Vachellia farnesiana Pods or a Polyphenolic Extract Derived from Them Exert Immunomodulatory, Metabolic, Renoprotective, and Prebiotic Effects in Mice Fed a High-Fat Diet.

Obesity causes systemic inflammation, hepatic and renal damage, as well as gut microbiota dysbiosis. Alternative vegetable sources rich in polyphenols are known to prevent or delay the progression of metabolic abnormalities during obesity. Vachellia farnesiana (VF) is a potent source of polyphenols with antioxidant and anti-inflammatory activities with potential anti-obesity effects. We performed an in vivo preventive or an interventional experimental study in mice and in vitro experiments with different cell types. In the preventive study, male C57BL/6 mice were fed with a Control diet, a high-fat diet, or a high-fat diet containing either 0.1% methyl gallate, 10% powdered VFP, or 0.5%, 1%, or 2% of a polyphenolic extract (PE) derived from VFP (Vachellia farnesiana pods) for 14 weeks. In the intervention study, two groups of mice were fed for 14 weeks with a high-fat diet and then one switched to a high-fat diet with 10% powdered VFP for ten additional weeks. In the in vitro studies, we evaluated the effect of a VFPE (Vachellia farnesiana polyphenolic extract) on glucose-stimulated insulin secretion in INS-1E cells or of naringenin or methyl gallate on mitochondrial activity in primary hepatocytes and C2C12 myotubes. VFP or a VFPE increased whole-body energy expenditure and mitochondrial activity in skeletal muscle; prevented insulin resistance, hepatic steatosis, and kidney damage; exerted immunomodulatory effects; and reshaped fecal gut microbiota composition in mice fed a high-fat diet. VFPE decreased insulin secretion in INS-1E cells, and its isolated compounds naringenin and methyl gallate increased mitochondrial activity in primary hepatocytes and C2C12 myotubes. In conclusion VFP or a VFPE prevented systemic inflammation, insulin resistance, and hepatic and renal damage in mice fed a high-fat diet associated with increased energy expenditure, improved mitochondrial function, and reduction in insulin secretion.

Metabolomics analysis reveals a modified amino acid metabolism that correlates with altered oxygen homeostasis in COVID-19 patients.

We identified the main changes in serum metabolites associated with severe (n = 46) and mild (n = 19) COVID-19 patients by gas chromatography coupled to mass spectrometry. The modified metabolic profiles were associated to an altered amino acid catabolism in hypoxic conditions. Noteworthy, three α-hydroxyl acids of amino acid origin increased with disease severity and correlated with altered oxygen saturation levels and clinical markers of lung damage. We hypothesize that the enzymatic conversion of α-keto-acids to α- hydroxyl-acids helps to maintain NAD recycling in patients with altered oxygen levels, highlighting the potential relevance of amino acid supplementation during SARS-CoV-2 infection.

Transitioning pharmacoperones to therapeutic use: in vivo proof-of-principle and design of high throughput screens.

A pharmacoperone (from "pharmacological chaperone") is a small molecule that enters cells and serves as molecular scaffolding in order to cause otherwise-misfolded mutant proteins to fold and route correctly within the cell. Pharmacoperones have broad therapeutic applicability since a large number of diseases have their genesis in the misfolding of proteins and resultant misrouting within the cell. Misrouting may result in loss-of-function and, potentially, the accumulation of defective mutants in cellular compartments. Most known pharmacoperones were initially derived from receptor antagonist screens and, for this reason, present a complex pharmacology, although these are highly target specific. In this summary, we describe efforts to produce high throughput screens that identify these molecules from chemical libraries as well as a mouse model which provides proof-of-principle for in vivo protein rescue using existing pharmacoperones.

¿Cómo prepararnos para la deliberación ética en la práctica clínica en pediatría? / Rethinking ethical decision-making in pediatrics

En el siglo XXI, el reto para la medicina es utilizar nuevamente términos, como filantropía y filotecnia, para la práctica clínica contemporánea, ya que estos términos se adaptan a nuestro actual entendimiento de que la medicina basada en valores y la medicina basada en evidencias deben ir siempre de la mano. Nuestro propósito es proponer un método integral de deliberación ética que implique una visión holística de los dilemas éticos en la práctica clínica de la pediatría.

A challenge for 21st century medicine is to rediscover the value of philanthropy and philotechnia in contemporary clinical practice because both are terms that adapt to our more current understanding of how value-based medicine and evidence-based medicine must always go "hand in hand." Our proposal is to offer an integral ethical deliberation method that implies a holistic view of the ethical dilemmas in pediatric clinical practice.

Ecocardiografía transesofágica en niños / Transesophageal echocardiography in children

Objetivo: describir una muestra preliminar de ecocardiogramas realizados en niños con dos tipos de patología: endocarditis infecciosa (EI) y cardiopatías congénitas (CC), en quienes se compararan los informe obtenidos de dos métodos, ecoradiograma transtorácico (ETT) y ecocardiograma transesofágico (ETE) y se correlacionan con datos del diagnóstico de certeza obtenido por cateterismo cardiaco, por cirugía o por ambos. Material y métodos: se estudiaron 42 niños, cuya edad varió de un día a cuatro años. Se dividieron en dos grupos: Grupo I, 15 pacientes con diagnóstico clínico presunto de EI. El Grupo II, 27 pacientes con diagnóstico de CC. El diagnóstico de certeza para el grupo I se apoyó en datos clínicos, ecoardiograma y hemocultivos. En el grupo II, en alguno o varios de los siguientes métodos: cateterismo cardiaco, angiografía o cirugía. Resultados: en el grupo I, fueron 15 pacientes cuyas edades fluctuaron entre 43 días y cuatro años (media de 17.8 meses). No predominó un sexo. El peso varió ente 2,215 g y 14 kg. El diagnóstico de EI se apoyó en la presencia de fiebre en estudio y el antecedente de haber teido instalado un catéter endovenoso para administración de líquidos, de medicamentos, o de ambos. El dato para sustenta el diagnóstico de EI con el ETE fue la presencia de masas intracardiacas en distinto sitios que se interpretaron como vegetaciones y que se vieron en 8/15 casos. En el grupo II, hubo 27 pacientes con diversas CC de las cuales se cateterizaron 24/27. En ambos grupos se realizaron los dos tipos de ecocardiograma: ETT y ETE. Conclusión: la facilidad de registrar imágenes en forma biplanar, permite al ETE viasualizar áreas que no son accesibles en con ETT. Por esta razón entre otras, algunos investigadores insisten en que se recurra al ETE siempre que sea posible