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
• Adult MeSH
• Interpersonal Relations MeSH
• Middle Aged MeSH
• Humans MeSH
• Marriage psychology   MeSH
• Adolescent MeSH
• Young Adult MeSH
• Surveys and Questionnaires MeSH
• Self Concept MeSH
• Sexual Behavior psychology   MeSH
• Sexual Partners * psychology   MeSH
• Choice Behavior MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic 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
• Anticoagulants administration & dosage   therapeutic use   MeSH
• Adult MeSH
• Enoxaparin * administration & dosage   therapeutic use   adverse effects   MeSH
• Factor Xa Inhibitors administration & dosage   therapeutic use   MeSH
• Administration, Intravenous MeSH
• Hemorrhage * prevention & control   etiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Extracorporeal Membrane Oxygenation * adverse effects   methods   MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Feasibility Studies MeSH
• Thrombosis prevention & control   etiology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article 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
• Adjuvants, Immunologic therapeutic use   MeSH
• Administration, Intravesical MeSH
• BCG Vaccine * therapeutic use   MeSH
• Neoplasm Invasiveness MeSH
• Middle Aged MeSH
• Humans MeSH
• Non-Muscle Invasive Bladder Neoplasms MeSH
• Urinary Bladder Neoplasms * drug therapy   pathology   mortality   MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors * therapeutic use   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article 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
• Humans MeSH
• Postoperative Complications MeSH
• Aged MeSH
• Kidney Transplantation * MeSH
• Urolithiasis * therapy   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Publication type
• Case Reports 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
• Anti-Bacterial Agents * pharmacokinetics   administration & dosage   MeSH
• Models, Biological MeSH
• Renal Dialysis * MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Monte Carlo Method MeSH
• Drug Monitoring MeSH
• Obesity * complications   MeSH
• Cross-Sectional Studies MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Vancomycin * pharmacokinetics   administration & dosage   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article 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
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Pituitary Neoplasms * mortality   radiotherapy   secondary   MeSH
• Radiosurgery * adverse effects   methods   statistics & numerical data   MeSH
• Retrospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study 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
• Drug Implants MeSH
• Glutamic Acid metabolism   MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Neurons drug effects   MeSH
• Neuroprotective Agents * administration & dosage   chemistry   pharmacology   MeSH
• Polyesters chemistry   MeSH
• Spinal Cord Injuries * drug therapy   MeSH
• Riluzole * administration & dosage   chemistry   pharmacology   MeSH
• Drug Liberation MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article 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
• Energy Metabolism * drug effects   MeSH
• Phosphorylation drug effects   MeSH
• Glycolysis drug effects   MeSH
• Interleukin-6 * metabolism   MeSH
• Jurkat Cells MeSH
• Lactic Acid metabolism   MeSH
• Humans MeSH
• Oxidative Phosphorylation drug effects   MeSH
• Proto-Oncogene Proteins c-akt * metabolism   MeSH
• Signal Transduction * drug effects   MeSH
• TOR Serine-Threonine Kinases * metabolism   MeSH
• Inflammation * metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article 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
• Anesthetics, Intravenous * administration & dosage   pharmacokinetics   pharmacology   MeSH
• Models, Biological MeSH
• Infusions, Intravenous MeSH
• Humans MeSH
• Propofol * administration & dosage   pharmacokinetics   pharmacology   MeSH
• Machine Learning MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Systematic Review MeSH

PI3K signaling pathway is crucial for a plethora of cellular processes and is extensively linked with tumorigenesis and chemo-/radioresistance. Although a number of small molecule inhibitors have been synthesized to control PI3K-mediated signaling, only a limited clinical success has been reached. Thus, the search for novel promising candidates is still ongoing. Herein, we present a novel series of N-(5-(2-morpholino-4-oxo-3,4-dihydroquinazolin-8-yl)pyridin-2-yl)acylamides designed to simultaneously inhibit PI3K and DNA-PK activity. Compared to a commercial DNA-PK/PI3K inhibitor AZD7648, synthesized compounds generally exhibited markedly lower baseline cytotoxicity in all tested cell lines (MC38, B16F10, 4T1, CT26 and HEK-239). Through an array of biological experiments, we selected two most promising compounds, 2 and 6. While in cell-free conditions, 6 acted as a very efficient pan-PI3K and DNA-PK inhibitor, in physiological conditions, 2 performed better and acted as a potent chemosensitizer able to increase the amount of DNA double strand breaks induced by doxorubicin. This was plausibly due to its improved ability to accumulate in nuclei as evidenced by confocal analyses. Importantly, using P-gp overexpressing CT26 cells, we found that 2 is an efficient inhibitor of multidrug resistance (MDR) able to down-regulate expression of mRNA encoding MDR-driving proteins ABCB1A, ABCB1B and ABCC1. We also demonstrate that 2 can be simply loaded into lipid nanoparticles that retain its chemosensitizing properties. Taken together, the presented study provides a solid basis for a subsequent rational structure optimization towards new generation of multitarget inhibitors able to control crucial signaling pathways involved in tumorigenesis and drug resistance.

• MeSH
• Drug Resistance, Neoplasm * drug effects   MeSH
• Phosphatidylinositol 3-Kinases metabolism   MeSH
• Phosphoinositide-3 Kinase Inhibitors * pharmacology   MeSH
• Protein Kinase Inhibitors * pharmacology   chemistry   chemical synthesis   MeSH
• Humans MeSH
• Drug Resistance, Multiple * drug effects   MeSH
• Molecular Structure MeSH
• Mice MeSH
• Cell Line, Tumor MeSH
• ATP Binding Cassette Transporter, Subfamily B, Member 1 * antagonists & inhibitors   metabolism   MeSH
• Cell Proliferation drug effects   MeSH
• DNA-Activated Protein Kinase * antagonists & inhibitors   metabolism   MeSH
• Antineoplastic Agents * pharmacology   chemistry   chemical synthesis   MeSH
• Drug Screening Assays, Antitumor MeSH
• Dose-Response Relationship, Drug MeSH
• Structure-Activity Relationship MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH