The effective treatment of inflammatory diseases, particularly their chronic forms, is a key task of modern medicine. Herein, we report the synthesis and evaluation of biocompatible polymer conjugates based on N-2-(hydroxypropyl)methacrylamide copolymers enabling the controlled release of acetylsalicylic acid (ASA)-based anti-inflammatory drugs under specific stimuli. All polymer nanotherapeutics were proposed as water-soluble drug delivery systems with a hydrodynamic size below 10 nm ensuring suitability for the parenteral application and preventing opsonization by the reticuloendothelial system. The nanotherapeutics bearing an ester-bound ASA exhibited long-term release of the ASA/salicylic acid mixture, while the nanotherapeutics carrying salicylic acid hydrazide (SAH) ensured the selective release of SAH in the acidic inflammatory environment thanks to the pH-sensitive hydrazone bond between the polymer carrier and SAH. The ASA- and SAH-containing nanotherapeutics inhibited both cyclooxygenase isoforms and/or the production of pro-inflammatory mediators. Thanks to their favorable design, they can preferentially accumulate in the inflamed tissue, resulting in reduced side effects and lower dosage, and thus more effective and safer treatment.

• MeSH
• akrylamidy chemie   farmakologie   aplikace a dávkování   MeSH
• antiflogistika farmakologie   aplikace a dávkování   chemie   MeSH
• Aspirin * aplikace a dávkování   farmakologie   chemie   MeSH
• cyklooxygenasy metabolismus   MeSH
• inhibitory cyklooxygenasy farmakologie   aplikace a dávkování   chemie   MeSH
• léky s prodlouženým účinkem * MeSH
• mediátory zánětu metabolismus   MeSH
• myši MeSH
• nanočástice * chemie   MeSH
• nosiče léků chemie   MeSH
• polymery * chemie   aplikace a dávkování   MeSH
• uvolňování léčiv MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND AND PURPOSE: Intraarterial thrombolysis as an adjunct to mechanical thrombectomy is increasingly being considered to enhance reperfusion in acute ischemic stroke patients. Intraarterial thrombolysis may increase the risk of post-thrombectomy intracerebral hemorrhage (ICH) in certain patient subgroups. METHODS: We analyzed acute ischemic stroke patients treated with mechanical thrombectomy in a multicenter registry. The occurrence of any (asymptomatic and symptomatic) post-thrombectomy ICH was ascertained using standard definition requiring serial neurological examinations and computed tomographic scans acquired within 48 hours of the thrombectomy. We determined the risk of ICH in subgroups defined by clinical characteristics and the use of intravenous (IV) thrombolysis. RESULTS: A total of 146 (7.5%) patients received intraarterial thrombolysis among 1953 acute ischemic stroke patients who underwent mechanical thrombectomy. The proportion of patients who developed any ICH was 26 (17.8%) and 510 (28.2%) among patients who were and were not treated with intraarterial thrombolysis, respectively (p = .006). The proportion of patients who developed symptomatic ICH was 4 (2.7%) and 30 (1.7%) among patients who were and were not treated with intraarterial thrombolysis, respectively (p = .34). Among patients who received IV thrombolysis (n = 1042), the proportion of patients who developed any ICH was 9 (16.7%) and 294 (30.7%) among patients who were and were not treated with intraarterial thrombolysis, respectively (p = .028). The risk was not different in strata defined by age, gender, location of occlusion, preprocedure National Institutes of Health Stroke Scale score, time interval between symptom onset and thrombectomy, Alberta Stroke Program Early CT Score, systolic blood pressure, and serum glucose concentrations. CONCLUSIONS: In patients undergoing mechanical thrombectomy, the risk of any ICH and symptomatic ICH was not increased with intraarterial thrombolysis, including in those who had already received IV thrombolytics.

• MeSH
• cerebrální krvácení * diagnostické zobrazování   MeSH
• fibrinolytika * aplikace a dávkování   škodlivé účinky   MeSH
• ischemická cévní mozková příhoda * diagnostické zobrazování   chirurgie   MeSH
• kombinovaná terapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• registrace MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• trombektomie * metody   MeSH
• trombolytická terapie * škodlivé účinky   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Ballet class represents a considerable portion of professional ballet training, yet the external training load demands associated with class-and particularly the jumping demands-have not been investigated. The purpose of this study was to measure the jumping demands of ballet class by sex and rank. Eleven female and eight male elite professional ballet dancers participated in 109 ballet classes taught by 12 different teachers. Jump counts and jump heights were measured during each class. A Poisson generalized linear mixed effects model was used to examine the differences in jump counts between sexes and ranks. Greater jump counts were observed during class in men than in women (153, 95% confidence intervals [CI] [137, 170] vs. 119, 95% CI [109, 131], p = 0.004) and in junior ranking dancers compared with senior ranking dancers (151, 95% CI [138, 165] vs. 121, 95% CI [108, 135], p = 0.006). Female junior and senior ranking dancers jumped at rates of 9.2 ± 2.6 and 8.6 ± 4.7 jumps·min-1 , respectively, while male junior and senior ranking dancers jumped at rates of 9.1 ± 2.6 and 8.7 ± 2.6 jumps·min-1 , respectively. Across all classes, 73% of jumps observed were below 50% of maximum double-legged countermovement jump height. Unlike rehearsals and performances, class offers dancers an opportunity to self-regulate load, and as such, are a useful session to manage jump load, and facilitate gradual return-to-dance pathways. Communication between health care and artistic staff is essential to facilitate load management during class.

• MeSH
• lidé MeSH
• tanec * fyziologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: A comparison of fusion rates and clinical outcomes of instrumented transforaminal interbody fusion (TLIF) between polyetheretherketone (PEEK) and titanium-coated PEEK (Ti-PEEK) cages is not well documented. METHODS: A single-centre, prospective, randomised study included patients who underwent one-level TLIF between L3-S1 segments. Patients were randomised into one of two groups: TLIF surgery with the PEEK cage and TLIF surgery with the Ti-PEEK cage. Clinical results were measured. All patients were assessed by repeated X-rays and 3D CT scans. Cage integration was assessed using a modified Bridwell classification. The impact of obesity and smoking on fusion quality was also analysed. Patients in both groups were followed up for 2 years. RESULTS: Altogether 87 patients were included in the study: of these 87 patients, 81 (93.1%) completed the 2-year follow-up. A significant improvement in clinical outcome was found in the two measurements scales in both groups (RM: p = 0.257, VAS: p = 0.229). There was an increase in CobbS and CobbL angle in both groups (p = 0.172 for CobbS and p = 0.403for CobbL). Bony fusion was achieved in 37 of 40 (92.5%) patients in the TiPEEK group and 35 of 41 (85.4%) in the PEEK group (p = 0.157). Cage subsided in 2 of 40 patients (5%) in the TiPEEK group and 11 of 41 (26.8%) in the PEEK group (p = 0.007). Body mass index > 30 and smoking were not predictive factors of bony fusion achievement. CONCLUSION: There is no significant advantage of TiPEEK cages over PEEK cages in clinical outcome and fusion rate 2 years after surgery.

• MeSH
• bederní obratle chirurgie   MeSH
• benzofenony * MeSH
• fúze páteře * metody   MeSH
• ketony MeSH
• lidé MeSH
• polyethylenglykoly MeSH
• polymery * MeSH
• prospektivní studie MeSH
• titan * MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

Presence of minimal residual disease (MRD), detected by flow cytometry, is an important prognostic biomarker in the management of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, data-analysis remains mainly expert-dependent. In this study, we designed and validated an Automated Gating & Identification (AGI) tool for MRD analysis in BCP-ALL patients using the two tubes of the EuroFlow 8-color MRD panel. The accuracy, repeatability, and reproducibility of the AGI tool was validated in a multicenter study using bone marrow follow-up samples from 174 BCP-ALL patients, stained with the EuroFlow BCP-ALL MRD panel. In these patients, MRD was assessed both by manual analysis and by AGI tool supported analysis. Comparison of MRD levels obtained between both approaches showed a concordance rate of 83%, with comparable concordances between MRD tubes (tube 1, 2 or both), treatment received (chemotherapy versus targeted therapy) and flow cytometers (FACSCanto versus FACSLyric). After review of discordant cases by additional experts, the concordance increased to 97%. Furthermore, the AGI tool showed excellent intra-expert concordance (100%) and good inter-expert concordance (90%). In addition to MRD levels, also percentages of normal cell populations showed excellent concordance between manual and AGI tool analysis. We conclude that the AGI tool may facilitate MRD analysis using the EuroFlow BCP-ALL MRD protocol and will contribute to a more standardized and objective MRD assessment. However, appropriate training is required for the correct analysis of MRD data.

• MeSH
• dítě MeSH
• dospělí MeSH
• imunofenotypizace metody   MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• pre-B-buněčná leukemie * patologie   diagnóza   MeSH
• předškolní dítě MeSH
• průtoková cytometrie * metody   MeSH
• reprodukovatelnost výsledků MeSH
• reziduální nádor * patologie   diagnóza   MeSH
• senioři MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Background/Objectives: PET imaging of bacterial infection could potentially provide added benefits for patient care through non-invasive means. [68Ga]Ga-desferrioxamine B-a radiolabelled siderophore-shows specific uptake by human-pathogenic bacteria like Staphylococcus aureus or Pseudomonas aeruginosa and sufficient serum stability for clinical application. In this report, we present data for automated production of [68Ga]Ga-desferrioxamine B on two different cassette-based synthesis modules (Modular-Lab PharmTracer and GRP 3V) utilising commercially obtainable cassettes together with a licensed 68Ge/68Ga radionuclide generator. Methods: Quality control, including the determination of radiochemical purity, as well as a system suitability test, was set up via RP-HPLC on a C18 column. The two described production processes use an acetic acid/acetate buffer system with ascorbic acid as a radical scavenger for radiolabelling, yielding ready-to-use formulations with sufficient activity yield. Results: Batch data analysis demonstrated radiochemical purity of >95% by RP-HPLC combined with ITLC and excellent stability up to 2 h after synthesis. Specifications for routine production were set up and validated with four masterbatches for each synthesis module. Conclusions: Based on this study, an academic clinical trial for imaging of bacterial infection was initiated. Both described synthesis methods enable automated production of [68Ga]Ga-desferrioxamine B in-house with high reproducibility for clinical application.

• Publikační typ
• časopisecké články MeSH

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that affects the spine and sacroiliac joints. Early detection of axSpA is crucial to slow disease progression and maintain remission or low disease activity. However, current biomarkers are insufficient for diagnosing axSpA or distinguishing between its radiographic (r-axSpA) and non-radiographic (nr-axSpA) subsets. To address this, we conducted a study using miRNA profiling with massive parallel sequencing (MPS) and SmartChip qRT-PCR validation. The goal was to identify differentially expressed miRNAs in axSpA patients, specifically those subdiagnosed with nr-axSpA or r-axSpA. Disease activity was measured using C-reactive protein (CRP) and the Ankylosing Spondylitis Disease Activity Score (ASDAS). Radiographic assessments of the cervical and lumbar spine were performed at baseline and after two years. Out of the initial 432 miRNAs, 90 met the selection criteria, and 45 were validated out of which miR-1-3p was upregulated, whereas miR-1248 and miR-1246 were downregulated in axSpA patients. The expression of miR-1-3p correlated with interleukin (IL)-17 and tumour necrosis factor (TNF) levels, indicating its significant role in axSpA pathogenesis. Although specific miRNAs distinguishing disease subtypes or correlating with disease activity or spinal changes were not found, the study identified three dysregulated miRNAs in axSpA patients, with miR-1-3p linked to IL-17 and TNF, underscoring its pathogenetic significance. These findings could help improve the early detection and treatment of axSpA.

• Publikační typ
• časopisecké články MeSH

This state-of-the-art review aimed to synthesize evidence from various sex-stratified studies on aortic stenosis (AS), focusing on the difference in clinical presentation, anatomical characteristics, pathophysiology, and management of AS. In comparison to men, women with AS are present at later stages, are older, more symptomatic, frailer, and exhibit higher operative risk [Society of Thoracic Surgeons (STS) score]. Women tend to have smaller aortic valve (AV) areas and left ventricular (LV) outflow tract, leading to lower stroke volumes (SVs) than men and have a higher prevalence of paradoxical, low-flow, low-gradient AS. In women, chronic pressure overload due to AS results in concentric LV remodelling and hypertrophy, characterized by reduced LV cavities, higher filling pressures, lower wall stress, and more diastolic dysfunction. Conversely, men exhibit more dilated eccentric LV remodelling and hypertrophy. AVs in women are less calcified but more fibrotic. Moreover, women are often underdiagnosed, have severity underestimated, and experience delays or receive fewer referrals for AV replacement (AVR). However, women tend to benefit from transcatheter AVR (TAVR) with a long-term survival advantage over men, although the incidence of vascular complications and bleeding events in 30 days after TAVR is higher in women. Surgical AVR (SAVR) in women has high operative risk, is technically demanding and has poorer outcomes with increased mortality at 30 days compared to men. According to the STS score and EuroSCORE, the female sex itself is considered a risk factor for SAVR. Therefore, addressing sex-related disparities in AS and increasing awareness among physicians promises improved diagnosis and treatment, facilitating equitable care and the development of sex-specific personalized medicine.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Lung cancer is the leading cause of cancer-associated mortality worldwide. In the United Kingdom (UK), there has been a major reduction in smoking, the leading risk factor for lung cancer. Therefore, an up-to-date assessment of the trends of lung cancer is required in the UK. This study aims to describe lung cancer burden and trends in terms of incidence, prevalence, and survival from 2000-2021, using two UK primary care databases. METHODS: We performed a population-based cohort study using the UK primary care Clinical Practice Research Datalink (CPRD) GOLD database, compared with CPRD Aurum. Participants aged 18+ years, with 1-year of prior data availability, were included. We estimated lung cancer incidence rates (IRs), period prevalence (PP), and survival at 1, 5 and 10 years after diagnosis using the Kaplan-Meier (KM) method. RESULTS: Overall, 11,388,117 participants, with 45,563 lung cancer cases were studied. The IR of lung cancer was 52.0 [95% confidence interval (CI): 51.5 to 52.5] per 100,000 person-years, with incidence increasing from 2000 to 2021. Females aged over 50 years of age showed increases in incidence over the study period, ranging from increases of 8 to 123 per 100,000 person-years, with the greatest increase in females aged 80-89 years. Alternatively, for males, only cohorts aged over 80 years showed increases in incidence over the study period. The highest IR was observed in people aged 80-89 years. PP in 2021 was 0.18%, with the largest rise seen in participants aged over 60 years. Median survival post-diagnosis increased from 6.6 months in those diagnosed between 2000-2004 to 10.0 months between 2015-2019. Both short and long-term survival was higher in younger cohorts, with 82.7% 1-year survival in those aged 18-29 years, versus 24.2% in the age 90+ years cohort. Throughout the study period, survival was longer in females, with a larger increase in survival over time than in males. CONCLUSIONS: The incidence and prevalence of lung cancer diagnoses in the UK have increased, especially in female and older populations, with a small increase in median survival. This study will enable future comparisons of overall disease burden, so the overall impact may be seen.

• Publikační typ
• časopisecké články MeSH

This study presents a graphene field-effect transistor (gFET) biosensor with dual detection capabilities for SARS-CoV-2: one RNA detection assay to confirm viral positivity and the other for nucleocapsid (N-)protein detection as a proxy for infectiousness of the patient. This technology can be rapidly adapted to emerging infectious diseases, making an essential tool to contain future pandemics. To detect viral RNA, the highly conserved E-gene of the virus was targeted, allowing for the determination of SARS-CoV-2 presence or absence using nasopharyngeal swab samples. For N-protein detection, specific antibodies were used. Tested on 213 clinical nasopharyngeal samples, the gFET biosensor showed good correlation with RT-PCR cycle threshold values, proving its high sensitivity in detecting SARS-CoV-2 RNA. Specificity was confirmed using 21 pre-pandemic samples positive for other respiratory viruses. The gFET biosensor had a limit of detection (LOD) for N-protein of 0.9 pM, establishing a foundation for the development of a sensitive tool for monitoring active viral infection. Results of gFET based N-protein detection corresponded to the results of virus culture in all 16 available clinical samples and thus it also proved its capability to serve as a proxy for infectivity. Overall, these findings support the potential of the gFET biosensor as a point-of-care device for rapid diagnosis of SARS-CoV-2 infection and indirect assessment of infectiousness in patients, providing additional information for clinical and public health decision-making.

• MeSH
• biosenzitivní techniky * přístrojové vybavení   metody   MeSH
• COVID-19 * diagnóza   virologie   MeSH
• design vybavení MeSH
• elektronické tranzistory MeSH
• fosfoproteiny MeSH
• grafit * chemie   MeSH
• koronavirové nukleokapsidové proteiny izolace a purifikace   MeSH
• lidé MeSH
• limita detekce MeSH
• nazofarynx virologie   MeSH
• RNA virová * izolace a purifikace   analýza   MeSH
• SARS-CoV-2 * izolace a purifikace   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH