L'importanza del vaccino anti Covid-19 nei pazienti affetti da malattia del rene policistico autosomico dominante dell'adulto (ADPKD)

The SARS-CoV-2 (Covid-19) infection affected about 106 million people worldwide and the total amount of casualties now sits at a staggering 2 millions. Chronic Kidney Disease (CKD) emerged as the first risk factor in worst patients, not considering old age. Kidney disease and acute kidney injury have been correlated with a higher chance of death. This combination of CKD and higher Covid-19 related mortality requires immediate response from a prevention point of view at first and then from a therapeutic one. There is not a clear relation between Covid-19 and ADPKD. What can be inferred is the following: Covid uses the ACE2 receptors on cell membranes to "lock on" its target. It is well-established in fact that the RAAS is more active in ADPKD patients and it may represent an additional risk factor for these patients. At the moment three Covid-19 vaccines have been approved, and two of them have been already administered, such as Pfizer BioNTech and Moderna, sharing the same mechanism. AstraZeneca released a third option. All of them are completely safe and reliable, each one with its own feature. Therefore, considering how delicate ADPKD patients are, vaccination is strongly recommended

Trimetazidine Reduces Endogenous Free Fatty Acid Oxidation

INTRODUCTION: The metabolic modulator trimetazidine (TMZ) has been suggested to induce a metabolic shift from myocardial fatty acid oxidation (FAO) to glucose utilization, but this mechanism remains unproven in humans. The oxidation of plasma derived FA is commonly measured in humans, whereas the contribution of FA from triglycerides stored in the myocardium has been poorly characterized. AIMS: To verify the hypothesis that TMZ induces a metabolic shift, we combined positron emission tomography (PET) and magnetic resonance spectroscopy ((1)H-MRS) to measure myocardial FAO from plasma and intracellular lipids, and myocardial glucose metabolism. Nine obese subjects were studied before and after 1 month of TMZ treatment. Myocardial glucose and FA metabolism were assessed by PET with (18)F-fluorodeoxyglucose and (11)C-palmitate. (1)H-MRS was used to measure myocardial lipids, the latter being integrated into the PET data analysis to quantify myocardial triglyceride turnover. RESULTS: Myocardial FAO derived from intracellular lipids was at least equal to that of plasma FAs (P = NS). BMI and cardiac work were positively associated with the oxidation of plasma derived FA (P ≤ 0.01). TMZ halved total and triglyceride-derived myocardial FAO (32.7 ± 8.0 to 19.6 ± 4.0 μmol/min and 23.7 ± 7.5 to 10.3 ± 2.7 μmol/min, respectively; P ≤ 0.05). These changes were accompanied by increased cardiac efficiency since unchanged LV work (1.6 ± 0.2 to 1.6 ± 0.1 Watt/g × 10(2), NS) was associated with decreased work energy from the intramyocardial triglyceride oxidation (1.6 ± 0.5 to 0.4 ± 0.1 Watt/g × 10(2), P = 0.036). CONCLUSIONS: In obese subjects, we demonstrate that myocardial intracellular triglyceride oxidation significantly provides FA-derived energy for mechanical work. TMZ reduced the oxidation of triglyceride-derived myocardial FAs improving myocardial efficiency

Y nosotras... ¿qué hicimos? : luces y sombras sobre el programa “Ellas Hacen”

Fil: Amaya Guerrero, Romina Gabriela. Universidad Nacional de Quilmes; Argentina.Fil: Bucci, Valeria. Buenos Aires. Dirección Provincial de Planificación Estratégica; Argentina.Fil: Zorrozúa, Florencia Isola. Universidad Nacional de Quilmes; Argentina.Fil: Guerrero, Gabriela Nelba. Universidad Nacional de Quilmes; Argentina.Fil: Zangaro, Marcela. Grupo de Estudio sobre Sociología del Management; Argentina.Fil: Zangaro, Marcela. Alfatexto; Argentina.Este trabajo tiene como objetivo presentar un balance del desarrollo del programa “Ellas Hacen”, implementado en 2013 por la gestión de gobierno de Cristina Fernández de Kirchner (2007-2015) y destinado a mujeres madres de tres o más hijos e hijas, con hijos o hijas con discapacidad, o víctimas de violencia de género. Hasta el año 2018, “Ellas Hacen” funcionó en el marco del programa “Ingreso Social con Trabajo- Argentina Trabaja”. A partir de ese año sufrió una reconfiguración que terminó en su desarticulación y traspaso al programa “Hacemos futuro”. El balance que aquí presentamos se funda en indagaciones realizadas sobre el “Ellas Hacen” en el marco del Proyecto de Investigación en Temas de Vacancia de la unq “Economía del cuidado. Una mirada desde las políticas públicas y la ess ”, integrado por las autoras. Se realizaron encuestas y entrevistas a las mujeres integrantes del “Ellas Hacen” a fin de conocer los arreglos de cuidado que implementaron para cumplir con las tareas propuestas por el programa (con especial atención en los mecanismos comunitarios), así como las limitaciones que se manifestaron en el funcionamiento del programa y las formas de continuidad llevadas a cabo en el contexto de la reconfiguración planteada en 2018.This paper aims to show a review of the development of the “Ellas Hacen” program, implemented in 2013 by the government administration of Cristina Fernández de Kirchner (2007-2015) and focused to women mothers of three or more sons and daughters, with children or daughters with disabilities, or victims of gender violence. Until 2018, “Ellas Hacen” operated within the framework of the “Argentina Works” program. From that year on, it underwent a reconfiguration that ended in its disarticulation and transfer to the “Hacemos futuro” program. The balance that we present here is based on inquiries made about the “Ellas Hacen” within the framework of the Research Project on Vacancy Themes of the unq “Economía del cuidado. Una mirada desde las políticas públicas y la ess ” (“Care economy. A look from the public policies and the Social and Solidary Economics”), integrated by the authors. Surveys and interviews were carried out with the women members of “Ellas Hacen” in order to learn about the care arrangements they implemented to fulfill the tasks proposed by the program (with special attention to community mechanisms); the limitations that were manifested in the operation of the program and the forms of continuity carried out in the context of the reconfiguration proposed in 2018

Congenital solitary kidney in autosomal dominant polycystic kidney disease: Where do known genes end and the unknown begin?

Key Clinical Message We present the case of a 41‐year‐old man patient diagnosed with solitary left kidney with few cysts. He has a family history of unilateral renal agenesis (URA) but no for autosomal dominant polycystic kidney disease (ADPKD). Genetic testing revealed PKD1 gene intron 11 heterozygous nucleotide variant c.2854‐23G>T, but no gene mutation implicated in URA. Just eight cases of ADPKD with one kidney have been recorded globally. PC1 and PC2 disruption, causing primary cilia malformation or absence resulting in relevant in the first embryonic development alteration. Cillia's crucial significance in many diseases will require more research

A Rare Case of Concurrent 2q34q36 Duplication and 2q37 Deletion in a Neonate with Syndromic Features

Large-scale genomic structural variations can have significant clinical implications, depending on the specific altered genomic region. Briefly, 2q37 microdeletion syndrome is a prevalent subtelomeric deletion disorder characterized by variable-sized deletions. Affected patients exhibit a wide range of clinical manifestations, including short stature, facial dysmorphism, and features of autism spectrum disorder, among others. Conversely, isolated duplications of proximal chromosome 2q are rare and lack a distinct phenotype. In this report, we provide an extensive molecular analysis of a 15-day-old newborn referred for syndromic features. Our analysis reveals an 8.5 Mb microdeletion at 2q37.1, which extends to the telomere, in conjunction with an 8.6 Mb interstitial microduplication at 2q34q36.1. Our findings underscore the prominence of 2q37 terminal deletions as commonly reported genomic anomalies. We compare our patient’s phenotype with previously reported cases in the literature to contribute to a more refined classification of 2q37 microdeletion syndrome and assess the potential impact of 2q34q36.1 microduplication. We also investigate multiple hypotheses to clarify the genetic mechanisms responsible for the observed genomic rearrangement

Development of Resistance to the Atypical Retinoid, ST1926, in the Lung Carcinoma Cell Line H460 Is Associated with Reduced Formation of DNA Strand Breaks and a Defective DNA Damage Response

Atypical retinoids are potent inducers of apoptosis, but activation of the apoptotic pathway seems to be independent of retinoid receptors. Previous studies with a novel adamantyl retinoid, ST1926, have shown that apoptosis induction is associated with an early genotoxic stress. To better understand the relevance of these events, we have selected a subline of the H460 lung carcinoma cell line resistant to ST1926. Resistant cells exhibited cross-resistance to a related molecule, CD437, but not cross-resistance to agents with different mechanisms of action. In spite of a lack of defects in intracellular drug accumulation, induction of DNA strand breaks in resistant cells required exposure to a substantially higher concentration, which was consistent with the degree of resistance. At drug concentrations causing a similar antiproliferative effect (IC(80)) and a comparable extent of DNA lesions in sensitive and resistant cells, the apoptotic response was a delayed and less marked event in resistant cells, thus indicating a reduced susceptibility to apoptosis. In spite of recognition of DNA lesions in resistant cells, as supported by phosphorylation of p53 and histone H2AX, resistant cells exhibited no activation of the mitochondrial pathways of apoptosis. Following exposure to equitoxic drug concentrations, only sensitive cells exhibited a typical stress/DNA damage response, with activation of the S-phase checkpoint. The cellular resistance to ST1926 reflects alterations responsible for a reduced generation of DNA lesions and for an enhanced tolerance of the genotoxic stress, resulting in lack of activation of the intrinsic pathway of apoptosis. The defective DNA damage response, accompanied by a reduced susceptibility to apoptosis in resistant cells, provides further support to the involvement of genotoxic stress as a critical event in mediating apoptosis induction by ST1926

Human obesity is characterized by defective fat storage and enhanced muscle fatty acid oxidation, and trimetazidine gradually counteracts these abnormalities

Bucci M, Borra R, Nagren K, Maggio R, Tuunanen H, Oikonen V, Del Ry S, Viljanen T, Taittonen M, Rigazio S, Giannessi D, Parkkola R, Knuuti J, Nuutila P, Iozzo P. Human obesity is characterized by defective fat storage and enhanced muscle fatty acid oxidation, and trimetazidine gradually counteracts these abnormalities. Am J Physiol Endocrinol Metab 301: E105-E112, 2011. First published April 19, 2011; doi: 10.1152/ajpendo.00680.2010.-An impaired ability to store fatty acids (FA) in subcutaneous adipose tissue (SAT) may be implicated in the pathogenesis of obesity-related diseases via overexposure of lean tissues and production of free radicals from FA oxidation (FAO). We studied regional FA metabolism in skeletal muscle and adipose tissue in humans and investigated the long-term effects of the FAO inhibitor trimetazidine on glucose and FA metabolism. Positron emission tomography (PET) and [C-11] palmitate were used to compare FA metabolism in SAT and skeletal muscle between eight obese and eight nonobese subjects (BMI >=/<30 kg/m(2)). A subgroup of nine subjects underwent a 1-mo trimetazidine administration. PET with [C-11] palmitate and [F-18] fluorodeoxyglucose, indirect calorimetry, and MRI before and after this period were performed to characterize glucose and FA metabolism, fat masses, skeletal muscle triglyceride, and creatine contents. Obesity was characterized by a 100% elevation in FAO and a defect in the FA esterification rate constant (P <0.05) in skeletal muscle. FA esterification was reduced by similar to 70% in SAT (P <0.001) in obese vs. control subjects. The degrees of obesity and insulin resistance were both negatively associated with esterification-related parameters and positively with FAO (P <0.05). Trimetazidine increased skeletal muscle FA esterification (P <0.01) and mildly upregulated glucose phosphorylation (P = 0.066). Our data suggest that human obesity is characterized by a defect in tissue FA storage capability, which is accompanied by a (potentially compensatory) elevation in skeletal muscle FAO; trimetazidine diverted FA from oxidative to nonoxidative pathways and provoked an initial activation of glucose metabolism in skeletal muscle