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.

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.

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.

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.

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.

Maternal isolation during the first two postnatal weeks affects novelty-induced responses and sensitivity to ethanol-induced locomotor activity during infancy.

Animals exposed to chronic maternal separation (MS) exhibit enhanced ethanol self-administration and greater hormonal and behavioral responsiveness to stress in adulthood. Whether the effects of MS are immediately evident in infancy or whether they appear only later on development is still an unanswered question This study tested sensitivity to ethanol's behavioral stimulating effects in infant rats that experienced MS from postnatal Day 1-14. MS infants exhibited significantly greater reactivity to the motor stimulating effects of 1.25 g/kg ethanol than control animals, yet greater motor suppression after 2.5 g/kg ethanol. Baseline level of response to novelty was altered in MS infants, in a nor-binaltorphimine insensitive manner, that is, despite modified activity of the kappa-opioid system. These results indicate that the consequences of chronic maternal isolation emerge early in ontogeny, affecting ethanol sensitivity in infancy.

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.

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.

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.

[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.

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.

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.

Utility of implantable loop recorders for diagnosing unexplained syncope in clinical practice.

BACKGROUND: Establishing a symptom-rhythm correlation in patients with unexplained syncope is complicated because of its sporadic, infrequent, and unpredictable nature. Prolonged monitoring with an implantable loop recorder (ILR) allows the recording of electrocardiogram (ECG) data from a spontaneous syncopal event. HYPOTHESIS: The aim of this study was to evaluate the usefulness of the ILR for the diagnosis of syncope of unknown origin after conventional management in clinical practice. METHODS: We reviewed the results with ILR implantation in patients with syncope of unknown origin after conventional management in the cardiology department at HU Marques de Valdecilla (Santander, Cantabria, Spain). RESULTS: One hundred and forty patients (age 64 +/- 16 y; 86 male [62%]) with syncope of unknown etiology after conventional work-up underwent prolonged monitoring with an ILR from September 1998 to February 2006; 46 patients (33%) had structural heart disease. During a mean follow-up of 346 +/- 160 d, 51 patients (36.5%) had recurrent syncope with diagnostic ECG recording. An arrhythmic cause for syncope was found in 33 of them (64.5%), with bradycardia present in 27 (53%) and tachycardia in 6 (11%). There were no sudden deaths, and 1 patient suffered a complication related to a recurrence of syncope. CONCLUSION: Long-time experience with the ILR confirmed the utility of this device in the diagnosis of unexplained syncope in clinical practice. Most of these patients had syncope of arrhythmogenic etiology that could be successfully treated. This strategy of prolonged monitoring is safe even in patients with structural heart disease.

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.

Prenatal ethanol exposure potentiates isolation-induced ethanol consumption in young adult rats.

Prenatal and/or early postnatal ethanol exposure (PEE) is associated with significant behavioral and physiological deficits in offspring, including alterations in stress response systems and a greater likelihood of alcohol use disorders. Stress-induced ethanol drinking after PEE, however, has been largely unexplored. The present study analyzed ethanol intake in male Sprague-Dawley rats after protracted prenatal and early postnatal ethanol exposure and tested whether social isolation during the sensitive period of adolescence modulates the effects of PEE on ethanol drinking. The dams were given 10% ethanol (or its vehicle) as the sole drinking fluid from gestational day 0 (GD0) to postnatal day 7 (PD7). On PD21, male offspring were housed individually (isolated housing group) or in pairs in standard cages (standard housing group). From PD56 to PD84, these male rats were tested for ethanol intake in 24-h, intermittent two-bottle choice sessions that were conducted across 4 weeks. Maternal ethanol consumption during gestation and during the first week of life of the offspring averaged 6.10-8.20 g/kg/22 h. Isolation housing during adolescence increased free-choice ethanol drinking in young adulthood. The main novel finding was that this facilitative effect of isolation on absolute and percent ethanol intake was significantly greater in PEE rats than in control counterparts not exposed to the prenatal and early postnatal ethanol exposure (effect sizes [η2p]: 0.24-0.32). The present results suggest that PEE renders the individual sensitive to the facilitative effect of stress exposure on ethanol intake.

The offspring of rats selected for high or low ethanol intake at adolescence exhibit differential ethanol-induced Fos immunoreactivity in the central amygdala and in nucleus accumbens core.

Adolescents exhibit, when compared to adults, altered responsivity to the unconditional effects of ethanol. It is unclear if this has a role in the excessive ethanol intake of adolescents. Wistar rats from the third filial generation (F3) of a short-term breeding program which were selected for high (STDRHI) vs. low (STDRLO) ethanol intake during adolescence, were assessed for ethanol-induced (0.0, 1.25 or 2.5 g/kg) Fos immunoreactivity (Fos-ir) in the central (Ce), basolateral (BLA) and medial (Me) amygdaloid nuclei; nucleus accumbens core and shell (AcbC, AcbSh), ventral tegmental area (VTA), as well as prelimbic and infralimbic (PrL, IL) prefrontal cortices. Following i.p. administration of saline, and across the structures measured, Fos-ir was significantly greater in STDRHI than in STDRLO rats. Across both lines, baseline Fos-ir was significantly lower in BLA than in any other structure, whereas PrL, IL and Shell did not differ between each other and exhibited significantly greater level of baseline neural activation than Ce, Me, AcbC and VTA. STDRLO, but not STDRHI, rats exhibited ethanol-induced Fos-ir in Ce. STRDHI, but not STDRLO, rats exhibited an ethanol-induced Fos-ir depression in AcbC. Key maternal care behaviors (i.e., grooming of the pups, latency to retrieve the pups, time spent in the nest and time adopting a kiphotic posture) were fairly similar across lines. There were significant intergenerational variations in the amount self-licking behaviors in STDRHI dams as well as an increased amount of exploration of the cage in these animals, when compared to STDRLO counterparts. These results indicate that short term selection for differential alcohol intake during adolescence yields heightened neural activity at baseline (i.e., after vehicle) in STRDHI vs. STDRLO adolescent rats, and differential sensitivity to ethanol-induced Fos immunoreactivity in Ce and in AcbC. It is unlikely that rearing patterns explained the neural differences reported, between STDRHI and STDRLO rats.

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.