Search Results (9,724)

Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with a fivefold increase in stroke risk. Direct oral anticoagulants (DOACs), including apixaban, are now the preferred therapy for stroke prevention in patients with non-valvular AF (NVAF). However, interindividual variability in drug response and safety remains a major challenge, particularly in elderly patients with comorbidities and polypharmacy. Genetic polymorphisms in drug-metabolizing enzymes and transporters may contribute to variability in apixaban exposure and bleeding risk. This study aimed to evaluate the association of polymorphisms in ABCB1, CYP3A4, and CYP3A5 with steady-state plasma concentrations of apixaban (Cssmin) and hemorrhagic complications in elderly patients with NVAF. Methods: This cross-sectional study included 197 patients (mean age 83 ± 8 years; 67% women) with NVAF treated with apixaban (5 mg twice daily). Genotyping of ABCB1 (rs1045642, rs2032582, rs1128503), CYP3A4*22 (rs35599367), and CYP3A5*3 (rs776746) was performed using allele-specific real-time PCR. Cssmin of apixaban was determined by high-performance liquid chromatography coupled with tandem mass spectrometry. Associations with bleeding events were evaluated. Results: Bleeding events were recorded in 40 patients (20.3%). An association signal was observed for ABCB1 rs1045642, where carriers of the CC genotype had a higher risk of bleeding compared with alternative alleles (OR = 2.805; 95% CI: 1.326–5.935; p = 0.006). After correction for multiple testing, the association remained significant only under the log-additive model (OR = 1.93 per C allele; 95% CI: 1.17–3.20; q = 0.0275; p_adj = 0.044), while recessive and codominant effects did not withstand Bonferroni adjustment. No significant associations were observed for rs2032582, rs1128503, CYP3A4*22, or CYP3A5*3. None of the studied polymorphisms, including rs1045642, significantly affected Cssmin. Concomitant therapy, particularly with antiarrhythmic drugs and statins (rosuvastatin), also increased bleeding risk. Conclusions: The findings highlight the potential contribution of ABCB1 rs1045642 and specific drug–drug interactions to the risk of hemorrhagic complications in elderly NVAF patients receiving apixaban. Full article

The surface tensions (σ) of binary solutions of diiodomethane (DIM, 1)–furfural (FA, 2), DIM (1)–N,N-dimethylformamide (DMF, 2), and FA (1)–DMF (2) were determined at 25 °C over the entire bulk composition range, and the surface adsorption behavior was analyzed using the surface aggregation adsorption (SAA) model proposed recently. In particular, by combining the SAA model with the Gibbs adsorption equation, the changes in the Gibbs surface excess (Γ₂) and the adsorption layer thickness (τ) with the bulk composition (x_2,b) were investigated. The SAA model combined with the modified Eberhart model can well describe the σ-isotherms of the three binary solutions. The surface adsorption trends of component 2 in DIM–FA, DIM–DMF, and FA–DMF decrease in turn. The change trends of Γ₂ and τ with x_2,b are dependent on the SAA model parameters, namely, the adsorption equilibrium constant (K_x) and the average aggregation number (n). With an increase in x_2,b, Γ₂ continuously increases when K_x < 2v₁/[n(2n − 1)v₂] (where v₁ and v₂ are the partial molar volumes of components 1 and 2, respectively); otherwise (i.e., K_x ≥ 2v₁/[n(2n − 1)v₂]), Γ₂ initially increases and then decreases, showing a maximum on the Γ₂-isotherm. When n ≥ 1, τ gradually decreases with an increase in x_2,b; otherwise (i.e., n < 1), τ initially increases and then decreases, showing a maximum on the τ-isotherm. An increase in the adsorption trend leads to a decrease in both Γ₂ and τ. This work provides a better understanding of the surface adsorption behavior of liquid mixtures. Full article

Recently, the search for new antimicrobial compounds, including the secondary metabolites of basidiomycetes, has become increasingly important. Representatives of this division of higher fungi have high biosynthetic abilities, which contributes to their use as producers. In this work, extracts of culture liquids and submerged mycelia from 18 strains representing three different orders of basidiomycetes were studied. For this purpose, the submerged cultivation of strains, extraction of biological material, and evaluation of the extract’s antimicrobial activity using the agar well diffusion method were carried out. The minimum inhibitory concentration was determined for extracts with strong activity. The most promising ones were analyzed using HPLC-MS. As a result, it was found that 16 strains contained antimicrobial metabolites. Thus, the strains selected for further work were Hericium corraloides 4, which showed not only the antibacterial but also antifungal activity of cultural liquid and submerged mycelia extracts, and Fomitopsis betulina 3, Fomitopsis pinicola 2, Hericium erinaceus 1, and Laetiporus sulphureus 4, whose cultural liquid extracts exhibited high antibacterial activity against Gram-positive and Gram-negative test cultures. For these strains, metabolic profiles were obtained using the method HPLC-MS. Using this method, two metabolites were preliminary identified: hericerin in H. erinaceus 1 and sulfureuine H in L. sulphureus 4. Full article

Young child formula (YCF) products are important sources of nutrients for children 1–3 years of age. Salt equilibria and protein glycation are two of the crucial aspects affecting nutritional properties and digestive behaviors of YCF, but detailed insights into these two aspects of YCF products remains limited. This study analyzed the distribution of salts and the level of protein glycation in 25 commercial YCF products from the retail market in China. The YCF products were reconstituted (12 g of powder per 100 g of water) and the distribution of calcium and phosphorus between the sedimentable (at 200× g), protein-associated and soluble (10 kDa-permeable) fractions were determined. Blocked lysine and 5-hydroxymethylfurfural were analyzed using reversed-phase high-performance liquid chromatography. Varying proportions of calcium (3.0–39.3%) and phosphorus (1.2–29.8%) were sedimentable for the products. Notable proportions of calcium (28.9–62.7%) and phosphorus (27.4–57.9%) were associated with the proteins. The remainder of the calcium (24.9–41.4%) and phosphorus (34.2–62.1%) were soluble. When expressing the protein-associated calcium as a function of casein, i.e., casein mineralization, large differences (~1.7 fold) were found among products. Variation in blocked lysine (7.4–19.2% of total lysine) and 5-hydroxymethylfurfural contents (3.0–7.0 mg/100 g protein) among products was also observed, suggesting notable differences in heat-load during processing. This study revealed notable variation in salt distribution and protein glycation among the YCF products. These findings underscore the critical need for manufacturers to optimize formulation and processing approaches, e.g., using milk with a low level of casein mineralization and using milk protein sources as concentrated liquid rather than powder to reduce protein glycation, to improve nutritional properties of the products. Full article

Since H₂O and Ethylene Glycol Monomethyl Ether (EM) form a minimum-boiling azeotrope, 1-pentanol, 1-hexanol, and 1-heptanol are selected as entrainers to separate the azeotropic mixture (H₂O/EM) using azeotropic distillation. The binary vapor liquid equilibrium (VLE) data were determined at 101.3 kPa, including H₂O/EM, EM/1-pentanol, EM/1-hexanol, EM/1-heptanol, H₂O/1-pentanol, H₂O/1-hexanol and H₂O/1-heptanol. Meanwhile, the Herington area test was used to validate the thermodynamic consistency of the experimental binary data. The VLE data for the experimental binary system were analyzed using the NRTL, UNIQUAC, and Wilson activity coefficient models, showing excellent agreement between predictions and measurements. Finally, molecular simulations were employed to calculate interaction energies between components, providing insights into the VLE behavior. The azeotropic distillation process was simulated using Aspen Plus to evaluate the separation performance and determine the optimal operating parameters. Therefore, this study provides guidance and a foundational basis for the separation of H₂O/EM systems at 101.3 kPa. Full article

We refine a bottom-up, quantity-clearing framework of Bitcoin price formation that couples its fixed 21-million-coin cap with plausible demand growth and execution behavior. This approach relies on first-principles economic supply-and-demand dynamics rather than assumptions about anticipated Bitcoin price appreciation, its price history, or its potential effectiveness in demonetizing other asset classes. We considered five key high-level factors that may affect price determination: level of market demand; intertemporal investment preferences; fiat-denominated withdrawal sensitivity; initial liquid supply; and daily withdrawal levels from liquid supply. With a goal of both increasing understanding of the impacts of price drivers and developing probabilistic forecasts, we show two models: (1) a baseline to assess the impacts of parameter changes, alone and in combination, on Bitcoin price trajectories and liquid supply over time and (2) a Monte Carlo simulation that incorporates uncertainty across a range of uncertain parameterizations and presents probabilistic price and liquid supply forecasts to 2036. Our baseline model highlighted the importance of liquid supply and withdrawal sensitivity in price impacts. The Monte Carlo simulation results suggest a 50% likelihood that Bitcoin price will exceed USD 5.17 M by April 2036. Generally, prices from the low single millions to the low tens of millions per Bitcoin by 2036 emerge under broad parameter sets; hyperbolic paths to higher price levels are relatively rare and concentrate when liquid supply falls near or below BTC 2 M and withdrawal sensitivity is low. Our results help locate where right-tail risk and disorderly market outcomes concentrate and suggest that policy tools are available to help guide trajectories. Full article

Background: Pathological pregnancy is associated with various complications that may affect the health of both the mother and her offspring. In recent years, lipid metabolites such as hydroxyeicosatetraenoic (HETE) fatty acids and hydroxyoctadecadienoic (HODE) fatty acids have gained increasing interest as potential biomarkers of pathological processes in pregnancy. The aims of the present study were to investigate changes in HETE and HODE levels during pathological pregnancy and to assess their potential role in the development and monitoring of pregnancy complications. Attempts were made to determine associations in cross-sectional studies and relationships in longitudinal ones. Methods: In this study, a liquid chromatograph (HPLC) was used to separate the eicosanoids. The study group consisted of 72 Caucasian women, divided into a control group (n = 51) and a group with non-physiological pregnancy (n = 21). Results: The study results show that the levels of the tested metabolites of the cyclooxygenase (COX) and lipoxygenase (LOX) pathways increased as pregnancy progressed. Women with non-physiological courses of pregnancy who developed gestational diabetes and/or preeclampsia were characterized by dysregulation of the inflammatory signaling processes involving eicosanoids. Conclusions: Carbohydrate abnormalities during pregnancy were mainly associated with increased synthesis of 5-oxoETE and the use of 5-HETE in the control group but were not visible in the diabetic group. HODE acids probably do not play a significant role in pathological pregnancy. The relatively small size of the pathological group and the wide range of gestational age mean that the tests should be standardized and carried out on a larger scale. Full article

Given NMN’s (Nicotinamide mononucleotide, NMN) potential pet health benefits and wide use in pet foods, the lack of standardized detection methods hinders quality control. This study developed and validated a simple, rapid HPLC (High-Performance Liquid Chromatography, HPLC) method for NMN determination in pet foods. The method showed good linearity (5–500 μg/mL), LOD (1.0 mg/kg), LOQ (2.0 mg/kg), precision, stability, reproducibility, and spiked recoveries (97.3–109%, RSD < 6.0%). And most tested commercial samples met the standards. This method is simple, efficient, and accurate, supporting pet food NMN detection, quality control, regulation, and pet health protection. Full article

X-ray absorption spectroscopy (XAS) and X-ray emission spectroscopy (XES) are analytical techniques enabling precise analysis of the electronic structure and local atomic environment in chemical compounds and materials. Their application spans materials science, chemistry, biology, and environmental sciences, supporting studies on catalytic mechanisms, redox processes, and metal speciation. A key advantage of both techniques is element selectivity, allowing the analysis of specific elements without matrix interference. Their high sensitivity to chemical state and coordination enables determination of oxidation states, electronic configuration, and local geometry. These methods are applicable to solids, liquids, and gases without special sample preparation. Modern XAS and XES studies are typically performed using synchrotron radiation, which provides an intense, monochromatic X-ray source and allows advanced in situ and operando experiments. Sub-techniques such as XANES (X-ray absorption near-edge structure), EXAFS (Extended X-ray Absorption Fine Structure), and RIXS (resonant inelastic X-ray scattering) offer enhanced insights into oxidation states, local structure, and electronic excitations. Despite their broad scientific use, applications in pharmaceutical research remain limited. Nevertheless, recent studies highlight their potential in analyzing crystalline active pharmaceutical ingredients (APIs), drug–biomolecule interactions, and differences in drug activity. This review introduces the fundamental aspects of XAS and XES, with an emphasis on practical considerations for pharmaceutical applications, including experimental design and basic spectral interpretation. Full article

This research details the development and evaluation of a Modern Ultrasonic Cleaning Tank (MUCT) designed to enhance cleaning efficiency in jewelry manufacturing, particularly for silver jewelry, replacing the traditional method, which was less efficient and had higher operating costs. The MUCT offers capabilities of single- or dual-frequency ultrasonic operation (28 kHz and 40 kHz) and adjustable transducer positioning. An advanced method involving computer simulations, utilizing harmonic response analysis and transient dynamic analysis, was employed to determine the acoustic pressure inside the MUCT, thereby indicating the cavitation intensity required to achieve high cleaning efficiency. Simulation results confirm that this design can distribute acoustic pressure throughout the MUCT, as intended. A prototype MUCT was assembled, and its operation was validated through foil corrosion tests, ultrasonic power concentration (UPC) measurements, and jewelry cleaning tests. The results revealed that the MUCT’s center provided the maximum UPC of 28 W/L and an acoustic pressure of 30.43 MPa, effectively operating at single and dual frequencies, and achieving superior dirt removal. The highest cleaning efficiency of 100% was achieved using dual frequency with a 97% water and 3% dishwashing liquid mixture at 60 °C, exceeding the 23.52% obtained with water at 27 °C without ultrasonic treatment. The MUCT, successfully integrated into the manufacturing process, offers customizable features to meet various cleaning needs, providing flexibility, improved performance, and cost savings. Full article

Background: Clonazepam is a benzodiazepine drug indicated in all clinical forms of epileptic seizures, various forms of myoclonic seizures, myoclonus and other abnormal movements. At present, it is classified as a hazardous drug requiring special precautions for personnel at reproductive risk, according to a technical document produced by the Spanish National Institute for Safety and Health at Work (INSST), in collaboration with the Spanish Society of Hospital Pharmacy (SEFH). The commercial solutions of clonazepam, for oral and parenteral administration, are supplied by laboratories in glass containers. Repacking in pre-filled polypropylene (PP) syringes, made in the pharmacy service, and in aseptic conditions, may facilitate its administration and reduce the risks to the health or safety of nursing personnel. Nevertheless, there is a lack of stability studies of clonazepam in pre-filled PP syringes. Objectives: To evaluate the physicochemical stability of commercial clonazepam 2.5 mg/mL oral solution and 1 mg/mL parenteral solution repackaged in pre-filled PP syringes under various storage conditions. Methods: A rapid, linear, precise and sensitive high-performance liquid chromatography (HPLC) method for chemical stability studies of Clonazepam 1 mg/mL (parenteral use) and 2.5 mg/mL (oral use) in solution was implemented after repackaging in pre-filled PP syringes. The studies were conducted by measuring concentrations of oral and parenteral clonazepam in pre-filled syringes, at various time points, over 30 days in several different storage conditions: oral clonazepam protected from light in refrigerator and at controlled room temperature exposed to ambient light; parenteral clonazepam protected from light in a refrigerator and at controlled room temperature protected or unprotected from light. Visual aspects and pH change as well as crystal formation were checked to determine physical stability. Results: The degradation of the active ingredient in all groups was less than 10% after 30 days. No evidence of crystal formation, pH and visual aspect changes were observed. Conclusions: Clonazepam 1 mg/mL parenteral solution and 2.5 mg/mL oral solution in pre-filled PP syringes are stable for up to 30 days in the tested conditions. The centralized repackaging of clonazepam in pre-filled PP syringes, connected to a closed safety system, in the pharmacy service, reduces drug manipulation by nursing staff decreasing the risk of occupational exposure. Full article

The study aimed to evaluate the effect of betanin—a bioactive, natural pigment found in beetroot and prickly pear—on cognitive function, motor performance, and neurotransmission in a mouse model of Parkinson’s disease (PD). Aged mice with PD-like symptoms induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were pretreated with betanin (50 or 100 mg/kg b.w./day) via drinking water. Behavioural tests assessed motor skills, anxiety-related behaviour, and spatial memory. Biochemical analyses of central nervous system structures were conducted using high-performance liquid chromatography (HPLC) to determine neurotransmitter levels and metabolites. Betanin improved motor and cognitive functions in MPTP-treated mice. While learning ability remained unchanged, the 50 mg/kg dose alleviated spatial memory deficits. Biochemically, betanin moderately limited dopamine depletion and significantly influenced dopamine metabolism and serotonin levels. These findings suggest that betanin, as a functional food component, may exert neuroprotective effects and support cognitive and motor function in neurodegenerative conditions such as PD. Full article

Immortalized adrenal, placental and gonadal cell models are often termed steroidogenic based on steroid hormone production and steroidogenic enzymes. Profiling of ‘classic’ steroid metabolites is common; however, downstream untargeted metabolites remain unidentified. This study characterized steroidogenesis in human adrenal H295R and H295A; placental BeWo and JEG-3; mouse Leydig MA-10; and mouse adrenal Y-1 and OS-3 cells. Steroids were determined under basal, stimulated and serum-free conditions using liquid chromatography–mass spectrometry. This study identified distinct differences in mineralocorticoid and glucocorticoid production in the two human adrenal models and between the human and mouse adrenal models; unconventional hydroxylated progesterone steroid metabolites in all models which were most abundant in MA-10 cells; glucocorticoids and abundant classical androgens in MA-10 cells; 11-oxy androgens in H295R, H295A and MA-10 cells; comparable levels of the classical androgens in H295R and MA-10 cells, while 11-oxy androgen were more abundant in H295R and H295A cells; and high pregnenolone and progesterone in placental models with limited hydroxylated progesterone metabolites. Our detailed protocols and comprehensive steroid profiles provide an invaluable guide to researchers for in vitro investigations into steroidogenesis. Full article

Manure is a valuable organic resource for sustainable agriculture, enhancing soil fertility and promoting nutrient cycling; however, it also contributes significantly to methane and nitrous oxide emissions. The European Green Deal and Latvia’s National Energy and Climate Plan have set targets for reducing agricultural greenhouse gas (GHG) emissions, including those related to improved manure management. Therefore, this research aims to estimate the future manure production in Latvia to determine the potential for reducing GHG emissions by 2050. Using the LASAM model developed in Latvia, the number of farm animals, the amount of manure, and the associated GHG emissions were projected for the period up to 2050. The calculations followed the Intergovernmental Panel on Climate Change (IPCC) methodology and were based on national indicators and current national GHG inventory data covering the period of 2021–2050. Significant changes in the structure of manure in Latvia are predicted by 2050, with the proportion of liquid manure expected to increase while the amounts of solid manure and manure deposited by grazing animals are expected to decrease. The GHG emission projection results indicate that by 2050, total emissions from manure management will decrease by approximately 5%, primarily due to a decline in the number of farm animals and, consequently, a reduction in the amount of manure. In contrast, methane emissions are expected to increase by approximately 5% due to production intensification. The research results emphasise the need to introduce more effective methane emission reduction technologies and improved projection approaches. Full article

(1) Background: Caffeine is one of the most widely consumed psychoactive substances. Its safety profile and short half-life make it an ideal drug model for studying the pharmacokinetics of caffeine. This study aimed to develop a method for determination of caffeine in a small volume of saliva (200 µL). (2) Methods: Solid-phase extraction was employed to isolate caffeine from saliva, followed by quantitative analysis using liquid chromatography coupled with diode-array detection. Chromatographic separation was achieved on a C18 column, using a gradient mobile phase of acetonitrile and 0.1% formic acid. (3) Results: The method was validated for selectivity, linearity, precision, and accuracy. Linearity was established over the range of 10–10,000 ng/mL (R² = 0.995). The coefficients of variation for intra- and inter-day precision for the three tested caffeine concentrations did not exceed 12.11%. Recovery from spiked saliva samples exceeded 90.53%. The developed method was applied to preliminary studies to follow the pharmacokinetics of caffeine in saliva. The concentration of the substance was studied in the saliva obtained from a volunteer after espresso consumption. (4) Conclusions: The developed method will offer a reliable approach for non-invasive caffeine monitoring in clinical and research applications. Full article