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While there is substantial research on what people want in their romantic and sexual partners, much of this work focuses on WEIRD, youthful samples, fails to consider the role of undesirable characteristics (i.e., things people do not want in partners) at all, or in conjunction with desirable characteristics (i.e., things people do want in partners), and may be overly reliant on psychometric approaches to pivotal variables in mating psychology like mate value and sociosexuality. In a nationally representative (online) sample of 2280 people from Czechia (aged between 18 and 50 years old), we examined linear and quadratic age, education, and self-perceived mate value (desirability) effects on the desired levels in mate choice of eight undesirable and seven desirable characteristics in men and women in relation to ostensible metrics of mate value. Self-perceived mate value alone explained little variance (men 1%, women 2%), while all mate value and mating strategy indicators together explained little variance of mate preferences and aversions (men 3%, women 5%). Desirable characteristics were better explained by mate value than undesirable ones. Our results are in line with evolutionary predictions suggesting that women are more demanding. Also, more qualities to offer correlate with more expectations in a partner.
- MeSH
- dospělí MeSH
- interpersonální vztahy MeSH
- lidé středního věku MeSH
- lidé MeSH
- manželství psychologie MeSH
- mladiství MeSH
- mladý dospělý MeSH
- průzkumy a dotazníky MeSH
- sebepojetí MeSH
- sexuální chování psychologie MeSH
- sexuální partneři * psychologie MeSH
- výběrové chování MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: Unfractionated heparin is used as the most common anticoagulation for venovenous extracorporeal membrane oxygenation (VV ECMO) patients. However, it is accompanied by frequent bleeding and thrombotic complications. The aim of the study was to demonstrate the feasibility of Enoxaparin anticoagulation for VV ECMO patients. METHODS: This study is a retrospective analysis of VV ECMO patients on continuous intravenous Enoxaparin anticoagulation. The primary outcome was the incidence of bleeding, thrombotic, and neurological complications during ECMO support. The secondary outcome was an analysis of secondary and primary hemostasis profiles. RESULTS: Data from 38 patients were analyzed in this study. The incidence of bleeding complications was 5.3%, for thrombotic complications it was 2.6% and for neurological (bleeding/ischemic events) complications it was 10.5%. The targeted anti-Xa activity of 0.4-0.6 IU/mL was achieved and maintained during whole ECMO period in 28 patients (73.8%), not affecting the hemocoagulation profile represented by APTT-r 1.15 ± 0.2, TT 18.67 ± 3.35 s, PT/INR 1.21 ± 0.19, fibrinogen 5.39 ± 1.49 g/L, antithrombin, and platelet count. Primary hemostasis pathology was diagnosed in all patients by PFA 200 tests Col/EPI 279 ± 38 s and Col/ADP 249 ± 66 s. The running time of ECMO was 7.8 ± 3.4 days. CONCLUSIONS: Enoxaparin anticoagulation appears to be feasible for VV ECMO patients without an increase in adverse events. Further larger-sampled and comparative studies are needed in the future to support our findings.
- MeSH
- antikoagulancia aplikace a dávkování terapeutické užití MeSH
- dospělí MeSH
- enoxaparin * aplikace a dávkování terapeutické užití škodlivé účinky MeSH
- inhibitory faktoru Xa aplikace a dávkování terapeutické užití MeSH
- intravenózní podání MeSH
- krvácení * prevence a kontrola etiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mimotělní membránová oxygenace * škodlivé účinky metody MeSH
- retrospektivní studie MeSH
- senioři MeSH
- studie proveditelnosti MeSH
- trombóza prevence a kontrola etiologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: To investigate the influence of statins on the survival outcomes of patients with non-muscle-invasive bladder cancer (NMIBC) treated with adjuvant intravesical bacille Calmette-Guérin (BCG) immunotherapy. PATIENTS AND METHODS: A retrospective cohort of consecutive patients with NMIBC who received intravesical BCG therapy from 2001 to 2020 and statins prescription were identified. Overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and progression-free survival (PFS) were analysed between the Statins Group vs No-Statins Group using Kaplan-Meier method and multivariable Cox regression. RESULTS: A total of 2602 patients with NMIBC who received intravesical BCG were identified. The median follow-up was 11.0 years. On Kaplan-Meier analysis, the Statins Group had significant better OS (P < 0.001), CSS (P < 0.001), and PFS (P < 0.001). Subgroup analysis indicated statins treatment started before BCG treatment had better CSS (P = 0.02) and PFS (P < 0.01). Upon multivariable Cox regression analysis, the 'statins before BCG' group was an independent protective factor for OS (hazard ratio [HR] 0.607, 95% confidence interval [CI] 0.514-0.716), and CSS (HR 0.571, 95% CI 0.376-0.868), but not RFS (HR 0.885, 95% CI 0.736-1.065), and PFS (HR 0.689, 95% CI 0.469-1.013). CONCLUSIONS: Statins treatment appears to offer protective effects on OS and CSS for patients with NMIBC receiving adjuvant intravesical BCG.
- MeSH
- adjuvancia imunologická terapeutické užití MeSH
- aplikace intravezikální MeSH
- BCG vakcína * terapeutické užití MeSH
- invazivní růst nádoru MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory močového měchýře neinvadující svalovinu MeSH
- nádory močového měchýře * farmakoterapie patologie mortalita MeSH
- retrospektivní studie MeSH
- senioři MeSH
- statiny * terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
U pacientů s transplantovanou ledvinou představuje perkutánní extrakce konkrementu (PEK) zákrok vyžadující zohlednění specifických anatomických a fyziologických podmínek štěpu. Tato kazuistika popisuje případ 69letého muže, u něhož byla PEK indikována pro opakované záněty transplantované ledviny a progresi velikosti konkrementů. Zákrok byl úspěšně proveden bez reziduální litiázy, avšak pooperačně se objevily komplikace, včetně krvácení a infekce, které si vyžádaly akutní chirurgickou revizi a intenzivní péči. Díky rychlému zásahu a následné léčbě se podařilo zachovat funkci transplantované ledviny. Případ zdůrazňuje význam precizní diagnostiky, vhodného terapeutického postupu a pečlivého pooperačního sledování pro minimalizaci komplikací a dlouhodobé zachování štěpu.
In patients with a transplanted kidney, percutaneous nephrolithotomy (PCNL) is a procedure that requires consideration of the graft ́s specific anatomical and physiological conditions. This case report describes a 69-year-old man who underwent PCNL due to recurrent graft infections and the progression of stone size. The procedure was successfully completed without residual lithiasis; however, postoperative complications, including bleeding and infection, required emergency surgical revision and intensive care. Prompt intervention and subsequent treatment preserved the function of the transplanted kidney. This case highlights the importance of precise diagnosis, appropriate therapeutic strategies, and thorough postoperative monitoring to minimize complications and ensure the long-term preservation of the graft.
- MeSH
- lidé MeSH
- pooperační komplikace MeSH
- senioři MeSH
- transplantace ledvin * MeSH
- urolitiáza * terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH
This study aimed to develop a vancomycin population pharmacokinetic model in obese adult patients treated with intermittent haemodialysis and propose a model-based loading dose strategy ensuring attainment of newly recommended AUC-based PK/PD target. Retrospective cross-sectional analysis was performed among obese haemodialysis dependent adult patients treated with intravenous vancomycin. A pharmacokinetic population model was developed using a nonlinear mixed-effects modelling approach and Monte Carlo simulations were used to identify the optimal loading dose for PK/PD target attainment during the first 48 h of treatment. Therapeutic drug monitoring data from 27 patients with a BMI of 30.2-52.9 kg/m2 were analysed. Among all tested variables, only LBM as a covariate of vancomycin Vd significantly improved the model, while vancomycin CL did not correlate with any of the tested variables. The median (IQR) value from the conditional mean of individual estimates of Vd and CL was 68.4 (56.6-84.2) L and 0.86 (0.79-0.90) L/h, respectively. To ensure optimal vancomycin exposure during the first 48 h of therapy, the vancomycin loading dose of 1500, 1750, 2000, 2250, 2500 and 2750 mg should be administered to obese patients with a lean body mass of ˂50, 50-60, 60-70, 70-80, 80-85 and >85 kg, respectively.
- MeSH
- antibakteriální látky * farmakokinetika aplikace a dávkování MeSH
- biologické modely MeSH
- dialýza ledvin * MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- metoda Monte Carlo MeSH
- monitorování léčiv MeSH
- obezita * komplikace MeSH
- průřezové studie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- vankomycin * farmakokinetika 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
BACKGROUND: Pituitary metastases (PM) account for 0.4% of all intracranial metastases and typically present with visual and endocrinological deficits. Stereotactic radiosurgery (SRS) has shown excellent tumor control and safety profile in the management of intracranial metastases. However, its role and safety in managing metastases to the pituitary gland are not well-characterized. This study aims to evaluate SRS outcomes and safety profile in the management of PM in a multicenter international cohort. METHODS: The authors retrospectively analyzed data from 63 patients with PM treated with SRS across 12 institutions, assessing clinical and radiological outcomes, including survival rates, tumor control, visual and endocrinological outcomes, and post-treatment complications. RESULTS: Among 63 patients included in the study (median tumor volume: 1.5 cc), SRS demonstrated a local tumor control rate of 93.1% at 12 months. The median survival was 25.4 months and overall survival rates of 77.6%, 65.9%, and 55.1% at 6, 12, and 18 months, respectively. In multivariate analysis, a margin dose for PM > 10 Gy emerged as an independent predictor across progression-free survival (HR: 0.20, p < 0.01), distant metastasis-free survival (HR: 0.30, p = 0.01), and overall survival. (HR: 0.15, p < 0.01). Following SRS, most patients showed stable or improved visual function (n = 17/18). A small percentage of patients experienced complications: developed new visual deficits (n = 1/63), experienced new anterior pituitary hormone deficiency (n = 5/63), and developed arginine vasopressin (AVP)-deficiency post-treatment (n = 2/63). CONCLUSION: SRS is an important modality in the management of PM, offering excellent local tumor control and survival outcomes with minimal morbidity. These findings support the incorporation of SRS into the multidisciplinary management for treating patients with PM.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory hypofýzy * mortalita radioterapie sekundární MeSH
- radiochirurgie * škodlivé účinky metody statistika a číselné údaje MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři 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
- multicentrická studie MeSH
Spinal cord injury (SCI) results in paralysis, driven partly by widespread glutamate-induced secondary excitotoxic neuronal cell death in and around the injury site. While there is no curative treatment, the standard of care often requires interventive decompression surgery and repair of the damaged dura mater close to the injury locus using dural substitutes. Such intervention provides an opportunity for early and local delivery of therapeutics directly to the injured cord via a drug-loaded synthetic dural substitute for localized pharmacological therapy. Riluzole, a glutamate-release inhibitor, has shown neuroprotective potential in patients with traumatic SCI, and therefore, this study aimed to develop an electrospun riluzole-loaded synthetic dural substitute patch suitable for the treatment of glutamate-induced injury in neurons. A glutamate-induced excitotoxicity was optimized in SH-SY5Y cells by exploring the effect of glutamate concentration and exposure duration. The most effective timing for administering riluzole was found to be at the onset of glutamate release as this helped to limit extended periods of glutamate-induced excitotoxic cell death. Riluzole-loaded patches were prepared by using blend electrospinning. Physicochemical characterization of the patches showed the successful encapsulation of riluzole within polycaprolactone fibers. A drug release study showed an initial burst release of riluzole within the first 24 h, followed by a sustained release of the drug over 52 days to up to approximately 400 μg released for the highest loading of riluzole within fiber patches. Finally, riluzole eluted from electrospun fibers remained pharmacologically active and was capable of counteracting glutamate-induced excitotoxicity in SH-SY5Y cells, suggesting the clinical potential of riluzole-loaded dural substitutes in counteracting the effects of secondary injury in the injured spinal cord.
- MeSH
- implantované léky MeSH
- kyselina glutamová metabolismus MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- neurony účinky léků MeSH
- neuroprotektivní látky * aplikace a dávkování chemie farmakologie MeSH
- polyestery chemie MeSH
- poranění míchy * farmakoterapie MeSH
- riluzol * aplikace a dávkování chemie farmakologie MeSH
- uvolňování léčiv MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Numerous studies have reported that increased interleukin 6 (IL-6) and soluble IL-6 receptor (sIL-6) levels induce inflammatory conditions. However, the exact mechanisms by which IL-6 drives inflammatory conditions remain unclear. Therefore, we investigated the potential role of IL-6/sIL-6R in inducing energy metabolism, including glycolysis, oxidative phosphorylation, lactate secretion and Akt/mTOR phosphorylation, in Jurkat cells, and whether IL-6 would increase the risk of developing inflammatory conditions due to the high metabolic profile of the T cells. Jurkat CD4 T-cell lines were stimulated with IL-6/sIL-6R for 24 h prior to 48-h stimulation with anti-CD3/CD28. Lactate secretion, glycolysis and oxidative phosphorylation levels were characterized using the Seahorse XF analyser. The Akt and mTOR phosphorylation status was detected using Western blotting. IL-6/sIL-6R significantly induced glycolysis and oxidative phosphorylation and their related parameters, including glycolytic capacity and maximal respiration, followed by significantly increased lactate secretion. Akt and mTOR phosphorylation were increased, which could have resulted from energy metabolism. Here we show that IL-6 enhanced the metabolic profile of Jurkat cells. This effect could have consequences for the metabolism-related signalling pathways, including Akt and mTOR, suggesting that IL-6 might promote T-cell energy metabolism, where T-cell hyperactivity might increase the inflammatory disease risk. The findings should be validated using studies on primary cells isolated from humans.
- MeSH
- energetický metabolismus * účinky léků MeSH
- fosforylace účinky léků MeSH
- glykolýza účinky léků MeSH
- interleukin-6 * metabolismus MeSH
- Jurkat buňky MeSH
- kyselina mléčná metabolismus MeSH
- lidé MeSH
- oxidativní fosforylace účinky léků MeSH
- protoonkogenní proteiny c-akt * metabolismus MeSH
- signální transdukce * účinky léků MeSH
- TOR serin-threoninkinasy * metabolismus MeSH
- zánět * metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
This study presents a systematic review conducted according to the PRISMA 2020 guidelines, evaluating pharmacokinetic-pharmacodynamic (PK-PD) models for target-controlled infusion (TCI) of propofol. A structured search was performed across PubMed, Summon, Google Scholar, Web of Science, and Scopus, identifying 427 sources, of which 17 met the inclusion criteria. The analysis revealed that nine studies compared existing models, six focused on the development of new PK-PD models, and two explored broader implications of TCI in anesthesia. Comparative studies indicate that while the Eleveld model generally offers superior predictive accuracy, it does not consistently outperform the Marsh and Schnider models across all populations. The Schnider model demonstrated better bias control in elderly patients, while the Eleveld model improved drug clearance estimation in obese patients. However, inconsistencies remain in predicting brain concentrations of propofol. Newly proposed models introduce adaptive dosing strategies, incorporating allometric scaling, lean body weight, and machine learning techniques, yet require further external validation. The results highlight ongoing challenges in achieving universal applicability of TCI models, underscoring the need for future research in refining precision dosing and personalized anesthesia management.
- MeSH
- anestetika intravenózní * aplikace a dávkování farmakokinetika farmakologie MeSH
- biologické modely MeSH
- intravenózní infuze MeSH
- lidé MeSH
- propofol * aplikace a dávkování farmakokinetika farmakologie MeSH
- strojové učení MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- systematický přehled MeSH
Neurodegenerative disorders (NDs) are typically characterized by progressive loss of neuronal function and the deposition of misfolded proteins in the brain and peripheral organs. They are molecularly classified based on the specific proteins involved, underscoring the critical role of protein-processing systems in their pathogenesis. Alpha-synuclein (α-syn) is a neural protein that is crucial in initiating and progressing various NDs by directly or indirectly regulating other ND-associated proteins. Therefore, reducing the α-syn aggregation can be an excellent option for combating ND initiation and progression. This study presents an in silico phytochemical-based approach for discovering novel neuroprotective agents from bioactive compounds of the Lamiaceae family, highlighting the potential of computational methods such as functional networking, pathway enrichment analysis, molecular docking, and simulation in therapeutic discovery. Functional network and enrichment pathway analysis established the direct or indirect involvement of α-syn in various NDs. Furthermore, molecular docking interaction and simulation studies were conducted to screen 85 major bioactive compounds of the Lamiaceae family against the α-syn aggregation. The results showed that five compounds (α-copaene, γ-eudesmol, carnosol, cedryl acetate, and spathulenol) had a high binding affinity towards α-syn with potential inhibitory activity towards its aggregation. MD simulations validated the stability of the molecular interactions determined by molecular docking. In addition, in silico pharmacokinetic analysis underscores their potential as promising drug candidates, demonstrating excellent blood-brain barrier (BBB) permeability, bioactivity, and reduced toxicity. In summary, this study identifies the most suitable compounds for targeting the α-syn aggregation and recommends these compounds as potential therapeutic agents against various NDs, pending further in vitro and in vivo validation.
- Publikační typ
- časopisecké články MeSH