Predicting human cardiac QT alterations and pro-arrhythmic effects of compounds with a 3D beating heart-on-chip platform.

Determining the potential cardiotoxicity and pro-arrhythmic effects of drug candidates remains one of the most relevant issues in the drug development pipeline (DDP). New methods enabling to perform more representative preclinical in vitro studies by exploiting induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) are under investigation to increase the translational power of the outcomes. Here we present a pharmacological campaign conducted to evaluate the drug-induced QT alterations and arrhythmic events on uHeart, a 3D miniaturized in vitro model of human myocardium encompassing iPSC-CM and dermal fibroblasts embedded in fibrin.

Deriving and validating a risk prediction model for long COVID-19: protocol for an observational cohort study using linked Scottish data.

Introduction: COVID-19 is commonly experienced as an acute illness, yet some people continue to have symptoms that persist for weeks, or months (commonly referred to as 'long-COVID'). It remains unclear which patients are at highest risk of developing long-COVID. In this protocol, we describe plans to develop a prediction model to identify individuals at risk of developing long-COVID.

Impact on grafted kidney function of rocuronium-sugammadex vs cisatracurium-neostigmine strategy for neuromuscular block management. An Italian single-center, 2014-2017 retrospective cohort case-control study.

Background: The impact of sugammadex in patients with end-stage renal disease undergoing kidney transplantation is still far from being defined. The aim of the study is to compare sugammadex to neostigmine for reversal of rocuronium- and cisatracurium-induced neuromuscular block (NMB), respectively, in patients undergoing kidney transplantation.

Methods: A single-center, 2014-2017 retrospective cohort case-control study was performed.

Preoperative dexmedetomidine and intraoperative bradycardia in laparoscopic cholecystectomy: a meta-analysis with trial sequential analysis.

Background: While laparoscopic surgical procedures have various advantages over traditional open techniques, artificial pneumoperitoneum is associated with severe bradycardia and cardiac arrest. Dexmedetomidine, an imidazole derivative that selectively binds to α2-receptors and has sedative and analgesic properties, can cause hypotension and bradycardia. Our primary aim was to assess the association between dexmedetomidine use and intraoperative bradycardia during laparoscopic cholecystectomy.

Effect of dexmedetomidine on hemodynamic responses to tracheal intubation: A meta-analysis with meta-regression and trial sequential analysis.

Study Objective: An uncontrolled adrenergic response during tracheal intubation may lead to life-threatening complications. Dexmedetomidine binds to α2-receptors and may attenuate this response. The primary aim of our meta-analysis is to investigate dexmedetomidine efficacy in attenuating sympathetic response to tracheal intubation, compared with placebo or no dexmedetomidine, in terms of heart rate and blood pressure at intubation.

Micro-electrode channel guide (µECG) technology: an online method for continuous electrical recording in a human beating heart-on-chip.

Cardiac toxicity still represents a common adverse outcome causing drug attrition and post-marketing withdrawal. The development of relevantmodels resembling the human heart recently opened the path towards a more accurate detection of drug-induced human cardiac toxicity early in the drug development process. Organs-on-chip have been proposed as promising tools to recapitulatethe key aspects of thecardiac physiology and to provide a means to directly analyze functional readouts.

Analysis of Complex DNA Rearrangements during Early Stages of HAC Formation.

Human artificial chromosomes (HACs) are important tools for epigenetic engineering, for measuring chromosome instability (CIN), and for possible gene therapy. However, their use in the latter is potentially limited because the input HAC-seeding DNA can undergo an unpredictable series of rearrangements during HAC formation. As a result, after transfection and HAC formation, each cell clone contains a HAC with a unique structure that cannot be precisely predicted from the structure of the HAC-seeding DNA.

Are thromboelastometric and thromboelastographic parameters associated with mortality in septic patients? A systematic review and meta-analysis.

Background: Thromboelastometry/elastography (ROTEM/TEG) showed promising results for diagnosis of sepsis-induced coagulopathy, but their association with the outcome is unclear. Our aim was to assess any difference in ROTEM/TEG measurements between septic survivors and non-survivors.

Methods: Pubmed, Web of Science, Embase and Cochrane Library databases were investigated.

A Tumor-in-Host DEB-Based Approach for Modeling Cachexia and Bevacizumab Resistance.

Adequate energy intake and homeostasis are fundamental for the appropriate growth and maintenance of an organism; the presence of a tumor can break this equilibrium. Tumor energy requests can lead to extreme weight loss in animals and cachexia in cancer patients. Angiogenesis inhibitors, acting on tumor vascularization, counteract this tumor-host energy imbalance, with significant results in preclinical models and more limited results in the clinic.

Crude extract of cyanobacterium Radiocystis fernandoi strain R28 induces anemia and oxidative stress in fish erythrocytes.

The cyanobacterium Radiocystis fernandoi has been frequently identified in cyanobacterial blooms in Brazil. Recently, R. fernandoi strain R28, which produces microcystin (MC)-RR and MC-YR, was isolated from the Furnas reservoir, Minas Gerais, Brazil.

Overview of the toxic effects of titanium dioxide nanoparticles in blood, liver, muscles, and brain of a Neotropical detritivorous fish.

The toxicity of titanium dioxide nanoparticles (TiO -NP) in the blood, liver, muscle, and brain of a Neotropical detritivorous fish, Prochilodus lineatus, was tested. Juvenile fish were exposed to 0, 1, 5, 10, and 50 mg L of TiO -NP for 48 hours (acute exposure) or 14 days (subchronic exposure) to evaluate changes in hematology, red blood cell (RBC) genotoxicity/mutagenicity, liver function (reactive oxygen species (ROS) production, antioxidant responses, detoxification, and histopathology), acetylcholinesterase (AChE) activity in muscles and brain, and Ti bioaccumulation. TiO -NP did not cause genetic damage to RBC, but acutely decreased white blood cells (WBC) and increased monocytes.

Human Artificial Chromosome with Regulated Centromere: A Tool for Genome and Cancer Studies.

Since their description in the late 1990s, Human Artificial Chromosomes (HACs) bearing functional kinetochores have been considered as promising systems for gene delivery and expression. More recently a HAC assembled from a synthetic alphoid DNA array has been exploited in studies of centromeric chromatin and in assessing the impact of different epigenetic modifications on kinetochore structure and function in human cells. This HAC was termed the alphoid-HAC, as the synthetic monomers each contained a tetO sequence in place of the CENP-B box that can be targeted specifically with tetR-fusion proteins.

Common drivers of seasonal movements on the migration - residency behavior continuum in a large herbivore.

This study aimed to (1) identify the scale of environmental drivers of seasonal movements on the migration - residency behavior continuum in a large herbivore species and to (2) test the hypothesis that the same environmental drivers and spatio-temporal scaling should influence spatial processes in both migrants (long distance migration) and residents (short distance range shifts). We performed a comparative analysis of the influence of plant phenology and snow cover duration on seasonal movements of five partially migrating red deer populations with contrasting environmental conditions, at the seasonal range scale and at the study area scale. The five populations presented varying proportions of migrants, large gradients of migration distances and seasonal range shifts.

Modeling tumor growth inhibition and toxicity outcome after administration of anticancer agents in xenograft mice: A Dynamic Energy Budget (DEB) approach.

Host features, such as cell proliferation rates, caloric intake, metabolism and energetic conditions, significantly influence tumor growth; at the same time, tumor growth may have a dramatic impact on the host conditions. For example, in clinics, at certain stages of the tumor growth, cachexia (body weight reduction) may become so relevant to be considered as responsible for around 20% of cancer deaths. Unfortunately, anticancer therapies may also contribute to the development of cachexia due to reduced food intake (anorexia), commonly observed during the treatment periods.

Generation of a Synthetic Human Chromosome with Two Centromeric Domains for Advanced Epigenetic Engineering Studies.

It is generally accepted that chromatin containing the histone H3 variant CENP-A is an epigenetic mark maintaining centromere identity. However, the pathways leading to the formation and maintenance of centromere chromatin remain poorly characterized due to difficulties of analysis of centromeric repeats in native chromosomes. To address this problem, in our previous studies we generated a human artificial chromosome (HAC) whose centromere contains a synthetic alpha-satellite (alphoid) DNA array containing the tetracycline operator, the alphoid-HAC.

The natural history of achalasia: Evidence of a continuum-"The evolutive pattern theory".

Background: It is currently unclear if the three manometric patterns of esophageal achalasia represent distinct entities or part of a disease continuum. The study's aims were: a) to test the hypothesis that the three patterns represent different stages in the evolution of achalasia; b) to investigate whether manometric patterns change after Laparoscopic-Heller-Dor (LHD).

Methods: We assessed the patients diagnosed with achalasia who underwent LHD as their first treatment from 1992 to 2016.

Long-term wireless pH monitoring of the distal esophagus: prolonging the test beyond 48 hours is unnecessary and may be misleading.

Wireless pH monitoring of the esophagus has been widely used to detect GERD for more than a decade. It is generally well tolerated and accepted by patients, but it is still unclear whether prolonging a recording beyond the usual 48 hours can improve the test's diagnostic value. The aim of this study is to examine the diagnostic yield of 96-hour pH monitoring vis-à-vis 24- and 48-hour tests, and to ascertain whether any gain in diagnostic terms was of genuine clinical utility.

Effects of laparoscopic myotomy on the esophageal motility pattern of esophageal achalasia as measured by high-resolution manometry.

Background: Esophageal achalasia can be classified on the grounds of three distinct manometric patterns that correlate well with final outcome after laparoscopic Heller-Dor myotomy (LHM). No analytical data are available, however, on the postoperative picture and its possible correlation with final outcome. The aims of this study were: (a) to investigate whether manometric patterns change after LHM for achalasia; (b) to ascertain whether postoperative patterns and/or changes can predict final outcome; and (c) to test the hypothesis that the three known patterns represent different stages in the evolution of the disease.

Mucosal Perforation During Laparoscopic Heller Myotomy Has No Influence on Final Treatment Outcome.

Background: The aims of the study were (a) to examine the final outcome in patients experiencing accidental mucosal perforation during laparoscopic Heller myotomy with Dor fundoplication (LHD) and (b) to evaluate whether perforation episodes might influence the way in which surgeons subsequently approached the LHD procedure.

Methods: We studied all consecutive patients that underwent LHD between 1992 and 2015. Patients were divided into two main groups: those who experienced an intraoperative mucosal perforation (group P) and those whose LHD was uneventful (group NP).

Postoperative Gastroesophageal Reflux After Laparoscopic Heller-Dor for Achalasia: True Incidence with an Objective Evaluation.

Introduction: The most common complication after laparoscopic Heller-Dor (LHD) is gastroesophageal reflux disease (GERD). The present study aimed (a) to analyze the true incidence of postoperative reflux by objectively assessing a large group of LHD patients and (b) to see whether the presence of typical GERD symptoms correlates with the real incidence of postoperative reflux.

Methods: After LHD, patients were assessed by means of a symptom score, endoscopy, esophageal manometry, and 24-h pH monitoring.