Methoxphenidine (MXP) is classified as a new psychoactive substance that has recently emerged on the illicit drug market. Understanding the pharmacological and behavioural profiles of newly emerging drugs is essential for a better understanding of their psychotropic effects and potential toxicity. Therefore, in this study, we investigated a broad range of effects of acute MXP administration: pharmacokinetics in the brain and serum; behaviour (open field and prepulse inhibition), systemic toxicity (lethal dose; LD 50), and histopathology changes in parenchymal organs of Wistar rats. MXP rapidly crossed the blood-brain barrier, reaching peak median concentrations in both serum and brain 30 min post-administration, followed by an elimination phase with a half-life of 2.15 h. Locomotor activity in the open field test displayed a dose-response effect at low to moderate doses (10-20 mg/kg MXP). At higher doses (40 mg/kg), locomotor activity decreased. All doses of MXP significantly disrupted prepulse inhibition and the effect was present during the onset of its action as well as 60 min after treatment. Additionally, MXP demonstrated moderate acute toxicity, with an estimated LD50 of 500 mg/kg when administered subcutaneously. In summary, MXP exhibited a profile similar to typical dissociative anesthetics, producing stimulant and anxiogenic effects at lower doses, sedative effects at higher doses, and disrupting sensorimotor gating. The accumulation of MXP in brain tissue is likely to contribute to acute intoxication in humans, potentially leading to negative experiences. Our findings highlight the potentially dangerous effects of recreational MXP use and underscore the risks of inducing serious adverse health outcomes.
- MeSH
- chování zvířat účinky léků MeSH
- krysa rodu rattus MeSH
- LD50 MeSH
- mozek účinky léků metabolismus MeSH
- piperidiny farmakokinetika farmakologie MeSH
- pohybová aktivita účinky léků MeSH
- potkani Wistar * MeSH
- prepulsní inhibice účinky léků MeSH
- test otevřeného pole účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
RNA secondary (2D) structure visualization is an essential tool for understanding RNA function. R2DT is a software package designed to visualize RNA 2D structures in consistent, recognizable, and reproducible layouts. The latest release, R2DT 2.0, introduces multiple significant features, including the ability to display position-specific information, such as single nucleotide polymorphisms or SHAPE reactivities. It also offers a new template-free mode allowing visualization of RNAs without pre-existing templates, alongside a constrained folding mode and support for animated visualizations. Users can interactively modify R2DT diagrams, either manually or using natural language prompts, to generate new templates or create publication-quality images. Additionally, R2DT features faster performance, an expanded template library, and a growing collection of compatible tools and utilities. Already integrated into multiple biological databases, R2DT has evolved into a comprehensive platform for RNA 2D visualization, accessible at https://r2dt.bio.
Initially, molecular hydrogen was considered a physiologically inert and non-functional gas. However, experimental and clinical studies have shown that molecular hydrogen has anti-inflammatory, anti-apoptotic, and strong selective antioxidant effects. This study aimed to evaluate the effects of 60 minutes of molecular hydrogen inhalation on respiratory gas analysis parameters using a randomized, double-blind, placebo-controlled, crossover design. The study was conducted at Faculty of Physical Culture, Palacký University Olomouc from September 2022 to March 2023. Twenty, physically active female participants aged 22.1 ± 1.6 years who inhaled either molecular hydrogen or ambient air through a nasal cannula (300 mL/min) for 60 minutes while resting were included in this study. Metabolic response was measured using indirect calorimetry. Breath-by-breath data were averaged over four 15-minute intervals. Compared with placebo (ambient air), molecular hydrogen inhalation significantly decreased respiratory exchange ratio and ventilation across all intervals. Furthermore, the change in respiratory exchange ratio was negatively correlated with body fat percentage from 30 minutes onwards. In conclusion, 60 minutes of resting molecular hydrogen inhalation significantly increased resting fat oxidation, as evidenced by decreased respiratory exchange ratio, particularly in individuals with higher body fat percentages.
- MeSH
- aplikace inhalační MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- klinické křížové studie MeSH
- lidé MeSH
- mladý dospělý MeSH
- odpočinek * MeSH
- placebo MeSH
- vodík * aplikace a dávkování farmakologie MeSH
- zdraví dobrovolníci pro lékařské studie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
Background/Objectives: The DIEP flap is among the preferred techniques in autologous breast reconstruction due to better long-term outcomes, including higher satisfaction and more natural breast shape compared to implant-based breast reconstruction. With the rise in genetic testing, bilateral DIEP reconstructions are becoming more common, though they carry a higher risk of complications. This study aims to compare the risks between unilateral and bilateral procedures to improve surgical decision-making. Methods: A retrospective, single-center review was conducted on female patients who underwent DIEP flap breast reconstruction between January 2018 and May 2024. The study included patients with complete medical records and follow-up data, excluding those with incomplete records. Patient characteristics, operative details, and complications were thoroughly analyzed, with donor site complications assessed per patient and recipient site complications per breast. Results: During the study, 141 DIEP flaps were performed on 114 women, with 87 unilateral and 27 bilateral reconstructions. Age and BMI were similar between groups. However, chemotherapy was more common in the bilateral group (85% vs. 47%, p = 0.0011). Operative time was significantly longer in bilateral procedures (650 vs. 460 min, p < 0.0001). There were no statistically significant differences in recipient and donor site complications across groups. The hospital stay was significantly longer in the bilateral group (11 vs. 8.8 days, p = 0.024). Conclusions: Bilateral and unilateral DIEP flap breast reconstructions have similar complication and early take-back rates.
- Publikační typ
- časopisecké články MeSH
Ischemic stroke is a leading cause of mortality and long-term disability globally. One of its aspects is the breakdown of the blood-brain barrier (BBB). The disruption of BBB's integrity during stroke exacerbates neurological damage and hampers therapeutic intervention. Recent advances in regenerative medicine suggest that mesenchymal stem cells (MSCs) derived extracellular vesicles (EVs) show promise for restoring BBB integrity. This review explores the potential of MSC-derived EVs in mediating neuroprotective and reparative effects on the BBB after ischemic stroke. We highlight the molecular cargo of MSC-derived EVs, including miRNAs, and their role in enhancing angiogenesis, promoting the BBB and neural repair, and mitigating apoptosis. Furthermore, we discuss the challenges associated with the clinical translation of MSC-derived EV therapies and the possibilities of further enhancing EVs' innate protective qualities. Our findings underscore the need for further research to optimize the therapeutic potential of EVs and establish their efficacy and safety in clinical settings.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
This study investigated the combined impact of family dynamics and school environments on physical activity levels in children aged 3-9 years across distinct segments of the school day. Conducted as part of the FAMIPASS project in the Czech Republic, the study collected data in 2022 and 2023 from 502 families affiliated with 36 preschools and primary schools. The device-based monitoring of movement behaviors in children and their parents was conducted over a one-week period using ActiGraph accelerometers, complemented by detailed family questionnaires. Regression analysis revealed that parental physical activity, BMI, and education level significantly influenced children's moderate-to-vigorous physical activity, with educated parents more likely to raise active children. Active transport to school emerged as a key factor associated with higher child activity levels specifically in the time segment before school. This research underscores the role of family and school as critical arenas for promoting health and physical activity. These insights highlight the need for integrated family-school strategies to foster healthy activity habits in children, thereby laying the groundwork for a more active generation.
- Publikační typ
- časopisecké články MeSH
In previous research, we revealed that murine leukemia cells L1210 with induced expression of P-glycoprotein (P-gp, a membrane drug transporter, product of the Abcb1 gene) are better able to withstand endoplasmic reticulum (ER) stress (ERS) than their P-gp negative counterparts. This was associated with increased GRP78/BiP expression and modulation of the expression of several other proteins active in the cellular response to ERS (like CHOP, spliced XBP1, 50-kDa ATF6 protein fragment and others) in P-gp positive cells. Wolframin is an ER transmembrane protein, product of the WFS1 gene whose mutations are associated with Wolfram syndrome. However, this protein is frequently overexpressed in cells undergoing ERS and its expression may accompany changes in the above ERS markers. Therefore, our aim in this work was to investigate wolframin expression in P-gp-negative and P-gp-positive murine leukemia L1210 cells in relation to ERS related proteins in normal or ERS condition. We induced ERS in cells either by blocking N-glycosylation in the ER with tunicamycin or by blocking ER Ca2+-ATPase activity with thapsigargin, as known ER stressors. The results of this paper demonstrated increased wolframin expression in P-gp positive cells compared to P-gp negative cells. Immunoprecipitation experiments revealed the formation of complexes between wolframin and ERS related proteins (PERK, ATF6 and GRP78/BiP), the amount of which varied depending on the presence of the above ER stressors.
- Publikační typ
- časopisecké články MeSH
LIM and Src homology 3 (SH3) protein 2 (LASP2) is a small focal adhesion protein first identified as a splice variant of the nebulette gene (Nebl). As the newest member of the nebulin protein family, the regulation and function of LASP2 remain largely unknown. Our previous RNA-sequencing results identified Nebl as one of the most highly induced genes in the mouse liver in response to the activation of pregnane X receptor (PXR). In this study, we investigated this phenomenon further and show that PXR induces Lasp2 instead of Nebl, which partially use the same exons. Lasp2 was found to be induced in response to PXR ligand pregnenolone 16α-carbonitrile (PCN) treatment in mouse liver in vivo both after 4-day treatment and after long-term, 28-day treatment and in both male and female mice. Interestingly, the Lasp2 induction was more efficient in high-fat diet-fed mice (103-fold after 4-day PCN treatment) than in the normal chow-fed mice (32-fold after 4-day PCN treatment). Lasp2 induction was abolished in PXR knockout mice but could be rescued by re-expression of PXR, indicating that Lasp2 induction is PXR mediated. In mouse primary hepatocytes cycloheximide did not inhibit Lasp2 induction by PCN and a PXR binding site could be recognized upstream of the mouse Lasp2 gene suggesting direct regulation of Lasp2 by PXR. In human 3D hepatocytes, rifampicin induced only a modest increase in LASP2 expression. This study shows for the first time that PXR activation strongly induces Lasp2 expression in mouse liver and establishes Lasp2 as a novel PXR target gene. SIGNIFICANCE STATEMENT: RNA-sequencing results have previously identified nebulette (Nebl) to be efficiently induced by pregnane X receptor activating compounds. This study shows that instead of Nebl, LIM and Src homology 3 (SH3) protein 2 (Lasp2) coding for a small focal adhesion protein and partly sharing exons with the Nebl gene is a novel target of pregnane X receptor in mouse liver.
- MeSH
- adaptorové proteiny signální transdukční genetika metabolismus MeSH
- cytoskeletální proteiny * genetika metabolismus MeSH
- hepatocyty metabolismus účinky léků MeSH
- játra * metabolismus účinky léků MeSH
- lidé MeSH
- myši inbrední C57BL * MeSH
- myši knockoutované * MeSH
- myši MeSH
- pregnanový X receptor * genetika metabolismus MeSH
- pregnenolonkarbonitril farmakologie MeSH
- proteiny s doménou LIM * genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Health care provider payment schemes consist of a complex set of arrangements used to influence provider behavior towards specific health policy objectives. The study aimed at: 1) providing a structured, comparative overview of current payment schemes within the public health system in selected Central and Eastern European (CEE) countries for different health care providers; 2) identifying and comparing major changes in payment schemes since 2010. Methods included: 1) data collection form development; 2) desk research; 3) national experts' consultations; 4) comparative analysis. The results indicate that the nine CEE countries (Bulgaria, Croatia, Czechia, Estonia, Latvia, Lithuania, Hungary, Poland, and Romania) show numerous similarities in provider payment method mix and in the general direction of the recent changes conducted in this field. Output-based payment methods prevail across all countries and types of providers. Primary health care (PHC) providers are characterized by the most diverse payment method mix. PHC and hospital inpatient care have experienced the most frequent changes in their payment schemes within the last 13 years. These focused mostly on modifying existing payment methods (e.g. detailing payment categories), and applying additional methods to pay for specific services or performance (e.g. fee-for-service, bonus payments). The objectives of conducted change were often similar, thus, there is high potential for a shared, cross-country learning.
- MeSH
- dávkové mechanismy * MeSH
- lidé MeSH
- primární zdravotní péče ekonomika MeSH
- zdravotní politika MeSH
- zdravotnický personál MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- srovnávací studie MeSH
- Geografické názvy
- Česká republika MeSH
- Chorvatsko MeSH
- Estonsko MeSH
- Evropa MeSH
- Litva MeSH
- Lotyšsko MeSH
- Maďarsko MeSH
- Polsko MeSH
- Rumunsko MeSH
- východní Evropa MeSH
BACKGROUND: Primary plasma cell leukemia (PPCL) is the most aggressive disorder among plasma cell malignancies, with new diagnostic criteria recently established by the International Myeloma Working Group. Studies have shown that PPCL patients receiving a combination of novel agents, but not eligible for transplantation, may have a median survival up to 2 years, extended to 3 years or more in those undergoing transplant procedures. These findings remain unsatisfactory, particularly if compared with progresses obtained in multiple myeloma. DESIGN: A European Myeloma Network (EMN) expert panel reviewed the most recent literature and selected the areas of major concern in the management of PPCL by generating and rank ordering key questions using the criterion of clinical relevance. Multistep procedures were utilized to achieve a consensus on recommendations. The Delphi questionnaire method was used and a consensus of at least 80% was reached for all final statements. RESULTS: An extended overview of current biological, clinical, prognostic, and therapeutic aspects of PPCL, including ongoing and close to start clinical trials, is presented. Furthermore, updated guidelines for the management of PPCL and practical recommendations are provided, in the context of current knowledge about this disease, also looking at possible future perspectives to ameliorate the outcome of these patients. CONCLUSIONS: PPCL still remains an unmet clinical need. Notwithstanding, some not negligible progresses have been recently achieved. The European Myeloma Network panel strongly support ongoing and planned clinical trials, as well as biological studies based on novel technologies, strategies, and treatment options that could represent breakthroughs we have been waiting for too long.
