Ursodeoxycholic Acid Binds PERK and Ameliorates Neurite Atrophy in a Cellular Model of GM2 Gangliosidosis.

The Unfolded protein response (UPR), triggered by stress in the endoplasmic reticulum (ER), is a key driver of neurodegenerative diseases. GM2 gangliosidosis, which includes Tay-Sachs and Sandhoff disease, is caused by an accumulation of GM2, mainly in the brain, that leads to progressive neurodegeneration. Previously, we demonstrated in a cellular model of GM2 gangliosidosis that PERK, a UPR sensor, contributes to neuronal death. There is currently no approved treatment for these disorders. Chemical chaperones, such as ursodeoxycholic acid (UDCA), have been found to alleviate ER stress in cell and animal models. UDCA's ability to move across the blood-brain barrier makes it interesting as a therapeutic tool. Here, we found that UDCA significantly diminished the neurite atrophy induced by GM2 accumulation in primary neuron cultures. It also decreased the up-regulation of pro-apoptotic CHOP, a downstream PERK-signaling component. To explore its potential mechanisms of action, in vitro kinase assays and crosslinking experiments were performed with different variants of recombinant protein PERK, either in solution or in reconstituted liposomes. The results suggest a direct interaction between UDCA and the cytosolic domain of PERK, which promotes kinase phosphorylation and dimerization.

Consumption of ultra-processed food and its association with obesity in Chilean university students: A multi-center studyUltra-processed food and obesity in Chilean university students.

OBJECTIVE: To explore the associations between the consumption of three categories of ultra-processed food (sugary beverages, sweet, and salty snacks) and body mass index (BMI) among Chilean university students. METHODS: We conducted a multi-center, descriptive study among 2,039 students from 6 Chilean universities. Food consumption was surveyed using a validate food survey. That height and body weight were objectively measured to calculate BMI for determining weight status, and also, tobacco use and physical activity were measured. RESULTS: An intake equal to or higher than 1 serving of sugary beverage a day was associated with greater odds of obesity in university students (OR:1.32 [95% CI: 1.00, 1.74]), 2 servings/day (OR: 1.30 [95% CI: 1.04, 1.50]), and 3 servings/day (OR: 1.39 [95% CI: 1.05, 1.80]). Neither consumption of sweet nor salty snacks (≥1 servings/day) related to differential odds of obesity: (OR: 0.83 [95% CI: 0.42, 1.64]) and (OR: 1.79 [95% CI: 0.93, 3.41]), respectively. CONCLUSION: In a sample of Chilean university students, consumption of sugary beverages, and not consumption of sweet or salty snacks, was associated with obesity.

Chitosan/starch beads as bioinoculants carrier: long-term survival of bacteria and plant growth promotion.

Immobilization of microorganisms in biodegradable polymeric matrices constitutes a promising technology for plant growth promoting to overcome the challenging conditions of the rhizosphere. Previously, we demonstrated that beads prepared from blends of chitosan/starch of analytical grades ionically cross-linked are useful carriers for Azospirillum brasilense and Pseudomonas fluorescens. The aims of this work were to study A. brasilense Az39 and P. fluorescens ZME4 immobilization in industrial quality beads produced with a blend of chitosan/starch, to assess bacterial survival during long-term storage and biofilm distribution in the beads. We also proposed to analyze the consortia root colonization and its performance as plant growth-promoting bioinoculants compared to liquid counterpart. Our results revealed that A. brasilense Az39 and P. fluorescens ZME4 can coexist in industrial grade chitosan/starch beads, and this mixed immobilization benefits the survival rates of both species, even for more than a year under shelf storage. Confocal laser scanning microscopy with fluorescent dyed strains showed that both species remain mainly in different locations inside and over the beads. Additionally, maize seed treatment with beads-loaded bacteria resulted in growth promotion of roots in a similar manner than traditional liquid-based inoculation. The evidence collected here demonstrate that low-cost chitosan/starch beads are a suitable carrier for bacteria consortia and could be a reliable alternative to liquid inoculation in agronomic practices with additional benefits for industrial management. KEY POINTS: • Mixed immobilization increases bacterial survival in chitosan/starch industrial beads • Beads increase competence of bacteria in rhizosphere of maize • Inoculation mediated by beads promotes plant growth of maize.

Eating-to-Cope Motives and Uncontrolled Eating as Mediators Between Negative Emotional States and Food Addiction Among Argentinean Young Adults.

Negative emotional states (NES; i.e., depression, anxiety and stress) are likely contributors to the development of food addiction (FA). The association between NES and FA symptoms may be mediated by altered eating behaviors or by eating-to-cope motives. This study examined, in a sample of Argentinean young adults, the association between NES and FA symptoms via eating-to-cope motives and three patterns of eating behaviors. We also examined whether the model was invariant across college status. The transition from high school to college is usually associated with increased exposure to stress, which promotes the probability of engaging in altered eating behaviors. A sample of 499 Argentinean young adults (mean age = 24.9 ± 3.51 years) completed a survey that assessed FA symptoms, eating behaviors (i.e., uncontrolled, emotional, and restrained eating), eating-to-cope motives and NES. A path analysis tested the indirect association between NES and FA symptoms via uncontrolled, emotional or restrained eating, or by eating-to-cope. Stress and depression symptoms were indirectly associated with FA symptoms via uncontrolled eating and eating-to-cope motives. The model was invariant across college status. The findings suggest that NES are associated with FA symptoms by increasing uncontrolled eating and eating-to-cope motives. Young adults exhibiting greater depressive or stress symptoms, higher eating-to-cope, or higher uncontrolled eating may be at risk for FA. Future research should examine the significance of this pattern by tailoring interventions to these characteristics.

Potential of rhizobacteria native to Argentina for the control of Meloidogyne javanica / Potencial de rizobacterias nativas de Argentina para el control de Meloidogyne javanica

Abstract Biocontrol of the nematode Meloidogyne javanica was studied using the Argentinean strains Pseudomonas fluorescens MME3, TAE4, TAR5 and ZME4 and Bacillus sp. B7S, B9T and B19S. Pseudomonas protegens CHA0 was used as a positive control. Egg hatching and juvenile mortality were evaluated in vitro by exposure of nematodes to bacterial suspensions or their cell-free supernatants (CFS). The effect of bacteria on nematode infestation of lettuce was also studied. results showed that most of the tested strains and CFS reduced egg hatching and juvenile survival in vitro. The bacterial suspension of Bacillus sp. B9T produced the lowest hatching of eggs. Juvenile mortality was higher when M. javanica was exposed to Bacillus sp. than to Pseudomonas spp. suspensions. Except for CFS of B9T, all filtrates inhibited hatching at levels similar to or higher than the biocontrol strain P. protegens CHA0. The CFS of CHA0 showed the highest level of juvenile mortality followed by Bacillus sp. strains and P. fluorescens TAE4. None of the inoculated rhizobacteria reverted the negative effect of infestation on the aerial dry weight of lettuce plants. However, inoculation impacted on reproduction of M. javanica by reducing the development of galls and egg masses on roots and diminishing the number of individuals both on roots and in the substrate, as well as the reproduction factor. These results show that most of the analyzed native strains can control the nematode M. javanica. Among them, P. fluorescens TAE4 and Bacillus sp. B9T showed the most promising performances for the biocontrol of this pathogen and have a potential use in the formulation of commercial products.

Resumen Se estudiaron las cepas argentinas Pseudomonas fluorescens MME3, TAE4, TAR5 y ZME4 y Bacillus sp. B7S, B9T y B19S para el control del nematodo Meloidogyne javanica. Pseudomonas protegens CHA0 se utilizó como control positivo. La eclosión de huevos y la mortalidad de juveniles se evaluaron in vitro al exponerlos a suspensiones bacterianas y a sus sobrenadantes libres de células (SLC). Asimismo, se estudió la inoculación bacteriana sobre la infestación del nematodo en lechuga. Los resultados in vitro indicaron que la mayoría de las cepas, así como sus SLC redujeron la eclosión y la supervivencia de M. javanica. La suspensión de Bacillus sp. B9T produjo los menores niveles de eclosión. La mortalidad de juveniles fue mayor al exponerlos a suspensiones de Bacillus sp. respecto de Pseudomonas spp. Los SLC inhibieron la eclosión de huevos en niveles similares o superiores a P. protegens CHA0, excepto por el de B9T. La exposición a SLC de CHA0 registró la mayor mortalidad, seguido por las cepas de Bacillus sp. y P. fluorescens TAE4. La inoculación bacteriana no revertió el efecto de la infestación sobre el peso seco aéreo de las plantas, sin embargo, afectó la multiplicación de M. javanica lo que redujo el desarrollo de agallas y las masas de huevos, y disminuyó el número de individuos presentes tanto en la raíz como en el sustrato, así como el factor de reproducción. Los resultados indican que la mayoría de las cepas nativas evaluadas son capaces de controlar a M. javanica. Entre ellas, P. fluorescens TAE4 y Bacillus sp. B9T, se presentan como las más promisorias para el control de este patógeno, con potencialidad para ser utilizadas en la formulación de productos biológicos.

Ca2+ signalling system initiated by endoplasmic reticulum stress stimulates PERK activation.

The accumulation of unfolded proteins within the Endoplasmic Reticulum (ER) activates a signal transduction pathway termed the unfolded protein response (UPR), which attempts to restore ER homoeostasis. If this cannot be done, UPR signalling ultimately induces apoptosis. Ca2+ depletion in the ER is a potent inducer of ER stress. Despite the ubiquity of Ca2+ as an intracellular messenger, the precise mechanism(s) by which Ca2+ release affects the UPR remains unknown. Tethering a genetically encoded Ca2+ indicator (GCamP6) to the ER membrane revealed novel Ca2+ signalling events initiated by Ca2+ microdomains in human astrocytes under ER stress, induced by tunicamycin (Tm), an N-glycosylation inhibitor, as well as in a cell model deficient in all three inositol triphosphate receptor isoforms. Pharmacological and molecular studies indicate that these local events are mediated by translocons and that the Ca2+ microdomains impact (PKR)-like-ER kinase (PERK), an UPR sensor, activation. These findings reveal the existence of a Ca2+ signal mechanism by which stressor-mediated Ca2+ release regulates ER stress.

Factores que diferencian el consumo frecuente y esporádico de marihuana en estudiantes universitarios / Factors differentiating frequent and sporadic marijuana use in college students

Resumen Aunque el consumo de marihuana es altamente prevalente entre universitarios de Argentina, poco se sabe respecto a los factores que permiten distinguir a los consumidores frecuentes de marihuana de quienes consumen esporádicamente. Por esta razón, en el presente trabajo se indagó sobre las posibles variaciones en los contextos de consumo, motivos de consumo, normas percibidas y estrategias conductuales de protección entre universitarios con consumo frecuente o esporádico de marihuana, y se analizó la utilidad de este conjunto de variables para distinguir entre estos los tipos de consumidores mencionados. Para ello, se contó con una muestra de 1083 estudiantes universitarios argentinos que completó una encuesta en línea sobre el consumo de sustancias. En particular, este trabajo se realizó con la submuestra que reportó consumir marihuana en los últimos 30 días (n = 158; 51.3 % mujeres). Dicha encuesta interrogaba sobre el consumo de marihuana y las consecuencias negativas asociadas, así como por motivos de consumo, normas sociales percibidas y estrategias conductuales de protección. Como resultado, los consumidores frecuentes presentaron mayor cantidad de consecuencias negativas (M = 4.92) que los consumidores esporádicos (M = 1.82; p < .05), y se halló un perfil distintivo en un conjunto de variables. A nivel multivariado, los motivos de animación (OR = 1.230; p < .05), las estrategias conductuales de protección (OR = .941; p < .05), el consumo en solitario (OR = 2.024; p < .05) y el consumo en fiestas universitarias (OR = 2.669; p < .05) discriminaron significativamente entre ambas clases de consumidores. En general, los hallazgos revelaron subpoblaciones heterogéneas de consumidores de marihuana que difieren no solo en el consumo y sus consecuencias, sino también en los contextos de consumo y en un conjunto de variables relevantes. Estas subpoblaciones distintivas requieren de intervenciones diferentes y específicas.

Abstract Although marijuana use is highly prevalent among university students in Argentina, little is known about the factors that distinguish frequent marijuana users from sporadic users. For this reason, the present study investigated the possible variations in the contexts of consumption, motives for consumption, perceived norms, and protective behavioral strategies among university students with frequent or sporadic marijuana use, and analyzed the usefulness of this set of variables to distinguish between these two types of users. For this purpose, a sample of 1083 Argentine university students completed an online survey on substance use. In particular, this work was conducted with the subsample that reported using marijuana in the last 30 days (n = 158; 51.3 % female). The survey asked about marijuana use and associated negative consequences, as well as motives for use, perceived social norms, and protective behavioral strategies. As a result, frequent users had a higher number of negative consequences (M = 4.92) than sporadic users (M = 1.82; p < .05), and a distinctive profile was found on a set of variables. At the multivariate level, cheerleading motives (OR = 1.230; p < .05), protective behavioral strategies (OR = .941; p < .05), solo use (OR = 2.024; p < .05), and college party use (OR = 2.669; p < .05) discriminated significantly between the two classes of users. Overall, the findings revealed heterogeneous subpopulations of marijuana users that differ not only in use and its consequences, but also in contexts of use and in a set of relevant variables. These distinct subpopulations require different and specific interventions.

Potential of rhizobacteria native to Argentina for the control of Meloidogyne javanica.

Biocontrol of the nematode Meloidogyne javanica was studied using the Argentinean strains Pseudomonas fluorescens MME3, TAE4, TAR5 and ZME4 and Bacillus sp. B7S, B9T and B19S. Pseudomonas protegens CHA0 was used as a positive control. Egg hatching and juvenile mortality were evaluated in vitro by exposure of nematodes to bacterial suspensions or their cell-free supernatants (CFS). The effect of bacteria on nematode infestation of lettuce was also studied. results showed that most of the tested strains and CFS reduced egg hatching and juvenile survival in vitro. The bacterial suspension of Bacillus sp. B9T produced the lowest hatching of eggs. Juvenile mortality was higher when M. javanica was exposed to Bacillus sp. than to Pseudomonas spp. suspensions. Except for CFS of B9T, all filtrates inhibited hatching at levels similar to or higher than the biocontrol strain P. protegens CHA0. The CFS of CHA0 showed the highest level of juvenile mortality followed by Bacillus sp. strains and P. fluorescens TAE4. None of the inoculated rhizobacteria reverted the negative effect of infestation on the aerial dry weight of lettuce plants. However, inoculation impacted on reproduction of M. javanica by reducing the development of galls and egg masses on roots and diminishing the number of individuals both on roots and in the substrate, as well as the reproduction factor. These results show that most of the analyzed native strains can control the nematode M. javanica. Among them, P. fluorescens TAE4 and Bacillus sp. B9T showed the most promising performances for the biocontrol of this pathogen and have a potential use in the formulation of commercial products.

Asociación del consumo de desayuno con el índice de masa corporal, hábito tabáquico, actividad física y sueño en universitarios chilenos. Estudio multicéntrico / Association of the consumption of breakfast with the index of body mass, tobacco habit, physical activity and sleep in chilean university. Multicentric study

Fundamentos: El desayuno es una pieza clave de una alimentación saludable, asociándose con un menor IMC yunos mayores rendimientos académicos. Este trabajo pretende analizar la asociación entre el consumo de desayuno con la actividad física, consumo de tabaco, calidad de sueño e índice de masa corporal en universitarios chilenos. Métodos: Estudio multicéntrico, transversal, muestra no probabilística. A cada participante se le consultó lafrecuencia de consumo de desayuno. Además, se les aplicó el cuestionario de actividad física IPAQ, hábitotabáquico, encuesta de calidad de sueño de Pittsburgh y evaluación antropométrica. Resultados: participaron un total de 1454 estudiantes, un 77,9 % mujeres. El 44% de los estudiantes indicódesayunar todos los días, de las cuales las mujeres (46%), superaban a los hombres (36%) (p<0,001). Al comparar por estado nutricional los estudiantes con IMC>25 eran los que menos desayunaban p<0,05. Al comparar por tipos de carrera, los de carreras de la salud desayunaban a diario con mayor frecuencia que los demás (p<0,001), ademáslos sujetos que poseían hábito tabáquico desayunaban con menor frecuencia que los que no fumaban (p <0,01). La frecuencia de consumo de desayuno estuvo asociada a una mejor calidad de sueño (p<0,05). Finalmente, no se obtuvo relación estadísticamente significativa entre la frecuencia del desayuno y la actividad física.Conclusiones: En estudiantes universitarios, el mayor consumo de desayuno se asocia con el sexo femenino, estado nutricional normal, carreras del área de la salud, ausencia de hábito tabáquico y mejor sueño y sinasociación con actividad física. (AU)

Background: Breakfast is a key part of a healthy diet, associated with a lower BMI and higher academic performance. This work aims to analyze the association between breakfast consumption and physical activity, tobacco consumption, sleep quality and body mass index in Chilean university students. Methods: Multicenter, cross-sectional study, non-probability sample. Each participant was asked how often they eat breakfast. In addition, the IPAQ physical activity questionnaire, Pittsburgh sleep survey, smoking habits, and anthropometric evaluation were applied. Results: 1,454 students, 77.9% women. 44% of the students indicate having breakfast every day, of which women (46%) outnumber men (36%) (p<0.001). When comparing by nutritional status, students with BMI> 25 consume the least breakfast p <0.05. When comparing by type of career, those in health careers eat breakfast daily more frequently than the others (p <0.001), in addition, the subjects who have the smoking habit eat breakfast less frequently than those who do not smoke (p <0, 01). The frequency of breakfast consumption is associated with better sleep quality (p <0.05). Finally, no statistically significant relationship was obtained between the frequency of breakfast and physical activity. Conclusions: In university students, eating breakfast is associated with the female sex, normal nutritional status, health careers, absence of smoking and better sleep, but without any association with physical activity. (AU)

Tobacco consumption in Chilean university students and associations with anthropometry, eating habits and sleep quality multicentric study.

Tobacco Consumption (TC) is one of the main causes of the deterioration of health; however, there are few studies linking its consumption with diet and nutrition among university students. The objective of this study is to test the association of smoking with anthropometry, diet and sleep quality among Chilean university students. Cross-sectional study. University students (n = 1454) from the North, South and Central parts of Chile were evaluated. A self-assessment survey was used to evaluate healthy and unhealthy eating habits. Nutritional status was evaluated by Body Mass Index (BMI). Two surveys were used to assess sleep quality: the Questionnaire of Insomnia and the Epworth Scale. Finally, participants were consulted about Tobacco Consumption: 30% of the students consume tobacco and have a higher score in unhealthy food consumption, less frequent weekly breakfast consumption (< 0.01), lower daily fruit (< 0.01) and vegetables (< 0.05) consumption, higher alcohol consumption (< 0.05) and daily junk food consumption (< 0.05) compared to non-consuming students. Men who consume tobacco present greater insomnia (< 0.001), sleep latency (< 0.001) and daytime sleepiness (< 0.05) compared to non-consumers; and women who consume tobacco have a higher weight (< 0.001) and BMI (< 0.01). When performing logistic regression, tobacco consumption is positively associated with major alcohol consumption (< 0.001), whereas fish (< 0.05) and vegetable (< 0.05) consumption was negatively associated. In conclusion, students of both sexes who smoke have more unfavorable health factors and a poorer quality of life.

Visibilizando a las cirujanas en Chile / Making female surgeons visible in Chile

Resumen Introducción: La cirugía ha sido tradicionalmente considerada una especialidad masculina. Se desconoce si el aumento en el número de médicas en las últimas décadas ha producido un aumento significativo en el número de cirujanas. Objetivo: Analizar y visibilizar la participación actual e histórica de las mujeres en Medicina y en Cirugía General en Chile. Materiales y Método: Estudio retrospectivo de la cohorte de médicas/os y cirujanas/os egresados de escuelas de medicina chilenas desde el año 1970, complementado con estudio de corte transversal para conocer la información actual de las cirujanas y residentes. Las fuentes de datos fueron los Registros de la Superintendencia de Salud, CONACEM y el Catastro de la Asociación de Cirujanas. Resultados: Ha existido un aumento sostenido de médicas egresadas sobrepasando a sus pares masculinos a partir de 2018. Las cirujanas representan el 15% del total de cirujanas y cirujanos, y este número se ha duplicado por década a partir de los años 70. Actualmente, 33% de los residentes en formación son de género femenino. Las áreas más comunes de desarrollo son cirugía general (35%), y dentro de las subespecialidades: mama, plástica y cabeza y cuello. Conclusión: Las mujeres siguen siendo minoría en cirugía; sin embargo, se ha producido un aumento progresivo y se espera siga la misma tendencia. Es necesario visibilizar la importancia de las cirujanas para que sirvan como modelo a nuevas generaciones de estudiantes y así poder aumentar la representación femenina en la especialidad.

Introduction: Surgery traditionally has been considered a male discipline. It is unknown if the increase in the number of female doctors in the last decades has increased the number of female surgeons. Aim: Is to analyze and make visible the historical and current participation of women in Medicine and Surgery in Chile. Materials and Method: Retrospective cohort study of all medical doctors and surgeons graduated from chilean Universities since 1970 to date, and cross-sectional study to know current information of female surgeons and residents. Source of data were the Registries of Health Superintendence, CONACEM and the Registry of the Female Surgeon Association. Results: There has been a steady increase in the number of graduated female doctors in Chile, surpassing male doctors since 2018. Female surgeons are 15% of all surgeons, and the number has duplicated every decade since 1970s. Currently, 33% of the residents are female. Main area of developing is general surgery (35%), and within subspecialties: Breast, Plastics, and Head and Neck. Conclusions: Women are still underrepresented in Surgery: however, there has been a steady increase and that trend is expected to continue. It is necessary to make visible the importance of female surgeons to be able to increase female representation.

Prediction of ethanol self-administration in pre-weanling, adolescent, and young adult rats.

Alcohol (ethanol) use is almost normative by late adolescence, in most western countries. It is important to identify factors that distinguish those who progress from alcohol initiation to sustained use of the drug, from those that keep a controlled pattern of drinking. The factors precipitating this transition may change across development. This study analyzed associations between behavioral endophenotypes and ethanol intake at three developmental periods. Exp. 1 measured ethanol drinking at postnatal day 18, via an intraoral infusion procedure, in male or female pre-weanling rats screened for anxiety response in the light-dark box test and for distance traveled in a novel open field. Exp. 2 measured, in juvenile/adolescent or young adult rats, the association between shelter seeking, exploratory/risk-taking behaviors, anxiety or hedonic responses, and ethanol intake. Ethanol intake in pre-weanlings was explained by distance traveled in a novel environment, whereas anxiety responses, measured in the multivariate concentric square field apparatus (MSCF), selectively predicted ethanol intake at adolescence, but not at adulthood. Those juvenile/adolescents with lower mean duration of visit to areas of the MSCF that evoke anxiogenic responses exhibited heightened ethanol intake. These findings suggest that the association between anxiety and ethanol intake may be specifically relevant during adolescence.

[Therapeutic use of robotics in children with Autism Spectrum Disorder]. / Uso terapéutico de robótica en niños con Trastorno del Espectro Autista.

INTRODUCTION: Robot-assisted Therapy (RAT) can improve the behavior of children with Autism Spectrum Disorder (ASD) in a spontaneous and entertaining way. There are no previous experiences of this type of inter vention in our country. OBJECTIVE: To describe a clinical experience of using RAT and its impact on the behaviors of a group of children with ASD, in a therapeutic context. PATIENTS AND METHOD: Quasi experimental clinical experience type study. 4 children with a clinical diagnosis of ASD were selected, supported by the ADOS-2 (Autism Diagnostic Observation Schedule); aged between 9 and 13 years, and normal IQ according to the WISC-III (Wechsler Intelligence Scale for Children). This study was approved by the Central Metropolitan Ethics Committee. Patients attended 10 structured robot-as sisted therapy sessions, working collaboratively in pairs. Workshop attendance and parent and child satisfaction were evaluated through surveys, the adaptive behavior with the Vineland scale, and so cial interaction with video coding guidelines. RESULTS: Patients presented a very good adherence and satisfaction with the activity. There was an improvement in socialization behaviors and social age. Video-coding showed an increase in social interaction and improvement in the behavior of the pa tients after attending workshops. CONCLUSIONS: We observed that the experience with RAT, adapted to the context of a Chilean public health center, was highly attractive and beneficial for patients with ASD, improving core symptoms such as difficulties in social interaction and behavioral problems.

Environmental enrichment during adolescence heightens ethanol intake in female, but not male, adolescent rats that are selectively bred for high and low ethanol intake during adolescence.

Background: Discriminating between adolescents who will eventually have ethanol use problems from those who do not is important. Environmental enrichment is a promising approach to reduce drug-related problems, but its impact on ethanol's effects and intake is being scrutinized. Objective: We tested the effects of environmental enrichment on ethanol intake, preference, and anxiety-like response as well as shelter seeking and risk-taking behaviors. Methods: Experiment 1 examined ethanol intake, preference, and anxiety-like responses in 46 male and 54 female Wistar rats that were derived from a short-term breeding program that selected for high and low ethanol drinking during adolescence (ADHI2 and ADLO2 lines, respectively). Shelter-seeking and risk-taking behaviors were assessed (Experiment 2) in ADHI2 and ADLO2 rats (73 males, 76 females) reared under environmental enrichment or standard housing conditions and given doses of ethanol (2.5 g/kg, intraperitoneal) for 3 weeks. Environmental enrichment was applied on postnatal days 21-42. Ethanol intake was measured on postnatal days 42-68. Anxiety-like behavior and exploratory responses were assessed using the light-dark box and multivariate concentric square field test. Results: In Experiment 1, environmental enrichment increased ethanol intake in female, but not male, ADHI2 and ADLO2 rats (p < 0.05). In the baseline measurement of Experiment 2, ADHI2 rats exhibited reduced risk-taking and increased anxiety-like behavior (p < .05). After exposure to environmental enrichment the ADHI and ADLO rats, both males and females, exhibited increased risk-taking and exploratory behavior (p < 0.05). Conclusions: Environmental enrichment appears to increase ethanol intake in female rats by promoting the exploration of new environments or stimuli. The findings indicate that environmental enrichment increased ethanol intake in female, but not male, rats. Clinical programs that treat alcohol use disorder by emphasizing environmental stimulation should be designed with caution.

Selective alterations in endogenous opioid system genes expression in rats selected for high ethanol intake during adolescence.

Historically, the roots of alcoholism have been linked to either environment or heredity. However, the interaction between these factors is still largely unexplored. The evidence supports a link between alcohol consumption and the endogenous opioid system. We here studied the opioid genes expression in male and female Wistar rats derived from a short-term breeding program which selected -- at adolescence -- for high (ADHI line) or low (ADLO line) ethanol drinking. Specifically, in this work we analyzed central opioid gene expression in the rats of the second filial generation (S2-ADLO and S2-ADHI). Selective downregulation of pronociceptin (Pnoc) and its receptor (Oprl1) mRNA levels were observed in the prefrontal cortex of male S2-ADHI rats when compared to S2-ADLO, and for Oprl1 also in the nucleus accumbens. An increase in gene expression was instead observed for pro-opiomelanocortin (Pomc) in the nucleus accumbens of S2-ADHI males when compared to S2-ADLO, as well as for mu opioid receptor (Oprm1) but in females. The differences in mRNA levels may be due to the different alcohol consumption between the two groups of rats or may represent pre-existing differences between them. Moreover, we show a sex-specific modulation of the expression of these genes, thus pointing out the importance of sex on ethanol responses. The results might lead to more specific and effective pharmacological treatments for alcoholism.

Short-term selection for high and low ethanol intake during adolescence exerts lingering effects in stress-induced ethanol drinking and yields an anxiety-prone phenotype.

Ethanol use is widespread in adolescents, yet only some transition to problematic drinking. It is important to understand why the risk for problematic drinking varies across sub-groups of adolescents. This study reports a short-term selection program to generate Wistar rat lines (high and low adolescent ethanol drinking, ADHI and ADLO lines, respectively) that significantly differ in ethanol drinking at adolescence. The S0 generation and filial generations 1 (S1), S2, and S3 of ADHI and ADLO offspring were tested for basal or stress-induced ethanol intake at adulthood, or for shelter-seeking and risk-taking in the multivariate concentric square field test (MSCF). The study generated lines with significant differences in free-choice ethanol drinking at adolescence. The effects of the selection were observed at adulthood, beyond the stage in which the selection was conducted: S1-ADHI but not S1-ADLO adult male rats exhibited stress-induced drinking. These effects were associated with significant alterations in shelter-seeking and risk-taking behaviors. ADHI rats spent significantly less time in areas of the MSCF whose exploration entails risk-taking and significantly more time in dark, sheltered areas. Some of these effects were normalized by the administration of 0.5 g/kg ethanol. There were no line differences in ethanol-induced latency to lose the righting reflex or sleep time. These findings indicate that genetic risk of enhanced ethanol intake at adolescence is still present at adulthood, long after the developmental window when the selective breeding occurred. Exposure to stress at adulthood triggers the vulnerability associated with this genetic risk, an effect associated with enhanced anxiety.

Use of rivaroxaban in patients attending a hematology unit in clinical practice.

Aim: To determine drug persistence and rates of events among patients treated with rivaroxaban in a hematology unit. Methods: Retrospective study of patients that started treatment with rivaroxaban, in the hematology unit of a tertiary hospital. Results: A total of 161 patients were included, of whom 83.9% had atrial fibrillation and 11.2% venous thromboembolism, and 76.4% of patients were taking rivaroxaban 20 mg, 22.4% 15 mg and 1.2% 10 mg. After a follow-up of 1.8 ± 1.1 years, only four patients (2.5%) discontinued treatment. Rates of thromboembolic events, major bleeding/clinically relevant nonmajor bleeding and intracranial hemorrhage were 1.1, 2.8, 0.3 events per 100 patient-years, respectively. Conclusion: In patients attended in a hematology unit, medication persistence was high, and the incidence of outcomes low.

Consumo de frutas, verduras y legumbres en universitarios chilenos / Consumption of fruits, vegetables and legumes among Chilean university students

RESUMEN Recomendaciones internacionales indican que se deben consumir diariamente 400 g/día o su equivalente a 5 porciones de frutas, verduras o legumbres. Nuestro objetivo fue determinar la frecuencia de consumo de frutas, verduras y legumbres en estudiantes universitarios chilenos. Materiales y Métodos: Estudio transversal. Fueron evaluados estudiantes universitarios (n= 1454) del norte, centro y sur de Chile. Ellos completaron una encuesta alimentaria que se utiliza para determinar hábitos alimentarios saludables (frutas, verduras y legumbres). El 78% era de sexo femenino. Al analizar la frecuencia de consumo de frutas, verduras y legumbres según universidad, sólo frutas y verduras mostraron de diferencia estadísticamente significativa (p< 0,01). El 70% de los estudiantes no cumple con la recomendación de consumo de frutas; 72% con la de verduras y 77% con la de legumbres. En mujeres, un 6,3% del total de la muestra cumple con la recomendación de frutas y en hombres el valor alcanza al 8,4%; en verduras se observa que la recomendación alcanza al 29,5% en mujeres y 21,3% en hombres, y en legumbres, es 2,4% en mujeres y 5% en hombres. Se observa un bajo consumo de frutas, verduras y legumbres en universitarios muy lejos de las recomendaciones internaciones.

ABSTRACT International recommendations indicate that 400 g/ day or its equivalent to 5 servings of fruits, vegetables or legumes should be consumed daily. Our aim was to determine patterns of consumption of fruits, vegetables and legumes among Chilean university students. Materials and Methods: Cross-sectional study. University students (n= 1454) from the north, center and south of Chile were evaluated. A self-assessment survey was used to evaluate healthy eating habits (fruits, vegetables and legumes). Seventy-eight percent of participants were women. When analyzing the consumption frequency of fruits, vegetables and legumes according to different universities, only fruits and vegetables showed a statistically significant difference (p< 0.01). Seventy percent of students do not meet recommended amounts for fruit consumption; 72% for vegetables and 77% for legumes. Among women, 6.3% of the total sample met the recommendation for fruit, while, for men, the value was 8.4%; for vegetables, we observed that 29.5 and 21.3% of women and men, respectively, met the recommendation; for legumes, 2.4% of women and 5% of men met the recommendation. There was a low consumption of fruits, vegetables and legumes among university students, with levels far from the international recommendations.

Valuation of observable attributes in differentiated beef products in Chile using the hedonic price method.

Beef imports in Chile have increase annually by close to 10% in the past 10 years, threatening the national industry. Understanding the importance of different attributes may help guide a strategy for the local beef industry. Thus, the goal of the study was to identify which attributes observable at the point of sale influence the beef buying process. The sample was a set of 406 price observations, search attributes (intrinsic and extrinsic cues), and credence attributes of differentiated beef. The study was conducted in 15 counties in the Metropolitana region in Chile, and the results indicated that among differentiated beef, the highest valued attributes were low fat and natural. In addition, Angus and Wagyu beef, breeds associated by consumers with increased tenderness and flavor, were highly valued. Finally, processed beef products (portioned, marinated, or seasoned) were more valued than unprocessed products. An important and unexpected result is that highlighting Chile as the country of origin is a negatively valued attribute.

Restraint stress exacerbates cell degeneration induced by acute binge ethanol in the adolescent, but not in the adult or middle-aged, brain.

Restraint stress (RS) induces neurotoxicity in the hippocampus, yet most of the studies have employed protracted RS (i.e., ≈ 21 days). Binge ethanol can induce brain toxicity, an effect affected by age. It could be postulated that RS may facilitate ethanol-induced neurotoxicity, perhaps to a greater extent in adolescent vs. older subjects. We analyzed whether adolescent, adult or middle-aged male rats exposed to five episodes of RS followed, 72h later, by binge ethanol (i.e., two administrations of 2.5 g/kg ethanol) exhibited hippocampal neurotoxicity. Adolescents, but not adult or middle-aged rats, exhibited sensitivity to the neurotoxic effects of ethanol at dorsal CA2, ventral CA3 and ventral DG, and a neurotoxic effect of stress at dorsal CA1. Moreover, the combination of ethanol and stress exerted a synergistic effect upon cell degeneration at ventral CA1 and CA2, which was restricted to adolescents. Ethanol also increased cell degeneration, irrespective of age or stress, in dorsal CA3 and in dorsal DG; and ethanol and stress had, across all ages, a synergistic effect upon cell degeneration at the dorsal CA1. The greater neurotoxic response of adolescents to ethanol, stress, or ethanol+stress can put them at risk for the development of alcohol problems.