Variación intraespecífica e individual de los pelos de mamíferos del Estado de México: implicaciones en la identificación interespecífica

Se determinó la variación del pelo de guardia dorsal entre individuos de la misma especie y se comparó la variación de un individuo en diferentes regiones. Se midió la longitud total y diámetro de la médula, además se determinó el patrón de tonalidad y tipo de médula. En la comparación intraespecífica se caracterizaron 530 pelos de guardia dorsales de 53 organismos. A pesar de las variaciones en la longitud y diámetro de la médula, puede realizarse una identificación exitosa de los organismos en un plano específico utilizando la guía de identificación de mamíferos terrestres a partir del pelo de guardia, excepto para Canis latrans y Liomys irroratus. En la comparación individual se describieron 560 pelos de guardia de 14 especies. Se encontraron diferencias en la longitud total del pelo, en el diámetro de la médula y en la coloración; el único carácter que permaneció constante fue la médula.Se determinó la variación del pelo de guardia dorsal entre individuos de la misma especie y se comparó la variación de un individuo en diferentes regiones. Se midió la longitud total y diámetro de la médula, además se determinó el patrón de tonalidad y tipo de médula. En la comparación intraespecífica se caracterizaron 530 pelos de guardia dorsales de 53 organismos. A pesar de las variaciones en la longitud y diámetro de la médula, puede realizarse una identificación exitosa de los organismos en un plano específico utilizando la guía de identificación de mamíferos terrestres a partir del pelo de guardia, excepto para Canis latrans y Liomys irroratus. En la comparación individual se describieron 560 pelos de guardia de 14 especies. Se encontraron diferencias en la longitud total del pelo, en el diámetro de la médula y en la coloración; el único carácter que permaneció constante fue la médula

SISTEMA DE LOCALIZACIÓN POR RADAR PARA UN ROBOT DE CONFIGURACIÓN ACKERMANN (RADAR LOCATION SYSTEM FOR AN ACKERMANN CONFIGURATION ROBOT)

Resumen El proyecto consiste en desarrollar un sistema de localización capaz de llevar a cabo el control de la trayectoria de un robot móvil, este robot está diseñado bajo los parámetros de la configuración de movimiento Ackermann y fue construido con un chasis de acrílico de 3 mm en el que se montaron los componentes que lo conforman, los cuales son: el sistema de dirección, sistema de tracción y el sistema de control. Además, se recurrió a la tecnología de impresión 3D para fabricar una base necesaria para evitar interferencias en el escáner láser. Para la elaboración del sistema de localización se requiere el uso del escáner láser RPLiDAR modelo A1M8, que actúa como el principal componente para obtener una retroalimentación del ambiente. Esto se traduce como el uso de los datos que entrega el escáner, los cuales mediante análisis matemáticos ayudan al establecimiento de un sistema coordenado y el cálculo de la posición. La conexión del sistema de localización y el sistema de control brinda la posibilidad de programar las trayectorias a seguir por el robot, sin embargo, debido a la existencia de errores se implementa un sistema de recálculo de trayectoria que toma como principales herramientas de funcionamiento la cinemática del robot y el filtro de partículas creado para el cálculo de incertidumbre. Este recálculo reduce considerablemente el error en la trayectoria, lo cual queda demostrado en las pruebas realizadas en una trayectoria compuesta por: 3 movimientos rectos de 40 cm de longitud y 2 movimientos curvos con un radio de curvatura de 40 cm. La precisión en cuanto al cumplimiento de la trayectoria del sistema de recálculo es alta, ya que se observan variaciones por debajo de los 10 cm, comparado con un comportamiento ideal. Palabras clave: configuración Ackermann, escáner láser, robot móvil, incertidumbre, sistemas de radar, cinemática, filtro de partículas. Abstract The project consists of developing a location system capable of controlling the trajectory of a mobile robot, this robot is designed under the parameters of the Ackermann movement configuration and was built with a 3 mm acrylic chassis in the that the components that comprise it were assembled, which are: the steering system, traction system and the control system; In addition, 3D printing technology was used to manufacture a necessary base to avoid interference in the laser scanner. For the development of the location system, the use of the RPLiDAR model A1M8 laser scanner is required, which acts as the main component to obtain feedback from the environment in which the robot moves, this is translated as the use of the data provided by the scanner, which through mathematical analysis help the establishment of a coordinate system and the calculation of the position. The connection of the location system and the control system offers the possibility of programming the trajectories to be followed by the robot, however, due to the existence of errors, a trajectory recalculation system is implemented that takes the kinematics as its main operating tools. of the robot and the particle filter created for the uncertainty calculation; This recalculation considerably reduces the error in the trajectory, which is demonstrated in the tests carried out on a trajectory composed of 3 straight movements of 40 cm in length and 2 curved movements with a radius of curvature of 40 cm. The precision in terms of compliance with the trajectory of the recalculation system is high, since variations are observed below 10 cm compared to an ideal behavior. Keywords: Ackermann configuration, laser scanner, mobile robot, uncertainty, radar systems, kinematics, particle filter

Mitochondrial Na+ controls oxidative phosphorylation and hypoxic redox signalling

All metazoans depend on O2 delivery and consumption by the mitochondrial oxidative phosphorylation (OXPHOS) system to produce energy. A decrease in O2 availability (hypoxia) leads to profound metabolic rewiring. In addition, OXPHOS uses O2 to produce reactive oxygen species (ROS) that can drive cell adaptations through redox signalling, but also trigger cell damage1–4, and both phenomena occur in hypoxia4–8. However, the precise mechanism by which acute hypoxia triggers mitochondrial ROS production is still unknown. Ca2+ is one of the best known examples of an ion acting as a second messenger9, yet the role ascribed to Na+ is to serve as a mere mediator of membrane potential and collaborating in ion transport10. Here we show that Na+ acts as a second messenger regulating OXPHOS function and ROS production by modulating fluidity of the inner mitochondrial membrane (IMM). We found that a conformational shift in mitochondrial complex I during acute hypoxia11 drives the acidification of the matrix and solubilization of calcium phosphate precipitates. The concomitant increase in matrix free-Ca2+ activates the mitochondrial Na+/Ca2+ exchanger (NCLX), which imports Na+ into the matrix. Na+ interacts with phospholipids reducing IMM fluidity and mobility of free ubiquinone between complex II and complex III, but not inside supercomplexes. As a consequence, superoxide is produced at complex III, generating a redox signal. Inhibition of mitochondrial Na+ import through NCLX is sufficient to block this pathway, preventing adaptation to hypoxia. These results reveal that Na+ import into the mitochondrial matrix controls OXPHOS function and redox signalling through an unexpected interaction with phospholipids, with profound consequences in cellular metabolism

Characteristics of patients with type 2 diabetes mellitus newly treated with GLP-1 receptor agonists (CHADIG Study): a cross-sectional multicentre study in Spain

Objective: Several glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1Ra) have been made recently available in Spain for type 2 diabetes mellitus (DM2) treatment. There are no published data on the clinical and sociodemographic profile of patients initiating treatment with GLP-1Ra in Spain. Our objective was to understand these patients' characteristics in a real-world clinical practice setting. Design: Cross-sectional observational study. Setting: Spanish specialist outpatient clinics. Participants: 403 adults with DM2 initiating GLP-1Ra treatment were included. Primary and secondary outcome measures: Sociodemographic and DM2-related clinical data, including treatment at and after GLP-1Ra initiation and comorbidities, were collected. Results: Evaluable patients (n=403; 50.9% female) were included ( July 2013 to March 2014) at 24 centres by 53 specialists (47 endocrinology, 6 internal medicine), with the following profile (value±SD): age (58.3±10.4 years), diabetes duration (9.9±7 years), body mass index (BMI; 36.2±5.5) and glycated haemoglobin (HbA1c; 8.4±1.4%); 14% had HbA1c≤7%. Previous antidiabetic treatment: 53.8% only oral antidiabetic drugs (OADs), 5.2% insulin and 40% insulin and OAD; of those receiving OAD, 35% single drug, 38.2% 2 drugs and 24% 3 drugs. Concomitant to GLP-1Ra, 55.3% were only on OAD, 36.2% on insulin and OAD, and 7.2% only on insulin. Of those receiving OAD, the GLP-1Ra was mainly associated with 1 drug (65%) or 2 drugs (31.8%). GLP-1Ra are frequently added to existing antidiabetic drugs, with dipeptidyl peptidase-4 inhibitors being the OAD most frequently switched (45% receiving 1 before starting GLP-1Ra, only 2.7% receiving it concomitantly). Conclusions: In Spain, GLP-1Ra therapy is usually started in combination with OADs or OADs and insulin. These drugs are used in relatively young patients often not reaching therapeutic goals with other treatment combinations, roughly a decade after diagnosis and with a relatively high BMI. The latter could be explaine

Road safety evaluation through automatic extraction of road horizontal alignments from Mobile LiDAR System and inductive reasoning based on a decision tree

13 p.Safe roads are a necessity for any society because of the high social costs of traffic accidents. This challenge is addressed by a novel methodology that allows us to evaluate road safety from Mobile LiDAR System data, taking advantage of the road alignment due to its influence on the accident rate. Automation is obtained through an inductive reasoning process based on a decision tree that provides a potential risk assessment. To achieve this, a 3D point cloud is classified by an iterative and incremental algorithm based on a 2.5D and 3D Delaunay triangulation, which apply different algorithms sequentially. Next, an automatic extraction process of road horizontal alignment parameters is developed to obtain geometric consistency indexes, based on a joint triple stability criterion. Likewise, this work aims to provide a powerful and effective preventive and/or predictive tool for road safety inspections. The proposed methodology was implemented on three stretches of Spanish roads, each with different traffic conditions that represent the most common road types. The developed methodology was successfully validated through as-built road projects, which were considered as “ground truth.”S

Genomic Characterization of Host Factors Related to SARS-CoV-2 Infection in People with Dementia and Control Populations: The GR@ACE/DEGESCO Study

Emerging studies have suggested several chromosomal regions as potential host genetic factors involved in the susceptibility to SARS-CoV-2 infection and disease outcome. We nested a COVID-19 genome-wide association study using the GR@ACE/DEGESCO study, searching for susceptibility factors associated with COVID-19 disease. To this end, we compared 221 COVID-19 confirmed cases with 17,035 individuals in whom the COVID-19 disease status was unknown. Then, we performed a meta-analysis with the publicly available data from the COVID-19 Host Genetics Initiative. Because the APOE locus has been suggested as a potential modifier of COVID-19 disease, we added sensitivity analyses stratifying by dementia status or by disease severity. We confirmed the existence of the 3p21.31 region (LZTFL1, SLC6A20) implicated in the susceptibility to SARS-CoV-2 infection and TYK2 gene might be involved in COVID-19 severity. Nevertheless, no statistically significant association was observed in the COVID-19 fatal outcome or in the stratified analyses (dementia-only and non-dementia strata) for the APOE locus not supporting its involvement in SARS-CoV-2 pathobiology or COVID-19 prognosis

Effects of intubation timing in patients with COVID-19 throughout the four waves of the pandemic : a matched analysis

The primary aim of our study was to investigate the association between intubation timing and hospital mortality in critically ill patients with COVID-19-associated respiratory failure. We also analysed both the impact of such timing throughout the first four pandemic waves and the influence of prior non-invasive respiratory support on outcomes. This is a secondary analysis of a multicentre, observational and prospective cohort study that included all consecutive patients undergoing invasive mechanical ventilation due to COVID-19 from across 58 Spanish intensive care units (ICU) participating in the CIBERESUCICOVID project. The study period was between 29 February 2020 and 31 August 2021. Early intubation was defined as that occurring within the first 24 h of intensive care unit (ICU) admission. Propensity score (PS) matching was used to achieve balance across baseline variables between the early intubation cohort and those patients who were intubated after the first 24 h of ICU admission. Differences in outcomes between early and delayed intubation were also assessed. We performed sensitivity analyses to consider a different timepoint (48 h from ICU admission) for early and delayed intubation. Of the 2725 patients who received invasive mechanical ventilation, a total of 614 matched patients were included in the analysis (307 for each group). In the unmatched population, there were no differences in mortality between the early and delayed groups. After PS matching, patients with delayed intubation presented higher hospital mortality (27.3% versus 37.1%, p =0.01), ICU mortality (25.7% versus 36.1%, p=0.007) and 90-day mortality (30.9% versus 40.2%, p=0.02) when compared to the early intubation group. Very similar findings were observed when we used a 48-hour timepoint for early or delayed intubation. The use of early intubation decreased after the first wave of the pandemic (72%, 49%, 46% and 45% in the first, second, third and fourth wave, respectively; first versus second, third and fourth waves p<0.001). In both the main and sensitivity analyses, hospital mortality was lower in patients receiving high-flow nasal cannula (n=294) who were intubated earlier. The subgroup of patients undergoing NIV (n=214) before intubation showed higher mortality when delayed intubation was set as that occurring after 48 h from ICU admission, but not when after 24 h. In patients with COVID-19 requiring invasive mechanical ventilation, delayed intubation was associated with a higher risk of hospital mortality. The use of early intubation significantly decreased throughout the course of the pandemic. Benefits of such an approach occurred more notably in patients who had received high-flow nasal cannul

Prognostic implications of comorbidity patterns in critically ill COVID-19 patients: A multicenter, observational study

Background The clinical heterogeneity of COVID-19 suggests the existence of different phenotypes with prognostic implications. We aimed to analyze comorbidity patterns in critically ill COVID-19 patients and assess their impact on in-hospital outcomes, response to treatment and sequelae. Methods Multicenter prospective/retrospective observational study in intensive care units of 55 Spanish hospitals. 5866 PCR-confirmed COVID-19 patients had comorbidities recorded at hospital admission; clinical and biological parameters, in-hospital procedures and complications throughout the stay; and, clinical complications, persistent symptoms and sequelae at 3 and 6 months. Findings Latent class analysis identified 3 phenotypes using training and test subcohorts: low-morbidity (n=3385; 58%), younger and with few comorbidities; high-morbidity (n=2074; 35%), with high comorbid burden; and renal-morbidity (n=407; 7%), with chronic kidney disease (CKD), high comorbidity burden and the worst oxygenation profile. Renal-morbidity and high-morbidity had more in-hospital complications and higher mortality risk than low-morbidity (adjusted HR (95% CI): 1.57 (1.34-1.84) and 1.16 (1.05-1.28), respectively). Corticosteroids, but not tocilizumab, were associated with lower mortality risk (HR (95% CI) 0.76 (0.63-0.93)), especially in renal-morbidity and high-morbidity. Renal-morbidity and high-morbidity showed the worst lung function throughout the follow-up, with renal-morbidity having the highest risk of infectious complications (6%), emergency visits (29%) or hospital readmissions (14%) at 6 months (p<0.01). Interpretation Comorbidity-based phenotypes were identified and associated with different expression of in-hospital complications, mortality, treatment response, and sequelae, with CKD playing a major role. This could help clinicians in day-to-day decision making including the management of post-discharge COVID-19 sequelae. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd

The Chemotherapeutic Drug 5-Fluorouracil Promotes PKR-Mediated Apoptosis in a p53- Independent Manner in Colon and Breast Cancer Cells

The chemotherapeutic drug 5-FU is widely used in the treatment of a range of cancers, but resistance to the drug remains a major clinical problem. Since defects in the mediators of apoptosis may account for chemo-resistance, the identification of new targets involved in 5-FU-induced apoptosis is of main clinical interest. We have identified the ds-RNA-dependent protein kinase (PKR) as a key molecular target of 5-FU involved in apoptosis induction in human colon and breast cancer cell lines. PKR distribution and activation, apoptosis induction and cytotoxic effects were analyzed during 5-FU and 5-FU/IFNα treatment in several colon and breast cancer cell lines with different p53 status. PKR protein was activated by 5-FU treatment in a p53-independent manner, inducing phosphorylation of the protein synthesis translation initiation factor eIF-2α and cell death by apoptosis. Furthermore, PKR interference promoted a decreased response to 5-FU treatment and those cells were not affected by the synergistic antitumor activity of 5-FU/IFNα combination. These results, taken together, provide evidence that PKR is a key molecular target of 5-FU with potential relevance in the clinical use of this drug

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality