Globular Adiponectin Activates Motility and Regenerative Traits of Muscle Satellite Cells

Regeneration of adult injured skeletal muscle is due to activation of satellite cells, a population of stem cells resident beneath the basal lamina. Thus, information on soluble factors affecting satellite cell activation, as well as migration towards injury and fusion into new myofibers are essential. Here, we show that globular adiponectin (gAd), positively affects several features of muscle satellite cells. gAd activates satellite cells to exit quiescence and increases their recruitment towards myotubes. gAd elicits in satellite cells a specific motility program, involving activation of the small GTPase Rac1, as well as expression of Snail and Twist transcription factors driving a proteolytic motility, useful to reach the site of injury. We show that satellite cells produce autocrine full length adiponectin (fAd), which is converted to gAd by activated macrophages. In turns, gAd concurs to attract to the site of injury both satellite cells and macrophages and induces myogenesis in muscle satellite cells. Thus, these findings add a further role for gAd in skeletal muscle, including the hormone among factors participating in muscle regeneration

Effect of a vitamin/mineral supplement on children and adults with autism

<p>Abstract</p> <p>Background</p> <p>Vitamin/mineral supplements are among the most commonly used treatments for autism, but the research on their use for treating autism has been limited.</p> <p>Method</p> <p>This study is a randomized, double-blind, placebo-controlled three month vitamin/mineral treatment study. The study involved 141 children and adults with autism, and pre and post symptoms of autism were assessed. None of the participants had taken a vitamin/mineral supplement in the two months prior to the start of the study. For a subset of the participants (53 children ages 5-16) pre and post measurements of nutritional and metabolic status were also conducted.</p> <p>Results</p> <p>The vitamin/mineral supplement was generally well-tolerated, and individually titrated to optimum benefit. Levels of many vitamins, minerals, and biomarkers improved/increased showing good compliance and absorption. Statistically significant improvements in metabolic status were many including: total sulfate (+17%, p = 0.001), S-adenosylmethionine (SAM; +6%, p = 0.003), reduced glutathione (+17%, p = 0.0008), ratio of oxidized glutathione to reduced glutathione (GSSG:GSH; -27%, p = 0.002), nitrotyrosine (-29%, p = 0.004), ATP (+25%, p = 0.000001), NADH (+28%, p = 0.0002), and NADPH (+30%, p = 0.001). Most of these metabolic biomarkers improved to normal or near-normal levels.</p> <p>The supplement group had significantly greater improvements than the placebo group on the Parental Global Impressions-Revised (PGI-R, Average Change, p = 0.008), and on the subscores for Hyperactivity (p = 0.003), Tantrumming (p = 0.009), Overall (p = 0.02), and Receptive Language (p = 0.03). For the other three assessment tools the difference between treatment group and placebo group was not statistically significant.</p> <p>Regression analysis revealed that the degree of improvement on the Average Change of the PGI-R was strongly associated with several biomarkers (adj. R²= 0.61, p < 0.0005) with the initial levels of biotin and vitamin K being the most significant (p < 0.05); both biotin and vitamin K are made by beneficial intestinal flora.</p> <p>Conclusions</p> <p>Oral vitamin/mineral supplementation is beneficial in improving the nutritional and metabolic status of children with autism, including improvements in methylation, glutathione, oxidative stress, sulfation, ATP, NADH, and NADPH. The supplement group had significantly greater improvements than did the placebo group on the PGI-R Average Change. This suggests that a vitamin/mineral supplement is a reasonable adjunct therapy to consider for most children and adults with autism.</p> <p>Trial Registration</p> <p><b>Clinical Trial Registration Number: </b><a href="http://www.clinicaltrials.gov/ct2/show/NCT01225198">NCT01225198</a></p

Fluid challenges in intensive care: the FENICE study A global inception cohort study

Fluid challenges (FCs) are one of the most commonly used therapies in critically ill patients and represent the cornerstone of hemodynamic management in intensive care units. There are clear benefits and harms from fluid therapy. Limited data on the indication, type, amount and rate of an FC in critically ill patients exist in the literature. The primary aim was to evaluate how physicians conduct FCs in terms of type, volume, and rate of given fluid; the secondary aim was to evaluate variables used to trigger an FC and to compare the proportion of patients receiving further fluid administration based on the response to the FC.This was an observational study conducted in ICUs around the world. Each participating unit entered a maximum of 20 patients with one FC.2213 patients were enrolled and analyzed in the study. The median [interquartile range] amount of fluid given during an FC was 500 ml (500-1000). The median time was 24 min (40-60 min), and the median rate of FC was 1000 [500-1333] ml/h. The main indication for FC was hypotension in 1211 (59 %, CI 57-61 %). In 43 % (CI 41-45 %) of the cases no hemodynamic variable was used. Static markers of preload were used in 785 of 2213 cases (36 %, CI 34-37 %). Dynamic indices of preload responsiveness were used in 483 of 2213 cases (22 %, CI 20-24 %). No safety variable for the FC was used in 72 % (CI 70-74 %) of the cases. There was no statistically significant difference in the proportion of patients who received further fluids after the FC between those with a positive, with an uncertain or with a negatively judged response.The current practice and evaluation of FC in critically ill patients are highly variable. Prediction of fluid responsiveness is not used routinely, safety limits are rarely used, and information from previous failed FCs is not always taken into account

Acquired antibiotic resistance traits in commensal bacteria of wild land iguanas from a remote and protected island of the Galápagos Archipelago

In recent years, the presence of acquired resistance traits has been investigated in the wildlife commensal microbiota, to better understand the ecology and dynamics of antibiotic resistance determinants dissemination. Most of the available data concern mammals and birds from remote or more promiscuous settings . This study was aimed at collecting similar data on commensal bacteria from land iguanas living in a remote and protected environment, free from exposure to the selective pressure related by the use of antimicrobial agents and where close interactions with humans and other animal species are overall minimal. Methods: Cloacal swabs were collected from 96 iguanas in Santa Fè island (Conolophus pallidus) where tourists are restricted to well defined trails for animal viewing and human settlements are not allowed. Coliform bacteria were selected on MacConkey agar to determine the dominant species, and susceptibility to 10 antimicrobials (AMK, AMP, CIP, CHL, GEN, KAN, NAL, TET, STR, SXT ) was determined. Non-dominant resistant coliforms were detected by plating swabs onto MacConkey agar and looking for colonies grown inside the zone of inhibition of the antibiotic disks applied directly to the seeded plate. Results: In each animal, the dominant gut microbiota growing on McConkey medium consisted of one or two coliform species which included Escherichia coli in 77% of animals. In no case the antimicrobial susceptibility profile was suggestive for acquired resistance traits. Non-dominant resistant coliforms were obtained from 82 (85.4%) animals (overall, 126 non-duplicated isolates of various species). Of these, only 5 E. coli carried acquired resistance traits to AMP (n=3), TET + NAL (n=1), or to all the tested antibiotics but CIP, NAL and AMK (n=1). blaTEM, Tet A and Tet B were found as acquired resistance genes. Conclusions: Coliforms are normally represented in the gut microbiota of terrestrial iguanas. In this remote and protected natural environment acquired resistance traits were exceedingly rare. This study provides a “zero level” antibiotic resistance basis, which could prove useful also in bioconservation approaches

Antibiotico resistenza in batteri commensali delle iguane terrestri (Conolophus pallidus e C. subcristatus) delle Galápagos: studio del livello zero e della dinamica di disseminazione.

Per valutare la dinamica e l’ecologia di disseminazione dell’antibiotico-resistenza acquisita è stato studiato il microbiota commensale delle iguane terrestri dell’Arcipelago delle Galápagos, provenienti da aree differentemente esposte sia alla pressione selettiva dell’uso degli agenti antibatterici sia a interazioni con l’uomo e altre specie animali. Sono stati analizzati tamponi cloacali prelevati da 282 iguane provenienti da 6 isole; su MacConkey agar sono stati: selezionati coliformi e determinate specie dominanti e suscettibilità a 10 antibiotici (AMK, AMP, CIP, CHL, GEN, KAN, NAL, TET, STR, SXT). I risultati hanno dimostrato che l’acquisizione di caratteri di antibiotico resistenza è rara e che la frequenza relativa delle specie di enterobatteri dominanti è diversa nei diversi siti di campionamento. Lo studio ha permesso di individuare il “livello zero” di antibiotico-resistenza

Antibiotico resistenza in batteri commensali delle iguane terrestri (Conolophus pallidus e C. subcristatus) delle Galápagos: studio del livello zero e della dinamica di disseminazione.

Per valutare la dinamica e l’ecologia di disseminazione dell’antibiotico-resistenza acquisita è stato studiato il microbiota commensale delle iguane terrestri dell’Arcipelago delle Galápagos, provenienti da aree differentemente esposte sia alla pressione selettiva dell’uso degli agenti antibatterici sia a interazioni con l’uomo e altre specie animali. Sono stati analizzati tamponi cloacali prelevati da 282 iguane provenienti da 6 isole; su MacConkey agar sono stati: selezionati coliformi e determinate specie dominanti e suscettibilità a 10 antibiotici (AMK, AMP, CIP, CHL, GEN, KAN, NAL, TET, STR, SXT). I risultati hanno dimostrato che l’acquisizione di caratteri di antibiotico resistenza è rara e che la frequenza relativa delle specie di enterobatteri dominanti è diversa nei diversi siti di campionamento. Lo studio ha permesso di individuare il “livello zero” di antibiotico-resistenza

Acquired antibiotic resistance traits in commensal bacteria of wild land iguanas from a remote and protected island of the Galápagos Archipelago

In recent years, the presence of acquired resistance traits has been investigated in the wildlife commensal microbiota, to better understand the ecology and dynamics of antibiotic resistance determinants dissemination. Most of the available data concern mammals and birds from remote or more promiscuous settings . This study was aimed at collecting similar data on commensal bacteria from land iguanas living in a remote and protected environment, free from exposure to the selective pressure related by the use of antimicrobial agents and where close interactions with humans and other animal species are overall minimal. Methods: Cloacal swabs were collected from 96 iguanas in Santa Fè island (Conolophus pallidus) where tourists are restricted to well defined trails for animal viewing and human settlements are not allowed. Coliform bacteria were selected on MacConkey agar to determine the dominant species, and susceptibility to 10 antimicrobials (AMK, AMP, CIP, CHL, GEN, KAN, NAL, TET, STR, SXT ) was determined. Non-dominant resistant coliforms were detected by plating swabs onto MacConkey agar and looking for colonies grown inside the zone of inhibition of the antibiotic disks applied directly to the seeded plate. Results: In each animal, the dominant gut microbiota growing on McConkey medium consisted of one or two coliform species which included Escherichia coli in 77% of animals. In no case the antimicrobial susceptibility profile was suggestive for acquired resistance traits. Non-dominant resistant coliforms were obtained from 82 (85.4%) animals (overall, 126 non-duplicated isolates of various species). Of these, only 5 E. coli carried acquired resistance traits to AMP (n=3), TET + NAL (n=1), or to all the tested antibiotics but CIP, NAL and AMK (n=1). blaTEM, Tet A and Tet B were found as acquired resistance genes. Conclusions: Coliforms are normally represented in the gut microbiota of terrestrial iguanas. In this remote and protected natural environment acquired resistance traits were exceedingly rare. This study provides a “zero level” antibiotic resistance basis, which could prove useful also in bioconservation approaches