Clay Tailings Flocculated in Seawater and Industrial Water: Analysis of Aggregates, Sedimentation, and Supernatant Quality.

High-molecular-weight anionic polyacrylamide was used to analyze the effect of kaolin on the structure of particle aggregates formed in freshwater and seawater. Batch flocculation experiments were performed to determine the size of the flocculated aggregates over time by using focused beam reflectance measurements. Sedimentation tests were performed to analyze the settling rate of the solid-liquid interface and the turbidity of the supernatant. Subsequently, a model that relates the hindered settling rate to the aggregate size was used to determine the mass fractal dimension (Df). Flocculation kinetics revealed that greater amounts of kaolin generated larger aggregates because of its lamellar morphology. The maximum size was between 10 and 20 s of flocculation under all conditions. However, the presence of kaolin reduced the settling rate. The fractal dimension decreased with the increase in the kaolin content, resulting in the formation of irregular and porous aggregates. By contrast, factors such as the flocculation time, water quality, and quartz size had limited influences on the fractal dimension. Seawater produced a clearer supernatant because of its higher ionic strength and precoagulation of particles. Notably, the harmful effect of clays in seawater was reduced.

Molecular mechanisms of ischemia and glutamate excitotoxicity.

Excitotoxicity is classically defined as the neuronal damage caused by the excessive release of glutamate, and subsequent activation of excitatory plasma membrane receptors. In the mammalian brain, this phenomenon is mainly driven by excessive activation of glutamate receptors (GRs). Excitotoxicity is common to several chronic disorders of the Central Nervous System (CNS) and is considered the primary mechanism of neuronal loss of function and cell death in acute CNS diseases (e.g. ischemic stroke). Multiple mechanisms and pathways lead to excitotoxic cell damage including pro-death signaling cascade events downstream of glutamate receptors, calcium (Ca2+) overload, oxidative stress, mitochondrial impairment, excessive glutamate in the synaptic cleft as well as altered energy metabolism. Here, we review the current knowledge on the molecular mechanisms that underlie excitotoxicity, emphasizing the role of Nicotinamide Adenine Dinucleotide (NAD) metabolism. We also discuss novel and promising therapeutic strategies to treat excitotoxicity, highlighting recent clinical trials. Finally, we will shed light on the ongoing search for stroke biomarkers, an exciting and promising field of research, which may improve stroke diagnosis, prognosis and allow better treatment options.

Bioleaching Modeling-A Review.

The leaching of minerals is one of the main unit operations in the metal dissolution process, and in turn it is a process that generates fewer environmental liabilities compared to pyrometallurgical processes. As an alternative to conventional leaching methods, the use of microorganisms in mineral treatment processes has become widespread in recent decades, due to advantages such as the non-production of emissions or pollution, energy savings, low process costs, products compatible with the environment, and increases in the benefit of low-grade mining deposits. The purpose of this work is to introduce the theoretical foundations associated with modeling the process of bioleaching, mainly the modeling of mineral recovery rates. The different models are collected from models based on conventional leaching dynamics modeling, based on the shrinking core model, where the oxidation process is controlled by diffusion, chemically, or by film diffusion until bioleaching models based on statistical analysis are presented, such as the surface response methodology or the application of machine learning algorithms. Although bioleaching modeling (independent of modeling techniques) of industrial (or large-scale mined) minerals is a fairly developed area, bioleaching modeling applied to rare earth elements is a field with great growth potential in the coming years, as in general bioleaching has the potential to be a more sustainable and environmentally friendly mining method than traditional mining methods.

Experimental and Simulation Studies on Hematite Interaction with Na-Metasilicate Pentahydrate.

Iron ore is a fundamental pillar in construction globally, however, its process is highly polluting and deposits are becoming less concentrated, making reusing or reprocessing its sources a sustainable solution to the current industry. A rheological analysis was performed to understand the effect of sodium metasilicate on the flow curves of concentrated pulps. The study was carried out in an Anton Paar MCR 102 rheometer, showing that, in a wide range of dosages, the reagent can reduce the yield stress of the slurries, which would result in lower energy costs for transporting the pulps by pumping. To understand the behavior observed experimentally, computational simulation has been used by means of quantum calculations to represent the metasilicate molecule and the molecular dynamics to study the adsorption of metasilicate on the hematite surface. It has been possible to obtain that the adsorption is stable on the surface of hematite, where increasing the concentration of metasilicate increases its adsorption on the surface. The adsorption could be modeled by the Slips model where there is a delay in adsorption at low concentrations and then a saturated value is reached. It was found that metasilicate requires the presence of sodium ions to be adsorbed on the surface by means of a cation bridge-type interaction. It is also possible to identify that it is absorbed by means of hydrogen bridges, but to a lesser extent than the cation bridge. Finally, it is observed that the presence of metasilicate adsorbed on the surface modifies the net surface charge, increasing it and, thus, generating the effect of dispersion of hematite particles which experimentally is observed as a decrease in rheology.

Changes in Brain-Derived Neurotrophic Factor by different kind of military training / Cambios en el Factor Neurotrófico Derivado del Cerebro por diferentes tipos de entrenamiento militar

Abstract Background: Brain Derived Neurotrophic Factor (BDNF) serum levels change with age, physical exercise, and neuropsychiatric disorders such as dementia, depression, anxiety, schizophrenia, and bipolar disorder. Military personnel are physically and mental training with an increased risk of developing mental disorders. Objective: The main objective of this study was determinate the BDNF serum levels in four military samples. 132 participants, administrative personnel (control) and three different Special Operations Forces (SOF) groups participated in the study. Methods: A first group of SOFS was on a training course (SOF-TC), second group exposed to 48 hours of operational stress (SOF-48hS) and third group exposed to two-weeks of operational stress (SOF-2wS). The mini interview was conducted and CAPS, and BNF levels were determined by ELISA assays. Results: Differences in age, were evaluated by ANOVA post-hoc Tukey´s. Differences in BNDF levels are evaluated by the Kruskal-Wallis test post hoc Dunn's. Spearman's correlation was used to analyze the relationship between BDNF and age. The SOF-TC had a BDNF elevation in comparison with Control group that could be related to age differences or the physical and mental training.SOF-2wS had decreased BDNF levels in comparison to the other groups that could be related to the psychosocial stress or other mental disorders such as PTSD. That group, 2 participants showed signs of PTSD. Conclusion: BDNF levels are an accurate method for the evaluation of mental health to prevent, diagnose & treat mental disorders in military personnel exposed to operational stress.

Resumen Introducción: Los niveles séricos del factor neurotrófico derivado del cerebro (BDNF) cambian con la edad, el ejercicio físico y los trastornos neuropsiquiátricos como la demencia, la depresión, la ansiedad, la esquizofrenia y el trastorno bipolar. El personal militar está en formación física y mental con un mayor riesgo de desarrollar trastornos mentales. Objetivo: El objetivo principal de este estudio fue determinar los niveles séricos de BDNF en cuatro muestras militares. Participaron en el estudio 132 individuos entre personal administrativo (control) y tres grupos diferentes de Fuerzas de Operaciones Especiales (SOF). Métodos: Un primer grupo de SOFS estaba en un curso de capacitación (SOF-TC), el segundo grupo expuesto a 48 horas de estrés operativo (SOF-48hS) y el tercer grupo expuesto a dos semanas de estrés operativo (SOF-2wS). Se realizó la minientrevista y se determinaron los niveles de CAPS y BNF mediante ensayos ELISA. Resultados: Las diferencias en edad, se evaluaron mediante ANOVA post hoc de Tukey. Las diferencias en los niveles de BNDF se evalúan mediante la prueba de Dunn post hoc de Kruskal-Wallis. Se utilizó la correlación de Spearman para analizar la relación entre BDNF y la edad. El SOF-TC tuvo una elevación de BDNF en comparación con el grupo control que podría estar relacionado con las diferencias de edad o el entrenamiento físico y mental, tal como PTSD. En ese grupo, dos participantes mostraron signos de PTSD. Conclusión: Los niveles de BDNF son un método preciso para la evaluación de la salud mental para prevenir, diagnosticar y tratar los trastornos mentales en el personal militar expuesto al estrés operativo.

Burnout Syndrome in a Military Tertiary Hospital Staff during the COVID-19 Contingency.

(1) Background: Burnout syndrome (BOS) is defined as a psychological state of physical and mental fatigue associated with work. The COVID-19 pandemic greatly impacted the physical and mental wellbeing of health professionals. The objective of this work was to determine the impact on personnel, monitoring the frequency of BOS throughout the pandemic. (2) Methods: The Maslach Burnout Inventory (MBI) was self-applied in four periods of the pandemic according to sociodemographic and employment characteristics. In this study, all hospital personnel were included; the association of BOS with sex, age, type of participant (civilian or military), military rank and profession was analyzed. (3) Results: The frequency of BOS was 2.4% (start of the pandemic), 7.9% (peak of the first wave), 3.7% (end of the first wave) and 3.6% (peak of the third wave). Emotional exhaustion (EE) was the most affected factor, and the groups most affected were men under 30 years of age, civilians, chiefs and doctors, especially undergraduate medical doctors and specialty resident doctors, and nursing personnel were less affected. (4) Conclusions: The low BOS levels show that the containment measures and military training implemented by the hospital authorities were effective, although the chief personnel were more affected in the first wave. It is probable that this combination allowed the containment of BOS, which was not observed in civilians.

Posttranslational modifications of proteins are key features in the identification of CSF biomarkers of multiple sclerosis.

BACKGROUND: Multiple sclerosis is an inflammatory and degenerative disease of the central nervous system (CNS) characterized by demyelination and concomitant axonal loss. The lack of a single specific test, and the similarity to other inflammatory diseases of the central nervous system, makes it difficult to have a clear diagnosis of multiple sclerosis. Therefore, laboratory tests that allows a clear and definite diagnosis, as well as to predict the different clinical courses of the disease are of utmost importance. Herein, we compared the cerebrospinal fluid (CSF) proteome of patients with multiple sclerosis (in the relapse-remitting phase of the disease) and other diseases of the CNS (inflammatory and non-inflammatory) aiming at identifying reliable biomarkers of multiple sclerosis. METHODS: CSF samples from the discovery group were resolved by 2D-gel electrophoresis followed by identification of the protein spots by mass spectrometry. The results were analyzed using univariate (Student's t test) and multivariate (Hierarchical Cluster Analysis, Principal Component Analysis, Linear Discriminant Analysis) statistical and numerical techniques, to identify a set of protein spots that were differentially expressed in CSF samples from patients with multiple sclerosis when compared with other two groups. Validation of the results was performed in samples from a different set of patients using quantitative (e.g., ELISA) and semi-quantitative (e.g., Western Blot) experimental approaches. RESULTS: Analysis of the 2D-gels showed 13 protein spots that were differentially expressed in the three groups of patients: Alpha-1-antichymotrypsin, Prostaglandin-H2-isomerase, Retinol binding protein 4, Transthyretin (TTR), Apolipoprotein E, Gelsolin, Angiotensinogen, Agrin, Serum albumin, Myosin-15, Apolipoprotein B-100 and EF-hand calcium-binding domain-containing protein. ELISA experiments allowed validating part of the results obtained in the proteomics analysis and showed that some of the alterations in the CSF proteome are also mirrored in serum samples from multiple sclerosis patients. CSF of multiple sclerosis patients was characterized by TTR oligomerization, thus highlighting the importance of analyzing posttranslational modifications of the proteome in the identification of novel biomarkers of the disease. CONCLUSIONS: The model built based on the results obtained upon analysis of the 2D-gels and in the validation phase attained an accuracy of about 80% in distinguishing multiple sclerosis patients and the other two groups.

Intranasal dexamethasone: a new clinical trial for the control of inflammation and neuroinflammation in COVID-19 patients.

BACKGROUND: By end December of 2021, COVID-19 has infected around 276 million individuals and caused over 5 million deaths worldwide. Infection results in dysregulated systemic inflammation, multi-organ dysfunction, and critical illness. Cells of the central nervous system are also affected, triggering an uncontrolled neuroinflammatory response. Low doses of glucocorticoids, administered orally or intravenously, reduce mortality among moderate and severe COVID-19 patients. However, low doses administered by these routes do not reach therapeutic levels in the CNS. In contrast, intranasally administered dexamethasone can result in therapeutic doses in the CNS even at low doses. METHODS: This is an approved open-label, multicenter, randomized controlled trial to compare the effectiveness of intranasal versus intravenous dexamethasone administered in low doses to moderate and severe COVID-19 adult patients. The protocol is conducted in five health institutions in Mexico City. A total of 120 patients will be randomized into two groups (intravenous vs. intranasal) at a 1:1 ratio. Both groups will be treated with the corresponding dexamethasone scheme for 10 days. The primary outcome of the study will be clinical improvement, defined as a statistically significant reduction in the NEWS-2 score of patients with intranasal versus intravenous dexamethasone administration. The secondary outcome will be the reduction in mortality during hospitalization. CONCLUSIONS: This protocol is currently in progress to improve the efficacy of the standard therapeutic dexamethasone regimen for moderate and severe COVID-19 patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04513184 . Registered November 12, 2020. Approved by La Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS) with identification number DI/20/407/04/36. People are currently being recruited.

Reducing Magnesium within Seawater Used in Mineral Processing to Improve Water Recovery and Rheological Properties When Dewatering Clay-Based Tailings.

In areas where access to water for mineral processing is limited, the direct use of seawater in processing has been considered as an alternative to the expense of its desalination. However, efficient flotation of copper sulfides from non-valuable phases is best achieved at a pH > 10.5, and raising the pH of seawater leads to magnesium precipitates that adversely affect subsequent tailings dewatering. Seawater pre-treatment with lime can precipitate the majority of magnesium present, with these solids then being removed by filtration. To understand how such treatment may aid tailings dewatering, treated seawater (TSw) was mixed with raw seawater (Rsw) at different ratios, analyzing the impact on the flocculated settling rate, aggregate size as measured by focused beam reflectance measurement (FBRM), and vane yield stress for two synthetic clay-based tailings. A higher proportion of Tsw (10 mg/L Mg2+) led to larger aggregates and higher settling rates at a fixed dosage, with FBRM suggesting that higher calcium concentrations in Tsw may also favor fines coagulation. The yield stress of concentrated suspensions formed after flocculation decreased with higher proportions of Tsw, a consequence of lower flocculant demand and the reduced presence of precipitates; while the latter is a minor phase by mass, their high impact on rheology reflects a small particle size. Reducing magnesium concentrations in seawater in advance of use in processing offers advantages in the water return from thickening and subsequent underflow transport. However, this may not require complete removal, with blending Tsw and Rsw an option to obtain acceptable industrial performance.

Lime/Sodium Carbonate Treated Seawater to Improve Flocculation and Sedimentation of Clay-Based Tailings.

Seawater treated with lime and sodium carbonate in different proportions to reduce magnesium and calcium contents is used in flocculation and sedimentation tests of artificial quartz and kaolin tailings. Solid complexes were separated from water by vacuum filtration, and factors such as lime/sodium carbonate ratio, kaolin content, flocculation time, and flocculant dose are evaluated. The growth of the aggregates was captured in situ by a focused beam reflectance measurement (FBRM) probe. Solid magnesium and calcium complexes are formed in raw seawater at pH 11, impairing the performance of flocculant polymers based on polyacrylamides. The results show that the settling rate improved when the treatment's lime/sodium carbonate ratio increased. That is, when a greater removal of magnesium is prioritized over calcium. The amount of magnesium required to be removed depends on the mineralogy of the system: more clay will require more significant removal of magnesium. These results respond to the structural changes of the flocs, achieving that the more magnesium is removed, the greater the size and density of the aggregates. In contrast, calcium removal does not significantly influence flocculant performance. The study suggests the necessary conditions for each type of tailing to maximize water recovery, contributing to the effective closure of the water cycle in processes that use seawater with magnesium control.

Epidemiology of hospitalized patients with COVID-19 in a tertiary care hospital.

INTRODUCTION: COVID-19, caused by the betacoronavirus SARS-CoV-2, has overwhelmed the world's health systems. OBJECTIVE: To describe the epidemiological characteristics of patients treated in a tertiary care hospital. METHODS: A retrospective cohort study of patients diagnosed with or suspected of having COVID-19 from March 23 to July 31, 2020 was conducted. RESULTS: 4,401 patients were hospitalized at Central Military Hospital, out of which 35 % were beneficiaries, 26 % civilians, 28 % active military personnel, and only 11 %, retired military personnel. Male gender predominated, both in hospitalized patients and in those who died, as well as the O+ group and absence of comorbidities; among the observed comorbidities, the main ones were overweight and diabetes. Hospitalized patients' median age was 49 years, while median age of those who died was 62 years; women older than 51 years had a higher risk of dying. Adjusted case fatality rate was 18.5 %; 50 % died within the first six days. CONCLUSIONS: In this study, the epidemiological characteristics and main comorbidities in Mexican patients with SARS-CoV-2 infection were identified.

INTRODUCCIÓN: COVID-19, causada por el betacoronavirus SARS-CoV-2, ha saturado los sistemas de salud del mundo. OBJETIVO: Describir las características epidemiológicas de los pacientes atendidos en un hospital de tercer nivel. MÉTODOS: Se realizó una cohorte retrospectiva de pacientes con diagnóstico o sospecha de COVID-19, del 23 de marzo al 31 de julio de 2020. RESULTADOS: En el Hospital Central Militar se hospitalizaron 4401 pacientes, 35 % derechohabientes, 26 % civiles, 28 % militares en activo y solo 11 %, militares retirados. Predominó el sexo masculino, tanto en los pacientes hospitalizados como en los que fallecieron, el grupo O+ y la ausencia de comorbilidades; entre las comorbilidades que se observaron, las principales fueron el sobrepeso y la diabetes. La mediana de edad de los pacientes hospitalizados fue de 49 años, mientras que 62 años fue la edad de quienes fallecieron; las mujeres mayores de 51 años tuvieron mayor riesgo de fallecer. La tasa de letalidad ajustada fue de 18.5 %; 50 % falleció durante los primeros seis días. CONCLUSIONES: En este estudio se lograron identificar las características epidemiológicas y se destacaron las principales comorbilidades en pacientes mexicanos con infección por SARS-CoV-2.

Molecular Dynamics Study of the Conformation, Ion Adsorption, Diffusion, and Water Structure of Soluble Polymers in Saline Solutions.

Polymers have interesting physicochemical characteristics such as charge density, functionalities, and molecular weight. Such attributes are of great importance for use in industrial purposes. Understanding how these characteristics are affected is still complex, but with the help of molecular dynamics (MD) and quantum calculations (QM), it is possible to understand the behavior of polymers at the molecular level with great consistency. This study was applied to polymers derived from polyacrylamide (PAM) due to its great use in various industries. The polymers studied include hydrolyzed polyacrylamide (HPAM), poly (2-acrylamido-2-methylpropanesulfonate) (PAMPS), polyacrylic acid (PAA), polyethylene oxide polymer (PEO), and guar gum polysaccharide (GUAR). Each one has different attributes, which help in understanding the effects on the polymer and the medium in which it is applied along a broad spectrum. The results include the conformation, diffusion, ion condensation, the structure of the water around the polymer, and interatomic polymer interactions. Such characteristics are important to selecting a polymer depending on the environment in which it is found and its purpose. The effect caused by salinity is particular to each polymer, where polymers with an explicit charge or polyelectrolytes are more susceptible to changes due to salinity, increasing their coiling and reducing their mobility in solution. This naturally reduces its ability to form polymeric bridges due to having a polymer with a smaller gyration radius. In contrast, neutral polymers are less affected in their structure, making them favorable in media with high ionic charges.

GRASP1 ubiquitination regulates AMPA receptor surface expression and synaptic activity in cultured hippocampal neurons.

The synaptic expression of glutamate receptors of the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) type is dynamically controlled by interaction with binding partners and auxiliary proteins. These proteins can be regulated by posttranslational modifications, including ubiquitination. In this work, we investigated the regulation of glutamate receptor interacting protein-associated protein 1 (GRASP1) by ubiquitin-dependent mechanisms and its impact on surface expression and activity of synaptic AMPA receptors. Cotransfection of GFP-ubiquitin decreased myc-GRASP1 protein levels in HEK293T cells, and this effect was inhibited upon transfection of an ubiquitin mutant that cannot be ubiquitinated on Lys48. In addition, transfection of cultured hippocampal neurons with GFP-ubiquitin reduced the dendritic levels of endogenous GRASP1 and decreased the surface expression of GluA1 AMPA receptor subunits, an effect that was partly reversed by cotransfection with GRASP1. Similarly, transfection of hippocampal neurons with GFP-ubiquitin decreased the amplitude of miniature excitatory postsynaptic currents (mEPSCs) mediated by Ca2+ -impermeable AMPA receptors, and this effect was abrogated by cotransfection of GRASP1. Together, the results show a role for ubiquitination in the regulation of the postsynaptic protein GRASP1, which has an impact on the surface distribution of AMPA receptors and on their activity at the synapse.

Epidemiología de los pacientes hospitalizados con COVID-19 en un hospital de tercer nivel / Epidemiology of hospitalized patients with COVID-19 in a tertiary care hospital

Resumen Introducción: COVID-19, causada por el betacoronavirus SARS-CoV-2, ha saturado los sistemas de salud del mundo. Objetivo: Describir las características epidemiológicas de los pacientes atendidos en un hospital de tercer nivel. Métodos: Se realizó una cohorte retrospectiva de pacientes con diagnóstico o sospecha de COVID-19, del 23 de marzo al 31 de julio de 2020. Resultados: En el Hospital Central Militar se hospitalizaron 4401 pacientes, 35 % derechohabientes, 26 % civiles, 28 % militares en activo y solo 11 %, militares retirados. Predominó el sexo masculino, tanto en los pacientes hospitalizados como en los que fallecieron, el grupo O+ y la ausencia de comorbilidades; entre las comorbilidades que se observaron, las principales fueron el sobrepeso y la diabetes. La mediana de edad de los pacientes hospitalizados fue de 49 años, mientras que 62 años fue la edad de quienes fallecieron; las mujeres mayores de 51 años tuvieron mayor riesgo de fallecer. La tasa de letalidad ajustada fue de 18.5 %; 50 % falleció durante los primeros seis días. Conclusiones: En este estudio se lograron identificar las características epidemiológicas y se destacaron las principales comorbilidades en pacientes mexicanos con infección por SARS-CoV-2.

Abstract Introduction: COVID-19, caused by the betacoronavirus SARS-CoV-2, has overwhelmed the world's health systems. Objective: To describe the epidemiological characteristics of patients treated in a tertiary care hospital. Methods: A retrospective cohort study of patients diagnosed with or suspected of having COVID-19 from March 23 to July 31, 2020 was conducted. Results: 4,401 patients were hospitalized at the Central Military Hospital, out of which 35 % were beneficiaries, 26 % civilians, 28 % active military, and only 11%, retired military. Male gender predominated, both in hospitalized patients and in those who died, as well as the O+ group and absence of comorbidities; among the observed comorbidities, the main ones were overweight and diabetes. Hospitalized patients' median age was 49 years, while median age of those who died was 62 years; women older than 51 years had a higher risk of dying. Adjusted case fatality rate was 18.5 %; 50 % died within the first six days. Conclusions: In this study, the epidemiological characteristics and main comorbidities in Mexican patients with SARS-CoV-2 infection were identified.

Bloqueo de nervios esplácnicos para tratamiento del dolor abdominal crónico benigno. Reporte de caso con revisión temática / Splanchnic nerve block for the treatment of benign chronic abdominal pain. a case report and literature review

El dolor abdominal crónico de origen benigno puede ser incapacitante y disminuye significativamente la calidad de vida de algunos pacientes. Para su tratamiento es usual el uso crónico de opioides que se han asociado a originar otras fuentes de dolor, por lo que deberían sopesar tratamientos farmacológicos alternativos. Sin embargo, cuando estos no son efectivos, insuficientes u ocasionan efectos adversos intolerables, el manejo intervencionista del dolor debería considerarse. En este campo la inhibición de los nervios esplácnicos que es una técnica que puede ser empleada para el control del dolor oncológico, podría jugar un papel importante a pesar de que aún no cuenta con evidencia sólida de su aplicabilidad en tratar el dolor crónico de origen benigno. Hasta donde sabemos, en el Ecuador es la primera vez que se realiza este procedimiento y el presente informe sugiere que puede ofrecer buenos resultados, incluso después de terminado el efecto de los fármacos utilizados

Chronic abdominal pain of benign origin can be disabling and significantly reduces the quality of life of some patients. Common treatment includes the chronic use of opioids that have also been linked with causing different sources of pain, so alternative pharmacological treatments should be considered instead. However, when these are not effective, insufficient, or cause intolerable adverse effects, interventional pain management should be considered. In this field, the inhibition of splanchnic nerves, which is a technique that can be used to control cancer pain, could play an important role in the treatment of chronic pain of benign origin, despite the lack of solid evidence in its applicability. As far as we know, it is the first time that this procedure has been performed in Ecuador and this report suggests that it can offer positive results even after the effect of the drugs used has ended

BDNF-Live-Exon-Visualization (BLEV) Allows Differential Detection of BDNF Transcripts in vitro and in vivo.

Bdnf exon-IV and exon-VI transcripts are driven by neuronal activity and are involved in pathologies related to sleep, fear or memory disorders. However, how their differential transcription translates activity changes into long-lasting network changes is elusive. Aiming to trace specifically the network controlled by exon-IV and -VI derived BDNF during activity-dependent plasticity changes, we generated a transgenic reporter mouse for B DNF- l ive- e xon- v isualization (BLEV), in which expression of Bdnf exon-IV and -VI can be visualized by co-expression of CFP and YFP. CFP and YFP expression was differentially activated and targeted in cell lines, primary cultures and BLEV reporter mice without interfering with BDNF protein synthesis. CFP and YFP expression, moreover, overlapped with BDNF protein expression in defined hippocampal neuronal, glial and vascular locations in vivo. So far, activity-dependent BDNF cannot be explicitly monitored independent of basal BDNF levels. The BLEV reporter mouse therefore provides a new model, which can be used to test whether stimulus-induced activity-dependent changes in BDNF expression are instrumental for long-lasting plasticity modifications.

Preparation of Primary Cultures of Embryonic Rat Hippocampal and Cerebrocortical Neurons.

This protocol aims at standardizing the procedure to obtain primary cultures of hippocampal and cerebrocortical neurons for in vitro experiments. Cultures should be prepared from cells isolated during embryonic development when neuronal precursor cells are not yet fully differentiated. This helps increasing the quality and quantity of cells, while offering minimal cell death that often occurs during dissociation of differentiated neurons. Cells plated under the appropriate conditions, either in Petri-dishes or in multi-well plates, will develop and establish synaptic contacts over time since the neuronal culture medium provides the nutrients and trophic factors required for differentiation. In this protocol we describe the methodology for the preparation of both cortical and hippocampal neuronal cultures.

Calpains and neuronal damage in the ischemic brain: The swiss knife in synaptic injury.

The excessive extracellular accumulation of glutamate in the ischemic brain leads to an overactivation of glutamate receptors with consequent excitotoxic neuronal death. Neuronal demise is largely due to a sustained activation of NMDA receptors for glutamate, with a consequent increase in the intracellular Ca(2+) concentration and activation of calcium- dependent mechanisms. Calpains are a group of Ca(2+)-dependent proteases that truncate specific proteins, and some of the cleavage products remain in the cell, although with a distinct function. Numerous studies have shown pre- and post-synaptic effects of calpains on glutamatergic and GABAergic synapses, targeting membrane- associated proteins as well as intracellular proteins. The resulting changes in the presynaptic proteome alter neurotransmitter release, while the cleavage of postsynaptic proteins affects directly or indirectly the activity of neurotransmitter receptors and downstream mechanisms. These alterations also disturb the balance between excitatory and inhibitory neurotransmission in the brain, with an impact in neuronal demise. In this review we discuss the evidence pointing to a role for calpains in the dysregulation of excitatory and inhibitory synapses in brain ischemia, at the pre- and post-synaptic levels, as well as the functional consequences. Although targeting calpain-dependent mechanisms may constitute a good therapeutic approach for stroke, specific strategies should be developed to avoid non-specific effects given the important regulatory role played by these proteases under normal physiological conditions.

Gauging low-dose X-ray phase-contrast imaging at a single and large propagation distance.

The interactions of a beam of hard and spatio-temporally coherent X-rays with a soft-matter sample primarily induce a transverse distribution of exit phase variations δϕ (retardations or advancements in pieces of the wave front exiting the object compared to the incoming wave front) whose free-space propagation over a distance z gives rise to intensity contrast gz. For single-distance image detection and |δϕ| ≪ 1 all-order-in-z phase-intensity contrast transfer is linear in δϕ. Here we show that ideal coherence implies a decay of the (shot-)noise-to-signal ratio in gz and of the associated phase noise as z(-1/2) and z(-1), respectively. Limits on X-ray dose thus favor large values of z. We discuss how a phase-scaling symmetry, exact in the limit δϕ → 0 and dynamically unbroken up to |δϕ| ∼ 1, suggests a filtering of gz in Fourier space, preserving non-iterative quasi-linear phase retrieval for phase variations up to order unity if induced by multi-scale objects inducing phase variations δϕ of a broad spatial frequency spectrum. Such an approach continues to be applicable under an assumed phase-attenuation duality. Using synchrotron radiation, ex and in vivo microtomography on frog embryos exemplifies improved resolution compared to a conventional single-distance phase-retrieval algorithm.