Background and Objective: In silico methods have become the key for efficiently testing and qualifying drug properties. Due to the complexity of the LADME processes and drug characteristics associated to oral drug absorption , there is a growing demand in the development of Physiologically-based Pharmacokinetic (PBPK) software with greater flexibility. Thus, the aims of this work are (i) to develop a mechanistic-based modeling framework of dissolution, transit and absorption (Phys-DAT) processes in the PhysPK platform and (ii) to assess the predictive power of the acausal MOOM methodology embedded in Phys-DAT versus reference ODE-based PBPK software. Methods: A PBPK model was developed including unreleased, undissolved and dissolved thermodynamic states of the drug. The gastrointestinal tract (GI) was represented by nine compartments and first-order transit kinetics was assumed for the drug fractions. Dissolution processes were described using solubility-independent or solubility-dependent mechanisms and pH effects. Linear transit and linear absorption mechanisms including gradual decrease absorption rate were considered to represent the passive diffusion process. Internal validation of the Phys-DAT model was performed through simulation-based analysis, considering different theoretical scenarios. External validation was carried out using in silico and in vivo data of GI segments and plasma concentrations. Both BCS I and II class drugs were included. Results: The model predicts plasma-concentration profiles of each compartment for undissolved, dissolved, and absorbed fractions using PhysPK® v.2.4.1. Internal and external validations demonstrate that the model aligned with the theoretical assumptions and accurately predicted C max , T max , and AUC 0-t for both BCS I and II drugs. Average Fold Error (AFE), Absolute Average Fold Error (AAFE), and Percent Prediction Error (PPE) calculations indicate good predictive performance, with predicted/observed ratios falling within the acceptable range. Conclusions: Phys-DAT represents a mechanistic model for predicting oral absorption, including the dissolution, pH effect, transit, and absorption processes. PhysPK has shown to be a tool with strong prediction accuracy, similar to the obtained by ODE-based PBPK reference software, and the results obtained with the Phys-DAT model for oral administered drugs showed predictive reliability in healthy volunteers, setting the basis to determine the interchangeability of the acausal MOOM methodology with other modeling approaches.
This chapter analyzes how pseudo-media allegedly present themselves as information providers, by adopting visual traits and imitating the six journalistic role performance dimensions identified in conventional media. The results of a qualitative and quantitative analysis show that the most mimicked is the watchdog role. However, pseudo-media distort the essence of it by focusing their critical task in disrupting progressive policies, while offering the loyal-facilitator role to far-right representatives. This trend is also observed in the civic role performance, aimed at giving a voice to anti-abortion groups, or opposed to measures against COVID-19 and, to a lesser degree, imitating the service role to promote their activities. Although polarization and clickbait reinforce all roles, they are particularly notable in intervention and infotainment. This latter one, the second most imitated, particularly exacerbates sensationalism and violence.
Purpose Acute ingestion of a ketone monoester with co-ingestion of a carbohydrate (KME + CHO) compared to carbohydrate (CHO) was investigated on cycling performance and cognitive performance in trained females. Methods Using a two condition, placebo-controlled, double-blinded and crossover design, twelve trained females (mean ± SD: age, 23 ± 3 y; height, 1.64 ± 0.08 m; mass, 65.2 ± 12.7 kg) completed a baseline assessment of cognitive performance (psychomotor vigilance testing (PVT), task switching, and incongruent flanker), followed by 6x5-min intervals at 40%, 45%, 50%, 55%, 60%, and 65% of their maximal power output (Wmax) and then a 10-km time trial (TT), concluding with the same assessments of cognitive performance. Participants consumed either 375 mg·kg-1 body mass of KME with a 6% CHO solution (1 g·min-1 of exercise) or CHO alone, across 3 boluses (50:25:25). Results Blood β-hydroxybutyrate concentrations averaged 1.80 ± 0.07 mM and 0.13 ± 0.01 mM during exercise in KME + CHO and CHO, respectively. Blood glucose decreased following drink 1 of KME + CHO (~15%; P = 0.01) but not CHO, and lactate concentrations were lower in KME + CHO at 50%, 55%, 60%, and 65%Wmax (all P < 0.05), compared to CHO. Despite these changes, no differences were found between conditions for TT finishing times (KME + CHO, 29.7 ± 5.7 min; CHO, 29.6 ± 5.7 min; P = 0.92). However, only KME + CHO resulted in increases in PVT speed (~4%; P = 0.01), and faster reaction times (~14%; P < 0.01), speed (~15%; P < 0.01), and correct responses (~13%; P = 0.03) in the incongruent flanker during post-testing compared to CHO. Conclusions Acute ingestion of a KME + CHO elevated blood β-hydroxybutyrate and lowered glucose and lactate across multiple timepoints during exercise compared to CHO. Although these changes did not affect physical performance, several markers of cognitive performance were improved by the addition of a KME in trained females.
Resumen Introducción La artropatía radiocubital distal produce gran limitación funcional con dolor y pérdida de fuerza durante la pronosupinación del antebrazo. El objetivo de nuestro trabajo fue describir la técnica quirúrgica del procedimiento de Sauvé-Kapandji artroscópico con estabilización tendinosa proximal, así como sus resultados, complicaciones y ventajas. Material y método Se estudiaron 11 pacientes de forma retrospectiva intervenidos con la técnica de Sauvé-Kapandji artroscópica con estabilización tendinosa proximal por el mismo equipo de cirujanos. Se evaluaron la movilidad, fuerza de prensa, DASH, EVA y Mayo Wrist Score. Resultados 10 pacientes eran varones y 1 mujer con una edad media de 39.1 años. El seguimiento mínimo fue de 12 (12-36) meses. Se observaron mejorías significativas en la flexión (preoperatoria 48° / postoperatoria 74°), extensión (pre 34°/post 48°), pronación (pre 28°/post 88°) y supinación (pre 19°/post 88°), el dolor (EVA pre 7.1/ post 0.4), la fuerza de prensión (pre 19/ post 45 kg) y en las escalas QuickDash (pre 54/ post 2) y Mayo Wrist Score (pre 46/ post 91). Todos los pacientes estuvieron satisfechos con el procedimiento al final del seguimiento. Discusión El procedimiento de S-K es la técnica de elección en la artrosis radiocubital distal y puede realizarse con asistencia artroscópica, restaurando la movilidad de la muñeca, la estabilidad y la fuerza de prensa. La técnica artroscópica tiene una serie de ventajas como son preservar los estabilizadores secundarios articulares, mejorar la cruentación y la colocación anatómica de la articulación, provocar menos daño vascular y permitir una rehabilitación más precoz lo que favorece la menor incidencia de pseudoartrosis y con un mejor resultado estético. Conclusión La técnica de Sauvé-Kapandji artroscópica con estabilización tendinosa proximal ofrece unos resultados mejores que las técnicas abiertas a corto plazo, con una recuperación funcional más rápida y confortable, además de permitir una resección y reducción más precisa.
Despite recent research showing that early childhood education and daycare settings (ECEC) have an important role in promoting toddlers’ physical activity (PA), crucial information gaps remain regarding toddlers' PA and sedentary behavior (SB) in these outdoor settings. We aimed in this study to: (a) analyze PA patterns and SB during unstructured outdoor play time in preschool and daycare environments using accelerometry and systematic observation; (b) provide concurrent accelerometry and observational data to help validate the Observational System for Recording Physical Activity in Children-Preschool Version (OSRAC-P); and (c) examine individual, social and environmental correlates of PA and SB during toddlers’ unstructured outdoor play time. We found that: (a) toddlers displayed high amounts of PA with no sex, BMI, and/or age differences in PA and SB levels,; (b) environmental variables (e.g., fixed equipment and playground density) were not associated with PA levels or SB intensity; (c) the OSRAC-P was a reliable and valid means of observing and analyzing toddlers’ PA patterns during unstructured outdoor play time; and (e) different social patterns between boys and girls did not impact PA levels or patterns. Combining different measurement methods permitted an improved understanding of unstructured outdoor play in preschool and daycare settings.
We tested the effects of a weight-loss intervention encouraging energy-reduced MedDiet and physical activity (PA) in comparison to ad libitum MedDiet on COVID-19 incidence in older adults. Secondary analysis of PREDIMED-Plus, a prospective, ongoing, multicentre randomized controlled trial. Community-dwelling, free-living participants in PREDIMED-Plus trial. 6,874 Spanish older adults (55–75 years, 49% women) with overweight/obesity and metabolic syndrome. Participants were randomised to Intervention (IG) or Control (CG) Group. IG received intensive behavioural intervention for weight loss with an energy-reduced MedDiet intervention and PA promotion. CG was encouraged to consume ad libitum MedDiet without PA recommendations. COVID-19 was ascertained by an independent Event Committee until December 31, 2021. COX regression models compared the effect of PREDIMED-Plus interventions on COVID-19 risk. Overall, 653 COVID-19 incident cases were documented (IG:317; CG:336) over a median (IQR) follow-up of 5.8 (1.3) years (inclusive of 4.0 (1.2) years before community transmission of COVID-19) in both groups. A significantly lowered risk of COVID-19 incidence was not evident in IG, compared to CG (fully-adjusted HR (95% CI): 0.96 (0.81,1.12)). There was no evidence to show that an intensive weight-loss intervention encouraging energy-reduced MedDiet and PA significantly lowered COVID-19 risk in older adults with overweight/ obesity and metabolic syndrome in comparison to ad libitum MedDiet. Recommendations to improve adherence to MedDiet provided with or without lifestyle modification suggestions for weight loss may have similar effects in protecting against COVID-19 risk in older adults with high cardiovascular risks.
Background and aims Time perception is a cognitive process involving both the ability to estimate the duration of an event (time estimation, TE) and the subjective perception of its passage (time passage, TP). Studies show that alteration in TE/TP is associated with substance use disorders. However, little is known about the impact of these alterations in potentially problematic online behaviors. We explore TE and TP while participants were exposed to cues related to videogames, pornography, and TV series, and the relationship of TE and TP with scores from instruments that measure problematic gaming (PG), problematic pornography use (PPU), and problematic binge-watching (BW). Methods Participants from three independent samples (40 men from Luxembourg; 99 Spanish men, 111 Spanish women) completed an experimental task designed to assess TE and TP while they were exposed to short clips related to videogames, pornography, TV series, and documentaries (control condition). Participants also completed different self-reports. Results Whereas men underestimated the time that they were exposed to pornography and TV series, women overestimated it. For videogames, we showed a consistent pattern of overestimation of time duration. Time was systematically perceived as passing faster while participants were presented with TV series and pornography. Regarding the association between time perception and PG, PPU, and BW, TE did not correlate with any of the indicators of problematic engagement assessed; but TP correlated with several of these indicators. Discussion and conclusions The present preliminary results showed mixed evidence regarding the involvement of time perception in gaming, pornography use, and binge-watching.
Climate change is leading to more extreme weather hazards, forcing human populations to be displaced. We employ explainable machine learning techniques to model and understand internal displacement flows and patterns from observational data alone. For this purpose, a large, harmonized, global database of disaster-induced movements in the presence of floods, storms, and landslides during 2016–2021 is presented. We account for environmental, societal, and economic factors to predict the number of displaced persons per event in the affected regions. Here we show that displacements can be primarily attributed to the combination of poor household conditions and intense precipitation, as revealed through the interpretation of the trained models using both Shapley values and causality-based methods. We hence provide empirical evidence that differential or uneven vulnerability exists and provide a means for its quantification, which could help advance evidence-based mitigation and adaptation planning efforts.
Introduction The scientific literature argues the urgent need for adequate tools to assess burnout in human service professionals, however, little progress has been made on this in university teachers in hybrid environments, even though after the pandemic, these work scenarios are predominant. Objective To determine the psychometric properties of invariance between male and female teachers of hybrid education in the Spanish Burnout Inventory (SBI). Method The anonymous, self-administered SBI was administered to 1060 university teachers in Lima, Peru, from online random sampling. Of the total number of participants, 626 were women (59.1%) and 434 were men (40.9%), with an age range of 22 to 76 years, with a mean of 46.97 and a standard deviation of 10.256. It should be noted that 74.5% of the teachers worked full time. The analysis used the statistical programs AMOS v24, SPSS v26 and R-Project v4.1.2. First, a descriptive analysis of the data was performed, as well as a multivariate normality test of the data. Secondly, confirmatory factor analysis was performed; finally, a factorial invariance test was performed. Results Cronbach's alpha of the SBI was 0.827, and for each subscale: Enthusiasm toward the job (0.742), Psychological exhaustion (0.889), Indolence (0.819), Guilt (0.816). According to the fit indicators, the confirmatory factor model is adequate. The results supported configural invariance, metric invariance, scalar invariance, and strict invariance in the male and female groups, although further investigation of some items specific to the indolence factor is needed. Conclusion The SBI is a valid instrument to assess burnout in university teachers in hybrid environments. Studies associated with the SBI focus on its psychometric properties, burnout prevalence, related variables, and literature reviews. The validation of the SBI in various countries and service areas is discussed, as well as future implications for intervention in burnout prevention and mastery.
Main conclusion The complexes involving MYBPA2, TT2b, and TT8 proteins are the critical regulators of ANR and LAR genes to promote the biosynthesis of proanthocyanidins in the leaves of Lotus spp. Abstract The environmental impact and health of ruminants fed with forage legumes depend on the herbage's concentration and structure of proanthocyanidins (PAs). Unfortunately, the primary forage legumes (alfalfa and clover) do not contain substantial levels of PAs. No significant progress has been made to induce PAs to agronomically valuable levels in their edible organs by biotechnological approaches thus far. Building this trait requires a profound knowledge of PA regulators and their interplay in species naturally committed to accumulating these metabolites in the target organs. Against this background, we compared the shoot transcriptomes of two inter-fertile Lotu s species, namely Lotus tenuis and Lotus corniculatus , polymorphic for this trait, to search for differentially expressed MYB and bHLH genes. We then tested the expression of the above-reported regulators in L. tenuis x L. corniculatus interspecific hybrids, several Lotus spp., and different L. corniculatus organs with contrasting PA levels. We identified a novel MYB activator and MYB-bHLH-based complexes that, when expressed in Nicotiana benthamiana, trans-activated the promoters of L. corniculatus anthocyanidin reductase and leucoanthocyanidin reductase 1 genes. The last are the two critical structural genes for the biosynthesis of PAs in Lotus spp. Competition between MYB activators for the transactivation of these promoters also emerged. Overall, by employing Lotus as a model genus, we refined the transcriptional network underlying PA biosynthesis in the herbage of legumes. These findings are crucial to engineering this trait in pasture legumes.
Little is known about exposure determinants of acrylamide (AA), a genotoxic food-processing contaminant, in Europe. We assessed determinants of AA exposure, measured by urinary mercapturic acids of AA (AAMA) and glycidamide (GAMA), its main metabolite, in 3157 children/adolescents and 1297 adults in the European Human Biomonitoring Initiative. Harmonized individual-level questionnaires data and quality assured measurements of AAMA and GAMA (urine collection: 2014–2021), the short-term validated biomarkers of AA exposure, were obtained from four studies (Italy, France, Germany, and Norway) in children/adolescents (age range: 3–18 years) and six studies (Portugal, Spain, France, Germany, Luxembourg, and Iceland) in adults (age range: 20–45 years). Multivariable-adjusted pooled quantile regressions were employed to assess median differences (β coefficients) with 95% confidence intervals (95% CI) in AAMA and GAMA (µg/g creatinine) in relation to exposure determinants. Southern European studies had higher AAMA than Northern studies. In children/adolescents, we observed significant lower AA associated with high socioeconomic status (AAMA:β = − 9.1 µg/g creatinine, 95% CI − 15.8, − 2.4; GAMA: β = − 3.4 µg/g creatinine, 95% CI − 4.7, − 2.2), living in rural areas (AAMA:β = − 4.7 µg/g creatinine, 95% CI − 8.6, − 0.8; GAMA:β = − 1.1 µg/g creatinine, 95% CI − 1.9, − 0.4) and increasing age (AAMA:β = − 1.9 µg/g creatinine, 95% CI − 2.4, − 1.4; GAMA:β = − 0.7 µg/g creatinine, 95% CI − 0.8, − 0.6). In adults, higher AAMA was also associated with high consumption of fried potatoes whereas lower AAMA was associated with higher body-mass-index. Based on this large-scale study, several potential determinants of AA exposure were identified in children/adolescents and adults in European countries.
Aims The aim of this study was to determine the global incidence of type 1 diabetes mellitus (T1DM) in children and adolescents under 20 years of age from 2000 to 2022. Materials and Methods Two reviewers searched three electronic databases (PubMed, Web of Science, and CINAHL) for studies published between January 2000 and November 2022. Pooled estimates of T1DM incidence with a 95% confidence interval (CI) per 100,000 person‐years were calculated by country/region, sex, age, and COVID‐19 pandemic period (pre‐COVID‐19 and pandemic). Results The study included 126 studies from 55 countries and 18 regions. The incidence rate (IR) of T1DM from 2000 to 2022 was 14.07 (95%CI, 12.15–16.29) per 100,000 person‐years. Finland and high‐income North America had the highest IR, with 56.81 (95%CI, 55.91–57.73) and 28.77 (95%CI, 26.59–31.13) per 100,000 person‐years, respectively. The IR was 13.37 (95%CI, 10.60–16.88) per 100,000 person‐years in boys and 13.87 (95%CI, 11.51–16.70) per 100,000 person‐years in girls. There were statistically significant differences among different age ranges: 0–4 versus 5–9 and 10–14 years old ( p < 0.001); 5–9 versus 15–19 ( p < 0.001) and 10–14 versus 15–19 years old ( p = 0.003). Finally, during the pandemic period (2020–2022), the IR was 24.84 (95%CI, 17.16–35.96) per 100,000 person‐years, which was higher but not significant compared with the prepandemic period (2017–2019) of 13.56 (95%CI, 7.49–24.56) per 100,000 person‐years ( p = 0.090). Conclusions The IR of T1DM in children and adolescents under 20 years of age is substantial, especially during the pandemic period, although it varies across regions. More reliable data from additional countries are needed to determine the worldwide incidence of T1DM.
A wide variety of insect-specific non-retroviral RNA viruses specifically infect insects. During viral infection, fragments of viral sequences can integrate into the host genomes creating non-retroviral endogenous viral elements (nrEVEs). Although the exact function of nrEVEs is so far unknown, some studies suggest that nrEVEs may interfere with virus replication by producing PIWI-interacting RNAs (piRNAs) that recognize and degrade viral RNAs through sequence complementarity. In this article, we identified the nrEVEs repertoire of ten species within the dipteran family Tephritidae (true fruit flies), which are considered a major threat to agriculture worldwide. Our results suggest that each of these species contains nrEVEs, although in limited numbers, and that nrEVE integration may have occurred both before and after speciation. Furthermore, the majority of nrEVEs originated from viruses with negative single-stranded RNA genomes and represent structural viral functions. Notably, these nrEVEs exhibit low similarity to currently known circulating viruses. To explore the potential role of nrEVEs, we investigated their transcription pattern and the production of piRNAs in different tissues of Ceratitis capitata. We successfully identified piRNAs that are complementary to the sequence of one nrEVE in C. capitata, thereby highlighting a potential link between nrEVEs and the piRNA pathway. Overall, our results provide valuable insights into the comparative landscape of nrEVEs in true fruit flies, contributing to the understanding of the intimate relation between fruit flies and their past and present viral pathogens.
Plant sterols are minor bioactive components of food lipids, which are often used for the formulation of functional foods due to their cholesterol-lowering properties. However, they have low solubility and tend to crystallize, which may affect their biological effects, the sensory profile of the sterol-enriched food, and its consumer acceptability. Moreover, due to the unsaturated structure of sterols, they are susceptible to oxidation, so different encapsulation systems have been developed to improve their dispersibility/solubility, stability, delivery, and bioaccessibility. This chapter provides an overview of the main encapsulation systems currently used for plant sterols and their application in model and food systems, with a particular focus on their efficiency and impact on sterol bioaccessibility.
The objective of this work is to identify the different names, positions, and roles of editorial board members (EBMs) of journals in the Information Science and Library Science (ISLS) field of the Journal Citation Reports (JCR) and to establish a classification of the different roles to improve communication between editors and researchers. Among the 86 journals included in the ISLS field, the first and last names, position, and institutional affiliation of each EBM were extracted from 84 journals that allowed access to committee information. The information was standardized, and the positions were classified by consensus into major groups according to the role they play in the journals. The 84 journals included 4,122 positions held by EBMs, distributed in 201 positions and classified into 11 broad categories. The majority of positions were included in the Editorial Board category (n = 1,516), followed by Editorial Advisory Board (n = 734) and Associate Editor (n = 566). The journals were published by 36 publishers, with Elsevier and Taylor & Francis contributing the most journals (11 each). The journals in which the EBMs had the highest percentage of foreign members were those published in the Netherlands. This study provides a picture of the broad distribution of the roles and terminological titles that EBMs have in Information Science and Library Science journals. Because of this diversity, it is advisable to develop a guide to good editorial practices that includes both a description of the complex range of roles performed by EBMs and a unified nomenclature for these universal positions.
Gridded high-resolution climate datasets are increasingly important for a wide range of modelling applications. Here we present PISCOt (v1.2), a novel high spatial resolution (0.01°) dataset of daily air temperature for entire Peru (1981–2020). The dataset development involves four main steps: (i) quality control; (ii) gap-filling; (iii) homogenisation of weather stations, and (iv) spatial interpolation using additional data, a revised calculation sequence and an enhanced version control. This improved methodological framework enables capturing complex spatial variability of maximum and minimum air temperature at a more accurate scale compared to other existing datasets (e.g. PISCOt v1.1, ERA5-Land, TerraClimate, CHIRTS). PISCOt performs well with mean absolute errors of 1.4 °C and 1.2 °C for maximum and minimum air temperature, respectively. For the first time, PISCOt v1.2 adequately captures complex climatology at high spatiotemporal resolution and therefore provides a substantial improvement for numerous applications at local-regional level. This is particularly useful in view of data scarcity and urgently needed model-based decision making for climate change, water balance and ecosystem assessment studies in Peru.
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