A humoral stress response protects Drosophila tissues from antimicrobial peptides.

7An efficient immune system must provide protection against a broad range of pathogens without causing excessive collateral tissue damage. While immune effectors have been well characterized, we know less about the resilience mechanisms protecting the host from its own immune response. Antimicrobial peptides (AMPs) are small, cationic peptides that contribute to innate defenses by targeting negatively charged membranes of microbes. While protective against pathogens, AMPs can be cytotoxic to host cells. Here, we reveal that a family of stress-induced proteins, the Turandots, protect the Drosophila respiratory system from AMPs, increasing resilience to stress. Flies lacking Turandot genes are susceptible to environmental stresses due to AMP-induced tracheal apoptosis. Turandot proteins bind to host cell membranes and mask negatively charged phospholipids, protecting them from cationic pore-forming AMPs. Collectively, these data demonstrate that Turandot stress proteins mitigate AMP cytotoxicity to host tissues and therefore improve their efficacy.

Deep Learning-Assisted Single-Molecule Detection of Protein Post-translational Modifications with a Biological Nanopore.

Protein post-translational modifications (PTMs) play a crucial role in countless biological processes, profoundly modulating protein properties on both spatial and temporal scales. Protein PTMs have also emerged as reliable biomarkers for several diseases. However, only a handful of techniques are available to accurately measure their levels, capture their complexity at a single molecule level, and characterize their multifaceted roles in health and disease. Nanopore sensing provides high sensitivity for the detection of low-abundance proteins, holding the potential to impact single-molecule proteomics and PTM detection, in particular. Here, we demonstrate the ability of a biological nanopore, the pore-forming toxin aerolysin, to detect and distinguish α-synuclein-derived peptides bearing single or multiple PTMs, namely, phosphorylation, nitration, and oxidation occurring at different positions and in various combinations. The characteristic current signatures of the α-synuclein peptide and its PTM variants could be confidently identified by using a deep learning model for signal processing. We further demonstrate that this framework can quantify α-synuclein peptides at picomolar concentrations and detect the C-terminal peptides generated by digestion of full-length α-synuclein. Collectively, our work highlights the advantage of using nanopores as a tool for simultaneous detection of multiple PTMs and facilitates their use in biomarker discovery and diagnostics.

A versatile approach to high-density microcrystals in lipidic cubic phase for room-temperature serial crystallography.

Serial crystallography has emerged as an important tool for structural studies of integral membrane proteins. The ability to collect data from micrometre-sized weakly diffracting crystals at room temperature with minimal radiation damage has opened many new opportunities in time-resolved studies and drug discovery. However, the production of integral membrane protein microcrystals in lipidic cubic phase at the desired crystal density and quantity is challenging. This paper introduces VIALS (versatile approach to high-density microcrystals in lipidic cubic phase for serial crystallography), a simple, fast and efficient method for preparing hundreds of microlitres of high-density microcrystals suitable for serial X-ray diffraction experiments at both synchrotron and free-electron laser sources. The method is also of great benefit for rational structure-based drug design as it facilitates in situ crystal soaking and rapid determination of many co-crystal structures. Using the VIALS approach, room-temperature structures are reported of (i) the archaerhodopsin-3 protein in its dark-adapted state and 110 ns photocycle intermediate, determined to 2.2 and 1.7 Å, respectively, and (ii) the human A2A adenosine receptor in complex with two different ligands determined to a resolution of 3.5 Å.

Evaluation of Changes in Hydration and Body Cell Mass with Bioelectrical Impedance Analysis after Exercise Program for Rheumatoid Arthritis Patients.

Rheumatoid arthritis (RA) is a debilitating disease that can result in complications such as rheumatoid cachexia. While physical exercise has shown benefits for RA patients, its impact on hydration and body cell mass remains uncertain. The presence of pain, inflammation, and joint changes often restrict activity and make traditional body composition assessments unreliable due to altered hydration levels. Bioelectrical impedance is a commonly used method for estimating body composition, but it has limitations since it was primarily developed for the general population and does not consider changes in body composition. On the other hand, bioelectrical impedance vectorial analysis (BIVA) offers a more comprehensive approach. BIVA involves graphically interpreting resistance (R) and reactance (Xc), adjusted for height, to provide valuable information about hydration status and the integrity of the cell mass. Twelve women with RA were included in this study. At the beginning of the study, hydration and body cell mass measurements were obtained using the BIVA method. Subsequently, the patients participated in a six-month dynamic exercise program encompassing cardiovascular capacity, strength, and coordination training. To evaluate changes in hydration and body cell mass, the differences in the R and Xc parameters, adjusted for height, were compared using BIVA confidence software. The results showed notable changes: resistance decreased after the exercise program, while reactance increased. BIVA, as a classification method, can effectively categorize patients into dehydration, overhydration, normal, athlete, thin, cachectic, and obese categories. This makes it a valuable tool for assessing RA patients, as it provides information independent of body weight or prediction equations. Overall, the implementation of BIVA in this study shed light on the effects of the exercise program on hydration and body cell mass in RA patients. Its advantages lie in its ability to provide comprehensive information and overcome the limitations of traditional body composition assessment methods.

Corrigendum: Intra-accumbens raclopride administration prevents behavioral changes induced by intermittent access to sucrose solution.

[This corrects the article DOI: 10.3389/fnins.2018.00074.].

Impacto del uso de la mascarilla durante la realización de la prueba de esfuerzo en tapiz rodante / Impact of face masks during the treadmill exercise tests

Introducción y objetivos: Existe poca literatura sobre el uso de la mascarilla en la realización de una prueba de esfuerzo (PE) durante la pandemia de COVID-19. El objetivo de este estudio es analizar el impacto del uso de la mascarilla durante la realización de una PE en un grupo de pacientes que han realizado al menos una PE con y sin mascarilla.MétodosEstudio observacional retrospectivo unicéntrico de pacientes sometidos a una PE con tapiz rodante. El criterio de inclusión fue tener más de 16años y haber realizado al menos una PE en época prepandemia (sin mascarilla) y pospandemia (con mascarilla).ResultadosUn total de 1.655 pacientes fueron incluidos en el estudio; 935 (56,5%) eran varones y 720 (43,5%) eran mujeres. La edad media fue de 57,3±14,9 años y el tiempo medio de seguimiento fue de 15,4 meses. El 53% de los pacientes presentaron antecedentes personales de hipertensión arterial; el 20%, dislipemia; el 12%, diabetes mellitus; el 8%, hábito tabáquico; el 19%, cardiopatía isquémica; el 5%, EPOC; el 8%, asma bronquial, y el 8%, fibrilación auricular. En la casi totalidad de las variables estudiadas en la PE, incluida la aparición de arritmias ventriculares, no se evidenciaron diferencias significativas, ni por edad ni por sexo, salvo la existencia de una muy leve disminución en la capacidad de ejercicio con el uso de mascarilla en los pacientes de mayor edad (>65años).ConclusionesEl uso de mascarillas quirúrgicas o FFP2 durante la PE no afectó a la capacidad funcional, a la presión arterial, a la frecuencia cardiaca ni incrementó las arritmias ventriculares. (AU)

Introduction and objective: There is little literature on the use of face masks in a treadmill test (TMT) during the COVID-19 pandemic. The objective of this study is to analyze the impact of face masks during a TMT performed during the prepandemic (without face mask) and postpandemic (with face mask) era.MethodsRetrospective observational unicentric study of patients undergoing TMT. The inclusion criterion were being over 16years old and having performed at least one TMT in the prepandemic and postpandemic period.ResultsOne thousand six hundred fifty-five patients were included in the study. Nine hundred thirty-five (56.5%) were men and 720 (43.5%) women. The mean age was 57.3±14.9 and the mean follow-up time was 15.4 months. Fifty-three percent patients had arterial hypertension, 20% dyslipidemia, 12% diabetes mellitus, 8% smoking habit, 19% personal history of ischemic heart disease, 5% COPD, 8% bronchial asthma, and 8% atrial fibrillation. In almost all the variables studied in PE, including the appearance of ventricular arrhythmias, no significant differences were found, neither by age nor sex, except for the existence of a very slight decrease in exercise capacity with mask use in older patients (>65years).ConclusionsThe use of surgical or FFP2 face masks during the TMT did not affect functional capacity, blood pressure, heart rate, or increased ventricular arrhythmias. (AU)

Impact of face masks during the treadmill exercise tests. / Impacto del uso de la mascarilla durante la realización de la prueba de esfuerzo en tapiz rodante.

INTRODUCTION AND OBJECTIVE: There is little literature on the use of face masks in a treadmill test (TMT) during the COVID-19 pandemic. The objective of this study is to analyze the impact of face masks during a TMT performed during the prepandemic (without face mask) and postpandemic (with face mask) era. METHODS: Retrospective observational unicentric study of patients undergoing TMT. The inclusion criterion were being over 16years old and having performed at least one TMT in the prepandemic and postpandemic period. RESULTS: One thousand six hundred fifty-five patients were included in the study. Nine hundred thirty-five (56.5%) were men and 720 (43.5%) women. The mean age was 57.3±14.9 and the mean follow-up time was 15.4 months. Fifty-three percent patients had arterial hypertension, 20% dyslipidemia, 12% diabetes mellitus, 8% smoking habit, 19% personal history of ischemic heart disease, 5% COPD, 8% bronchial asthma, and 8% atrial fibrillation. In almost all the variables studied in PE, including the appearance of ventricular arrhythmias, no significant differences were found, neither by age nor sex, except for the existence of a very slight decrease in exercise capacity with mask use in older patients (>65years). CONCLUSIONS: The use of surgical or FFP2 face masks during the TMT did not affect functional capacity, blood pressure, heart rate, or increased ventricular arrhythmias.

Cachexia measured by bioelectrical impedance vector analysis and risk of infection in women with rheumatoid arthritis.

Rheumatoid arthritis (RA) patients have a higher frequency of infections than the healthy population. The reason has yet to be explained but involves several factors, of which body composition and rheumatoid cachexia are often overlooked. This study aimed to evaluate whether patients with cachexia, measured by bioelectrical impedance vector analysis, are at an increased risk of developing infections compared with patients without cachexia. A secondary analysis of 186 women with RA enrolled in a randomized trial (ClinicalTrials.gov ID: NCT02900898, September 14, 2016) was completed. Medical records and phone calls were used to record infectious events diagnosed and treated during follow-up. Hazard ratios were calculated using Cox proportional hazard regression analysis, and a predictive model of infection was created. After 36 months of follow-up, 62 patients (26.7% non-cachectic and 44.3% cachectic, p < 0.01) developed at least one infectious event. The most common site of was the urinary tract, followed by the lungs and respiratory tract. The presence of cachexia (HR 1.90, 95% CI 1.15-3.13) and the use of glucocorticoids (HR 1.77, 95% CI 1.01-3.09) were associated with infection in univariate and multivariate models. Body mass index (BMI), smoking, and methotrexate use were not associated with a higher frequency of infections. The presence of cachexia and the use of glucocorticoids were identified as predictors of infections in a cohort of female RA patients. More extensive measurements of body composition should be performed beyond BMI in RA patients to better understand its impact and to prevent additional comorbidities and complications. Key Points • The presence of cachexia measured by bioelectrical impedance vector analysis was associated with infectious events in women with rheumatoid arthritis, whereas body mass index did not show an association. • Glucocorticoids were the only drug associated with a higher frequency of infection. None of the disease-modifying antirheumatic drugs, including methotrexate, showed an association.

Prueba de Push-Out para Evaluar la Fuerza de Adhesión entre dos Tipos de Postes Estéticos

Posterior a un tratamiento endodóntico, muchas veces el remanente es insuficiente para la retención de un material de restauración, por este motivo es necesario la colocación de un sistema de poste-muñón para otorgar retención a la restauración final. Con la aparición de diversos materiales para las restauraciones estéticas, se utilizan actualmente resinas reforzadas con fibra de vidrio como sistemas de postes y muñones para la restauración de dientes tratados endodónticamente. El objetivo del presente trabajo fue comparar la fuerza de adhesión en la prueba push-out de dos diferentes tipos de postes de fibra de vidrio; 3M RelyX y Rebilda Post GT (VOCO) adheridos con cementos duales correspondientes a la marca de los postes; RelyX U-200® Automix (3M ESPE) y Rebilda DC (VOCO). Se llevó a cabo un análisis de ANOVA de dos vías para comparar la fuerza adhesiva con la prueba push-out entre ambos grupos de estudio. Pese a que se observó que los postes Rebilda presentaron una media de fuerza de adhesión ligeramente mayor en comparación con los postes 3M (sin diferencia estadística significativa P>0,05) los últimos son clínicamente más fáciles de colocar, lo cual pudiera ser un factor decisivo para el clínico en el momento de la elección de un poste y su sistema de adhesión.

After an endodontic treatment, many times the remnant is insufficient for the retention of a restorative material, for this reason it is necessary to place a post-stump system to provide retention to the final restoration. With the advent of various materials for esthetic restorations, fiberglass-reinforced resins are now used as post and core systems for the restoration of endodontically treated teeth. The objective of the present work was to compare the bond strength in the push-out test of 2 different types of fiberglass posts; 3M RelyX and Rebilda Post GT (VOCO) bonded with dual cements corresponding to the post brand; RelyX U-200® Automix (3M ESPE) and Rebilda DC (VOCO). A 2-way ANOVA analysis was performed to compare push-out strength between both study groups. Although it was observed that the Rebilda posts presented a slightly higher mean bond strength compared to the 3M posts (with no significant statistical difference P>0.05), the latter are clinically easier to place, which could be a decisive factor for the clinician at the time of choosing a post and its adhesion system.

Índice de eficiencia miocárdica en cardiópatas posterior a un programa de rehabilitación cardiaca / Myocardial efficiency index in patients with heart disease after a cardiac rehabilitation program

Resumen Objetivo: El índice de eficiencia miocárdica (IEM) correlaciona el consumo miocárdico de oxígeno (MVO2) con el consumo máximo de oxígeno, el cual proporciona información sobre la eficiencia cardiovascular (EfCV). En deportistas, el IEM mejora posterior a un microciclo de entrenamiento, en el paciente con enfermedad cardiovascular sometido a un programa de rehabilitación cardiaca y prevención secundaria PRHCyPS, el comportamiento del IEM podría resultar un estimador relacionado con mejoría derivado de un periodo de entrenamiento. El objetivo del estudio fue determinar el comportamiento del IEM posterior a un PRCyPS en pacientes con cardiopatías y riesgo cardiovascular alto (RCVA). Métodos: Estudio de cohorte ambilectivo, descriptivo, analítico, no aleatorizado. Se seleccionaron pacientes con cardiopatías de etiología mixta con RCVA ingresados a un PRCyPS durante 4-6 semanas. A todos los pacientes se les realizó una prueba de ejercicio máximo en banda antes y después del PRCyPS. Se determinaron umbrales de consumo de oxígeno (VO2) pico, equivalentes metabólicos-carga, doble producto e IEM. Se estableció un punto de corte del IEM mediante una curva ROC con un valor de 7.37 con un área bajo la curva de 0.68 (IC 95%: 0.61-0.76; p < 0.001), sensibilidad 0.60 y 1-especificidad de 0.35. Resultados: Se incluyeron 193 pacientes con una media de edad de 62.3 años, en su mayoría del sexo masculino (66.2%). Se observaron porcentajes de cambio en el IEM -27.1% (p < 0.001), MET 43.1% (p < 0.001), doble producto 5.7% (p < 0.01) y MVO2: 8.3% (p < 0.01) al término del PRCyPS. Conclusiones: Se observó un cambio significativo en el IEM posterior a un PRCyPS, lo cual se asoció a una mejoría en la EfCV, sugiriendo que este pueda considerarse como un parámetro clínico que evaluar en los programas de rehabilitación cardiaca.

Abstract Objective: The myocardial efficiency index (MEI) correlates the Myocardial Oxygen Consumption (MVO2) with the Maximum Oxygen Consumption (VO2max), this index provides information about the cardiovascular efficiency (CVEf). In athletes, the MEI improves after a micro-cycle training, however in patients with cardiovascular disease undergoing Cardiac Rehabilitation Program (CRP), IEM behavior could be a good estimator related to the improvement training period. The objective of this study was to determine the myocardial efficiency index behavior in patients with heart disease and high cardiovascular risk (HCVR) after a CRP. Methods: Ambilective, descriptive, analytical, non-randomized cohort study was conducted. Patients with heart disease of mixed etiology and HCVR admitted to a CRP for 4-6 weeks were selected. All patients performed a maximal exercise test in band before and after the CPR. Thresholds of VO2 peak, METs-load, Double product (DP) and MEI were determined. A cut-off point for the MEI was established using a ROC curve with a value of 7.37, area under the curve: 0.68 (95% CI 0.61 - 0.76, p < 0.001), sensitivity 0.60 and 1-specificity 0.35. Results: 193 patients with a mean age of 62.3 years were included, predominantly men (66.2%). Percentages changes in the MEI-27.1% (p < 0.001),METs-43.1% (p < 0.001),DP 5.7% (p < 0.01), and MVO2: 8.3% (p < 0.01) were observed at the end of CRP. Conclusions: Significant change in the MEI were observed after CRP associated to CVEf improvement, suggesting that this parameter could be considered as a good clinical tool in the CRP care programs.

The metabolic phenotype of the patient influences the reduction in carotid intima-media thickness achieved following metabolic surgery.

OBJECTIVES: To determine whether metabolic phenotype is associated with the change in carotid intima-media thickness (CIMT) in patients undergoing bariatric /metabolic surgery (BMS). METHODS: We performed a case-control study of BMS candidates who had metabolically unhealthy obesity (MUO) or metabolically healthy obesity (MHO). We measured the change in CIMT during the 9 months following BMS. The plasma tumor necrosis factor-α, interleukin-1ß, adiponectin, leptin, nitric oxide (NO), vascular endothelial growth factor A (VEGF-A), and malondialdehyde concentrations were determined, adipocyte area was measured histologically, and adipose tissue area was estimated using computed tomography. RESULTS: Fifty-six patients (mean age 44.5 years, mean body mass index 44.9 kg/m2, 53% women, and 53% had MUO) were studied. Nine months following BMS, the MUO phenotype was not associated with a significant reduction in CIMT, and that of the MHO group was larger. In addition, fewer participants achieved a 10% reduction in CIMT in the MUO group. A CIMT reduction was associated with lower VEGF-A and NO in the MUO group, while that in the MHO group was associated with a higher NO concentration. CONCLUSION: The metabolic phenotype of patients may influence their change in CIMT following BMS, probably through circulating vasodilatory and pro-inflammatory molecules.

Epidemiological Profile and Social Welfare Index as Factors Associated with COVID-19 Hospitalization and Severity in Mexico City: A Retrospective Analysis.

Epidemiological data indicate that Mexico holds the 19th place in cumulative cases (5506.53 per 100,000 inhabitants) of COVID-19 and the 5th place in cumulative deaths (256.14 per 100,000 inhabitants) globally and holds the 4th and 3rd place in cumulative cases and deaths in the Americas region, respectively, with Mexico City being the most affected area. Several modifiable and non-modifiable risk factors have been linked to a poor clinical outcome in COVID-19 infection; however, whether socioeconomic and welfare factors are associated with clinical outcome has been scanty addressed. This study tried to investigate the association of Social Welfare Index (SWI) with hospitalization and severity due to COVID-19. A retrospective analysis was conducted at the Centro Médico Nacional "20 de Noviembre"-ISSSTE, based in Mexico City, Mexico. A total of 3963 patients with confirmed or suspected COVID-19, registered from March to July 2020, were included, retrieved information from the Virology Analysis and Reference Unit Database. Demographic, symptoms and clinical data were analyzed, as well as the SWI, a multidimensional parameter based on living and household conditions. An adjusted binary logistic regression model was performed in order to compare the outcomes of hospitalization, mechanical ventilation requirement (MVR) and mortality between SWI categories: Very high (VHi), high (Hi), medium (M) and low (L). The main findings show that lower SWI were independently associated with higher probability for hospital entry: VHi vs. Hi vs. M vs. L-SWI (0 vs. +0.24 [OR = 1.24, CI95% 1.01-1.53] vs. +0.90 [OR = 1.90, CI95% 1.56-2.32] vs. 0.73 [OR = 1.73, CI95% 1.36-2.19], respectively); Mechanical Ventilation Requirement: VHi vs. M vs. L-SWI (0 vs. +0.45 [OR = 1.45, CI95% 1.11-1.87] vs. +0.35 [OR = 1.35, CI95% 1.00-1.82]) and mortality: VHi vs. Hi vs. M (0 vs. +0.54 [OR = 1.54, CI95% 1.22-1.94] vs. +0.41 [OR = 1.41, CI95% 1.13-1.76]). We concluded that SWI was independently associated with the poor clinical outcomes in COVID-19, beyond demographic, epidemiological and clinical characteristics.

Myocardial efficiency index in patients with heart disease after a cardiac rehabilitation program.

OBJECTIVE: The myocardial efficiency index (MEI) correlates the Myocardial Oxygen Consumption (MVO2) with the Maximum Oxygen Consumption (VO2max), this index provides information about the cardiovascular efficiency (CVEf). In athletes, the MEI improves after a micro-cycle training, however in patients with cardiovascular disease undergoing Cardiac Rehabilitation Program (CRP), IEM behavior could be a good estimator related to the improvement training period. The objective of this study was to determine the myocardial efficiency index behavior in patients with heart disease and high cardiovascular risk (HCVR) after a CRP. METHODS: Ambilective, descriptive, analytical, non-randomized cohort study was conducted. Patients with heart disease of mixed etiology and HCVR admitted to a CRP for 4-6 weeks were selected. All patients performed a maximal exercise test in band before and after the CPR. Thresholds of VO2 peak, METs-load, Double product (DP) and MEI were determined. A cut-off point for the MEI was established using a ROC curve with a value of 7.37, area under the curve: 0.68 (95% CI 0.61 - 0.76, p < 0.001), sensitivity 0.60 and 1-specificity 0.35. RESULTS: 193 patients with a mean age of 62.3 years were included, predominantly men (66.2%). Percentages changes in the MEI-27.1% (p < 0.001),METs-43.1% (p < 0.001),DP 5.7% (p < 0.01), and MVO2: 8.3% (p < 0.01) were observed at the end of CRP. CONCLUSIONS: Significant change in the MEI were observed after CRP associated to CVEf improvement, suggesting that this parameter could be considered as a good clinical tool in the CRP care programs.

OBJETIVO: El índice de eficiencia miocárdica (IEM) correlaciona el consumo miocárdico de oxígeno (MVO2) con el consumo máximo de oxígeno, el cual proporciona información sobre la eficiencia cardiovascular (EfCV). En deportistas, el IEM mejora posterior a un microciclo de entrenamiento, en el paciente con enfermedad cardiovascular sometido a un programa de rehabilitación cardiaca y prevención secundaria PRHCyPS, el comportamiento del IEM podría resultar un estimador relacionado con mejoría derivado de un periodo de entrenamiento. El objetivo del estudio fue determinar el comportamiento del IEM posterior a un PRCyPS en pacientes con cardiopatías y riesgo cardiovascular alto (RCVA). MÉTODOS: Estudio de cohorte ambilectivo, descriptivo, analítico, no aleatorizado. Se seleccionaron pacientes con cardiopatías de etiología mixta con RCVA ingresados a un PRCyPS durante 4-6 semanas. A todos los pacientes se les realizó una prueba de ejercicio máximo en banda antes y después del PRCyPS. Se determinaron umbrales de consumo de oxígeno (VO2) pico, equivalentes metabólicos-carga, doble producto e IEM. Se estableció un punto de corte del IEM mediante una curva ROC con un valor de 7.37 con un área bajo la curva de 0.68 (IC 95%: 0.61-0.76; p < 0.001), sensibilidad 0.60 y 1-especificidad de 0.35. RESULTADOS: Se incluyeron 193 pacientes con una media de edad de 62.3 años, en su mayoría del sexo masculino (66.2%). Se observaron porcentajes de cambio en el IEM ­27.1% (p < 0.001), MET 43.1% (p < 0.001), doble producto 5.7% (p < 0.01) y MVO2: 8.3% (p < 0.01) al término del PRCyPS. CONCLUSIONES: Se observó un cambio significativo en el IEM posterior a un PRCyPS, lo cual se asoció a una mejoría en la EfCV, sugiriendo que este pueda considerarse como un parámetro clínico que evaluar en los programas de rehabilitación cardiaca.

Amplification of RUNX1 in a Patient With AML.

OBJECTIVES: Acute myeloid leukemia (AML) is a heterogeneous disease, characterized by clonal expansion of undifferentiated myeloid precursors, leading to alterations in hematopoiesis and bone marrow failure. Characteristic chromosomal abnormalities in AML are translocations t(8;21), inv(16), t(15;17), t(9;22), as well as mutations of genes that regulate proliferation and survival (FLT 3, PTPN 11, ETV 6/PDGFB), or genes responsible for differentiation and apoptosis (RUNX-1/RUNX1T1, PML/RARA, KMT2A, CEBPA and CBFB). Amplification of RUNX1 is a rare event in AML. Herein we described a 60-year-old patient that was admitted to the hospital due to a clinical picture of symptoms of acute anemia, thrombocytopenia, leukocytosis, and profuse nasal bleeding, hepatomegaly, splenomegaly, and gallstones. The blood cell count indicated the presence of 72% blasts. The bone marrow also showed 97% of blasts of myeloid lineage. The flow cytometry study also showed findings compatible with AML (MPOneg/+, CD34+, CD19neg /+d, CD117+, CD38neg /+, HLA-DR ++, CD13neg /+, CD33neg, CD15neg, D56neg, CD123+, CD7neg, CD11bneg, CD64neg, CD41aneg, which represented 68% of the pathological cellularity). Chromosome analysis showed additional copies of an isochromosome 21q. FISH studies revealed five copies of RUNX1. Amplification of RUNX1 is a rare event in AML with only a few cases reported in the literature (mainly therapy related AML) and it is usually associated with poor prognosis.

ECG Patient Simulator Based on Mathematical Models.

In this work, we propose a versatile, low-cost, and tunable electronic device to generate realistic electrocardiogram (ECG) waveforms, capable of simulating ECG of patients within a wide range of possibilities. A visual analysis of the clinical ECG register provides the cardiologist with vital physiological information to determine the patient's heart condition. Because of its clinical significance, there is a strong interest in algorithms and medical ECG measuring devices that acquire, preserve, and process ECG recordings with high fidelity. Bearing this in mind, the proposed electronic device is based on four different mathematical models describing macroscopic heartbeat dynamics with ordinary differential equations. Firstly, we produce full 12-lead ECG profiles by implementing a model comprising a network of heterogeneous oscillators. Then, we implement a discretized reaction-diffusion model in our electronic device to reproduce ECG waveforms from various rhythm disorders. Finally, in order to show the versatility and capabilities of our system, we include two additional models, a ring of three coupled oscillators and a model based on a quasiperiodic motion, which can reproduce a wide range of pathological conditions. With this, the proposed device can reproduce around thirty-two cardiac rhythms with the possibility of exploring different parameter values to simulate new arrhythmias with the same hardware. Our system, which is a hybrid analog-digital circuit, generates realistic ECG signals through digital-to-analog converters whose amplitudes and waveforms are controlled through an interactive and friendly graphic interface. Our ECG patient simulator arises as a promising platform for assessing the performance of electrocardiograph equipment and ECG signal processing software in clinical trials. Additionally the produced 12-lead profiles can be tested in patient monitoring systems.

Comparison of the Impacts of a Dynamic Exercise Program vs. a Mediterranean Diet on Serum Cytokine Concentrations in Women With Rheumatoid Arthritis. A Secondary Analysis of a Randomized Clinical Trial.

Background: Rheumatoid arthritis (RA) is a disease characterized by a chronic inflammatory state. High pro-inflammatory cytokine levels are associated with disease activity. Exercise and the Mediterranean diet (MD) exert anti-inflammatory effects; however, their impacts on inflammation in RA patients remains unknown. This study aimed to compare the effects of six-months of dynamic exercise program (DEP) vs. MD on pro- and anti-inflammatory cytokine serum concentrations. Methods: Secondary analysis of a randomized clinical trial in which 90 women with RA were randomly assigned to the DEP (n = 30), MD (n = 30), or control group (n = 30). All patients received pharmacological treatment. Serum concentrations of pro-inflammatory (TNF-α, TNF-ß, IL-1ß, IL-6 pg/mL) and anti-inflammatory (IL-10, IL-Ra pg/mL) cytokines were measured at baseline and after 6 months using the Luminex technique. Results: After 6 months of follow-up, we found an improvement of the median percentages changes concentrations of TNF-α (DEP, -12.3; MD, -13.3; control, 73.2; p = 0.01), TNF-ß (DEP, -67.4; MD, -54.9; control, 0; p = 0.04), and IL-6 (DEP, -19.9; MD, -37.7; control, 45.5; p = 0.04) in the DEP and MED groups in comparison with control group. IL-1Ra concentrations increased only in the MD group (13.8) compared to levels in the control group (-31.7), p = 0.04. There were no statistically significant differences between DEP and MD groups. Only n = 27 participants in the DEP group, n = 26 in the MD group, and n = 21 in the control group completed the follow-up. Conclusion: The DEP and the MD have potential effects in the concentrations of pro-inflammatory cytokines compared with those in a control group. Only the MD elevated the concentration of IL-Ra. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT02900898].

Two states of a light-sensitive membrane protein captured at room temperature using thin-film sample mounts.

Room-temperature diffraction methods are highly desirable for dynamic studies of biological macromolecules, since they allow high-resolution structural data to be collected as proteins undergo conformational changes. For crystals grown in lipidic cubic phase (LCP), an extruder is commonly used to pass a stream of microcrystals through the X-ray beam; however, the sample quantities required for this method may be difficult to produce for many membrane proteins. A more sample-efficient environment was created using two layers of low X-ray transmittance polymer films to mount crystals of the archaerhodopsin-3 (AR3) photoreceptor and room-temperature diffraction data were acquired. By using transparent and opaque polymer films, two structures, one corresponding to the desensitized, dark-adapted (DA) state and the other to the ground or light-adapted (LA) state, were solved to better than 1.9 Šresolution. All of the key structural features of AR3 were resolved, including the retinal chromophore, which is present as the 13-cis isomer in the DA state and as the all-trans isomer in the LA state. The film-sandwich sample environment enables diffraction data to be recorded at room temperature in both illuminated and dark conditions, which more closely approximate those in vivo. This simple approach is applicable to a wide range of membrane proteins crystallized in LCP and light-sensitive samples in general at synchrotron and laboratory X-ray sources.

Changes in hand grip strength and body weight after a dynamic exercise program and Mediterranean diet in women with rheumatoid arthritis: a randomized clinical trial.

BACKGROUND: In patients with rheumatoid arthritis (RA) exercise improves muscle strength and decreases fat mass, whereas the consumption of a Mediterranean diet (MD) also has been associated with higher grip strength. Therefore, it is important to explore the combined effects of these interventions on hand grip strength and weight in RA. OBJECTIVE: To determine the combined effect of an MD and a dynamic exercise program (DEP) on hand grip strength in women with RA. METHOD: In a randomized clinical trial, 106 women with RA were included and assigned to the DEP-MD, DEP and MD groups. Weight, body circumferences, Disease Activity Score-28, Health Assessment Questionnaire Disability Index [HAQ-DI], and hand grip strength were measured at baseline and 24 weeks after the interventions. RESULTS: After 24 weeks, hand grip strength showed a significant increase in the DEP group (median 2 kg) compared with DEP-MD (median 0.5 kg) and MD (median -0.5 kg) groups (p = 0.03). In the MD group weight and waist circumference showed a significant decrease (-2.2 kg and -4.3 cm) compared with DEP-MD (0.85 kg and 1.9 cm) and DEP (0.35 kg and 0.5 cm) groups (p < 0.01). Finally, a significant decrease was observed in the HAQ-DI after treatment in the DEP-MD group of -0.5 and the DEP group of -0.25 compared with the MD group with no change (p = 0.03). CONCLUSION: In women with RA, in addition to pharmacological treatment, DEP increases hand grip strength and an MD decreases weight and waist circumferences, while the combination of DEP and MD improves disability.

Populism in Peru: Populist attitudes and perception of the populist offer and its relationship with political cynicism and attitudes toward democracy.

Populism is a phenomenon that is gaining attention in Political Psychology. The goal of the current study was to determine the relationship between populist attitudes, based on the populist demand and the perception of the populist offer, and several indices of political cynicism and attitudes toward democracy in Peru. To do this, a quantitative correlational study including 391 participants from diverse Peruvian locations was carried out. Both populist attitudes and critical perception of the populist offer are found to be directly related to Political Cynicism in its dimensions of Political Distrust, Political Hopelessness, and Political Moral Laxity, and inversely related to the dimension of Political System Change. Similarly, both dimensions of populism are directly related to Democratic Support and inversely related to Democratic Satisfaction. The findings support the notion that populist attitudes emerge in the context of distrust of the system and express an ambivalent relationship with democracy. Furthermore, the various approaches developed by the social sciences to address the populist phenomenon are discussed in terms of their strengths and limitations.

Neurological Manifestations and Outcomes in a Retrospective Cohort of Mexican Inpatients with SARS-CoV-2 Pneumonia: Design of a Risk Profile.

We analyzed the neurological manifestations in Mexican patients hospitalized with pneumonia due to COVID-19 and investigated the association between demographic, clinical, and biochemical variables and outcomes, including death. A retrospective, analytical study was conducted using the electronic records of patients hospitalized between 1 April 2020 and 30 September 2020. Records of 1040 patients were analyzed: 31.25% died and 79.42% had neurological symptoms, including headache (80.62%), anosmia (32.20%), ageusia (31.96%), myopathy (28.08%), disorientation (14.89%), encephalopathy (12.22%), neuropathy (5.4%), stroke (1.3%), seizures (1.3%), cerebral hemorrhage (1.08%), encephalitis (0.84%), central venous thrombosis (0.36%), and subarachnoid hemorrhage (0.24%). Patients also had comorbidities, such as hypertension (42.30%), diabetes mellitus (38.74%), obesity (61.34%), chronic obstructive pulmonary disease (3.17%), and asthma (2.01%). Factors associated with neurological symptoms were dyspnea, chronic obstructive pulmonary disease, advanced respiratory support, prolonged hospitalization, and worsening fibrinogen levels. Factors associated with death were older age, advanced respiratory support, amine management, chronic obstructive pulmonary disease, intensive care unit management, dyspnea, disorientation, encephalopathy, hypertension, neuropathy, diabetes, male sex, three or more neurological symptoms, and obesity grade 3. In this study we designed a profile to help predict patients at higher risk of developing neurological complications and death following COVID-19 infection.