Microscopic fractional anisotropy outperforms multiple sclerosis lesion assessment and clinical outcome associations over standard fractional anisotropy tensor.

We aimed to compare the ability of diffusion tensor imaging and multi-compartment spherical mean technique to detect focal tissue damage and in distinguishing between different connectivity patterns associated with varying clinical outcomes in multiple sclerosis (MS). Seventy-six people diagnosed with MS were scanned using a SIEMENS Prisma Fit 3T magnetic resonance imaging (MRI), employing both conventional (T1w and fluid-attenuated inversion recovery) and advanced diffusion MRI sequences from which fractional anisotropy (FA) and microscopic FA (µFA) maps were generated. Using automated fiber quantification (AFQ), we assessed diffusion profiles across multiple white matter (WM) pathways to measure the sensitivity of anisotropy diffusion metrics in detecting localized tissue damage. In parallel, we analyzed structural brain connectivity in a specific patient cohort to fully grasp its relationships with cognitive and physical clinical outcomes. This evaluation comprehensively considered different patient categories, including cognitively preserved (CP), mild cognitive deficits (MCD), and cognitively impaired (CI) for cognitive assessment, as well as groups distinguished by physical impact: those with mild disability (Expanded Disability Status Scale [EDSS] <=3) and those with moderate-severe disability (EDSS >3). In our initial objective, we employed Ridge regression to forecast the presence of focal MS lesions, comparing the performance of µFA and FA. µFA exhibited a stronger association with tissue damage and a higher predictive precision for focal MS lesions across the tracts, achieving an R-squared value of .57, significantly outperforming the R-squared value of .24 for FA (p-value <.001). In structural connectivity, µFA exhibited more pronounced differences than FA in response to alteration in both cognitive and physical clinical scores in terms of effect size and number of connections. Regarding cognitive groups, FA differences between CP and MCD groups were limited to 0.5% of connections, mainly around the thalamus, while µFA revealed changes in 2.5% of connections. In the CP and CI group comparison, which have noticeable cognitive differences, the disparity was 5.6% for FA values and 32.5% for µFA. Similarly, µFA outperformed FA in detecting WM changes between the MCD and CI groups, with 5% versus 0.3% of connections, respectively. When analyzing structural connectivity between physical disability groups, µFA still demonstrated superior performance over FA, disclosing a 2.1% difference in connectivity between regions closely associated with physical disability in MS. In contrast, FA spotted a few regions, comprising only 0.6% of total connections. In summary, µFA emerged as a more effective tool than FA in predicting MS lesions and identifying structural changes across patients with different degrees of cognitive and global disability, offering deeper insights into the complexities of MS-related impairments.

Impact of hypochloremia as a prognostic factor in patients with heart failure, a retrospective cohort study.

BACKGROUND: some studies suggest that hypochloremia is a risk factor in the prognosis of heart failure (HF) in patients with recent decompensation. MATERIALS AND METHODS: retrospective cohort study of patients discharged due to HF decompensation who began follow-up in a specialized clinic. Two groups are defined: patients with hypochloremia (chloride < 98 mmol/L) and normochloremic patients (chloride > 98 mmol/L) in the initial assessment within the first month after discharge. The rate of intravenous diuretic rescue, emergency department visits, readmission for HF and cardiovascular (CV) death are compared using a Cox proportional hazards model. RESULTS: 165 patients were included (59% women, mean age 85 years), with 60 (36%) having hypochloremia. Both groups were comparable in terms of baseline characteristics, except for female sex, presence of peripheral artery disease, moderate-to-severe liver disease (more prevalent in the hypochloremia group), PROFUND index, and baseline furosemide dose (higher in patients with hypochloremia). The incidence of the primary event was higher in subjects with hypochloremia than in normochloremic subjects (HR: 1.59, 95% CI 0.97-2.62), mainly due to the need for intravenous diuretic rescue (HR: 1.86, 95% CI 1.07-3.24). CONCLUSIONS: hypochloremia following admission for HF decompensation is associated with a greater need for intravenous diuretic rescue therapy and probably worse overall prognosis across the spectrum of the disease, regardless of left ventricular ejection fraction (LVEF).

Upregulation of the secretory pathway Ca2+/Mn2+-ATPase isoform 1 in LPS-stimulated microglia and its involvement in Mn2+-induced Golgi fragmentation.

Microglia play an important protective role in the healthy nervous tissue, being able to react to a variety of stimuli that induce different intracellular cascades for specific tasks. Ca2+ signaling can modulate these pathways, and we recently reported that microglial functions depend on the endoplasmic reticulum as a Ca2+ store, which involves the Ca2+ transporter SERCA2b. Here, we investigated whether microglial functions may also rely on the Golgi, another intracellular Ca2+ store that depends on the secretory pathway Ca2+/Mn2+-transport ATPase isoform 1 (SPCA1). We found upregulation of SPCA1 upon lipopolysaccharide stimulation of microglia BV2 cells and primary microglia, where alterations of the Golgi ribbon were also observed. Silencing and overexpression experiments revealed that SPCA1 affects cell morphology, Golgi apparatus integrity, and phagocytic functions. Since SPCA1 is also an efficient Mn2+ transporter and considering that Mn2+ excess causes manganism in the brain, we addressed the role of microglial SPCA1 in Mn2+ toxicity. Our results revealed a clear effect of Mn2+ excess on the viability and morphology of microglia. Subcellular analysis showed Golgi fragmentation and subsequent alteration of SPCA1 distribution from early stages of toxicity. Removal of Mn2+ by washing improved the culture viability, although it did not effectively reverse Golgi fragmentation. Interestingly, pretreatment with curcumin maintained microglia cultures viable, prevented Mn2+-induced Golgi fragmentation, and preserved SPCA Ca2+-dependent activity, suggesting curcumin as a potential protective agent against Mn2+-induced Golgi alterations in microglia.

Providing an in vitro depiction of microglial cells challenged with immunostimulatory extracellular vesicles of Naegleria fowleri.

Naegleria fowleri is the causative agent of primary amoebic meningoencephalitis, a rapid and acute infection of the central nervous system with a fatal outcome in >97% of cases. Due to the infrequent report of cases and diagnostic gaps that hinder the possibility of recovering clinic isolates, studies related to pathogenesis of the disease are scarce. However, the secretion of cytolytic molecules has been proposed as a factor involved in the progression of the infection. Several of these molecules could be included in extracellular vesicles (EVs), making them potential virulence factors and even modulators of the immune response in this infection. In this work, we evaluated the immunomodulatory effect of EVs secreted by two clinic isolates of Naegleria fowleri using in vitro models. For this purpose, characterization analyses between EVs produced by both isolates were first performed, for subsequent gene transcription analyses post incubation of these vesicles with primary cultures from mouse cell microglia and BV-2 cells. Analyses of morphological changes induced in primary culture microglia cells by the vesicles were also included, as well as the determination of the presence of nucleic acids of N. fowleri in the EV fractions. Results revealed increased expression of NOS, proinflammatory cytokines IL-6, TNF-α, and IL-23, and the regulatory cytokine IL-10 in primary cultures of microglia, as well as increased expression of NOS and IL-13 in BV-2 cells. Morphologic changes from homeostatic microglia, with small cellular body and long processes to a more amoeboid morphology were also observed after the incubation of these cells with EVs. Regarding the presence of nucleic acids, specific Naegleria fowleri DNA that could be amplified using both conventional and qPCR was confirmed in the EV fractions. Altogether, these results confirm the immunomodulatory effects of EVs of Naegleria fowleri over microglial cells and suggest a potential role of these vesicles as biomarkers of primary acute meningoencephalitis.

LPS-stimulated microglial cells promote ganglion cell death in organotypic cultures of quail embryo retina.

During development microglia colonize the central nervous system (CNS) and play an important role in programmed cell death, not only because of their ability to remove dead cells by phagocytosis, but also because they can promote the death of neuronal and glial cells. To study this process, we used as experimental systems the developing in situ quail embryo retina and organotypic cultures of quail embryo retina explants (QEREs). In both systems, immature microglia show an upregulation of certain inflammatory markers, e.g., inducible NO synthase (iNOS), and nitric oxide (NO) under basal conditions, which can be further enhanced with LPS-treatment. Hence, we investigated in the present study the role of microglia in promoting ganglion cell death during retinal development in QEREs. Results showed that LPS-stimulation of microglia in QEREs increases (i) the percentage of retinal cells with externalized phosphatidylserine, (ii) the frequency of phagocytic contacts between microglial and caspase-3-positive ganglion cells, (iii) cell death in the ganglion cell layer, and (iv) microglial production of reactive oxygen/nitrogen species, such as NO. Furthermore, iNOS inhibition by L-NMMA decreases cell death of ganglion cells and increases the number of ganglion cells in LPS-treated QEREs. These data demonstrate that LPS-stimulated microglia induce ganglion cell death in cultured QEREs by a NO-dependent mechanism. The fact that phagocytic contacts between microglial and caspase-3-positive ganglion cells increase suggests that this cell death might be mediated by microglial engulfment, although a phagocytosis-independent mechanism cannot be excluded.

Diffusion tensor imaging metrics associated with future disability in multiple sclerosis.

The relationship between brain diffusion microstructural changes and disability in multiple sclerosis (MS) remains poorly understood. We aimed to explore the predictive value of microstructural properties in white (WM) and grey matter (GM), and identify areas associated with mid-term disability in MS patients. We studied 185 patients (71% female; 86% RRMS) with the Expanded Disability Status Scale (EDSS), timed 25-foot walk (T25FW), nine-hole peg test (9HPT), and Symbol Digit Modalities Test (SDMT) at two time-points. We used Lasso regression to analyse the predictive value of baseline WM fractional anisotropy and GM mean diffusivity, and to identify areas related to each outcome at 4.1 years follow-up. Motor performance was associated with WM (T25FW: RMSE = 0.524, R2 = 0.304; 9HPT dominant hand: RMSE = 0.662, R2 = 0.062; 9HPT non-dominant hand: RMSE = 0.649, R2 = 0.139), and SDMT with GM diffusion metrics (RMSE = 0.772, R2 = 0.186). Cingulum, longitudinal fasciculus, optic radiation, forceps minor and frontal aslant were the WM tracts most closely linked to motor dysfunction, and temporal and frontal cortex were relevant for cognition. Regional specificity related to clinical outcomes provide valuable information that can be used to develop more accurate predictive models that could improve therapeutic strategies.

Trombosis venosa de retina. Auditoría de un programa de atención especializada / Retinal vein occlusion. Audit of a specialized care program

Background and objectives Retinal vein occlusion (RVO) is the second most frequent cause of retinal vascular disease and is related to classic cardiovascular risk factors. A specific program was designed to detect and treat risk factors in patients with RVO. The aim of this study is to audit the results of this program. Patients and methods The program consisted of a multidisciplinary clinical evaluation by the Ophthalmology and Internal Medicine Departments. All patients with RVO were screened, at minimum, for hypertension, diabetes, dyslipidemia, smoking, overweight, and antiphospholipid syndrome. New risk factors or poor control of known risk factors were expected to be found in at least one-third of the patients. Among them, therapeutic measures were expected to be taken in at least two-thirds. A dissociated automated search of the data of all patients who entered the program between April 2021 and April 2022 was performed. Results Fifty-six patients were included for analysis. Of these, 39 (69.6%) had at least one new or poorly controlled risk factor and 43 (76.8%) had their treatment modified in some way. Antiphospholipid syndrome was detected in five (8.9%). Only one patient had low-risk hereditary thrombophilia. After an exhaustive examination, no risk factors were found in 11 patients. Conclusion This specific program has been effective in detecting new or poorly controlled risk factors and improving their treatment (AU)

Antecedentes y objetivo La trombosis venosa de retina (TVR) es la segunda causa más frecuente de enfermedad vascular de la retina y se relaciona con factores de riesgo cardiovascular clásicos. Se diseñó un programa específico para detección y tratamiento de factores de riesgo en pacientes con TVR. El objetivo de este estudio es auditar los resultados de dicho programa. Pacientes y métodos El programa consistió en una evaluación clínica multidisciplinar por parte de Oftalmología y Medicina Interna. A todos los pacientes con TVR se les realizó cribado, al menos, de hipertensión arterial, diabetes, dislipidemia, tabaquismo, sobrepeso y síndrome antifosfolípido. Se esperó encontrar nuevos factores de riesgo o pobre control de los ya conocidos en, al menos, un tercio de los pacientes. Entre ellos, se esperó tomar alguna medida terapéutica en, al menos, dos tercios. Se llevó a cabo una búsqueda automatizada disociada de los datos de todos los pacientes que entraron en el programa entre abril de 2021 y abril de 2022. Resultados Cincuenta y seis pacientes se incluyeron para el análisis. De ellos, 39 (69,6%) tenían al menos un factor de riesgo nuevo o mal controlado, y 43 (76,8%) vieron modificado en algún modo su tratamiento. Se detectó síndrome antifosfolípido en 5 (8,9%). Solo un paciente tenía una trombofilia hereditaria de bajo riesgo. Tras un examen exhaustivo no se encontró factor de riesgo alguno en 11 pacientes. Conclusión Este programa específico ha sido efectivo para detectar factores de riesgo nuevos o mal controlados y mejorar su tratamiento (AU)

Retinal vein occlusion. Audit of a specialized care program.

BACKGROUND AND OBJECTIVES: Retinal vein occlusion (RVO) is the second most frequent cause of retinal vascular disease and is related to classic cardiovascular risk factors. A specific program was designed to detect and treat risk factors in patients with RVO. The aim of this study is to audit the results of this program. PATIENTS AND METHODS: The program consisted of a multidisciplinary clinical evaluation by the Ophthalmology and Internal Medicine Departments. All patients with RVO were screened, at minimum, for hypertension, diabetes, dyslipidemia, smoking, overweight, and antiphospholipid syndrome. New risk factors or poor control of known risk factors were expected to be found in at least one-third of the patients. Among them, therapeutic measures were expected to be taken in at least two-thirds. A dissociated automated search of the data of all patients who entered the program between April 2021 and April 2022 was performed. RESULTS: Fifty-six patients were included for analysis. Of these, 39 (69.6%) had at least one new or poorly controlled risk factor and 43 (76.8%) had their treatment modified in some way. Antiphospholipid syndrome was detected in five (8.9%). Only one patient had low-risk hereditary thrombophilia. After an exhaustive examination, no risk factors were found in 11 patients. CONCLUSION: This specific program has been effective in detecting new or poorly controlled risk factors and improving their treatment.

Synthesis, Optical Properties, and Antiproliferative Evaluation of NBD-Triterpene Fluorescent Probes.

A fluorescent labeling protocol for hydroxylated natural compounds with promising antitumor properties has been used to synthesize, in yields of 72-86%, 12 derivatives having fluorescent properties and biological activity. The reagent used for the synthesis of these fluorescent derivatives was 7-nitrobenzo-2-oxa-1,3-diazole chloride (NBD-Cl). The linkers employed to bind the NBD-Cl reagent to the natural compounds were ω-amino acids (Aa) of different chain lengths. The natural triterpene compounds chosen were oleanolic and maslinic acid, as their corresponding 28-benzylated derivatives. Thus, 12 NBD-Aa-triterpene conjugates have been studied for their optical fluorescence properties and their biological activities against cell proliferation in three cancer cell lines (B16-F10, HT-29, and HepG2), compared with three nontumor cell lines (HPF, IEC-18, and WRL68) from different tissues. The results of the fluorescence study have shown that the best fluorescent labels are those in which the ω-amino acid chain is shorter, and the carboxylic group is not benzylated. Analysis by confocal microscopy showed that these compounds were rapidly incorporated into cells in all three cancer cell lines, with these same derivatives showing the highest toxicity against the cancer cell lines tested. Then, the fluorescent labeling of these NBD-Aa-triterpene conjugates enabled their uptake and subcellular distribution to be followed in order to probe in detail their biological properties at the cellular and molecular level.

Microglia and Microglia-Like Cells: Similar but Different.

Microglia are the tissue-resident macrophages of the central nervous parenchyma. In mammals, microglia are thought to originate from yolk sac precursors and posteriorly maintained through the entire life of the organism. However, the contribution of microglial cells from other sources should also be considered. In addition to "true" or "bona-fide" microglia, which are of embryonic origin, the so-called "microglia-like cells" are hematopoietic cells of bone marrow origin that can engraft the mature brain mainly under pathological conditions. These cells implement great parts of the microglial immune phenotype, but they do not completely adopt the "true microglia" features. Because of their pronounced similarity, true microglia and microglia-like cells are usually considered together as one population. In this review, we discuss the origin and development of these two distinct cell types and their differences. We will also review the factors determining the appearance and presence of microglia-like cells, which can vary among species. This knowledge might contribute to the development of therapeutic strategies aiming at microglial cells for the treatment of diseases in which they are involved, for example neurodegenerative disorders like Alzheimer's and Parkinson's diseases.

Switching Roles: Beneficial Effects of Adipose Tissue-Derived Mesenchymal Stem Cells on Microglia and Their Implication in Neurodegenerative Diseases.

Neurological disorders, including neurodegenerative diseases, are often characterized by neuroinflammation, which is largely driven by microglia, the resident immune cells of the central nervous system (CNS). Under these conditions, microglia are able to secrete neurotoxic substances, provoking neuronal cell death. However, microglia in the healthy brain carry out CNS-supporting functions. This is due to the ability of microglia to acquire different phenotypes that can play a neuroprotective role under physiological conditions or a pro-inflammatory, damaging one during disease. Therefore, therapeutic strategies focus on the downregulation of these neuroinflammatory processes and try to re-activate the neuroprotective features of microglia. Mesenchymal stem cells (MSC) of different origins have been shown to exert such effects, due to their immunomodulatory properties. In recent years, MSC derived from adipose tissue have been made the center of attention because of their easy availability and extraction methods. These cells induce a neuroprotective phenotype in microglia and downregulate neuroinflammation, resulting in an improvement of clinical symptoms in a variety of animal models for neurological pathologies, e.g., Alzheimer's disease, traumatic brain injury and ischemic stroke. In this review, we will discuss the application of adipose tissue-derived MSC and their conditioned medium, including extracellular vesicles, in neurological disorders, their beneficial effect on microglia and the signaling pathways involved.

Epidemiología del espectro de neuromielitis óptica. Nuevos y viejos desafíos / Epidemiology of neuromyelitis optica spectrum. New and old challenges

Introducción: La presente revisión epidemiológica sobre el espectro de neuromielitis óptica (NMOSD) se focaliza en la descripción metodológica de los estudios realizados bajo los criterios del NMOSD de 2015, en la descripción de estudios realizados en España y Latinoamérica, así como en los factores relacionados con el pronóstico de la enfermedad. Desarrollo: La metodología utilizada en los estudios varía fundamentalmente en la aplicación de diferentes criterios diagnósticos, fuentes de registros, técnicas de detección de anticuerpos y métodos de estandarización. Sin embargo, en términos generales, el NMOSD tiene una distribución mundial con una mayor incidencia/prevalencia en las mujeres que en los hombres, y en los países asiáticos y afroamericanos que en los países occidentales. La frecuencia aumenta de manera paralela a la edad, con un pico de incidencia/prevalencia en el rango entre 40 y 59 años. La población latinoamericana presenta unas características epidemiológicas particulares ligadas a su mezcla racial y genética. Finalmente, variables epidemiológicas, como la raza negra, una mayor edad en el inicio y el sexo femenino, se asocian a un peor pronóstico funcional. Conclusiones: Los datos epidemiológicos del NMOSD varían entre los diferentes estudios, debido, en gran parte, a discrepancias en los diseños metodológicos. Aunque son escasos los estudios latinoamericanos, los hallazgos descritos se asocian a su mezcla étnica. La homogeneización de criterios, utilización de técnicas diagnósticas y métodos de estandarización similares es de fundamental aplicación para el correcto estudio de la epidemiología del NMOSD.

Introduction: This epidemiological review on neuromyelitis optica spectrum disorder (NMOSD) focuses on describing the methodologies employed in studies conducted under the 2015 NMOSD criteria and the studies conducted in Spain and Latin America, as well as examining factors related to the prognosis of the disease. Development: The methodology used in the studies varies essentially in the application of different diagnostic criteria, sources of records, antibody detection techniques and standardisation methods. However, in general terms, NMOSD is distributed worldwide with an incidence/prevalence that is higher in women than in men, and in Asian and African-American countries than in Western countries. The frequency increases in parallel to age, with a peak incidence/prevalence in the 40-59 age range. The Latin American population has particular epidemiological characteristics linked to its racial and genetic mix. Finally, epidemiological variables, such as belonging to the black race, being of older age at onset and being female, are associated with a worse functional prognosis. Conclusions: Epidemiological data on NMOSD vary from one study to another, largely due to discrepancies in the methodological designs. Although Latin American studies are scarce, the findings described are associated with their ethnic mix. The homogenisation of criteria and the use of similar diagnostic techniques and standardisation methods must be implemented for the correct study of the epidemiology of NMOSD.(AU)

Risk factors of severe COVID-19 in people with multiple sclerosis : A systematic review and meta-analysis.

OBJECTIVES: To gather, synthesize, and meta-analyze data regarding the risk factors associated with a severe course of COVID-19 among patients with multiple sclerosis (pwMS). METHODS: MEDLINE, Embase, Scopus, and WoS were searched in May 2021. Briefly, the eligibility criteria included: 1) studies assessing COVID-19 severity among adult pwMS; 2) definitive diagnoses or high clinical suspicion of COVID-19; 3) a categorization of COVID-19 severity into at least two categories; 4) quantitative effect size and precision measurements; and 5) English language; and 6) clear effect size/precision measures. internal validity of studies was assessed using the NIH Quality Assessment Tools. A list of possible risk factors was created based on the search results and was later used in extraction, synthesis, and meta-analysis of the data. RESULTS: Thirteen studies were included in the syntheses. Outcome measures were either extracted from the papers, obtained from the primary researchers or calculated manually. The meta-analyses showed a significantly (P<0.05) increased odds of a severe COVID-19 in pwMS with all of the assessed risk factors, except smoking and most DMTs. CONCLUSION: This study facilitates evidence-based risk/benefit assessments in practice. Older men with progressive MS on anti-CD20 therapies are more at risk of an unfortunate COVID-19 outcome.

[Epidemiology of neuromyelitis optica spectrum. New and old challenges]. / Epidemiología del espectro de neuromielitis óptica. Nuevos y viejos desafíos.

INTRODUCTION: This epidemiological review on neuromyelitis optica spectrum disorder (NMOSD) focuses on describing the methodologies employed in studies conducted under the 2015 NMOSD criteria and the studies conducted in Spain and Latin America, as well as examining factors related to the prognosis of the disease. DEVELOPMENT: The methodology used in the studies varies essentially in the application of different diagnostic criteria, sources of records, antibody detection techniques and standardisation methods. However, in general terms, NMOSD is distributed worldwide with an incidence/prevalence that is higher in women than in men, and in Asian and African-American countries than in Western countries. The frequency increases in parallel to age, with a peak incidence/prevalence in the 40-59 age range. The Latin American population has particular epidemiological characteristics linked to its racial and genetic mix. Finally, epidemiological variables, such as belonging to the black race, being of older age at onset and being female, are associated with a worse functional prognosis. CONCLUSIONS: Epidemiological data on NMOSD vary from one study to another, largely due to discrepancies in the methodological designs. Although Latin American studies are scarce, the findings described are associated with their ethnic mix. The homogenisation of criteria and the use of similar diagnostic techniques and standardisation methods must be implemented for the correct study of the epidemiology of NMOSD.

TITLE: Epidemiología del espectro de neuromielitis óptica. Nuevos y viejos desafíos.Introducción. La presente revisión epidemiológica sobre el espectro de neuromielitis óptica (NMOSD) se focaliza en la descripción metodológica de los estudios realizados bajo los criterios del NMOSD de 2015, en la descripción de estudios realizados en España y Latinoamérica, así como en los factores relacionados con el pronóstico de la enfermedad. Desarrollo. La metodología utilizada en los estudios varía fundamentalmente en la aplicación de diferentes criterios diagnósticos, fuentes de registros, técnicas de detección de anticuerpos y métodos de estandarización. Sin embargo, en términos generales, el NMOSD tiene una distribución mundial con una mayor incidencia/prevalencia en las mujeres que en los hombres, y en los países asiáticos y afroamericanos que en los países occidentales. La frecuencia aumenta de manera paralela a la edad, con un pico de incidencia/prevalencia en el rango entre 40 y 59 años. La población latinoamericana presenta unas características epidemiológicas particulares ligadas a su mezcla racial y genética. Finalmente, variables epidemiológicas, como la raza negra, una mayor edad en el inicio y el sexo femenino, se asocian a un peor pronóstico funcional. Conclusiones. Los datos epidemiológicos del NMOSD varían entre los diferentes estudios, debido, en gran parte, a discrepancias en los diseños metodológicos. Aunque son escasos los estudios latinoamericanos, los hallazgos descritos se asocian a su mezcla étnica. La homogeneización de criterios, utilización de técnicas diagnósticas y métodos de estandarización similares es de fundamental aplicación para el correcto estudio de la epidemiología del NMOSD.

[Analgesia, sedation, neuromuscular blockade and delirium management practices in Chilean intensive care units]. / Prácticas nacionales de analgesia, sedación y delirium en las Unidades de Cuidados Intensivos de adultos en Chile.

BACKGROUND: The appropriate use of analgesia, sedation, neuromuscular blockade and the diagnosis and prevention of delirium (ASBD) are associated with better outcomes in critically ill patients at Intensive Care Unit (ICUs). AIM: To know the practices about analgesia, sedation, delirium, and neuromuscular blockade use among healthcare professionals working in adult ICUs in Chile. MATERIAL AND METHODS: An electronic survey was sent to 812 professionals working in ICUs using a previously published instrument, which was adapted and authorized by the author. RESULTS: We received 278 surveys. Fifty two percent of respondents were physicians, 34% nurses and 11% physical therapists. Their age ranged between 30 and 39 years in 43% and was over 50 years in 9%. Eighty four percent evaluated pain routinely, but only 26% use a validated scale. Sedation was routinely evaluated with a validated scale and 73% referred to have a protocol. Neuromuscular block is seldom used, and little monitoring occurs (43%). Delirium is routinely evaluated by 48% of respondents, usually using the CAM-ICU scale. CONCLUSIONS: There is a heterogeneous adherence to the ASBD recommended practices. The main gaps are in the assessment of pain, monitoring of neuromuscular blockade and diagnosis of delirium through validated instruments.

Efficient In Vitro and In Vivo Anti-Inflammatory Activity of a Diamine-PEGylated Oleanolic Acid Derivative.

Recent evidence has shown that inflammation can contribute to all tumorigenic states. We have investigated the anti-inflammatory effects of a diamine-PEGylated derivative of oleanolic acid (OADP), in vitro and in vivo with inflammation models. In addition, we have determined the sub-cytotoxic concentrations for anti-inflammatory assays of OADP in RAW 264.7 cells. The inflammatory process began with incubation with lipopolysaccharide (LPS). Nitric oxide production levels were also determined, exceeding 75% inhibition of NO for a concentration of 1 µg/mL of OADP. Cell-cycle analysis showed a reversal of the arrest in the G0/G1 phase in LPS-stimulated RAW 264.7 cells. Furthermore, through Western blot analysis, we have determined the probable molecular mechanism activated by OADP; the inhibition of the expression of cytokines such as TNF-α, IL-1ß, iNOS, and COX-2; and the blocking of p-IκBα production in LPS-stimulated RAW 264.7 cells. Finally, we have analyzed the anti-inflammatory action of OADP in a mouse acute ear edema, in male BL/6J mice treated with OADP and tetradecanoyl phorbol acetate (TPA). Treatment with OADP induced greater suppression of edema and decreased the ear thickness 14% more than diclofenac. The development of new derivatives such as OADP with powerful anti-inflammatory effects could represent an effective therapeutic strategy against inflammation and tumorigenic processes.

Fishers' perception of the interaction between the South American sea lions and the Chinook salmon fishery in southern Chile.

We studied how the South American sea lion (SASL, Otaria flavescens) interacts with the operation of an artisanal fishery of Chinook salmon, a non-native species in Chile, using a combination of biological and social approaches, including a valuation by fishers about this interaction. During austral summer of 2019, an observer onboard artisanal fishing boats characterized the attack behavior of SASLs to gillnet-captured Chinook salmon during 33 hauls and analyzed which factors may affect the intensity of attacks. To analyze the relationship between fishers and SASLs, a Likert scale about the perception and views about nature was applied. A total of 23 interviews-including 35 open and 16 closed questions-with fishers were conducted to describe how they perceived the interactions with SASLs. Interactions with SASLs were recorded in 35% of the fishing events and varied depending on both operational factors, such as the number of boats, as well as environmental factors, such as moon's luminosity. Even though SASL interactions resulted in seven fish (~ 70 kg) damaged of a total catch of 2815 kg (2.5%) during the survey, boats with a damaged catch by SASL lost up to 11% of their revenue. This is consistent with 87% of the interviewed fishers who considered that the conflict with the SASL negatively impacts their activity and results in economic losses. A negative perception towards SASLs likely results from personal experience and revenue loss, even though impacts of SASL interactions at the scale of the entire fishery may be less important. While older fishers with less formal education have a productivist and instrumental focus, younger fishers with a more sustainable and conservationist view of fishing offer an opportunity to lead an improved local understanding of the relationship between salmon, SASLs, and humans.

[Debate on the return to face-to-face classes in Pandemic]. / Debate sobre el retorno a clases presenciales en Pandemia.

The implications of closing educational establishments during the COVID-19 pandemic and the dis cussion about the opening of them, invite and require us to consider, from different positions and responsibilities, the changes that we must make as a society at the educational level. In this article, a group of health professionals collects information and reflects on the repercussions of returning or not to school activities, in terms of physical and emotional health and academic education. Based on what is known to be protective factors and possible threats to return, it is possible to conclude that each local reality must make its own informed decision, with the participation of all its members, seeking the common good, which favors students, protects teachers, and privileges the role of the educational system in socio-emotional learning. School is a space for containing the emotions and adaptation needs that students and their families have experienced in these uncertain times. We all have a level of responsibility in building a new civilization around these issues that link education, physical and mental health, social collaboration, and individual responsibility. Differences in people's living conditions and unequal opportunities have become more visible than before (others are still hidden) and create an opportunity for changes that we must face together.