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.

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.

[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.

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.

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.

Neurodevelopmental Malformations of the Cerebellar Vermis in Genetically Engineered Rats.

The cerebellar vermis is particularly vulnerable to neurodevelopmental malformations in humans and rodents. Sprague-Dawley, and Long-Evans rats exhibit spontaneous cerebellar malformations consisting of heterotopic neurons and glia in the molecular layer of the vermis. Malformations are almost exclusively found along the primary fissure and are indicative of deficits of neuronal migration during cerebellar development. In the present report, we test the prediction that genetically engineered rats on Sprague-Dawley or Long-Evans backgrounds will also exhibit the same cerebellar malformations. Consistent with our hypothesis, we found that three different transgenic lines on two different backgrounds had cerebellar malformations. Heterotopia in transgenic rats had identical cytoarchitecture as that observed in wild-type rats including altered morphology of Bergmann glia. In light of the possibility that heterotopia could affect results from behavioral studies, these data suggest that histological analyses be performed in studies of cerebellar function or development when using genetically engineered rats on these backgrounds in order to have more careful interpretation of experimental findings.

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.

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.

A behavioral and molecular analysis of ketamine in zebrafish.

Ketamine exerts powerful anesthetic, psychotic, and antidepressant effects in both healthy volunteers and clinically depressed patients. Although ketamine targets particular glutamate receptors, there is a dearth of evidence for additional, alternative molecular substrates for the behavioral actions of this N-methyl-D-aspartate (NMDA) receptor antagonist drug. Here, we provide behavioral and molecular evidence for the actions of ketamine using a new vertebrate model for psychiatric disorders: the zebrafish. Subanesthetic doses of ketamine produced a variety of abnormal behaviors in zebrafish that were qualitatively analogous to those previously measured in humans and rodents treated with drugs that produce transient psychosis. In addition, we revealed that the transcription factor Phox2b is a molecular substrate for the actions of ketamine, particularly during periods of hypoxic stress. Finally, we also show that SIRT1, a histone deacetylase widely recognized for its link to cell survival is also affected by hypoxia crises. These results establish a relevant assay system in which the effects of psychotomimetic drugs can rapidly be assessed, and provide a plausible and novel neuronal mechanism through which ketamine affects critical sensory circuits that monitor breathing behavior.

Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury.

Mesenchymal stem cells (MSCs) have been exploited as cellular vectors to treat a wide array of diseases but the mechanisms responsible for their therapeutic effect remain indeterminate. Previously, we reported that MSCs inhibit bleomycin (BLM)-induced inflammation and fibrosis within the lungs of mice. Interrogation of the MSC transcriptome identified interleukin 1 receptor antagonist (IL1RN) as a potential mediator of this effect. Fractionation studies indicated that MSCs are the principal source of IL1RN in murine bone marrow and that its expression is restricted to a unique subpopulation of cells. Moreover, MSC-conditioned media was shown to block proliferation of an IL-1alpha-dependent T cell line and inhibit production of TNF-alpha by activated macrophages in vitro. Studies conducted in mice revealed that MSC administration was more effective than recombinant IL1RN delivered via adenoviral infection or osmotic pumps in inhibiting BLM-induced increases in TNF-alpha, IL-1alpha, and IL1RN mRNA in lung, IL1RN protein in bronchoalveolar lavage (BAL) fluid, and trafficking of lymphocytes and neutrophils into the lung. Therefore, MSCs protect lung tissue from BLM-induced injury by blocking TNF-alpha and IL-1, two fundamental proinflammatory cytokines in lung. Identification of IL1RN-expressing human MSC subpopulations may provide a novel cellular vector for treating chronic inflammatory diseases in humans.

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.

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.

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.

A ChIP-cloning approach linking SIRT1 to transcriptional modificationof DNA targets.

The mammalian protein deacetylase SIRT1 (sirtuin1) is widely recognized for its link to calorie restriction and longevity. SIRT1 not only modulates the function of protein targets such as p53 or NFkappaB, but it also affects gene transcription by causing hypoacetylation of associated nucleosomal histones. However, the identification of SIRT1-specific DNA targets that confer chromosomal stability and cell longevity have remained elusive. Here, we report the usefulness of a ChIP-cloning approach for the identification of an endogenous DNA target intimately linked with SIRT1 activity. Using the aforementioned technique, we identified a gene encoding the neuro-oncological ventral antigen2 (nova2) as a SIRT1 target. Nova2 regulates the alternative splicing of scn1a, which encodes the alpha-subunit of a neuronal sodium channel targeted by antiepileptic drugs. This finding demonstrates that ChIP-cloning is an innovative approach for the identification of SIRT1-specific DNA targets.

Magnetic resonance imaging and spectroscopy in a mouse model of schizophrenia.

Metabolic brain abnormalities, as demonstrated by (1)H-magnetic resonance spectroscopy, are common occurrences in adult schizophrenia. As mice share important biochemical and genomic similarities with humans, we tested whether brain metabolic abnormalities also occur in a transgenic mouse model of schizophrenia. In vivo(1)H-magnetic resonance spectroscopy at 4.7T of the chakragati mouse brain revealed abnormalities in relative levels of choline and N-acetylaspartate compounds. These results are consistent with a prior proposal that deficits in metabolite ratios may be common features of psychotic disorders. Thus, chakragati mice recapitulate certain aspects of the human disease phenotype and further support the utility of this animal model for understanding causal factors underlying uniquely human brain diseases.

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.