RESUMO
Chagas Disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi, affecting 6-8 million people, mainly in Latin America. The medical treatment is based on two compounds, benznidazole and nifurtimox, with limited effectiveness and that produce severe side effects; consequently, there is an urgent need to develop new, safe, and effective drugs. Amphotericin B is the most potent antimycotic known to date. A21 is a derivative of this compound with the property of binding to ergosterol present in cell membranes of some organisms. In the search for a new therapeutic drug against T. cruzi, the objective of this work was to study the in vitro and in vivo effects of A21 derivative on T. cruzi. Our results show that the A21 increased the reactive oxygen species and reduced the mitochondrial membrane potential, affecting the morphology, metabolism, and cell membrane permeability of T. cruzi in vitro. Even more important was finding that in an in vivo murine model of infection, A21 in combination with benznidazole was able to reduce blood parasitemia, diminish the immune inflammatory infiltrate in skeletal muscle and rescue all the mice from death due to a virulent T. cruzi strain.
RESUMO
Mexican Afro-descendant is a population poorly studied in many aspects, between them the infectious diseases that they suffer. This population is mainly found in the country's Pacific (Oaxaca and Guerrero states) and Atlantic (Veracruz) coast. In these regions, a diversity of triatomine vectors of the Chagas disease is found. Also, all the genotypes of Trypanosoma cruzi DTUs have been reported. That is why the present study aimed to study the presence of antibodies against T. cruzi and cardiac pathology associated with the Chagas disease in the Mexican Afro-descendant population of Guerrero and Oaxaca. ELISA, Western blot, and recombinant antigen's ELISA were used to evaluate the seropositivity of these communities. Furthermore, an electrocardiographic study and evaluation of risk factors associated with T. cruzi infection in the Oaxaca and Guerrero populations were conducted. 26.77% of the analyzed population was positive for two serological tests. These percentages are higher than the previously reported for the mestizo population in similar studies. Electrocardiographic results showed cardiac disorder associated with the Chagas disease in the population. Also, risk factors were identified associated with the men's activities in the outdoor working areas.
RESUMO
BACKGROUND: The risk of radiogenic cancer induction due to radiotherapy depends on the dose received by the patient's organs. Knowing the position of all organs is needed to assess this dose in a personalized way. However, radiotherapy planning computed tomography (pCT) scans contain truncated patient anatomy, limiting personalized dose evaluation. PURPOSE: To develop a simple and freely available computational tool that adapts an ICRP reference computational phantom to generate a patient-specific whole-body CT for peripheral dose computations. METHODS: Various bone-segmentation methods were explored onto fifteen pCTs, and the one with the highest Sørensen-Dice coefficient was implemented. The reference phantom is registered to the pCT, obtaining a registration transform matrix, which is then applied to create the whole-body virtual CT. Additional validation involved a comparison of absorbed doses to organs delineated on both the pCT and the virtual CT. RESULTS: A dedicated graphical user interface was designed and implemented to house the developed functions for i) selecting a registration region on which automatic bone segmentation and rigid registration will occur, ii) displaying the results of these processes under selectable views, and iii) exporting the final patient-specific whole-body CT. This software was termed IS2aR. The tested whole-body virtual CT generated by IS2aR fulfilled our requirements. CONCLUSIONS: IS2aR is a user-friendly computational software to create a personalized whole-body CT containing the original structures in the reference phantom. The personalized dose deposited in peripheral organs can be estimated further to assess second cancer induction risk in epidemiological studies.
Assuntos
Software , Tomografia Computadorizada por Raios X , Humanos , Tomografia Computadorizada por Raios X/métodos , Imagens de Fantasmas , Planejamento da Radioterapia Assistida por Computador/métodosRESUMO
Determination of live weight, which is one of the most important features that determine meat production, is a very important issue for herd management and sustainable livestock. In this context, the necessity of finding alternative methods has emerged, especially in rural conditions, due to the difficulties to be experienced in finding the weighing tool. Especially for conditions with no weighing tool, it has been tried to establish relations between the information obtained from body measurements and live weight. Since these studies will differ from species to species and breed to breed, the need for new studies is extremely high. For this aim, it is to evaluate the body measurement information obtained with the present study using several statistical approaches. To implement this aim, several data mining and machine learning algorithms such as multivariate adaptive regression splines (MARS), classification and regression tree (CART), and support vector machine regression (SVR) algorithms were used for training (70%) and test (30%) sets. To predict final body weight, 280 hair sheep breeds (162 female and 118 male) ranging from 2 months to 3 years were used with different data mining and machine learning approaches. Various goodness-of-fit criteria were used to evaluate the performances of the aforementioned algorithms. Although the MARS and SVR algorithms gave the same and highest results in terms of R2 and r values for both the train and the test sets, the SVR algorithm is one of the methods to be recommended as a result of this study, especially when other goodness-of-fit criteria are evaluated. In conclusion, the usage of SVR algorithms may be a useful tool of machine learning approaches for detecting the hair sheep breed standards and may contribute to increasing the sheep meat quality in Mexico.
Assuntos
Biometria , Carneiro Doméstico , Ovinos , Animais , Algoritmos , Mineração de Dados , Aprendizado de Máquina , Peso CorporalRESUMO
Introducción: La enfermedad hepática grasa no alcohólica es una afección clínica- morfológica que se caracteriza por una infiltración grasa del hígado en más de un 5 %; tiene dos estadios: esteatosis simple y esteatohepatitis, la cual puede progresar a: fibrosis, cirrosis y hepatocarcinoma. Objetivo: Determinar la relación entre las variables clínicas y epidemiológicas con esta enfermedad, así como los índices de fibrosis y su relación. Métodos: Se realizó un estudio descriptivo con diseño transversal en los pacientes atendidos en la consulta de hígado y vías biliares del Hospital Universitario « Dr. Celestino Hernández Robau», en la etapa de enero- diciembre de 2017. Se trabajó con una población conformada por 60 pacientes, mayores o igual a 20 años de edad, con diagnóstico de enfermedad hepática grasa no alcohólica primaria, sobrepesos u obesos. Resultados: Predominó el grupo etario entre 50-59 años de edad, del sexo femenino, obesos y con esteatosis grado I. Se constató que el 73,33% de los pacientes tenían síndrome metabólico y en ellos prevaleció el grado II de esteatosis. Al relacionar los riesgos de fibrosis se encontraron 28 pacientes con riesgo indeterminado y alto en las clasificaciones FIB-4 y NFS, respectivamente, y 5 presentaron alto riesgo en ambas variables. Los índices de FIB-4 y NFS tuvieron una correlación significativa, directamente proporcional y considerable. Conclusiones: La correlación detectada entre los índices FIB-4 y NFS reafirmó el valor en la detección de sospecha de fibrosis y orientó, en la práctica clínica, la conducta ante los diferentes pacientes con esta afección.
Introduction: non-alcoholic fatty liver disease is a clinical and morphological condition characterized by fatty infiltration of the liver in more than 5%; it has two stages: simple steatosis and steatohepatitis, which can progress to fibrosis, cirrhosis and hepatocellular carcinoma. Objective: to determine the relationship between clinical and epidemiological variables with this disease, as well as fibrosis indices and their relationship. Methods: a cross-sectional descriptive study was carried out in patients seen in the liver and biliary tract consultation at " Dr. Celestino Hernández Robau" University Hospital from January to December 2017. We worked with a population made up of 60 overweight or obese patients older than or equal to 20 years who were diagnosed with primary non-alcoholic fatty liver disease. Results: the age group between 50-59 years of age, female gender, obese ones and with grade I steatosis prevailed. We found that 73.33% of the patients had metabolic syndrome and grade II steatosis prevailed in them. A number of 28 patients were found with indeterminate and high risk in the FIB-4 and NAFLD classifications, respectively, when relating the risks of fibrosis, as well as 5 had high risk in both variables. The FIB-4 and NAFLD indices had a significant, directly proportional, and considerable correlation. Conclusions: the correlation detected between the FIB-4 and NAFLD indices reaffirmed the value in the detection of suspected fibrosis and guided, in clinical practice, the conduct of different patients with this condition.
Assuntos
Síndrome Metabólica , Hepatopatia Gordurosa não AlcoólicaRESUMO
Trypanosoma cruzi is the etiologic agent of Chagas disease, a parasitic disease of great medical importance on the American continent. Trypomastigote infection's initial step in a mammalian host is vital for the parasite's life cycle. A trypomastigote's surface presents many molecules, some of which have been proposed to be involved in the infection process, including a glycoprotein family called mucin-associated surface proteins (MASPs). This work describes a 49-kDa molecule (MASP49) that belongs to this family and is expressed mainly on the surfaces of amastigotes and trypomastigotes but can be found in extracts and the membrane-enriched fractions of epimastigotes. This protein is partially GPI-anchored to the surface and has a role during the internalization process, since its blockade with specific antibodies decreases parasite entry into Vero cells by 62%. This work shows that MASP49 binds to peritoneal macrophages and rat cardiomyocytes, undergoes glycosylation via galactose N-acetylgalactosamine, and can attach to the macrophage murine C-type lectin receptor (mMGL). These results suggest that MASP49 can be considered a virulence factor in T. cruzi, and a better understanding of its role in the infection process is necessary.
RESUMO
Introducción: la formación de los residentes deviene proceso fundamental para garantizar especialistas con una sólida preparación profesional. Objetivo: exponer un conjunto de ideas, posicionamientos teóricos y metodológicos orientados a elevar la calidad de la formación del residente en Gastroenterología desde un enfoque creativo y tecnológico. Métodos: se realizó una revisión bibliográfica sistemática para desarrollar un análisis del contenido de documentos, tesis de doctorado, maestría, artículos originales y de revisión publicados entre 1981 y 2022 en español. Se consultaron 47 artículos y se seleccionaron 28. La búsqueda fue realizada en las bases de datos SciELO y Google académico de julio a septiembre de 2022. Tras la identificación de los estudios preseleccionados, se llevó a cabo la lectura de los títulos, resumen y palabras claves para comprobar su pertinencia con el estudio. Desarrollo: la revisión documental permitió esclarecer una serie de dificultades presentes en el proceso de formación de los especialistas en Gastroenterología y hacer propuestas que pueden contribuir en este sentido desde las nuevas concepciones de la educación como la creatividad, el trabajo colaborativo y la enseñanza problémica, usando las ventajas de las tecnologías de la información y las comunicaciones. Conclusiones: el proceso de formación de los residentes en Gastroenterología necesita adaptarse a las nuevas exigencias de la educación. Potencializar la creatividad desde la perspectiva de la enseñanza problémica y el trabajo colaborativo mediante el uso de las herramientas que brindan las tecnologías de la información y la comunicación, debe ser la directriz, en este propósito.
Introduction: The training of residents becomes a fundamental process to guarantee specialists with a solid professional preparation. Objective: To present a set of ideas, theoretical and methodological positions that guide how to raise the quality of the resident's training in Gastroenterology from a creative and technological approach. Method: A systematic bibliographic review was carried out to develop an analysis of the content of documents, doctoral theses, master's degrees, original and review articles published from 1981 to 2022 in Spanish. We consulted 47 articles and selected 26. The search was carried out in the SciELO and Google scholar databases from July to September 2022, after the identification of the pre-selected studies, the titles, abstract and keywords were read to check their relevance to the study. Development: The documentary review allowed to clarify a series of difficulties in the training process of specialists in gastroenterology and make proposals that can contribute in this sense from the new conceptions of education, such as creativity, collaborative work, problem-solving teaching using the advantages of information and communication technologies. Conclusions: The training process of residents in gastroenterology needs to adapt to the new demands of education. Potentiating creativity from the perspective of probability teaching and collaborative work through the use of the tools provided by information and communication technologies, should be the guideline, in this purpose.
Assuntos
Criatividade , Educação Médica , Tecnologia da Informação , GastroenterologiaRESUMO
Considering that cancer survival rates have been growing and that nearly two-thirds of those survivors were exposed to clinical radiation during its treatment, the study of long-term radiation effects, especially secondary cancer induction, has become increasingly important. To correctly assess this risk, knowing the dose to out-of-field organs is essential. As it has been reported, commercial treatment planning systems do not accurately calculate the dose far away from the border of the field; analytical dose estimation models may help this purpose. In this work, the development and validation of a new three-dimensional (3D) analytical model to assess the photon peripheral dose during radiotherapy is presented. It needs only two treatment-specific input parameter values, plus information about the linac-specific leakage, when available. It is easy to use and generates 3D whole-body dose distributions and, particularly, the dose to out-of-field organs (as dose-volume histograms) outside the 5% isodose for any isocentric treatment using coplanar beams [including intensity modulated radiotherapy and volumetric modulated arc therapy (VMAT)]. The model was configured with the corresponding Monte Carlo simulation of the peripheral absorbed dose for a 6 MV abdomen treatment on the International Comission on Radiological Protection (ICRP) 110 computational phantom. It was then validated with experimental measurements using thermoluminescent dosimeters in the male ATOM anthropomorphic phantom irradiated with a VMAT treatment for prostate cancer. Additionally, its performance was challenged by applying it to a lung radiotherapy treatment very different from the one used for training. The model agreed well with measurements and simulated dose values. A graphical user interface was developed as a first step to making this work more approachable to a daily clinical application.
RESUMO
RESUMEN Introducción: El esófago de Barrett es una condición esofágica adquirida, que puede evolucionar a un adenocarcinoma. Con el paso de los años, la terapia endoscópica ha remplazado la cirugía en el tratamiento de esta afección. Objetivos: Mostrar los resultados de la aplicación de la técnica de resección endoscópica de la mucosa y la ablación con Hibrid-APC en pacientes portadores de esófago de Barrett con displasia de bajo o alto grado. Métodos: Se realizó un estudio descriptivo y retrospectivo en 29 pacientes entre los años 2014-2019, en el Servicio de endoscopias del Centro Nacional de Cirugía de Mínimo Acceso. Se estudiaron variables sociodemográficas, se estableció la clasificación endoscópica del esófago de Barrett, se describieron las características de la lesión, el diagnóstico histológico, la terapéutica endoscópica, la presencia de complicaciones, la resección incompleta y recidiva. Se aplicaron técnicas de estadística descriptiva y métodos no paramétricos. Resultados: Predominó el sexo masculino (58,62 %) y el grupo de 41-60 años (58,62 %). El segmento corto con lesiones planas y el largo con lesiones elevadas fueron más frecuentes (37,93 %). Se realizaron 15 resecciones y 14 ablaciones con Hibrid-APC; se observó una estenosis como complicación de la resección endoscópica de la mucosa y recidivas con ambas técnicas (5 pacientes, 17 %), tres relacionadas con la resección y dos con el Hibrid-APC. El Hibrid-APC alcanzó una efectividad terapéutica del 85,71 % y la resección del 80 %. Conclusiones: El tratamiento endoscópico con displasia de bajo y alto grado, mostró ser un procedimiento efectivo y seguro, con bajo porciento de complicaciones y recidivas.
ABSTRACT Introduction: Barrett's esophagus is an acquired esophageal condition that can evolve into an adenocarcinoma. Over the years, endoscopic therapy has replaced surgery in the treatment of this condition. Objectives: to show the results of the application of the endoscopic mucosal resection and Hybrid-APC ablation technique in patients with Barrett's esophagus with low-grade or high-grade dysplasia. Methods: a descriptive and retrospective study was carried out in 29 patients between 2014 and 2019, in the Endoscopy service of the National Center for Minimal Access Surgery. Social and demographic variables were studied; endoscopic classification of Barrett's esophagus was established, as well as the characteristics of the lesion, histological diagnosis, endoscopic therapy, the presence of complications, incomplete resection and recurrence were described. Descriptive statistics techniques and non-parametric methods were applied. Results: male gender (58.62%) and the group aged 41-60 years (58.62%) predominated. The short segment with flat lesions and the long segment with raised lesions were more frequent (37.93%). A number of 15 resections and 14 ablations were performed with Hybrid-APC; one stricture was observed as a complication of endoscopic mucosal resection and recurrences with both techniques (5 patients, 17%), three related to resection and two to Hybrid-APC. The Hybrid-APC achieved a therapeutic effectiveness of 85.71% and the resection one of 80%. Conclusions: endoscopic treatment with low- and high-grade dysplasia proved to be an effective and safe procedure, with a low percentage of complications and recurrences.
Assuntos
Esôfago de Barrett/cirurgia , Cirurgia Endoscópica por Orifício Natural , Coagulação com Plasma de ArgônioRESUMO
Oral acquisition of Trypanosoma cruzi is a foodborne transmission by juices and fruits contaminated with metacyclic trypomastigotes (MT) or by the ingestion of wild reservoirs infected with blood trypomastigotes (BT). In Mexico, hunting and food consumption of wild animals are current practices, which could represent a risk factor for oral infection in the rural population. In this work, Balb/c mice were inoculated by oral route with BT of a highly virulent T. cruzi Mexican strain (DTU I) to evaluate the establishment of the infection, and the humoral and cellular immune response in the acute phase of the infection. We show that BT induces blood and tissue parasitism producing an inflammatory process in the heart and skeletal muscle and low parasitism and inflammation in the digestive tract of orally infected mice. Besides, in the acute phase, the BT promotes splenomegaly, intense damage in skeletal and cardiac muscles, a humoral response dominated by the IgG isotype, and the expression of pro-inflammatory cytokines.
Assuntos
Doença de Chagas , Trypanosoma cruzi , Animais , Imunidade , Camundongos , Camundongos Endogâmicos BALB C , Miocárdio , ParasitemiaRESUMO
The Santiago River (Jalisco) is a major waterway in western Mexico and has received considerable attention due to its severe pollution. Understanding the impact of reduced human activity on water quality in the Santiago River during the COVID-19 lockdown (April-May 2020) is critical for river management and restoration. However, there has been no published study in this context, presenting a significant knowledge gap. Hence, this study focuses on determining if the nationwide COVID-19 lockdown influenced or improved surface water quality in a 262-km stretch of the Santiago River upstream. Data for 15 water quality parameters collected during the lockdown were compared to levels obtained in 2019 (pre-lockdown), 2021 (unlock), and the previous eleven years (2009-2019). The values of turbidity, BOD, COD, TSS, f. coli, t. coli, nitrate, sulfate, and Pb decreased by 4-36%, while pH, EC, total nitrogen, and As increased by 0.3-21% during the lockdown compared to the pre-lockdown period, indicating a reduction in organic load in the river due to the temporary closure of industrial and commercial activities. An eleven-year comparison estimated a 0-38% decline in pH, TSS, COD, total nitrogen, sulfates, nitrates, and Pb. The unlock-period comparison showed a significant rise of 3-37% in all parameters except As, highlighting the potential repercussions of restoring activity along the Santiago River. Estimated water quality indices demonstrated short-term improvements in river water quality during the lockdown when compared to other time periods investigated. According to factor analysis, the main pollution sources influencing river water quality were untreated household sewage, industrial wastewater, and agricultural effluents. Overall, our analysis showed that the COVID-19-imposed lockdown improved the water quality of the Santiago River, laying the groundwork for local officials to identify pollution sources and better support environmental policies and water quality improvement plans. Supplementary Information: The online version contains supplementary material available at 10.1007/s12665-022-10430-9.
RESUMO
The objective of this study was to determine post-mortem measurements for predicting carcass traits in growing rabbits. A total of 50 clinically healthy New Zealand White × Californian male rabbits with a body weight (BW) of 1351 ± 347 g between 60 to 80 days of age were used. Body weight was recorded 12 h before slaughtering. Data recorded at slaughtering included carcass weights (HCW). After cooling at 4 °C for 24 h, carcasses were weighed (CCW) and then were carefully split longitudinally with a band saw to obtain left and right halves. In the right half carcass, the following measurements were recorded using a tape measure: dorsal length (DL), thoracic depth (TD), thigh length (TL), carcass length (CL), lumbar circumference (LC). The compactness index (CCI) was calculated as the CCW divided by the CL. Thereafter, the right half carcass was weighed and manually deboned to record weights of muscle (TCM), and bone (TCB). The CCI explained of 93% of variation for TCM (R2 = 0.93 and a CV = 9.30%). In addition, the DL was the best predictor (p < 0.001) for TCB (R2 = 0.60 and a CV = 18.9%). Our results indicated that the use of carcass measurements could accurately and precisely (R2 = ≥ 0.60 and ≤0.95) be used as alternatives to predict the carcass tissues composition in growing rabbits.
RESUMO
This research aims to describe the relationship between resilience and burnout facing COVID-19 pandemics. The sample was n = 831 lecturers and professors of a Mexican public university. This study is a quantitative, non-experimental, cross-sectional, explanatory, and ex post facto research using Structural Equations Modeling with latent variables under the partial least square's method technique. We used the CD-RISC-25 and SBI questionnaires to measure resilience and burnout, respectively. Structural Equations Modeling (SEM-PLS) allowed the visualization of the exogenous variable (resilience) in endogenous variables (dimensions of SBI burnout: E9 guilt, E7 emotional exhaustion, E8 indolence, and E6 work illusion). To this day, there are very few previous studies that jointly analyze in Mexico the characteristics of resilience and burnout in the face of the COVID-19 pandemic. Findings show that resources availability has the strongest correlation with accomplishment in teaching, followed by cynicism and emotional exhaustion. These results have important professional implications.
Assuntos
Esgotamento Profissional , COVID-19 , Resiliência Psicológica , Esgotamento Profissional/epidemiologia , Esgotamento Psicológico , Estudos Transversais , Docentes , Humanos , Pandemias , SARS-CoV-2 , Inquéritos e QuestionáriosRESUMO
This research uses structural equation modeling to determine the influence of uncertainty due to the COVID-19 pandemic as an independent variable in the negative emotional states and resilience (as mediating variables) vs. drug addiction, alcoholism, and suicide ideation as dependent variables in 5557 students from a public state university in Northern Mexico. The five variables are related through eight hypotheses and tested using partial least squares. We used an adapted questionnaire sent by email in May 2020. Findings show that uncertainty facing the COVID-19 pandemic had a direct and significant influence on negative emotional states and a significant inverse effect on resilience; in the trajectory, drug addiction and alcoholism, and suicide ideation are explained.
Assuntos
Alcoolismo , COVID-19 , Transtornos Relacionados ao Uso de Substâncias , Alcoolismo/epidemiologia , Humanos , Pandemias , SARS-CoV-2 , Ideação Suicida , IncertezaRESUMO
Defensins are one of the major families of antimicrobial peptides (AMPs) that are widely distributed in insects. In Triatomines (Hemiptera: Reduviidae) vectors of Trypanosoma cruzi the causative agent of Chagas disease, two large groups of defensin isoforms have been described: type 1 and type 4. The aim of this study was to analyze the trypanocidal activity of a type 1 recombinant defensin (rDef1.3) identified in Triatoma (Meccus) pallidipennis, an endemic specie from México. The trypanocidal activity of this defensin was evaluated in vitro, against the parasites T. cruzi, T. rangeli, and two species of Leishmania (L. mexicana and L. major) both causative agents of cutaneous leishmaniasis. Our data demonstrated that the defensin was active against all the parasites although in different degrees. The defensin altered the morphology, reduced the viability and inhibited the growth of T.cruzi. When tested against T. rangeli (a parasite that infects a variety of mammalian species), stronger morphological effects where observed. Surprisingly the greatest effects were observed against the two Leishmania species, of which L. major was the parasite most affected with 50% of dead cells or with damaged membranes, in addition of a reduction in its proliferative capacity in culture. These results suggest that rDef1.3 has an important antimicrobial effect against trypanosomatids which cause some of the more important neglected tropical diseases transmitted by insect vectors.
Assuntos
Defensinas/genética , Proteínas de Insetos/genética , Leishmania/efeitos dos fármacos , Triatoma/química , Tripanossomicidas/farmacologia , Trypanosoma/efeitos dos fármacos , Sequência de Aminoácidos , Animais , Defensinas/química , Defensinas/metabolismo , Proteínas de Insetos/química , Proteínas de Insetos/metabolismo , Filogenia , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Alinhamento de Sequência , Triatoma/genéticaRESUMO
Agmatine is the product of the decarboxylation of L-arginine by the enzyme arginine decarboxylase. This amine has been attributed to neurotransmitter functions, anticonvulsant, anti-neurotoxic, and antidepressant in mammals and is a potential therapeutic agent for diseases such as Alzheimer's, Parkinson's, and cancer. Agmatinase enzyme hydrolyze agmatine into urea and putrescine, which belong to one of the pathways producing polyamines, essential for cell proliferation. Agmatinase from Escherichia coli (EcAGM) has been widely studied and kinetically characterized, described as highly specific for agmatine. In this study, we analyze the amino acids involved in the high specificity of EcAGM, performing a series of mutations in two loops critical to the active-site entrance. Two structures in different space groups were solved by X-ray crystallography, one at low resolution (3.2 Å), including a guanidine group; and other at high resolution (1.8 Å) which presents urea and agmatine in the active site. These structures made it possible to understand the interface interactions between subunits that allow the hexameric state and postulate a catalytic mechanism according to the Mn2+ and urea/guanidine binding site. Molecular dynamics simulations evaluated the conformational dynamics of EcAGM and residues participating in non-binding interactions. Simulations showed the high dynamics of loops of the active site entrance and evidenced the relevance of Trp68, located in the adjacent subunit, to stabilize the amino group of agmatine by cation-pi interaction. These results allow to have a structural view of the best-kinetic characterized agmatinase in literature up to now.
Assuntos
Proteínas de Escherichia coli/química , Escherichia coli/química , Ureo-Hidrolases/química , Agmatina/metabolismo , Domínio Catalítico , Cristalografia por Raios X , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , Modelos Moleculares , Conformação Proteica , Multimerização Proteica , Especificidade por Substrato , Ureo-Hidrolases/metabolismoRESUMO
The present study evaluated the impact of Saharan dust event on particulate matter (PM: PM10 and PM2.5) concentrations by analyzing the daily average PM data between Saharan dust days (June 23-29, 2020) and non-Saharan dust days (June 15 to June 22 and June 30 to July 12, 2020) for four majorly affected regions in Mexico and by comparing with three major previous events (2015, 2018, and 2019). The results showed that PM10 and PM2.5 concentrations were 2-5 times higher during the Saharan dust event with the highest daily averages of 197 µg/m3 and 94 µg/m3, respectively, and exceeded the Mexican standard norm (NOM-020-SSA1-2014). When comparing with the previous Saharan dust episodes of 2015, 2018, and 2019, the levels of PM10 and PM2.5 considerably increased and more than doubled across Mexico. The correlation analysis revealed a positive association of PM levels with the number of daily COVID-19 cases and deaths during Saharan dust event. Furthermore, the human health risk assessment showed that the chronic daily intake and hazard quotient values incremented during Saharan dust days compared to non-Saharan days, indicating potential health effects and importance of taking necessary measures to ensure better air quality following the COVID-19 pandemic.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , COVID-19 , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Poeira/análise , Monitoramento Ambiental , Humanos , México , Pandemias , Material Particulado/análise , SARS-CoV-2RESUMO
INTRODUCTION: With a global adult prevalence of 24%, non-alcoholic fatty liver disease is a global health problem that parallels the worldwide increase of obesity. Its frequency, clinical characteristics and related diseases in Cuba remain unknown. OBJECTIVE: Describe the clinical characteristics, comorbidities and personal habits of patients with non-alcoholic fatty liver disease who are being treated in secondary and tertiary health facilities in seven Cuban provinces. METHODS: A cross-sectional, multicenter study was carried out in 6601 adults seen at gastroenterology outpatient clinics of nine hospitals in seven Cuban provinces from September 2018 through May 2019. Non-alcoholic fatty liver disease was diagnosed by abdominal ultrasound. The study included 1070 patients who met the diagnostic and study criteria and agreed to participate. Their personal habits and anthropometric and clinical characteristics, comorbidities and other aspects of their medical histories were recorded. RESULTS: Of the 1070 participants, 60.7% (649) were women. Participants' average age was 54.5 years and average body mass index was 30.5 kg/m2. A total of 397 (37.1%) were overweight and 574 (53.6%) were obese, 945 (88.3%) led a sedentary lifestyle, 564 (52.7%) had high blood pressure, 406 (37.9%) had lipid disorders and 301 (28.1%) were diabetic. While 484 (45.2%) of patients were asymptomatic, the most frequent clinical signs and symptoms were fatigue (262; 24.5%), dyspepsia (209; 19.5%), abdominal pain (306; 28.5%) and hepatomegaly (189; 17.7%). Liver cirrhosis was present in 37 (3.5%) patients at the time of diagnosis. Family history of type 2 diabetes mellitus and obesity were identified in 391 (36.5%) and 279 (26.1%) of participants, respectively. CONCLUSIONS: Prevalence of non-alcoholic fatty liver disease in these Cuban patients coincides with that reported in the Caribbean region, which has high levels of obesity, overweight and sedentary lifestyles. Most were asymptomatic, female or had metabolism-related comorbidities such as high blood pressure, type 2 diabetes mellitus and dyslipidemia.
Assuntos
Hepatopatia Gordurosa não Alcoólica/epidemiologia , Índice de Massa Corporal , Estudos Transversais , Cuba/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Dislipidemias/epidemiologia , Feminino , Humanos , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de RiscoRESUMO
Trypanosoma cruzi is the etiological agent of Chagas disease, whose clinical outcome ranges from asymptomatic individuals to chronic fatal megasyndromes. Despite being central to pathogenesis, the regulation of parasite virulence factors' expression remains largely unknown. In this work, the relative expression of several parasite virulence factors between two TcI strains (Ninoa, low virulence and Qro, high virulence) was assessed by qRT-PCR of total and of polysome-associated mRNA, as well as by western blots. Trypomastigotes were also incubated with specific anti-sense morpholino oligonucleotides to block the translation of a selected virulence factor, calreticulin, in both strains. Ninoa trypomastigotes showed significantly lower levels of trypomastigote-decay acceleration factor, complement regulatory protein, complement C2 receptor inhibitor trispanning, and glycoproteins 82 and 90 mRNAs compared with Qro. There was a significantly lower recruitment of complement regulatory protein and complement C2 receptor inhibitor trispanning mRNAs to polysomes and higher recruitment of MASP mRNA to monosomes in Ninoa strain. Calreticulin mRNA displayed both a higher total mRNA level and recruitment to translationally active polysomes in the Ninoa strain (low virulence) than in the Qro strain (high virulence). When calreticulin was downregulated by ≈ 50% by anti-sense morpholino oligonucleotides, a significant decrease of parasite invasion in mammalian cells was found in both strains. Calreticulin downregulation, however, only increased significantly the activation of the complement system by Ninoa trypomastigotes. These results suggest a role for the regulation of virulence factors' gene expression in the differential virulence among T. cruzi strains. Furthermore, a possible function of calreticulin in parasite invasion not related to its binding to complement factors is shown.