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

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

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

Examining explainable clinical decision support systems with think aloud protocols.

Machine learning tools are increasingly used to improve the quality of care and the soundness of a treatment plan. Explainable AI (XAI) helps users in understanding the inner mechanisms of opaque machine learning models and is a driver of trust and adoption. Explanation methods for black-box models exist, but there is a lack of user studies on the interpretability of the provided explanations. We used a Think Aloud Protocol (TAP) to explore oncologists' assessment of a lung cancer relapse prediction system with the aim of refining the purpose-built explanation model for better credibility and utility. Novel to this context, TAP is used as a neutral methodology to elicit experts' thought processes and judgements of the AI system, without explicit prompts. TAP aims to elicit the factors which influenced clinicians' perception of credibility and usefulness of the system. Ten oncologists took part in the study. We conducted a thematic analysis of their verbalized responses, generating five themes that help us to understand the context within which oncologists' may (or may not) integrate an explainable AI system into their working day

Appendix A: Think aloud protocol.

Machine learning tools are increasingly used to improve the quality of care and the soundness of a treatment plan. Explainable AI (XAI) helps users in understanding the inner mechanisms of opaque machine learning models and is a driver of trust and adoption. Explanation methods for black-box models exist, but there is a lack of user studies on the interpretability of the provided explanations. We used a Think Aloud Protocol (TAP) to explore oncologists’ assessment of a lung cancer relapse prediction system with the aim of refining the purpose-built explanation model for better credibility and utility. Novel to this context, TAP is used as a neutral methodology to elicit experts’ thought processes and judgements of the AI system, without explicit prompts. TAP aims to elicit the factors which influenced clinicians’ perception of credibility and usefulness of the system. Ten oncologists took part in the study. We conducted a thematic analysis of their verbalized responses, generating five themes that help us to understand the context within which oncologists’ may (or may not) integrate an explainable AI system into their working day.</div

Patient inclusion/exclusion criteria, reproduced from [34].

Patient inclusion/exclusion criteria, reproduced from [34].</p