Quality of Recovery After Unplanned and Planned Cesarean Deliveries: A Prospective Observational Study Using the Obstetric Quality of Recovery-10 Tool.

BACKGROUND: There is a paucity of literature examining the differences between patient-reported outcome measures after planned and unplanned cesarean delivery using a validated quality of recovery tool. The Obstetric Quality of Recovery-10 (ObsQoR-10) scoring tool has been validated to quantify functional recovery after cesarean delivery. We aimed to use the ObsQoR-10 to compare the postoperative recovery characteristics of patients undergoing planned and unplanned cesarean deliveries. METHODS: We conducted a prospective single-center observational study. Patients undergoing planned and unplanned cesarean deliveries under neuraxial anesthesia were asked to complete the ObsQoR-10 questionnaire 24 hours, 48 hours, and 1 week postpartum. We collected information on total in-hospital postoperative opioid consumption and patients´ perception of readiness for discharge at 24 and 48 hours postpartum. Additionally, patient characteristics were collected to assess their correlation with our findings. RESULTS: We included 112 patients (56 in each group). No statistical differences in ObsQoR-10 scores at 24 hours, 48 hours, and 1 week postpartum were observed between the planned and unplanned cesarean deliveries. Additionally, there was no difference between the groups in patients' perception of readiness for hospital discharge at 24 and 48 hours and opioid consumption in the first 2 days after surgery. Most patients in both groups did not think they would be ready for discharge at 24 hours postpartum. Analysis of the individual components of ObsQoR-10 at 24 hours showed a difference in the responses assessing the severity of shivering (higher in unplanned cesarean deliveries) and the ability to look after personal hygiene (lower in unplanned cesarean deliveries). CONCLUSIONS: As assessed by the ObsQoR-10, no significant difference in the quality of recovery was observed between patients undergoing planned and unplanned cesarean delivery.

Evidence for environment hypothesis: Cross-cultural measurement invariance of the composite scale of morningness across Bangladesh and Spain.

Morningness-eveningness reflects individual differences in circadian functioning and is related to health and well-being. Cross-cultural comparison could facilitate understanding of the environmental factors affecting morningness-eveningness, which requires establishing cross-cultural validity of the relevant assessment tools. In this study, we applied the Composite Scale of Morningness (CSM) to Bangladeshi (n = 1015; 37.9% women) and Spanish (n = 1054; 73.2% women) university students (aged 18-27 years) to evaluate alternative factorial models of the CSM and to test its measurement invariance across cultures. Moreover, this study tested environment hypothesis, suggesting that higher average temperatures and lower latitudes would be related to greater morningness. From nine competing factorial models, a bifactor model with two specific factors (morning preference and morning affect) showed the best fit for both cultures. The two-factor bifactor model had full metric invariance with partial scalar and strict invariance across cultures. The Bangladesh-Spain comparison of the CSM scores revealed higher morningness in Bangladeshi students which supports the environment hypothesis. Overall, this research confirms that morningness-eveningness construct is perceived and interpreted similarly by the Bangladeshi and Spanish students. Importantly, this study highlights the effects of environmental factors including latitude and temperature on morningness-eveningness, and thus facilitates further cross-cultural morningness-eveningness research.

Spanish adaptation of the Gender-Related Variables for Health Research (GVHR): Factorial Structure and Relationship with Health Variables.

The aim of the present study was to conduct a preliminary study of the Stanford Gender-Related Variables for Health Research (GVHR) adapted to the Spanish population, testing its factor structure, sex factorial invariance and relationship with health variables. Participants were 438 adults between 19-73 years old (M = 31.90, SD = 12.12) who completed the GVHR and measures of health-related quality of life, psychological health, and health-risk behaviors. The confirmatory factorial analysis of the GVHR indicated an acceptable fit to the 7-factor structure as proposed for the North American population. Emotional intelligence and independence factors had low internal consistency, therefore, a five-factor model was tenable in the Spanish population. Sex scalar invariance was tenable, indicating that the factors latent means can be meaningfully compared across sex. Univariate logistic regressions indicated that women reported worse mental and physical health and more health limitations, but this effect dissipated when gender variables were considered. Caregiver and work strain stood out as the variables related to gender that predicted worse health-related quality of life, psychological health, and health-risk behaviors. In conclusion, factorial structure of the GVHR may differ from one culture to another. Additionally, the variables related to gender in the GVHR give a better account of the differences in health compared to biological sex.

Spanish adaptation of the Gender-Related Variables for Health Research (GVHR): Factorial Structure and Relationship with Health Variables

The aim of the present study was to conduct a preliminary study of the Stanford Gender-Related Variables for Health Research (GVHR) adapted to the Spanish population, testing its factor structure, sex factorial invariance and relationship with health variables. Participants were 438 adults between 19–73 years old (M = 31.90, SD = 12.12) who completed the GVHR and measures of health-related quality of life, psychological health, and health-risk behaviors. The confirmatory factorial analysis of the GVHR indicated an acceptable fit to the 7-factor structure as proposed for the North American population. Emotional intelligence and independence factors had low internal consistency, therefore, a five-factor model was tenable in the Spanish population. Sex scalar invariance was tenable, indicating that the factors latent means can be meaningfully compared across sex. Univariate logistic regressions indicated that women reported worse mental and physical health and more health limitations, but this effect dissipated when gender variables were considered. Caregiver and work strain stood out as the variables related to gender that predicted worse health-related quality of life, psychological health, and health-risk behaviors. In conclusion, factorial structure of the GVHR may differ from one culture to another. Additionally, the variables related to gender in the GVHR give a better account of the differences in health compared to biological sex. (AU)

The influence of a permanent double-shift school start time on adolescent sleep and chronotype across different age groups.

The main objective of this study was to explore the differences in sleep habits and chronotype across different age groups in Mexican adolescents attending a permanent double-shift school system. This cross-sectional study consisted of 1,969 (1,084 girls) students from public elementary, secondary, and high schools, as well as undergraduate university students from Mexico. Age range was 10-22 [15.33 ± 3.28 (mean ± SD)] years, 988 morning shift and 981 afternoon shift students. Questions regarding usual self-reported bedtime and rise time were collected, and from that, estimates for time in bed, midpoint of sleep, social jetlag, and chronotype were evaluated. Afternoon shift students reported later rise times, bedtimes, midpoint of sleep, and longer time in bed on school days than morning shift students, as well as less social jetlag. Overall, afternoon shift students reported a later chronotype than morning shift students. Peak lateness of chronotype in afternoon shift students was at age 15, with girls peaking at age 14 and boys at age 15. Meanwhile, morning shift students reported peak lateness of chronotype around age 20. In this study, adolescents from different age ranges attending an extremely delayed school start time reported adequate sleep compared with adolescents attending a fixed morning school start time. In addition, the analysis presented in this study seems to suggest that the peak of late chronotype may be influenced by school start times.

Clinical tools to assess functional capacity before elective non-cardiac surgery: a scoping review protocol.

OBJECTIVE: The objective of this scoping review is to map the evidence on clinical tools to assess functional capacity prior to elective non-cardiac surgery. INTRODUCTION: Functional capacity is a strong prognostic indicator before surgery, which can be used to identify patients at elevated risk of postoperative complications, yet, there is no consensus on which clinical tools should be used to assess functional capacity in patients prior to non-cardiac surgery. INCLUSION CRITERIA: This review will consider any randomized or non-randomized studies that evaluate the performance of a functional capacity assessment tool in adults (≥18 years) prior to non-cardiac surgery. For studies to be included, the tool must be used clinically for risk stratification. We will exclude studies on lung and liver transplant surgery, as well as ambulatory procedures performed under local anesthesia. METHODS: The review will be conducted in line with the JBI methodology for scoping reviews. A peer-reviewed search strategy will be used to query relevant databases (ie, MEDLINE, Embase, EBM Reviews). Additional sources of evidence will include databases of non-peer-reviewed literature and the reference lists of included studies. Two independent reviewers will identify eligible studies in 2 stages: stage 1, based on titles and abstracts; and stage 2, based on full texts. Information on study details, measurement properties, pragmatic qualities, and/or clinical utility metrics will be charted in duplicate onto standardized data collection forms. The results will be presented using descriptive summaries, frequency tables, and visual plots that highlight the extent of evidence and remaining gaps in the validation process of each tool. REVIEW REGISTRATION: Open Science Framework https://osf.io/6nfht.

Factors Underpinning the Shift to Eveningness during Early Adolescence: Pubertal Development and Family Conflicts.

Biological and psychosocial factors have been related to the shift to eveningness during early adolescence but it is necessary to study them from a longitudinal perspective. This longitudinal study examined the contribution of these factors to the onset of a shift towards eveningness in early adolescence. A sample of 440 (49.9% boys) Spanish adolescents were assessed for pubertal development, family conflicts, and morningness/eveningness. The same measures were taken twice at the age of 12 and one year later (T1: M = 12.47, SD = 0.75 and T2: M = 13.64, SD = 0.78). Pubertal development and family conflicts were considered predictors of morningness/eveningness in a mixed-effects multilevel model. The developmental shift towards eveningness appeared in girls but not in boys. The shift was related to more advanced pubertal development and more conflicts in the family. This study has implications for shaping healthy sleep habits in adolescents and possible interventions focused on family dynamics.

The psychometric properties of the Spanish version of the Morningness-Eveningness Stability Scale improved (MESSi) in adolescents.

The aim of the present study was to adapt the Morningness-Eveningness-Stability Scale improved (MESSi) to the Spanish adolescent population, testing its factor structure and construct validity. The participants were 725 adolescents (52.9% girls; M = 14.8, SD = 1.99) who completed the MESSi, the Morningness Eveningness Scale of Children (MESC), questions about sleep habits adapted from the School Sleep Habits Survey, and self-reported academic performance. The psychometric results support a three-factor model with the factors of morning affect, eveningness, and distinctness, which show good internal consistency. The pattern of correlations between MESSi and the other measures was in the expected direction. The MESC correlated positively with morning affect and negatively with eveningness, whereas distinctness was uncorrelated. Boys reported higher morningness, whereas girls reported higher distinctness. Eveningness was negatively related to academic performance. Overall, the results support the validity and reliability of the Spanish adolescent version of the MESSi.

Sex differences in the relationship between morningness-eveningness components, mood and well-being among Bangladeshi university students.

On the Morningness/Eveningness (M/E) continuum, eveningness has been related to mood disorder and poor well-being. M/E differs between men and women throughout their lifespan. However, there is a lack of information on sex differences in the relationship between M/E, mood, and well-being. This study aimed to test sex differences in the M/E, mood, and well-being relationship with consideration of two components of M/E, morning affect, and morning preference. A sample of 981 Bangladeshi university students (607 men) aged 18 to 27 (M = 21.95) completed Bangla versions of the Composite Scale of Morningness (CSM), BRUnel Mood Scale (BRUMS), and Positive Mental Health scale (PMH-scale) through an online survey. Multiple regression analyses were used to test the relationship of M/E components with mood and well-being. The results showed that the relationship between M/E, mood, and well-being was greater in women than in men. A lower score on both M/E components was related to higher negative moods (anger, confusion, depression, fatigue, and tension) and poor well-being. In regression analysis, only morning affect was found to be significant, which means that morning affect mainly contributes to the relation between M/E, mood, and well-being. Finally, sex by morning affect interaction indicated that the relation was higher for women. Therefore, higher eveningness could be more hazardous for women than men. Greater insight into the independent contribution of morning affect may facilitate understanding of the chronotype effects on psychological outcomes in men and women.

Sleep and Depressive Symptoms in the Morningness/Eveningness-Suicidal Ideation Relationship Depend on School Shift in Mexican Adolescents.

The aim was to analyze the morningness/eveningness (M/E) effect on suicidal ideation through sleep and depressive symptoms mediators with school shift (i.e., morning and afternoon) as moderator. In this study, 586 Mexican adolescents, with a mean age of 16.31 ± 0.92, from a public high school in a double-shift school system (298 from the morning shift and 288 from the afternoon shift) participated. Measurements of sleep, morningness/eveningness (circadian preference), depressive symptomology, and suicidal ideation were completed. Adolescents in the afternoon shift reported a later rise time, bedtime, greater time in bed sleep length, and less social jet lag than in the morning shift. Considering the moderated-mediated analysis, circadian preference and suicidal ideation were mediated by both depressive symptoms and school day's sleep length in the morning shift. In the afternoon shift, no mediation effect was significant. When weekend sleep length was considered in the model, only depressive symptoms had a mediating effect between circadian preference and suicidal ideation in the morning shift; no significant mediating effect was found on the afternoon shift. The results suggest that an afternoon school schedule may act as a protective factor for the adolescent's mental health and may represent a viable option for future interventions.

Sleep habits and circadian preferences in school-aged children attending a Mexican double-shift school system.

OBJECTIVE: To determine the differences between sleep habits and circadian preference in school-aged children attending a Mexican double-shift school system. METHODS: This cross-sectional study consisted of 400 elementary public-school children (mean age = 10.77, SD = 0.70 y, from fourth, fifth and sixth grades) in Reynosa, Tamaulipas, in northeastern Mexico. Attending a double-shift school system: 200 from the morning shift and 200 in the afternoon shift. Specific questions regarding sleep habits were collected and for circadian preference, the Morningness-Eveningness Scale for Children (MESC) was used. RESULTS: Multivariate analysis reported no sex differences. Children attending at the morning shift during weekdays rose earlier, reported shorter time in bed and earlier midpoint of sleep than those in the afternoon shift. On weekends, morning shift children went to bed later than afternoon shift. Morning shift reported greater social jetlag, shorter average sleep length and more sleep deficit than afternoon shift. During weekdays and weekends evening type children went to bed later, rose later and reported later midpoint of sleep. Also, evening type reported more social jetlag than morning types. CONCLUSION: This study suggests that early school start times can have a detrimental effect on Mexican children. Moreover, the morning shift children may be at more risk of poor health due to the higher social jetlag, as well as a higher tendency to be sleep deprived. On the other hand, the afternoon shift represents an important social environment that allows children to follow their natural physiological needs and a more optimal sleep health.

Positive Predictive Value Surfaces as a Complementary Tool to Assess the Performance of Virtual Screening Methods.

BACKGROUND: Since their introduction in the virtual screening field, Receiver Operating Characteristic (ROC) curve-derived metrics have been widely used for benchmarking of computational methods and algorithms intended for virtual screening applications. Whereas in classification problems, the ratio between sensitivity and specificity for a given score value is very informative, a practical concern in virtual screening campaigns is to predict the actual probability that a predicted hit will prove truly active when submitted to experimental testing (in other words, the Positive Predictive Value - PPV). Estimation of such probability is however, obstructed due to its dependency on the yield of actives of the screened library, which cannot be known a priori. OBJECTIVE: To explore the use of PPV surfaces derived from simulated ranking experiments (retrospective virtual screening) as a complementary tool to ROC curves, for both benchmarking and optimization of score cutoff values. METHODS: The utility of the proposed approach is assessed in retrospective virtual screening experiments with four datasets used to infer QSAR classifiers: inhibitors of Trypanosoma cruzi trypanothione synthetase; inhibitors of Trypanosoma brucei N-myristoyltransferase; inhibitors of GABA transaminase and anticonvulsant activity in the 6 Hz seizure model. RESULTS: Besides illustrating the utility of PPV surfaces to compare the performance of machine learning models for virtual screening applications and to select an adequate score threshold, our results also suggest that ensemble learning provides models with better predictivity and more robust behavior. CONCLUSION: PPV surfaces are valuable tools to assess virtual screening tools and choose score thresholds to be applied in prospective in silico screens. Ensemble learning approaches seem to consistently lead to improved predictivity and robustness.

Sleep habits, circadian preferences and substance use in a Mexican population: the use of the Morningness-Eveningness-Stability-Scale improved (MESSi).

This study aimed to validate the Morningness-Eveningness-Stability-Scale improved (MESSi) in Mexico, analyzing the factor structure and sleep habits, combined with the proposal of cutoff values for the scales, and to assess the relationship with substance use. We applied the questionnaires through an online survey to a total sample of 510 Mexicans, aged 18-77 years (M = 27.79, SD = 10.24). The MESSi showed an acceptable fit and the Cronbach's alpha coefficients were good to satisfactory in the Mexican sample in every subscale: Morning Affect (MA, α = 0.90), Eveningness (EV, α = 0.88), Distinctness (DI, α = 0.80). In order to obtain a better interpretation of the MESSi subscales, we decided to propose cutoff points corresponding to the 25th-75th percentile. The categories were depicted as strong trait presence, intermediate trait presence and weak trait presence. When applying the cutoff points for the MESSi sub-scales, with Morning Affect (MA), strong-types went to bed and woke up earlier and had more sleep than weak-types during weekdays and weekends and reported less social jetlag. For Eveningness (EV), strong-types went to bed and woke up later than weak-types on weekdays and weekends. Also, strong-types had a shorter time in bed during weekdays but not on weekends and reported more social jetlag. Lastly, with Distinctness (DI), the results reported that those with a strong-type showed greater amplitude on weekdays and weekends. Furthermore, the MESSi scale found that evening people consumed more alcohol and tobacco. Our study supported the validity and reliability of the MESSi in a Mexican population and the relationship between eveningness and substance consumption. Furthermore, the proposed cutoff scores for the MESSi sub-scales add a novel approach for the measurement and interpretation of the scale.

Circadian preference and relationship satisfaction among three types of couples.

Mate selection is part of a growing interest in the study of processes by which couples are established, consolidated and/or separated. Similarity in psychological traits has been related to the well-being of couples, but given the possible effect of temporal convergence, it is necessary to control for the relationship length and whether or not both members of the couple live together. The aim of this study was to analyse the association between Morningness/Eveningness (M/E) similarity and relationship satisfaction in young-dating-non-cohabiting, young-married-cohabiting and old-married-cohabiting couples. Participants included 357 heterosexual couples (357 women and 357 men) with a mean age of 38.42 years old (SD = 13.11; age range between 19 and 69) who completed M/E (Composite Scale of Morningness) and relationship satisfaction measures (Comprehensive Marital Satisfaction Scale). Similarity in M/E was positively related to greater relationship satisfaction in both young cohabiting and non-cohabiting couples. In women, their own M/E was related to their own relationship satisfaction, whereas the level of relationship satisfaction in men was related to their partner's M/E. This relationship was observed in young-married-cohabiting couples. M/E similarity may operate differently as a function of the relationship stage.

Molecular Topology and Other Promiscuity Determinants as Predictors of Therapeutic Class - A Theoretical Framework to Guide Drug Repositioning?

Much interest has been paid in the last decade on molecular predictors of promiscuity, including molecular weight, log P, molecular complexity, acidity constant and molecular topology, with correlations between promiscuity and those descriptors seemingly being context-dependent. It has been observed that certain therapeutic categories (e.g. mood disorders therapies) display a tendency to include multi-target agents (i.e. selective non-selectivity). Numerous QSAR models based on topological descriptors suggest that the topology of a given drug could be used to infer its therapeutic applications. Here, we have used descriptive statistics to explore the distribution of molecular topology descriptors and other promiscuity predictors across different therapeutic categories. Working with the publicly available ChEMBL database and 14 molecular descriptors, both hierarchical and non-hierchical clustering methods were applied to the descriptors mean values of the therapeutic categories after the refinement of the database (770 drugs grouped into 34 therapeutic categories). On the other hand, another publicly available database (repoDB) was used to retrieve cases of clinically-approved drug repositioning examples that could be classified into the therapeutic categories considered by the aforementioned clusters (111 cases), and the correspondence between the two studies was evaluated. Interestingly, a 3- cluster hierarchical clustering scheme based on only 14 molecular descriptors linked to promiscuity seem to explain up to 82.9% of approved cases of drug repurposing retrieved of repoDB. Therapeutic categories seem to display distinctive molecular patterns, which could be used as a basis for drug screening and drug design campaigns, and to unveil drug repurposing opportunities between particular therapeutic categories.

Cascade Ligand- and Structure-Based Virtual Screening to Identify New Trypanocidal Compounds Inhibiting Putrescine Uptake.

Chagas disease is a neglected tropical disease endemic to Latin America, though migratory movements have recently spread it to other regions. Here, we have applied a cascade virtual screening campaign combining ligand- and structure-based methods. In order to find novel inhibitors of putrescine uptake in Trypanosoma cruzi, an ensemble of linear ligand-based classifiers obtained by has been applied as initial screening filter, followed by docking into a homology model of the putrescine permease TcPAT12. 1,000 individual linear classifiers were inferred from a balanced dataset. Subsequently, different schemes were tested to combine the individual classifiers: MIN operator, average ranking, average score, average voting, with MIN operator leading to the best performance. The homology model was based on the arginine/agmatine antiporter (AdiC) from Escherichia coli as template. It showed 64% coverage of the entire query sequence and it was selected based on the normalized Discrete Optimized Protein Energy parameter and the GA341 score. The modeled structure had 96% in the allowed area of Ramachandran's plot, and none of the residues located in non-allowed regions were involved in the active site of the transporter. Positivity Predictive Value surfaces were applied to optimize the score thresholds to be used in the ligand-based virtual screening step: for that purpose Positivity Predictive Value was charted as a function of putative yields of active in the range 0.001-0.010 and the Se/Sp ratio. With a focus on drug repositioning opportunities, DrugBank and Sweetlead databases were subjected to screening. Among 8 hits, cinnarizine, a drug frequently prescribed for motion sickness and balance disorder, was tested against T. cruzi epimastigotes and amastigotes, confirming its trypanocidal effects and its inhibitory effects on putrescine uptake. Furthermore, clofazimine, an antibiotic with already proven trypanocidal effects, also displayed inhibitory effects on putrescine uptake. Two other hits, meclizine and butoconazole, also displayed trypanocidal effects (in the case of meclizine, against both epimastigotes and amastigotes), without inhibiting putrescine uptake.

Age and Sex Differences in Morningness/Eveningness Along the Life Span: A Cross-Sectional Study in Spain.

Work psychology has noted the importance of considering the temporal dimension of behavior in organizations. Given that society widely operates on a 24-hr schedule, it is important to know how circadian typologies are distributed in the general population. In this study, diurnal preference was analyzed among 4,175 Spanish participants (61.3% women), 12-59 years old, who completed the Composite Scale of Morningness (Smith, Reilly, & Midkiff, 1989). Several measurement models of the CSM were analyzed using exploratory structural equation modeling and confirmatory factor analysis. The bifactor model showed the best fit, with a general factor (morningness/eveningness) and three subfactors (morningness, morning affect, and time of retiring). The age and sex factorial invariance of the bifactor model were tenable at the latent variance-covariance level. Next, age and sex differences analysis indicated a progressive increase in morningness with age, but over 40 years old, men were more morningness oriented than women were. These results indicate that morningness/eveningness can be considered a multidimensional construct and that psychosocial factors must be considered when estimating the prevalence of morningness/eveningness in different populations or countries.

Morningness-eveningness is not associated with academic performance in the afternoon school shift: Preliminary findings.

BACKGROUND: The effect of morningness-eveningness, sleep habits, and intelligence on academic performance has been studied in a fixed morning school shift. However, no studies have analysed these variables in an afternoon school shift and tested whether morningness-eveningness is related to academic performance beyond sleep habits and intelligence effects. AIMS: The psychometric properties of the Morningness-Eveningness Scale for Children (MESC) were analysed. Additionally, academic performance, sex, intelligence, sleep habits, and morningness-eveningness relationship in a morning and afternoon school shift were compared. SAMPLE: The sample consisted of 400 students at a secondary public school in Reynosa, Tamaulipas, in north-eastern Mexico (195 boys and 205 girls; mean ± SD: 13.85 ± 0.70 years old) attending a double-shift school system: 200 from the morning shift (99 boys and 101 girls) and 200 from the afternoon shift (96 boys and 104 girls). METHODS: The students completed the MESC as a measure of morningness-eveningness, a sleep habits survey, a test of academic performance, and the inductive reasoning subtest (R) of the Primary Mental Abilities battery. RESULTS: Adolescents in the two school shifts did not differ in academic performance and intelligence. In the afternoon shift, adolescents slept longer, reported less sleep deficit and social jet lag, and were more oriented to eveningness than adolescents in the morning shift. Sex (girls), sleep length, inductive reasoning, and morningness were associated with academic performance in the morning shift but only sex and intelligence in the afternoon shift. CONCLUSIONS: The role of morningness-eveningness in academic performance in the afternoon shift is examined.

Validation of the MESSi among adult workers and young students: General health and personality correlates.

The aim of this study was to provide validity for the Spanish version of the Morningness-Eveningness-Stability Scale - improved (MESSi), a novel evolved assessment of circadian typology which considers the subjective phase and amplitude by morning affect (MA), eveningness (EV) and distinctness (DI; subjective amplitude) sub-scales. Convergence validity of the MESSi with the reduced Morningness-Eveningness Questionnaire (rMEQ) and relationships with the General Health Questionnaire (GHQ-12) and sensitivity to reward and punishment (SR and SP) were analyzed. Two different Spanish samples, young undergraduate students (n = 891, 18-30 years) and adult workers (n = 577, 31-65 years) participated in this study. Exploratory structural equation modeling (ESEM) of MESSi displayed acceptable fit of a three-factors measurement model. Percentiles of the MA, EV and DI sub-scales were obtained for students and adults. The MESSi showed good convergence validity with the rMEQ scores, with a higher correlation coefficient between MA, EV and lower with DI sub-scales. In both, young students and adult workers, MA was negatively related with the GHQ-12 and SP, but the percentage of explained variance (6% and 3%) was lower than the positive correlations between DI, the GHQ-12 and SP (20% and 13%). Morning types presented higher MA and lower EV scores than the other two typologies in both students and adult workers, whereas only differences in DI were found among students (lowest in evening type). Candidates to psychological symptoms and mental disorders ("true cases"), with the clinical cut-off criteria of the GHQ-12, showed lower MA and higher DI in students, whereas only DI was higher for "true cases" among adults. These results supported that subjective amplitude is a factor related to, but also differentiated of, morningness-eveningness (preferred time for a certain activity). The measure of amplitude might be more important than circadian phase in health consequences.

Development and Validation of a Computational Model Ensemble for the Early Detection of BCRP/ABCG2 Substrates during the Drug Design Stage.

Breast Cancer Resistance Protein (BCRP) is an ATP-dependent efflux transporter linked to the multidrug resistance phenomenon in many diseases such as epilepsy and cancer and a potential source of drug interactions. For these reasons, the early identification of substrates and nonsubstrates of this transporter during the drug discovery stage is of great interest. We have developed a computational nonlinear model ensemble based on conformational independent molecular descriptors using a combined strategy of genetic algorithms, J48 decision tree classifiers, and data fusion. The best model ensemble consists in averaging the ranking of the 12 decision trees that showed the best performance on the training set, which also demonstrated a good performance for the test set. It was experimentally validated using the ex vivo everted rat intestinal sac model. Five anticonvulsant drugs classified as nonsubstrates for BRCP by the model ensemble were experimentally evaluated, and none of them proved to be a BCRP substrate under the experimental conditions used, thus confirming the predictive ability of the model ensemble. The model ensemble reported here is a potentially valuable tool to be used as an in silico ADME filter in computer-aided drug discovery campaigns intended to overcome BCRP-mediated multidrug resistance issues and to prevent drug-drug interactions.