Analysis and control of biomolecular networks by microfluidics

The process by which the cells respond and adapt to internal and external stimuli, is almost always controlled by a complex network of genes, proteins, small molecules, and their mutual interactions, called signalling network. Over the last years, it has become apparent that quantitative and methodological tools from Biomedical and Control Engineering can be used to understand how these networks work, but also to engineer "synthetic" networks to robustly steer cellular behavior in a prescribed fashion. This possibility will be transformative, enabling myriad applications in biotechnology, chemical industry, health and biomedicine, food, and the environment. Cybergenetics is a new discipline merging the tools of Synthetic Biology with those of Biomedical and Control Engineering, with the aim of building robust synthetic gene networks to engineer biological processes. This Thesis is within this research topic, and comprises two different applications, one in yeast cells and one in human cells: (1) closed-loop feedback control to synchronise the cell cycle across a population of yeast cells (Saccharomyces cerevisiae); (2) quantitative analysis and model of TFEB nuclear translocation dynamics following mTOR inhibition in human cells (HeLa)

Correction: catalytic enantioselective synthesis of α-nitroepoxides via aminolytic kinetic resolution

Correction for 'Catalytic enantioselective synthesis of α-nitroepoxides via aminolytic kinetic resolution' by Sara Meninno et al., Catal. Sci. Technol., 2015, 5, 124–128

Neutrophil unsaturated fatty acid release by GM-CSF is impaired in cystic fibrosis

Dysregulated inflammation in cystic fibrosis (CF) is attributed to an altered production of inflammatory mediators derived from polyunsaturated lipids. In comparison to the arachidonic acid (AA) cascade, little is known about the modulation of docosahexaenoic acid (DHA) membrane release. We compared data on neutrophil DHA- and AA- release from both control (CT) and patients with CF using [3H]AA or [14C]DHA as a markers for, respectively, AA and DHA- release. Granulocyte-macrophage-colony stimulating factor stimulated DHA release from CT, but not CF, neutrophils. Comparison showed that both [14C]DHA and [3H]AA liberated after stimulation was higher in CT than in CF neutrophils. Since bioactive mediators derived from DHA are resolving factors and those derived from AA are both pro- and anti- inflammatory, these results suggest that CF is associated with a reduction of the release of PUFA-precursors of lipooxygenated resolving mediators. This leads to the hypothesis that defects in the resolving factors production could contribute to the inflammatory dysregulated processes in CF. Furthermore, the methodology used may help to improve knowledge on the regulation and resolution of inflammation

Perturbation of Serotonin Homeostasis during Adulthood Affects Serotonergic Neuronal Circuitry

Growing evidence shows that the neurotransmitter serotonin (5-HT) modulates the fine-tuning of neuron development and the establishment of wiring patterns in the brain. However, whether serotonin is involved in the maintenance of neuronal circuitry in the adult brain remains elusive. Here, we use a Tph2(fl)°(x) conditional knockout (cKO) mouse line to assess the impact of serotonin depletion during adulthood on serotonergic system organization. Data show that the density of serotonergic fibers is increased in the hippocampus and decreased in the thalamic paraventricular nucleus (PVN) as a consequence of brain serotonin depletion. Strikingly, these defects are rescued following reestablishment of brain 5-HT signaling via administration of the serotonin precursor 5-hydroxytryptophan (5-HTP). Finally, 3D reconstruction of serotonergic fibers reveals that changes in serotonin homeostasis affect axonal branching complexity. These data demonstrate that maintaining proper serotonin homeostasis in the adult brain is crucial to preserve the correct serotonergic axonal wiring

Il ruolo dell’endoscopia nei tumori neuroendocrini gastroenteropancreatici

Gastroenteropancreatic (GEP) neuroendocrine tumors (NET) are rare neoplasia arisen from neuroendocrine cells present in the gut mucosa and pancreas. Digestive endoscopy and endoscopic ultrasonography play a relevant role in NET diagnosis, stadiation and surveillance. Moreover, in selected patients, surgical endoscopy allows the tratment of these cancers at an early stage

First trimester screening for pre-eclampsia and targeted aspirin prophylaxis: a cost-effectiveness cohort study

Objective: Investigate cost-effectiveness of first trimester pre-eclampsia screening using the Fetal Medicine Foundation (FMF) algorithm and targeted aspirin prophylaxis in comparison with standard care. // Design: Retrospective observational study. // Setting: London tertiary hospital. // Population: 5957 pregnancies screened for pre-eclampsia using the National Institute for Health and Care Excellence (NICE) method. // Methods: Differences in pregnancy outcomes between those who developed pre-eclampsia, term pre-eclampsia and preterm pre-eclampsia were compared by the Kruskal–Wallis and Chi-square tests. The FMF algorithm was applied retrospectively to the cohort. A decision analytic model was used to estimate costs and outcomes for pregnancies screened using NICE and those screened using the FMF algorithm. The decision point probabilities were calculated using the included cohort. // Main outcome measures: Incremental healthcare costs and QALY gained per pregnancy screened. // Results: Of 5957 pregnancies, 12.8% and 15.9% were screen-positive for development of pre-eclampsia using the NICE and FMF methods, respectively. Of those who were screen-positive by NICE recommendations, aspirin was not prescribed in 25%. Across the three groups, namely, pregnancies without pre-eclampsia, term pre-eclampsia and preterm pre-eclampsia there was a statistically significant trend in rates of emergency caesarean (respectively 21%, 43% and 71.4%; P < 0.001), admission to neonatal intensive care unit (NICU) (5.9%, 9.4%, 41%; P < 0.001) and length of stay in NICU. The FMF algorithm was associated with seven fewer cases of preterm pre-eclampsia, cost saving of £9.06 and QALY gain of 0.00006/pregnancy screened. // Conclusions: Using a conservative approach, application of the FMF algorithm achieved clinical benefit and an economic cost saving

Deposition of Antioxidant and Cytocompatible Caffeic Acid-Based Thin Films onto Ti6Al4V Alloys through Hexamethylenediamine-Mediated Crosslinking

A promising approach for advanced bone implants is thedepositionon titanium surfaces of organic thin films with improved therapeuticperformances. Herein, we reported the efficient dip-coating depositionof caffeic acid (CA)-based films on both polished and chemically pre-treatedTi6Al4V alloys by exploiting hexamethylenediamine (HMDA) crosslinkingability. The formation of benzacridine systems, resulting from theinteraction of CA with the amino groups of HMDA, as reported in previousstudies, was suggested by the yellow/green color of the coatings.The coated surfaces were characterized by means of the Folin-Ciocalteumethod, fluorescence microscopy, water contact angle measurements,X-ray photoelectron spectroscopy (XPS), zeta-potential measurements,and Fourier transform infrared spectroscopy, confirming the presenceof a uniform coating on the titanium surfaces. The optimal mechanicaladhesion of the coating, especially on the chemically pre-treatedsubstrate, was also demonstrated by the tape adhesion test. Interestingly,both films exhibited marked antioxidant properties (2,2-diphenyl-1-picrylhydrazyland ferric reducing antioxidant power assays) that persisted overtime and were not lost even after prolonged storage of the material.The feature of the coatings in terms of the exposed groups (XPS andzeta potential titration evidence) was apparently dependent on thesurface pre-treatment of the titanium substrate. Cytocompatibility,scavenger antioxidant activity, and antibacterial properties of thedeveloped coatings were evaluated. The most promising results wereobtained in the case of the chemically pre-treated CA/HMDA-based coatedsurface that showed good cytocompatibility and high reactive oxygenspecies' scavenging ability, preventing their intracellularaccumulation under pro-inflammatory conditions; moreover, an anti-foulingeffect preventing the formation of 3D biofilm-like bacterial aggregateswas observed by scanning electron microscopy. These results open newperspectives for the development of innovative titanium surfaces withthin coatings from naturally occurring phenols for bone contact implants

Pedagogical strategies to improve emotional competencies in nursing students: A systematic review

Objectives: To reveal the effectiveness of didactic architectures and pedagogical strategies to be implemented in nursing curricula to develop and improve Emotional Competencies (EC) in undergraduate nursing students. Design: Systematic review of effectiveness conducted according to Joanna Briggs Institute (JBI) guidelines. We followed the PRISMA statement to guarantee the transparency of the review and the GRADE to report the strength of evidence. Data sources: Seven databases were searched: MEDLINE, The Cochrane Library, SCOPUS, CINAHL, EMBASE, PsycINFO and ERIC. Grey literature was also searched through the OpenGrey database. Review methods: Studies focusing on educational programmes and/or activities to develop EC in nursing curricula, published in English or Italian were included. Quality assessment of the studies was evaluated using JBI critical evaluation tools and the Mixed Methods Appraisal Tool (MAAT). Following JBI guidelines, a narrative synthesis was performed. Results: A total of 19 studies from 8 countries were included. The population varied from first to fourth-year students in relation to the duration of the undergraduate nursing program across the various countries. Most of the students were females. The age of the participants ranged between18 and 56&nbsp;years. The most common pedagogical strategies were simulation, role playing, and face-to-face lessons. In some cases, studies combined two or three pedagogical strategies in the same intervention. The most effective strategy was simulation, which improved EC, compassion, self-awareness, self-efficacy, empathy, critical thinking, clinical practice skills, and teamwork skills. Furthermore, the combination of lessons, simulation, and literature exploration effectively developed communication skills, and improved students' satisfaction. Conclusions: Investing in simulation, role-playing activities, and lessons regarding the importance of EI, empathy and compassion, and the role of an emotionally competent nurse leads to improved nursing care and wellbeing

Draft Methodology for FAIR-by-Design Learning Materials

This document describes a methodology for FAIR-by-design production of learning materials based on the backward instructional process that is extended with additional activities focusing on the implementation of the FAIR guiding principles. A general discussion on important aspect of implementation such as granularity, scope, metadata schema, interoperability and publication in relevant repositories is provided together with a step by step six stage workflow and checklists that help implement the FAIR-by-design process. The outlined methodology will be used as a blueprint for a train-the-trainer course aiming to present the practical FAIR-by-design instructional design