Hepatic hematoma following endoscopic retrograde cholangiopancreatography: overview and case report

Endoscopic retrograde cholangiopancreatography (ERCP) is a procedure with a high risk of complications. Hepatic subcapsular hematoma is an infrequent complication, with few cases reported in the international literature. Treatment can be conservative with the patient under close surveillance in an intensive care unit and surgical management is reserved for failure of conservative treatment and cases with hemodynamic instability. We present a case of subcapsular and intraparenchymal hepatic hematoma in an adult male who presented sudden hemodynamic instability, associated with hemoglobin decrease, which required surgical management. The challenge in the therapeutic decision due to sudden hemodynamic instability is clearly demonstrated; therefore, there was a need for surgical treatment as the best measure of hemorrhage control. Conservative management should be reserved for hemodynamically stable patients and invasive management by interventional radiology or surgery for cases of acute abdomen associated with hemodynamic instability

Pranlukast Antagonizes CD49f and Reduces Sternness in Triple-Negative Breast Cancer Cells

Introduction: Cancer stem cells (CSCs) drive the initiation, maintenance, and therapy response of breast tumors. CD49f is expressed in breast CSCs and functions in the maintenance of stemness. Thus, blockade of CD49f is a potential therapeutic approach for targeting breast CSCs. In the present study, we aimed to repurpose drugs as CD49f antagonists. Materials and Methods: We performed consensus molecular docking using a subdomain of CD49f that is critical for heterodimerization and a collection of pharmochemicals clini-cally tested. Molecular dynamics simulations were employed to further characterize drug-target binding. Using MDA-MB-231 cells, we evaluated the effects of potential CD49f antagonists on 1) cell adhesion to laminin; 2) mammosphere formation; and 3) cell viability. We analyzed the effects of the drug with better CSC-selectivity on the activation of CD49f-downstream signaling by Western blot (WB) and co-immunoprecipitation. Expressions of the stem cell markers CD44 and SOX2 were analyzed by flow cytometry and WB, respectively. Transactivation of SOX2 promoter was evaluated by luciferase reporter assays. Changes in the number of CSCs were assessed by limiting-dilution xenotransplantation. Results: Pranlukast, a drug used to treat asthma, bound to CD49f in silico and inhibited the adhesion of CD49f+ MDA-MB-231 cells to laminin, indicating that it antagonizes CD49f-containing integrins. Molecular dynamics analysis showed that pranlukast binding induces con-formational changes in CD49f that affect its interaction with β1-integrin subunit and constrained the conformational dynamics of the heterodimer. Pranlukast decreased the clonogenicity of breast cancer cells on mammosphere formation assay but had no impact on the viability of bulk tumor cells. Brief exposure of MDA-MB-231 cells to pranlukast altered CD49f-dependent signaling, reducing focal adhesion kinase (FAK) and phosphatidylinositol 3-kinase (PI3K) activation. Further, pranlukast-treated cells showed decreased CD44 and SOX2 expression, SOX2 promoter transacti-vation, and in vivo tumorigenicity, supporting that this drug reduces the frequency of CSC. Conclusion: Our results support the function of pranlukast as a CD49f antagonist that reduces the CSC population in triple-negative breast cancer cells. The pharmacokinetics and toxicology of this drug have already been established, rendering a potential adjuvant therapy for breast cancer patients

Phylogenetically Diverse Mesorhizobium Strains: Effect in the Root Colonization and Development of Tomato Seedlings.

Mesorhizobium contains species widely known as nitrogen-fixing bacteria with legumes, but their ability to promote the growth of non-legumes has been poorly studied. Here, we analyzed the production of indole acetic acid (IAA), siderophores and the solubilization of phosphate and potassium in a collection of 24 strains belonging to different Mesorhizobium species. All these strains produce IAA, 46% solubilized potassium, 33% solubilize phosphate and 17% produce siderophores. The highest production of IAA was found in the strains Mesorhizobium ciceri CCANP14 and Mesorhizobium tamadayense CCANP122, which were also able to solubilize potassium. Moreover, the strain CCANP14 showed the maximum phosphate solubilization index, and the strain CCANP122 was able to produce siderophores. These two strains were able to produce cellulases and cellulose and to originate biofilms in abiotic surfaces and tomato root surface. Tomato seedlings responded positively to the inoculation with these two strains, showing significantly higher plant growth traits than uninoculated seedlings. This is the first report about the potential of different Mesorhizobium species to promote the growth of a vegetable. Considering their use as safe for humans, animals and plants, they are an environmentally friendly alternative to chemical fertilizers for non-legume crops in the framework of sustainable agricultur

Papatrónica – dispositivo de código abierto para la medición de golpes y prevención de daños mecánicos

En Argentina, según datos de la Secretaría de Agroindustria, se pierden y desperdician anualmente 14,5 millones de toneladas de alimentos en las etapas de producción, almacenamiento, transporte y procesamiento, siendo la cadena frutihortícola la que presenta mayor proporción de pérdidas. Los daños mecánicos generados por golpes ocasionan una parte importante de estas pérdidas, directamente como consecuencia de la ruptura de células y tejidos, e indirectamente por generar lesiones que permiten el ingreso de patógenos que producen necrosis o pudriciones. El objetivo de este trabajo fue prototipar una plataforma abierta y modular de código abierto y bajo costo que permita determinar los puntos donde se producen golpes que puedan afectar los tubérculos de papa, pero también fácilmente adaptable a otros cultivos o productos, o a la medición de otras variables.Sociedad Argentina de Informática e Investigación Operativ

Estimation of coupling between oscillators from short time series via phase dynamics modeling: limitations and application to EEG data

We demonstrate in numerical experiments that estimators of strength and directionality of coupling between oscillators based on modeling of their phase dynamics [D.A. Smirnov and B.P. Bezruchko, Phys. Rev. E 68, 046209 (2003)] are widely applicable. Namely, although the expressions for the estimators and their confidence bands are derived for linear uncoupled oscillators under the influence of independent sources of Gaussian white noise, they turn out to allow reliable characterization of coupling from relatively short time series for different properties of noise, significant phase nonlinearity of the oscillators, and non-vanishing coupling between them. We apply the estimators to analyze a two-channel human intracranial epileptic electroencephalogram (EEG) recording with the purpose of epileptic focus localization.Comment: 22 pages, 7 figures, the paper is to be published in Chaos, 2005, vol.15, issue 2, see http://chaos.aip.org

Motor Decline in Clinically Presymptomatic Spinocerebellar Ataxia Type 2 Gene Carriers

BACKGROUND: Motor deficits are a critical component of the clinical characteristics of patients with spinocerebellar ataxia type 2. However, there is no current information on the preclinical manifestation of those motor deficits in presymptomatic gene carriers. To further understand and characterize the onset of the clinical manifestation in this disease, we tested presymptomatic spinocerebellar ataxia type 2 gene carriers, and volunteers, in a task that evaluates their motor performance and their motor learning capabilities. METHODS AND FINDINGS: 28 presymptomatic spinocerebellar ataxia type 2 gene carriers and an equal number of control volunteers matched for age and gender participated in the study. Both groups were tested in a prism adaptation task known to be sensible to both motor performance and visuomotor learning deficits. Our results clearly show that although motor learning capabilities are intact, motor performance deficits are present even years before the clinical manifestation of the disease start. CONCLUSIONS: The results show a clear deficit in motor performance that can be detected years before the clinical onset of the disease. This motor performance deficit appears before any motor learning or clinical manifestations of the disease. These observations identify the performance coefficient as an objective and quantitative physiological biomarker that could be useful to assess the efficiency of different therapeutic agents

Mechanisms explaining transitions between tonic and phasic firing in neuronal populations as predicted by a low dimensional firing rate model

Several firing patterns experimentally observed in neural populations have been successfully correlated to animal behavior. Population bursting, hereby regarded as a period of high firing rate followed by a period of quiescence, is typically observed in groups of neurons during behavior. Biophysical membrane-potential models of single cell bursting involve at least three equations. Extending such models to study the collective behavior of neural populations involves thousands of equations and can be very expensive computationally. For this reason, low dimensional population models that capture biophysical aspects of networks are needed. \noindent The present paper uses a firing-rate model to study mechanisms that trigger and stop transitions between tonic and phasic population firing. These mechanisms are captured through a two-dimensional system, which can potentially be extended to include interactions between different areas of the nervous system with a small number of equations. The typical behavior of midbrain dopaminergic neurons in the rodent is used as an example to illustrate and interpret our results. \noindent The model presented here can be used as a building block to study interactions between networks of neurons. This theoretical approach may help contextualize and understand the factors involved in regulating burst firing in populations and how it may modulate distinct aspects of behavior.Comment: 25 pages (including references and appendices); 12 figures uploaded as separate file

Re-thinking the Etiological Framework of Neurodegeneration

Neurodegenerative diseases are among the leading causes of disability and death worldwide. The disease-related socioeconomic burden is expected to increase with the steadily increasing life expectancy. In spite of decades of clinical and basic research, most strategies designed to manage degenerative brain diseases are palliative. This is not surprising as neurodegeneration progresses "silently" for decades before symptoms are noticed. Importantly, conceptual models with heuristic value used to study neurodegeneration have been constructed retrospectively, based on signs and symptoms already present in affected patients;a circumstance that may confound causes and consequences. Hence, innovative, paradigm-shifting views of the etiology of these diseases are necessary to enable their timely prevention and treatment. Here, we outline four alternative views, not mutually exclusive, on different etiological paths toward neurodegeneration. First, we propose neurodegeneration as being a secondary outcome of a primary cardiovascular cause with vascular pathology disrupting the vital homeostatic interactions between the vasculature and the brain, resulting in cognitive impairment, dementia, and cerebrovascular events such as stroke. Second, we suggest that the persistence of senescent cells in neuronal circuits may favor, together with systemic metabolic diseases, neurodegeneration to occur. Third, we argue that neurodegeneration may start in response to altered body and brain trophic interactions established via the hardwire that connects peripheral targets with central neuronal structures or by means of extracellular vesicle (E\-mediated communication. Lastly, we elaborate on how lifespan body dysbiosis may be linked to the origin of neurodegeneration. We highlight the existence of bacterial products that modulate the gut-brain axis causing neuroinflammation and neuronal dysfunction. As a concluding section, we end by recommending research avenues to investigate these etiological paths in the future. We think that this requires an integrated, interdisciplinary conceptual research approach based on the investigation of the multimodal aspects of physiology and pathophysiology. It involves utilizing proper conceptual models, experimental animal units, and identifying currently unused opportunities derived from human data. Overall, the proposed etiological paths and experimental recommendations will be important guidelines for future cross-discipline research to overcome the translational roadblock and to develop causative treatments for neurodegenerative diseases

The 2HWC HAWC Observatory Gamma Ray Catalog

We present the first catalog of TeV gamma-ray sources realized with the recently completed High Altitude Water Cherenkov Observatory (HAWC). It is the most sensitive wide field-of-view TeV telescope currently in operation, with a 1-year survey sensitivity of ~5-10% of the flux of the Crab Nebula. With an instantaneous field of view >1.5 sr and >90% duty cycle, it continuously surveys and monitors the sky for gamma ray energies between hundreds GeV and tens of TeV. HAWC is located in Mexico at a latitude of 19 degree North and was completed in March 2015. Here, we present the 2HWC catalog, which is the result of the first source search realized with the complete HAWC detector. Realized with 507 days of data and represents the most sensitive TeV survey to date for such a large fraction of the sky. A total of 39 sources were detected, with an expected contamination of 0.5 due to background fluctuation. Out of these sources, 16 are more than one degree away from any previously reported TeV source. The source list, including the position measurement, spectrum measurement, and uncertainties, is reported. Seven of the detected sources may be associated with pulsar wind nebulae, two with supernova remnants, two with blazars, and the remaining 23 have no firm identification yet.Comment: Submitted 2017/02/09 to the Astrophysical Journa

The Sensitivity of HAWC to High-Mass Dark Matter Annihilations

The High Altitude Water Cherenkov (HAWC) observatory is a wide field-of-view detector sensitive to gamma rays of 100 GeV to a few hundred TeV. Located in central Mexico at 19 degrees North latitude and 4100 m above sea level, HAWC will observe gamma rays and cosmic rays with an array of water Cherenkov detectors. The full HAWC array is scheduled to be operational in Spring 2015. In this paper, we study the HAWC sensitivity to the gamma-ray signatures of high-mass (multi- TeV) dark matter annihilation. The HAWC observatory will be sensitive to diverse searches for dark matter annihilation, including annihilation from extended dark matter sources, the diffuse gamma-ray emission from dark matter annihilation, and gamma-ray emission from non-luminous dark matter subhalos. Here we consider the HAWC sensitivity to a subset of these sources, including dwarf galaxies, the M31 galaxy, the Virgo cluster, and the Galactic center. We simulate the HAWC response to gamma rays from these sources in several well-motivated dark matter annihilation channels. If no gamma-ray excess is observed, we show the limits HAWC can place on the dark matter cross-section from these sources. In particular, in the case of dark matter annihilation into gauge bosons, HAWC will be able to detect a narrow range of dark matter masses to cross-sections below thermal. HAWC should also be sensitive to non-thermal cross-sections for masses up to nearly 1000 TeV. The constraints placed by HAWC on the dark matter cross-section from known sources should be competitive with current limits in the mass range where HAWC has similar sensitivity. HAWC can additionally explore higher dark matter masses than are currently constrained.Comment: 15 pages, 4 figures, version to be published in PR