Outcomes and effect of somatic mutations after erythropoiesis stimulating agents in patients with lower-risk myelodysplastic syndromes.

Background: Erythropoiesis stimulating agents (ESAs) are the first-line therapy in patients with lower-risk myelodysplastic syndromes (LR-MDS). Some predictive factors for ESAs response have been identified. Type and number of somatic mutations have been associated with prognosis and response to therapies in MDS patients. Objectives: The objective was to evaluate the outcomes after ESAs in patients with LR-MDS and to address the potential predictive value of somatic mutations in ESAs-treated patients. Design: Multi-center retrospective study of a cohort of 722 patients with LR-MDS included in the SPRESAS (Spanish Registry of Erythropoietic Stimulating Agents Study) study. Retrospective analysis of 65 patients with next generation sequencing (NGS) data from diagnosis. Methods: ESAs' efficacy and safety were evaluated in patients receiving ESAs and best supportive care (BSC). To assess the potential prognostic value of somatic mutations in erythroid response (ER) rate and outcome, NGS was performed in responders and non-responders. Results: ER rate for ESAs-treated patients was 65%. Serum erythropoietin (EPO) level <200 U/l was the only variable significantly associated with a higher ER rate (odds ratio, 2.45; p = 0.036). Median overall survival (OS) in patients treated with ESAs was 6.7 versus 3.1 years in patients receiving BSC (p < 0.001). From 65 patients with NGS data, 57 (87.7%) have at least one mutation. We observed a trend to a higher frequency of ER among patients with a lower number of mutated genes (40.4% in <3 mutated genes versus 22.2% in ⩾3; p = 0.170). The presence of ⩾3 mutated genes was also significantly associated with worse OS (hazard ratio, 2.8; p = 0.015), even in responders. A higher cumulative incidence of acute myeloid leukemia progression at 5 years was also observed in patients with ⩾3 mutated genes versus <3 (33.3% and 10.7%, respectively; p < 0.001). Conclusion: This large study confirms the beneficial effect of ESAs and the adverse effect of somatic mutations in patients with LR-MDS.

Application of the Delphi Method for Content Validity Analysis of a Questionnaire to Determine the Risk Factors of the Chemsex.

Chemsex is understood as "the intentional use of stimulant drugs to have sex for an extended time among gay, bisexual, and other men who have sex with men". It is a public health problem because of the increased incidence of cases and because of the consequences on the physical and mental health of those who practice it. AIM: This study aimed to analyze, with the help of the Delphi method, the content validity of a new instrument to assess the risk of behaviors associated with the chemsex phenomenon. METHOD: First, a bank of items identified from the literature was elaborated. Secondly, 50 experts with knowledge of the chemsex phenomenon at the national level were contacted. A Delphi group was formed with them to carry out two rounds of item evaluation. The linguistic evaluation (comprehension and appropriateness) was assessed using a Likert scale from 1 to 5 for each item. Items that did not reach a mean score of 4 were eliminated. Content assessment was calculated using each item's content validity index (CVI) and Aiken's V (VdA). A minimum CVI and VdA value of 0.6 was established to include the items in the questionnaire. RESULTS: A total of 114 items were identified in the literature. In the first round of Delphi evaluation, 36 experts evaluated the items. A total of 58 items were eliminated for obtaining a CVI or VdA of less than 0.6, leaving 56 items. In a second Delphi round, 30 experts re-evaluated the 56 selected items, where 4 items were eliminated for being similar, and 10 items were also eliminated for not being relevant to the topic even though they had values higher than 0.6, leaving the scale finally composed of 52 items. CONCLUSION: A questionnaire has been designed to assess the risk of behaviors associated with the chemsex phenomenon. The items that make up the questionnaire have shown adequate content and linguistic validity. The Delphi method proved to be a helpful technique for the proposed objective.

Analysis of Psychological Well-Being from a Compositional Data Analysis Perspective: A New Approach.

Well-being is a widely studied construct in psychology. In 1989, Carol Ryff proposed the "Scale of Psychological Well-Being (SPWB)", which has been validated in multiple languages. The instrument assesses six dimensions of psychological well-being: Self-acceptance, Positive Relationships with Others, Autonomy, Environmental Mastery, Purpose in Life, and Personal Growth. In this article, we propose to enrich the traditional approach of directly interpreting the raw scores in each dimension by incorporating Compositional Data Analysis. This new approach aims to identify "what proportion" of each dimension constitutes well-being, which will allow us to analyze the interactions between the different dimensions of well-being and balance among them. To achieve this, we introduce two position ratios (PR1 and PR2) and a general adjustment indicator called the General Indicator of Subjective Psychological Well-Being (GISPW), which characterizes individuals in a compositional manner, providing a fresh perspective in the interpretation of psychological test results, specifically those related to PWB. The proposal is illustrated with three cases taken from a study involving 628 university students who completed the psychological well-being scale questionnaire. The results show that the GISPW, PR1, and PR2 obtained offer relevant information about the overall balance of each case in the different dimensions.

Exploring the Link between Interoceptive Body Awareness and Suicidal Orientation in University Students: A Cross-Sectional Study.

INTRODUCTION: The transition to college life can impact the mental health of students. There are mental health care strategies that promote connection with the body's internal signals, which can help to improve mental well-being, manage emotions, and reduce the risk of suicide in university students. AIM: This study aimed to examine the association between interoceptive body awareness variables and suicidal orientation in a sample of 169 undergraduate students in Colombia. METHODS: An observational, cross-sectional study was conducted in 2023 with Colombian students as the participants. RESULTS: The findings revealed a significant and moderately negative correlation between the Multidimensional Assessment of Interoceptive Awareness (MAIA) total score and the Inventory of Suicide Orientation (ISO-30) total score (r = -0.54, p < 0.001). Confidence and self-regulation were identified as the most influential factors in the relationship between MAIA and ISO-30. Significant correlations were observed (p < 0.001), indicating moderate correlation values ranging from -0.43 to -0.57. DISCUSSION: Our findings support the existence of a negative correlation between interoceptive body awareness and suicidal orientation. Further research is needed to better understand this relationship and to develop specific interventions based on body awareness to prevent suicide orientation. CONCLUSION: There are practical implications associated with recognizing the importance of body awareness in relation to decreasing suicidal orientation, and multidisciplinary teams addressing mental health can incorporate this knowledge.

Predictive Value of Cervical Shear Wave Elastography in the Induction of Labor in Late-Term Pregnancy Nulliparous Women: Preliminary Results.

The prediction of induction of labor continues to be a paradigm nowadays. Bishop Score is the traditional widely spread method but with a low reliability. Ultrasound cervical assessment has been proposed as an instrument of measurement. Shear wave elastography (SWE) should be a promising tool in the prediction of the success of labor induction in nulliparous late-term pregnancies. Ninety-two women with nulliparous late-term pregnancies who were going to be induced were included in the study. A shear wave measurement of the cervix divided into six regions (inner, middle and outer in both cervical lips), cervical length and fetal biometry was performed by blinded investigators prior to routine hand cervical assessment (Bishop Score (BS)) and induction of labor. The primary outcome was success of induction. Sixty-three women achieved labor. Nine women did not, and they underwent a cesarean section due to failure to induce labor. SWE was significantly higher in the inner part of the posterior cervix (p < 0.0001). SWE showed an area under the curve (AUC): 0.809 (0.677-0.941) in the inner posterior part. For CL, AUC was 0.816 (0.692-0.984). BS AUC was 0.467 (0.283-0.651). The ICC of inter-observer reproducibility was ≥0.83 in each region of interest (ROI). The cervix elastic gradient seems to be confirmed. The inner part of the posterior cervical lip is the most reliable region to predict induction of labor results in SWE terms. In addition, cervical length seems to be one of the most important procedures in the prediction of induction. Both methods combined could replace the Bishop Score.

Exposure to Morphine and Cocaine Modify the Transcriptomic Landscape in Zebrafish Embryos.

Morphine and other opioid analgesics are the drugs of election to treat moderate-to-severe pain, and they elicit their actions by binding to the opioid receptors. Cocaine is a potent inhibitor of dopamine, serotonin, and noradrenaline reuptake, as it blocks DAT, the dopamine transporter, causing an increase in the local concentration of these neurotransmitters in the synaptic cleft. The molecular effects of these drugs have been studied in specific brain areas or nuclei, but the systemic effects in the whole organism have not been comprehensively analyzed. This study aims to analyze the transcriptomic changes elicited by morphine (10 uM) and cocaine (15 uM) in zebrafish embryos. An RNAseq assay was performed with tissues extracts from zebrafish embryos treated from 5 hpf (hours post fertilization) to 72 hpf, and the most representative deregulated genes were experimentally validated by qPCR. We have found changes in the expression of genes related to lipid metabolism, chemokine receptor ligands, visual system, hemoglobins, and metabolic detoxification pathways. Besides, morphine and cocaine modified the global DNA methylation pattern in zebrafish embryos, which would explain the changes in gene expression elicited by these two drugs of abuse.

Early and late results of open surgical and endovascular treatment of infrarenal abdominal aortic aneurysms, selected according to surgical risk.

BACKGROUND: Open surgical repair (OSR) and endovascular aneurysm repair (EVAR) surgery are alternative treatments for infrarenal abdominal aortic aneurysm (IRAAA). OBJECTIVES: To compare OSR and EVAR for the treatment of IRAAA. METHODS: 119 patients with IRAAA were electively operated by the same surgeon between January 1, 2006 and December 31, 2015, following selection for OSR or EVAR according to surgical risk. Complications, reinterventions, failures, and early and late mortality were analyzed. RESULTS: 63 OSR and 56 EVAR patients were analyzed. They were similar in terms of age (70 years), gender (92% men), and average diameter of IRAAA (6.5 cm), but with different comorbidities, surgical risk, and anatomy. EVAR was better than OSR regarding time in the operating theatre (177.5 vs. 233.3 minutes), need for transfusion (25 vs. 73%), and length of stay in ICU (1.3 vs. 3.3 days) and hospital (8.1 vs. 11.1 days). OSR allowed more associated procedures to be conducted simultaneously (19.0 vs. 1.8%). There were no significant differences between the groups with respect to complications (25.4 vs. 25.1%), reinterventions (3.2 vs. 5.2%), or early mortality (1.6 vs. 0%). During follow-up, OSR was associated with fewer revisions (3.13 vs. 4.21), angio-CTs (0.22 vs. 3.23), complications (6.4 vs. 37.5%), reinterventions (3.2 vs. 23.2%), and failures (1.6 vs. 10.7%), and had better survival (78.2 vs. 63.2%). CONCLUSIONS: Correct selection of patients achieves excellent results because it avoids OSR in patients at high risk and avoids EVAR in patients with high anatomical complexity, achieving similar results in the perioperative period, but better results for OSR over the course of follow-up.

CONTEXTO: A cirurgia aberta (CA) e o reparo endovascular de aneurisma (REVA) são tratamentos alternativos para o aneurisma da aorta abdominal infrarrenal (AAAIR). OBJETIVOS: Comparar CA e REVA no tratamento do AAAIR. MÉTODOS: Foram incluídos 119 pacientes com AAAIR, operados eletivamente pelo mesmo cirurgião entre 1 de janeiro de 2006 e 31 de dezembro de 2015, após seleção para CA ou REVA de acordo com o risco cirúrgico. Complicações, reintervenções, falhas e mortalidade precoce e tardia foram analisadas. RESULTADOS: Foram analisados 63 pacientes de CA e 56 de REVA, com semelhanças de idade (70 anos), sexo (92% homens) e diâmetro médio do AAAIR (6,5 cm), mas com diferentes comorbidades, riscos cirúrgicos e anatomias. O REVA foi melhor que a CA em relação ao tempo na sala de cirurgia (177,5 vs. 233,3 minutos), necessidade de transfusão (25 vs. 73%) e tempo de permanência na unidade de terapia intensiva (1,3 vs. 3,3 dias) e no hospital (8,1 vs. 11,1 dias). A CA permitiu que mais procedimentos associados fossem realizados simultaneamente (19,0 vs. 1,8%). Não houve diferenças significativas entre os grupos em relação a complicações (25,4 vs. 25,1%), reintervenções (3,2 vs. 5,2%) e mortalidade precoce (1,6 vs. 0%). Durante o acompanhamento, a CA apresentou menos revisões (3,13 vs. 4,21), angiotomografias (0,22 vs. 3,23), complicações (6,4 vs. 37,5%), reintervenções (3,2 vs. 23,2%) e falhas (1,6 vs. 10,7%), além de ter melhor sobrevida (78,2 vs. 63,2%). CONCLUSÕES: A seleção correta dos pacientes proporciona excelentes resultados porque evita pacientes com alto risco para CA e com complexidade anatômica para REVA. Os resultados são semelhantes no período perioperatório, mas melhores para CA durante o acompanhamento.

Incidence of Neonatal Abstinence Syndrome (NAS) in Castilla y Leon (Spain).

INTRODUCTION: Neonatal Abstinence Syndrome (NAS) is considered a Public Health problem that is defined as a group of symptoms that appear in the newborn due to withdrawal from intrauterine drug exposure. OBJECTIVE: The aim of this study was to analyze the incidence of NAS in Castilla y León from 2000 to 2019. METHODOLOGY: Data of NAS cases in Castilla y León from 2000 to 2019 were obtained. NAS incidence per 1000 births was calculated and the correlation among data from different provinces and years was analyzed. RESULTS: The cumulative incidence of NAS in Castilla y León per 1000 births between 2000-2019 was 0.91‱, with great interprovincial variability. The provinces of Zamora and Palencia stand out, with high incidence rates of NAS despite their low birth rates. The temporal trend points towards a decrease in incidence from 2000 to 2019. Opioids such as methadone, cannabis, benzodiazepines and poly-drug use are the most prevalent drugs causing NAS, and it has also been observed that methadone is being replaced by cannabis as the major cause of NAS cases at the University Hospital in Salamanca in recent years. CONCLUSIONS: The incidence of NAS in Castilla y León decreased in 2004 and remained constant until 2019, but it shows great interprovincial variability. It is necessary to implement a national NAS Registry to obtain comprehensive information regarding its incidence.

Early and late results of open surgical and endovascular treatment of infrarenal abdominal aortic aneurysms, selected according to surgical risk / Resultados precoces e tardios dos tratamentos aberto e endovascular de aneurismas da aorta abdominal infrarrenal, selecionados de acordo com o risco cirúrgico

Abstract Background Open surgical repair (OSR) and endovascular aneurysm repair (EVAR) surgery are alternative treatments for infrarenal abdominal aortic aneurysm (IRAAA). Objectives To compare OSR and EVAR for the treatment of IRAAA. Methods 119 patients with IRAAA were electively operated by the same surgeon between January 1, 2006 and December 31, 2015, following selection for OSR or EVAR according to surgical risk. Complications, reinterventions, failures, and early and late mortality were analyzed. Results 63 OSR and 56 EVAR patients were analyzed. They were similar in terms of age (70 years), gender (92% men), and average diameter of IRAAA (6.5 cm), but with different comorbidities, surgical risk, and anatomy. EVAR was better than OSR regarding time in the operating theatre (177.5 vs. 233.3 minutes), need for transfusion (25 vs. 73%), and length of stay in ICU (1.3 vs. 3.3 days) and hospital (8.1 vs. 11.1 days). OSR allowed more associated procedures to be conducted simultaneously (19.0 vs. 1.8%). There were no significant differences between the groups with respect to complications (25.4 vs. 25.1%), reinterventions (3.2 vs. 5.2%), or early mortality (1.6 vs. 0%). During follow-up, OSR was associated with fewer revisions (3.13 vs. 4.21), angio-CTs (0.22 vs. 3.23), complications (6.4 vs. 37.5%), reinterventions (3.2 vs. 23.2%), and failures (1.6 vs. 10.7%), and had better survival (78.2 vs. 63.2%). Conclusions Correct selection of patients achieves excellent results because it avoids OSR in patients at high risk and avoids EVAR in patients with high anatomical complexity, achieving similar results in the perioperative period, but better results for OSR over the course of follow-up.

Resumo Contexto A cirurgia aberta (CA) e o reparo endovascular de aneurisma (REVA) são tratamentos alternativos para o aneurisma da aorta abdominal infrarrenal (AAAIR). Objetivos Comparar CA e REVA no tratamento do AAAIR. Métodos Foram incluídos 119 pacientes com AAAIR, operados eletivamente pelo mesmo cirurgião entre 1 de janeiro de 2006 e 31 de dezembro de 2015, após seleção para CA ou REVA de acordo com o risco cirúrgico. Complicações, reintervenções, falhas e mortalidade precoce e tardia foram analisadas. Resultados Foram analisados 63 pacientes de CA e 56 de REVA, com semelhanças de idade (70 anos), sexo (92% homens) e diâmetro médio do AAAIR (6,5 cm), mas com diferentes comorbidades, riscos cirúrgicos e anatomias. O REVA foi melhor que a CA em relação ao tempo na sala de cirurgia (177,5 vs. 233,3 minutos), necessidade de transfusão (25 vs. 73%) e tempo de permanência na unidade de terapia intensiva (1,3 vs. 3,3 dias) e no hospital (8,1 vs. 11,1 dias). A CA permitiu que mais procedimentos associados fossem realizados simultaneamente (19,0 vs. 1,8%). Não houve diferenças significativas entre os grupos em relação a complicações (25,4 vs. 25,1%), reintervenções (3,2 vs. 5,2%) e mortalidade precoce (1,6 vs. 0%). Durante o acompanhamento, a CA apresentou menos revisões (3,13 vs. 4,21), angiotomografias (0,22 vs. 3,23), complicações (6,4 vs. 37,5%), reintervenções (3,2 vs. 23,2%) e falhas (1,6 vs. 10,7%), além de ter melhor sobrevida (78,2 vs. 63,2%). Conclusões A seleção correta dos pacientes proporciona excelentes resultados porque evita pacientes com alto risco para CA e com complexidade anatômica para REVA. Os resultados são semelhantes no período perioperatório, mas melhores para CA durante o acompanhamento.

A Computational Model of Tonal Tension Profile of Chord Progressions in the Tonal Interval Space.

In tonal music, musical tension is strongly associated with musical expression, particularly with expectations and emotions. Most listeners are able to perceive musical tension subjectively, yet musical tension is difficult to be measured objectively, as it is connected with musical parameters such as rhythm, dynamics, melody, harmony, and timbre. Musical tension specifically associated with melodic and harmonic motion is called tonal tension. In this article, we are interested in perceived changes of tonal tension over time for chord progressions, dubbed tonal tension profiles. We propose an objective measure capable of capturing tension profile according to different tonal music parameters, namely, tonal distance, dissonance, voice leading, and hierarchical tension. We performed two experiments to validate the proposed model of tonal tension profile and compared against Lerdahl's model and MorpheuS across 12 chord progressions. Our results show that the considered four tonal parameters contribute differently to the perception of tonal tension. In our model, their relative importance adopts the following weights, summing to unity: dissonance (0.402), hierarchical tension (0.246), tonal distance (0.202), and voice leading (0.193). The assumption that listeners perceive global changes in tonal tension as prototypical profiles is strongly suggested in our results, which outperform the state-of-the-art models.

Chronic graft-versus-host disease could ameliorate the impact of adverse somatic mutations in patients with myelodysplastic syndromes and hematopoietic stem cell transplantation.

Somatic mutations in patients with myelodysplastic syndromes (MDS) undergoing allogeneic hematopoietic stem cell transplantation (HSTC) are associated with adverse outcome, but the role of chronic graft-versus-host disease (cGVHD) in this subset of patients remains unknown. We analyzed bone marrow samples from 115 patients with MDS collected prior to HSCT using next-generation sequencing. Seventy-one patients (61%) had at least one mutated gene. We found that patients with a higher number of mutated genes (more than 2) had a worse outcome (2 years overall survival [OS] 54.8% vs. 31.1%, p = 0.035). The only two significant variables in the multivariate analysis for OS were TET2 mutations (p = 0.046) and the development of cGVHD, considered as a time-dependent variable (p < 0.001), correlated with a worse and a better outcome, respectively. TP53 mutations also demonstrated impact on the cumulative incidence of relapse (CIR) (1 year CIR 47.1% vs. 9.8%, p = 0.006) and were related with complex karyotype (p = 0.003). cGVHD improved the outcome even among patients with more than 2 mutated genes (1-year OS 88.9% at 1 year vs. 31.3%, p = 0.02) and patients with TP53 mutations (1-year CIR 20% vs. 42.9%, p = 0.553). These results confirm that cGVHD could ameliorate the adverse impact of somatic mutations in patients with MDS with HSCT.

The Neuronal Ischemic Tolerance Is Conditioned by the Tp53 Arg72Pro Polymorphism.

Cerebral preconditioning (PC) confers endogenous brain protection after stroke. Ischemic stroke patients with a prior transient ischemic attack (TIA) may potentially be in a preconditioned state. Although PC has been associated with the activation of pro-survival signals, the mechanism by which preconditioning confers neuroprotection is not yet fully clarified. Recently, we have described that PC-mediated neuroprotection against ischemic insult is promoted by p53 destabilization, which is mediated by its main regulator MDM2. Moreover, we have previously described that the human Tp53 Arg72Pro single nucleotide polymorphism (SNP) controls susceptibility to ischemia-induced neuronal apoptosis and governs the functional outcome of patients after stroke. Here, we studied the contribution of the human Tp53 Arg72Pro SNP on PC-induced neuroprotection after ischemia. Our results showed that cortical neurons expressing the Pro72-p53 variant exhibited higher PC-mediated neuroprotection as compared with Arg72-p53 neurons. PC prevented ischemia-induced nuclear and cytosolic p53 stabilization in Pro72-p53 neurons. However, PC failed to prevent mitochondrial p53 stabilization, which occurs in Arg72-p53 neurons after ischemia. Furthermore, PC promoted neuroprotection against ischemia by controlling the p53/active caspase-3 pathway in Pro72-p53, but not in Arg72-p53 neurons. Finally, we found that good prognosis associated to TIA within 1 month prior to ischemic stroke was restricted to patients harboring the Pro72 allele. Our findings demonstrate that the Tp53 Arg72Pro SNP controls PC-promoted neuroprotection against a subsequent ischemic insult by modulating mitochondrial p53 stabilization and then modulates TIA-induced ischemic tolerance.

Seven methods to determine the dimensionality of tests: application to the General Self-Efficacy Scale in twenty-six countries / Siete métodos para evaluar la dimensionalidad de los test: aplicación a la General Self-Efficacy Scale en veintiséis países

BACKGROUND: One of the most important concepts within Cognitive Social Theory as framed by Bandura is the perceived self-efficacy; this concept became widespread in 1981 when Mathias Jerusalem and Ralf Schwarzer, using 10 items, established a one-dimensional and universal construct of this scale. The main purpose of this study is to show that the General Self-Efficacy Scale (GSE) is not a one-dimensional and universal construct, as is currently assumed. METHOD: The data from 19,719 people from 26 countries were analyzed. In order to identify and understand invariance we applied seven multivariate statistical techniques. RESULTS: The findings suggest the existence of a multidimensional structure and differential item functioning by country. Insofar as there is differential item functioning by country and it is not possible to universalize it, and there are several items on the scale that statistically constitute additional factors. The results confirm that the self-efficacy construct is neither universal nor unidimensional. CONCLUSIONS: A psychometric instrument must be valued and used with great care; the one in question is being used in a generalized way

ANTECEDENTES: uno de los conceptos más importantes en la Teoría Social Cognitiva desarrollada por Bandura es la auto-eficacia percibida. Este concepto ha sido generalizado en 1981 por Mathias Jerusalem and Ralf Schwarzer con una escala de 10 ítems, quienes establecieron que esta escala es un constructo unidimensional y universal. El objetivo principal de este trabajo es demostrar que la Escala General de Autoeficacia (GSE) no es un constructo unidimensional ni universal, como actualmente se asume. MÉTODO: los datos analizados corresponden a 19.719 personas de 26 países. Con el fin de identificar y entender la invariancia hemos utilizado siete técnicas estadísticas multivariantes. RESULTADOS: los hallazgos sugieren la existencia de una estructura multidimensional y un funcionamiento diferencial por país. En la medida que haya funcionamiento diferencial por país, no es posible universalizar el constructo. También existen varios ítems de la escala que constituyen factores adicionales. El resultado confirma que el constructo auto-eficacia no es universal ni unidimensional. CONCLUSIONES: un instrumento psicométrico debe ser evaluado y usado con extremo cuidado, la escala GSE analizada está siendo utilizada de manera general

Seven methods to determine the dimensionality of tests: application to the General Self-Efficacy Scale in twenty-six countries.

BACKGROUND: One of the most important concepts within Cognitive Social Theory as framed by Bandura is the perceived self-efficacy; this concept became widespread in 1981 when Mathias Jerusalem and Ralf Schwarzer, using 10 items, established a one-dimensional and universal construct of this scale. The main purpose of this study is to show that the General Self-Efficacy Scale (GSE) is not a one-dimensional and universal construct, as is currently assumed. METHOD: The data from 19,719 people from 26 countries were analyzed. In order to identify and understand invariance we applied seven multivariate statistical techniques. RESULTS: The findings suggest the existence of a multidimensional structure and differential item functioning by country. Insofar as there is differential item functioning by country and it is not possible to universalize it, and there are several items on the scale that statistically constitute additional factors. The results confirm that the self-efficacy construct is neither universal nor unidimensional. CONCLUSIONS: A psychometric instrument must be valued and used with great care; the one in question is being used in a generalized way.

Multiclassifier Systems for Predicting Neurological Outcome of Patients with Severe Trauma and Polytrauma in Intensive Care Units.

This paper presents an ensemble based classification proposal for predicting neurological outcome of severely traumatized patients. The study comprises both the whole group of patients and a subgroup containing those patients suffering traumatic brain injury (TBI). Data was gathered from patients hospitalized in the Intensive Care Unit (ICU) of the University Hospital in Salamanca. Predictive models were induced from both epidemiologic and clinical variables taken at the emergency room and along the stay in the ICU. The large number of variables leads to a low accuracy in the classifiers even when feature selection methods are used. In addition, the presence of a much larger number of instances of one of the classes in the subgroup of TBI patients produces a significantly lesser precision for the minority class. Usual ways of dealing with the last problem is to use undersampling and oversampling strategies, which can lead to the loss of valuable data and overfitting problems respectively. Our proposal for dealing with these problems is based in the use of ensemble multiclassifiers as well as in the use of an ensemble playing the role of base classifier in multiclassifiers. The proposed strategy gave the best values of the selected quality measures (accuracy, precision, sensitivity, specificity, F-measure and area under the Receiver Operator Characteristic curve) as well as the closest values of precision for the two classes under study in the case of the classification from imbalanced data.

Predictive Capacity of Cloninger's temperament and character inventory (TCI-R) in alcohol use disorder outcomes. / Capacidad de predicción del inventario de temperamento y carácter de Cloninger (TCI-R) en la evolución de los trastornos por uso de alcohol.

OBJECTIVE: to investigate the ability to predict the outcome of alcohol use disorders through Cloninger's temperament and character inventory (TCI-R). METHODS: this is a prospective study consisting of 237 outpatients with alcohol use disorders who underwent follow-up treatment for 6 months and whose personality traits were studied using TCI-R. At the end of that period, the scores of each TCI-R trait were analyzed in terms of those who remained in treatment and those who dropped out. RESULTS: The whole group scored highly in novelty seeking (NS) and harm avoidance (HA) and produced low scores in self-directedness (SD), these last traits are considered prominent. The drop-out group scored significantly (p=.004) higher in novelty seeking (NS) than the follow-up group. Also, when the score was higher than the 67 percentile the likelihood of abandoning the treatment was 1.07 times higher. CONCLUSIONS: Cloninger's temperament and character inventory is a good instrument to predict the outcome of treatment of patients with alcohol use disorders and the novelty seeking (NS) dimension is strongly related to therapeutic drop-out.

Objetivo: se pretende investigar la capacidad de predicción del inventario de temperamento y carácter de Cloninger (TCI-R) en la evolución de los trastornos por uso de alcohol. Metodología: Es un estudio longitudinal de 237 pacientes con trastornos por uso de alcohol, en tratamiento ambulatorio y seguimiento durante seis meses, cuya personalidad fue estudiada mediante el inventario TCI-R. Se analizó la puntuación de cada una de las dimensiones del inventario TCI-R en función de su situación (retención o abandono) al final del estudio. Resultados: La muestra presentaba puntuaciones  elevadas en búsqueda de novedad (BN) y evitación del daño (ED) y baja en autodirección (AD), definidas, estas últimas, como prominentes. El grupo que abandonó presentaba una puntuación significativamente (p= .004) más elevada en búsqueda de novedad (BN) que el grupo en seguimiento; además cuando la puntuación era superior al percentil 67 la probabilidad de abandonar era 1,07 veces superior. Conclusiones: El inventario de temperamento y carácter de Cloninger (TCI-R) es un buen instrumento para predecir la evolución de los pacientes con trastorno por uso de alcohol y la dimensión búsqueda de novedad (BN) está fuertemente relacionada con el abandono terapéutico.

High-resolution copy number analysis of paired normal-tumor samples from diffuse large B cell lymphoma.

Copy number analysis can be useful for assessing prognosis in diffuse large B cell lymphoma (DLBCL). We analyzed copy number data from tumor samples of 60 patients diagnosed with DLBCL de novo and their matched normal samples. We detected 63 recurrent copy number alterations (CNAs), including 33 gains, 30 losses, and nine recurrent acquired copy number neutral loss of heterozygosity (CNN-LOH). Interestingly, 20 % of cases acquired CNN-LOH of 6p21 locus, which involves the HLA region. In normal cells, there were no CNAs but we observed CNN-LOH involving some key lymphoma regions such as 6p21 and 9p24.1 (5 %) and 17p13.1 (2.5 %) in DLBCL patients. Furthermore, a model with some specific CNA was able to predict the subtype of DLBCL, 1p36.32 and 10q23.31 losses being restricted to germinal center B cell-like (GCB) DLBCL. In contrast, 8p23.3 losses and 11q24.3 gains were strongly associated with the non-GCB subtype. A poor prognosis was associated with biallelic inactivation of TP53 or 18p11.32 losses, while prognosis was better in cases carrying 11q24.3 gains. In summary, CNA abnormalities identify specific DLBCL groups, and we describe CNN-LOH in germline cells from DLBCL patients that are associated with genes that probably play a key role in DLBCL development.

Association of Lysyl Oxidase-Like 1 Gene Polymorphisms in Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma in a Spanish Population.

PURPOSE: To evaluate the association of the lysyl oxidase-like 1 (LOXL1) single nucleotide polymorphisms (SNPs) in a Spanish population with pseudoexfoliation syndrome (XFS) and pseudoexfoliation glaucoma (XFG). MATERIALS AND METHODS: The present case-control study included 100 Spanish patients (60 patients with XFS and 40 patients with XFG) and 90 control subjects. Genotypes of the three single nucleotide polymorphisms of LOXL1 (rs1048661, rs3825942, and rs2165241) were analyzed with direct sequencing. RESULTS: The G allele and the GG genotype of SNP rs3825942 were detected at a statistically higher frequency in pseudoexfoliation patients than in control subjects (p = 3.36 × 10(-5), OR = 5.71, 95% CI: 2.30-14.18; p = 3.38 × 10(-5), OR = 6.91, 95% CI: 2.51-19.03 respectively). The T allele and the TT genotype of SNP rs2165241 presented at significantly higher frequencies in pseudoexfoliation patients than in controls (p = 2.50 × 10(-4), OR = 2.18, 95% CI: 1.43-3.33; p = 1.21 × 10(-2), OR = 2.13, 95% CI: 1.75-3.85 respectively). No significant association between XFS/XFG and the rs1048661 was observed. The GGT haplotype composed of all three risk alleles was determined to be significantly associated with pseudoexfoliation. The genotypic and allelic distributions of the three SNPs were similar between XFS and XFG. CONCLUSIONS: This is the first study associating two SNPs of LOXL1 (rs3825942 and rs2165241) and XFS/XFG in a Spanish population, confirming findings in patients from Europe. However rs1048661 SNP did not show an association with XFS.

Capacidad de predicción del inventario de temperamento y carácter de Cloninger (TCI-R) en la evolución de los trastornos por uso de alcohol / Predictive Capacity of Cloninger’s temperament and character inventory (TCI-R) in alcohol use disorder outcomes

Objetivo: se pretende investigar la capacidad de predicción del inventario de temperamento y carácter de Cloninger (TCI-R) en la evolución de los trastornos por uso de alcohol. Metodología: Es un estudio longitudinal de 237 pacientes con trastornos por uso de alcohol, en tratamiento ambulatorio y seguimiento durante seis meses, cuya personalidad fue estudiada mediante el inventario TCI-R. Se analizó la puntuación de cada una de las dimensiones del inventario TCI-R en función de su situación (retención o abandono) al final del estudio. Resultados: La muestra presentaba puntuaciones elevadas en búsqueda de novedad (BN) y evitación del daño (ED) y baja en autodirección (AD), definidas, estas últimas, como prominentes. El grupo que abandonó presentaba una puntuación significativamente (p= .004) más elevada en búsqueda de novedad (BN) que el grupo en seguimiento; además cuando la puntuación era superior al percentil 67 la probabilidad de abandonar era 1,07 veces superior. Conclusiones: El inventario de temperamento y carácter de Cloninger (TCI-R) es un buen instrumento para predecir la evolución de los pacientes con trastorno por uso de alcohol y la dimensión búsqueda de novedad (BN) está fuertemente relacionada con el abandono terapéutico

Objective: to investigate the ability to predict the outcome of alcohol use disorders through Cloninger’s temperament and character inventory (TCI-R). Methods: this is a prospective study consisting of 237 outpatients with alcohol use disorders who underwent follow-up treatment for 6 months and whose personality traits were studied using TCI-R. At the end of that period, the scores of each TCI-R trait were analyzed in terms of those who remained in treatment and those who dropped out. Results: The whole group scored highly in novelty seeking (NS) and harm avoidance (HA) and produced low scores in self-directedness (SD), these last traits are considered prominent. The drop-out group scored significantly (p=.004) higher in novelty seeking (NS) than the follow-up group. Also, when the score was higher than the 67 percentile the likelihood of abandoning the treatment was 1.07 times higher. Conclusions: Cloninger’s temperament and character inventory is a good instrument to predict the outcome of treatment of patients with alcohol use disorders and the novelty seeking (NS) dimension is strongly related to therapeutic drop-out

Comparative effect of two pan-class I PI3K inhibitors used as anticancer drugs on human T cell function.

The phosphatidylinositol 3-kinase (PI3K) pathway is commonly deregulated in cancer and, thus, PI3K has been recognized as an attractive molecular target for novel anti-cancer therapies. However, the effect of PI3K inhibitors on T-cell function, a key component of antitumor immunity, has been scantly explored. The objective of this study was to investigate the effect on human T-cell activation of two PI3K inhibitors currently being tested in clinical trials: PX-866 and BKM120. Their activity against a leukemic T cell line was also assessed. For that purpose, Jurkat cells or anti-CD3/anti-CD28 stimulated human peripheral blood mononuclear cells were cultured in the presence of different concentrations of PX-866 or BKM120 and their effect on T-cell proliferation, apoptosis, expression of activation markers and cytokine secretion was analyzed by flow cytometry. In addition, Akt and Erk phosphorylation was analyzed by Western blotting. Both PX-866 and BKM120 decreased viability of Jurkat cells and blocked cell cycle progression. Regarding primary T cells, both compounds similarly inhibited expression of activation markers and cytokine secretion, although they did not induce apoptosis of stimulated T cells. Interestingly, we found differences in their ability to block T-cell proliferation and IL-2 secretion, exerting BKM120 a more potent inhibition. These disparate effects could be related to differences observed in PI3K/Akt and RAS/MEK/ERK signaling between PX-866 and BKM120 treated cells. Our results suggest that, when selecting a PI3K inhibitor for cancer therapy, immunosuppressive characteristics should be taken into account in order to minimize detrimental effects on immune function.