Venous and arterial thrombotic risks with thalidomide: evidence and practical guidance.

Oral immunomodulatory drugs (IMiDs), namely thalidomide, lenalidomide and pomalidomide, interfere with several pathways important for disease progression. Today they play a crucial role in the treatment of multiple myeloma patients, and have considerably improved myeloma outcomes. These agents, and thalidomide in particular, are associated with higher rates of thromboembolic events, both venous and arterial. Individual risk factors for thromboembolic events include advanced age, previous history of thromboembolism, an indwelling central venous catheter, comorbid conditions (e.g. infections, diabetes, cardiac disease, obesity), current or recent immobilization, recent surgery and inherited thrombophilic abnormalities. Cancer therapy and cancer itself also increase the risk of thromboembolic events. The aim of this review is to help clinicians to define the risk of thrombotic events in patients treated with thalidomide and thus to provide practical recommendations to manage thromboprophylaxis in these patients

Emplacement of sandstone intrusions during contractional tectonics

Acknowledgments We acknowledge the support of sponsoring companies of Phase 3 of the Sand Injection Research Group (SIRG). We are very grateful to John Waldron and Jessica Ross for the constructive reviews of the manuscript. We also wish to thank and acknowledge the continuing help and access provided by the Bureau of Land Management.Peer reviewedPostprin

COMBINED FUNCTIONAL, CELLULAR AND BEHAVIOURAL STUDIES TO GET INSIGHTS ON SENSORY ORGANS OF CIONA ROBUSTA LARVAE

The ascidian Ciona robusta is a powerful model system to approach, in a “simple context”, both cellular, developmental, or behavioral strategies adopted in the lineage of chordates. In particular, the simplicity of Ciona CNS (Central Nervous System) permits to follow the fate of each blastomere from neural plate up to the larval stage, thus representing a huge advantage, compared to the thousands of cells present in vertebrates. Furthermore, the lineage specific promoters collected by ascidian community in the last years, coupled with the electroporation method, permit to label unique or small groups of cells in the developing CNS and visualize them in their final differentiated state in swimming larvae. In the course of my thesis studies, I have exploited all these advantages to study early developmental mechanisms guiding the correct specification of blastomeres of a-lineage row III, the anterior part of neural plate, that give rise to most of the structures of the sensory vesicle of the larva. By transgenesis and chemical inhibition experiments, I have proved the involvement of three signaling pathways, Nodal, Delta-like/Notch and FGF, in the activation of markers specific of each blastomere pairs of a-lineage row III. As further step, I have demonstrated a direct transcriptional control of FGF signaling on one of these markers, the Para-Hox transcription factor Gsx. Interestingly, Gsx has been instrumental also for the continuation of my studies, since, at later stages of development, it revealed to be a useful marker also for photoreceptor cells differentiation up to the larval stage. The data on this part of work further support the evidences, previously collected by the former PhD student of the Lab, on the involvement of Ciona Gsx in the developmental programs leading to photoreceptor cells differentiation, which opens new perspectives about the function of this transcription factor in nervous system formation during evolution. In the last part of my PhD studies, I spent three months in Gaspar Jekely lab, at the Max Planck Institute for developmental biology, to explore the possibility of Ciona larva to sense hydrostatic pressure changes. My experiments showed, for the first time, that Ciona sense the pressure increases by swimming faster upward during a precise developmental window after hatching. Furthermore I have tested the potential involvement of coronet cells, a group of cells close to the group III photoreceptor cells present in the sensory vesicle, as candidate for pressure detection. These experiments indicated that coronet cells are not involved in pressure perception but, may be, could play a role in the modulation of photic response

Modelling the spread of Covid19 in Italy using a revised version of the SIR model

In this paper, we present a model to predict the spread of the Covid-19 epidemic and apply it to the specific case of Italy. We started from a simple Susceptible, Infected, Recovered (SIR) model and we added the condition that, after a certain time, the basic reproduction number $R_0$ exponentially decays in time, as empirically suggested by world data. Using this model, we were able to reproduce the real behavior of the epidemic with an average error of 5\%. Moreover, we illustrate possible future scenarios, associated to different intervals of $R_0$. This model has been used since the beginning of March 2020, predicting the Italian peak of the epidemic in April 2020 with about 100.000 detected active cases. The real peak of the epidemic happened on the 20th of April 2020, with 108.000 active cases. This result shows that the model had predictive power for the italian case.Comment: The model presented in this paper has been adopted on Covstat.it. Errata corrige in the abstrac

Cella di prova automatizzata per verifiche a fatica del "gruppo cambio" a variatore continuo e discreto

Questo studio, svolto in collaborazione con la “Divisione Veicoli Trasporto Leggero (VTL)-Prototipi e Prove” della Piaggio&C.s.p.a. di Pontedera (Pi), ha avuto come scopo la progettazione di una cella di prova automatizzata per eseguire prove di verifiche a fatica del “gruppo cambio” di veicoli a quattro ruote, seguendo la normativa Fiat 7-T4147. Attualmente tale prova si esegue su pista con notevole dispendio di tempo e risorse umane. Obbiettivo di questo progetto è di eseguire tali prove di verifica a fatica in una cella automatizzata per poter abbattere i costi di sviluppo di progetto. Potenzialità di tale progetto è la sua applicazione ad ogni tipologia di veicolo a quattro ruote, grazie ad una struttura modulare che la rende altamente flessibile, e possibilità di impiegare tale cella automatizzata anche in altre tipologie di prove

Neurotrophins in Zebrafish Taste Buds

SIMPLE SUMMARY: Zebrafish is a powerful vertebrate model organism, whose similarities with mammals are fundamental to validate its use for experimental purposes. In this study, the authors demonstrate the presence of neurotrophic factors, namely neurotrophins, in numerous taste bud cells of this fish. The reported results suggest an essential role of these factors in taste bud function. Interestingly, the results described in this study are in accordance with those reported in some mammalian species. Therefore, despite the different anatomical characteristics of the anterior digestive tract in mammals and fish, the taste buds maintain similarities in both shape and functional mechanisms in the two classes. ABSTRACT: The neurotrophin family is composed of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), Neurotrophin 3 (NT3) and NT4. These neurotrophins regulate several crucial functions through the activation of two types of transmembrane receptors, namely p75, which binds all neurotrophins with a similar affinity, and tyrosine kinase (Trk) receptors. Neurotrophins, besides their well-known pivotal role in the development and maintenance of the nervous system, also display the ability to regulate the development of taste buds in mammals. Therefore, the aim of this study is to investigate if NGF, BDNF, NT3 and NT4 are also present in the taste buds of zebrafish (Danio rerio), a powerful vertebrate model organism. Morphological analyses carried out on adult zebrafish showed the presence of neurotrophins in taste bud cells of the oropharyngeal cavity, also suggesting that BDNF positive cells are the prevalent cell population in the posterior part of the oropharyngeal region. In conclusion, by suggesting that all tested neurotrophins are present in zebrafish sensory cells, our results lead to the assumption that taste bud cells in this fish species contain the same homologous neurotrophins reported in mammals, further confirming the high impact of the zebrafish model in translational research

BDNF, Brain, and Regeneration: Insights from Zebrafish.

Zebrafish (Danio rerio) is a teleost fish widely accepted as a model organism for neuroscientific studies. The adults show common basic vertebrate brain structures, together with similar key neuroanatomical and neurochemical pathways of relevance to human diseases. However, the brain of adult zebrafish possesses, differently from mammals, intense neurogenic activity, which can be correlated with high regenerative properties. Brain derived neurotrophic factor (BDNF), a member of the neurotrophin family, has multiple roles in the brain, due also to the existence of several biologically active isoforms, that interact with different types of receptors. BDNF is well conserved in the vertebrate evolution, with the primary amino acid sequences of zebrafish and human BDNF being 91% identical. Here, we review the available literature regarding BDNF in the vertebrate brain and the potential involvement of BDNF in telencephalic regeneration after injury, with particular emphasis to the zebrafish. Finally, we highlight the potential of the zebrafish brain as a valuable model to add new insights on future BDNF studies

Heart transplantation in patients with dystrophinopathic cardiomyopathy: Review of the literature and personal series

Cardiomyopathy associated with dystrophinopathies [Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), X-linked dilated cardiomyopathy (XL-dCM) and cardiomyopathy of Duchenne/Becker (DMD/BMD) carriers] is an increasing recognized manifestation of these neuromuscular disorders and notably contributes to their morbidity and mortality. Dystrophinopathic cardiomyopathy (DCM) is the result of the dystrophin protein deficiency at the myocardium level, parallel to the deficiency occurring at the skeletal muscle level. It begins as a "presymptomatic" stage in the first decade of life and evolves in a stepwise manner toward pictures of overt cardiomyopathy (hypertrophic stage, arrhythmogenic stage and dilated cardiomyopathy). The final stage caused by the extensive loss of cardiomyocytes results in an irreversible cardiac failure, characterized by frequent episodes of acute congestive heart failure (CHF), despite a correct pharmacological treatment. The picture of a severe dilated cardiomyopathy with intractable heart failure is typical of BMD, XL-dCM and cardiomyopathy of DMD/BMD carriers, while it is less frequently observed in patients with DMD. Heart transplantation (HT) is the only curative therapy for patients with dystrophinopathic end-stage heart failure who remain symptomatic despite an optimal medical therapy. However, no definitive figures exist in literature concerning the number of patients with DCM transplanted, and their outcome. This overview is to summarize the clinical outcomes so far published on the topic, to report the personal series of dystrophinopathic patients receiving heart transplantation and finally to provide evidence that heart transplantation is a safe and effective treatment for selected patients with end-stage DCM

The Tumey Giant Injection Complex, Tumey Hill, California (USA)

The authors gratefully acknowledge support from Shell Brazil and CNPq through the “BG05: UoAUFRGS-SWB Sedimentary Systems” project at UFRGS and UoA and the strategic importance of the support given by ANP through the R&D levy regulation. We also wish to thank the support from the Sand Injection Research Group (SIRG) and the researchers who collaborated during fieldwork. We also wish to thank the support and help of the Bureau of Land Management (CA) providing guidance and legal access to the study area.Postprin

Seismic imaging of complex geometry : Forward modeling of sandstone intrusions

We acknowledge the support of sponsoring companies of Phase 3 of the Sand Injection Research Group (SIRG). The Norwegian Petroleum Directorate (NPD) are thanked for providing seismic data from Volund oil field. Also, we wish to acknowledge NORSAR Innovation AS for providing the academic licence for the SeisRoX software and the California Bureau of Land Management for facilitating access to the outcrop area.Peer reviewedPostprin