The aim of this study was to develop multifunctional magnetic poly(ε-caprolactone) (PCL) mats with antibacterial properties for bone tissue engineering and osteosarcoma prevention. To provide good dispersion of magnetic iron oxide nanoparticles (IONs), they were first grafted with PCL using a novel three-step approach. Then, a series of PCL-based mats containing a fixed amount of ION@PCL particles and an increasing content of ascorbic acid (AA) was prepared by electrospinning. AA is known for increasing osteoblast activity and suppressing osteosarcoma cells. Composites were characterized in terms of morphology, mechanical properties, hydrolytic stability, antibacterial performance, and biocompatibility. AA affected both the fiber diameter and the mechanical properties of the nanocomposites. All produced mats were nontoxic to rat bone marrow-derived mesenchymal cells; however, a composite with 5 wt.% of AA suppressed the initial proliferation of SAOS-2 osteoblast-like cells. Moreover, AA improved antibacterial properties against Staphylococcus aureus and Escherichia coli compared to PCL. Overall, these magnetic composites, reported for the very first time, can be used as scaffolds for both tissue regeneration and osteosarcoma prevention.
- MeSH
- antibakteriální látky chemie farmakologie MeSH
- Escherichia coli účinky léků MeSH
- kosti a kostní tkáň MeSH
- krysa rodu rattus MeSH
- kyselina askorbová * chemie farmakologie MeSH
- lidé MeSH
- magnetické nanočástice chemie MeSH
- nádorové buněčné linie MeSH
- nanokompozity chemie MeSH
- osteoblasty metabolismus cytologie MeSH
- osteosarkom patologie MeSH
- polyestery * chemie MeSH
- Staphylococcus aureus * účinky léků růst a vývoj MeSH
- testování materiálů MeSH
- tkáňové inženýrství * MeSH
- tkáňové podpůrné struktury chemie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The aim of the present study was to examine the effects of attentional focus instructions on acute changes in the transverse relaxation time (T2) of the femorotibial cartilage and in cartilage volume during repeated drop-jump landings. Ten healthy females (Mage = 20.4 ± 0.8 years) performed a drop landing task from a 50 cm high box over the course of 3 days (50 repetitions each day) across three attentional focus conditions: external focus (EF: focus on landing as soft as possible), internal focus (IF: focus on bending your knees when you land), and control (CON: no-focus instruction), which was counterbalanced across focus conditions. T2 mapping and the volume of femorotibial cartilage were determined from magnetic resonance imaging scans at 1.5 T for the dominant knee before and after completing the drop landings in each attentional focus condition per day. Results indicated a smaller change in cartilage T2 relaxation time and volumetry in the central load-bearing lateral cartilage under the EF, compared to IF and CON. Moreover, the change in T2 and cartilage volume was greater for lateral tibial cartilage as compared to femoral cartilage and was independent of attentional focus instructions. No significant acute quantitative changes were observed in the medial compartment. The peak vertical ground reaction force was found to be the lowest under the EF, compared to IF and CON. These findings suggest that external focus of attention may reduce cartilage load, potentially aiding in the control or management of cartilage injuries during landing in female athletes.
- MeSH
- biomechanika MeSH
- kloubní chrupavka * fyziologie diagnostické zobrazování MeSH
- kolenní kloub fyziologie MeSH
- lidé MeSH
- magnetická rezonanční tomografie * MeSH
- mladý dospělý MeSH
- plyometrická cvičení MeSH
- pozornost * fyziologie MeSH
- tibie fyziologie diagnostické zobrazování MeSH
- zatížení muskuloskeletálního systému * fyziologie MeSH
- Check Tag
- lidé MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND/AIM: Cemiplimab in patients with non-small cell lung cancer (NSCLC) with PD-L1 (programmed death ligand type 1) expression ≥50% showed a significant improved overall survival (OS) with increasing expression of PD-L1. To our knowledge there exist no similar data published for pembrolizumab regarding the increased OS in relation to the PD-L1 expression. Therefore, the objective of our study was to determine whether improvement in OS reflects increased expression levels of PD-L1 (≥50%) in patients with NSCLC. PATIENTS AND METHODS: Retrospective data from 9 Czech and 1 Polish comprehensive oncology Centers were used. All patients with stage IV NSCLC and PD-L1 expression ≥50% treated with pembrolizumab in daily practice were included. The groups of patients according to the expression of PD-L1 were determined as follows: PD-L1 50-59%, 60-69%, 70-79%, 80-89% and 90-100%. The log-rank test and the Cox regression model were used to compare survival between study groups. RESULTS: A total of 617 patients were included in the study. We did not observe a statistically significant difference in OS between groups of patients with different levels of PD-L1 expression in the pooled comparison (p=0.445). Furthermore, we did not observe a statistically significant difference even when comparing OS in patients with PD-L1expression of 50-59% (reference) with the group of other patients according to the level of expression of PD-L1 in the Cox regression model including the effect covariates. CONCLUSION: PD-L1 expression showed no significant effect on OS in patients with NSCLC with PD-L1≥50% treated with pembrolizumab.
- MeSH
- antigeny CD274 * metabolismus genetika MeSH
- dospělí MeSH
- humanizované monoklonální protilátky * terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádorové biomarkery metabolismus MeSH
- nádory plic * farmakoterapie mortalita metabolismus patologie genetika MeSH
- nemalobuněčný karcinom plic * farmakoterapie mortalita metabolismus patologie genetika MeSH
- prognóza MeSH
- protinádorové látky imunologicky aktivní terapeutické užití MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- staging nádorů MeSH
- výsledek terapie 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
Since the emergence of SARS-CoV-2, mutations in all subunits of the RNA-dependent RNA polymerase (RdRp) of the virus have been repeatedly reported. Although RdRp represents a primary target for antiviral drugs, experimental studies exploring the phenotypic effect of these mutations have been limited. This study focuses on the phenotypic effects of substitutions in the three RdRp subunits: nsp7, nsp8, and nsp12, selected based on their occurrence rate and potential impact. We employed nano-differential scanning fluorimetry and microscale thermophoresis to examine the impact of these mutations on protein stability and RdRp complex assembly. We observed diverse impacts; notably, a single mutation in nsp8 significantly increased its stability as evidenced by a 13°C increase in melting temperature, whereas certain mutations in nsp7 and nsp8 reduced their binding affinity to nsp12 during RdRp complex formation. Using a fluorometric enzymatic assay, we assessed the overall effect on RNA polymerase activity. We found that most of the examined mutations altered the polymerase activity, often as a direct result of changes in stability or affinity to the other components of the RdRp complex. Intriguingly, a combination of nsp8 A21V and nsp12 P323L mutations resulted in a 50% increase in polymerase activity. To our knowledge, this is the first biochemical study to demonstrate the impact of amino acid mutations across all components constituting the RdRp complex in emerging SARS-CoV-2 subvariants.
- MeSH
- COVID-19 virologie MeSH
- koronavirová RNA-replikasa * genetika metabolismus chemie MeSH
- lidé MeSH
- mutace * MeSH
- RNA-dependentní RNA-polymerasa genetika chemie metabolismus MeSH
- SARS-CoV-2 * genetika enzymologie MeSH
- stabilita proteinů MeSH
- vazba proteinů MeSH
- virové nestrukturální proteiny * genetika chemie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Live donor kidney transplantation is considered the optimal choice for renal replacement therapy, providing established benefits, such as superior patient survival and improved quality of life. However, immunological challenges, including ABO blood group incompatibility and, particularly, donor-specific HLA antibodies, may impact long-term outcomes considerably or even prevent safe direct transplantation with the intended donor. METHODS: In this review, the authors discuss kidney paired donation (KPD) as a viable strategy to overcome immunological barriers to living donation through organ exchanges. We thereby lay special focus on the Czech-Austrian transnational KPD program. RESULTS: While the benefits of KPD programs are well established for adult recipients, recent data suggest that this may hold true also for pediatric patients. Complex algorithms, considering factors like the intricate patterns of HLA sensitization, play a pivotal role in predicting suitable matches, but for pediatric patients also non-immunological factors including age and weight match may play a role. As pool size proves crucial for program efficacy, several countries in Europe have now initiated transnational collaborations to maximize match rates. Among those, the Czech-Austrian transnational joint program, established in 2015 and now expanded to a cooperation with the Israel transplant program to further increase transplant rates, represents a successful example. CONCLUSION: KPD programs, with their innovative approaches and international partnerships, hold promise for enhancing outcomes and addressing the increasing demand for kidney transplantation.
- MeSH
- dítě MeSH
- dospělí MeSH
- HLA antigeny imunologie MeSH
- lidé MeSH
- transplantace ledvin * MeSH
- žijící dárci * MeSH
- získávání tkání a orgánů * MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Geografické názvy
- Česká republika MeSH
- Evropa MeSH
Intense sports training increases the frequency of menstrual cycle disorders. The aim of this study was to examine female taekwondo athletes (N = 33), active competitors, about their experience of menstruation, their physical ability to train and compete, as well as their mental ability. Another objective was to determine the connection between the frequent reduction in body weight before the competition and the occurrence of various menstrual disorders. The negative effects of menstruation that most affect the physical fitness of the participants are the physical symptoms of premenstrual syndrome and severe menstrual cramps, while the emotional symptoms of premenstrual syndrome most affect their mental preparation. Menstruation did not show a limiting effect on achieving sports success and participation in sports activities at full intensity. The participants predominantly do not miss training or competition due to menstruation. The highest level of limitation was manifested in sparring activities and explosiveness training. Even 87.8% of female athletes have the experience of intentional weight loss before the competition (from which 24.2% always), and 51.5% declare that constant change in body weight before competition affects the menstrual regularity. It is important to respect the individual characteristics of female athletes during menstruation and to encourage them to take care of the relationship between menstruation and sports activities. Training programs should include plans for determining body weight and long-term body composition.
Vitamin D is an important steroid hormone that exerts immunomodulatory actions, controls calcium and phosphate homeostasis, and significantly affects human health. Vitamin D deficiency is a global health problem, affecting approximately 60% of adults worldwide, and has been implicated in a range of different types of diseases, e.g., cancer. Vitamin D is involved in the regulation of cell proliferation, differentiation, energetic metabolism, and different types of cell death (e.g., apoptosis, autophagy, etc.). In physiological conditions, it is also able to modulate immune responses, angiogenesis, etc., which belongs to fundamental cancer-related processes. Vitamin D deficiency has been associated with an increased risk of some types of cancer, e.g., colorectal, breast, ovarian, prostate, pancreatic, etc. The role of vitamin D in cancer prevention, carcinogenesis, and cancer treatment is still under investigation and depends on the type of cancer. This review summarizes the role of vitamin D in all three above-mentioned aspects and discusses the mechanism of action and potential possibilities in cancer treatment.
- MeSH
- lidé MeSH
- nádory * prevence a kontrola farmakoterapie MeSH
- nedostatek vitaminu D komplikace MeSH
- potravní doplňky * MeSH
- vitamin D * terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The optimal treatment of oropharyngeal cancer (OPC) associated with human papillomavirus (HPV) is currently a subject of clinical research. This questionnaire study investigated current trends in the treatment of HPV-associated (HPV+) OPC in Slovakia with the incorporation of deintensification of oncological treatment into routine clinical practice outside of clinical trials. The Slovak Cooperative Head and Neck Cancer Group (SCHNCG) developed a questionnaire aimed at identifying trends in the oncological treatment of HPV+ OPC intended for all radiation oncology (RO) facilities in Slovakia. Specialists in the field of RO responded to general questions about the character of their individual institutions as well as to 4 theoretical clinical scenarios (case reports) regarding the treatment of HPV+ OPC, focusing primarily on the applied dose of radiotherapy (RT), the extent of target volumes, and the type of concurrent chemotherapy (CHT). The questionnaire study involved 35 RO specialists from 14 institutions in Slovakia. Regarding primary chemoradiotherapy (CRT) in T1N1M0 HPV+ OPC, 16 respondents (45.7%) would consider de-escalation of the RT dose to <70 Gy. In the case of postoperative RT in pT1pN1M0 HPV+ OPC with negative resection margins (R0) and absent extracapsular extension (ECE), 4 physicians (11.4%) would consider de-escalation of the RT dose to <60 Gy in the tumor bed area, while the majority of the treating specialists (n=19, 54.3%) would omit concurrent CHT. In the case of primary RT in elderly patient with T2N1M0 HPV+ OPC, the same number of physicians (n=16, 45.7%) would consider de-escalation of the RT dose to <70 Gy, and 14 respondents (40.0%) would completely omit CHT. In a high-risk patient with T2N3M0 HPV+ OPC with a complete response after 3 cycles of induction chemotherapy (iCHT), none of the respondents would indicate a reduction in the RT dose to the area of the original tumor and lymphadenopathy to <60 Gy. The doses and extent of irradiated volumes in the treatment of HPV+ OPC in Slovakia vary among different institutions. The tendency to de-escalate RT doses and reduce doses of concurrent systemic therapy in Slovakia is high and there was also an observed trend to reduce the extent of radiation treatment fields.
- MeSH
- chemoradioterapie * MeSH
- infekce papilomavirem * virologie komplikace terapie MeSH
- lidé MeSH
- lidské papilomaviry MeSH
- nádory orofaryngu * virologie terapie MeSH
- Papillomaviridae MeSH
- průzkumy a dotazníky MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Slovenská republika MeSH
BackgroundCOVID-19 remains a major infectious disease with substantial implications for individual and public health including the risk of a post-infection syndrome, long COVID. The continuous changes in dominant variants of SARS-CoV-2 necessitate a careful study of the effect of preventative strategies.AimWe aimed to estimate the effectiveness of post-vaccination, post-infection and hybrid immunity against severe cases requiring oxygen support caused by infections with SARS-CoV-2 variants BA1/2 and BA4/5+, and against long COVID in the infected population and their changes over time.MethodsWe used a Cox regression analysis with time-varying covariates and calendar time and logistic regression applied to national-level data from Czechia from December 2021 until August 2023.ResultsRecently boosted vaccination, post-infection and hybrid immunity provide significant protection against a severe course of COVID-19, while unboosted vaccination more than 10 months ago has a negligible protective effect. The post-vaccination immunity against the BA1/2 or BA4/5+ variants, especially based on the original vaccine types, appears to wane rapidly compared with post-infection and hybrid immunity. Once infected, however, previous immunity plays only a small protective role against long COVID.ConclusionVaccination remains an effective preventative measure against a severe course of COVID-19 but its effectiveness wanes over time thus highlighting the importance of booster doses. Once infected, vaccines may have a small protective effect against the development of long COVID.
- MeSH
- COVID-19 * imunologie prevence a kontrola epidemiologie MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- postakutní syndrom COVID-19 MeSH
- SARS-CoV-2 * imunologie MeSH
- sekundární imunizace MeSH
- senioři MeSH
- vakcinace 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
- Geografické názvy
- Česká republika MeSH
BACKGROUND: The highest mortality and morbidity worldwide is associated with atherosclerotic cardiovascular disease (ASCVD), which has in background both environmental and genetic risk factors. Apolipoprotein L1 (APOL1) variability influences the risk of ASCVD in Africans, but little is known about the APOL1 and ASCVD in other ethnic groups. METHODS: To investigate the role of APOL1 and ASCVD, we have genotyped four (rs13056427, rs136147, rs10854688 and rs9610473) APOL1 polymorphisms in a group of 1541 male patients with acute coronary syndrome (ACS) and 1338 male controls. RESULTS: Individual APOL1 polymorphisms were not associated with traditional CVD risk factors such as smoking, hypertension or diabetes prevalence, with BMI values or plasma lipid levels. Neither individual polymorphisms nor haplotypes were associated with an increased risk of ACS nor did they predict total or cardiovascular mortality over the 10.2 ± 3.9 years of follow-up. CONCLUSIONS: We conclude that APOL1 genetic variability has no major effect on risk of ACS in Caucasians.
- MeSH
- akutní koronární syndrom * genetika MeSH
- apolipoprotein L1 * genetika MeSH
- apolipoproteiny genetika MeSH
- běloši genetika MeSH
- genetická predispozice k nemoci MeSH
- haplotypy MeSH
- jednonukleotidový polymorfismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipoproteiny HDL genetika MeSH
- rizikové faktory MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH