Search Results (174)

Background/Objectives: Propofol is frequently used as an intravenous anesthetic and is rapidly metabolized. Therefore, if it could be administered non-invasively (e.g., orally) as premedication, it might hasten emergence from anesthesia, thereby improving patient safety. However, it undergoes extensive first-pass metabolism in the liver and intestines, limiting the route for premedication. We evaluated whether intranasal delivery of a propofol-encapsulated liposome solution improves systemic exposure and bioavailability in rabbits. Methods: A propofol-encapsulated liposome solution was administered to rabbits via the intravenous, oral, and intranasal routes. Blood propofol concentrations were measured for up to 60 min after administration and the area under the concentration–time curve (AUC_0–60) and bioavailability of the propofol-encapsulated liposome solution were compared with those of the non-encapsulated propofol formulation. The differences were tested by two-way analysis of variance (ANOVA) with Šidák’s post hoc multiple-comparisons test and the Mann–Whitney test (α = 0.05). Results: The AUC_0–60 for blood propofol concentrations after intravenous administration was significantly higher with the propofol-encapsulated liposome solution than with the non-encapsulated propofol formulation (3038.8 ± 661.5 vs. 1929.8 ± 58.2 ng·min/mL; p = 0.0286). By contrast, no increase in blood propofol concentrations was observed after oral administration, whereas intranasal administration increased blood propofol concentrations and yielded significantly higher bioavailability compared with the non-encapsulated propofol formulation (16.4 ± 7.3% vs. 2.0 ± 1.2%; p = 0.0286). Conclusions: The findings of the present study suggest that intranasal liposomal propofol increased systemic availability compared with a non-encapsulated formulation, supporting further evaluation as a candidate premedication approach for propofol. Full article

We investigate the effect of general relativity on the Sitnikov problem. The Sitnikov problem is one of the simplest three-body problems, in which the two primary bodies (a binary system) have equal mass m and orbit their barycenter, while the third body is treated as a test particle under Newtonian gravity. The trajectory of the test particle is perpendicular to the orbital plane of the binary (along z-axis) and passes through the barycenter of the two primaries. To study the general relativistic contributions, we first derive the equations of motion for both the binary and the test particle based on the first post-Newtonian Einstein–Infeld–Hoffmann equation, and integrate these equations numerically. We examine the behavior of the test particle (third body) as a function of the orbital eccentricity of the central binary e, the dimensionless gravitational radius $\lambda$, which characterizes the strength of general relativistic effect, and the initial position of the test particle ${\overline{z}}_0$. Our numerical calculations reveal the following; as general relativistic effects $\lambda$ increase and the eccentricity e of the binary orbit grows, the distance $\overline{r}$ between the test particle and the primary star undergoes complicated oscillations over time. Consequently, the gravitational force acting on the test particle also varies in a complex manner. This leads to a resonance state between the position $\overline{z}$ of the test particle and the distance $\overline{r}$, causing the energy E of the test particle to become $E\ge 0$. This triggers the effective ejection of the test particle due to the gravitational slingshot effect. In this paper, we shall refer to this ejection mechanism of test particle as the “Sitnikov mechanism.” As a concrete phenomenon that becomes noticeable, the increase in general relativistic effects and the eccentricity of the binary orbit leads to the following: (a) ejection of test particles from the system in a shorter time, and (b) increasing escape velocity of the test particle from the system. As an astrophysical application, we point out that the high-velocity ejection of test particles induced by the Sitnikov mechanism could contribute to elucidating the formation processes of astrophysical jets and hyper-velocity stars. Full article

We propose a novel telescope concept based on Earth’s gravitational lensing effect, optimized for the detection of distant dark matter sources, particularly axion-like particles (ALPs). When a unidirectional flux of dark matter passes through Earth at sufficiently high velocity, gravitational lensing can concentrate the flux at a distant focal region in space. Our method combines this lensing effect with stimulated backward reflection (SBR), arising from ALP decays that are induced by directing a coherent electromagnetic beam toward the focal point. The aim of this work is to numerically analyze the structure of the focal region and to develop a framework for estimating the sensitivity to ALP–photon coupling via this mechanism. Numerical calculations show that, assuming an average ALP velocity of 520 km/s—as suggested by the observed stellar stream S1—the focal region extends from $9\times {10}^9$ m to $1.4\times {10}^{10}$ m, with peak density near $9.6\times {10}^9$ m. For a conservative point-like ALP source located approximately 8 kpc from the solar system, based on the S1 stream, the estimated sensitivity in the eV mass range reaches $g/M=\mathcal{O}\left({10}^{-22}\right){\mathrm{GeV}}^{-1}$. This concept thus opens a path toward a general-purpose, space-based ALP observatory that could, in principle, detect more distant sources—well beyond $\mathcal{O}\left(10\right)\mathrm{kpc}$—provided that ALP–photon coupling is sufficiently strong, that is, $M\ll M_{\mathrm{Planck}}$. Full article

Introduction: The sodium-to-potassium (Na:K) ratio in the diet is a critical biomarker for cardiovascular and metabolic health, yet global adherence to recommended levels remains poor. Objectives: The objective of this study was to identify dietary determinants of the dietary Na:K ratio and its associations with micronutrient intake and diet quality. Methods: An observational cross-sectional survey was conducted in a representative sample of manufacturing workers through a combined stratified proportional and two-stage probability sampling plan, with strata defined by company size and industrial sector from the state of Rio Grande do Norte, Brazil. Dietary intake was assessed using 24 h recalls via the Multiple Pass Method, with Na:K ratios calculated from quantified food composition data. Diet quality was assessed with the Diet Quality Index-International (DQI-I). Multiple linear regression was used to analyze associations of Na:K ratio with the study variables. Results: The survey was conducted in the state of Rio Grande do Norte, Brazil, in 921 randomly selected manufacturing workers. The sample mean age was 38.2 ± 10.7 years, 55.9% males, mean BMI 27.2 ± 4.80 kg/m². The mean Na:K ratio was 1.97 ± 0.86, with only 0.54% of participants meeting the WHO recommended target (<0.57). Fast food (+3.29 mg/mg per serving, p < 0.001), rice, bread, and red meat significantly increased the ratio, while fruits (−0.16 mg/mg), dairy, white meat, and coffee were protective. Higher Na:K ratios were associated with lower intake of calcium, magnesium, phosphorus, and vitamins C, D, and E, as well as poorer diet quality (DQI-I score: −0.026 per 1 mg/mg increase, p < 0.001). Conclusions: These findings highlight the critical role of processed foods in elevating Na:K ratios and the potential for dietary modifications to improve both electrolyte balance and micronutrient adequacy in industrial workers. The study underscores the need for workplace interventions that simultaneously address sodium reduction, potassium enhancement, and overall diet quality improvement tailored to socioeconomic and cultural contexts, a triple approach not previously tested in intervention studies. Future studies should further investigate nutritional consequences of imbalanced Na:K intake. Full article

Foeniculum vulgare Mill. (Apiaceae) is an aromatic medicinal plant known for its anti-inflammatory, antispasmodic, antiseptic, carminative, diuretic, and analgesic properties. This study aimed to investigate the effects of F. vulgare essential oil (FVEO; 25, 150, and 300 μL/L) on the cognitive performance and brain oxidative stress in a scopolamine (SCOP; 100 μM)-induced zebrafish model of cognitive impairment. Additionally, the pharmacokinetic properties and bioactivity profiles of the main FVEO constituents were predicted to be used in silico tools, including SwissADME, pkCSM, PASS online, and ADMETlab 2.0. Behavioral assays, novel tank diving test (NTT), Y-maze, and novel object recognition (NOR) test, were used to evaluate anxiety-like behavior, spatial memory, and recognition memory, respectively. Biochemical assessments of acetylcholinesterase (AChE) activity and oxidative stress biomarkers were also conducted. The results demonstrated that FVEO significantly improved cognitive performance in SCOP-treated zebrafish, normalized AChE activity, and reduced oxidative stress in the brain. These findings suggest the therapeutic potential of FVEO in ameliorating memory impairment and oxidative damage associated with neurodegenerative disorders such as Alzheimer’s disease (AD). Full article

Extending the recovery ratio (RR) of brackish water reverse osmosis (RO) plants to zero liquid discharge (ZLD, i.e., ≥95%) is vital, particularly inland, where the cost of safe retentate disposal is substantial. Various suggestions appear in the literature; however, many of these are impractical in the real world. Often, the limiting parameter that determines the maximal recovery is the SiO₂ concentration that develops in the RO retentate and the need to further desalinate the high osmotic pressure retentates produced in the process. This work combines well-proven treatment schemes to attain RR ≥ 95% at a realistic cost. The raw brackish water undergoes first a 94% recovery nanofiltration (NF) step, whose permeate undergoes a further 88-RR RO step. To increase the overall RR, the retentate of the 1st RO step undergoes SiO₂ removal performed via iron electro-dissolution and then a 2nd, 43% recovery, RO pass. The retentate of this step is combined with the NF retentate, and the mix is treated with mechanical vapor recompression (MVR) (RR = 62.7%). The results show that >95% recovery can be attained by the suggested process at an overall cost of ~USD 0.70/m³. This is ~60% higher than the USD 0.44/m³ calculated for the baseline operation (RR = 82.7%), making the concept feasible when either the increase in the plant’s capacity is regulatorily requested, or when the available retentate discharge method is very costly. The cost assessment accuracy was approximated at >80%. Full article

The role of weirs in flow regulation in water resources infrastructure and flood control is well known. In the meantime, the study of full-width plate weirs (FWPW), due to their wide application and lacking findings, is of great importance. In this study, experimental models were conducted at Babol Noshirvani University of Technology to investigate flow passing through FWPWs with five different heights (p = 0.07, 0.09, 0.11, and 0.15 m) under eight discharge conditions (Q = 1.4 to 6.3 L/s). The experiments were carried out in a flume measuring 4 m in length, 0.6 m in width, and 0.2 m in height. The discharges were measured with a calibrated flowmeter, and the water depths upstream of the weir (h) and the tailwater depths (h₁) were measured with a point gauge with an accuracy of 0.1 mm. For each test, the discharge coefficient (C_d), relative residual energy (E₁/E₀), and relative energy dissipation ((E₀ − E₁)/E₀) were computed. The proposed equation for calculating discharge achieved good accuracy with RMSE = 0.0002, MAE=0.0002, and R² = 0.997. Results show a reducing trend of C_d by increasing h/P, which is compatible with previous results. It was observed that at a constant discharge, relative residual energy reduces by an average of 47% by increasing weir height, and at a constant P, increasing flow discharge increases it a little. A novel accurate equation for relative energy dissipation in FWPW was proposed based on h/P that provided specific constant coefficients for each p value. Full article

Background and Objectives: Nonischemic cardiomyopathies comprise a wide spectrum of heart muscle disorders characterized by different morphological, functional, and tissue abnormalities. Cardiovascular magnetic resonance (CMR) represents the gold standard imaging modality for assessing cardiac morphology, systolic function, and tissue characterization, thereby aiding in early diagnosis, precise phenotyping, and tailored treatment. The aim of this review is to provide an up-to-date overview of CMR techniques for studying myocardial perfusion and their applications to nonischemic cardiomyopathy, not only to rule out an underlying ischemic aetiology but also to investigate the pathophysiological characteristics of microcirculatory dysfunction in these patients. Materials and Methods: We performed a structured review of the literature focusing on first-pass gadolinium perfusion sequences, stress protocols, and emerging pixel-wise perfusion mapping approaches. Studies were selected to illustrate the methods for image acquisition, post-processing, and quantification of myocardial blood flow (MBF) and myocardial perfusion reserve (MPR), as well as to highlight associations with clinical endpoints. Results: First-pass CMR perfusion imaging reliably detects diffuse and regional microvascular dysfunction across cardiomyopathies. Semi-quantitative parameters (e.g., upslope, MPRI) and quantitative MBF mapping (mL/g/min) have demonstrated that impaired perfusion correlates with disease severity, extent of fibrosis, and adverse outcomes, including heart failure hospitalization, arrhythmias, and mortality. Novel automated pixel-wise mapping enhances reproducibility and diagnostic accuracy, distinguishing coronary microvascular dysfunction from balanced three-vessel disease. Microvascular dysfunction—present in approximately 50–60% of dilated cardiomyopathy (DCM), 40–80% of hypertrophic cardiomyopathy (HCM), and >95% of cardiac amyloidosis (CA) patients—has emerged as a key driver of adverse outcomes. Perfusion defects appear early, often preceding overt hypertrophy or fibrosis, and provide incremental prognostic value beyond conventional CMR metrics. Conclusions: CMR represents a powerful tool for detecting myocardial perfusion abnormalities in nonischemic cardiomyopathies, improving phenotyping, risk stratification, and personalized management. Further standardization of quantitative perfusion techniques will facilitate broader clinical adoption. Full article

The Vinca alkaloid vindoline was coupled at position 17 with several trisubstituted phosphine derivatives and their in vitro anticancer activities on 60 human tumor cell lines (NCI60) were investigated. This phosphonium-type ionic side chain is beneficial because it allows therapeutic molecules to pass through the cell membrane. Thus, the candidates coupled to it can exert their activities in the mitochondria. The coupling of vindoline with the trisubstituted phosphines was achieved through flexible or rigid linkers. Instead of the ionic phosphonium structural part, a neutral moiety, namely the triphenylmethyl group, was also added to the side chain, being sterically similar but without a charge and phosphorus atom. In addition, the triphenylphosphine element was also built at position 10 of vindoline. Most of the derivatives showed low micromolar growth inhibition (GI₅₀) values against most cell lines. Among them, conjugate 9e was outstanding: it exhibited nanomolar anticancer activity on the RPMI-8226 leukemia cell line (GI₅₀ = 20.0 nM). Compound 9g elicited cell cycle disturbance and apoptosis on A2780 ovary cancer cells and inhibited their migration at subantiproliferative concentrations. The selectivity of the conjugates was determined by their effects on non-tumor Chinese hamster ovary (CHO) cells in the CellTiter-Glo Luminescent Cell Viability Assay. Compound 9e showed an estimated half-maximal inhibitory concentration (IC₅₀) value of 1.36 µM, suggesting good selectivity on cancer cells. These results open new perspectives of novel phosphonium-based vindoline derivatives as anticancer compounds. Full article

Cathinones, a class of synthetic new psychoactive substances (NPSs), continue to emerge and pose public threats. Government control efforts often lead to the emergence of new isomers, which have adverse repercussions on NPSs identification and risk prediction. This work reports on the synthesis and structural characterization of twenty chloro-cathinones, including different isomers, to create analytical data to facilitate their identification in forensic and clinical contexts. Additionally, the potential of these cathinones to cause neuronal damage was evaluated. In vitro cytotoxicity was assessed using a differentiated human neuroblastoma cell line (SH-SY5Y) as a dopaminergic neuronal model. The tested cathinones showed LC₅₀ values from 0.6 to 2.5 mM, with 4-CBC being the most cytotoxic. The most toxic cathinones increase reactive oxygen species levels and/or cause mitochondrial membrane potential depolarization. Furthermore, this study explored, for the first time, the effect of cathinones on the cholinergic system through acetylcholinesterase (AChE) inhibition. All tested cathinones inhibited AChE with IC₅₀ values between 0.1 and 2 mM. Molecular docking analysis revealed that the most inhibitory cathinones interacted with the CASs and PASs in AChE’s active gorge. These findings provide valuable insights into the effects of cathinones, highlighting potential health risks and structural features that may influence their toxicity towards the cholinergic system and neuronal damage. Full article

In this paper, we have investigated the existence of normalized solutions for a class of fractional Kirchhoff equations involving nonlinearity and critical nonlinearity. The nonlinearity satisfies $L^2$-supercritical conditions. We transform the problem into an extremal problem within the framework of Lagrange multipliers by utilizing the energy functional of the equation in the fractional Sobolev space and applying the mass constraint condition (i.e., for given $m>0,$${\int }_{{\mathbb{R}}^N}{|u|}^{2}dx=m^2$). We introduced a new set and proved that it is a natural constraint. The proof is based on a constrained minimization method and some characterizations of the mountain pass levels are given in order to prove the existence of ground state normalized solutions. Full article

AIM: Higher exercise blood pressure in adults correlates with many cardiometabolic markers. The aim of this study was to investigate the main determinants of longitudinal variations in exercise blood pressure in young athletes. METHODS: A longitudinal retrospective study was conducted on adolescent athletes who underwent at least two sport-related pre-participation screening visits, including exercise testing with a standardized incremental ramp protocol on treadmill. Blood pressure was assessed at rest (SBP_rest), at the 3rd minute of exercise (SBP_3min), and at peak exercise (SBP_peak). Predictors of blood pressure response (i.e., respective changes vs. baseline (Δ)) were determined by multivariate regression models after adjustment for age, sex, follow-up duration, related baseline SBP values, characteristics of sport, and ΔBMI. RESULTS: A total of 351 young athletes (mean age at baseline 13 ± 2 years, 54% boys, average follow-up duration 3.4 ± 2.2 years) were enrolled. BMI increased by 1.5 ± 1.8 kg/m² (p < 0.001) during follow-up. At baseline, mean SBP_rest was 103 ± 14 mmHg, mean SBP_3min 124 ± 18 mmHg, and mean SBPpeak 154 ± 23 mmHg. A significant between-visit increase in SBP_rest (ΔSBP_rest 7.0 ± 17.4 mmHg; p < 0.001), ΔSBP_3min (4.8 ± 11 mmHg, p < 0.001), and ΔSBP_peak (11.7 ± 24 mmHg, p < 0.001) was observed. ΔSBP_3min was significantly predicted by male sex (p < 0.01), baseline BMI (p < 0.01), ΔBMI (p < 0.01), and number of practiced sports (p < 0.05), whereas ΔSBP_peak was positively predicted by male gender (p < 0.01), baseline BMI (p < 0.05), and ΔBMI (p < 0.01) and negatively by baseline resting heart rate (p < 0.01). In a logistic regression model, ΔBMI was the only independent determinant of passing from a lower to an upper quartile of SBP_3min (p < 0.001), while ΔBMI and male sex were independent determinants of moving to a higher quartile of SBP_peak (p < 0.001). CONCLUSIONS: Increase in BMI during development and male sex are independent determinants of the increase in exercise blood pressure, both at light and maximal intensity, in a population of adolescent athletes. Full article

Background: Surgery in periampullary cancers (PAC) is associated with high morbimortality rates. There are multiple scores used to predict surgical risk. This study aims to identify a possible correlation between POSSUM, P-POSSUM, E-PASS, and mE-PASS scores and morbimortality in patients operated on for PAC. Methods: POSSUM, P-POSSUM, E-PASS, and mE-PASS were calculated for patients operated for PAC in Hospital de Braga between 1 January 2011 and 31 August 2021. The calibration and discrimination of scores were analyzed by comparing the predicted mortality and morbidity with the observed one and by evaluating the Receiver Operating Characteristic (ROC) curve, respectively. Results: The study included 58 patients. The most frequent location was the ampulla of Vater (AVC) (43.10%), and the most frequent stage was IIb (48.28%). The postoperative mortality and morbidity observed at 30 days were 3.45% and 37.93%, respectively. P-POSSUM (O:E 0.45), POSSUM (O:E 0.16), and E-PASS (O:E 0.03) overestimated mortality, and mE-PASS underestimated it (O:E 1.89). In most subgroups, both POSSUM scores showed the best calibration. CRS and E-PASS showed the highest discriminative ability for mortality (AUC 0.982). In the pancreatic head carcinoma subgroup, the SSS showed better calibration for morbidity. The operative score had the best discrimination for the CAV subgroup (AUC 0.767) and for stage IIb (AUC 0.900). No scale showed discriminative ability in overall morbidity. Conclusions: POSSUM and P-POSSUM obtained the best calibration regarding subgroup mortality. E-PASS and CRS showed the highest discrimination for mortality, and the operative score showed the greatest discrimination for morbidity in the subgroups. Full article

Durability is crucial for reinforced concrete, directly influencing the service life of structures. The presence of aggressive agents, especially chloride ions, significantly impacts durability. This study investigates the differences between ASTM C1202 and IBRACON/NT Build 492 standards in concrete containing various types of cement designed for a characteristic compressive strength of 40 MPa. Forty-eight cylindrical samples were prepared using eight types of Portland cement, including those with blast furnace slag, filler, and pozzolanic materials. Chloride migration tests were performed according to the ASTM C1202/2022 and IBRACON/NT Build 492/1999 methodologies. At a 95% confidence level, the results indicated that concrete made with filler-containing cement (PCII F-SR and PC II F) showed the poorest chloride resistance, with charge passing values exceeding 4000 coulombs (ASTM C1202) and diffusion coefficients above 10 × 10⁻¹² m²/s (IBRACON/NT Build 492). In contrast, concrete containing high slag cement (PC III-SR) and pozzolan cement (PC IV) demonstrated superior resistance to chloride penetration, with charge passing values below 1500 coulombs and diffusion coefficients under 5 × 10⁻¹² m²/s. Notably, discrepancies in classification were observed, as PC II Z (fly-ash based) and PC II E-SR (slag-based) received different ratings under the two methods. ASTM C1202 was found to be more stringent than NT Build 492, highlighting significant variations in the classification criteria between these standards. Based on the findings, new interval values are proposed for classifying concrete regarding the risk of chloride ion penetration, particularly for the ASTM C1202 standard, in order to better align with performance-based durability criteria and improve classification accuracy. Full article

Phytolacca americana fruits exhibit a wide range of biological activities, including antimicrobial, anti-inflammatory, and anticancer properties. This study aims to investigate the phenolic profile of hydroethanolic extracts from both fresh (PEC) and dried (PEU) fruits of P. americana using high-performance liquid chromatography (HPLC) and to evaluate their impact on anxiety-like behavior, memory, oxidative stress, and cholinergic status in zebrafish (Danio rerio, Tübingen strain) treated with scopolamine (SCO, 100 μM). Acute administration of PEC and PEU (0.1, 0.5, and 1 mg/L) was conducted for one hour per day. In silico analyses were performed to evaluate the pharmacokinetic characteristics of the phenolic compounds discerned in the two extracts, using platforms such as SwissAdme, Molinspiration, ProToX-III, AdmetLab 3.0, PKCSM, and PASS. Anxiety-like behavior and memory performance were assessed through specific behavioral assays, including the novel tank test (NTT), light/dark test (LD), novel approach test (NAT), Y-maze, and novel object recognition (NOR). Subsequently, the activity of acetylcholinesterase (AChE) and the extent of oxidative stress in the zebrafish brain were investigated. Our findings suggest that both PEC and PEU possess anxiolytic effects, alleviating SCO-induced anxiety and enhancing cognitive performance in amnesic zebrafish. Furthermore, these extracts demonstrated the ability to mitigate cholinergic deficits by inhibiting AChE activity and supporting antioxidant defense mechanisms through increased activity of antioxidant enzymes and reduced lipid and protein peroxidation. These results highlight the potential use of P. americana fruit extracts in managing anxiety and cognitive impairments related to dementia conditions. Full article