A New Set of in Silico Tools to Support the Interpretation of ATM Missense Variants Using Graphical Analysis.

Establishing the pathogenic nature of variants in ATM, a gene associated with breast cancer and other hereditary cancers, is crucial for providing patients with adequate care. Unfortunately, achieving good variant classification is still difficult. To address this challenge, we extended the range of in silico tools with a series of graphical tools devised for the analysis of computational evidence by health care professionals. We propose a family of fast and easy-to-use graphical representations in which the impact of a variant is considered relative to other pathogenic and benign variants. To illustrate their value, the representations are applied to three problems in variant interpretation. The assessment of computational pathogenicity predictions showed that the graphics provide an intuitive view of prediction reliability, complementing and extending conventional numerical reliability indexes. When applied to variant of unknown significance populations, the representations shed light on the nature of these variants and can be used to prioritize variants of unknown significance for further studies. In a third application, the graphics were used to compare the two versions of the ATM-adapted American College of Medical Genetics and Genomics and Association for Molecular Pathology guidelines, obtaining valuable information on their relative virtues and weaknesses. Finally, a server [ATMision (ATM missense in silico interpretation online)] was generated for users to apply these representations in their variant interpretation problems, to check the ATM-adapted guidelines' criteria for computational evidence on their variant(s) and access different sources of information.

(-)-Oleocanthal induces death preferentially in tumor hematopoietic cells through caspase dependent and independent mechanisms.

Olive oil is a key component of the highly cardiovascular protective Mediterranean diet. (-)-Oleocanthal (OLC) is one of the most interesting phenolics present in virgin olive oil, and is formed from secoiridoid ligustroside during the processing of olives to yield the oil. Anti-inflammatory and anti-oxidant properties were identified shortly after OLC isolation, followed by the discovery of anti-tumor activities in a few non-hematopoietic cell lineages. Because of the scarcity of tissues potentially targeted by OLC analyzed so far and the unresolved mechanism(s) for OLC anti-tumor properties, we used a panel of 17 cell lines belonging to 11 tissue lineages to carry out a detailed examination of targets and pathways leading to cell growth inhibition and death. We found that OLC inhibits cell proliferation and induces apoptotic death as revealed by sub-G1 cell cycle analyses and Annexin-V staining in all lineages analyzed except lung carcinoma cell lines. Hematopoietic tumor cell lines, untested until now, were the most sensitive to OLC treatment, whereas non-transformed cells were significantly resistant to cell death. The specificity of OLC-mediated caspase activation was confirmed by blocking experiments and the use of transfectants overexpressing anti apoptotic genes. OLC triggers typical mediators of the intrinsic apoptotic pathway such as production of reactive oxygen species and mitochondrial membrane depolarization (Δψm). Complete blockade of caspases, however, did not result in parallel abrogation of Annexin-V staining, thus suggesting that complex mechanisms are involved in triggering OLC-mediated cell death. Our results demonstrate that OLC preferentially targets hematopoietic tumor cell lines and support that cell death is mediated by caspase-dependent and independent mechanisms.

Cultivating Successful Students in a Culturally Diverse Classroom.

In 2018, Gateway Community College reported that of its 5950 students who enrolled that year, 49% had classified themselves as minority. Roughly 28% of those students reported speaking a language other than English in the home setting.1 Developing course material and assignments that assist all students in the first semesters of a healthcare program are difficult. Successfully accomplishing this task with students whose first language is not English adds to that level of difficulty. This study examined the global classroom achievements of first semester respiratory program students when additional vocabulary and purposeful terminology assignments are given, where the concentrated emphasis is on those students who speak English as a second language.

Identification of compounds with activity against Trypanosoma cruzi within a collection of synthetic nucleoside analogs.

Introduction: Chagas disease is caused by the protozoan parasite Trypanosoma cruzi, and it is the most important neglected tropical disease in the Americas. Two drugs are available to treat the infection, but their efficacy in the chronic stage of the disease, when most cases are diagnosed, is reduced. Their tolerability is also hindered by common adverse effects, making the development of safer and efficacious alternatives a pressing need. T. cruzi is unable to synthesize purines de novo, relying on a purine salvage pathway to acquire these from its host, making it an attractive target for the development of new drugs. Methods: We evaluated the anti-parasitic activity of 23 purine analogs with different substitutions in the complementary chains of their purine rings. We sequentially screened the compounds' capacity to inhibit parasite growth, their toxicity in Vero and HepG2 cells, and their specific capacity to inhibit the development of amastigotes. We then used in-silico docking to identify their likely targets. Results: Eight compounds showed specific anti-parasitic activity, with IC50 values ranging from 2.42 to 8.16 µM. Adenine phosphoribosyl transferase, and hypoxanthine-guanine phosphoribosyl transferase, are their most likely targets. Discussion: Our results illustrate the potential role of the purine salvage pathway as a target route for the development of alternative treatments against T. cruzi infection, highlithing the apparent importance of specific substitutions, like the presence of benzene groups in the C8 position of the purine ring, consistently associated with a high and specific anti-parasitic activity.

Novel Purine Chemotypes with Activity against Plasmodium falciparum and Trypanosoma cruzi.

Malaria and Chagas disease, caused by Plasmodium spp. and Trypanosoma cruzi parasites, remain important global health problems. Available treatments for those diseases present several limitations, such as lack of efficacy, toxic side effects, and drug resistance. Thus, new drugs are urgently needed. The discovery of new drugs may be benefited by considering the significant biological differences between hosts and parasites. One of the most striking differences is found in the purine metabolism, because most of the parasites are incapable of de novo purine biosynthesis. Herein, we have analyzed the in vitro anti-P. falciparum and anti-T. cruzi activity of a collection of 81 purine derivatives and pyrimidine analogs. We firstly used a primary screening at three fixed concentrations (100, 10, and 1 µM) and progressed those compounds that kept the growth of the parasites < 30% at 100 µM to dose-response assays. Then, we performed two different cytotoxicity assays on Vero cells and human HepG2 cells. Finally, compounds specifically active against T. cruzi were tested against intracellular amastigote forms. Purines 33 (IC50 = 19.19 µM) and 76 (IC50 = 18.27 µM) were the most potent against P. falciparum. On the other hand, 6D (IC50 = 3.78 µM) and 34 (IC50 = 4.24 µM) were identified as hit purines against T. cruzi amastigotes. Moreover, an in silico docking study revealed that P. falciparum and T. cruzi hypoxanthine guanine phosphoribosyltransferase enzymes could be the potential targets of those compounds. Our study identified two novel, purine-based chemotypes that could be further optimized to generate potent and diversified anti-parasitic drugs against both parasites.

Predicting mortality in hemodialysis patients using machine learning analysis.

BACKGROUND: Besides the classic logistic regression analysis, non-parametric methods based on machine learning techniques such as random forest are presently used to generate predictive models. The aim of this study was to evaluate random forest mortality prediction models in haemodialysis patients. METHODS: Data were acquired from incident haemodialysis patients between 1995 and 2015. Prediction of mortality at 6 months, 1 year and 2 years of haemodialysis was calculated using random forest and the accuracy was compared with logistic regression. Baseline data were constructed with the information obtained during the initial period of regular haemodialysis. Aiming to increase accuracy concerning baseline information of each patient, the period of time used to collect data was set at 30, 60 and 90 days after the first haemodialysis session. RESULTS: There were 1571 incident haemodialysis patients included. The mean age was 62.3 years and the average Charlson comorbidity index was 5.99. The mortality prediction models obtained by random forest appear to be adequate in terms of accuracy [area under the curve (AUC) 0.68-0.73] and superior to logistic regression models (ΔAUC 0.007-0.046). Results indicate that both random forest and logistic regression develop mortality prediction models using different variables. CONCLUSIONS: Random forest is an adequate method, and superior to logistic regression, to generate mortality prediction models in haemodialysis patients.

Synthesis and screening of 6-alkoxy purine analogs as cell type-selective apoptotic inducers in Jurkat cells.

Purines are ubiquitous structures in cell biology involved in a multitude of cellular processes, because of which substituted purines and analogs are considered excellent scaffolds in drug design. In this study, we explored the key structural features of a purine-based proapoptotic hit, 8-tert-butyl-9-phenyl-6-benzyloxy-9H-purine (1), by setting up a library of 6-alkoxy purines with the aim of elucidating the structural requirements that govern its biological activity and to study the cell selectivity of this chemotype. This was done by a phenotypic screening approach based on cell cycle analysis of a panel of six human cancer cell lines, including T cell leukemia Jurkat cells. From this study, two derivatives (12 and 13) were identified as Jurkat-selective proapoptotic compounds, displaying superior potency and cell selectivity than hit 1.

Hyperspectral Imagery for Assessing Laser-Induced Thermal State Change in Liver.

This work presents the potential of hyperspectral imaging (HSI) to monitor the thermal outcome of laser ablation therapy used for minimally invasive tumor removal. Our main goal is the establishment of indicators of the thermal damage of living tissues, which can be used to assess the effect of the procedure. These indicators rely on the spectral variation of temperature-dependent tissue chromophores, i.e., oxyhemoglobin, deoxyhemoglobin, methemoglobin, and water. Laser treatment was performed at specific temperature thresholds (from 60 to 110 °C) on in-vivo animal liver and was assessed with a hyperspectral camera (500-995 nm) during and after the treatment. The indicators were extracted from the hyperspectral images after the following processing steps: the breathing motion compensation and the spectral and spatial filtering, the selection of spectral bands corresponding to specific tissue chromophores, and the analysis of the areas under the curves for each spectral band. Results show that properly combining spectral information related to deoxyhemoglobin, methemoglobin, lipids, and water allows for the segmenting of different zones of the laser-induced thermal damage. This preliminary investigation provides indicators for describing the thermal state of the liver, which can be employed in the future as clinical endpoints of the procedure outcome.

A Collaborative Effort to Define Classification Criteria for ATM Variants in Hereditary Cancer Patients.

BACKGROUND: Gene panel testing by massive parallel sequencing has increased the diagnostic yield but also the number of variants of uncertain significance. Clinical interpretation of genomic data requires expertise for each gene and disease. Heterozygous ATM pathogenic variants increase the risk of cancer, particularly breast cancer. For this reason, ATM is included in most hereditary cancer panels. It is a large gene, showing a high number of variants, most of them of uncertain significance. Hence, we initiated a collaborative effort to improve and standardize variant classification for the ATM gene. METHODS: Six independent laboratories collected information from 766 ATM variant carriers harboring 283 different variants. Data were submitted in a consensus template form, variant nomenclature and clinical information were curated, and monthly team conferences were established to review and adapt American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) criteria to ATM, which were used to classify 50 representative variants. RESULTS: Amid 283 different variants, 99 appeared more than once, 35 had differences in classification among laboratories. Refinement of ACMG/AMP criteria to ATM involved specification for twenty-one criteria and adjustment of strength for fourteen others. Afterwards, 50 variants carried by 254 index cases were classified with the established framework resulting in a consensus classification for all of them and a reduction in the number of variants of uncertain significance from 58% to 42%. CONCLUSIONS: Our results highlight the relevance of data sharing and data curation by multidisciplinary experts to achieve improved variant classification that will eventually improve clinical management.

Neuroblastoma cervical: presentación de casos y revisión actualizada del tema / Cervical neuroblastoma: presentation of cases and updated review of the topic

El neuroblastoma es uno de los tumores sólidos extracraneales más comunes en la edad pediátrica, y se origina en células precursoras del sistema nervioso simpático. La ubicación cervical corresponde a un 2-5% del total de los neuroblastomas y puede tener distintas manifestaciones clínicas, tales como masa cervical, disnea, estridor, síndrome de Horner o disfagia. Esta entidad debe ser considerada dentro del diagnóstico diferencial de una masa cervical pediátrica, especialmente ante la presencia de masas sólidas, laterales o paramedianas, palpables o no al examen físico. El tratamiento específico del neuroblastoma depende de la clasificación de riesgo del paciente, pudiendo ser expectante en casos específicos, exclusivamente quirúrgico, o bien requerir complementarse con otras terapias. En este artículo se presentan 2 casos clínicos de pacientes pediátricos con neuroblastoma cervical tratados de forma exclusiva y exitosa con cirugía, y una revisión del tema.

Neuroblastoma is one of the commonest extracranial solid tumors at pediatric age, originating from sympathetic nervous system precursor cells. Cervical position stands for 2-5% of all neuroblastomas, with variable clinical expression that includes cervical mass, dyspnea, stridor, Horner syndrome and dysphagia. This condition must be considered in the differential diagnosis of a pediatric cervical mass, specially in those solid, lateral/paramedian masses that could be palpable or not at physical examination. The specific treatment in neuroblastoma depends on patient´s risk group, including conservative follow-up in selected cases, surgery alone, or complementary perioperative therapy with chemotherapy and others. In this article, the group report two cases of cervical neuroblastoma exclusively treated with surgery with good results, and a literature review.

Reconstitution of the Ataxia-Telangiectasia Cellular Phenotype With Lentiviral Vectors.

Ataxia-telangiectasia (A-T) is a complex disease arising from mutations in the ATM gene (Ataxia-Telangiectasia Mutated), which plays crucial roles in repairing double-strand DNA breaks (DSBs). Heterogeneous immunodeficiency, extreme radiosensitivity, frequent appearance of tumors and neurological degeneration are hallmarks of the disease, which carries high morbidity and mortality because only palliative treatments are currently available. Gene therapy was effective in animal models of the disease, but the large size of the ATM cDNA required the use of HSV-1 or HSV/AAV hybrid amplicon vectors, whose characteristics make them unlikely tools for treating A-T patients. Due to recent advances in vector packaging, production and biosafety, we developed a lentiviral vector containing the ATM cDNA and tested whether or not it could rescue cellular defects of A-T human mutant fibroblasts. Although the cargo capacity of lentiviral vectors is an inherent limitation in their use, and despite the large size of the transgene, we successfully transduced around 20% of ATM-mutant cells. ATM expression and phosphorylation assays indicated that the neoprotein was functional in transduced cells, further reinforced by their restored capacity to phosphorylate direct ATM substrates such as p53 and their capability to repair radiation-induced DSBs. In addition, transduced cells also restored cellular radiosensitivity and cell cycle abnormalities. Our results demonstrate that lentiviral vectors can be used to rescue the intrinsic cellular defects of ATM-mutant cells, which represent, in spite of their limitations, a proof-of-concept for A-T gene therapy.

[Polygraphy in hospitalized children under 3 months]. / Poligrafía en menores de 3 meses hospitalizados.

Apnea and apparently lethal events have great etiological diversity thus complementary tests may help diagnosis. The aim of this study was to describe the results of polygraph studies of children under 3 months hospitalized with suspected apnea. PATIENTS AND METHODS: Retrospective case series. Children under 3 months with suspected apnea were considered and in whom a polygraphy (PG) was performed during hospitalization. General data, the apnea/hypopnea index (AHI), index of central. apnea, obstructive apnea index, average and minimum saturation were recorded. Desaturation index (ID) below 80% higher 1 per hour, one or more events of desaturation below 80% for more than 20 seconds or an AHI greater than or equal 1 were considered as criteria of sleep disorder breathing (SLB). Descriptive analysis was performed and the associations between AHI and saturation parameters were determined. RESULTS: 51 patients, 32 males, entered the study. 15,6% had altered PG. In 5 of them coexisted more than one diagnostic criterion. Iin 15,6% of the patients was observed an IAH greater 1, in 7.8% a desaturation index below 80% and in 11,8% a desaturation index under 80% for 20 seconds greater than 1. The AHI was associated with the parameters of saturation. CONCLUSION: Most of the patients had normal PG and among patients with a suggestive SLB a pattern of respiratory immaturity prevailed, which is characteristic of this age.

Poligrafía en menores de 3 meses hospitalizados / Polygraphy in hospitalized children under 3 months

La apnea y eventos aparentemente letales poseen una gran diversidad etiológica por tanto exámenes complementarios podrían contribuir a su diagnóstico. El objetivo del presente estudio fue describir los resultados de estudios poligráficos de niños menores de 3 meses hospitalizados con sospecha de apnea. PACIENTES Y MÉTODO: Serie retrospectiva de casos. Se consideraron niños menores de 3 meses con sospecha de apnea y en quienes se realizó una poligrafía (PG) durante su hospitalización. Se registraron datos generales, así como también, el índice de apnea/hipopnea (IAH), índice de apnea central, índice de apnea obstructiva, saturación promedio y mínima. Como criterios de trastornos respiratorios del sueño (TRS) fueron considerados: índice de desaturaciones (ID) por debajo de 80% mayor 1 por hora; uno o más eventos de desaturaciones por debajo de 80% por más de 20 segundos; o un IAH mayor o igual 1. Se realizó estadística descriptiva y se determinó la posible asociación entre el IAH y parámetros de saturación. RESULTADOS: Ingresaron 51 pacientes, 32 varones. 8 (15,6%) presento PG alteradas, de ellos, en 5 coexistió más de un criterio diagnóstico. En el 15,6% se observó un IAH mayor o igual a 1, en el 7,8% se observó un índice de desaturación bajo 80% y en el 11,8% un índice de desaturación bajo 80% por más de 20 segundos. El IAH se asoció con los parámetros de saturación. CONCLUSIÓN: La mayoría de los pacientes presentó PG normales y entre los pacientes con TRS predominó un patrón poligráfico sugerente de inmadurez respiratoria, lo cual, es característico de esta edad.

Apnea and apparently lethal events have great etiological diversity thus complementary tests may help diagnosis. The aim of this study was to describe the results of polygraph studies of children under 3 months hospitalized with suspected apnea. PATIENTS AND METHODS: Retrospective case series. Children under 3 months with suspected apnea were considered and in whom a polygraphy (PG) was performed during hospitalization. General data, the apnea/hypopnea index (AHI), index of central. apnea, obstructive apnea index, average and minimum saturation were recorded. Desaturation index (ID) below 80% higher 1 per hour, one or more events of desaturation below 80% for more than 20 seconds or an AHI greater than or equal 1 were considered as criteria of sleep disorder breathing (SLB). Descriptive analysis was performed and the associations between AHI and saturation parameters were determined. RESULTS: 51 patients, 32 males, entered the study. 15,6% had altered PG. In 5 of them coexisted more than one diagnostic criterion. Iin 15,6% of the patients was observed an IAH greater 1, in 7.8% a desaturation index below 80% and in 11,8% a desaturation index under 80% for 20 seconds greater than 1. The AHI was associated with the parameters of saturation. CONCLUSION: Most of the patients had normal PG and among patients with a suggestive SLB a pattern of respiratory immaturity prevailed, which is characteristic of this age.

Molecular and Functional Characterization of a Cohort of Spanish Patients with Ataxia-Telangiectasia.

Ataxia-telangiectasia is a multisystemic disease with severe neurological affectation, immunodeficiency and telangiectasia. The disorder is caused by alterations in the ATM gene, whose size and complexity make molecular diagnosis difficult. We designed a target-enrichment next-generation sequencing strategy to characterize 28 patients from several regions of Spain. This approach allowed us to identify gene variants affecting function in 54 out of the 56 alleles analyzed, although the two unresolved alleles belong to brothers. We found 28 ATM gene mutations, of which 10 have not been reported. A total of 171 gene variants not affecting function were also found, of which 22 are reported to predispose to disease. Interestingly, all Roma (Spanish Gypsies) patients are homozygous for the same mutation and share the H3 ATM haplotype, which is strong evidence of a founder effect in this population. In addition, we generated a panel of 27 primary T cell lines from A-T patients, which revealed significant expression of ATM in two patients and traces of the protein in nine more. None of them retained residual ATM activity, and almost all T cell lines show increased or intermediate radiosensitivity.

Regulated expression of murine CD40L by a lentiviral vector transcriptionally targeted through its endogenous promoter.

BACKGROUND: Targeted lentiviral vectors may contribute to circumventing genotoxicity associated with uncontrolled transcription of therapeutic genes. Some vectors replacing strong viral sequences for gene promoters such as ß-globin, CD4, CD19 or Igκ were able to drive tissue-specific expression of the transgene. Gene therapy, however, faces even greater hurdles when the therapeutic transgene is subject to strict regulatory mechanisms. This is the case of the CD40LG gene, which encodes for the CD154 (also known as CD40L) molecule, transiently expressed upon activation on CD4(+) T cells. Mutations in this gene cause the X-linked hyper IgM syndrome (HIGM1) in humans because the interaction of CD40L with its ligand CD40 triggers signals that are critical for the immunobiology of B lymphocytes. METHODS: We developed a lentiviral vector containing the murine Cd40lg cDNA under the control of its endogenous promoter. RESULTS: The CD4(+) BW5147 T cells transduced with the pCd40lg-Cd40lg lentiviral vector express CD40L only upon stimulation. The intensity of the expression correlates with the number of vector integrations per cell and detected molecules rapidly decay after removing the stimulating agent. The tissue-specific, activation-dependent and reversible expression of CD40L fully mimics the physiological induction and disappearance of the molecule from the surface of murine T lymphocytes. The functional activity of the regulated lentiviral vector is demonstrated by the ability of transduced BW5147 cells to promote the proliferation of purified B cell splenocytes. CONCLUSIONS: We have developed a fine-regulated lentiviral vector that can be a model for expressing molecules subject to stringent regulatory mechanisms.

Synthesis of 6,8,9 poly-substituted purine analogue libraries as pro-apoptotic inducers of human leukemic lymphocytes and DAPK-1 inhibitors.

A 18-member library of 6,8,9-poly-substituted purines was prepared from pyrimidines, primary alcohols, and N,N-dimethylamides under basic conditions via a novel one-pot synthetic pathway controlled by amide sizes and the novel analogues were tested against two leukemia cell lines: Jurkat (acute T cell leukemia) and K562 (chronic erythroleukemia) cells. Compounds having a benzoxy group at C6 position of the aromatic ring exhibited antiproliferative activity in Jurkat cells whereas all compounds induced a lower effect on K562 cells. Analysis of cell cycle, Annexin-V staining, and cleavage of initiator caspases assays showed that the active purine analogues induce cell death by apoptosis. Based on these results, a new purine derivative was synthesized, 6-benzyloxy-9-tert-butyl-8-phenyl-9H-purine (6d), which displayed the highest activity of the series against Jurkat cell lines. Finally, (33)P-radiolabeled kinase assays using 96 recombinant human kinases known to be involved in apoptotic events were performed. Just one of the kinases tested, DAPK-1, was inhibited 50% or more by the phenotypic hits at 10 µM, suggesting that the inhibition of this target could be responsible for the induction of cell death by apoptosis. In agreement with the phenotypic results, the most active antiproliferative agent, 6d, displayed also the lowest IC50 value against recombinant DAPK1 (2.5 µM), further supporting the potential role of this protein on the observed functional response. DAPK-1 inhibition led by 6d together with its pro-apoptotic properties against the Jurkat line makes it an interesting candidate to further investigate the role of DAPK1 kinase in triggering apoptosis in cancer cells, a role which is attracting recent interest.

Modeling bacterial population growth from stochastic single-cell dynamics.

A few bacterial cells may be sufficient to produce a food-borne illness outbreak, provided that they are capable of adapting and proliferating on a food matrix. This is why any quantitative health risk assessment policy must incorporate methods to accurately predict the growth of bacterial populations from a small number of pathogens. In this aim, mathematical models have become a powerful tool. Unfortunately, at low cell concentrations, standard deterministic models fail to predict the fate of the population, essentially because the heterogeneity between individuals becomes relevant. In this work, a stochastic differential equation (SDE) model is proposed to describe variability within single-cell growth and division and to simulate population growth from a given initial number of individuals. We provide evidence of the model ability to explain the observed distributions of times to division, including the lag time produced by the adaptation to the environment, by comparing model predictions with experiments from the literature for Escherichia coli, Listeria innocua, and Salmonella enterica. The model is shown to accurately predict experimental growth population dynamics for both small and large microbial populations. The use of stochastic models for the estimation of parameters to successfully fit experimental data is a particularly challenging problem. For instance, if Monte Carlo methods are employed to model the required distributions of times to division, the parameter estimation problem can become numerically intractable. We overcame this limitation by converting the stochastic description to a partial differential equation (backward Kolmogorov) instead, which relates to the distribution of division times. Contrary to previous stochastic formulations based on random parameters, the present model is capable of explaining the variability observed in populations that result from the growth of a small number of initial cells as well as the lack of it compared to populations initiated by a larger number of individuals, where the random effects become negligible.

La interpretación de enunciados condicionales como bicondicionales y su problemática en la tarea de selección / The interpretation of conditional statements as biconditional statements and its problems to selection task

En diversas ocasiones, los enunciados condicionales son perfeccionados, esto es, entendidos como bicondicionales. Este hecho provoca problemas para la interpretación de textos en general y para la comprensión correcta de las instrucciones de la tarea de selección en particular. Habitualmente, los resultados de esta tarea son extraños y, por ello, han surgido teorías que tratan de explicarlos a partir de hipótesis relativas a determinados mecanismos mentales o tipos de razonamiento especiales en los seres humanos. En este trabajo, tratamos de demostrar, revisando críticamente un experimento concreto presente en la literatura, que no es necesario aceptar tales hipótesis y que se puede explicar lo que sucede en dicho experimento asumiendo, simplemente, que los participantes perfeccionan algunas reglas condicionales que se proponen en él.

On several occasions, conditional statements are perfected, that is, are understood as biconditional statements. This causes problems for texts interpretation in general and for the correct understanding of the instructions of the selection task in particular. Usually, the results of this task are unexpected and, due to this, theories have been raised in order to try to explain them from hypotheses about certain mental mechanisms or special types of reasoning in human beings. In this paper, I try to demonstrate, through a critical review of a particular experiment in the literature, that it is not necessary to assume such hypotheses and that it is possible to explain what happens in such experiment simply assuming that participants perfect some conditional rules proposed in it.