Effect of plasma exchange with albumin replacement on albumin functionality and organ dysfunction in acute-on-chronic liver failure.

Background & Aims: Effective treatments for acute-on-chronic liver failure (ACLF) are a major unmet need. This proof-of-concept pilot study was aimed at evaluating the effects of plasma exchange (PE) with albumin 5% (PE-A5%) on albumin functional capacity and organ dysfunction in patients with ACLF. Methods: Ten adult patients were enrolled in a single-center phase II, prospective, open-label, non-controlled study. Six PE-A5% sessions were performed in 10 days followed by a 1-month follow-up visit. Albumin functional capacity and circulatory function were assessed, as were renal, cerebral, and liver function, and systemic inflammation. The main safety variable was the percentage of PE sessions associated with at least one procedure-related adverse event (AE). Results: Patients with ACLF showed lower albumin binding capacity, lower antioxidant capacity, and lower levels of albumin with preserved structure compared to healthy donors (n = 19). From baseline to day 11, PE-A5% treatment increased albumin levels and improved albumin binding capacity to Sudlow site II (15.3±1.6 mg/ml to 18.9±1.7 mg/ml; p = 0.003), fatty acid-binding capacity (8.2±1.4 µM to 3.1±1.5 µM; p = 0.013) and antioxidant capacity (human mercaptalbumin 9.5±1.5 mg/ml to 14.6±1.6 mg/ml; p = 0.001). Native albumin levels were increased throughout day 1-11 PE-A5% sessions (6.5±1.0 mg/ml to 10.2±1.4 mg/ml; p = 0.035). PE-A5% improved systemic hemodynamics (mean arterial pressure, heart rate, cardiac index), renal function (creatinine level, blood urea nitrogen), cerebral function (hepatic encephalopathy grade), liver parameters (transaminases, bilirubin) and inflammatory parameters (C-reactive protein, leukocyte count). All patients had at least one of the 78 AEs reported, mostly mild (product/procedure-related: 36%). Sixteen serious AEs were reported in eight patients (procedure/product-related: none). Conclusions: PE-A5% was a safe procedure associated with positive effects on albumin functionality, and circulatory, renal, cerebral, and liver function in patients with ACLF. Impact and implications: Acute-on-chronic liver failure (ACLF) is a clinical condition characterized by severe systemic inflammation, organ failure, and high mortality. Plasma exchange removes patient's plasma containing pathogenic substances, replacing it with 5% albumin and fresh frozen plasma (PE-A5%). In this study, cirrhotic patients with ACLF were treated with PE-A5%, which was a safe procedure that increased binding and antioxidant capacity of patients' albumin, while improving circulatory, kidney, brain, and liver functions. These beneficial effects could impact survival in ACLF. ClinicalTrialsgov Identifier: NCT01201720. EudraCT number: 2010-021360-15.

Longitudinal paths between parents' use of rewards and young adolescents' moral traits and prosocial behaviors.

BACKGROUND: Although prior research shows supportive evidence that parental practices are associated with adolescents' prosocial behaviors, limited evidence exists on the effects of parents' use of social and material rewards on distinct forms of prosocial behaviors, and the mediating effects of sociocognitive and socioemotive traits in these relations. AIMS: The present study was designed to examine the longitudinal relations among parents' use of social and material rewards, youth prosocial traits, and prosocial behaviors. MATERIALS & METHODS: Participants were 417 adolescents (M age = 14.70 years; 225 girls) from Valencia, Spain who completed surveys on parents' use of social and material reward practices, prosocial moral reasoning, empathic concern, and six types of prosocial behaviors. RESULTS: Path analyses showed that parents' use of social rewards was indirectly, positively related to emotional, dire, altruistic, public (negatively), and compliant prosocial behaviors via empathic concern. The use of social rewards was also indirectly positively linked to altruistic prosocial behaviors via both empathic concern and prosocial moral reasoning. In contrast, parents' use of material rewards predicted less prosocial moral reasoning, which in turn, was linked to more altruistic, prosocial behaviors. DISCUSSION AND CONCLUSIONS: The implications for parental socialization and self-determination theories of prosocial and moral development are discussed.

Psychosocial Effects of COVID-19 in the Ecuadorian and Spanish Populations: A Cross-Cultural Study.

The world's population is currently overcoming one of the worst pandemics, and the psychological and social effects of this are becoming more apparent. We will present an analysis of the psychosocial effects of COVID-19: first, a cross-sectional study in an Ecuadorian sample (n = 301) and second, a comparative study between two samples from the Ecuadorian and Spanish populations (n = 83 each one). Participants completed an online survey to (1) describe how they felt (depression, anxiety, and stress) before and after confinement; (2) analyze which emotional and behavioral variables predict depressive symptoms, anxiety, and stress perceived after the confinement; (3) carry out a comparative study in a sample of Ecuadorian and Spanish surveys. Results indicate, first, that Ecuadorians experience significantly more depressive symptoms, anxiety, and stress after confinement. Second, variables which predict depressive symptoms and anxiety are greater public prosocial tendency, less stress as a challenge, and greater stress as a threat, as well as an empathetic tendency that implies greater emotional regulation. Experienced stress after confinement was predicted by a greater public prosocial tendency, as well as an empathetic tendency. Finally, scores for depression, anxiety, and stress are higher after confinement in both countries. However, results reveal the similarity of the psychosocial effects that are being experienced, regardless of the country, and the differences in the variables that can help explain these effects. This can contribute to the constitution of intervention plans which aim to soften and alleviate the effects produced by a situation such as that experienced with COVID-19.

Traditional Masculinity and Aggression in Adolescence: Its Relationship with Emotional Processes.

Traditional masculinity includes norms that encourage many of the aggressive behaviors whereas traditional femininity emphasizes aggression very little. In addition, the lack of emotional regulation as well as a poor impulse control have been related to aggression and, in particular, with reactive and proactive aggression. The objective of this study is to examine the role of gender stereotypes (masculinity/femininity) in reactive and proactive aggression, through regulatory emotional self-efficacy and emotion regulation. A total of 390 adolescents participated in a longitudinal study in Valencia, Spain. Structural equations modeling (SEM) was employed to explore a two-wave longitudinal model. The results show that femininity relates to reactive aggression through regulatory emotional self-efficacy and emotion regulation. This way, both emotional self-efficacy and emotional regulation mediate the relation between femininity and reactive aggression. Furthermore, reactive and proactive aggression relate positively and directly to masculinity and negatively to femininity. Therefore, violence prevention programs with adolescents should incorporate information to break down gender stereotypes and promote strategies to manage emotions. Such efforts may be helpful to reduce aggressive behaviors and violence.

Worry about COVID-19 contagion and general anxiety: Moderation and mediation effects of cognitive emotion regulation.

The global pandemic caused by coronavirus disease 2019 (COVID-19) occasioned that most of the population in Spain was confined to home to reduce the risk of contagion. This affected mental health, increasing anxiety and worry about COVID-19 contagion. The aim of this study was assessing the moderation and mediation effect of cognitive emotion regulation strategies (CERS) on general anxiety and whether the mediation effect was moderated by gender and/or age. A total of 1753 Spanish adults (78,6% female; M = 40.4 years, SD = 12.9) participated in an online survey that was available from March 26 to April 25 (2020) during the time period in which the population in Spain was confined. Participants completed measures of worry about COVID-19 contagion, the Cognitive Emotion Regulation Questionnaire-Short (CERQ-Short) and the Generalized Anxiety Disorder-7 (GAD-7). Several models were tested through structural equation modelling. Moderation analyses reported that maladaptive strategies moderated positively anxiety, whereas adaptive strategies moderated negatively anxiety. Also, the best fitted mediation model found that worry about COVID-19 contagion and general anxiety was mediated by CERS in different directions. Maladaptive CERS increased anxiety, whereas adaptive CERS reduced anxiety. Age (not gender) also moderated this mediation, were younger adults presented an indirect effect only through maladaptive CERS, but older adults through both adaptive and maladaptive. Limitations are related to the study design which was a convenience sample. CERS moderated and mediated between worry about COVID-19 contagion and general anxiety. Prevention programs for mental health problems during the pandemic must be provided, especially for younger adults.

Victimization and Peer and Parents Attachment: The Mediating Effect of Regulatory Emotional Self-Efficacy.

Studies of the Spanish adolescent population has concluded that victimization is related to lack of emotional regulation and impulse control. Therefore, if a victim is unable to recognize, understand and regulate their emotions, this can result in rejection by their peers. A cross-sectional study was conducted to examine regulatory emotional self-efficacy as a possible mediator in the association between peer and parents attachment and victimization. Adolescents (n = 563) completed Regulatory Emotional Self-Efficacy, Inventory of Parents and Peer Attachment and Kid at School questionnaires. Structural equation models (SEMs) were used to predict a latent variable of victimization with parents and peer attachment, emphasizing the mediating role of regulatory emotional self-efficacy, as comprised by a positive and a negative aspect. Results showed that peer attachment had an indirect negative effect, through perceived self-efficacy, in managing a positive effect in victimization, while father attachment had an indirect negative affect, through perceived self-efficacy, in managing a negative affect in victimization, and Mother attachment had no statistically significant indirect effect in victimization. This study suggests that the roles of parents and peers, and also between mothers and fathers, are different in relation to the perception of victimization of adolescents. Findings provide relevant information regarding implications for prevention and intervention in victimization.

Enzymatic glycosylation of bioactive acceptors catalyzed by an immobilized fungal ß-xylosidase and its multi-glycoligase variant.

A recombinant ß-xylosidase (rBxTW1) from the ascomycete Talaromyces amestolkiae and a mutant derived from it, with mostly synthetic activity, have been immobilized as magnetic cross-linked enzyme aggregates (mCLEAs). The mCLEAs of rBxTW1 kept the excellent hydrolytic and O-transxylosylating activities of the free enzyme and had improved thermal and pH stability. The mCLEAs of the mutant also maintained or improved the catalytic properties of the soluble enzyme, synthetizing the O-xylosides of vanillin and (-)-epigallocatechin gallate, and the N- and S-xyloside of 3,5-dibromo-1,2,4-triazole and thiophenol, respectively. The mCLEAs were recyclable across 4 cycles of synthesis of the O-xylosides through a green and highly selective process. The magnetic properties of the scaffold used for immobilization may allow the easy recovery and reuse of the biocatalyst even from reactions containing insoluble lignocellulosic biomass.

Alpha1-antitrypsin ameliorates islet amyloid-induced glucose intolerance and ß-cell dysfunction.

OBJECTIVE: Pancreatic ß-cell failure is central to the development and progression of type 2 diabetes (T2D). The aggregation of human islet amyloid polypeptide (hIAPP) has been associated with pancreatic islet inflammation and dysfunction in T2D. Alpha1-antitrypsin (AAT) is a circulating protease inhibitor with anti-inflammatory properties. Here, we sought to investigate the potential therapeutic effect of AAT treatment in a mouse model characterized by hIAPP overexpression in pancreatic ß-cells. METHODS: Mice overexpressing hIAPP (hIAPP-Tg) in pancreatic ß-cells were used as a model of amyloid-induced ß-cell dysfunction. Glucose homeostasis was evaluated by glucose tolerance tests and insulin secretion assays. Apoptosis and amyloid formation was assessed in hIAPP-Tg mouse islets cultured at high glucose levels. Dissociated islet cells were cocultured with macrophages obtained from the peritoneal cavity. RESULTS: Nontreated hIAPP-Tg mice were glucose intolerant and exhibited impaired insulin secretion. Interestingly, AAT treatment improved glucose tolerance and restored the insulin secretory response to glucose in hIAPP-Tg mice. Moreover, AAT administration normalized the expression of the essential ß-cell genes MafA and Pdx1, which were downregulated in pancreatic islets from hIAPP-Tg mice. AAT prevented the formation of amyloid deposits and apoptosis in hIAPP-Tg islets cultured at high glucose concentrations. Since islet macrophages mediate hIAPP-induced ß-cell dysfunction, we investigated the effect of AAT in cocultures of macrophages and islet cells. AAT prevented hIAPP-induced ß-cell apoptosis in these cocultures without reducing the hIAPP-induced secretion of IL-1ß by macrophages. Remarkably, AAT protected ß-cells against the cytotoxic effects of conditioned medium from hIAPP-treated macrophages. Similarly, AAT also abrogated the cytotoxic effects of exogenous proinflammatory cytokines on pancreatic ß-cells. CONCLUSIONS: These results demonstrate that treatment with AAT improves glucose homeostasis in mice overexpressing hIAPP and protects pancreatic ß-cells from the cytotoxic actions of hIAPP mediated by macrophages. These results support the use of AAT-based therapies to recover pancreatic ß-cell function for the treatment of T2D.

Increased Albumin Oxidation in Cerebrospinal Fluid and Plasma from Alzheimer's Disease Patients.

BACKGROUND: Oxidative stress in the brain and peripheral systems is considered a major player in Alzheimer's disease (AD). Albumin is the main transporter and the main extracellular antioxidant in the human body. OBJECTIVE: Here we explore for the first time the oxidation status of cerebrospinal fluid (CSF) and plasma albumin in AD in comparison to healthy subjects. METHODS: Plasma and CSF samples were obtained from mild-moderate AD patients and control healthy age-matched donors. Albumin redox state forms (reduced: HMA; reversibly oxidized: HNA1; irreversibly oxidized: HNA2) were determined by HPLC. Albumin post-translational modifications (PTM) analysis was performed by mass spectrometry. RESULTS: HPLC showed less HMA in AD plasma than in controls (54.1% versus 65.2% ; p < 0.0001), mainly at expense of HNA1 (42.8% versus 32.5% ; p < 0.0001). In AD CSF, HMA was drastically decreased compared to controls (9.6% versus 77.4% ; p < 0.0001), while HNA2 was increased (52.8% versus 7.4% ; p < 0.0001). In AD patients but not in healthy controls, CSF albumin was much more irreversibly oxidized than in plasma (close to 20-fold increase in HNA2). PTM analysis showed that AD CSF albumin samples behave as a differentiated cluster, thus confirming the albumin oxidative pattern observed by HPLC. CONCLUSION: CSF albumin oxidation in AD patients was dramatically increased comparing to healthy controls, while in plasma this increase was smaller. CSF albumin in AD patients was much more oxidized than in plasma, but this effect was not observed in healthy controls. These results suggest that albumin oxidation, especially in CSF, and its role in AD deserves further investigation.

Negative emotions and behaviour: The role of regulatory emotional self-efficacy.

The objective of this study is to test a longitudinal model that analyses the direct effect of negative emotions (anger, depression and anxiety, wave 1) on prosocial and aggressive behaviour (wave 2) in adolescents. And the indirect effect of negative emotions (wave 1) on prosocial and aggressive behaviour (wave 2) through regulatory emotional self-efficacy. Data was obtained from 417 adolescents in a two-wave longitudinal study (225 girls, M age = 14.70 years) from schools located in Valencia, Spain. SEM was employed to explore longitudinal models. The results showed that anger had a direct relationship with prosocial behaviour and aggression, measured two years later. However, the depression and anxiety states did not predict prosociality and aggressiveness. The mediation role of regulatory emotional self-efficacy between negative emotion and behaviours was only partially confirmed. Finally, only the perception of self-efficacy in expressing positive affect is related to prosociality and aggressiveness.

Depression and aggressive behaviour in adolescents offenders and non-offenders.

BACKGROUND: Adolescent behaviour is strongly linked to emotions. The aim of this study is 1) analyse the differences between young offenders and non-offenders in emotional instability, anger, aggressive behaviour, anxiety and depression, and also the differences according to sex; and 2) compare the relation between emotional instability and anxiety, depression and aggressive behaviour mediated or modulated by anger in both groups. METHOD: participants are 440 adolescents, both male and female (15-18 years old). 220 were young offenders from four different correctional centres of the Valencia Region. The other 220 participants were randomly chosen from ten public and private schools in the Valencia metropolitan area. In the Schools the instruments were applied collectively in the classroom, with a 50 minutes maximum duration. In the Youth Detention Centre the application was carried out in small groups. RESULTS: The structural equation model (SEM) carried out on each group, young offenders and non-offenders show a relation between the assessed variables. Emotional instability appears strongly related with anger in both samples, but anger just predicts depression and aggressive behaviour in the offender population. CONCLUSIONS: The results give relevant information for treatment and prevention of aggressive behaviour and delinquency in teenagers through emotional regulation.