An Insertion Within SIRPß1 Shows a Dual Effect Over Alzheimer's Disease Cognitive Decline Altering the Microglial Response.

Background: Microglial dysfunction plays a causative role in Alzheimer's disease (AD) pathogenesis. Here we focus on a germline insertion/deletion variant mapping SIRPß1, a surface receptor that triggers amyloid-ß(Aß) phagocytosis via TYROBP. Objective: To analyze the impact of this copy-number variant in SIRPß1 expression and how it affects AD molecular etiology. Methods: Copy-number variant proxy rs2209313 was evaluated in GERALD and GR@ACE longitudinal series. Hippocampal specimens of genotyped AD patients were also examined. SIRPß1 isoform-specific phagocytosis assays were performed in HEK393T cells. Results: The insertion alters the SIRPß1 protein isoform landscape compromising its ability to bind oligomeric Aß and its affinity for TYROBP. SIRPß1 Dup/Dup patients with mild cognitive impairment show an increased cerebrospinal fluid t-Tau/Aß ratio (p = 0.018) and a higher risk to develop AD (OR = 1.678, p = 0.018). MRIs showed that Dup/Dup patients exhibited a worse initial response to AD. At the moment of diagnosis, all patients showed equivalent Mini-Mental State Examination scores. However, AD patients with the duplication had less hippocampal degeneration (p < 0.001) and fewer white matter hyperintensities. In contrast, longitudinal studies indicate that patients bearing the duplication allele show a slower cognitive decline (p = 0.013). Transcriptional analysis also shows that the SIRPß1 duplication allele correlates with higher TREM2 expression and an increased microglial activation. Conclusions: The SIRPß1 internal duplication has opposite effects over MCI-to-Dementia conversion risk and AD progression, affecting microglial response to Aß. Given the pharmacological approaches focused on the TREM2-TYROBP axis, we believe that SIRPß1 structural variant might be considered as a potential modulator of this causative pathway.

The Genetic Research in Alzheimer Disease (GERALD) Initiative Finds rs9320913 as a Neural eQTL of lincRNA AL589740.1.

Alzheimer's disease is the most common cause of dementia worldwide, and longitudinal studies are crucial to find the factors affecting disease development. Here, we describe a novel initiative from southern Spain designed to contribute in the identification of the genetic component of the cognitive decline of Alzheimer's disease patients. The germline variant rs9320913 is a C>A substitution mapping within a gene desert. Although it has been previously associated to a higher educational achievement and increased fluid intelligence, its role on Alzheimer's disease risk and progression remains elusive. A total of 407 subjects were included in the study, comprising 153 Alzheimer disease patients and 254 healthy controls. We have explored the rs9320913 contribution to both Alzheimer disease risk and progression according to the Mini-Mental State Exams. We found that rs9320913 maps within a central nervous system lincRNA AL589740.1. eQTL results show that rs9320913 correlated with the brain-frontal cortex (beta = -0.15, p value = 0.057) and brain-spinal cord (beta of -0.23, p value = 0.037). We did not find rs9320913 to be associated to AD risk, although AA patients seemed to exhibit a less pronounced Mini-Mental State Exam score decline.

Modeling Wording Effects Does Not Help in Recovering Uncontaminated Person Scores: A Systematic Evaluation With Random Intercept Item Factor Analysis.

The item wording (or keying) effect consists of logically inconsistent answers to positively and negatively worded items that tap into similar (but polarly opposite) content. Previous research has shown that this effect can be successfully modeled through the random intercept item factor analysis (RIIFA) model, as evidenced by the improvements in the model fit in comparison to models that only contain substantive factors. However, little is known regarding the capability of this model in recovering the uncontaminated person scores. To address this issue, the study analyzes the performance of the RIIFA approach across three types of wording effects proposed in the literature: carelessness, item verification difficulty, and acquiescence. In the context of unidimensional substantive models, four independent variables were manipulated, using Monte Carlo methods: type of wording effect, amount of wording effect, sample size, and test length. The results corroborated previous findings by showing that the RIIFA models were consistently able to account for the variance in the data, attaining an excellent fit regardless of the amount of bias. Conversely, the models without the RIIFA factor produced increasingly a poorer fit with greater amounts of wording effects. Surprisingly, however, the RIIFA models were not able to better estimate the uncontaminated person scores for any type of wording effect in comparison to the substantive unidimensional models. The simulation results were then corroborated with an empirical dataset, examining the relationship between learning strategies and personality with grade point average in undergraduate studies. The apparently paradoxical findings regarding the model fit and the recovery of the person scores are explained, considering the properties of the factor models examined.

Entropy Fit Indices: New Fit Measures for Assessing the Structure and Dimensionality of Multiple Latent Variables.

The accurate identification of the content and number of latent factors underlying multivariate data is an important endeavor in many areas of Psychology and related fields. Recently, a new dimensionality assessment technique based on network psychometrics was proposed (Exploratory Graph Analysis, EGA), but a measure to check the fit of the dimensionality structure to the data estimated via EGA is still lacking. Although traditional factor-analytic fit measures are widespread, recent research has identified limitations for their effectiveness in categorical variables. Here, we propose three new fit measures (termed entropy fit indices) that combines information theory, quantum information theory and structural analysis: Entropy Fit Index (EFI), EFI with Von Neumman Entropy (EFI.vn) and Total EFI.vn (TEFI.vn). The first can be estimated in complete datasets using Shannon entropy, while EFI.vn and TEFI.vn can be estimated in correlation matrices using quantum information metrics. We show, through several simulations, that TEFI.vn, EFI.vn and EFI are as accurate or more accurate than traditional fit measures when identifying the number of simulated latent factors. However, in conditions where more factors are extracted than the number of factors simulated, only TEFI.vn presents a very high accuracy. In addition, we provide an applied example that demonstrates how the new fit measures can be used with a real-world dataset, using exploratory graph analysis.

Recambio por aféresis de glóbulos rojos. Primer registro de un hospital pediátrico en Quito-Ecuador / Red blood cell exchange. First report in a pediatric Hospital in Quito-Ecuador

Introducción: La anemia falciforme es la hemoglobinopatía estructural más frecuente en todo el mundo y es causada por la producción de hemoglobina S (HbS) a consecuencia de una mutación puntual en el gen de la beta globina.Objetivo: Mostrar los beneficios del recambio de glóbulos rojos por aféresis en la presentación del síndrome torácico agu-do, causado por la anemia drepanocítica.Presentación del caso: Se describe el manejo de una paciente de trece años de edad, con anemia drepanocítica que, al momento de su ingreso al hospital, presentó crisis vaso- oclusiva secundaria a su patología de base. Al segundo día presen-tó síndrome de tórax agudo, por lo que se solicitó al Servicio de Medicina Transfusional, el recambio eritrocitario. Analizado el caso, se realizó el cálculo de la volemia total de la paciente, se prepararon concentrados de glóbulos rojos (CGRs) com-patibles con la paciente: se filtraron; y se les cuantificó el hematocrito. El procedimiento se realizó con el equipo de aféresis COM.TEC. en el que se recambió 1.200 mililitros de eritrocitos totales. Discusión: El recambio eritrocitario por aféresis aportó una notable y visible mejoría clínica y laboratorial. Por lo que en nuestra experiencia consideramos que el procedimiento fue eficiente. Conclusiones: El recambio de eritrocitos por aféresis en el síndrome torácico agudo en crisis drepanocítica es un procedi-miento que se puede utilizar en pacientes que no responden a otras terapias por su mínima alteración de la viscosidad y volumen sanguíneo en el paciente, y disminuir la concentración de hemoglobina S.

Introduction: Sickle-cell anemia is the most common structural hemoglobinopathy worldwide and is caused by the pro-duction of hemoglobin S (HbS) as a result of a point mutation in the beta globin gene.Objective: Show the benefits of red blood cell replacement by apheresis in the presentation of acute chest syndrome, cau-sed by sickle-cell anemia.Case Presentation: We describe the management of a thirteen-year-old patient with sickle-cell anemia, who presented, at admission to the hospital, an occlusive vessel crisis, secondary to her underlying pathology. On the second day of admission, she presented acute chest syndrome. Erythrocyte replacement was requested to the hospital blood service. After analyzing the case, the total blood volume of the patient was calculated, red blood cell concentrates (RBCs) compatible with the pa-tient were prepared, all RBCs were filtered, and the hematocrit was quantified in all RBCs. The procedure was performed with the apheresis equipment COM.TEC. in which a total of 1,200 milliliters of erythrocytes was replaced. Discussion: The erythrocyte replacement by apheresis contributed a remarkable and visible clinical and laboratory impro-vement. In our view, we consider that the procedure was efficient.Conclusions: The replacement of erythrocytes by apheresis in the acute thoracic syndrome in sickle cell crisis is a procedure that may be used in patients who do not respond to other therapies, benefiting from minimal alteration of the viscosity and blood volume in the patient, as well as concomitant decrease of hemoglobin S concentration.

Investigating the performance of exploratory graph analysis and traditional techniques to identify the number of latent factors: A simulation and tutorial.

Exploratory graph analysis (EGA) is a new technique that was recently proposed within the framework of network psychometrics to estimate the number of factors underlying multivariate data. Unlike other methods, EGA produces a visual guide-network plot-that not only indicates the number of dimensions to retain, but also which items cluster together and their level of association. Although previous studies have found EGA to be superior to traditional methods, they are limited in the conditions considered. These issues are addressed through an extensive simulation study that incorporates a wide range of plausible structures that may be found in practice, including continuous and dichotomous data, and unidimensional and multidimensional structures. Additionally, two new EGA techniques are presented: one that extends EGA to also deal with unidimensional structures, and the other based on the triangulated maximally filtered graph approach (EGAtmfg). Both EGA techniques are compared with 5 widely used factor analytic techniques. Overall, EGA and EGAtmfg are found to perform as well as the most accurate traditional method, parallel analysis, and to produce the best large-sample properties of all the methods evaluated. To facilitate the use and application of EGA, we present a straightforward R tutorial on how to apply and interpret EGA, using scores from a well-known psychological instrument: the Marlowe-Crowne Social Desirability Scale. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Controlling for Response Biases in Self-Report Scales: Forced-Choice vs. Psychometric Modeling of Likert Items.

One important problem in the measurement of non-cognitive characteristics such as personality traits and attitudes is that it has traditionally been made through Likert scales, which are susceptible to response biases such as social desirability (SDR) and acquiescent (ACQ) responding. Given the variability of these response styles in the population, ignoring their possible effects on the scores may compromise the fairness and the validity of the assessments. Also, response-style-induced errors of measurement can affect the reliability estimates and overestimate convergent validity by correlating higher with other Likert-scale-based measures. Conversely, it can attenuate the predictive power over non-Likert-based indicators, given that the scores contain more errors. This study compares the validity of the Big Five personality scores obtained: (1) ignoring the SDR and ACQ in graded-scale items (GSQ), (2) accounting for SDR and ACQ with a compensatory IRT model, and (3) using forced-choice blocks with a multi-unidimensional pairwise preference model (MUPP) variant for dominance items. The overall results suggest that ignoring SDR and ACQ offered the worst validity evidence, with a higher correlation between personality and SDR scores. The two remaining strategies have their own advantages and disadvantages. The results from the empirical reliability and the convergent validity analysis indicate that when modeling social desirability with graded-scale items, the SDR factor apparently captures part of the variance of the Agreeableness factor. On the other hand, the correlation between the corrected GSQ-based Openness to Experience scores, and the University Access Examination grades was higher than the one with the uncorrected GSQ-based scores, and considerably higher than that using the estimates from the forced-choice data. Conversely, the criterion-related validity of the Forced Choice Questionnaire (FCQ) scores was similar to the results found in meta-analytic studies, correlating higher with Conscientiousness. Nonetheless, the FCQ-scores had considerably lower reliabilities and would demand administering more blocks. Finally, the results are discussed, and some notes are provided for the treatment of SDR and ACQ in future studies.

Assessing the Big Five with bifactor computerized adaptive testing.

Multidimensional computerized adaptive testing based on the bifactor model (MCAT-B) can provide efficient assessments of multifaceted constructs. In this study, MCAT-B was compared with a short fixed-length scale and computerized adaptive testing based on unidimensional (UCAT) and multidimensional (correlated-factors) models (MCAT) to measure the Big Five model of personality. The sample comprised 826 respondents who completed a pool with 360 personality items measuring the Big Five domains and facets. The dimensionality of the Big Five domains was also tested. With only 12 items per domain, the MCAT and MCAT-B procedures were more efficient to assess highly multidimensional constructs (e.g., Agreeableness), whereas no differences were found with UCAT and the short scale with traits that were essentially unidimensional (e.g., Extraversion). Furthermore, the study showed that MCAT and MCAT-B provide better content-balance of the pool because, for each Big Five domain, items from all the facets are selected in similar proportions. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

[Abnormal glycemic metabolism in essential hypertension. Role of the an oral glucose tolerance test]. / Alteraciones del metabolismo glucídico en la hipertensión arterial esencial. Papel de la sobrecarga oral con glucosa.

BACKGROUND AND OBJECTIVE: There is a high prevalence of diabetes in essential hypertensive patients, hence increasing the cardiovascular risk of these subjects. Our aim was to test the importance of a routine assessment of an oral glucose tolerance test (OGTT) in a sample of recently diagnosed essential hypertensives. PATIENTS AND METHOD: We studied 270 recently diagnosed untreated hypertensives (56% males). We measured fasting lipids and plasma glucose and insulin at baseline and after OGTT. RESULTS: 38.5% of the studied subjects had any abnormality of glucose metabolism, glucose intolerance (22.2%) and type 2 diabetes (12.2%) being the most common. An impaired fasting glucose was present in 4.1% of subjects. Patients with intolerance or type 2 diabetes had a worse plasma lipid profile, and those with impaired fasting glucose, a higher HOMA index. CONCLUSIONS: The high incidence of glucidic abnormalities found in hypertensive patients signals a need to perform an OGTT test in them. This can lead to the implementation of strategies aimed at halting vascular impairment in hypertensives with type 2 diabetes and delay the development of type 2 diabetes in patients with glucose intolerance.