Search Results (158)

Background/Objectives: Accurate and timely triage is essential for optimizing clinical outcomes and resource allocation in emergency departments (EDs). The Peripheral Perfusion Index (PPI), a non-invasive and objective parameter derived from pulse oximetry, may offer added value in early risk stratification. This study aimed to analyze the correlation between the PPI measured at triage and at Emergency Severity Index (ESI) levels, as well as to determine if the PPI may function as a predictive tool to facilitate early risk identification before patient disposition. Methods: In this prospective cross-sectional study, adult ambulatory patients presenting to a tertiary care ED were enrolled. At triage, PPI and standard vital signs were recorded, and patients were classified using the five-level ESI system. The diagnostic performance of PPI and ESI in predicting ED discharge was assessed using receiver operating characteristic (ROC) curve analysis, with comparative evaluation performed via DeLong’s test. Results: Lower PPI values were consistently associated with higher ESI acuity levels and more intensive care requirements. Patients who were discharged had significantly higher median PPI values (4.0) compared to those admitted to wards (2.1) or intensive care units (1.9). PPI also distinguished survivors from non-survivors (median PPI: 3.60 vs. 1.15). ROC analysis showed that the PPI demonstrated a good discriminative capacity for forecasting ED discharge, equal to the efficacy of ESI (AUC: 0.926 vs. 0.903; p < 0.001). Conclusions: The PPI could improve post-triage risk classification and enhance current triage techniques like ESI, especially in cases of unclear or borderline presentations, but further validation in prospective trials is required. Full article

Propolis is a natural resinous substance produced by honeybees that has many biological activities. For thousands of years, it has been widely used as a dietary supplement and traditional medicine to treat a variety of ailments due to its antimicrobial, anti-inflammatory, antioxidant, immunomodulatory, and wound-healing properties. Nutritional supplements and foods may interact with drugs both pharmacodynamically and pharmacokinetically, which could raise clinical concerns. Background/Objectives: This study aimed to investigate the effect of propolis on the plasma disposition of enrofloxacin and to assess the potential pharmacokinetic interaction in rabbits. Methods: In this study, enrofloxacin was applied per os (20 mg/kg) and IM (10 mg/kg) and with propolis (100 mg resin/kg) administration in four groups of rabbits (each of six individuals). Heparinized blood samples were collected at 0, 0.1, 0.3, 0.5, 1, 2, 4, 8, 12, and 24 h post-administration. HPLC-FL was used to analyze the plasma concentrations of enrofloxacin and its active metabolite ciprofloxacin following liquid–liquid phase extraction, i.e., protein precipitation with acetonitrile and partitioning with sodium sulfate. Results: The results revealed that propolis coadministration significantly affected the plasma disposition of enrofloxacin and its active metabolite after both per os and intramuscular administration routes. Significantly greater AUC (48.91 ± 11.53 vs. 26.11 ± 12.44 µg.h/mL), as well as longer T_1/2λz (11.75 ± 3.20 vs. 5.93 ± 2.51 h) and MRT (17.26 ± 4.55 vs. 8.96 ± 3.82 h) values of enrofloxacin and its metabolite ciprofloxacin, were observed after the coadministration of propolis compared to enrofloxacin alone following both per os and IM routes in rabbits. Conclusions: The concurrent use of propolis and prescription medications may prolong the half-life (T_1/2λz) and increase the systemic availability of chronically used drugs with narrow therapeutic indices. The repeated use of drugs such as antibiotics, heart medications, and antidepressants, or drugs with a narrow therapeutic index such as antineoplastic and anticoagulant agents, can cause toxic effects by raising blood plasma levels. Considering the varied metabolism of rabbits and humans, further validation of this study may require thorough clinical trials in humans. Full article

Background: Glucuronide recycling in the gut and liver profoundly affects the systemic and/or local exposure of drugs and their glucuronide metabolites, impacting both clinical efficacy and toxicity. This recycling also alters drug exposure in the colon, making it critical to establish local concentration for drugs targeting colon (e.g., drugs for colon cancer and inflammatory bowel disease). Methods: In this study, a parent–metabolite middle-out physiologically based pharmacokinetic (PBPK) model was built for genistein and its glucuronide metabolite to estimate the systemic and local exposure of the glucuronide and its corresponding aglycone in rats by incorporating UDP-glucuronosyltransferase (UGT)-mediated metabolism and transporter-dependent glucuronide disposition in the liver and intestine, as well as gut microbial-mediated deglucuronidation that enables the recycling of the parent compound. Results: This parent–metabolite middle-out rat PBPK model utilized in vitro-to-in vivo extrapolated (IVIVE) metabolic and transporter clearance values based on in vitro kinetic parameters from surrogate species, the rat tissue abundance of relevant proteins, and saturable Michaelis–Menten mechanisms. Inter-system extrapolation factors (ISEFs) were used to account for transporter protein abundance differences between in vitro systems and tissues and between rats and surrogate species. Model performance was evaluated at multiple dose levels for genistein and its glucuronide. Model sensitivity analyses demonstrated the impact of key parameters on the plasma concentrations and local exposure of genistein and its glucuronide. Our model was applied to simulate the quantitative impact of glucuronide recycling on the pharmacokinetic profiles in both plasma and colonocytes. Conclusions: Our study underlines the importance of glucuronide recycling in determining local drug concentrations in the intestine and provides a preliminary modeling tool to assess the influence of transporter-mediated drug–drug interactions on glucuronide recycling and local drug exposure, which are often misrepresented by systemic plasma concentrations. Full article

Background: Although the value of point-of-care ultrasound (PoCUS) is well-established for specific diseases and in the hands of trained users, its broader impact on overall ED efficiency is not yet fully known. This study aims to evaluate the association of early PoCUS, performed within 1 h of presentation, with ED patient flow, healthcare resource utilization, and quality of care in adults with non-traumatic abdominal pain. Method: This retrospective cohort study included 44,863 adult patients (≥18 years) presenting with non-traumatic abdominal pain from January 2021 to December 2023. Patients were grouped into PoCUS and no-PoCUS categories, with a subgroup analysis for those receiving PoCUS within 1 h, to evaluate ED LOS, and costs for different ED dispositions. Outcomes measured included hospital LOS, costs, mortality, and ICU admission. Results: The mean age of the subjects was 44.4 ± 17.9 years, and 61.2% were female. PoCUS was performed in 39.7% of cases, with 69.6% of these conducted within one hour. Additionally, 30.5% underwent CT. The PoCUS group had a significantly shorter ED LOS compared to the no-PoCUS group among patients admitted to general wards (p < 0.001), but not in outpatient dispositions (p = 0.282) or ICU admissions (p = 0.081). Subgroup analysis of patients receiving PoCUS within 1 h showed a significantly shorter LOS for both outpatient dispositions (p < 0.001) and general ward admissions (p < 0.001), with no effect on ICU admissions (p = 0.869). The presence or absence of CT did not alter these findings. Multivariable analysis indicated that patients who received PoCUS within one hour alone at index visit and admitted after an unscheduled return visit had lower initial ED costs (−9436.1 TWD, p < 0.001) and shorter ED LOS (−11.59 min, p < 0.001) than patients admitted directly at the index visit, with no significant increase in total resource utilization or adverse outcomes after return visits. Conclusions: PoCUS, especially when performed within one hour, was associated with reduced ED LOS and healthcare resource utilization for both outpatient dispositions and inpatient admissions without compromising patient safety or quality of care. Full article

Type 2 diabetes mellitus (T2DM) represents a significant global health burden, especially in populations where rice constitutes a dietary staple. Parboiled rice (PBR), known for its lower glycemic index compared to conventional white rice (WR), may offer benefits in managing postprandial hyperglycemia. Nevertheless, the impact of PBR consumption on insulin sensitivity, β-cell function, and incretin hormone responses remains poorly understood. Methods: This randomized crossover pilot study aimed to assess and compare the acute effects of PBR and WR intake on postprandial glucose regulation, insulin sensitivity, β-cell functionality, and glucagon-like peptide-1 (GLP-1) responses in healthy subjects and individuals with T2DM. A total of 20 participants were recruited and evenly allocated into healthy (n = 10) and T2DM (n = 10) groups. Following the ingestion of either PBR or WR, blood samples were collected at fasting and various postprandial intervals to determine glucose, insulin, and GLP-1 levels. Insulin sensitivity and β-cell function were evaluated using HOMA-IR, Matsuda Index (MI), and Disposition Index (DI). Results: As expected, T2DM participants exhibited significantly elevated fasting glucose and insulin levels compared to healthy controls. Consumption of PBR led to significantly lower postprandial glucose responses in healthy subjects relative to WR. Although a similar trend of reduced glucose levels was observed in T2DM subjects after PBR intake, this reduction did not reach statistical significance. Parallel trends were observed in insulin secretion patterns. Moreover, GLP-1 responses were notably diminished in T2DM individuals compared to healthy participants. Importantly, MI and DI values significantly increased after PBR consumption in healthy individuals compared to those with T2DM, indicating improved insulin sensitivity and β-cell responsiveness. Conclusions: These preliminary findings suggest that PBR consumption may confer beneficial effects by lowering postprandial glucose and enhancing insulin sensitivity. Further studies with larger cohorts are warranted to confirm these outcomes and elucidate the physiological mechanisms behind PBR’s potential role in dietary management strategies for T2DM. Full article

Successful marketing of fresh fruits requires careful attention to the details involved in postharvest handling (PH), which protects fruit’s quality and nutritive and economic value. This study assessed the PH practices of sweet orange marketers in Benue State. Six (6) major orange markets were purposively selected. Thereafter, a total of 104 marketers were randomly sampled. The data were collected using an interview schedule and analysed using the frequencies, percentages, means, Chi-squares, and Pearson’s Product Moment Correlations at α_0.05. The knowledge of PH practices and the level of PH practice utilisation were high. Marketers’ age (r = −0.220, p < 0.05), the use of sacks for packaging (χ² = 23.314, p < 0.01), knowledge of PH (r = 0.272, p < 0.01), and attitudinal disposition towards PH (r = 0.492, p < 0.01) significantly influence the utilisation of PH practices. This study recommends the generation of awareness and sensitisation among marketers by horticultural crop institutions on improved preservation and packaging methods for sweet oranges. Full article

Background: Recent evidence has shown that insulin resistance (IR), a hallmark of nonalcoholic fatty liver disease, predicts bladder cancer (BC) presence. However, the best surrogate marker of IR in predicting BC is still unclear. This study examined the relationships among ten surrogate markers of IR and the presence of BC. Methods: Data from 209 patients admitted to two urology departments from September 2021 to October 2024 were retrospectively analyzed. Individuals (median age 70 years) were divided into two groups (123 and 86 patients, respectively) based on the presence/absence after cystoscopy/TURB of non-metastatic BC. Univariate logistic regression was used to determine the relationships between groups, and the following IR parameters: Triglyceride–Glucose (TyG) index, TyG-BMI, HOMA-IR HOMAB, MetS-IR, Single Point Insulin Sensitivity Estimator, Disposition Index, non-HDL/HDL, TG/HDL-C ratio and Lipoprotein Combine Index. Stepwise logistic regressions were carried out to evaluate the significant predictions and LASSO regression to confirm any significant variable(s). The predictive value of the index test for coexistent BC was evaluated using receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC). Results: The univariate analysis revealed that the TyG index and MetS-IR were associated with the BC presence. Specifically, the associations of the TyG index and MetS-IR were more significant in participants =/> 65 years old. In multivariate analysis, the stepwise logistic regression, evaluating the most representative variables at univariate analysis, revealed a prediction of BC by only TyG index (OR 2.51, p = 0.012), confirmed by LASSO regression, with an OR of 3.13, p = 0.004). Assessing the diagnostic reliability of TyG, it showed an interesting predictive value for the existence of BC (AUC = 0.60; 95% CI, 0.51–0.68, cut-off 8.50). Additionally, a restricted cubic spline model to fit the dose–response relationship between the values of the index text (TyG) and the BC evidenced the presence of a non-linear association, with a high predictive value of the first knot, corresponding to its 10th percentile. The decision curve analysis confirmed that the model (TyG) has utility in supporting clinical decisions. Conclusions: Compared to other surrogate markers of IR, the TyG index is effective in identifying individuals at risk for BC. A TyG threshold of 8.5 was highly sensitive for detecting BC subjects and may be suitable as an auxiliary diagnostic criterion for BC in adults, mainly if less than 65 years old. Full article

Background: Physiologically based pharmacokinetic (PBPK) modeling for biopharmaceutics applications (i.e., physiologically based biopharmaceutics modeling (PBBM)) enables mechanistic modeling from dissolution to absorption and disposition, facilitating the prediction of bioequivalence (BE) outcomes and the delimitation of the safe space. This study aims to identify the product-related parameter driving ibuprofen dissolution to upgrade an existing PBPK model, so that an in vitro safe space and virtual BE (VBE) predictions of IR ibuprofen tablets can be performed. Methods: C_max within- and between-subject variabilities of a previous PBPK model were optimized after identifying crucial physiological parameters for ibuprofen absorption and disposition. In vitro data modeling was performed to estimate the value of the parameter driving ibuprofen dissolution. A safe space was defined for this parameter and the sample size to declare BE was calculated. Finally, VBE simulations were performed to explore the effect of sample size as well as number of trial replicates and runs. Results: C_max variability was adequately predicted after changing V_ss and MRT in stomach and small intestine CV (%) to 10 and 150%, respectively. Particle surface pH was identified as the dissolution key parameter for ibuprofen. A safe space for test product surface pH values of 5.64–6.40 was defined in order to achieve a 90%CI for the C_max ratio within the 80–125% range when the reference product surface pH is 6.02. R-ibuprofen was identified as the most discriminative enantiomer. VBE studies with 24 individuals showed BE outcomes that are sensitive to the number of trial replicates and runs. Conclusions: Ibuprofen particle surface pH has been identified as the in vitro parameter governing dissolution in maleate buffer 7 mM with HCl pH 2.0 pretreatment, allowing to establish an in vitro safe space useful for calculating sample sizes and to evaluate the BE success rate through PBBM/PBPK model-informed VBE simulations. Full article

The present study was undertaken to characterize the plasma kinetic disposition of tolfenamic acid (TA) in freshwater crocodiles. In total, 15 freshwater crocodiles were used in the experiment and randomly divided into three groups, with TA administered at 2 mg/kg body weight (b.w.) intravenously (IV) or at 2 or 4 mg/kg b.w. intramuscularly (IM). Blood samples were collected at predetermined times up to 168 h after IV or IM drug administration. Plasma concentrations of TA were determined using validated high-performance liquid chromatography with a UV detector and then analyzed based on the non-compartmental method. The maximum concentration values of TA were 3.03 µg/mL and 6.83 µg/mL following IM administration at a dose of 2 mg/kg b.w. or 4 mg/kg b.w., respectively. The elimination half-lives were 21.89 h (2 mg/kg; IV), 17.74 h (2 mg/kg; IM), and 13.57 h (4 mg/kg; IM). Following IV administration, the volume of distribution and clearance were 1.58 L/kg and 50.04 mL/h/kg, respectively. The absolute IM bioavailability was 71.0% at a dose of 2 mg/kg b.w. and 92.63% at a dose of 4 mg/kg b.w. The average ± SD of plasma protein binding of TA was 26.15 ± 4.93%. Good bioavailability levels and favorable plasma concentrations of TA were obtained in freshwater crocodiles after IM administrations, considering that this is the preferred route of drug administration in freshwater crocodiles. Multi-dose and pharmacodynamic studies are needed to better establish the safety and efficacy of using TA in this crocodilian species. Full article

Introduction: Dalbavancin (DAL) is a long-acting lipoglycopeptide active against Gram-positive bacteria, including multidrug-resistant isolates. A growing body of evidence supports its efficacy in various difficult-to-treat infections. DAL shows time-dependent bactericidal activity in vitro at free drug concentrations equal to 4×MIC values. However, the optimal dosing scheme for achieving the PK/PD target in multidose treatment has not been fully established. Methods: Pharmacokinetic analysis was based on a nonlinear mixed effects modelling approach performed in NONMEM v7.5/Pirana, while R was used for data management and graphical summaries. Final model parameters were used to simulate the plasma disposition of DAL by Monte Carlo simulations to determine the multidose DAL regimen associated with a 90% target attainment of 100% fT > 4×MIC. Results: A two-compartmental model with first-order elimination and allometric-scaled bodyweight best described DAL disposition in patients with CLcr > 30 mL/min. Monte Carlo simulations showed that two 1500 mg DAL doses 7 days apart granted an optimal PTA > 90% of 100% fT > 4×MIC up to 5, 4, and 3 weeks in patients weighting from 40–80 kg, 80–120 kg and 120–200 kg, respectively. An additional third 1500 mg dose at the above time points by weight bands may extend the optimal PTA up to 9, 7, and 6 weeks of total treatment. Conclusions: Two 1500 mg DAL doses administered 7 days apart could be a valuable starting strategy for patients of all weight classes with CLcr > 30 mL/min. In patients requiring long-term DAL treatment, the optimal timing of additional administrations should be guided by routine TDM or empirically through patients’ total body weight when TDM is unavailable. Full article

Microplastics represent a threat due to their ability to enter the food chain, with harmful consequences for living organisms. The riskiness of these particles is also linked to the release of other contaminants, such as heavy metals. Solute Carriers (SLCs) represent eminent examples of first-level targets of heavy metals due to their localization on the cell surface. Putative targets of heavy metals are the organic cation transporters that form a sub-clade of the SLC22 family. Besides the physiological role in the absorption/release of endogenous organic cations, these transporters are crucial in drug disposition and their interaction with xenobiotics. In this work, the human SLC22A4, commonly known as OCTN1, was used as a benchmark to test interactions with heavy metals released by microplastics, exploiting the proteoliposome tool. The potency of metals to interfere with the OCTN1 function has been evaluated by measuring IC50 values calculated in the micromolar range. The molecular mechanism of interaction has been defined using site-directed mutagenesis and computational analyses. Finally, some chemical and physiological thiol-reacting compounds show the capacity to rescue the metal-inhibited OCTN1 function. The conclusions drawn on OCTN1 can be extended to other members of the SLC22 family and orthologous transporters in fish. Full article

Research reveals a positive impact on educational achievement for Indigenous students when their teachers are also Indigenous. The educational value of shared identity between students and teachers manifests in the form of increased student attendance rates, grades, and graduation rates. Fewer than 5% of public-school teachers in Alaska are Indigenous, while nearly 20% of students are Indigenous. Thus, it is unlikely that most Indigenous students in Alaska will experience a shared cultural identity with their teachers—nor would it be desirable, in this age of global mobility, for society to strive for teachers and students to share cultural identity in all instances. Yet it is important to discern what teaching practices and teacher dispositions support the cultural identity development (CID) of Indigenous children. This project brought together Indigenous educators from across Alaska to critically examine their practice as educators and to seek answers to the research question. Utilizing a collaborative autoethnographic framework, qualitative data were coded and analyzed to uncover answers to the research question. Key findings from this study indicate that teaching and using the local Indigenous language, shared cultural history documented in stories, and experiences related to the Land contribute to students’ CID. Furthermore, findings reveal that micro cultural validations, fleeting interactions between teachers and students, play a significant role in supporting the cultural identity development of Indigenous youth. Findings also suggest that Indigenous teachers are best positioned to discern the teaching practices that contribute to students’ cultural identity development. Full article

Global wealth is distributed highly unequally, and this issue has worsened in recent years. Such inequality threatens human well-being and fundamental values. In response, this paper aims to explore the wealth inequality phenomenon from the perspective of investment psychology. Recognizing wealth return heterogeneity as a crucial source of inequality, the paper establishes a psychological model focused on two investment skill factors that can partially explain this heterogeneity. The theoretical foundation of this model includes the conservation of resources (COR) theory, prospect theory, and performance determinants theory. In our model, risk preference and asset-holding periods sequentially mediate the relationship between family wealth and asset returns. Moreover, risk preference and the disposition effect are identified as serial mediators in this relationship. Financial literacy also moderates the relationship between the risk preference, asset-holding period, and disposition effect. This proposed model not only provides a richer explanation for wealth return heterogeneity through the lens of investment skill but also extends the application of COR theory to investment psychology, thereby enhancing our understanding of resources. Moreover, it offers a novel explanation for the relationship between risk preference and the deposition effect, enriching prospect theory. Finally, the inclusion of financial literacy’s role broadens the scope of performance determinants theory. Full article

The purposes of this systematic review (PROSPERO ID: CRD42024510614, no funding source) were to quantify relationships between situational and dispositional dichotomous achievement goals and sport performance and explore potential relationship moderators. Published studies that reported at least one situational or dispositional achievement goal and a performance score were included. Studies without performance scores or based in a non-sport context were excluded. Information sources consisted of studies found in relevant published meta-analyses and EBSCOhost databases (finalized September 2024). The following statistics were conducted to assess the risk of bias: class-fail-safe n, Orwin’s fail-safe n, and funnel plots with trim and fill estimates. The summary statistics were r and d. Thirty studies from 1994 to 2024 met all inclusion criteria with 8708 participants from Europe, Asia, North America, and Oceania. The majority of samples were non-elite male youths and adolescents. The random-effects relationships (r) between task climate, 0.20 [0.14, 0.25], task orientation, 0.17 [0.12, 0.23], ego orientation, 0.09 [0.03, 0.16], and sport performance were small and significantly different (p < 0.05) from zero, while the ego motivational climate relationship was not, −0.00 [−0.48, 0.05]. The random-effects standard differences in means (d) for both the task orientation, 0.08 [0.02, 0.14], and ego orientation, 0.11 [−0.05, 0.26] were minimal in meaningfulness. Mixed-effects moderator analyses resulted in the following significant (p < 0.05) sub-group differences: subjective compared to objective performance measures (task orientation), elite compared to non-elite samples (task climate), and athlete-completed compared to coach-completed performance measures and performance records (task orientation). Finding only 30 studies meeting the inclusion criteria, which limited sub-group samples for moderation analyses, was the main limitation. Despite this limitation, AGT provides athletes and practitioners performance enhancement strategies. However, caution is warranted regarding relationship expectations given the small mean effect size values and the true prediction interval ranging from negative to positive, perhaps as a result of the heterogeneous samples and performance measures. A clear line of future research, considering the reviewed studies, with elite athletes is needed to verify the performance benefits of the task climate and ego orientation as well as the use of the ego goal orientation in selection decisions. Full article

This paper presents a detailed gross description of all anatomical elements of the humerus in the African green monkey and provides comparative and differential elements on monkey osteology. The osteometric investigation adds value to the gross morphological investigation, adjoining metric data to the gross descriptive data set. An in-depth investigation of the microstructural aspects of the humeral bone tissue is provided, with qualitative and quantitative details and potential for diagnostic applications. Of the gross morphological elements described, several unique features specific to this species include the humeral head shape that presents with distinctive low convexity and caudal placement, the shape of the intertubercular groove, the less developed greater tubercle, and the disposition of the rotator cuff muscle insertion. Furthermore, the overall cranio-lateral curvature of the bone shaft was found to have a distinctive 154–155 degree of angulation of the diaphysis, and the well-developed medial epicondyle was observed with its distinctive medio-caudal retroflexion. The histological investigation was more indicative of a typical non-primate organization of the bone tissue, with laminar vascular and avascular structures combined with the presence of the secondary Haversian system involving a mixture of scattered and dense unorganized secondary osteonal structures. The histomorphometric investigation yielded metrical data for the secondary osteonal structures in terms of area (20,331 ± 5105 µm²), perimeter, and vascular canal area (64,769 ± 257 µm²). Full article