikace se zaměřuje na farmakorezistenci u schizofrenie, deprese, úzkosti a obsedantně-kompulzivní poruchy. Určeno odborné veřejnosti.

• MeSH
• duševní poruchy MeSH
• léková rezistence MeSH
• psychotropní léky MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Psychiatrie
• NLK Obory
• psychiatrie
• psychofarmakologie

Cardiac involvement (CI) in phosphomannomutase 2-congenital disorders of glycosylation (PMM2-CDG) is part of the multisystemic presentation contributing to high mortality rates. The most common cardiac manifestations are pericardial effusion, cardiomyopathy, and structural heart defects. A genotype-phenotype correlation with organ involvement has not yet been described. We analyzed clinical, biochemical, and molecular genetic data of 222 patients from eight European centers and characterized the natural course of patients with CI. Fifty-seven patients (45 children) presented with CI, of whom 24 died (median age 21 months, standard deviation 49.8). Pericardial effusion was the most frequent manifestation (55.4%), occurring mostly within the first 6 months of life. The most common pathogenic variants in patients with CI were p.(Arg141His) in 74%, followed by p.(Val231Met) in 36%, which is 3.5 times higher than in PMM2-CDG patients without CI (p < 0.0001). Twenty-one out of 36 patients with p.(Val231Met) had CI; among them, 15 died, compared to 33 out of 166 patients without p.(Val231Met) who had CI (p < 0.0001). Nine out of 33 patients died (p = 0.0015), indicating greater clinical severity. Furthermore, the p.(Val231Met) variant is predominant in Eastern Europe, suggesting a founder effect. Cardiac complications in PMM2-CDG patients are common and serious. The variant p.(Val231Met) profoundly influences the extent of CI and mortality rates. Therefore, we recommend cardiac surveillance be included in the follow-up protocols for PMM2-CDG.

• MeSH
• dítě MeSH
• fenotyp * MeSH
• fosfotransferasy (fosfomutasy) * genetika   nedostatek   MeSH
• genetické asociační studie MeSH
• kardiomyopatie genetika   MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mutace MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• stupeň závažnosti nemoci MeSH
• vrozené poruchy glykosylace * genetika   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH

BACKGROUND: Patients with severe aortic stenosis present frequently (∼50%) with concomitant obstructive coronary artery disease. Current guidelines recommend combined surgical aortic valve replacement (SAVR) and coronary artery bypass grafting (CABG) as the preferred treatment. Transcatheter aortic valve implantation (TAVI) and fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) represent a valid treatment alternative. We aimed to test the non-inferiority of FFR-guided PCI plus TAVI versus SAVR plus CABG in patients with severe aortic stenosis and complex coronary artery disease. METHODS: This international, multicentre, prospective, open-label, non-inferiority, randomised controlled trial was conducted at 18 tertiary medical centres across Europe. Patients (aged ≥70 years) with severe aortic stenosis and complex coronary artery disease, deemed feasible for percutaneous or surgical treatment according to the on-site Heart Team, were randomly assigned (1:1) to FFR-guided PCI plus TAVI or SAVR plus CABG according to a computer-generated sequence with random permuted blocks sizes stratified by site. The primary endpoint was a composite of all-cause mortality, myocardial infarction, disabling stroke, clinically driven target-vessel revascularisation, valve reintervention, and life-threatening or disabling bleeding at 1 year post-treatment. The trial was powered for non-inferiority (with a margin of 15%) and if met, for superiority. The primary and safety analyses were done per an intention-to-treat principle. This trial is registered with ClinicalTrials.gov (NCT03424941) and is closed. FINDINGS: Between May 31, 2018, and June 30, 2023, 172 patients were enrolled, of whom 91 were assigned to the FFR-guided PCI plus TAVI group and 81 to the SAVR plus CABG group. The mean age of patients was 76·5 years (SD 3·9). 118 (69%) of 172 patients were male and 54 (31%) patients were female. FFR-guided PCI plus TAVI resulted in favourable outcomes for the primary endpoint (four [4%] of 91 patients) versus SAVR plus CABG (17 [23%] of 77 patients; risk difference -18·5 [90% CI -27·8 to -9·7]), which was below the 15% prespecified non-inferiority margin (pnon-inferiority<0·001). FFR-guided PCI plus TAVI was superior to SAVR plus CABG (hazard ratio 0·17 [95% CI 0·06-0·51]; psuperiority<0·001), which was driven mainly by all-cause mortality (none [0%] of 91 patients vs seven (10%) of 77 patients; p=0·0025) and life-threatening bleeding (two [2%] vs nine [12%]; p=0·010). INTERPRETATION: The TCW trial is the first trial to compare percutaneous treatment versus surgical treatment in patients with severe aortic stenosis and complex coronary artery disease, showing favourable primary endpoint and mortality outcomes with percutaneous treatment. FUNDING: Isala Heart Centre and Medtronic.

• MeSH
• aortální stenóza * chirurgie   komplikace   MeSH
• chirurgická náhrada chlopně metody   MeSH
• frakční průtoková rezerva myokardu * MeSH
• koronární angioplastika * metody   MeSH
• koronární bypass * metody   MeSH
• lidé MeSH
• nemoci koronárních tepen * chirurgie   komplikace   terapie   MeSH
• prospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• transkatetrální implantace aortální chlopně * metody   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• hodnocení ekvivalence MeSH
• multicentrická studie MeSH
• srovnávací studie MeSH

• MeSH
• buněčný tracking metody   MeSH
• fluor chemie   MeSH
• fluorokarbony MeSH
• kontrastní látky MeSH
• pohyb buněk MeSH
• zobrazování fluorovou magnetickou rezonancí MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• radiologie, nukleární medicína a zobrazovací metody
• NLK Publikační typ
• kolektivní monografie

BACKGROUND: Vaccination against 5 prominent meningococcal serogroups (A/B/C/W/Y) is necessary for broad disease protection. We report immunopersistence through 4 years after a 2-dose (6-month interval) pentavalent MenABCWY primary vaccine series and safety and immunogenicity of a booster administered 4 years after primary vaccination. METHODS: This randomized, active-controlled, observer-blinded study was conducted in the United States and Europe. In stage 1, healthy MenACWY vaccine-naive or -experienced 10- to 25-year-olds were randomized 1:2 to receive MenABCWY and placebo or MenB-fHbp and MenACWY-CRM. Eligible participants were randomly selected to participate in stage 2, which was an open-label immunopersistence and booster extension. Immunogenicity was assessed through serum bactericidal antibody using human complement (hSBA) assays with serogroups A/C/W/Y (MenA/C/W/Y) and 4 primary serogroup B (MenB) test strains. Immunogenicity endpoints included hSBA seroprotection rates through 48 months after primary vaccination and 1 month after the booster. Safety endpoints included booster reactogenicity events and adverse events (AEs). RESULTS: Of 1379 eligible participants, 353 entered stage 2; 242 completed the 48-month blood draw after primary vaccination and 240 completed the booster vaccination phase. MenA/C/W/Y seroprotection rates remained high for 4 years following a 2-dose MenABCWY primary series (MenACWY-naive, 62.0 %-100.0 %; MenACWY-experienced, 98.7 %-100.0 %) and trended higher than those after a single MenACWY-CRM dose (MenACWY-naive, 38.1 %-95.2 %; MenACWY-experienced, 89.7 %-100.0 %). Corresponding seroprotection rates against MenB remained stable and generally higher than baseline (MenABCWY, 18.2 %-36.6 %; MenB-fHbp, 16.2 %-31.9 % across strains). Following a booster, seroprotection rates against all 5 serogroups were ≥ 93.8 % across groups. Most booster dose reactogenicity events were mild or moderate in severity, and AEs were infrequent. CONCLUSIONS: Immune responses remained high for MenA/C/W/Y and above baseline for MenB through 4 years after the MenABCWY primary series, with robust responses for all 5 serogroups observed following a booster. The MenABCWY booster had an acceptable safety and tolerability profile consistent with the primary series. NCT03135834.

• MeSH
• dítě MeSH
• dospělí MeSH
• imunogenicita vakcíny MeSH
• komplement imunologie   MeSH
• lidé MeSH
• meningokokové infekce * prevence a kontrola   imunologie   MeSH
• meningokokové vakcíny * imunologie   škodlivé účinky   aplikace a dávkování   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• Neisseria meningitidis imunologie   MeSH
• protilátky bakteriální * krev   MeSH
• sekundární imunizace * metody   MeSH
• séroskupina MeSH
• vakcíny konjugované imunologie   aplikace a dávkování   škodlivé účinky   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Evropa MeSH
• Spojené státy americké MeSH

BACKGROUND: Renal cell carcinoma (RCC) is a disease typified by anomalies in cell metabolism. The function of mitochondria, including subunits of mitochondrial respiratory complex II (CII), in particular SDHB, are often affected. Here we investigated the state and function of CII in RCC patients. METHODS: We evaluated tumour tissue as well as the adjacent healthy kidney tissue of 78 patients with RCC of different histotypes, focusing on their mitochondrial function. As clear cell RCC (ccRCC) is by far the most frequent histotype of RCC, we focused on these patients, which were grouped based on the pathological WHO/ISUP grading system to low- and high-grade patients, indicative of prognosis. We also evaluated mitochondrial function in organoids derived from tumour tissue of 7 patients. RESULTS: ccRCC tumours were characterized by mutated von Hippel-Lindau gene and high expression of carbonic anhydrase IX. We found low levels of mitochondrial DNA, protein and function, together with CII function in ccRCC tumour tissue, but not in other RCC types and non-tumour tissues. Mitochondrial content increased in high-grade tumours, while the function of CII remained low. Tumour organoids from ccRCC patients recapitulated molecular characteristics of RCC tissue. CONCLUSIONS: Our findings suggest that the state of CII, epitomized by its assembly and SDHB levels, deteriorates with the progressive severity of ccRCC. These observations hold the potential for stratification of patients with worse prognosis and may guide the exploration of targeted therapeutic interventions.

• MeSH
• antigeny nádorové MeSH
• dospělí MeSH
• karboanhydrasa IX metabolismus   genetika   MeSH
• karcinom z renálních buněk * patologie   metabolismus   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mitochondriální DNA genetika   metabolismus   MeSH
• mitochondrie * metabolismus   patologie   genetika   MeSH
• mutace MeSH
• nádorový supresorový protein VHL genetika   metabolismus   MeSH
• nádory ledvin * patologie   metabolismus   genetika   MeSH
• respirační komplex II * metabolismus   genetika   MeSH
• senioři MeSH
• sukcinátdehydrogenasa genetika   metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: This study aims to explore the lasting effects of stress experienced by pregnant women during World War II (WWII) on body and head measurements of their adult daughters. METHODS: The research sample consists of 336 female university students born in Poland between 1925 and 1951. The data include body measurements and socioeconomic information (parental occupation and number of siblings) acquired from questionnaires collected between the 1950s and 1970s. Student's t-test, Mann-Whitney test and Analysis of Variance were used to analyze differences in body measurements between groups of women born before and during the war, as well as the possible influences of socioeconomic variables. RESULTS: The mean measurements of body height, symphysion height, and waist circumference were lower in women conceived and born during the war compared to those born in the pre-war period. In contrast, the mean measurements of biacromial (shoulder) width, trunk length, and three head dimensions were higher in women conceived and born during the war. Additionally, the number of siblings appeared to be a significant factor that may have influenced the body measurements of women in both groups. For instance, a higher number of living siblings, particularly sisters, was associated with reduced body dimensions, such as body height and waist circumference, while a greater number of deceased siblings was linked to an increase in certain body dimensions. CONCLUSION: The results suggest that war-related prenatal conditions may have influenced the postnatal growth and development of women conceived and born during the war. Notably, the direction of these changes varied, which indicates that the growth response to the war-related conditions was a complex adaptation, reflecting both positive and negative changes in different body parts, rather than a uniform pattern of growth suppression.

• MeSH
• 2. světová válka * MeSH
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• psychický stres MeSH
• socioekonomické faktory MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Polsko MeSH

A tubular microdialysis probe is made from polysulfone hollow fibre for human haemodialysis, which has an inner diameter of 200 μm and a thickness of 20 μm. Milk is deposited to the outer surface of the hollow fibre and allowed to dry to form a dry sample. The tubular probe is then connected to the syringe pump and microdialysis of the dry sample into 0.5 mol/L HCl as acceptor is performed. 2.5 μL of microdialysate is obtained and analyzed for inorganic cations by capillary electrophoresis with contactless conductivity detection. Baseline separation of NH4+, K+, Ca2+, Na+, Mg2+, Li+ is achieved in 5.5 mol/L acetic acid as background electrolyte using a fused silica capillary with inner diameter of 25 μm and length of 31.5 cm. The reproducibility of dry sample microdialysis including CE analysis for peak area ranges from 2.4 to 3.9 % after normalization to Li+ as internal standard.

• MeSH
• elektroforéza kapilární * přístrojové vybavení   metody   MeSH
• kationty * analýza   MeSH
• mikrodialýza * přístrojové vybavení   metody   MeSH
• mléko * chemie   MeSH
• skot MeSH
• zvířata MeSH
• Check Tag
• skot MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH

PURPOSE: The aim of this study was to develop a simple, robust, and easy-to-use calibration procedure for correcting misalignments in rosette MRI k-space sampling, with the objective of producing images with minimal artifacts. METHODS: Quick automatic calibration scans were proposed for the beginning of the measurement to collect information on the time course of the rosette acquisition trajectory. A two-parameter model was devised to match the measured time-varying readout gradient delays and approximate the actual rosette sampling trajectory. The proposed calibration approach was implemented, and performance assessment was conducted on both phantoms and human subjects. RESULTS: The fidelity of phantom and in vivo images exhibited significant improvement compared with uncorrected rosette data. The two-parameter calibration approach also demonstrated enhanced precision and reliability, as evidenced by quantitative T2*$$ {\mathrm{T}}_2^{\ast } $$ relaxometry analyses. CONCLUSION: Adequate correction of data sampling is a crucial step in rosette MRI. The presented experimental results underscore the robustness, ease of implementation, and suitability for routine experimental use of the proposed two-parameter rosette trajectory calibration approach.

• MeSH
• algoritmy * MeSH
• artefakty * MeSH
• fantomy radiodiagnostické * MeSH
• kalibrace MeSH
• lidé MeSH
• magnetická rezonanční tomografie * metody   MeSH
• mozek diagnostické zobrazování   MeSH
• počítačové zpracování obrazu * metody   MeSH
• reprodukovatelnost výsledků MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Despite the lower virulence of current SARS-CoV-2 variants and high rates of vaccinated and previously infected subjects, COVID-19 remains a persistent threat in kidney transplant recipients (KTRs). This study evaluated the parameters of anti-SARS-CoV-2 antibody production in 120 KTRs. The production of neutralizing antibodies in KTRs, following booster vaccination with the mRNA vaccine BNT162b2, was significantly decreased and their decline was faster than in healthy subjects. Factors predisposing to the downregulation of anti-SARS-CoV-2 neutralizing antibodies included age, lower estimated glomerular filtration rate, and a full dose of mycophenolate mofetil. Neutralizing antibodies correlated with those targeting the SARS-CoV-2 receptor binding domain (RBD), SARS-CoV-2 Spike trimmer, total SARS-CoV-2 S1 protein, as well as with antibodies to the deadly SARS-CoV-1 virus. No cross-reactivity was found with antibodies against seasonal coronaviruses. KTRs exhibited lower postvaccination production of neutralizing antibodies against SARS-CoV-2; however, the specificity of their humoral response did not differ compared to healthy subjects.

• MeSH
• COVID-19 * imunologie   prevence a kontrola   MeSH
• dospělí MeSH
• glykoprotein S, koronavirus imunologie   MeSH
• humorální imunita MeSH
• lidé středního věku MeSH
• lidé MeSH
• neutralizující protilátky * krev   imunologie   MeSH
• příjemce transplantátu * MeSH
• protilátky virové * krev   imunologie   MeSH
• SARS-CoV-2 * imunologie   MeSH
• sekundární imunizace MeSH
• senioři MeSH
• transplantace ledvin * škodlivé účinky   MeSH
• vakcína BNT162 imunologie   aplikace a dávkování   MeSH
• vakcíny proti COVID-19 imunologie   aplikace a dávkování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH