Development of a New Tool for 3D Modeling for Regenerative Medicine

The effectiveness of therapeutic treatment based on regenerative medicine for degenerative diseases (i.e., neurodegenerative or cardiac diseases) requires tools allowing the visualization and analysis of the three-dimensional (3D) distribution of target drugs within the tissue. Here, we present a new computational procedure able to overcome the limitations of visual analysis emerging by the examination of a molecular signal within images of serial tissue/organ sections by using the conventional techniques. Together with the 3D anatomical reconstitution of the tissue/organ, our framework allows the detection of signals of different origins (e.g., marked generic molecules, colorimetric, or fluorimetric substrates for enzymes; microRNA; recombinant protein). Remarkably, the application does not require the employment of specific tracking reagents for the imaging analysis. We report two different representative applications: the first shows the reconstruction of a 3D model of mouse brain with the analysis of the distribution of the β-Galactosidase, the second shows the reconstruction of a 3D mouse heart with the measurement of the cardiac volume

Efficacy of selective histone deacetylase 6 inhibition in mouse models of Pseudomonas aeruginosa infection: A new glimpse for reducing inflammation and infection in cystic fibrosis

The latest studies identified the histone deacetylase (HDAC) class of enzymes as strategic components of the complex molecular machinery underlying inflammation in cystic fibrosis (CF). Compelling new support has been provided for HDAC6 isoform as a key player in the generation of the dysregulated proinflammatory phenotype in CF, as well as in the immune response to the persistent bacterial infection accompanying CF patients. We herein provide in vivo proof-of-concept (PoC) of the efficacy of selective HDAC6 inhibition in contrasting the pro-inflammatory phenotype in a mouse model of chronic P. aeruginosa respiratory infection. Upon careful selection and in-house re-profiling (in vitro and cell-based assessment of acetylated tubulin level through Western blot analysis) of three potent and selective HDAC6 inhibitors as putative candidates for the PoC, we engaged the best performing compound 2 for pre-clinical studies. Compound 2 demonstrated no toxicity and robust anti-inflammatory profile in a mouse model of chronic P. aeruginosa respiratory infection upon repeated aerosol administration. A significant reduction of leukocyte recruitment in the airways, in particular neutrophils, was observed in compound 2-treated mice in comparison with the vehicle; moreover, quantitative immunoassays confirmed a significant reduction of chemokines and cytokines in lung homogenate. This effect was also associated with a modest reduced bacterial load after compound 2-treatment in mice compared to the vehicle. Our study is of particular significance since it demonstrates for the first time the utility of selective drug-like HDAC6 inhibitors in a relevant in vivo model of chronic P. aeruginosa infection, thus supporting their potential application for reverting CF phenotype

Notulae to the Italian alien vascular flora: 14

In this contribution, new data concerning the distribution of vascular flora alien to Italy are presented. It includes new records, confirmations, and status changes for Italy or for Italian administrative regions. Nomenclatural and distribution updates, published elsewhere, and corrections are provided as Suppl. materia

Notulae to the Italian alien vascular flora: 14

In this contribution, new data concerning the distribution of vascular flora alien to Italy are presented. It includes new records, confirmations, and status changes for Italy or for Italian administrative regions. Nomenclatural and distribution updates, published elsewhere, and corrections are provided as Suppl. material

Predicting needlestick and sharps injuries in nursing students: Development of the SNNIP scale

© 2020 The Authors. Nursing Open published by John Wiley & Sons Ltd. Aim: To develop an instrument to investigate knowledge and predictive factors of needlestick and sharps injuries (NSIs) in nursing students during clinical placements. Design: Instrument development and cross-sectional study for psychometric testing. Methods: A self-administered instrument including demographic data, injury epidemiology and predictive factors of NSIs was developed between October 2018–January 2019. Content validity was assessed by a panel of experts. The instrument's factor structure and discriminant validity were explored using principal components analysis. The STROBE guidelines were followed. Results: Evidence of content validity was found (S-CVI 0.75; I-CVI 0.50–1.00). A three-factor structure was shown by exploratory factor analysis. Of the 238 participants, 39% had been injured at least once, of which 67.3% in the second year. Higher perceptions of “personal exposure” (4.06, SD 3.78) were reported by third-year students. Higher scores for “perceived benefits” of preventive behaviours (13.6, SD 1.46) were reported by second-year students

MicroRNAs and Molecular Mechanisms of Neurodegeneration

During the last few years microRNAs (miRNAs) have emerged as key mediators of post-transcriptional and epigenetic regulation of gene expression. MiRNAs targets, identified through gene expression profiling and studies in animal models, depict a scenario where miRNAs are fine-tuning metabolic pathways and genetic networks in both plants and animals. MiRNAs have shown to be differentially expressed in brain areas and alterations of miRNAs homeostasis have been recently correlated to pathological conditions of the nervous system, such as cancer and neurodegeneration. Here, we review and discuss the most recent insights into the involvement of miRNAs in the neurodegenerative mechanisms and their correlation with significant neurodegenerative disorders

Assessment of myocardial viability by tissue Doppler and strain rate dobutamine echocardiography: comparison with rest-distribution thallium-201 spect.

Background. The introduction of Doppler measurement of myocardial wall velocities (tissue Doppler imaging, TDI) and the recently developed strain rate (SR) imaging technique have made possible a more adequate assessment of global and regional systolic and diastolic myocardial function. However, no study has so far tested the diagnostic accuracy of SR during dobutamine testing for detecting myocardial viability and predicting recovery of chronic ischemic LV dysfunction. Our purpose was: 1) to establish the accuracy of quantitative segmental analysis by SR during dobutamine testing for detecting myocardial viability in patients with chronic ischemic regional LV dysfunction; 2) to compare results of dobutamine SR with those of rest-4h-24h redistribution Thallium SPECT (T1 SPECT), a well validated method for assessing hibernating myocardium. Methods. Twenty-seven patients (age 5313 years) with chronic ischemic regional LV dysfunction (EF 2811%) underwent dobutamine SR and T1 SPECT on different days and in random order, within 15 days before myocardial revascularization (PTCA in 15 and CABG in 12). Functional recovery was identified at 9619 days after coronary revascularization by means of resting 2D echocardiography. Offline analysis of the myocardial velocity data sets was performed using dedicated software (Aplio, Toshiba Corp.). Velocity and strain traces from different wall segments were processed simultaneously in the same cineloop. Dobutamine was administered by infusion pump, at 3 min intervals up to a maximum of 20 mcg/Kg/min. Each patient was injected i.v. with 3.0 mCi of Tl in the rest state. Four hours and 24 hours after injection, delayed Tl SPECT acquisitions were performed using the same parameters. A 16-segment- 4-grade score model was used for analysis of both Dobutamine SR and Tl SPECT. Results. Of 163 segments with baseline WMA, 56 (34%) segments showed viability on Dobutamine SR, and 67 (41%) on Tl SPECT. Positive and negative predictive values were 87% and 60% for Dobutamine SR and 78% and 63% for Tl SPECT (p=NS). The sensitivity, specificity and accuracy of SR dobutamine echocardiography were 75%, 84%, and 82%, respectively; those of thallium tomography were 80%, 66%, and 71%, respectively. Conclusion. Segmental analysis of SR images during dobutamine infusion appears to be as feasible as visual diagnosis of regional wall motion changes but with the advantage of being automated and quantitative. Regional LV contractile reserve assessed by dobutamine SR is highly concordant with Tl SPECT in identifying hibernating myocardium