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Diet habits and nutrition quality significantly impact health and disease. Here is delve into the intricate relationship between diet habits, nutrition quality, and their direct impact on health and homeostasis. Focusing on (-)-Epicatechin, a natural flavanol found in various foods like green tea and cocoa, known for its positive effects on cardiovascular health and diabetes prevention. The investigation encompasses the absorption, metabolism, and distribution of (-)-Epicatechin in the human body, revealing a diverse array of metabolites in the circulatory system. Notably, (-)-Epicatechin demonstrates an ability to activate nitric oxide synthase (eNOS) through the G protein-coupled estrogen receptor (GPER). While the precise role of GPER and its interaction with classical estrogen receptors (ERs) remains under scrutiny, the study employs computational methods, including density functional theory, molecular docking, and molecular dynamics simulations, to assess the physicochemical properties and binding affinities of key (-)-Epicatechin metabolites with GPER. DFT analysis revealed distinct physicochemical properties among metabolites, influencing their reactivity and stability. Rigid and flexible molecular docking demonstrated varying binding affinities, with some metabolites surpassing (-)-Epicatechin. Molecular dynamics simulations highlighted potential binding pose variations, while MMGBSA analysis provided insights into the energetics of GPER-metabolite interactions. The outcomes elucidate distinct interactions, providing insights into potential molecular mechanisms underlying the effects of (-)-Epicatechin across varied biological contexts.

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ABSTRACT Global advances in reproductive biotechnology have allowed for the transfer of embryos from donor females with high genetic merit to recipients using the cryopreservation technique, which preserves an embryo of excellent quality and viability, thereby achieving a feasible pregnancy rate. The objective of this study was to evaluate the quality and viability of Holstein embryos that have been cryopreserved for more than 40 years under glycerol freezing. The embryos were transferred to the recipient heifers using a non-surgical method. Two 17-month-old Holstein heifers (360 kg live weights) which were clinically healthy and reproductively active were used as the recipients. Two bovine embryos of Grade 1 quality were thawed and evaluated for their morphology. Of the two embryo transfers, one pregnancy was achieved, resulting in the birth of a calf. Therefore, embryos frozen in liquid nitrogen and glycerol as a cryopreservative for more than 40 years maintained their quality and viability to produce a live calf.

RESUMO Os avanços globais em biotecnologia reprodutiva permitiram a transferência de embriões de fêmeas doadoras com alto mérito genético para receptoras, usando-se a técnica de criopreservação, que preserva um embrião de excelente qualidade e viabilidade, alcançando, assim, uma taxa de gravidez viável. O objetivo deste estudo foi avaliar a qualidade e a viabilidade de embriões Holstein, criopreservados por mais de 40 anos, sob congelamento de glicerol. Os embriões foram transferidos para as novilhas receptoras, usando-se um método não cirúrgico. Duas novilhas Holstein de 17 meses de idade (360kg de peso vivo), que eram clinicamente saudáveis e reprodutivamente ativas, foram utilizadas como receptoras. Dois embriões bovinos de qualidade Grau 1 foram descongelados e avaliados quanto à sua morfologia. Das duas transferências embrionárias, uma gravidez foi obtida, resultando no nascimento de um bezerro. Portanto, os embriões congelados em nitrogênio líquido e glicerol como criopreservante por mais de 40 anos mantiveram sua qualidade e viabilidade para produzir um bezerro vivo.

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The objective of this study was to determine the risk factors and prevalence of trematodes in south-eastern Mexico. The prevalence of trematodes was determined in 1010 bovines. The study was carried out from October 2018 (n=291) to December 2019 (n=719). Only in 2019 rumen and liver fluke eggs were differentiated. Faecal samples (n=311) were obtained from farms in southeast Mexico located in Tabasco, Chiapas and Campeche. In addition, the presence of flukes in liver and rumen from slaughtered cattle in abattoirs was recorded with a total of 408 samples. A logistic procedure was used to obtain the prevalence and the effect of main risk factors such as land physiography (flooded areas and hills), year, sex, animals' age and type of sample obtained (eggs in faeces and flukes). The general prevalence of flukes in cattle was 32.3 % in 2018 and 41.7 % in 2019. Prevalence of F. hepatica (liver fluke) was 18.6 % (134/719) and that of paramphistomids (rumen fluke) was 33.4 % (240/719). The infected cattle from the slaughterhouse indicated a lower prevalence of F. hepatica (1 %) and rumen fluke (26.7 %) than in farms detected by egg in faeces (41.8 % and 42.1 %, respectively). The physiographic zone was decisive in the presence of F. hepatica and rumen fluke, while sex did not represent a risk factor (P > 0.05). The environmental conditions of the Mexican southeast favour the presence of both liver and rumen fluke.

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Skeletal muscle (SkM) comprises slow and fast-twitch fibers, which differ in molecular composition, function, and systemic energy consumption. In addition, muscular dystrophies (DM), a group of diverse hereditary diseases, present different patterns of muscle involvement, progression, and severity, suggesting that the regeneration-degeneration process may differ depending on the muscle type. Therefore, the study aimed to explore the expression of proteins involved in the repair process in different muscles at an early stage of muscular dystrophy in the δ-sarcoglycan null mice (Sgcd-null), a limb-girdle muscular dystrophy 2 F model. Hematoxylin & Eosin (H&E) Staining showed a high number of central nuclei in soleus (Sol), tibialis (Ta), gastrocnemius (Gas), and extensor digitorum longus (Edl) from four months Sgcd-null mice. However, fibrosis, determined by trichrome of Gomori modified staining, was only observed in Sgcd-null Sol. In addition, the number of Type I and II fibers variated differentially in the Sgcd-null muscles vs. wild-type muscles. Besides, the protein expression level of ß-catenin, myomaker, MyoD, and myogenin also presented different expression levels in all the Sgcd-null muscles studied. In summary, our study reveals that muscles with different metabolic characteristics showed distinct expression patterns of proteins involved in the muscle regeneration process. These results could be relevant in designing therapies for genetic and acquired myopathy.

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The flavanol (-)-epicatechin has exercise-mimetic properties. Besides, several miRNAs play a role in modulating the adaptation of the muscle to different training protocols. However, notwithstanding all information, few studies aimed to determine if (-)-epicatechin can modify the expression of miRNAs related to skeletal muscle development and regeneration. Mice were treated for fifteen days by oral gavage with the flavanol (-)-epicatechin. After treatment, the quadriceps of the mice was dissected, and total RNA was extracted. The expression level of miR-133, -204, -206, -223, -486, and -491 was analyzed by qRT-PCR. We also used bioinformatic analysis to predict the participation of these miRNAs in different skeletal muscle signal transduction pathways. Additionally, we analyzed the level of the myogenic proteins MyoD and myogenin by Western blot and measured the cross-sectional area of muscle fibers stained with E&H. (-)-Epicatechin upregulated the expression of miR-133, -204, -206, -223, and -491 significantly, which was associated with an increase in the level of the myogenic proteins MyoD and Myogenin and an augment in the fiber size. The bioinformatics analysis showed that the studied miRNAs might participate in different signal transduction pathways related to muscle development and adaptation. Our results showed that (-)-epicatechin upregulated miRNAs that participate in skeletal exercise muscle adaptation, induced muscle hypertrophy, and increased the level of myogenic proteins MyoD and MyoG.

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Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disorder characterized by cerebellar ataxia and retinopathy. SCA7 is caused by a CAG expansion in the ATXN7 gene, which results in an extended polyglutamine (polyQ) tract in the encoded protein, the ataxin-7. PolyQ expanded ataxin-7 elicits neurodegeneration in cerebellar Purkinje cells, however, its impact on the SCA7-associated retinopathy remains to be addressed. Since Müller glial cells play an essential role in retinal homeostasis, we generate an inducible model for SCA7, based on the glial Müller MIO-M1 cell line. The SCA7 pathogenesis has been explained by a protein gain-of-function mechanism, however, the contribution of the mutant RNA to the disease cannot be excluded. In this direction, we found nuclear and cytoplasmic foci containing mutant RNA accompanied by subtle alternative splicing defects in MIO-M1 cells. RNA foci were also observed in cells from different lineages, including peripheral mononuclear leukocytes derived from SCA7 patient, suggesting that this molecular mark could be used as a blood biomarker for SCA7. Collectively, our data showed that our glial cell model exhibits the molecular features of SCA7, which makes it a suitable model to study the RNA toxicity mechanisms, as well as to explore therapeutic strategies aiming to alleviate glial dysfunction.

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COVID-19 pandemic created a global shortage of medical protective equipment. Here, we considered ozone (O3) a disinfectant alternative due to its potent oxidative activity against biological macromolecules. The O3 decontamination assays were done using SARS-CoV-2 obtained from patients to produce artificial contamination of N95 masks and biosecurity gowns. The quantification of SARS-CoV-2 was performed before and after exposing the samples to different ozone gas concentrations for times between 5 and 30 min. Viral loads as a function of the O3 exposure time were estimated from the data obtained by the RT-PCR technique. The genetic material of the virus was no longer detected for any tested concentrations after 15 min of O3 exposure, which means a disinfection Concentration-Time above 144 ppm min. Vibrational spectroscopies were used to follow the modifications of the polymeric fibers after the O3 treatment. The results indicate that the N95 masks could be safely reused after decontamination with treatments of 15 min at the established O3 doses for a maximum of 6 cycles.

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ABSTRACT This article proposes two methodologies for the detection of lesions in the retina, which may indicate the presence of diabetic retinopathy (DR). Through the use of digital image processing techniques, it is possible to isolate the pixels that correspond to a lesion of RD, to achieve segmenting microaneurysms, the edges of the objects contained in the image are highlighted in order to detect the contours of the objects to select by size those that meet an area of 15 to 25 pixels in the case of 512x512 images and identify the objects as possible microaneurysms, while for the detection of exudates the green channel is selected to contrast the luminous objects in the retinography and from the conversion to gray scale, a histogram is graphed to identify the ideal threshold for the segmentation of the pixels that belong to the exudates at the end of the optical disk previously identified by a specialist. A confusion matrix supervised by an ophthalmologist was created to quantify the results obtained by the two methodologies, obtaining a specificity of 0.94 and a sensitivity of 0.97, values that are outstanding to proceed with the classification stage.

RESUMEN Este artículo propone dos metodologías para la detección de lesiones en la retina, que pueden significar la presencia de retinopatía diabética (RD). Mediante el uso de técnicas de procesamiento de imágenes digitales se logra aislar los pixeles que corresponden a una lesión propia de RD, para lograr segmentar microaneurismas se resaltan los bordes de los objetos contenido en la imagen con la finalidad de detectar los contornos de los objetos para seleccionar por tamaño los que cumplan con un área de 15 a 25 pixeles en el caso de imágenes de 512x512 y se identifiquen los objetos como posibles microaneurismas, mientras que para la detección de exudados se selecciona el canal verde para contrastar los objetos luminosos en la retinografía y a partir de la conversión a escala de grises se grafica un histograma para identificar el umbral idóneo para la segmentación de los pixeles que pertenecen a los exudados al final eliminar el disco óptico previamente identificado por un especialista. Se creó una matriz de confusión supervisada por un oftalmólogo para cuantificar los resultados obtenidos por las dos metodologías obteniendo una especificidad del 0.94 y una sensibilidad del 0.97, unos valores que son sobresalientes para proceder con la etapa de clasificación.

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Myotonic dystrophy type 1 (DM1), the most frequent inherited muscular dystrophy in adults, is caused by the CTG repeat expansion in the 3'UTR of the DMPK gene. Mutant DMPK RNA accumulates in nuclear foci altering diverse cellular functions including alternative splicing regulation. DM1 is a multisystemic condition, with debilitating central nervous system alterations. Although a defective neuroglia communication has been described as a contributor of the brain pathology in DM1, the specific cellular and molecular events potentially affected in glia cells have not been totally recognized. Thus, to study the effects of DM1 mutation on glial physiology, in this work, we have established an inducible DM1 model derived from the MIO-M1 cell line expressing 648 CUG repeats. This new model recreated the molecular hallmarks of DM1 elicited by a toxic RNA gain-of-function mechanism: accumulation of RNA foci colocalized with MBNL proteins and dysregulation of alternative splicing. By applying a microarray whole-transcriptome approach, we identified several gene changes associated with DM1 mutation in MIO-M1 cells, including the immune mediators CXCL10, CCL5, CXCL8, TNFAIP3, and TNFRSF9, as well as the microRNAs miR-222, miR-448, among others, as potential regulators. A gene ontology enrichment analyses revealed that inflammation and immune response emerged as major cellular deregulated processes in the MIO-M1 DM1 cells. Our findings indicate the involvement of an altered immune response in glia cells, opening new windows for the study of glia as potential contributor of the CNS symptoms in DM1.

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Cellular commitment and differentiation involve highly coordinated mechanisms by which tissue-specific genes are activated while others are repressed. These mechanisms rely on the activity of specific transcription factors, chromatin remodeling enzymes, and higher-order chromatin organization in order to modulate transcriptional regulation on multiple cellular contexts. Tissue-specific transcription factors are key mediators of cell fate specification with the ability to reprogram cell types into different lineages. A classic example of a master transcription factor is the muscle specific factor MyoD, which belongs to the family of myogenic regulatory factors (MRFs). MRFs regulate cell fate determination and terminal differentiation of the myogenic precursors in a multistep process that eventually culminate with formation of muscle fibers. This developmental progression involves the activation and proliferation of muscle stem cells, commitment, and cell cycle exit and fusion of mononucleated myoblast to generate myotubes and myofibers. Although the epigenetics of muscle regeneration has been extensively addressed and discussed over the recent years, the influence of higher-order chromatin organization in skeletal muscle regeneration is still a field of development. In this review, we will focus on the epigenetic mechanisms modulating muscle gene expression and on the incipient work that addresses three-dimensional genome architecture and its influence in cell fate determination and differentiation to achieve skeletal myogenesis. We will visit known alterations of genome organization mediated by chromosomal fusions giving rise to novel regulatory landscapes, enhancing oncogenic activation in muscle, such as alveolar rhabdomyosarcomas (ARMS).

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Resumen El objetivo de esta investigación es la modelación del dominio de un marco técnico de compartición e interacción de un expediente clínico electrónico (ECE) entre diversas instituciones de salud, públicas o privadas, como primer paso para lograr un marco técnico de refererencia para la interoperabilidad de sistemas de ECE en México. Se ha utilizado el proceso sistemático KMOS-RE para obterner los diversos artefactos que conforman el modelo: el léxico extendido del conocimiento del domino, los modelos conceptuales del dominio de aplicación y del dominio de la solución y los modelos de estados. Debido a que el diseño e implementación de los sistemas de ECE de cada una de las instituciones de salud se generan de manera independiente, realizar un marco técnico de referencia representa un gran desafío y una gran oportunidad, ya que ofrecerá ventajas importantes, como el hecho de contar con la información clínica de manera oportuna en cualquier institución de salud, la posibilidad de que el propio paciente acceda a su información y la facilidad de realizar investigación clínica a partir de los datos compartidos. Aún cuando la modelación de un dominio es dinámica, el contar con un modelo del dominio lo más preciso posible en este punto, facilitará los siguientes pasos para lograr el marco técnico de referencia propuesto.

Abstract This paper presents the domain modeling of a technical framework of sharing and interaction of an electronic medical record among different healthcare institutions, both public or private, as a first step to establish a technical reference framework for the interoperability of electronic medical record systems in Mexico. The artefact that make up the domain model were carried out using the KMOS-RE systematic process. Through this process, the following components have been obtained: the knowledge domain extended lexicon, the conceptual models, one for the application domain and another for the solution domain, as well as the state models. Since the design and implementation of the electronic medical record systems of different healthcare institutions are generated independently, having a technical reference framework represents a great challenge but also a great opportunity, since it will offer important advantages, such as having the clinical information in a timely manner in any healthcare institution, the possibility of the patient accessing their own information and the ease of conducting clinical research from the shared data. Even when a domain modeling is a dynamic task, having a precise domain model at this point will facilitate the next steps to achieve the proposed technical reference framework.

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Stage III non-small cell lung cancer (NSCLC) is a very heterogeneous disease that encompasses patients with resected, potentially resectable and unresectable tumours. To improve the prognostic capacity of the TNM classification, it has been agreed to divide stage III into sub-stages IIIA, IIIB and IIIC that have very different 5-year survival rates (36, 26 and 13%, respectively). Currently, it is considered that both staging and optimal treatment of stage III NSCLC requires the joint work of a multidisciplinary team of expert physicians within the tumour committee. To improve the care of patients with stage III NSCLC, different scientific societies involved in the diagnosis and treatment of this disease have agreed to issue a series of recommendations that can contribute to homogenise the management of this disease, and ultimately to improve patient care.

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Epigenetic regulation is achieved at many levels by different factors such as tissue-specific transcription factors, members of the basal transcriptional apparatus, chromatin-binding proteins, and noncoding RNAs. Importantly, chromatin structure dictates the availability of a specific genomic locus for transcriptional activation as well as the efficiency with which transcription can occur. Chromatin immunoprecipitation (ChIP) is a method that allows elucidating gene regulation at the molecular level by assessing if chromatin modifications or proteins are present at a specific locus. Initially, the majority of ChIP experiments were performed on cultured cell lines and more recently this technique has been adapted to a variety of tissues in different model organisms. Using ChIP on mouse embryos, it is possible to document the presence or absence of specific proteins and chromatin modifications at genomic loci in vivo during mammalian development and to get biological meaning from observations made on tissue culture analyses. We describe here a ChIP protocol on freshly isolated mouse embryonic somites for in vivo analysis of muscle specific transcription factor binding on chromatin. This protocol has been easily adapted to other mouse embryonic tissues and has also been successfully scaled up to perform ChIP-Seq.

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Antecedentes: La frecuencia informada de CAA en pacientes con lesiones traumáticas oscila entre 0.5 y 5 por ciento, con una mortalidad que varía entre 7 y 75 por ciento, valores determinados por reporte de casos o series retrospectivas. Objetivo: Determinar la frecuencia de colecistitis aguda acalculosa (CAA) en una población de pacientes con trauma contuso grave y las implicaciones clínicas que tiene, así como los factores de riesgo que puedan precipitar su aparición, evaluación de cambios morfológicos tempranos, tratamiento quirúrgico y morbi-mortalidad. Pacientes y métodos: Estudio prospectivo, observacional, longitudinal y descriptivo inferencial conducido entre ocubre de 1994 y junio de 1995. Se incluyeron 28 pacientes adultos consecutivos con trauma contuso al menos en dos regiones corporales. Se estimó la severidad de las lesiones con una escala fisiológica (Revised Trauma Score = RTS) y una anatómica (Injury Severity Score = ISS). Todos los pacientes se sometieron a ultrasonido de hígado y vías biliares a su ingreso y cada 5 a 7 días para la detección temprana de cambios sonográficos o concluyentes de CAA. Cada paciente recibió tratamiento conveniente de acuerdo a sus lesiones. La evaluación fue clínica, laboratorial y de los posibles factores de riesgo para el desarrollo de esta alteración. Mediciones: Prueba exacta de Fisher de dos colas para las variables cualitativas y prueba U de Mann-Withney para las cuantitativas. Resultados: Del total 21 correspondieron al sexo masculino (75 por ciento) y 7 al femenino (25 por ciento) con un promedio de edad de 45.5 años y un período de observación promedio de 22.5 días. Siete de los pacientes (25 por ciento) desarrollaron cambios sonográficos a partir del noveno día de manejo, 4 fueron concluyentes de CAA demostrados histológicamente, de los cuales tres se sometieron a colecistectornía abierta sin morbilidad y mortalidad y mejoría de sus condiciones clínicas. El otro caso falleció por hipovolemia sin ofrecerle tratamiento quirúrgico. Los factores de riesgo con significancia estadística fueron: Estancia prolongada, fiebre, dolor abdominal, evaluación de la fosfatasa alcalina, hipoalbuminemia, uso de nutrición parenteral total y casos complicados con neumonía intrahospitalaria (P = < 0.05). Hubo significancia marginal con el uso de analgesia-sedación. La mortalidad global fue del 18 por ciento. Conclusiones: La frecuencia es mayor a la informada previamente y no hubo mortalidad relacionada a la presencia de la CAA. El ultrasonido detecta fácilmente los cambios morfológicos vesiculares. No hubo morbilidad y mortalidad atribuida a la colecistectomía.

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BACKGROUND: The incidence of AAC on patients with traumatic lesions fluctuates between 0.5 to 5%, with mortality which varies between 7 and 75%. These values are determined by case reports or retrospective series. AIM: To determine the incidence of acute acalculous cholecystitis (AAC) in a number of patients with severe trauma and its clinical implications, as well as the risk factors that can favour the development of this pathology, evaluation of early morphological changes, surgical treatment and morbidity and mortality. PATIENTS AND METHODS: Prospective, observational, longitudinal and descriptive inferential study conducted from October 1994 to June 1995. Twenty eight consecutive adult patients with contusion severe trauma on at least two corporal regions were included. The severity of lesions was estimated with a physiologic scale (Revised Trauma Score = RTS) and an anatomic one (Injury Severity Score = ISS). All patients were submitted to ultrasound of the liver and biliary tract on their admittance and every 5 or 7 days for an early detection of sonographic changes or conclusive of AAC. Each patient was treated conveniently in accordance with his or her lesions. The patients were evaluated clinically, with laboratory exams, and for possible risk factors for the development of this pathology. MEASUREMENTS: Two Tailed Fisher's Exact Test for qualitative variables and Mann-Withney U Test for the quantitatives. RESULTS: Twenty one patients were male (75%) and 7 were female (25%), average age 45.5 years and an average observation period of 22.5 days. Seven of these patients (25%) developed sonographic changes starting the 9th day after admission, 4 were conclusive of AAC proved histologically, three of these underwent open cholecystectomy with no morbidity and mortality and improvement of their clinical conditions. The other patient died due to hypovolemia without having been offered surgical treatment. The risks factors with statistical significance were: Long in-hospital stay, fever, abdominal pain, elevation of alkaline phosphatase, hypoalbuminemia, use of parenteral nutritional support and nosocomial pneumonia (P = < 0.05). There was a marginal significance with the use of sedatives and analgesics. Global mortality was 18%. CONCLUSIONS: The incidence is more than the one previously informed and there was no mortality related the presence of AAC. The ultrasound easily detects the gallbladder morphological changes. There was no morbidity or mortality due to the cholecystectomy.

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Hospital-acquired bacteremia is a common cause of morbidity and mortality, mainly in pediatric units. In a 25 month retrospective study, we analyzed the blood cultures from the Hospital General Regional of the city of Leon, Guanajuato State, Mexico, in order to establish the causal agents of nosocomial bacteremia and infer some associations with contaminated intravenous infusion fluids. In addition we performed a two month study to culture the flasks and intravenous tubing used in our infusions. Five hundred and fifty one blood cultures drawn from August 1990 to September 1992 were analyzed. A total of 135 (24.5%) were positive, most of them (51.8%) with strains of the Klebsielleae tribe (SKT) (Klebsiella, Enterobacter, Serratia). The global incidence of bacteremia in the two year period was 4.3%. In the infusion study, 230 intravenous fluids were cultured, with 68 isolates (30%) most from the SKT tribe. A final consideration is made on the role that inadequate management of intravenous liquids could play in the development of endemic and epidemic nosocomial bacteremia in our hospital, and the eventual utility of making cultures of the i.v. liquids.

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