Multivariate Base Rates of Low Scores on Tests of Learning and Memory among Spanish-Speaking Children

ABSTRACT

To determine the prevalence of low scores on two neuropsychological tests commonly used to evaluate learning and memory in children. 6,030 healthy children from 10 countries in Latin America and Spain were administered Rey–Osterrieth Complex Figure (ROCF) and the Test de Aprendizaje y Memoria Verbal–Infantil (TAMV-I). Results showed that low scores are common when multiple neuropsychological outcomes (tests and/or scores) are evaluated in healthy individuals. Clinicians should consider the higher probability of low scores in a given individual when evaluating learning and memory using various sets of scores to reduce false-positive diagnoses of cognitive deficits in pediatric populations.     

Identification of 26 new constitutional RB1 gene mutations in Spanish, Colombian, and Cuban retinoblastoma patients

Constitutional mutations in the RB1 gene predispose to retinoblastoma development. Hence genetic screening of retinoblastoma patients and relatives is important for genetic counseling purposes. In addition, RB1 gene mutation studies may help decipher the molecular mechanisms leading to tumors with different degrees of penetrance or expressivity. In the course of genetically screening of 107 hereditary and non-hereditary retinoblastoma patients (11 familiar bilateral, 4 familiar unilateral, 49 sporadic bilateral and 43 sporadic unilateral) and kindred from Spain, Colombia and Cuba, using direct PCR sequencing, we observed 45 distinct mutations and four RB1 deletions in 53 patients (9 familiar bilateral, 2 familiar unilateral, 31 sporadic bilateral and 11 sporadic unilateral). Most of these mutations (26/45, 57%) have not been reported before. In 32 patients, the predisposing mutations correspond to nonsense (mainly CpG transitions) and small insertions or deletions whose expected outcome is a truncated Rb protein that lacks the functional pockets and tail. Five single aminoacid replacements and seventeen mutations affecting splicing sites were also observed in retinoblastoma patients. Two of these sixteen mutations are of unclear pathogenic nature.     

Cost and Mortality Analysis of an Intermediate Respiratory Care Unit. Is It Really Efficient and Safe?

IntroductionHistorically, it has been assumed that Intermediate Respiratory Care Units (IRCU) were efficient, because they saved costs by reducing the number of admissions to intensive care units (ICU), and effective, because they specialized in respiratory diseases.MethodsThe number of IRCU admissions and mortality rate, historically and in 2016, were evaluated. For 2016, the grouped Related Diagnostic Groups (DRGs) were also described, and the savings achieved under all budgetary headings by avoiding UCI stays were calculated. A multivariate analysis was performed to associate costs with mean weights and complexity, and multiple logistic regression was performed on all patients admitted from 2004 to 2017 to describe the variables associated with mortality in our unit.ResultsAn IRCU generates savings of €500,000/year by reducing length of ICU stay. Analysis of the 2016 cohort shows that costs correlate with mean weight and mortality, and consequently complexity. The multivariate logistic regression analysis of the 2004–2017 cohort found respiratory frequency, leukopenia, anemia, hyperkalemia, and acidosis to be the variables best associated with mortality. The area under the curve for the logistic model was 0.75.ConclusionThe IRCU analyzed in our study was efficient in terms of ‘avoided costs’ and savings associated with complexity. Our results suggest that IRCUs have a lower mortality rate than other similar units, and are therefore a safe environment for patients.     

The Practice of Child Neuropsychology in Spanish-speaking Countries: What We’ve Learned and Where to Go from Here

ABSTRACT

The characteristics and current situation of pediatric neuropsychologists across Spanish-speaking countries was examined. A total of 409 self-identified professionals working in child neuropsychology from 12 Latin American countries and Spain completed an online survey between June and October 2018. Results revealed that pediatric neuropsychology as a related but distinct discipline within neuropsychology presents with a series of unique challenges to practitioners in Spanish-speaking countries. Efforts and initiatives are required to increase awareness of the field, define the core competencies, foster more opportunities for training, and conduct research to understand sociocultural characteristics and develop culturally specific tools.     

Rendimiento diagnóstico de la secuenciación de genes de hipercolesterolemia familiar en sujetos con hipercolesterolemia primaria

Introduction and objectivesOur objective was to approximate the prevalence of mutations in candidate genes for familial hypercholesterolemia (FH) in a middle-aged Spanish population and to establish the predictive value of criteria for clinical suspicion in the detection of causative mutations.MethodsUnrelated individuals aged ≥ 18 years from the Aragon Workers’ Health Study (AWHS) with high low-density lipoprotein cholesterol (LDL-C) and clinical suspicion of FH (participants with LDL-C concentrations above the 95th percentile, participants with premature cardiovascular disease and/or participants with high LDL-C [130 mg/dL] under statin therapy), assuming that any participant with FH exhibits at leats 1 trait, were selected and the LDLR, APOB, PCSK9, APOE, STAP1 and LDLRAP1 genes were sequenced by next generation sequencing technology.ResultsOf 5400 individuals from the AWHS, 4514 had complete data on lipid levels and lipid-lowering drugs, 255 participants (5.65%) met the criteria for suspicion of FH, 24 of them (9.41%) were diagnosed with hyperlipoproteinemia(a), and 16 (6.27% of those sequenced) were found to carry causative mutations in candidate genes: 12 participants carried 11 different pathogenic LDLR alleles and 4 participants carried 1 pathogenic mutation in PCSK9. LDL-C concentrations > 220 mg/dL and LDL-C > 130 mg/dL despite statin therapy showed the strongest association with the presence of mutations (P = .011).ConclusionsOur results show that the prevalence of FH in Spain is 1:282 and suggest that the combination of high untreated LDL-C and high levels of LDL-C despite statin therapy are the best predictors of a positive FH genetic test.     

Differential Interleukin-8 thresholds for chemotaxis and netosis in human neutrophils

In humans, IL-8 (CXCL8) is a key chemokine for chemotaxis of polymorphonuclear leukocytes and monocytes/macrophages when acting on CXCR1 and CXCR2. CXCL8 activity on neutrophils includes chemotaxis and eliciting the extrusion of neutrophil extracellular traps (NETs). In this study, we show that concentrations of IL-8 that induce NETosis surpass in at least one order of magnitude those required to elicit chemoattraction in human neutrophils. IL-8-induced NETosis was less dependent on G-proteins than migration, while extracellular Ca⁺² chelation similarly inhibited both processes. Reactive oxygen species (ROS) were more important for NETosis than for chemotaxis as evidenced by neutralization with N-acetyl -cysteine. Interestingly, selective blockade with anti-CXCR1 mAb inhibited NETosis much more readily than chemotaxis, while pharmacological inhibition of both CXCR1 and CXCR2, or selective inhibition for CXCR2 alone, similarly inhibited both functions. Together, these results propose a model according to which low concentrations of IL-8 in a gradient attract neutrophils to the inflammatory foci, while high receptor-saturating concentrations of IL-8 give rise to NETosis once leukocytes reach the core of the inflammatory insult.