Pruritus: a useful sign for predicting the haemodynamic changes that occur following administration of vancomycin

INTRODUCTION: The aim of this study was to investigate the haemodynamic changes that follow the appearance of pruritus during vancomycin administration. METHODS: We studied 50 patients scheduled for coronary artery bypass surgery, and we compared data from patients who exhibited pruritus with those from patients who did not. After the monitoring devices had been positioned, vancomycin (15 mg/kg) was continuously infused at a constant rate over 30 min, before induction of anaesthesia. Haemodynamic profiles were recorded before vancomycin infusion (time point 1); at 15 (time point 2) and 30 min (time point 3) after the beginning of vancomycin infusion; and 15 min after vancomycin infusion had been stopped (time point 4). At each time arterial and mixed venous blood samples were drawn to calculate the shunt fraction (Qsp/Qt). RESULTS: In patients who exhibited pruritus (group A, n = 17) at time point 3 versus time point 1, systemic vascular resistance index (SVRI) and arterial oxygen tension (PaO(2)) decreased significantly; cardiac index (CI), stroke volume index (SVI) and Qsp/Qt increased significantly; and mean systemic pressure and heart rate were stable. Those changes were observed only in patients not treated with a β-blocker before surgery, whereas no change occurred in patients treated with the drug. In the patients who were free from pruritus (group B, n = 28), we did not observe any significant change. CONCLUSION: The appearance of pruritus during vancomycin administration indicates that SVRI is declining, thus exposing the patient to risk for hypotension. Therapy with a β-blocker appears to confer protection against this hemodynamic reaction

R-Roscovitine (Seliciclib) prevents DNA damage-induced cyclin A1 upregulation and hinders non-homologous end-joining (NHEJ) DNA repair

<p>Abstract</p> <p>Background</p> <p>CDK-inhibitors can diminish transcriptional levels of cell cycle-related cyclins through the inhibition of E2F family members and CDK7 and 9. Cyclin A1, an E2F-independent cyclin, is strongly upregulated under genotoxic conditions and functionally was shown to increase NHEJ activity. Cyclin A1 outcompetes with cyclin A2 for CDK2 binding, possibly redirecting its activity towards DNA repair. To see if we could therapeutically block this switch, we analyzed the effects of the CDK-inhibitor <it>R</it>-Roscovitine on the expression levels of cyclin A1 under genotoxic stress and observed subsequent DNA damage and repair mechanisms.</p> <p>Results</p> <p>We found that <it>R</it>-Roscovitine alone was unable to alter cyclin A1 transcriptional levels, however it was able to reduce protein expression through a proteosome-dependent mechanism. When combined with DNA damaging agents, <it>R</it>-Roscovitine was able to prevent the DNA damage-induced upregulation of cyclin A1 on a transcriptional and post-transcriptional level. This, moreover resulted in a significant decrease in non-homologous end-joining (NHEJ) paired with an increase in DNA DSBs and overall DNA damage over time. Furthermore, microarray analysis demonstrated that <it>R</it>-Roscovitine affected DNA repair mechanisms in a more global fashion.</p> <p>Conclusions</p> <p>Our data reveal a new mechanism of action for <it>R</it>-Roscovitine on DNA repair through the inhibition of the molecular switch between cyclin A family members under genotoxic conditions resulting in reduced NHEJ capability.</p

Dissecting a Data-driven Prognostic Pipeline: A Powertrain use case

Nowadays, cars are instrumented with thousands of sensors continuously collecting data about its components. Thanks to the concept of connected cars, this data can be now transferred to the cloud for advanced analytics functionalities, such as prognostic or predictive maintenance. In this paper, we dissect a data-driven prognostic pipeline and apply it in the automotive scenario. Our pipeline is composed of three main steps: (i) selection of most important signals and features describing the scenario for the target problem, (ii) creation of machine learning models based on different classification algorithms, and (iii) selection of the model that works better for a deployment scenario. For the development of the pipeline, we exploit an extensive experimental campaign where an actual engine runs in a controlled test bench under different working conditions. We aim to predict failures of the High-Pressure Fuel System, a key part of the diesel engine responsible for delivering high-pressure fuel to the cylinders for combustion. Our results show the advantage of data-driven solutions to automatically discover the most important signals to predict failures of the High-Pressure Fuel System. We also highlight how an accurate model selection step is fundamental to identify a robust model suitable for deployment

A modified Rives–Stoppa technique with composite mesh (FLaPp) in large incisional hernia: a multicentric retrospective cohort study

Background Large incisional hernias (LIH) are challenging conditions, often necessitating complex surgical procedures such as transversus abdominis muscle release (TAR). We evaluated the feasibility and effectiveness of tension-free abdominal wall repair of LIH with an innovative modified Rives–Stoppa procedure employing a composite free lateral polypropylene (FLaPp) prosthesis. Methods Symptomatic patients affected by LIH and treated with FLaPp composite prosthesis between April 2010 and December 2016 were retrospectively analyzed. The FLaPp prosthesis is made up of two layers: an internal layer based on a polypropylene film that can be used in contact with the intestinal loops to address the posterior peritoneal defect, and an external layer based on a macroporous lightweight mesh, with which a classic repair according to Rives–Stoppa is carried out. Results Forty-three patients were enrolled in the study. All hernias were W3. Early complications were seroma (16.3%), hematoma (11.6%), wound infection (7.0%), and bowel injury (2.3%). Late complications were sinus tract (4.7%), occasional pain (2.3%), and stiff abdomen (9.3%). The median operative time was 126 min and median hospitalization was 8 days. At the median follow-up of 40 months (range 37.5–117), the recurrence rate was 9.3% (4/43). Conclusion Use of FLaPp mesh with a tension-free surgical approach is an effective strategy for managing LIH in selected cases with the presence of a posterior defect, with low rates of complications and recurrences

Further characterization of NFIB-associated phenotypes: Report of two new individuals

Nuclear Factor I B (NFIB) haploinsufficiency has recently been identified as a cause of intellectual disability (ID) and macrocephaly. Here we report on two new individuals carrying a microdeletion in the chromosomal region 9p23-p22.3 containing NFIB. The first is a 7-year 9-month old boy with developmental delays, ID, definite facial anomalies, and brain and spinal cord magnetic resonance imaging findings including periventricular nodular heterotopia, hypoplasia of the corpus callosum, arachnoid cyst in the left middle cranial fossa, syringomyelia in the thoracic spinal cord and distal tract of the conus medullaris, and a stretched appearance of the filum terminale. The second is a 32-year-old lady (the proband' mother) with dysmorphic features, and a history of learning disability, hypothyroidism, poor growth, left inguinal hernia, and panic attacks. Her brain magnetic resonance imaging findings include a dysmorphic corpus callosum, and a small cyst in the left choroidal fissure that marks the hippocampal head. Array-based comparative genomic hybridization identified, in both, a 232 Kb interstitial deletion at 9p23p22.3 including several exons of NFIB and no other known genes. Our two individuals add to the knowledge of this rare disorder through the addition of new brain and spinal cord MRI findings and dysmorphic features. We propose that NFIB haploinsufficiency causes a clinically recognizable malformation-ID syndrome

Echocardiographic Screening of Anomalous Origin of Coronary Arteries in Athletes with a Focus on High Take-Off

Anomalous aortic origin of coronary arteries (AAOCA) represents a rare congenital heart disease. However, this disease is the second most common cause of sudden cardiac death in apparently healthy athletes. The aim of this systematic review is to analyze the feasibility and the detection rate of AAOCA by echocardiography in children and adults. A literature search was performed within the National Library of Medicine using the following keywords: coronary artery origin anomalies and echocardiography; then, the search was redefined by adding the keywords: athletes, children, and high take-off. Nine echocardiographic studies investigating AAOCA and a total of 33,592 children and adults (age range: 12-49 years) were included in this review. Of these, 6599 were athletes (12-49 years). All studies demonstrated a high feasibility and accuracy of echocardiography for the evaluation of coronary arteries origin as well as their proximal tracts. However, some limitations exist: the incidence of AAOCA varied from 0.09% to 0.39% (up to 0.76%) and was lower than described in computed tomography series (0.3-1.8%). Furthermore, echocardiographic views for the evaluation of AAOCA and the definition of minor defects (e.g., high take-off coronary arteries) have not been standardized. An echocardiographic protocol to diagnose the high take-off of coronary arteries is proposed in this article. In conclusion, the screening of AAOCA by echocardiography is feasible and accurate when appropriate examinations are performed; however, specific acoustic windows and definitions of defects other than AAOCA need to be standardized to improve sensitivity and specificity