External Evaluation of Population Pharmacokinetic Models of Piperacillin in Preterm and Term Patients from Neonatal Intensive Care.

BACKGROUND AND OBJECTIVES: Piperacillin/tazobactam is extensively used off-label to treat late-onset neonatal sepsis, but safety and pharmacokinetic data in this population are limited. Additionally, the organic immaturity of the newborns contributes to a high piperacillin pharmacokinetic variability. This affects the clinical efficacy of the antibiotic treatment and increases the probability of developing drug resistance. This study aimed to evaluate the predictive performance of reported piperacillin population pharmacokinetic models for their application in a model-informed precision dosing strategy in preterm and term Mexican neonatal intensive care patients. METHODS: Published population pharmacokinetic models for piperacillin which included neonates in their study population were identified. From the reference models, structured models, population pharmacokinetic parameters, and interindividual and residual variability data were extracted to be replicated in pharmacokinetic software (NONMEM® version 7.4). For the clinical study, a sampling schedule was designed, and 2-3 blood samples of 250 µL were taken from neonates who met the inclusion criteria. Piperacillin plasma concentrations were determined by liquid chromatography/tandem mass spectrometry. The clinical treatment data were collected, and piperacillin plasma concentrations were estimated using reference pharmacokinetic models for an a priori or Bayesian approach. Statistical methods were used in terms of bias and precision to evaluate the differences between observed and estimated neonatal piperacillin plasma concentrations with the different approaches and to identify the pharmacokinetic model that best fits the neonatal data. RESULTS: A total of 70 plasma samples were collected from 25 neonatal patients, of which 15 were preterm neonates. The overall median value (range) postnatal age, gestational age, body weight, and serum creatinine at the sampling collecting day were 12 (3-26) days, 34.2 (26-41.1) weeks, 1.78 (0.08-3.90) Kg, 0.47 (0.20-0.90) mg/dL, respectively. Three population pharmacokinetic models for piperacillin in infants up to 2 months were identified, and their predictive performance in neonatal data was evaluated. No pharmacokinetic model was suitable for our population using an a priori approach. The model published by Cohen-Wolkowiez et al. in 2014 with a Bayesian approach showed the best performance of the pharmacokinetic models evaluated in our neonatal data. The procedure requires two blood samples (predose and postdose), and, when applied, it predicted 66.6% of the observations with a relative median absolute predicted error of less than 30%. CONCLUSIONS: The population pharmacokinetic model developed by Cohen-Wolkowiez et al. in 2014 demonstrated superior performance in predicting the plasma concentration of piperacillin in preterm and term Mexican neonatal intensive care patients. The Bayesian approach, including two different piperacillin plasma concentrations, was clinically acceptable regarding bias and precision. Its application for model-informed precision dosing can be an option to optimize the piperacillin dosage in our population.

The Urinary Metabolome of Newborns with Perinatal Complications.

Maternal pathological conditions such as infections and chronic diseases, along with unexpected events during labor, can lead to life-threatening perinatal outcomes. These outcomes can have irreversible consequences throughout an individual's entire life. Urinary metabolomics can provide valuable insights into early physiological adaptations in healthy newborns, as well as metabolic disturbances in premature infants or infants with birth complications. In the present study, we measured 180 metabolites and metabolite ratios in the urine of 13 healthy (hospital-discharged) and 38 critically ill newborns (admitted to the neonatal intensive care unit (NICU)). We used an in-house-developed targeted tandem mass spectrometry (MS/MS)-based metabolomic assay (TMIC Mega) combining liquid chromatography (LC-MS/MS) and flow injection analysis (FIA-MS/MS) to quantitatively analyze up to 26 classes of compounds. Average urinary concentrations (and ranges) for 167 different metabolites from 38 critically ill NICU newborns during their first 24 h of life were determined. Similar sets of urinary values were determined for the 13 healthy newborns. These reference data have been uploaded to the Human Metabolome Database. Urinary concentrations and ranges of 37 metabolites are reported for the first time for newborns. Significant differences were found in the urinary levels of 44 metabolites between healthy newborns and those admitted at the NICU. Metabolites such as acylcarnitines, amino acids and derivatives, biogenic amines, sugars, and organic acids are dysregulated in newborns with bronchopulmonary dysplasia (BPD), asphyxia, or newborns exposed to SARS-CoV-2 during the intrauterine period. Urine can serve as a valuable source of information for understanding metabolic alterations associated with life-threatening perinatal outcomes.

Grandparents' and Grandchildren's Shared Festive Leisure.

Festive leisure provides experiences that can generate intergenerational well-being. The study aimed to examine the festive leisure activities shared by grandparents and grandchildren, and the link with times, spaces, motives, and well-being that these activities bring to both generations. A cross-sectional telematic survey was carried out with 357 grandparents living in the northern part of Spain, who had grandchildren aged between 6 and 12 years. Both a descriptive and inferential analysis was performed. A high proportion of grandparents and grandchildren share festive activities, which occur on weekends and holiday periods. Private spaces, such as bars, cafeterias, and restaurants are the ones chosen for going out to eat or drink, and open public spaces like parks, squares, and streets are dedicated to traditional festivals, and are excellent scenarios for coexistence and intergenerational social interaction. The reasons that drive this practice are associated with the strengthening of emotional ties and family intimacy. Grandparents consider the practice of shared festive leisure to be beneficial for their personal development because they perceive that, thanks to this leisure, they improve their creativity, physical condition, their happiness and fun, the relationship with their grandchildren, and develop new manual and technical skills.

Assessment of Healthy and Harmful Maillard Reaction Products in a Novel Coffee Cascara Beverage: Melanoidins and Acrylamide.

Our research aimed to evaluate the formation of Maillard reaction products in sun-dried coffee cascara and their impact on the safety and health promoting properties of a novel beverage called "Instant Cascara" (IC) derived from this coffee by-product. Maillard reaction products in sun-dried coffee cascara have never been reported. "Instant Cascara" (IC) extract was obtained by aqueous extraction and freeze-drying. Proteins, amino acids, lipids, fatty acid profile, sugars, fiber, minerals, and vitamins were analyzed for its nutritional characterization. Acrylamide and caffeine were used as chemical indicators of safety. Colored compounds, also called melanoidins, their stability under 40 °C and in light, and their in vitro antioxidant capacity were also studied. A safe instant beverage with antioxidant properties was obtained to which the following nutritional claims can be assigned: "low fat", "low sugar" "high fiber" and "source of potassium, magnesium and vitamin C". For the first time, cascara beverage color was attributed to the presence of antioxidant melanoidins (>10 kDa). IC is a potential sustainable alternative for instant coffee, with low caffeine and acrylamide levels and a healthy composition of nutrients and antioxidants.

Psychological factors related to physical education classes as predictors of students' intention to partake in leisure-time physical activity.

In view of the rise in sedentary lifestyle amongst young people, knowledge regarding their intention to partake in physical activity can be decisive when it comes to instilling physical activity habits to improve the current and future health of school students. Therefore, the object of this study was to find a predictive model of the intention to partake in leisure- time physical activity based on motivation, satisfaction and competence. The sample consisted of 347 Spanish, male, high school students and 411 female students aged between 13 and 18 years old. We used a questionnaire made up of the Sport Motivation Scale, Sport Satisfaction Instrument, and the competence factor in the Basic Psychological Needs in Exercise Scale and Intention to Partake in Leisure-Time Physical Activity, all of them adapted to school Physical Education. We carried out confirmatory factor analyses and structural equation models. The intention to partake in leisure-time physical activity was predicted by competence and the latter by satisfaction/fun. Intrinsic motivation was revealed to be the best predictor of satisfaction/fun. Intrinsic motivation should be enhanced in order to predict an intention to partake in physical activity in Physical Education students.

Factores psicológicos relacionados con las clases de educación física como predictores de la intención de la práctica de actividad física en el tiempo libre en estudiantes / Psychological factors related to physical education classes as predictors of students’ intention to partake in leisure-time physical activity

Resumen Debido al aumento del sedentarismo entre los jóvenes, conocer la intención de práctica de actividad física en esta población puede ser determinante a la hora de inculcar futuros hábitos de práctica física para mejorar la salud actual y futura de los escolares. Así, el objetivo de este trabajo fue hallar un modelo predictivo de la intención de práctica de actividad física en tiempo libre a partir de la motivación, la satisfacción y la competencia. La muestra fue de 347 hombres y 411 mujeres de educación secundaria en España, con edades de entre 13 y 18 años. Se utilizó un cuestionario compuesto por el Sport Motivation Scale, Sport Satisfaction Instrument, el factor competencia de Basic Psychological Needs in Exercise Scalee Intention to partake in leisure-time physicalactivity, todos ellos adaptados a la Educación Física escolar. Se realizaron análisis factoriales confirmatorios y modelos de ecuaciones estructurales. La intención de práctica fue predicha por la competencia y ésta por la satisfacción/diversión. La motivación intrínseca se mostró como el mejor predictor de la satisfacción/diversión. Para predecir la intención de práctica física se debería potenciar la motivación intrínseca entre el alumnado de Educación Física.

Abstract In view of the rise in sedentary lifestyle amongst young people, knowledge regarding their intention to partake in physical activity can be decisive when it comes to instilling physical activity habits to improve the current and future health of school students. Therefore, the object of this study was to find a predictive model of the intention to partake in leisure- time physical activity based on motivation, satisfaction and competence. The sample consisted of 347 Spanish, male, high school students and 411 female students aged between 13 and 18 years old. We used a questionnaire made up of the Sport Motivation Scale, Sport Satisfaction Instrument, and the competence factor in the Basic Psychological Needs in Exercise Scale and Intention to Partake in Leisure-Time Physical Activity, all of them adapted to school Physical Education. We carried out confirmatory factor analyses and structural equation models. The intention to partake in leisure-time physical activity was predicted by competence and the latter by satisfaction/fun. Intrinsic motivation was revealed to be the best predictor of satisfaction/fun. Intrinsic motivation should be enhanced in order to predict an intention to partake in physical activity in Physical Education students.

Validación de un Cuestionario sobre Valores en los Deportes de Equipo en Contextos Didácticos / Validation of a Questionnaire on Values in Team Sports in Didactic Contexts

El objeto de este estudio fue diseñar y analizar las propiedades psicométricas de un cuestionario para conocer los valores que los niños toman como referencia, cuando practican deportes de equipo. Para la validación y fiabilidad del cuestionario, se contó con 16 expertos, todos profesores universitarios y especialistas en deporte y educación en valores, y con 244 estudiantes de 11 a 12 años de edad. Una vez analizados los instrumentos existentes, revisadas las fuentes bibliográficas y definidas las variables, se elaboró la versión preliminar del Cuestionario sobre Valores en los Deportes de Equipo, integrada por varios interrogantes iniciales sobre los contextos de práctica de actividad deportiva de los encuestados, por la "Escala de valores en los deportes de equipo" en la que se medía la importancia que los jóvenes atribuyen a 32 valores cuando participan en juegos de equipo, y la "Escala de jerarquía de valores en los deportes de equipo" que recogía la jerarquía a la que someten a los citados valores. Tras los resultados del análisis de las consistencias lógicas, el cuestionario se ve modificado, reduciendo ambas escalas, pasando, de estar compuestas por 32 valores, a conformarse por 19 de ellos. Los resultados confirmaron la validez de contenido y de constructo, y la fiabilidad de esta última versión, para conocer los valores de los niños de 11 a 12 años en los deportes de equipo. En ambas escalas, los niveles de a de Cronbach resultaron satisfactorios (0.691 y 0.738). En relación con los instrumentos elaborados por otros autores, para el estudio de los valores en la actividad deportiva, el presente cuestionario añade mayores cotas de especificidad, al focalizar su atención únicamente en los deportes de equipo, que presenta singularidades propias derivadas tanto de su concepción social, como de la lógica interna basada en las relaciones de cooperación-oposición.

The aim of this study was to design and analyze the psychometric properties of a questionnaire to determine the values that children 11-12 years old take as a reference in team sports. Participants: 8 experts, university professors and specialists in sports and education in values, and 61 students, 11-12 years old. The "Values in Team Sports Questionnaire" was designed comprising the "scale of values in team sports" and "Scale hierarchy of values in team sports". The results confirmed that the questionnaire has construct validity and reliability to understanding the values of children of 11-12 years, in team sports. Cronbach's alpha levels were satisfactory for both scales (0.691 and 0.738). With regard to tools developed by other authors for the study of values in sport, this questionnaire adds greater levels of specificity, to focus their attention solely on team sports, which has singularities derived either from its conception social, and internal logic based on relations of cooperation and opposition.

Parental predictors of physical inactivity in spanish adolescents.

The purpose of this study was to determine some parental predictors of physical inactivity in Spanish adolescents. The sample comprised 1,978 children, aged between 12 and 16 years. A quantitative and qualitative technical triangulation was employed. The study analyzed data of the parents' educational level, the importance they grant to physical-sport activities, and their physical-sport practice. Quantitative technique: a questionnaire (MACOFYD) was used to collect the data. Descriptive, bivariate, and multinomial regression analyses were employed. Statistical significance was set at p < 0.05. Qualitative technique: four discussion groups were conducted, consisting of parents, physical education teachers, teachers of other subjects, and children aged between 12 and 16 years. The results indicated that adolescents are four times more likely to be physically inactive if their parents have never exercised (odds ratio [OR] = 4.065, and = 3.487, for the fathers and mothers, respectively, p < 0.05). When parents grant "some" or "much" importance to physical-sport practice, adolescents are less likely to be physically inactive (OR = 0.185 and 0.118 respectively, p < 0.01). No significant correlation was found between adolescents' physical-sport activity and parents' educational level. However, young people reproach their parents because they emphasize academic goals more than physical-sport practice-an observation that teachers also confirm. Young people perceive their parents as being the education agents with the greatest influence over their inactive lifestyles. Many parents are unaware of their influence and, therefore, do not take responsibility, declaring that the teachers' influence is greater.

Reduced faecal shedding of Escherichia coli O157:H7 in cattle following systemic vaccination with γ-intimin C280 and EspB proteins.

Enterohaemorrhagic Escherichia coli (EHEC) O157:H7 is the most prevalent EHEC serotype that has been recovered from patients with haemolytic uremic syndrome (HUS) worldwide. Vaccination of cattle, the main reservoir of EHEC O157:H7, could be a logical strategy to fight infection in humans. This study evaluated a vaccine based on the carboxyl-terminal fragment of 280 amino acids of γ-intimin (γ-intimin C280) and EspB, two key colonization factors of E. coli O157:H7. Intramuscular immunization elicited significantly high levels of serum IgG antibodies against both proteins. Antigen-specific IgA and IgG were also induced in saliva, but only the IgA response was significant. Following experimental challenge with E. coli O157:H7, a significant reduction in bacterial shedding was observed in vaccinated calves, compared to control group. These promising results suggest that systemic immunization of cattle with intimin and EspB could be a feasible strategy to reduce EHEC O157:H7 faecal shedding in cattle.

Necrotic enteritis in young calves.

Non-enterotoxin (CPE)-producing Clostridium perfringens type A has been associated with enteritis in calves. Recent evidence has suggested that a novel toxin, named beta2 (CPB2), is implicated in the pathogenesis of this disease, although there is little evidence supporting this. In the current study, the role of C. perfringens type A in an outbreak of enteritis in calves was studied. Two 20-day-old dairy calves exhibiting apathy and reluctance to eat, with paresis of the anterior limbs, were euthanized for postmortem examination. Gross and histological changes compatible with acute enteritis, rumenitis, meningitis, and pneumonia were seen in both calves. Clostridium perfringens type A non-CPE, non-CPB2 was isolated from the abomasum and the small intestine. Escherichia coli ONTH8 (with cdtBIII and f17 virulence genes detected by polymerase chain reaction) was also isolated from the brain, abomasum, and intestine from both calves. All the samples were negative for Salmonella spp. When the C. perfringens strain was inoculated into bovine ligated small and large intestinal loops, cell detachment, erosion, and hemorrhage of the lamina propria were observed, predominantly in the small intestine. The results suggest that non-CPE, non-CPB2 C. perfringens type A is able to induce pathologic changes in the intestine of calves, probably enhanced by other pathogens, such as some pathogenic E. coli strains.

Upper alimentary tract papillomas in calves related to papillomavirus infection.

This study reports 3 cases of spontaneous papillomavirus infection in 1-week-old calves. Thickening of the omasum and abomasum wall, with acute inflammation, necrosis, ulceration, and neoplastic changes were seen in 1 calf. In the other 2, small papillomas were observed in the omasal mucosa, exhibiting proliferation of the parakeratinized epithelium. Papillomavirus antigens were detected by immunohistochemistry and virus-like particles were seen through electron microscopy.

Effect of tannins on the in vitro growth of Clostridium perfringens.

Vegetable tannins are water-soluble polyphenolic compounds of varying molecular weights that occur abundantly in nature. The diet of many free-ranging wild animals contains significant amounts of tannins. Also, commercial tannins are used in animal industry as food additives to improve animal performance. In order to further determine the capacity of tannins to inhibit the development of intestinal diseases produced by Clostridium pefringens, we evaluated here the effect of tannins from quebracho, chestnut or combinations of both on C. perfringens and their toxins. The C. perfringens (types A, B, C, D and E) growth obtained from the intestine of healthy and diseased animals was reduced in a dose-dependent manner in the presence of quebracho tannins, chestnut tannins, combinations of both or a commercial formula based in these tannins. Although the minimal inhibitory concentration of both tannins varied between isolates, no statistically significant differences were observed between isolates from healthy or sick animals. Comparative analysis showed that the concentrations of quebracho tannin inhibiting the growth of C. perfringens were higher than chestnut tannin. In fact, antibacterial effect of quebracho tannin was increased up to 20 times with the addition of 25% of chestnut tannin and 85 times with 75% of chestnut tannin. Antibacterial activity of the commercial product was up to ~50 times higher than quebracho tannin alone. Quebracho tannin showed partial bactericidal activity, whereas chestnut tannin activity was stronger. Both tannins were able to reduce the alpha toxin lecithinase activity and epsilon toxin cytotoxicity in MDCK cells. These results suggest that tannin-supplemented diet could be useful to prevent some clostridial diseases.

A satisfação com o serviço de atividades físico-desportivas de tempo livre: o caso da comunidade universitária de "La Rioja" (Espanha) / Satisfaction according to the physical sport activities service of free time: the specific case of the community of the university of La Rioja (Spain) / La satisfacción con el servicio de actividades físico-deportivas de tiempo libre: el caso concreto de la comunidad universitaria de La Rioja (España)

O presente estudo pretende dar a conhecer, por um lado, o grau de satisfação dos usuários reais e potenciais em relação à oferta de atividades físico-desportivas de tempo livre da comunidade universitária de La Rioja (Espanha) e, por outro, constatar que atributos, referidos às instalações, recursos e atividades, se associam a dita satisfação. Na pesquisa se detecta que as infra-estruturas e sua manutenção (conservação, dimensões, cobertura, número de espaços físico-desportivos, limpeza e iluminação) são os atributos externos que mais determinam a satisfação dos usuários, tanto reais como potenciais

Satisfaction with physical and sport based free time activities. The concrete example of the univesitarian community of La Rioja (Spain). The following study intends, on the one hand, to show the level of satisfaction linked to the offer of physical and sport based free time activities in the univesitarian community of La Rioja (Spain) as well as, on the other hand, to check all the attributes (facilities, courses and activities) directly linked to this satisfaction. The study shows that the facilities and their maintenance (the upkeep, the size, the numbers of physical education areas, the cleanliness and the lighting) are at the origin of the satisfaction of potential and actual users

La presente investigación pretende dar a conocer, por una parte, el grado de satisfacción de los usuarios reales y potenciales sobre la oferta de actividades físico-deportivas de tiempo libre de la comunidad universitaria de La Rioja (España) y, por otra, constatar qué atributos, referidos a las instalaciones, recursos y actividades, se asocian a dicha satisfacción. Del estudio se detecta que las infraestructuras y su mantenimiento (conservación, dimensiones, cobertura, número de espacios físico-deportivos, limpieza e iluminación) son los atributos externos que más determinan la satisfacción de los usuarios, tanto reales como potenciales

Congenital cytomegalovirus infection in San Luis Potosi, Mexico.

The incidence of congenital cytomegalovirus infection in Mexico is unknown. We evaluated the presence of cytomegalovirus infection in 560 newborn infants at a public general hospital. There were five (0.89%) infected newborns. Infants with congenital infection were more likely to be born to primigravid mothers (P = 0.01) and were more often from rural areas (P = 0.058) than were noninfected newborns.