Cardiac electrical defects in progeroid mice and Hutchinson-Gilford progeria syndrome patients with nuclear lamina alterations

Hutchinson–Gilford progeria syndrome (HGPS) is a rare genetic disease caused by defective prelamin A processing, leading to nuclear lamina alterations, severe cardiovascular pathology, and premature death. Prelamin A alterations also occur in physiological aging. It remains unknown how defective prelamin A processing affects the cardiac rhythm. We show age-dependent cardiac repolarization abnormalities in HGPS patients that are also present in the Zmpste24-/- mouse model of HGPS. Challenge of Zmpste24-/- mice with the ß-adrenergic agonist isoproterenol did not trigger ventricular arrhythmia but caused bradycardia-related premature ventricular complexes and slow-rate polymorphic ventricular rhythms during recovery. Patch-clamping in Zmpste24-/- cardiomyocytes revealed prolonged calcium-transient duration and reduced sarcoplasmic reticulum calcium loading and release, consistent with the absence of isoproterenol-induced ventricular arrhythmia. Zmpste24-/- progeroid mice also developed severe fibrosis-unrelated bradycardia and PQ interval and QRS complex prolongation. These conduction defects were accompanied by overt mislocalization of the gap junction protein connexin43 (Cx43). Remarkably, Cx43 mislocalization was also evident in autopsied left ventricle tissue from HGPS patients, suggesting intercellular connectivity alterations at late stages of the disease. The similarities between HGPS patients and progeroid mice reported here strongly suggest that defective cardiac repolarization and cardiomyocyte connectivity are important abnormalities in the HGPS pathogenesis that increase the risk of arrhythmia and premature death.Peer ReviewedPostprint (published version

Investigación e impacto de materiales

A través de este proyecto, se buscó desarrollar e implementar metodologías que evalúen y generen la información que describe el desempeño de las empresas productoras de materiales, como consecuencia de su falta de regulación. Lo anterior, se logró a través de dos líneas de trabajo: una ecoetiqueta que permita certificar a las empresas mexicanas luego de la evaluación del impacto ambiental generado en las etapas del ciclo de vida de un material en específico y una base de datos que permite conocer las distintas opciones de materiales que cumplan las características necesarias para el producto deseado. Esto se logró con la con ayuda de las normas y leyes mexicanas, así como de las EPD’s internacionales y la metodología de Ashby. Finalmente, se obtuvo como resultado del proyecto cinco entregables: ECOMAT y su correspondiente manual de usuario, las metodologías necesarias para el acercamiento y seguimiento de empresas, un formato interno tipo EPD para los materiales de Materioteca ITESO, un formato mejorado de la ficha física de Materioteca ITESO y una base de datos de los tipos de materiales dentro de ésta última.ITESO, A.C

Influence of Protein Carbonylation on Human Adipose Tissue Dysfunction in Obesity and Insulin Resistance

Background: Obesity is characterized by adipose tissue dysregulation and predisposes individuals to insulin resistance and type 2 diabetes. At the molecular level, adipocyte dysfunction has been linked to obesity-triggered oxidative stress and protein carbonylation, considering protein carbonylation as a link between oxidative stress and metabolic dysfunction. The identification of specific carbonylated proteins in adipose tissue could provide novel biomarkers of oxidative damage related to metabolic status (i.e prediabetes). Thus, we aimed at characterizing the subcutaneous and omental human adipose tissue carbonylome in obesity-associated insulin resistance. Methods: 2D-PAGE was used to identify carbonylated proteins, and clinical correlations studies and molecular biology approaches including intracellular trafficking, reactive oxygen species assay, and iron content were performed using in vitro models of insulin resistance. Results: The carbonylome of human adipose tissue included common (serotransferrin, vimentin, actin, and annexin A2) and depot-specific (carbonic anhydrase and α-crystallin B in the subcutaneous depot; and α-1-antitrypsin and tubulin in the omental depot) differences that point out the complexity of oxidative stress at the metabolic level, highlighting changes in carbonylated transferrin expression. Posterior studies using in vitro prediabetic model evidence alteration in transferrin receptor translocation, linked to the prediabetic environment. Finally, ligand-receptor molecular docking studies showed a reduced affinity for carbonylated transferrin binding to its receptor compared to wild-type transferrin, emphasizing the role of transferrin carbonylation in the link between oxidative stress and metabolic dysfunction. Conclusions: The adipose tissue carbonylome contributes to understanding the molecular mechanism driving adipocyte dysfunction and identifies possible adipose tissue carbonylated targets in obesity-associated insulin resistance

Ventilación líquida. Metaanálisis y revisión sistemática de la literatura

Introducción: En 1990 con base en las propiedades de los pfc (perfluorocarbonos) se realizó el primer ensayo clínico de ventilación líquida en humanos, en seis recién nacidos prematuros con insuficiencia respiratoria grave observándose mejoría significativa en la oxigenación y en la distensibilidad pulmonar. ¿Qué son los pfc? Producidas en la Segunda Guerra Mundial, son sustancias químicas cuyas propiedades dependen de la unión de los átomos de Fluor-Carbono. Su utilidad para la ventilación mecánica depende de su capacidad de disolver 20 veces más O2 y 3 veces más CO2, que el plasma, evaporándose más rápidamente que el agua a temperatura corporal. Los pfc han sido aprobados para aplicaciones biomédicas como transportadores de oxigeno aplicados intravenosos en situaciones de desastres o en individuos que rechazan ser transfundidos, sin embargo, el interés se ha despertado para su uso en la ventilación mecánica y en el síndrome de insuficiencia respiratoria aguda (sira). Por ello, el objetivo de este metaanálisis y revisión sistemática es la valoración de su uso, en especial de la década de los 90 hasta 2020. Analizando lo que dice la literatura y cómo ha funcionado en pacientes con Covid-19 y sira que ameritaron internamiento en unidades de cuidados intensivos. Material y métodos: Se buscaron revisiones sistemáticas, metaanálisis y ensayos clínicos de las revistas The New England Journal of Medicine, The Lancet , Science, Journal of Apply Physiology, Crit Care Med, Chest, Lung, Journal of Pediatrics, American Journal of Respiratory and Critical Care Medicine, Medicina Intensiva, Revista de la Facultad de Medicina de la UNAM, utilizando las bases de datos de Pubmed, medline, y www.mdconsult.com. Se buscó que los artículos estuvieran enfocados en los resultados del uso de la Ventilación Líquida, tanto en recién nacidos, prematuros, en lactantes y en adultos. El estudio se llevó a cabo de agosto de 2021 a febrero de 2022 y se realizó en el Departamento de Neumología de la Facultad de Medicina de la Universidad Autónoma del Estado de México. Resultados y Discusión: Para el año 2000 existían 1104 publicaciones sobre ventilación líquida, y 564 de ellas eran ensayos clínicos en humanos (medline), que demostraban que la Ventilación Líquida Parcial resulta más ventajosa en neonatos. En adultos sólo ha habido pocos resultados buenos con la Ventilación Líquida Total que mantiene recirculando los pfc dentro de un sistema cerrado. En las revisiones de la Fundación Cochrane se ha demostrado en dos revisiones sistemáticas y en dos metaanálisis que no hay pruebas de efectos beneficiosos de la ventilación líquida parcial en adultos con lesión pulmonar aguda. Sin embargo, surge la pregunta del uso de los pfc asociados al surfactante artificial y de mayor número de estudios con grandes grupos comparativos. La pandemia ocasionada por el Covid-19 ha generalizado el uso de la ventilación mecánica en las unidades de cuidados intensivos. Conclusiones: La ventilación líquida con pfc es una realidad y constituye una nueva alternativa terapéutica para el manejo de los enfermos con síndrome de insuficiencia respiratoria aguda. Su uso con la ventilación líquida parcial no ha demostrado la utilidad esperada en adultos, que seguramente requerirán de la ventilación líquida total. En los neonatos con la ventilación líquida parcial existe ya suficiente evidencia para tenerla como una alternativa en los prematuros y el uso combinado con la administración de surfactante no se debe pasar por alto en los Hospitales de Perinatología a nivel mundial

Insoluble and Thermostable Polyhydroxyesters From a Renewable Natural Occurring Polyhydroxylated Fatty Acid

To explore the potential of long chain polyhydroxyalkanoates as non-toxic food packaging materials, the characterization of polyesters prepared from a natural occurring polyhydroxylated C16 carboxylic acid (9,10,16-trihydroxyhexadecanoic or aleuritic acid) has been addressed. Such monomer has been selected to elucidate the reactivity of primary and secondary hydroxyl groups and their contribution to the structure and properties of the polyester. Resulting polyaleuritate films have been produced using an open mold in one-step, solvent-free self-polycondensation in melt state and directly in air to evaluate the effect of oxygen in their final physical and chemical properties. These polymers are amorphous, insoluble, and thermostable, being therefore suitable for solvent, and heat resistant barrier materials. Structurally, most of primary hydroxyls are involved in ester bonds, but there is some branching arising from the partial participation of secondary O-H groups. The oxidative cleavage of the vicinal diol moiety and a subsequent secondary esterification had a noticeable effect on the amorphization and stiffening of the polyester by branching and densification of the ester bond network. A derivation of such structural modification was the surface compaction and the reduction of permeability to water molecules. The addition of Ti(OiPr)4 as a catalyst had a moderate effect, likely because of a poor diffusion within the melt, but noticeably accelerated both the secondary esterification and the oxidative processes. Primary esterification was a high conversion bulk reaction while oxidation and secondary esterification was restricted to nearby regions of the air exposed side of cast films. The reason was a progressive hindering of oxygen diffusion as the reaction progresses and a self-regulation of the altered layer growth. Despite such a reduced extent, the oxidized layer noticeably increased the UV-vis light blockage capacity. In general, characterized physical properties suggest a high potential of these polyaleuritate polyesters as food preserving materials.Peer reviewe

Knowledge elicitation of pedagogical needs for TEL-based minimally invasive surgery learning of multiple skills

Technology enhanced learning (TEL) is nowadays consolidated as a complement for training the different skills required in minimally invasive surgery (MIS). However, its use is fragmented, depending on the availability of TEL resources in hospitals and training centres, addressing individual skills rather than all skills as a whole, and lacking a pedagogical model to support efficient learning. The EASIER project will implement a learning platform supported by a validated pedagogical model and integrate tools and resources to train and assess together all skills required from new surgeons. In this study, we present the early definition stages, in which a knowledge elicitation methodology is developed to capture the know-how of surgeons, engineers and educational psychologists. First results are presented in the form of learning actions and potential means of implementation. This knowledge will be key in defining the pedagogical needs of the platforms

Results of may measurement Month 2018 campaign in Venezuela.

Cardiovascular diseases, mainly coronary heart disease and stroke, are the main cause of death in Venezuela; hypertension is the primary risk factor. The May Measurement Month (MMM) study is a global initiative aimed at raising awareness of elevated blood pressure (BP). The previous MMM 2017 campaign showed 48.9% of participants had hypertension, higher than previous Venezuelan epidemiological studies. The MMM 2018 campaign included 28 649 participants screened [mean age: 54.2 (SD 15.13) years; female 62.8%] carried out mainly in pharmacies in 61 sites. Physical measurements included height, weight, and BP, taken in sitting position three times. After multiple imputations, 48.4% had hypertension, of which 87.7% were aware of their diagnosis. Of the individuals not receiving antihypertensive medication, 14.0% had hypertension and 33.7% of those receiving treatment had uncontrolled hypertension. Overall, the percentage of hypertensives with controlled hypertension was 54.8%. Body mass index was calculated for the total population, and it was on average 25.2 (SD: 4.65) kg/m2. Of all, 14.2% was classified as obese and 32.6% as overweight; meanwhile 4.8% as underweight. Diabetes was reported by 9.5%. These results suggest that repeated screening like the MMM campaign can routinely identify hypertension and consequently implement programmes of treatment in Venezuela, also other common risk factors, like obesity or diabetes

Results of the May measurement month 2017: blood pressure campaign in Venezuela-Americas.

Cardiovascular diseases, mainly coronary heart disease and stroke, are the first cause of death in Venezuela; and hypertension is the main risk factor. May Measurement Month (MMM) is a global initiative aimed at raising awareness of elevated blood pressure (BP) and to act as a temporary solution to the lack of regular screening programmes. Some representative studies indicate prevalence of hypertension in Venezuela between 24 and 39%, and control rate around 20%. Sixty-four sites were included to participate in MMM, mainly in pharmacies. Physical measurements included height, weight, and abdominal circumference. Blood pressure was measured in the sitting position three times after resting for 5 min, 1 min apart, using validated oscillometric devices. 21 644 individuals were screened. After multiple imputation, 10 584 individuals [48.9% (50.7% male; 47.7% female)] had hypertension. Of individuals not receiving antihypertensive medication, 1538 (12.2%) were hypertensive. Of individuals receiving antihypertensive medication, 2974 (32.9%) had uncontrolled BP. About 16% had obesity calculated by body mass index; 43.8% of women and 20.7% of men had abdominal obesity. This was the largest BP screening carried out in Venezuela, in which 48.9% of the individuals had elevated BP, untreated hypertension was 12.2%, and one-third of subjects taking treatment were not controlled. About 16% had obesity by body mass index, and abdominal obesity is more common in women. These results suggest that repeated screening like MMM17 can identify hypertension in important numbers and can also evaluate programmes of hypertension treatment and control in Venezuela