RESUMEN
Introduction: The consensus on recovery from alcohol use disorder (AUD) has shifted toward encompassing psychological wellbeing and quality of life dimensions. However, few studies have explored the long-term recovery process and its dimensions, timing, styles, and modes. The aim of this study was to investigate the extent, timing, and process of psychological wellbeing and quality of life recovery in alcohol use disorder (AUD) patients, as well as the relationship with classic dimensions of AUD recovery. Method: A cross-sectional study has been carried out with 348 participants with AUD, in different abstinence periods (1 month-28 years), and 171 control subjects. Participants underwent a psychological evaluation, which included self-informed measures of psychological wellbeing, quality of life, negative emotionality, and coping strategies related to alcohol consumption avoidance. Statistical analysis included linear and non-linear regression models between psychological dimensions and maintenance of abstinence, as well as matching the scores of the sample with AUD to those of controls. Scatter plots were used to explore inflection points. In addition, mean comparison tests were performed between participants with AUD and controls and by gender. Results: In general, according to the regression models, there were pronounced increases in indices of wellbeing and coping strategies (and pronounced decreases in negative emotionality) during the first 5 years of abstinence, followed by less pronounced improvements. The matching of AUD subjects in wellbeing and negative emotionality indices with controls occurs at different times: (a) 1 year or less: physical health; (b) 1-4 years: psychological health; (c) 4-10 years: social relationships, wellbeing, and negative emotionality; and (d) more than 10 years: autonomy and self-acceptance. There are statistically significant differences by gender for the negative emotionality and physical health variables. Conclusion: Recovery from AUD is a long process that involves improvements in wellbeing and quality of life. Four stages can be described in this process, with the most pronounced changes occurring during the first 5 years of abstinence. However, AUD patients take more time to obtain similar scores to controls in several psychological dimensions.
RESUMEN
Proteins containing C2 domains are the sensors for Ca(2+) and PI(4,5)P2 in a myriad of secretory pathways. Here, the use of a free-mounting system has enabled us to capture an intermediate state of Ca(2+) binding to the C2A domain of rabphilin 3A that suggests a different mechanism of ion interaction. We have also determined the structure of this domain in complex with PI(4,5)P2 and IP3 at resolutions of 1.75 and 1.9 Å, respectively, unveiling that the polybasic cluster formed by strands ß3-ß4 is involved in the interaction with the phosphoinositides. A comparative study demonstrates that the C2A domain is highly specific for PI(4,5)P2/PI(3,4,5)P3, whereas the C2B domain cannot discriminate among any of the diphosphorylated forms. Structural comparisons between C2A domains of rabphilin 3A and synaptotagmin 1 indicated the presence of a key glutamic residue in the polybasic cluster of synaptotagmin 1 that abolishes the interaction with PI(4,5)P2. Together, these results provide a structural explanation for the ability of different C2 domains to pull plasma and vesicle membranes close together in a Ca(2+)-dependent manner and reveal how this family of proteins can use subtle structural changes to modulate their sensitivity and specificity to various cellular signals.
