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Aim: The present study was designed to evaluate the clinical characteristics of COVID-19 and mortality-associated factors during the first year of the pandemic in patients from southeastern Mexico. Patient & methods: A total of 953 records from patients with COVID-19 were cross-sectionally studied in a primary care hospital in southeast Mexico between 2020 and 2021. Results: The prevalent symptoms were fever (78.6%), cough (80.5%) and headache (82.8%) and dyspnea reached 13.5%. The mortality rate was 7.63% and the clinical variables associated with it were age >60 years, hypertension, severe disease, radiographic pneumonia, days to diagnosis and having two Mayan surnames. Conclusion: Future health strategies should consider age, comorbidities, disease severity, clinical manifestations and possessing ethnicity of risk (i.e., Mayan genetic background).

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We previously reported preliminary characterization of adipose tissue (AT) dysfunction through the adiponectin/leptin ratio (ALR) and fasting/postprandial (F/P) gene expression in subcutaneous (SQ) adipose tissue (AT) biopsies obtained from participants in the GEMM study, a precision medicine research project. Here we present integrative data replication of previous findings from an increased number of GEMM symptom-free (SF) adults (N = 124) to improve characterization of early biomarkers for cardiovascular (CV)/immunometabolic risk in SF adults with AT dysfunction. We achieved this goal by taking advantage of the rich set of GEMM F/P 5 h time course data and three tissue samples collected at the same time and frequency on each adult participant (F/P blood, biopsies of SQAT and skeletal muscle (SKM)). We classified them with the presence/absence of AT dysfunction: low (<1) or high (>1) ALR. We also examined the presence of metabolically healthy (MH)/unhealthy (MUH) individuals through low-grade chronic subclinical inflammation (high sensitivity C-reactive protein (hsCRP)), whole body insulin sensitivity (Matsuda Index) and Metabolic Syndrome criteria in people with/without AT dysfunction. Molecular data directly measured from three tissues in a subset of participants allowed fine-scale multi-OMIC profiling of individual postprandial responses (RNA-seq in SKM and SQAT, miRNA from plasma exosomes and shotgun lipidomics in blood). Dynamic postprandial immunometabolic molecular endophenotypes were obtained to move towards a personalized, patient-defined medicine. This study offers an example of integrative translational research, which applies bench-to-bedside research to clinical medicine. Our F/P study design has the potential to characterize CV/immunometabolic early risk detection in support of precision medicine and discovery in SF individuals.

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A large number of studies have shown that the baboon is one of the most commonly used non-human primate (NHP) research model for the study of immunometabolic complex traits such as type 2 diabetes (T2D), insulin resistance (IR), adipose tissue dysfunction (ATD), dyslipidemia, obesity (OB) and cardiovascular disease (CVD). This paper reports on innovative technologies and advanced research strategies for energetics and translational medicine with this NHP model. This includes the following: measuring resting energy expenditure (REE) with the mobile indirect calorimeter Breezing®; monitoring daily body temperature using subcutaneously implanted data loggers; quantifying metabolic heat with veterinary infrared thermography (IRT) imaging, and non-viral non-invasive, tissue-specific ultrasound-targeted microbubble destruction (UTMD) gene-based therapy. These methods are of broad utility; for example, they may facilitate the engineering of ectopic overexpression of brown adipose tissue (BAT) mUCP-1 via UTMD-gene therapy into baboon SKM to achieve weight loss, hypophagia and immunometabolic improvement. These methods will be valuable to basic and translational research, and human clinical trials, in the areas of metabolism, cardiovascular health, and immunometabolic and infectious diseases.

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An altered immune response to pathogens has been suggested to explain increased susceptibility to infectious diseases in patients with diabetes. Recent evidence has documented several immunometabolic pathways in patients with diabetes directly related to the COVID-19 infection. This also seems to be the case for prediabetic subjects with proinflammatory insulin resistance syndrome accompanied with prothrombotic hyperinsulinemic and dysglycemic states. Patients with frank hyperglycemia, dysglycemia and/or hyperinsulinemia develop systemic immunometabolic inflammation with higher levels of circulating cytokines. This deleterious scenario has been proposed as the underlying mechanism enhancing a cytokine storm-like hyperinflammatory state in diabetics infected with severe COVID-19 triggering multi-organ failure. Compared with moderately affected COVID-19 patients, diabetes was found to be highly prevalent among severely affected patients suggesting that this non-communicable disease should be considered as a risk factor for adverse outcomes. The COVID-19 pandemic mirrors with the diabetes pandemic in many pathobiological aspects. Our interest is to emphasize the ties between the immunoinflammatory mechanisms that underlie the morbidity and lethality when COVID-19 meets diabetes. This review brings attention to two pathologies of highly complex, multifactorial, developmental and environmentally dependent manifestations of critical importance to human survival. Extreme caution should be taken with diabetics with suspected symptoms of COVID-19 infection.

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Interactions between macrophages and adipocytes are early molecular factors influencing adipose tissue (AT) dysfunction, resulting in high leptin, low adiponectin circulating levels and low-grade metaflammation, leading to insulin resistance (IR) with increased cardiovascular risk. We report the characterization of AT dysfunction through measurements of the adiponectin/leptin ratio (ALR), the adipo-insulin resistance index (Adipo-IRi), fasting/postprandial (F/P) immunometabolic phenotyping and direct F/P differential gene expression in AT biopsies obtained from symptom-free adults from the GEMM family study. AT dysfunction was evaluated through associations of the ALR with F/P insulin-glucose axis, lipid-lipoprotein metabolism, and inflammatory markers. A relevant pattern of negative associations between decreased ALR and markers of systemic low-grade metaflammation, HOMA, and postprandial cardiovascular risk hyperinsulinemic, triglyceride and GLP-1 curves was found. We also analysed their plasma non-coding microRNAs and shotgun lipidomics profiles finding trends that may reflect a pattern of adipose tissue dysfunction in the fed and fasted state. Direct gene differential expression data showed initial patterns of AT molecular signatures of key immunometabolic genes involved in AT expansion, angiogenic remodelling and immune cell migration. These data reinforce the central, early role of AT dysfunction at the molecular and systemic level in the pathogenesis of IR and immunometabolic disorders.

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Cardiovascular disease (CVD) and type 2 diabetes (T2D) are increasing worldwide. This is mainly due to an unhealthy nutrition, implying that variation in CVD risk may be due to variation in the capacity to manage a nutritional load. We examined the genomic basis of postprandial metabolism. Our main purpose was to introduce the GEMM Family Study (Genetics of Metabolic Diseases in Mexico) as a multi-center study carrying out an ongoing recruitment of healthy urban adults. Each participant received a mixed meal challenge and provided a 5-hours' time course series of blood, buffy coat specimens for DNA isolation, and adipose tissue (ADT)/skeletal muscle (SKM) biopsies at fasting and 3 h after the meal. A comprehensive profiling, including metabolomic signatures in blood and transcriptomic and proteomic profiling in SKM and ADT, was performed to describe tendencies for variation in postprandial response. Our data generation methods showed preliminary trends indicating that by characterizing the dynamic properties of biomarkers with metabolic activity and analyzing multi-OMICS data it could be possible, with this methodology and research design, to identify early trends for molecular biology systems and genes involved in the fasted and fed states.

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The prevalence of type 2 diabetes (T2D) is rising rapidly and in Mexicans is ~19%. T2D is affected by both environmental and genetic factors. Although specific genes have been implicated in T2D risk few of these findings are confirmed in studies of Mexican subjects. Our aim was to replicate associations of 39 single nucleotide polymorphisms (SNPs) from 10 genes with T2D-related phenotypes in a community-based Mexican cohort. Unrelated individuals (n = 259) living in southeastern Mexico were enrolled in the study based at the University of Yucatan School of Medicine in Merida. Phenotypes measured included anthropometric measurements, circulating levels of adipose tissue endocrine factors (leptin, adiponectin, pro-inflammatory cytokines), and insulin, glucose, and blood pressure. Association analyses were conducted by measured genotype analysis implemented in SOLAR, adapted for unrelated individuals. SNP Minor allele frequencies ranged from 2.2 to 48.6%. Nominal associations were found for CNR1, SLC30A8, GCK, and PCSK1 SNPs with systolic blood pressure, insulin and glucose, and for CNR1, SLC30A8, KCNJ11, and PCSK1 SNPs with adiponectin and leptin (p < 0.05). P-values greater than 0.0014 were considered significant. Association of SNPs rs10485170 of CNR1 and rs5215 of KCNJ11 with adiponectin and leptin, respectively, reached near significance (p = 0.002). Significant association (p = 0.001) was observed between plasma leptin and rs5219 of KCNJ11.

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Whole-transcriptome expression profiling provides novel phenotypes for analysis of complex traits. Gene expression measurements reflect quantitative variation in transcript-specific messenger RNA levels and represent phenotypes lying close to the action of genes. Understanding the genetic basis of gene expression will provide insight into the processes that connect genotype to clinically significant traits representing a central tenet of system biology. Synchronous in vivo expression profiles of lymphocytes, muscle, and subcutaneous fat were obtained from healthy Mexican men. Most genes were expressed at detectable levels in multiple tissues, and RNA levels were correlated between tissue types. A subset of transcripts with high reliability of expression across tissues (estimated by intraclass correlation coefficients) was enriched for cis-regulated genes, suggesting that proximal sequence variants may influence expression similarly in different cellular environments. This integrative global gene expression profiling approach is proving extremely useful for identifying genes and pathways that contribute to complex clinical traits. Clearly, the coincidence of clinical trait quantitative trait loci and expression quantitative trait loci can help in the prioritization of positional candidate genes. Such data will be crucial for the formal integration of positional and transcriptomic information characterized as genetical genomics.

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OBJECTIVE: We describe the methodology used to analyze multiple transcripts using microarray techniques in simultaneous biopsies of muscle, adipose tissue and lymphocytes obtained from the same individual as part of the standard protocol of the Genetics of Metabolic Diseases in Mexico: GEMM Family Study. METHODS: We recruited 4 healthy male subjects with BM1 20-41, who signed an informed consent letter. Subjects participated in a clinical examination that included anthropometric and body composition measurements, muscle biopsies (vastus lateralis) subcutaneous fat biopsies anda blood draw. All samples provided sufficient amplified RNA for microarray analysis. Total RNA was extracted from the biopsy samples and amplified for analysis. RESULTS: Of the 48,687 transcript targets queried, 39.4% were detectable in a least one of the studied tissues. Leptin was not detectable in lymphocytes, weakly expressed in muscle, but overexpressed and highly correlated with BMI in subcutaneous fat. Another example was GLUT4, which was detectable only in muscle and not correlated with BMI. Expression level concordance was 0.7 (p< 0.001) for the three tissues studied. CONCLUSIONS: We demonstrated the feasibility of carrying out simultaneous analysis of gene expression in multiple tissues, concordance of genetic expression in different tissues, and obtained confidence that this method corroborates the expected biological relationships among LEPand GLUT4. TheGEMM study will provide a broad and valuable overview on metabolic diseases, including obesity and type 2 diabetes.

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Objetivo: Describir la metodología de análisis de múltiples transcritos con técnicas de microarreglo en biopsias simultáneas de tejido muscular, adiposo y sangre en un mismo individuo, como parte de la estandarización del estudio GEMM (Genética de las Enfermedades Metabólicas en México). Material y métodos: Se incluyó a cuatro sujetos con índice de masa corporal (IMC) entre 20 y 41. Se registró estatura, talla y composición corporal. Se realizó biopsia muscular (vasto lateral), de tejido adiposo subcutáneo y muestra de sangre completa. El ARN total fue extraído de los tejidos y amplificado para análisis de microarreglos. Resultados: De 48 687 potenciales transcritos, 39.4% fue detectable en al menos uno de los tejidos. La expresión de leptina no fue detectable en linfocitos, débilmente expresada en músculo, alta expresión en el tejido adiposo y correlacionó con el IMC. El GLUT4 también ilustra la especificidad para el músculo sin verse afectado por el IMC. La concordancia en la expresión de transcritos fue 0.70 (p<0.001) para los tres tejidos. Conclusiones: Fue factible cuantificar simultáneamente la expresión genética de miles de transcritos, hubo concordancia en la expresión entre diferentes tejidos obtenidos en un mismo individuo, y confiabilidad del método al reproducir las relaciones biológicas esperadas. El estudio GEMM podrá analizar las correlaciones de los transcritos expresados dentro de un órgano y luego entre diferentes tejidos, y proveerá endofenotipos cuantitativos novedosos que proporcionarán un amplio panorama de información sobre las enfermedades metabólicas, incluyendo obesidad y diabetes tipo 2.

OBJECTIVE: We describe the methodology used to analyze multiple transcripts using microarray techniques in simultaneous biopsies of muscle, adipose tissue and lymphocytes obtained from the same individual as part of the standard protocol of the Genetics of Metabolic Diseases in Mexico: GEMM Family Study. METHODS: We recruited 4 healthy male subjects with BM1 20-41, who signed an informed consent letter. Subjects participated in a clinical examination that included anthropometric and body composition measurements, muscle biopsies (vastus lateralis) subcutaneous fat biopsies anda blood draw. All samples provided sufficient amplified RNA for microarray analysis. Total RNA was extracted from the biopsy samples and amplified for analysis. RESULTS: Of the 48,687 transcript targets queried, 39.4% were detectable in a least one of the studied tissues. Leptin was not detectable in lymphocytes, weakly expressed in muscle, but overexpressed and highly correlated with BMI in subcutaneous fat. Another example was GLUT4, which was detectable only in muscle and not correlated with BMI. Expression level concordance was 0.7 (p< 0.001) for the three tissues studied. CONCLUSIONS: We demonstrated the feasibility of carrying out simultaneous analysis of gene expression in multiple tissues, concordance of genetic expression in different tissues, and obtained confidence that this method corroborates the expected biological relationships among LEPand GLUT4. TheGEMM study will provide a broad and valuable overview on metabolic diseases, including obesity and type 2 diabetes.

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Benomile is one of the most used fungicides in the growing fields. In the rainy season brings benomilo with the planktonic communities. The effect of nominal concentrations of benomile under acute and chronic exposure was tested in the cladoceran Ceriodaphnia reticulata that were used. The value of LC(50) was calculated as 2.0 mg L(- 1)+/- 0.15 mg L(- 1) of benomile. In all concentrations, the demographic variables showed inhibition of reproduction. The unique behaviour of Ceriodaphnia reticulata with this particular toxicant is the diminution in the reproduction without affecting the survivorship.

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BACKGROUND: Meningeal melanocytomas are rare, benign central nervous system lesions with a high probability of recurrence. To the authors' knowledge, approximately 100 cases have been reported since 1972, when the entity first was described. In the current study, four therapies were compared with regard to local control and survival to identify which is best. METHODS: All reported cases were reviewed with regard to extent of resection, radiotherapy, local control, and survival. If published data were incomplete, the authors were contacted for additional data. Patients were categorized by therapy: complete resection (CTR), complete resection followed by radiotherapy (CTR-RT), incomplete resection (ITR), and incomplete resection followed by radiotherapy (ITR-RT). Local control and survival were calculated using the Kaplan-Meier method. A multivariate analysis was performed including age, gender, tumor location, confirmation of extent of resection, and treatment schedule. RESULTS: A total of 89 patients were included: 46 with CTR, 3 with CTR-RT, 23 with ITR, and 17 with ITR-RT. The 5-year local control rate was 80% after CTR, 100% after CTR-RT, and 72% after ITR-RT versus 18% after ITR (P < 0.001). The 5-year survival rate was 100% after CTR, CTR-RT, and ITR-RT, respectively, versus 46% after ITR (P < 0.001). Multivariate analysis demonstrated that therapy was the only variable that affected local control and survival significantly. In 14 patients treated with ITR-RT, RT was restricted to the tumor region. The radiation dose was 30-40 grays (Gy) in 6 patients, 45-55 Gy in 7 patients, and unknown in 1 patient. The 5-year local control rate was 86% after a dose of 45-55 Gy versus 27% after a dose of 30-40 Gy (P = 0.1). CONCLUSIONS: CTR was found to be significantly superior to ITR with regard to both local control and survival. Outcome was significantly improved by RT after ITR. Doses of 45-55 Gy appeared to be more beneficial than doses of < or = 40 Gy.

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Se describe un paciente de 52 años de edad que presentó 5 tumoraciones subcutaneas adheridas a diferentes nervios periféricos. La anatomía patológica de todas ellas, indicó que se trataba de schwannomas. Una TAC de cerebro demostró una tumoración en lóbulo temporal isquierdo con calcificaciones en su interior, compatible a meningioma. La ausencia de criterios diagnósticos para neurofibromatosis I y II y la característica particular del cuadro, schwannomas múltiples asociados a tumoracíon endocraneana, sugieren el diagnóstico de schwannomatosis

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Foram revistas 73 autópsias de pacientes que faleceram por infarto agudo do miocárdio (IAM); 38 eram fumantes crônicos e 35 näo fumantes, constituindo dois grupos, que foram comparados. Näo houve diferença entre ambos quanto a sexo e idade. A incidência de arritmias foi significativamente maior no grupo de fumantes (36/38 vs 26/35, p < 0,025), assim como os distúrbios de conduçäo (24/38 vs 12/35, p < 0,05). Näo houve correlaçäo entre o hábito de fumar e a falência ventricular esquerda ou choque cardiogênico. A massa infartada, o grau de estenose coronária e a incidência de trombose coronária recente foram similares nos dois grupos. A prevalência de IAM subendocárdico foi significativamente maior no grupo de fumantes (14/38 vs 7/35, p < 0,025). Raramente se encontraram trombos plaquetários. O presente relato confirma a incidência maior de arritmias nos fumantes crônicos, mas näo as de trombose coronária recente e trombos plaquetários, pelo menos no momento da morte. A maior incidência de infarto subendocárdico sugere um mecanismo espástico

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El Registro Latinoamericano de Tumores del Sistema Nervioso fue creado por el Dr. Moisés Polak en 1943, a instancias de la Sociedad Latinoamericana de Neurocirugía. Hasta la desaparición de Polak fueron registrados 8.825 tumores, lo cual resume su labor y la de la mayoría de los neurocirujanos del país. Con el objeto de difundirlo como aporte al conocimiento, se confeccionó la estadística a partir del fichero y los libros de entrada. Su ordenamiento corresponde a la clasificación Del Rio Hortega-Polak, la que fácilmente permite efectuar sinonimias con otras clasificaciones. Los casos, en números absolutos según los grupos, son los siguientes: 1. Tumores del parénquina nervioso 4.020, Tumores neuronales 377, Tumores gliales 3.571, Tumores microgliales 72; 2. Tumores de los neuroepitelios 47, Olfatorio 8, Retina 39; 3. Tumores de los anexos 538, Región hipofisaria 444, Región pineal 50, Plexos coroideos 44; 4. Tumores de las envolturas meníngeas 1.596, Meningiomas 1.335, Varios 261; 5. Tumores del sistema nervioso simpático 99; 6. Tumores de nervios y terminaciones nerviosas 1.160; 7. Tumores de los ganglios raquídeos 4; 8. Tumores metastásicos 1.228; 9. Misceláneas 114; 10. Inclasificables 19. El Registro se halla en las instalaciones del Instituto de Investigaciones Neurológicas "Dr. R. Carrea", FLENI, a disposición de los profesionales interesados en su consulta

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El Registro Latinoamericano de Tumores del Sistema Nervioso fue creado por el Dr. Moisés Polak en 1943, a instancias de la Sociedad Latinoamericana de Neurocirugía. Hasta la desaparición de Polak fueron registrados 8.825 tumores, lo cual resume su labor y la de la mayoría de los neurocirujanos del país. Con el objeto de difundirlo como aporte al conocimiento, se confeccionó la estadística a partir del fichero y los libros de entrada. Su ordenamiento corresponde a la clasificación Del Rio Hortega-Polak, la que fácilmente permite efectuar sinonimias con otras clasificaciones. Los casos, en números absolutos según los grupos, son los siguientes: 1. Tumores del parénquina nervioso 4.020, Tumores neuronales 377, Tumores gliales 3.571, Tumores microgliales 72; 2. Tumores de los neuroepitelios 47, Olfatorio 8, Retina 39; 3. Tumores de los anexos 538, Región hipofisaria 444, Región pineal 50, Plexos coroideos 44; 4. Tumores de las envolturas meníngeas 1.596, Meningiomas 1.335, Varios 261; 5. Tumores del sistema nervioso simpático 99; 6. Tumores de nervios y terminaciones nerviosas 1.160; 7. Tumores de los ganglios raquídeos 4; 8. Tumores metastásicos 1.228; 9. Misceláneas 114; 10. Inclasificables 19. El Registro se halla en las instalaciones del Instituto de Investigaciones Neurológicas "Dr. R. Carrea", FLENI, a disposición de los profesionales interesados en su consulta (AU)

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