MEDICIONES ULTRASONOGRAFICAS Y DE TOMOGRAFIA COMPUTADA DE ADIPOSIDAD Y ALTERACIONES METABOLICAS ASOCIADAS A OBESIDAD EN NIÑOS

Introducción. La obesidad infantil es un problema de salud pública de prevalencia creciente y consecuencias a futuro. El compartimiento adiposo intraperitoneal estaría asociado a factores de riesgo metabólicos propios de la obesidad. No existe una estandarización de mediciones de tejido adiposo en imágenes en niños. Objetivos. Estudiar la asociación entre mediciones de tejido graso abdominal con insulinemia, en niños. Sujetos y Métodos. Se estudiaron 37 escolares prepuberales obesos (IMC ? p95), de ambos sexos, entre 6 y 12 años, con técnicas antropométricas, imagenológicas (US y TC) y de laboratorio (glicemia, insulinemia). Resultados. Las mediciones del tejido adiposo abdominal mediante US presentaron altas correlaciones con las mismas mediciones por TC (r= 0,79; pIntroduction. Childhood obesity is increasing over the world with serious health consequences. Intraabdominal fat is associated to some metabolic alterations in obesity. It does not exist a standard imaging method to measure adipose tissue in children. Objectives: In obese children to study the association between insulinemia and subcutaneous or intraabdominal fat evaluated by ultrasonographic (US) or computed tomography (CT). Subjects and Methods. 37 obese (BMI ? p95) prepubertal obese children (ages from 6 to 12 years) were assessed using anthropometric, US and CT for fat areas and linear intrabdominal segments measurements. Laboratory techniques were also performed: insulinemia and glycemia. Results. We found good correlations between US and TC intra-abdominal adipose tissue measurements (r= 0,79; p< 0,001). US (r=0.56) and CT (r=0.53) visceral fat assessment had better correlations with insulinemia than anthropometric measurements (BMI, r= 0,33; waist, r= 0.42). Conclusions. US and CT measurements of intraabdominal fat emerge as promising techniques to identify obesity-associated metabolic risk in childhoo

Ultrasonographic and by computed tomography measurements of adipose tissue and metabolic changes associated with obesity in children Mediciones ultrasonograficas y de tomografia computada de adiposidad y alteraciones metabolicas asociadas a obesidad en ni

Introduction. Childhood obesity is increasing over the world with serious health consequences. Intraabdominal fat is associated to some metabolic alterations in obesity. It does not exist a standard imaging method to measure adipose tissue in children. Objectives: In obese children to study the association between insulinemia and subcutaneous or intraabdominal fat evaluated by ultrasonographic (US) or computed tomography (CT). Subjects and Methods. 37 obese (BMI ? p95) prepubertal obese children (ages from 6 to 12 years) were assessed using anthropometric, US and CT for fat areas and linear intrabdominal segments measurements. Laboratory techniques were also performed: insulinemia and glycemia. Results. We found good correlations between US and TC intra-abdominal adipose tissue measurements (r= 0,79; p&lt; 0,001). US (r=0.56) and CT (r=0.53) visceral fat assessment had better correlations with insulinemia than anthropometric measurements (BMI, r= 0,33; waist, r= 0.42). Conclusions. US an

Molecular Typing of Staphylococcus aureus Isolated from Patients with Autosomal Dominant Hyper IgE Syndrome

Autosomal dominant hyper IgE syndrome (AD-HIES) is a primary immunodeficiency caused by a loss-of-function mutation in the Signal Transducer and Activator of Transcription 3 (STAT3). This immune disorder is clinically characterized by increased susceptibility to cutaneous and sinopulmonary infections, in particular with Candida and Staphylococcus aureus. It has recently been recognized that the skin microbiome of patients with AD-HIES is altered with an overrepresentation of certain Gram-negative bacteria and Gram-positive staphylococci. However, these alterations have not been characterized at the species- and strain-level. Since S. aureus infections are influenced by strain-specific expression of virulence factors, information on colonizing strain characteristics may provide insights into host-pathogen interactions and help guide management strategies for treatment and prophylaxis. The aim of this study was to determine whether the immunodeficiency of AD-HIES selects for unique strains of colonizing S. aureus. Using multi-locus sequence typing (MLST), protein A (spa) typing, and PCR-based detection of toxin genes, we performed a detailed analysis of the S. aureus isolates (n = 13) found on the skin of twenty-one patients with AD-HIES. We found a low diversity of sequence types, and an abundance of strains that expressed methicillin resistance, Panton-Valentine leukocidin (PVL), and staphylococcal enterotoxins K and Q (SEK, SEQ). Our results indicate that patients with AD-HIES may often carry antibiotic-resistant strains that harbor key virulence factors

Semisynthetic antimycobacterial c-3 silicate and c-3/c-21 ester derivatives of fusidic acid: Pharmacological evaluation and stability studies in liver microsomes, rat plasma, and mycobacterium tuberculosis culture

Fusidic acid (FA), a natural product fusidane triterpene-based antibiotic with unique structural features, is active in vitro against Mycobacterium tuberculosis, the causative agent of tuberculosis (TB). While possessing good pharmacokinetics in man, FA is rapidly metabolized in rodents, thus complicating proof-of-concept studies in this model. Toward the repositioning of FA as an anti-TB agent, we herein describe the synthesis, activity, and metabolism of FA and semisynthesized ester derivatives in rat liver microsomes, rat plasma, and mycobacterial cell culture. FA and derivative molecules with a free C-3 OH underwent species-specific metabolism to the corresponding 3-OH epimer, 3-epifusidic acid (3-epiFA). FA was also metabolized in rat plasma to form FA lactone. These additional routes of metabolism may contribute to the more rapid clearance of FA observed in rodents. C-3 alkyl and aryl esters functioned as classic prodrugs of FA, being hydrolyzed to FA in microsomes, plasma, and Mycobacterium tuberculosis culture. In contrast, C-3 silicate esters and C-21 esters were inert to hydrolysis and so did not act as prodrugs. The antimycobacterial activity of the C-3 silicate esters was comparable to that of FA, and these compounds were stable in microsomes and plasma, identifying them as potential candidates for evaluation in a rodent model of tuberculosis

The Dynamic Nonprime Binding of Sampatrilat to the C‑Domain of Angiotensin-Converting Enzyme

Sampatrilat is a vasopeptidase inhibitor that inhibits both angiotensin I-converting enzyme (ACE) and neutral endopeptidase. ACE is a zinc dipeptidyl carboxypeptidase that contains two extracellular domains (nACE and cACE). In this study the molecular basis for the selectivity of sampatrilat for nACE and cACE was investigated. Enzyme inhibition assays were performed to evaluate the in vitro ACE domain selectivity of sampatrilat. The inhibition of the C-domain (<i>K</i>_i = 13.8 nM) by sampatrilat was 12.4-fold more potent than that for the N-domain (171.9 nM), indicating differences in affinities for the respective ACE domain binding sites. Interestingly, replacement of the P₂ group of sampatrilat with an aspartate abrogated its C-selectivity and lowered the potency of the inhibitor to activities in the micromolar range. The molecular basis for this selective profile was evaluated using molecular modeling methods. We found that the C-domain selectivity of sampatrilat is due to occupation of the lysine side chain in the S₁ and S₂ subsites and interactions with Glu748 and Glu1008, respectively. This study provides new insights into ligand interactions with the nonprime binding site that can be exploited for the design of domain-selective ACE inhibitors

Whole Genome Sequence, Variant Discovery and Annotation in Mapuche-Huilliche Native South Americans

Abstract Whole human genome sequencing initiatives help us understand population history and the basis of genetic diseases. Current data mostly focuses on Old World populations, and the information of the genomic structure of Native Americans, especially those from the Southern Cone is scant. Here we present annotation and variant discovery from high-quality complete genome sequences of a cohort of 11 Mapuche-Huilliche individuals (HUI) from Southern Chile. We found approximately 3.1 × 106 single nucleotide variants (SNVs) per individual and identified 403,383 (6.9%) of novel SNVs events. Analyses of large-scale genomic events detected 680 copy number variants (CNVs) and 4,514 structural variants (SVs), including 398 and 1,910 novel events, respectively. Global ancestry composition of HUI genomes revealed that the cohort represents a sample from a marginally admixed population from the Southern Cone, whose main genetic component derives from Native American ancestors. Additionally, we found that HUI genomes contain variants in genes associated with 5 of the 6 leading causes of noncommunicable diseases in Chile, which may have an impact on the risk of prevalent diseases in Chilean and Amerindian populations. Our data represents a useful resource that can contribute to population-based studies and for the design of early diagnostics or prevention tools for Native and admixed Latin American populations

K2-287 b: An Eccentric Warm Saturn Transiting a G-dwarf

We report the discovery of K2-287b, a Saturn mass planet orbiting a G-dwarf with a period of P ≈ 15 days. First uncovered as a candidate using K2 campaign 15 data, follow-up photometry and spectroscopy were used to determine a mass {M}{{P}}=0.317+/- 0.026 {M}{{J}}, radius {R}{{P}}=0.833+/- 0.013 {R}{{J}}, period P=14.893291+/- 0.000025 days, and eccentricity e=0.476+/- 0.026. The host star is a metal-rich V = 11.410 ± 0.129 mag G-dwarf for which we estimate a mass {M}\star ={1.056}-0.021+0.022 {M}☉ , radius {R}\star =1.070+/- 0.010 {R}☉ , metallicity [Fe/H] = 0.20 ±0.05, and {T}eff}=5673+/- 75 K. This warm eccentric planet with a time-averaged equilibrium temperature of {T}eq}≈ 800 K adds to the small sample of giant planets orbiting nearby stars whose structure is not expected to be affected by stellar irradiation. Follow-up studies on the K2-287 system could help constrain theories of planet migration in close-in orbits