Stochastic image spectroscopy: a discriminative generative approach to hyperspectral image modelling and classification.

This paper introduces a new latent variable probabilistic framework for representing spectral data of high spatial and spectral dimensionality, such as hyperspectral images. We use a generative Bayesian model to represent the image formation process and provide interpretable and efficient inference and learning methods. Surprisingly, our approach can be implemented with simple tools and does not require extensive training data, detailed pixel-by-pixel labeling, or significant computational resources. Numerous experiments with simulated data and real benchmark scenarios show encouraging image classification performance. These results validate the unique ability of our framework to discriminate complex hyperspectral images, irrespective of the presence of highly discriminative spectral signatures.

Novel Dry Hyaluronic Acid-Vancomycin Complex Powder for Inhalation, Useful in Pulmonary Infections Associated with Cystic Fibrosis.

Polyelectrolyte-drug complexes are interesting alternatives to improve unfavorable drug properties. Vancomycin (VAN) is an antimicrobial used in the treatment of methicillin-resistant Staphylococcus aureus pulmonary infections in patients with cystic fibrosis. It is generally administered intravenously with a high incidence of adverse side effects, which could be reduced by intrapulmonary administration. Currently, there are no commercially available inhalable formulations containing VAN. Thus, the present work focuses on the preparation and characterization of an ionic complex between hyaluronic acid (HA) and VAN with potential use in inhalable formulations. A particulate-solid HA-VAN25 complex was obtained by spray drying from an aqueous dispersion. FTIR spectroscopy and thermal analysis confirmed the ionic interaction between HA and VAN, while an amorphous diffraction pattern was observed by X-ray. The powder density, geometric size and morphology showed the suitable aerosolization and aerodynamic performance of the powder, indicating its capability of reaching the deep lung. An in vitro extended-release profile of VAN from the complex was obtained, exceeding 24 h. Microbiological assays against methicillin-resistant and -sensitive reference strains of Staphylococcus aureus showed that VAN preserves its antibacterial efficacy. In conclusion, HA-VAN25 exhibited interesting properties for the development of inhalable formulations with potential efficacy and safety advantages over conventional treatment.

Theoretical study of PdNi and PdCu clusters embedded on graphene modified by monovacancy and nitrogen doping.

The stability and reactivity of Pd4Ni4 and Pd4Cu4 clusters embedded on graphene modified by monovacancy and nitrogen doping were investigated using auxiliary density functional theory (ADFT) calculations. The most stable structure of the Pd4Ni4 cluster is found in high spin multiplicity, whereas the lowest stable energy structure of the Pd4Cu4 cluster is a close shell system. The interaction energies between the bimetallic clusters and the defective graphene systems are significantly higher than those reported in the literature for the Pd-based clusters deposited on pristine graphene. It is observed that the composites studied present a HOMO-LUMO gap less than 1 eV, which suggests that they may present a good chemical reactivity. Therefore, from the results obtained in this work it can be inferred that the single vacancy graphene and pyridinic N-doped graphene are potentially good support materials for Pd-based clusters.

Exploring self-care practices and health beliefs among men in the context of emerging infectious diseases: Lessons from the Mpox pandemic in Brazil.

Our goal was to explore self-care practices among men who have sex with men in the context of Mpox in Brazil. This study used qualitative research methods, including interviews and thematic analysis, to collect and analyze data from male participants across the Brazilian territory. The narratives unveil men's perspectives on self-care, risk reduction, and health beliefs during the Mpox pandemic. Our findings highlight a multifaceted approach to self-care among men, encompassing hygiene, physical contact management, mask usage, skin lesion vigilance, and adherence to official guidelines. Men's attitudes toward sexual behaviors emphasize the importance of reducing sexual partners, practicing safe sex, and combating misinformation through accurate information dissemination. The development of these behaviors and self-care practices can be facilitated by nurses guided by Dorothea Orem's Self-Care Theory, supported by patient-centered care, with strategies to address and confront the stigma associated with the disease and provide emotional support. Thus, the study underscores the pivotal role of self-care in mitigating infection risks, especially in the context of emerging infectious diseases. It acknowledges the impact of socio-cultural factors and healthcare policies on men's preventive measures. However, it also recognizes limitations, such as potential bias due to stigma concerns and a nonrepresentative sample. Ultimately, the research advocates for tailored education, promotion of gender equity, and healthcare empowerment to effectively manage health risks in such contexts.

Dynamic methylation pattern of H19DMR and KvDMR1 in bovine oocytes and preimplantation embryos.

PURPOSE: This study aimed to evaluate the epigenetic reprogramming of ICR1 (KvDMR1) and ICR2 (H19DMR) and expression of genes controlled by them as well as those involved in methylation, demethylation, and pluripotency. METHODS: We collected germinal vesicle (GV) and metaphase II (MII) oocytes, and preimplantation embryos at five stages [zygote, 4-8 cells, 8-16 cells, morula, and expanded blastocysts (ExB)]. DNA methylation was assessed by BiSeq, and the gene expression was evaluated using qPCR. RESULTS: H19DMR showed an increased DNA methylation from GV to MII oocytes (68.04% and 98.05%, respectively), decreasing in zygotes (85.83%) until morula (61.65%), and ExB (63.63%). H19 and IGF2 showed increased expression in zygotes, which decreased in further stages. KvDMR1 was hypermethylated in both GV (71.82%) and MII (69.43%) and in zygotes (73.70%) up to morula (77.84%), with a loss of methylation at the ExB (36.64%). The zygote had higher expression of most genes, except for CDKN1C and PHLDA2, which were highly expressed in MII and GV oocytes, respectively. DNMTs showed increased expression in oocytes, followed by a reduction in the earliest stages of embryo development. TET1 was downregulated until 4-8-cell and upregulated in 8-16-cell embryos. TET2 and TET3 showed higher expression in oocytes, and a downregulation in MII oocytes and 4-8-cell embryo. CONCLUSION: We highlighted the heterogeneity in the DNA methylation of H19DMR and KvDMR1 and a dynamic expression pattern of genes controlled by them. The expression of DNMTs and TETs genes was also dynamic owing to epigenetic reprogramming.

HIDSAG: Hyperspectral Image Database for Supervised Analysis in Geometallurgy.

Supervised analysis using spectral data requires a well-informed characterisation of the response variables and abundant spectral data points. The presented hyperspectral dataset comes from five sets of geometallurgical samples, each characterised by different methods. To provide the spectral data, all mineral samples were scanned with SPECIM VNIR and SWIR hyperspectral cameras. For each subset the following data are provided 1) hyperspectral reflectance images in the VNIR spectral range (400-1000 nm wavelength); 2) hyperspectral reflectance images in the SWIR spectral range (900-2500 nm wavelength); 3) hyperspectral reflectance images in the VNIR-SWIR range (merged to SWIR spatial resolution); 4) RGB images constructed from hyperspectral data using a Bilateral Filter based sensor fusion method; 5) response variables representing mineral sample characterisation results, provided as training and validation data. This dataset is intended for use in general regression and classification research and experiments. All subsets were validated using machine learning models with satisfactory results.

DNA methylation in regulatory elements of the FKBP5 and NR3C1 gene in mother-child binomials with depression.

BACKGROUND: The FKBP5 and NR3C1 genes play an important role in stress response, thus impacting mental health. Stress factor exposure in early life, such as maternal depression, may contribute to epigenetic modifications in stress response genes, increasing the susceptibility to different psychopathologies. The present study aimed to evaluate the DNA methylation profile in maternal-infant depression in regulatory regions of the FKBP5 gene and the alternative promoter of the NR3C1 gene. METHODS: We evaluated 60 mother-infant pairs. The levels of DNA methylation were analyzed by the MSRED-qPCR technique. RESULTS: We observed an increased DNA methylation profile in the NR3C1 gene promoter in children with depression and children exposed to maternal depression (p < 0.05). In addition, we observed a correlation of DNA methylation between mothers and offspring exposed to maternal depression. This correlation shows a possible intergenerational effect of maternal MDD exposure on the offspring. For FKBP5, we found a decrease in DNA methylation at intron 7 in children exposed to maternal MDD during pregnancy and a correlation of DNA methylation between mothers and children exposed to maternal MDD (p < 0.05). LIMITATIONS: Although the individuals of this study are a rare group, the sample size of the study was small, and we evaluated the DNA methylation of only one CpG site for each region. CONCLUSION: These results indicate changes in DNA methylation levels in regulatory regions of FKBP5 and NR3C1 in the mother-child MDD context and represent a potential target of studies to understand the depression etiology and how it occurs between generations.

Prevalencia de las cardiopatías congénitas en relación con la altura sobre el nivel del mar en una región de Colombia / Prevalence of congenital heart disease in relation to height above sea level in a region of Colombia

Resumen Introducción: Las cardiopatías congénitas son los trastornos congénitos más frecuentes en la población mundial, se manifiestan generalmente después del nacimiento. Las altitudes entre 2,500 y 3,500 metros sobre el nivel del mar se han relacionado con la alta incidencia de cardiopatías congénitas como el ductus arterioso persistente, los defectos del septum auricular y los defectos del septum ventricular. Objetivo: Caracterizar clínica y sociodemográficamente los pacientes con diagnóstico de cardiopatías congénitas procedentes de altitudes bajas, moderadas y altas en un hospital regional de Colombia. Metodología: Estudio observacional, descriptivo retrospectivo. Se incluyeron todos los pacientes menores de 18 años con diagnóstico de cardiopatías congénitas, atendidos en el Hospital Universitario San Rafael de Tunja entre el 2015 y 2021. Resultados: El 51.9% de los pacientes eran de sexo masculino, el 16.3% tenían antecedente de prematurez y el 9.1% tenían diagnóstico de síndrome de Down. Las cardiopatías más frecuentes fueron: ductus arterioso persistente (35.1%), seguido de comunicación interventricular (21.6%) y comunicación intrauricular (19.7%). Conclusiones: Se deben establecer estrategias como el tamizaje y diagnóstico oportuno de las cardiopatías congénitas en poblaciones de riesgo con el fin de mejorar el pronóstico de vida de los pacientes y desenlace de la enfermedad.

Abstract Introduction: Congenital heart diseases are the most common congenital disorders in the world population, they generally manifest after birth. Altitudes between 2,500-3,500 meters above sea level have been linked to the high incidence of congenital heart diseases such as patent ductus arteriosus, atrial septum defects, and ventricular septum defects. Objetives: To characterize clinically and sociodemographically the patients diagnosed with congenital heart disease from low, moderate and high altitudes in a regional hospital in Colombia. Methodology: Observational, descriptive retrospective study. All patients under 18 years of age with a diagnosis of congenital heart disease, treated at the San Rafael de Tunja University Hospital between 2015 and 2021, were included. Results: 51.9% of the patients were male, 16.3% had a history of prematurity and 9.1% had a diagnosis of Down syndrome. The most frequent heart diseases were: persistent ductus arteriosus 35.1%, followed by ventricular communication representing 21.6% and intra-atrial communication with 19.7%). Conclusions: They must eestablish strategies such as screening and timely diagnosis of congenital heart disease in at-risk populations in order to improve the life prognosis of patients and the outcome of the disease.

Prevalence of congenital heart disease in relation to height above sea level in a region of Colombia.

INTRODUCTION: Congenital heart diseases are the most common congenital disorders in the world population, they generally manifest after birth. Altitudes between 2,500-3,500 meters above sea level have been linked to the high incidence of congenital heart diseases such as patent ductus arteriosus, atrial septum defects, and ventricular septum defects. OBJETIVES: To characterize clinically and sociodemographically the patients diagnosed with congenital heart disease from low, moderate and high altitudes in a regional hospital in Colombia. METHODOLOGY: Observational, descriptive retrospective study. All patients under 18 years of age with a diagnosis of congenital heart disease, treated at the San Rafael de Tunja University Hospital between 2015 and 2021, were included. RESULTS: 51.9% of the patients were male, 16.3% had a history of prematurity and 9.1% had a diagnosis of Down syndrome. The most frequent heart diseases were: persistent ductus arteriosus 35.1%, followed by ventricular communication representing 21.6% and intra-atrial communication with 19.7%). CONCLUSIONS: They must eestablish strategies such as screening and timely diagnosis of congenital heart disease in at-risk populations in order to improve the life prognosis of patients and the outcome of the disease.

INTRODUCCIÓN: Las cardiopatías congénitas son los trastornos congénitos más frecuentes en la población mundial, se manifiestan generalmente después del nacimiento. Las altitudes entre 2,500 y 3,500 metros sobre el nivel del mar se han relacionado con la alta incidencia de cardiopatías congénitas como el ductus arterioso persistente, los defectos del septum auricular y los defectos del septum ventricular. OBJETIVO: Caracterizar clínica y sociodemográficamente los pacientes con diagnóstico de cardiopatías congénitas procedentes de altitudes bajas, moderadas y altas en un hospital regional de Colombia. METODOLOGÍA: Estudio observacional, descriptivo retrospectivo. Se incluyeron todos los pacientes menores de 18 años con diagnóstico de cardiopatías congénitas, atendidos en el Hospital Universitario San Rafael de Tunja entre el 2015 y 2021. RESULTADOS: El 51.9% de los pacientes eran de sexo masculino, el 16.3% tenían antecedente de prematurez y el 9.1% tenían diagnóstico de síndrome de Down. Las cardiopatías más frecuentes fueron: ductus arterioso persistente (35.1%), seguido de comunicación interventricular (21.6%) y comunicación intrauricular (19.7%). CONCLUSIONES: Se deben establecer estrategias como el tamizaje y diagnóstico oportuno de las cardiopatías congénitas en poblaciones de riesgo con el fin de mejorar el pronóstico de vida de los pacientes y desenlace de la enfermedad.

Machine learning partners in criminal networks.

Recent research has shown that criminal networks have complex organizational structures, but whether this can be used to predict static and dynamic properties of criminal networks remains little explored. Here, by combining graph representation learning and machine learning methods, we show that structural properties of political corruption, police intelligence, and money laundering networks can be used to recover missing criminal partnerships, distinguish among different types of criminal and legal associations, as well as predict the total amount of money exchanged among criminal agents, all with outstanding accuracy. We also show that our approach can anticipate future criminal associations during the dynamic growth of corruption networks with significant accuracy. Thus, similar to evidence found at crime scenes, we conclude that structural patterns of criminal networks carry crucial information about illegal activities, which allows machine learning methods to predict missing information and even anticipate future criminal behavior.

Performance of the CORB (Confusion, Oxygenation, Respiratory Rate, and Blood Pressure) Scale for the Prediction of Clinical Outcomes in Pneumonia.

Background: Community-acquired pneumonia (CAP) is a common cause of morbidity and mortality due to misdiagnosis and inappropriate treatment approaches. Objective: To assess the performance of the CORB score in subjects with CAP for predicting in-hospital mortality, death within 30 days of admission, and requirement for invasive mechanical ventilation (IMV) and vasopressor support. Methods: A retrospective, cohort study with diagnostic test analysis of CORB and CURB-65 scores in subjects with CAP according to ATS criteria was undertaken. An alternative CORB score was estimated by replacing SpO2 ≤90% by the SpO2/FiO2 ratio. Crude and adjusted odd ratios (AOR) were calculated for each variable. The area under the receiver operating characteristics curve (AUROC) was constructed for each score, and outcomes were analyzed. AUROCs were compared with the DeLong test, considering a p value <0,05 statistically significant. Results: From 1,811 subjects who entered the analysis, 15.1% (273/1,811) died in hospital, 8.78% required IMV (159/1,811), and 9.77% (177/1,811) needed vasopressor support. CORB had an AUROC of 0,660 (95% CI: 0,623-0,697) for in-hospital mortality; an AUROC of 0,657 (95% CI: 0,621-0,692) for 30-day mortality; an AUROC of 0,637 (CI 95%: 0,589-0,685) for IMV requirement; and an AUROC of 0,635 (95% CI: 0,589-0,681) for vasopressor support. CORB performance increases when the SpO2/FiO2 ratio <300 is used as oxygenation criterion in the prediction of requirement for IMV and vasopressor support, with AUROC of 0,700 (95% CI: 0,654-0,746; p < 0.001) and AUROC of 0,702 (95% CI: 0,66-0,745; p < 0.001), respectively. CURB-65 score presents an in-hospital mortality AUROC of 0,727 (95% CI: 0,695-0,759) and 30-day mortality AUROC of 0,726 (95% CI: 0,695-0,756). Conclusions: CORB score has a good performance in predicting the need for IMV and vasopressor support in CAP patients. This performance improves when the SpO2/FiO2 ratio <300 is used instead of the SpO2 ≤90% as the oxygenation parameter. CURB-65 score is superior in the prediction of mortality.

Mortality markers in outpatients diagnosed with heart failure / Marcadores de mortalidad en pacientes ambulatorios con diagnóstico de insuficiencia cardíaca

Abstract Introduction: Heart failure is a global health problem. In Ecuador it is estimated that between 1% and 2% of the population suffers this disease. Objective: To determine mortality markers in outpatients with a diagnosis of heart failure in the Ecuadorian Andean population. Methods: A cross-sectional and monocentric study was carried out in 230 mestizo, indigenous and Afro-descendant patients diagnosed with heart failure. The differences between the three ethnic groups were statistically analyzed by one-way ANOVA and Crammer’s V test. Additionally, a logistic regression analysis was performed. Results: The predominant ethnic group was mestizo (73.5%), followed by indigenous people (15.5%) and afro-descendants (10.5%). The logistic regression analysis showed that age (OR: 1.046; 95% CI: 1.014-1.078; p = 0.04), ethnicity (OR: 1.713; 95% CI: 1.053-2.78; p = 0.030), the presence of atrial fibrillation (OR: 2.711; 95% CI: 1.03-7.12; p = 0.042) and the number of hospitalizations (OR: 3.026; 95% CI: 1.85-4.94; p = 0.000), were markers of poor prognosis. On the other hand, mean arterial pressure (OR: 0.969; 95% CI: 0.94-0.99; p = 0.010), absence of ischemic cerebrovascular event (OR: 0.15; 95% CI: 0.48-0.527; p = 0.03) and total cholesterol levels (OR: 0.991; 95% CI: 0.987-0.996; p = 0.000) were protection markers. Conclusions: In this population, ethnicity, atrial fibrillation, mean arterial pressure, ischemic cerebrovascular event, total cholesterol levels and the number of hospitalizations were established as mortality markers in outpatients diagnosed with heart failure.

Resumen Introducción: La insuficiencia cardíaca es un problema de salud global. En Ecuador se estima que entre el 1 y el 2% de la población padece esta enfermedad. Objetivo: determinar los marcadores de mortalidad en los pacientes ambulatorios con diagnóstico de insuficiencia cardíaca en población andina ecuatoriana. Métodos: Se llevó a cabo un estudio transversal y monocéntrico en 230 pacientes mestizos, indígenas y afrodescendientes diagnosticados con insuficiencia cardíaca. Las diferencias entre los tres grupos étnicos fueron analizadas estadísticamente por ANOVA unidireccional y el test V de Crammer. Adicionalmente, se realizó un análisis de regresión logística. Resultados: El grupo étnico predominante fue el mestizo (73,5%), seguido por el indígena (15,5%) y por el afrodescendiente (10,5%). El análisis de regresión logística mostró que la edad (OR: 1,046; IC 95%: 1,014-1,078; p = 0,04), la etnia (OR: 1,713; IC 95%: 1,053-2,78; p = 0,030), la presencia de fibrilación auricular (OR: 2,711; IC 95%: 1,03-7,12; p = 0,042) y el número de hospitalizaciones (OR: 3,026; IC 95%: 1,85-4,94; p = 0,000), fueron marcadores de mal pronóstico. Por otro lado, la presión arterial media (OR: 0,969; IC 95%: 0,94-0,99; p = 0,010), la ausencia de evento cerebrovascular isquémico (OR: 0,15; IC 95%: 0,48-0,527; p = 0,03) y los niveles de colesterol total (OR 0,991; IC 95%: 0,987-0,996; p = 0,000) fueron marcadores de protección. Conclusiones: En esta población, la etnia, la fibrilación auricular, la presión arterial media, el evento cerebrovascular isquémico, el colesterol total y el número de hospitalizaciones se configuraron como marcadores de mortalidad en pacientes ambulatorios con diagnóstico de insuficiencia cardíaca.

Posterior Leg Pain: Understanding Soleus Muscle Injuries.

Soleus muscle injuries are frequently unrecognized, representing a common cause of sports inactivity. This is mainly because little is known about the anatomy of the soleus muscle and the clinical manifestations of injury. Unlike other muscles, the soleus muscle has a complex myoconnective structure with three intramuscular tendons, which makes the interpretation of muscle pathologic conditions challenging. Soleus muscle injuries can be acute or chronic and are usually considered to be a minor discomfort by both the patient and the sports medicine physician, leading to a relatively quick return to sporting activity with a high risk for reinjury. The authors review the soleus muscle anatomy and the importance of being familiar with the most frequent locations of injuries, which are fundamental aspects that every radiologist should understand to avoid underdiagnosis. The role of imaging, the clinical manifestations of injuries, and the differential diagnoses are key aspects to know when evaluating posterior leg pain. The online slide presentation from the RSNA Annual Meeting is available for this article. ©RSNA, 2022.

Universality of political corruption networks.

Corruption crimes demand highly coordinated actions among criminal agents to succeed. But research dedicated to corruption networks is still in its infancy and indeed little is known about the properties of these networks. Here we present a comprehensive investigation of corruption networks related to political scandals in Spain and Brazil over nearly three decades. We show that corruption networks of both countries share universal structural and dynamical properties, including similar degree distributions, clustering and assortativity coefficients, modular structure, and a growth process that is marked by the coalescence of network components due to a few recidivist criminals. We propose a simple model that not only reproduces these empirical properties but reveals also that corruption networks operate near a critical recidivism rate below which the network is entirely fragmented and above which it is overly connected. Our research thus indicates that actions focused on decreasing corruption recidivism may substantially mitigate this type of organized crime.

Implicancias sobre la Adaptación de la Escala de Inteligencia para Niños de Wechsler IV (WISC-IV) en Argentina. Corrección de WISC-IV según diferentes baremos argentinos / Implications on the Adaptation of the Wechsler Intelligence Scale for Children IV (WISC-IV) in Argentina. Comparison of the WISC-IV Standardized Data from two Argentine Regions

Resumen La utilización de pruebas psicológicas validadas y de confiabilidad comprobadas aportan evidencias valiosas al profesional en una multiplicidad de actividades, que comprenden desde el diagnóstico, el plan y el seguimiento de tratamiento hasta la selección laboral, la orientación vocacional, las pericias judiciales e investigación; sin embargo, no siempre se disponen de baremos adaptados a la región en la que se pretende aplicar un instrumento y, en ocasiones, siquiera corresponden a datos normativos del país. En Argentina, la WISC-IV fue adaptada considerando población perteneciente al Área Metropolitana de Buenos Aires, no se incluye muestra de otras regiones del extenso país. Por lo tanto, se realizó una investigación cuantitativa no experimental, exploratoria- descriptiva, con el objetivo de determinar la importancia de contar con baremos adaptados de la WISC-IV para diferentes regiones de un mismo país; para ello, se analizaron comparativamente los índices obtenidos por 520 escolares de 6 a 14 años (agrupados según los rangos de edad 6-8, 9-11 y 12-14) al aplicar dos baremos argentinos (Buenos Aires y Resistencia) para su corrección mediante un análisis de ANOVA mixto. Los resultados evidenciaron diferencias significativas según el baremo sea de Buenos Aires o de Resistencia, en 4 de los 5 índices de la WISC-IV, al abarcar tanto en aspectos relacionados con el funcionamiento cognitivo general (i.e., CIT), como en campos más específicos (i.e., memoria de trabajo - IMO, velocidad de procesamiento - IVP y razonamiento perceptivo - IRP); además, se observaron diferencias entre baremos en CIT, ICV, IRP e IMO y sugerir comportamientos diferentes en los distintos índices según el tipo de baremo aplicado en los diferentes grupos de edad. Los resultados sugieren que la corrección de la escala a un/a estudiante, según las normativas establecidas para una región con características sociodemográficas distintas a la que pertenece el individuo, podría derivar en errores interpretativos de sus aptitudes cognitivas, por lo que se determina la importancia de contar con adaptaciones de las pruebas psicológicas para arribar a interpretaciones que eviten infra o sobrevalorar sus puntuaciones.

Abstract: The use of validated psychological tests provides valuable evidence to specialists in a multiplicity of activities (e.g., predicting diagnoses, guiding treatment and follow-up plans, guiding the job selection process and vocational orientation, determining disability levels for medico-legal purposes). However, a psychological instrument is not generally adapted and standardized in the country in which it is intended to be applied. In Argentina, the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) was standardized in the Buenos Aires Metropolitan Area; but did not include samples from other regions across the vast country. This situation is problematic, because Argentina presents disparities in its socio-demographic characteristics across the territory, and an accurate interpre- tation of intelligence test performance, depends on the use of appropriately standardized data. Hence, a quantitative non-experimental, exploratory-descriptive study was conducted to determine the importance of obtaining locally standardized data for WISC-IV. To this end, the indices obtained from 520 children and adolescents aged 6 to 14 years (grouped according to age ranges 6-8, 9-11 and 12-14) were comparatively analyzed, by analyzing two Argentine adaptations (Buenos Aires and Resistencia). Results revealed differences between normative data from the country's different regions in four indices, which included both aspects of general cognitive functioning (i.e., CIT) and more specific processes (i.e., working memory - IMO, processing speed - IVP, and perceptual reasoning - IRP). These results suggest that the assessment of students, according to non-locally established standardized data, could lead to interpretative errors regarding their cognitive abilities. Thus, the study contributes to knowledge about the importance of using contextually appropriate standardized data in the implementation of intelligence tests, to arrive at evaluations that avoid over- or under- estimating students' abilities.

Regulatory functions of FKBP5 intronic regions associated with psychiatric disorders.

The FKBP5 gene codifies a co-chaperone protein associated with the modulation of glucocorticoid receptor interaction involved in the adaptive stress response. The FKBP5 intracellular concentration affects the binding affinity of the glucocorticoid receptor (GR) to glucocorticoids (GCs). This gene has glucocorticoid response elements (GREs) located in introns 2, 5 and 7, which affect its expression. Recent studies have examined GRE activity and the effects of genetic variants on transcript efficiency and their contribution to susceptibility to behavioral disorders. Epigenetic changes and environmental factors can influence the effects of these allele-specific variants, impacting the response to GCs of the FKBP5 gene. The main epigenetic mark investigated in FKBP5 intronic regions is DNA methylation, however, few studies have been performed for all GREs located in these regions. One of the major findings was the association of low DNA methylation levels in the intron 7 of FKBP5 in patients with psychiatric disorders. To date, there are no reports of DNA methylation in introns 2 and 5 of the gene associated with diagnoses of psychiatric disorders. This review highlights what has been discovered so far about the relationship between polymorphisms and epigenetic targets in intragenic regions, and reveals the gaps that need to be explored, mainly concerning the role of DNA methylation in these regions and how it acts in psychiatric disease susceptibility.

Regulation of Lin28a-miRNA let-7b-5p pathway in skeletal muscle cells by peroxisome proliferator-activated receptor delta.

Lin28a/miRNA let-7b-5p pathway has emerged as a key regulators of energy homeostasis in the skeletal muscle. However, the mechanism through which this pathway is regulated in the skeletal muscle has remained unclear. We have found that 8 wk of aerobic training (Tr) markedly decreased let-7b-5p expression in murine skeletal muscle, whereas high-fat diet (Hfd) increased its expression. Conversely, Lin28a expression, a well-known inhibitor of let-7b-5p, was induced by Tr and decreased by Hfd. Similarly, in human muscle biopsies, Tr increased LIN28 expression and decreased let-7b-5p expression. Bioinformatics analysis of LIN28a DNA sequence revealed that its enrichment in peroxisome proliferator-activated receptor delta (PPARδ) binding sites, which is a well-known metabolic regulator of exercise. Treatment of primary mouse skeletal muscle cells or C2C12 cells with PPARδ activators GW501516 and AICAR increased Lin28a expression. Lin28a and let-7b-5p expression was also regulated by PPARδ coregulators. While PPARγ coactivator-1α (PGC1α) increased Lin28a expression, corepressor NCoR1 decreased its expression. Furthermore, PGC1α markedly reduced the let-7b-5p expression. PGC1α-mediated induction of Lin28a expression was blocked by the PPARδ inhibitor GSK0660. In agreement, Lin28a expression was downregulated in PPARδ knocked-down cells leading to increased let-7b-5p expression. Finally, we show that modulation of the Lin28a-let-7b-5p pathway in muscle cells leads to changes in mitochondrial metabolism in PGC1α dependent fashion. In summary, we demonstrate that Lin28a-let-7b-5p is a direct target of PPARδ in the skeletal muscle, where it impacts mitochondrial respiration.

Evaluation of the Drug Release Kinetics in Assembled Modular Systems Based on the Dome Matrix Technology.

Mathematical models are an important tool in pharmaceutical formulations development, to evaluate in vitro and in vivo drug release processes and to optimize the design of new systems. Dome Matrix technology allows the combination of modules with different types of drugs, doses, and releases kinetics. This work aimed to design drug release systems based on Dome Matrix technology, with different swelling and erosion properties, to obtain complex drug release profiles and analyze them with simple mathematical models. Most of the release profiles followed a sigmoid curve, with an inflection point corresponding to a change in the release rate behavior. The experimental data were fitted with a simple model recently developed, named the Dual Release model, which consists in the combination of a modified Korsmayer-Peppas model from the beginning to the inflection point and the Lumped model from there until the end. This approach allowed determining relevant pharmaceutical parameters, such as the maximum release rate and the dissolution efficiency, among others. The use of the Dual Release model and the pharmaceutical parameters that characterize the different Dome Matrix modules allows optimizing the choice of the composition and the configuration during the development of a drug delivery system.

Thermally self-assembled biodegradable poly(casein-g-N-isopropylacrylamide) unimers and their application in drug delivery for cancer therapy.

In this work, we report the synthesis of graft copolymers based on casein and N-isopropylacrylamide, which can self-assemble into biodegradable micelles of approximately 80 nm at physiological conditions. The obtained copolymers were degraded by trypsin, an enzyme that is overexpressed in several malignant tumors. Moreover, graft copolymers were able to load doxorubicin (Dox) by ionic interaction with the casein component. In vitro release experiments showed that the in situ assembled micelles can maintain the cargo at plasma conditions but release Dox immediately after their exposition at pH 5.0 and trypsin. Cellular uptake and cytotoxicity assays revealed the efficient delivery to the nucleus and antiproliferative efficacy of Dox in the breast cancer cell line MDA231. Both delivery and therapeutic activity were enhanced in presence of trypsin. Overall, the prepared micelles hold a great potential for their utilization as dual responsive trypsin/pH drug delivery system.

Echocardiographic Measurements in a Preclinical Model of Chronic Chagasic Cardiomyopathy in Dogs: Validation and Reproducibility.

Background: The failure to translate preclinical results to the clinical setting is the rule, not the exception. One reason that is frequently overlooked is whether the animal model reproduces distinctive features of human disease. Another is the reproducibility of the method used to measure treatment effects in preclinical studies. Left ventricular (LV) function improvement is the most common endpoint in preclinical cardiovascular disease studies, while echocardiography is the most frequently used method to evaluate LV function. In this work, we conducted a robust echocardiographic evaluation of LV size and function in dogs chronically infected by Trypanosoma cruzi. Methods and Results: Echocardiography was performed blindly by two distinct observers in mongrel dogs before and between 6 and 9 months post infection. Parameters analyzed included end-systolic volume (ESV), end-diastolic volume (EDV), ejection fraction (EF), and fractional shortening (FS). We observed a significant LVEF and FS reduction in infected animals compared to controls, with no significant variation in volumes. However, the effect of chronic infection in systolic function was quite variable, with EF ranging from 17 to 66%. Using the cut-off value of EF ≤ 40%, established for dilated cardiomyopathy (DCM) in dogs, only 28% of the infected dogs were affected by the chronic infection. Conclusions: The canine model of CCC mimics human disease, reproducing the percentage of individuals that develop heart failure during the chronic infection. It is thus mandatory to establish inclusion criteria in the experimental design of canine preclinical studies to account for the variable effect that chronic infection has on systolic function.