Conceptualizing Epigenetics and the Environmental Landscape of Autism Spectrum Disorders.

Complex interactions between gene variants and environmental risk factors underlie the pathophysiological pathways in major psychiatric disorders. Autism Spectrum Disorder is a neuropsychiatric condition in which susceptible alleles along with epigenetic states contribute to the mutational landscape of the ailing brain. The present work reviews recent evolutionary, molecular, and epigenetic mechanisms potentially linked to the etiology of autism. First, we present a clinical vignette to describe clusters of maladaptive behaviors frequently diagnosed in autistic patients. Next, we microdissect brain regions pertinent to the nosology of autism, as well as cell networks from the bilateral body plan. Lastly, we catalog a number of pathogenic environments associated with disease risk factors. This set of perspectives provides emerging insights into the dynamic interplay between epigenetic and environmental variation in the development of Autism Spectrum Disorders.

A Spatial Kinetic Model of Crowd Evacuation Dynamics with Infectious Disease Contagion.

This paper proposes a kinetic theory approach coupling together the modeling of crowd evacuation from a bounded domain with exit doors and infectious disease contagion. The spatial movement of individuals in the crowd is modeled by a proper description of the interactions with people in the crowd and the environment, including walls and exits. At the same time, interactions among healthy and infectious individuals may generate disease spreading if exposure time is long enough. Immunization of the population and individual awareness to contagion is considered as well. Interactions are modeled by tools of game theory, that let us propose the so-called tables of games that are introduced in the general kinetic equations. The proposed model is qualitatively studied and, through a series of case studies, we explore different scenarios related to crowding and gathering formation within indoor venues under the spread of a respiratory infectious disease, obtaining insights on specific policies to reduce contagion that may be implemented.

Indoor Air Pollution and Decision-Making Behavior: An Interdisciplinary Review.

The human brain is constantly exposed to air pollutants, some of which might be disruptive or even lethal to certain neurons implicated in abstract features of cognitive function. In this review, we present new evidence from behavioral and neural studies in humans, suggesting a link between indoor fine particulate matter and decision-making behavior. To illustrate this relationship, we use qualitative sources, such as historical documents of the Vietnam War to develop hypotheses of how aerial transmission of pollutants might obstruct alternative choices during the evaluation of policy decisions. We first describe the neural circuits driving decision-making processes by addressing how neurons and their cognate receptors directly evaluate and transduce physical phenomena into sensory perceptions that allow us to decide the best course of action among competing alternatives. We then raise the possibility that indoor air pollutants might also impact cell-signaling systems outside the brain parenchyma to further obstruct the computational analysis of the social environment. We also highlight how particulate matter might be pathologically integrated into the brain to override control of sensory decisions, and thereby perturb selection of choice. These lines of research aim to extend our understanding of how inhalation of airborne particulates and toxicants in smoke, for example, might contribute to cognitive impairment and negative health outcomes.

Deep 3D Neural Network for Brain Structures Segmentation Using Self-Attention Modules in MRI Images.

In recent years, the use of deep learning-based models for developing advanced healthcare systems has been growing due to the results they can achieve. However, the majority of the proposed deep learning-models largely use convolutional and pooling operations, causing a loss in valuable data and focusing on local information. In this paper, we propose a deep learning-based approach that uses global and local features which are of importance in the medical image segmentation process. In order to train the architecture, we used extracted three-dimensional (3D) blocks from the full magnetic resonance image resolution, which were sent through a set of successive convolutional neural network (CNN) layers free of pooling operations to extract local information. Later, we sent the resulting feature maps to successive layers of self-attention modules to obtain the global context, whose output was later dispatched to the decoder pipeline composed mostly of upsampling layers. The model was trained using the Mindboggle-101 dataset. The experimental results showed that the self-attention modules allow segmentation with a higher Mean Dice Score of 0.90 ± 0.036 compared with other UNet-based approaches. The average segmentation time was approximately 0.038 s per brain structure. The proposed model allows tackling the brain structure segmentation task properly. Exploiting the global context that the self-attention modules incorporate allows for more precise and faster segmentation. We segmented 37 brain structures and, to the best of our knowledge, it is the largest number of structures under a 3D approach using attention mechanisms.

A Saliency-Based Sparse Representation Method for Point Cloud Simplification.

High-resolution 3D scanning devices produce high-density point clouds, which require a large capacity of storage and time-consuming processing algorithms. In order to reduce both needs, it is common to apply surface simplification algorithms as a preprocessing stage. The goal of point cloud simplification algorithms is to reduce the volume of data while preserving the most relevant features of the original point cloud. In this paper, we present a new point cloud feature-preserving simplification algorithm. We use a global approach to detect saliencies on a given point cloud. Our method estimates a feature vector for each point in the cloud. The components of the feature vector are the normal vector coordinates, the point coordinates, and the surface curvature at each point. Feature vectors are used as basis signals to carry out a dictionary learning process, producing a trained dictionary. We perform the corresponding sparse coding process to produce a sparse matrix. To detect the saliencies, the proposed method uses two measures, the first of which takes into account the quantity of nonzero elements in each column vector of the sparse matrix and the second the reconstruction error of each signal. These measures are then combined to produce the final saliency value for each point in the cloud. Next, we proceed with the simplification of the point cloud, guided by the detected saliency and using the saliency values of each point as a dynamic clusterization radius. We validate the proposed method by comparing it with a set of state-of-the-art methods, demonstrating the effectiveness of the simplification method.

Fiebre y sus implicaciones en el diagnóstico del paciente neurológico, revisión narrativa de la literatura / Fever and Its Implications in the Diagnosis of the Neurological Patient: A Review / Febre e suas implicações no diagnostico do paciente neurológico, uma revisão narrativa da literatura

Introducción: La fiebre se considera uno de los primeros síntomas registrados en pacientes hospitalizados y se ha convertido en un importante marcador de enfermedad. La presente revisión buscó recopilar evidencia en torno a la fiebre y su importancia en los diferentes escenarios clínicos que se presentan en el paciente neurológico, ya que en los últimos años se ha logrado comprender mejor el papel que desempeña el sistema nervioso central dentro de la termorregulación. Metodología: Búsqueda de la literatura en bases de datos como Pubmed, OVID, Epistemonikos, SciELO y Google Scholar, durante los años 2009 al 2019 en español e inglés, sobre fiebre e implicaciones en pacientes neurológicos, usando palabras clave como fiebre, sensibilidad, especificidad, likelihood ratio, enfermedades del sistema nervio-so, neurología, encefalitis, neuritis y traumatismo del sistema nervioso. Resultados: Se encontraron 374 artículos, de los cuales 48 cumplieron con los criterios de inclusión. Se incluyeron libros de texto, como metaanálisis, revisiones sistemáticas, revisiones scoping, artículos de revisión y estudios ob-servacionales. Se analizaron y subdividieron en 8 apartados con temáticas en común para su estudio. Conclusiones: En etapas tempranas de eventos cerebro-vasculares isquémicos o hemorrágicos la fiebre se com-porta como una respuesta sistémica secundaria al daño de base, y es crucial corregirla tempranamente. Al mismo tiempo, en traumatismos del sistema nervioso central, la fiebre en las primeras 72 horas se identifica como un marcador de mal pronóstico

Introduction: Fever is considered one of the first symptoms registered in hospitalized patients, beco-ming an important marker of disease. The present review sought to collect evidence on fever and its importance in the different clinical scenarios that occur in neurological patients, since in recent years it has been possible to better understand the role of the central nervous system within the thermo-regulation. Methodology: A literature search was carried out in databases such as Pubmed, OVID, Epistemoni-kos, SciELO and Google Scholar during the years 2009 to 2019 in Spanish and English languages, on fever and implications in neurological patients, using keywords such as fever, sensitivity, specificity, likelihood ratio, diseases of the nervous system, neurology, encephalitis, neuritis and trauma of the nervous system. Results: A total of 374 articles were found, of which 48 articles met the inclusion criteria, for the construction of this review article. Textbooks, as well as meta-analyzes, systematic reviews, scoping reviews, and review articles were included. They were analyzed and subdivided into 8 sections with common themes for their study. Conclusions: In early stages of ischemic or hemorrhagic CVD, fever behaves as a systemic response secondary to the underlying injury, and it is crucial to correct it early. At the same time, in CNS trauma, fever in the first 72 hours is identified as a poor prognostic marker

Introdução: A febre é considerada um dos primeiros sintomas registrados em pacientes hospitaliza-dos e tornou-se um importante marcador de doença. A presente revisão procurou reunir evidencias em torno da febre e sua importância nos diferentes panoramas clínicos no paciente neurológico, uma vez que nos últimos anos foi possível compreender melhor o papel do sistema nervoso central no processo de termo regulação. Metodologia: Foi realizada uma pesquisa de literatura em bases de dados como Pubmed, OVID, Epis-temonikos, SciELO e Google Acadêmico, durante os anos 2009 a 2019 em espanhol e inglês, sobre febre e suas implicações em pacientes neurológicos, utilizando palavras-chave como febre, sensibili-dade, especificidade, likelihood ratio, doenças do sistema nervoso, neurologia, encefalite, neurite e trauma do sistema nervoso. Resultados: Foi encontrado um total de 374 artigos, dos quais 48 abrangiam os critérios de inclusão. Foram incluídos livros de texto, como meta-análises, revisões sistemáticas, revisões Scoping, artigos de revisão e estudos observacionais. Foram analisadas e subdivididas em 8 secções com assuntos comuns para seu estudo. Conclusões: Em fases iniciais de eventos cerebrovasculares isquêmicos ou hemorrágicos, a febre se comporta como uma resposta sistêmica secundária ao dano de base, e é crucial corrigi-la precoce-mente. Enquanto, em traumatismos do sistema nervoso central, a febre nas primeiras 72 horas é identificada como um marcador de mau prognóstico

[National surveillance of clinical isolates of Enterococcus faecalis resistant to linezolid carrying the optrA gene in Colombia, 2014-2019]. / Vigilancia nacional de aislamientos clínicos de Enterococcus faecalis resistentes al linezolid portadores del gen optrA en Colombia, 2014-2019.

OBJECTIVE: To describe the epidemiological, phenotypical and genetic characteristics of clinical isolates carrying the optrA gene identified in antimicrobial resistance surveillance by the laboratory of the National Institute of Health of Colombia. METHODS: Between October 2014 and February 2019, 25 isolates of Enterococcus spp. resistant to linezolid were received. Antimicrobial identification and sensitivity were determined using Vitek 2 and the minimum inhibitory concentration (MIC) to linezolid was established with E-test. The optrA gene was detected by PCR, and the genetic diversity of optrA-positive isolates was tested with Diversilab®. Six isolates were selected to perform whole genome sequencing. RESULTS: The optrA gene was confirmed in 23/25 isolates of E. faecalis from seven departments in Colombia. The isolates presented a MIC to linezolid between 8 and >256µg/mL. Typing by Diversilab® showed a wide genetic variability. All the isolates analyzed by whole genome sequencing showed the resistance genes fexA, ermB, lsaA, tet(M), tet(L) and dfrG in addition to optrA and were negative for other mechanisms of resistance to linezolid. Three type sequences and three optrA variants were identified: ST16 (optrA-2), ST476 (optrA-5) and ST618 (optrA-6). The genetic environment of the optrA-2 (ST16) isolates presented the impB, fex, optrA segment, associated with plasmid, while in two isolates (optrA-6 and optrA-5) the transferable chromosomal element Tn6674-like was found. CONCLUSION: OptrA-positive clinical isolates present a high genetic diversity, with different optrA clones and variants related to two types of structures and different mobile genetic elements.

Vigilancia nacional de aislamientos clínicos de Enterococcus faecalis resistentes al linezolid portadores del gen optrA en Colombia, 2014-2019

Objetivo. Describir las características epidemiológicas, fenotípicas y genéticas de aislamientos clínicos portadores de optrA identificados en la vigilancia de resistencia antimicrobiana por el laboratorio del Instituto Nacional de Salud de Colombia. Métodos. Entre octubre de 2014 y febrero 2019, se recibieron 25 aislamientos de Enterococcus spp. resistentes al linezolid. La identificación y sensibilidad antimicrobiana se determinó con Vitek 2 y la concentración inhibitoria mínima (CIM) al linezolid se estableció con E-test. El gen optrA se detectó mediante PCR. La diversidad genética de aislamientos positivos para optrA se analizó con Diversilab®. Se seleccionaron seis aislamientos para llevar a cabo la secuenciación del genoma completo. Resultados. Se confirmó el gen optrA en 23/25 aislamientos de E. faecalis de siete departamentos de Colombia. Los aislamientos presentaron una CIM al linezolid entre 8 y >256μg/mL. La tipificación por Diversilab® indicó una amplia variabilidad genética. Todos los aislamientos analizados mediante secuenciación del genoma completo, presentaron genes de resistencia fexA, ermB, lsaA, tet(M), tet(L) y dfrG además de optrA y fueron negativos para otros mecanismos de resistencia al linezolid. Se identificaron tres secuencias tipos y tres variantes de optrA: ST16 (optrA-2), ST476 (optrA-5) y ST618 (optrA-6). El entorno genético de los aislamientos optrA-2 (ST16) presentó el segmento impB, fex, optrA, asociado a plásmido, mientras que en dos aislamientos (optrA-6 y optrA-5) se encontró el elemento cromosómico transferible Tn6674-like. Conclusión. Los aislamientos clínicos positivos para optrA presentan una alta diversidad genética, con diferentes clones y variantes de optrA relacionados con dos tipos de estructuras y diferentes elementos genéticos móviles.

Objective. To describe the epidemiological, phenotypical and genetic characteristics of clinical isolates carrying the optrA gene identified in antimicrobial resistance surveillance by the laboratory of the National Institute of Health of Colombia. Methods. Between October 2014 and February 2019, 25 isolates of Enterococcus spp. resistant to linezolid were received. Antimicrobial identification and sensitivity were determined using Vitek 2 and the minimum inhibitory concentration (MIC) to linezolid was established with E-test. The optrA gene was detected by PCR, and the genetic diversity of optrA-positive isolates was tested with Diversilab®. Six isolates were selected to perform whole genome sequencing. Results. The optrA gene was confirmed in 23/25 isolates of E. faecalis from seven departments in Colombia. The isolates presented a MIC to linezolid between 8 and >256μg/mL. Typing by Diversilab® showed a wide genetic variability. All the isolates analyzed by whole genome sequencing showed the resistance genes fexA, ermB, lsaA, tet(M), tet(L) and dfrG in addition to optrA and were negative for other mechanisms of resistance to linezolid. Three type sequences and three optrA variants were identified: ST16 (optrA-2), ST476 (optrA-5) and ST618 (optrA-6). The genetic environment of the optrA-2 (ST16) isolates presented the impB, fex, optrA segment, associated with plasmid, while in two isolates (optrA-6 and optrA-5) the transferable chromosomal element Tn6674-like was found. Conclusion. OptrA-positive clinical isolates present a high genetic diversity, with different optrA clones and variants related to two types of structures and different mobile genetic elements.

Nutraceutical potential of flours from tomato by-product and tomato field waste.

Tomato field wastes and industrial by-products represents a valuable source of compounds with nutraceutical potential, and therefore of raw material to obtain food ingredients and additives. The objective of this study was to obtain a flour from tomato industrial by-product and from tomato field waste, dried by a conventional method, that allows to remain important nutraceutical compounds, which in the future, can be used for biotechnological purposes. We found that the drying procedure that allowed to reach an adequate water activity (0.4-0.6) in a forced convection oven were: 55 °C during 120 min. Both, the by-product and the field waste are potential sources for the extraction of phenolic and carotenoid compounds, getting up 11.26 µg/mg dry extract of lycopene and 162.82 µg/mg dry extract of phenolic compounds, highlighting the flavonoids: naringenin, catechin, and rutin. On the other hand, antioxidant analysis showed that oven dried by-product exhibits an inhibition around 80% against hydroxyl and peroxyl radicals, and a positive correlation of both lycopene and ß-carotene with myoglobin protection ratio against these radicals. We concluded that the flour from tomato industrial by-products and field waste have nutraceutical properties attractive to the food industry.

Perspectives of Pitocin administration on behavioral outcomes in the pediatric population: recent insights and future implications.

Oxytocin plays an important role in the regulation of parturition as this peptide hormone promotes uterine smooth muscle contractility in gravid women undergoing labor. Here, we review the impact of Pitocin administration on behavioral outcomes in the pediatric population. Pitocin is a synthetic preparation of oxytocin widely used in the obstetric practice for the management of labor and postpartum hemorrhage. We begin by tracing the neuroanatomy of oxytocin-containing cells from an evolutionary perspective and then summarize key findings on behavioral and neural activity reported from offspring dosed with Pitocin during vaginal delivery. Finally, we discuss future directions that are experimentally tractable for understanding the developmental consequences of Pitocin administration on a small but growing subset of children worldwide. Given that fetal past experiences can shape the future behavior of the adult, further work on oxytocin signaling pathways will provide valuable references and insights for early-brain development and state-dependent regulation of behavioral outcome.

Sparse Regularization-Based Approach for Point Cloud Denoising and Sharp Features Enhancement.

Denoising the point cloud is fundamental for reconstructing high quality surfaces with details in order to eliminate noise and outliers in the 3D scanning process. The challenges for a denoising algorithm are noise reduction and sharp features preservation. In this paper, we present a new model to reconstruct and smooth point clouds that combine L1-median filtering with sparse L1 regularization for both denoising the normal vectors and updating the position of the points to preserve sharp features in the point cloud. The L1-median filter is robust to outliers and noise compared to the mean. The L1 norm is a way to measure the sparsity of a solution, and applying an L1 optimization to the point cloud can measure the sparsity of sharp features, producing clean point set surfaces with sharp features. We optimize the L1 minimization problem by using the proximal gradient descent algorithm. Experimental results show that our approach is comparable to the state-of-the-art methods, as it filters out 3D models with a high level of noise, but keeps their geometric features.

The porcine biomodel in translational medical research: From biomodel to human lung transplantation / El biomodelo porcino en la investigación médica traslacional: del biomodelo al humano en trasplante pulmonar.

Introduction: Human and porcine anatomy are comparable. In consequence, the porcine biomodel has the potential to be implemented in the training of surgical professionals in areas such as solid organ transplantation. Objectives: We described the procedures and findings obtained in the experiments of translational respiratory medicine with the porcine biomodel, within an experimentation animal laboratory, and we present a comparative review between human and porcine lung. Materials and methods: The experiment was done in nine pigs of hybrid race within a laboratory of experimental surgery. The anatomy and histology of the respiratory tract were studied with fibrobronchoscopy, bronchial biopsy and bronchoalveolar lavage. The bronchoalveolar lavage was studied with liquid-based cytology and assessed with Papanicolau and hematoxylin-eosin staining. Molecular pathology techniques such as immunohistochemistry, flow cytometry, and electronic microscopy were implemented. The pigs were subjected to left pneumonectomy with posterior implantation of the graft into another experimental pig. Results: Histopathologic and molecular studies evidenced predominance of alveolar macrophages (98%) and T-lymphocytes (2%) in the porcine bronchoalveolar lavage. Studies on the porcine lung parenchyma revealed hyperplasic lymphoid tissue associated with the bronchial walls. Electronic microscopy evidenced the presence of T-lymphocytes within the epithelium and the cilia diameter was similar to the human. Conclusions: The porcine biomodel is a viable tool in translational research applied to the understanding of the respiratory system anatomy and the training in lung transplantation. The implementation of this experimental model has the potential to strength the groups who plan to implement an institutional program of lung transplantation in humans.

Introducción. La anatomía humana y porcina son comparables. En consecuencia, el biomodelo porcino tiene el potencial de ser implementado para entrenar al profesional quirúrgico en áreas como el trasplante de órganos sólidos. Objetivo. Describir los procedimientos y hallazgos obtenidos mediante experimentos de medicina respiratoria traslacional con biomodelos porcinos realizados en un laboratorio de experimentación animal, y hacer una revisión comparativa entre el pulmón humano y el porcino. Materiales y métodos. El experimento se llevó a cabo en nueve cerdos de raza híbrida en un laboratorio de cirugía experimental. Se estudiaron la anatomía y la histología de las vías respiratorias mediante fibrobroncoscopia, biopsia bronquial y lavado broncoalveolar. El lavado broncoalveolar se estudió con citología en base líquida y se evaluó con las coloraciones de Papanicolau y hematoxilina y eosina. Se utilizaron técnicas de patología molecular, como inmunohistoquímica, citometría de flujo y microscopía electrónica. Los cerdos se sometieron a neumonectomía izquierda con posterior implante del injerto en otro cerdo experimental. Resultados. Los estudios histopatológicos y moleculares evidenciaron un predominio de macrófagos alveolares (98 %) y linfocitos T (2 %) en el lavado broncoalveolar porcino. En los estudios del parénquima pulmonar porcino se encontró tejido linfoide hiperplásico asociado a las paredes bronquiales. La microscopía electrónica evidenció linfocitos T dentro del epitelio y el diámetro de las cilias porcinas fue similar al de las humanas. Conclusiones. El biomodelo porcino es viable en la investigación traslacional para el entendimiento de la anatomía del sistema respiratorio y el entrenamiento en trasplante pulmonar. La implementación de este modelo experimental podría fortalecer los grupos que planean implementar un programa institucional de trasplante pulmonar en humanos.

El biomodelo porcino en la investigación médica traslacional: del biomodelo al humano en trasplante pulmonar / The porcine biomodel in translational medical research: From biomodel to human lung transplantation

Resumen Introducción. La anatomía humana y porcina son comparables. En consecuencia, el biomodelo porcino tiene el potencial de ser implementado para entrenar al profesional quirúrgico en áreas como el trasplante de órganos sólidos. Objetivo. Describir los procedimientos y hallazgos obtenidos mediante experimentos de medicina respiratoria traslacional con biomodelos porcinos realizados en un laboratorio de experimentación animal, y hacer una revisión comparativa entre el pulmón humano y el porcino. Materiales y métodos. El experimento se llevó a cabo en nueve cerdos de raza híbrida en un laboratorio de cirugía experimental. Se estudiaron la anatomía y la histología de las vías respiratorias mediante fibrobroncoscopia, biopsia bronquial y lavado broncoalveolar. El lavado broncoalveolar se estudió con citología en base líquida y se evaluó con las coloraciones de Papanicolau y hematoxilina y eosina. Se utilizaron técnicas de patología molecular, como inmunohistoquímica, citometría de flujo y microscopía electrónica. Los cerdos se sometieron a neumonectomía izquierda con posterior implante del injerto en otro cerdo experimental. Resultados. Los estudios histopatológicos y moleculares evidenciaron un predominio de macrófagos alveolares (98 %) y linfocitos T (2 %) en el lavado broncoalveolar porcino. En los estudios del parénquima pulmonar porcino se encontró tejido linfoide hiperplásico asociado a las paredes bronquiales. La microscopía electrónica evidenció linfocitos T dentro del epitelio y el diámetro de las cilias porcinas fue similar al de las humanas. Conclusiones. El biomodelo porcino es viable en la investigación traslacional para el entendimiento de la anatomía del sistema respiratorio y el entrenamiento en trasplante pulmonar. La implementación de este modelo experimental podría fortalecer los grupos que planean implementar un programa institucional de trasplante pulmonar en humanos.

Abstract Introduction: Human and porcine anatomy are comparable. In consequence, the porcine biomodel has the potential to be implemented in the training of surgical professionals in areas such as solid organ transplantation. Objectives: We described the procedures and findings obtained in the experiments of translational respiratory medicine with the porcine biomodel, within an experimentation animal laboratory, and we present a comparative review between human and porcine lung. Materials and methods: The experiment was done in nine pigs of hybrid race within a laboratory of experimental surgery. The anatomy and histology of the respiratory tract were studied with fibrobronchoscopy, bronchial biopsy and bronchoalveolar lavage. The bronchoalveolar lavage was studied with liquid-based cytology and assessed with Papanicolau and hematoxylin-eosin staining. Molecular pathology techniques such as immunohistochemistry, flow cytometry, and electronic microscopy were implemented. The pigs were subjected to left pneumonectomy with posterior implantation of the graft into another experimental pig. Results: Histopathologic and molecular studies evidenced predominance of alveolar macrophages (98%) and T-lymphocytes (2%) in the porcine bronchoalveolar lavage. Studies on the porcine lung parenchyma revealed hyperplasic lymphoid tissue associated with the bronchial walls. Electronic microscopy evidenced the presence of T-lymphocytes within the epithelium and the cilia diameter was similar to the human. Conclusions: The porcine biomodel is a viable tool in translational research applied to the understanding of the respiratory system anatomy and the training in lung transplantation. The implementation of this experimental model has the potential to strength the groups who plan to implement an institutional program of lung transplantation in humans.

Clonal Dispersal of Cryptococcus gattii VGII in an Endemic Region of Cryptococcosis in Colombia.

This study characterized the genotype and phenotype of Cryptococcus gattii VGII isolates from Cucuta, an endemic region of cryptococcal disease in Colombia, and compared these traits with those from representative isolates from the Vancouver Island outbreak (VGIIa and VGIIb). Genetic diversity was assessed by multilocus sequence typing (MLST) analysis. Phenotypic characteristics, including growth capacity under different temperature and humidity conditions, macroscopic and microscopic morphology, phenotypic switching, mating type, and activity of extracellular enzymes were studied. Virulence was studied in vivo in a mouse model. MLST analysis showed that the isolates from Cucuta were highly clonal, with ST25 being the most common genotype. Phenotypically, isolates from Cucuta showed large cell and capsular sizes, and shared phenotypic traits and enzymatic activities among them. The mating type a prevailed among the isolates, which were fertile and of considerable virulence in the animal model. This study highlights the need for a continuous surveillance of C. gattii in Colombia, especially in endemic areas like Cucuta, where the highest number of cryptococcosis cases due to this species is reported. This will allow the early detection of potentially highly virulent strains that spread clonally, and can help prevent the occurrence of outbreaks in Colombia and elsewhere.

An Evolutionary Perspective of Neoplastic Diseases in the Universe.

The existence of exoplanets orbiting low mass-stars is one of the most significant discoveries of our time. Especially intriguing to us is the possibility that Earth-sized exoplanets within a habitable zone might harbor life-forms that resemble our own RNA/DNA-based species. We further narrow this theoretical possibility with the following question: if alien life does indeed exist elsewhere, would extraterrestrial life be burdened with earthly diseases? Given that the chemistry of the universe is subject to specific rules, restraints, and predictable outcomes, we argue that cancer-signaling pathways might be programmed into the life cycle of habitable exoplanets. This hypothetical prediction is also based on evolutionary convergence, the repeated emergence of biological similarity that occurs when disparate life-forms adapt to comparable selection pressures. The possibility that mutations and nucleotide base rearrangements that drive cancer growth might be fixed in the chemical hardware of alien life provides us with the opportunity to wonder and consider the origins, evolution, and ubiquity of disease beyond Earth.

Morphological Area Gradient: System-independent Dense Tissue Segmentation in Mammography Images.

Breast density has been identified as one of the strongest risk factors for breast cancer. However, the development of reliable and reproducible methods for the automatic dense tissue segmentation has been an important challenge. Due to the complexity of the acquisition process of mammography images, current approaches need to be calibrated for specific mammographic systems or require access to raw mammograms. In this work, we introduce the Morphological Area Gradient (MAG) as a generic measure for mammography images. MAG is generic in the sense that it does not need calibration or access to raw mammograms. At the core of MAG is the derivative of the area of segmented tissue with respect to the pixel intensity. We have found that the high-density regions can be automatically segmented by minimizing the MAG of a mammogram. To verify the performance of MAG, we collected 566 full-field digital mammograms using two different medical devices and a human expert manually annotated the high-density regions in each image. The proposed MAG method yields a median absolute error of 7.6% and a Dices similarity coefficient of 0.83, which are superior to other clinically validated state-of-the-art algorithms.

Central and Peripheral Expression of DNA Double-Strand Breaks in Human and Mouse Tissues.

Mammalian cells accumulate DNA lesions when they undergo phases of the cell cycle or during normal cellular activity. In this regard, several DNA repair signaling pathways have evolved to maintain genome stability and avoid the potential acquisition of mutations. To define and further characterize the expression of DNA double-strand breaks in humans and mice, we used immunocytochemistry to localize a DNA damage signal within the spatial confines of the cell nucleus. We show that DNA double-strand breaks are abundantly expressed in postmitotic neurons of the human and mouse brain. Notably, DNA double-strand breaks are present in human hypothalamic and mouse striatal and hippocampal cells, with stable expression of the nuclear signal detected throughout the mammalian brain. Analysis of the mouse tongue, heart, and testis shows that expression of DNA double-strand breaks is only demonstrated in circumscribed populations of peripheral cells. These data suggest that levels of DNA double-strand breaks are tissue-specific with the tongue, heart and testicular tissue having different thresholds of DNA repair and DNA damage from those outlined at the brain level. Anat Rec, 301:1251-1257, 2018. © 2018 Wiley Periodicals, Inc.

Ketamine intervention limits pathogen expansion in vitro.

Ketamine is one of several clinically important drugs whose therapeutic efficacy is due in part to their ability to act upon ion channels prevalent in nearly all biological systems. In studying eukaryotic and prokaryotic organisms in vitro, we show that ketamine short-circuits the growth and spatial expansion of three microorganisms, Stachybotrys chartarum, Staphylococcus epidermidis and Borrelia burgdorferi, at doses efficient at reducing depression-like behaviors in mouse models of clinical depression. Although our findings do not reveal the mechanism(s) by which ketamine mediates its antifungal and antibacterial effects, we hypothesize that a function of L-glutamate signal transduction is associated with the ability of ketamine to limit pathogen expansion. In general, our findings illustrate the functional similarities between fungal, bacterial and human ion channels, and suggest that ketamine or its metabolites not only act in neurons, as previously thought, but also in microbial communities colonizing human body surfaces.

Linking Brain Arteriovenous Malformations With Anorectal Hemorrhoids: A Clinical and Anatomical Review.

Patients who harbor brain arteriovenous malformations are at risk for intracranial hemorrhage. These malformations are often seen in inherited vascular diseases such as hereditary hemorrhagic telangiectasia. However, malformations within the brain also sporadically occur without a hereditary-coding component. Here, we review recent insights into the pathophysiology of arteriovenous malformations, in particular, certain signaling pathways that might underlie endothelial cell pathology. To better interpret the origins, determinants and consequences of brain arteriovenous malformations, we present a clinical case to illustrate the phenotypic landscape of the disease. We also propose that brain arteriovenous malformations might share certain signaling dimensions with those of anorectal hemorrhoids. This working hypothesis provides casual anchors from which to understand vascular diseases characterized by arteriovenous lesions with a hemorrhagic- or bleeding-risk component. Anat Rec, 2017. © The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists. Anat Rec, 300:1973-1980, 2017. © 2017 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.

A case report of spinal dural arteriovenous fistula: origins, determinants, and consequences of abnormal vascular malformations.

A spinal dural arteriovenous fistula is an abnormally layered connection between radicular arteries and venous plexus of the spinal cord. This vascular condition is relatively rare with an incidence of 5-10 cases per million in the general population. Diagnosis of spinal dural arteriovenous fistula is differentiated by contrast-enhanced magnetic resonance angiography or structural magnetic resonance imaging, but a definitive diagnosis requires spinal angiography methods. Here, we report a case of a 67-year-old female with a spinal dural arteriovenous fistula, provide a pertinent clinical history to the case nosology, and discuss the biology of adhesive proteins, chemotactic molecules, and transcription factors that modify the behavior of the vasculature to possibly cause sensorimotor deficits.