BACKGROUND: Myelodysplastic neoplasms (MDS) are heterogeneous hematopoietic disorders characterized by ineffective hematopoiesis and genome instability. Mobilization of transposable elements (TEs) is an important source of genome instability leading to oncogenesis, whereas small PIWI-interacting RNAs (piRNAs) act as cellular suppressors of TEs. However, the roles of TEs and piRNAs in MDS remain unclear. METHODS: In this study, we examined TE and piRNA expression through parallel RNA and small RNA sequencing of CD34+ hematopoietic stem cells from MDS patients. RESULTS: Comparative analysis of TE and piRNA expression between MDS and control samples revealed several significantly dysregulated molecules. However, significant differences were observed between lower-risk MDS (LR-MDS) and higher-risk MDS (HR-MDS) samples. In HR-MDS, we found an inverse correlation between decreased TE levels and increased piRNA expression and these TE and piRNA levels were significantly associated with patient outcomes. Importantly, the upregulation of PIWIL2, which encodes a key factor in the piRNA pathway, independently predicted poor prognosis in MDS patients, underscoring its potential as a valuable disease marker. Furthermore, pathway analysis of RNA sequencing data revealed that dysregulation of the TE‒piRNA axis is linked to the suppression of processes related to energy metabolism, the cell cycle, and the immune response, suggesting that these disruptions significantly affect cellular activity. CONCLUSIONS: Our findings demonstrate the parallel dysregulation of TEs and piRNAs in HR-MDS patients, highlighting their potential role in MDS progression and indicating that the PIWIL2 level is a promising molecular marker for prognosis.
- Publication type
- Journal Article MeSH
Background/Objectives: Acute appendicitis (AA) is one of the most common causes of emergency department visits due to acute abdominal pain, with a lifetime risk of 7-8%. Managing AA presents significant challenges, particularly among vulnerable patient groups, due to its association with substantial morbidity and mortality. Methods: The EUPEMEN (European PErioperative MEdical Networking) project aims to optimize perioperative care for AA by developing multidisciplinary guidelines that integrate theoretical knowledge and clinical expertise from five European countries. This study presents the key elements of the EUPEMEN protocol, which focuses on reducing surgical stress, optimizing perioperative care, and enhancing postoperative recovery. Results: Through this standardized approach, the protocol aims to lower postoperative morbidity and mortality, shorten hospital stays, and improve overall patient outcomes. The recommendations are tailored to address the variability in clinical practice across Europe and are designed to be widely implementable in diverse healthcare settings. Conclusions: The conclusions drawn from this study highlight the potential for the EUPEMEN protocol to significantly improve perioperative care standards for AA, demonstrating its value as a practical, adaptable tool for clinicians.
- Publication type
- Journal Article MeSH
BACKGROUND: Surgical treatments of benign primary bone tumors of the femur face the challenge of limiting tissue damage and contamination while providing sufficient stabilization to avoid fracture. While no clear treatment guidelines exist, surgical treatment commonly consists of femoral fenestration and curettage with optional filling and plating of the defect. Mono- or bicortical plating of distal femoral defects aim to reduce fracture risk and have been shown to increase axial stability. However, it remains unclear whether plating increases torsional stability of the affected femur. QUESTIONS/PURPOSES: This biomechanical study aimed to determine how much additional stability can be achieved by mono- or bicortical plating of femoral defects after fenestration. The following hypotheses were investigated: 1. Preventive plating of distal femur bone defects enhances torsional stability when compared to femoral fenestration alone. 2. A condition close to the intact (nonpathological) bone can be achieved by bone plating. 3. Defect shape influences torsional stability. PATIENTS AND METHODS: Thiel embalmed human femora (n = 24) were left intact or subjected to the following surgical treatments (A) defect creation via fenestration, (B) defect with short monocortical plating, (C) defect with long bicortical plating. All femora were torsion tested in midstance position using pre-cycling and testing until failure. Quantitative computed tomography pre and post testing allowed bone mineral density calculation and crack path analysis. Finite element analysis provided insight into defect shape variations. RESULTS: Torsion experiments showed no relevant enhancement of torsional stability due to mono- or bicortical plating. There were no significant differences in maximum torque between unplated and plated femora with defect (defect: 35.38 ± 7.53 Nm, monocortical plating: 37.77 ± 9.82 Nm, bicortical plating: 50.27 ± 9.72 Nm, p > 0.05). Maximum torque for all treatment groups was significantly lower compared to intact femora (155-200 Nm, p < 0.001). Cracks originated predominantly from the proximal posterior corner of the defect and intersected with screw holes in plated femora. The influence of variations of the defect corner shapes had no significant influence on maximum torque and angle. CONCLUSION: This biomechanical study shows that mono- or bicortical plating is not an effective preventive treatment against torsional failure of femora with distal defects as the resulting maximum torque was drastically reduced compared to intact femora. Thus, the initial hypotheses have to be rejected. As habitual loading of the femur includes a combination of axial and torsional loading, the observed lack of prevention against torsional failure might help to explain the occurrence of fractures despite plating. Future research towards ameliorating clinical outcome should address the role of defect filling with bone cement or bone grafts regarding the improvement of torsional stability after primary bone tumor treatment in the femur.
- MeSH
- Biomechanical Phenomena MeSH
- Femur * surgery MeSH
- Bone Plates * MeSH
- Curettage MeSH
- Middle Aged MeSH
- Humans MeSH
- Mechanical Tests MeSH
- Aged MeSH
- Torsion, Mechanical MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
STATEMENT OF PROBLEM: Accurate implant placement is essential for the success of dental implants. This placement influences osseointegration and occlusal forces. The freehand technique, despite its cost-effectiveness and time efficiency, may result in significant angular deviations compared with guided implantation, but the effect of angular deviations on the stress-strain state of peri-implant bone is unclear. PURPOSE: The purpose of this finite element analysis (FEA) study was to examine the effects of angular deviations on stress-strain states in peri-implant bone. MATERIAL AND METHODS: Computational modeling was used to investigate 4 different configurations of dental implant positions, each with 3 angles of insertion. The model was developed using computed tomography images, and typical mastication forces were considered. Strains were analyzed using the mechanostat hypothesis. RESULTS: The location of the implant had a significant impact on bone strain intensity. An angular deviation of ±5 degrees from the planned inclination did not significantly affect cancellous bone strains, which primarily support the implant. However, it had a substantial effect on strains in the cortical bone near the implant. Such deviations also significantly influenced implant stresses, especially when the support from the cortical bone was uneven or poorly localized. CONCLUSIONS: In extreme situations, angular deviations can lead to overstraining the cortical bone, risking implant failure from unfavorable interaction with the implant. Accurate implant placement is essential to mitigate these risks.
The aim of this paper was to determine the type and frequency of injuries in kiteboarding, and to define causes of injuries in recreational and professional athletes engaged in kiteboarding. The research was conducted on the sample of 93 kiteboarders, of which 74 were male and 19 were female. Online questionnaire was applied with clearly defined completing instructions. In overall sample of examinees (93), there were 51 who were injured during kiteboarding. Out of total percentage of injured (54.8%), as many as 30.1% had more than one injury. Depending on the method of initial learning and training, 70% of examinees who were self-taught were injured, among those who were taught by a friend with kiteboarding experience 68.18% were injured, then there were 58.82% of injured among those who passed the kiteboarding course with an instructor without a valid license, and, finally, the smallest percentage of injured, 43,18%, among those who took the kiteboarding course with an instructor having a valid license. The most frequent injuries are foot and knee injuries (59.65%) and more than half of injuries (57.91%) is related to strains of ligaments and muscles. Most of the injuries happen during the performance of more advanced technical elements, particularly jumps (33.3 %), while the second most frequent cause of injuries is insufficient kite control (23.7%). Kiteboarders taught by licensed instructors had the smallest risk of injury, while the greatest risk of injury was for self-taught individuals. Mentioned data clearly suggests how important it is to take a verified course with educated instructors to reduce the risk of injuries to a minimum.
This study investigates the risk of head injuries, specifically concussions, from falling objects in workplace accidents. A case study focuses on a construction worker who sustained a head injury despite wearing a protective helmet. Utilizing finite element (FE) analysis, the helmet-head system was modeled to assess impact forces and head accelerations. The helmet, made of High-Density Polyethylene with a 6-point suspension system, was tested against falling objects of 332 g and 665 g. Simulations, conducted from heights of 5 to 25 m, revealed that objects weighing as little as 332 g could cause severe concussions from a 10-meter fall. These findings demonstrate that helmets, while mitigating some impact, absorb significantly less energy than the kinetic energy of falling objects. The analyses carried out confirmed the worker's statement that his injury was caused by a foreign object falling on his head, which was protected by a helmet.
- MeSH
- Finite Element Analysis MeSH
- Biomechanical Phenomena MeSH
- Brain Concussion * prevention & control MeSH
- Humans MeSH
- Accidents, Occupational * prevention & control MeSH
- Head Protective Devices * MeSH
- Accidental Falls * prevention & control MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
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Growing incidence of bacteria resistant to last-line antibiotics represents one of the most important medical issue, complicating the successful treatment of life-threatening infections. In this project, molecular-epidemiological and genomic analysis of carbapenemase-producing Enterobacterales (CPE) isolated from patients in Czech hospitals and its comparison with the carbapenem-susceptible population will be performed. Whole genome sequencing and bioinformatics analysis will allow to identify specific features of CPE, high-risk clones with increased importance for public health and mobile genetic elements associated with the dissemination of resistance to carbapenems in hospitals. Complex genomic analysis will reveal genetic structure of the studied bacterial populations including their dynamics through microevolutionary changes in the clinical context of a hospital outbreak. The project outcomes will be used to improve the diagnostics of infectious diseases and to outline effective interventions for the prevention and control of the transmission of bacterial pathogens.
Narůstající incidence bakterií rezistentních k antibiotikům poslední volby představuje jeden z nejvýznamnějších medicínských problémů, který komplikuje úspěšnou léčbu život ohrožujících infekcí. V rámci navrhovaného projektu bude provedena molekulárně-epidemiologická/genomická analýza Enterobacterales produkujících karbapenemázy (CPE) izolovaných z pacientů hospitalizovaných v českých nemocnicích a srovnání s bakteriální populací citlivou ke karbapenemům. S využitím nejmodernějších postupů celogenomového sekvenování a bioinformatické analýzy budou identifikovány jedinečné rysy CPE, vysoce rizikové klony se zvýšeným významem pro zdraví populace a mobilní genetické elementy spojené s šířením rezistence ke karbapenemům v nemocnicích. Komplexní genomická analýza umožní popsat genetickou strukturu sledovaných bakteriálních populací včetně její dynamiky prostřednictvím mikroevolučních změn během šíření nemocničních nákaz. Výsledky projektu budou bezprostředně využity pro zlepšení a zpřesnění diagnostiky infekčních nemocí a návrh účinnějších postupů v prevenci a kontrole šíření patogenů.
Urgentní příjmy jsou charakterem poskytované péče rizikovým prostředím. Chyby spojené s poskytováním zdravotní péče jsou z velké části preventabilní. Ke snížení bezpečnosti na urgentním příjmu přispívá nárazové přetížení, přerušování péče a multitasking, rušné prostředí, komplexita pacientů, časový tlak a nutnost stálého rozhodování a s tím spojená i zodpovědnost. Bezpečnost poskytované péče je jedním z klíčových prvků kvality. Je potřeba analyzovat data o nežádoucích událostech a bezpečnostních incidentech a na základě analýzy chyb provést preventivní opatření. Pozornost je potřeba věnovat i pracovním podmínkám personálu a eliminovat tak chyby ovlivněné únavou, vyčerpáním, ztrátou koncentrace nebo vyhořením.
Emergency department is by nature of the provided care a risky environment. Medical errors associated with providing care are in most cases preventable. Overcrowding, frequent disruption of care, multitasking, busy environment, complexity of cases, time pressure and continuous decision-making together with high responsibility are some of the reasons which decrease the safety at emergency departments. Safety of the provided care is one of key elements of quality. It is necessary to analyze the data on adverse events and safety incidents and take preventive measures based on this analysis. It is also importatnt to pay attention to working conditions of the personel and eliminate errors coming from fatigue, exhaustion, loss of concentration or burnout.
Genome-wide association studies (GWASs) based on common single nucleotide polymorphisms (SNPs) have identified several loci associated with the risk of monoclonal gammopathy of unknown significance (MGUS), a precursor condition for multiple myeloma (MM). We hypothesized that analyzing haplotypes might be more useful than analyzing individual SNPs, as it could identify functional chromosomal units that collectively contribute to MGUS risk. To test this hypothesis, we used data from our previous GWAS on 992 MGUS cases and 2910 controls from three European populations. We identified 23 haplotypes that were associated with the risk of MGUS at the genome-wide significance level (p < 5 × 10-8) and showed consistent results among all three populations. In 10 genomic regions, strong promoter, enhancer and regulatory element-related histone marks and their connections to target genes as well as genome segmentation data supported the importance of these regions in MGUS susceptibility. Several associated haplotypes affected pathways important for MM cell survival such as ubiquitin-proteasome system (RNF186, OTUD3), PI3K/AKT/mTOR (HINT3), innate immunity (SEC14L1, ZBP1), cell death regulation (BID) and NOTCH signaling (RBPJ). These pathways are important current therapeutic targets for MM, which may highlight the advantage of the haplotype approach homing to functional units.
- MeSH
- Genome-Wide Association Study * MeSH
- Genetic Predisposition to Disease * MeSH
- Haplotypes * MeSH
- Polymorphism, Single Nucleotide * MeSH
- Humans MeSH
- Multiple Myeloma genetics MeSH
- Monoclonal Gammopathy of Undetermined Significance * genetics MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Fosfomycin (FOS) is an effective antibiotic against multidrug-resistant Enterobacterales, but its effectiveness is reducing. Little is known on the current prevalence of FosA enzymes in low-risk pathogens, such as Citrobacter freundii. The aim of the study was the molecular characterization of a carbapenemase- and FosA-producing C. freundii collected in Italy. AK867, collected in 2023, showed an XDR profile, retaining susceptibility only to colistin. AK867 showed a FOS MIC >128 mg/L by ADM. Based on WGS, AK867 belonged to ST116 and owned a wide resistome, including fosA3, blaKPC-2, and blaVIM-1. fosA3 was carried by a conjugative pKPC-CAV1312 plasmid of 320,480 bp, on a novel composite transposon (12,907 bp). FosA3 transposon shared similarities with other fosA3-harboring pKPC-CAV1312 plasmids among Citrobacter spp. We report the first case of FosA3 production in clinical carbapenemase-producing C. freundii ST116. The incidence of FosA3 enzymes is increasing among Enterobacterales, affecting even low-virulence pathogens, as C. freundii.
- MeSH
- Anti-Bacterial Agents * pharmacology MeSH
- Bacterial Proteins * genetics metabolism MeSH
- beta-Lactamases * genetics metabolism MeSH
- Citrobacter freundii * genetics enzymology drug effects MeSH
- Enterobacteriaceae Infections * microbiology MeSH
- Fosfomycin * pharmacology MeSH
- Humans MeSH
- Microbial Sensitivity Tests MeSH
- Drug Resistance, Multiple, Bacterial genetics MeSH
- Plasmids genetics MeSH
- Whole Genome Sequencing MeSH
- DNA Transposable Elements MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Italy MeSH
