An automated 3D-printed perfusion bioreactor combinable with pulsed electromagnetic field stimulators for bone tissue investigations

In bone tissue engineering research, bioreactors designed for replicating the main features of the complex native environment represent powerful investigation tools. Moreover, when equipped with automation, their use allows reducing user intervention and dependence, increasing reproducibility and the overall quality of the culture process. In this study, an automated uni-/bi-directional perfusion bioreactor combinable with pulsed electromagnetic field (PEMF) stimulation for culturing 3D bone tissue models is proposed. A user-friendly control unit automates the perfusion, minimizing the user dependency. Computational fluid dynamics simulations supported the culture chamber design and allowed the estimation of the shear stress values within the construct. Electromagnetic field simulations demonstrated that, in case of combination with a PEMF stimulator, the construct can be exposed to uniform magnetic fields. Preliminary biological tests on 3D bone tissue models showed that perfusion promotes the release of the early differentiation marker alkaline phosphatase. The histological analysis confirmed that perfusion favors cells to deposit more extracellular matrix (ECM) with respect to the static culture and revealed that bi-directional perfusion better promotes ECM deposition across the construct with respect to uni-directional perfusion. Lastly, the Real-time PCR results of 3D bone tissue models cultured under bi-directional perfusion without and with PEMF stimulation revealed that the only perfusion induced a ~ 40-fold up-regulation of the expression of the osteogenic gene collagen type I with respect to the static control, while a ~ 80-fold up-regulation was measured when perfusion was combined with PEMF stimulation, indicating a positive synergic pro-osteogenic effect of combined physical stimulation

Codes of Commitment to Crime and Resistance: Determining Social and Cultural Factors over the Behaviors of Italian Mafia Women

This article categorizes thirty-three women in four main Italian Mafia groups and explores social and cultural behaviors of these women. This study introduces the feminist theory of belief and action. The theoretical inquiry investigates the sometimes conflicting behaviors of women when they are subject to systematic oppression. I argue that there is a cultural polarization among the categorized sub-groups. Conservative radicals give their support to the Mafia while defectors and rebels resist the Mafia. After testing the theory, I assert that emancipation of women depends on the strength of their beliefs to perform actions against the Mafiosi culture

VST project: mechanical design optimization

The VLT Survey Telescope (VST) is a cooperative program between the European Southern Observatory (ESO) and the INAF Capodimonte Astronomical Observatory (OAC), Naples, for the study, design, and realization of a 2.6-m wide-field optical imaging telescope to be operated at the Paranal Observatory, Chile. The VST has been specifically designed to carry out stand-alone observations in the UV to I spectral range and to supply target databases for the ESO Very Large Telescope (VLT). The telescope design, manufacturing and integration are responsibility of TWG and have been carried out on the base of a model of optimized design not only for mechanics but for all telescope subsystems. The paper is an overview on the telescope mechanical design and optimization

Surgical management of acutely presenting gastrointestinal stromal tumors of the stomach among elderly: experience of an emergency surgery department

Introduction: The incidence of gastrointestinal stromal tumors (GISTs), requiring often an emergency surgical management, is extremely rare among elderly. We aimed to present the experience of the Emergency Surgery Department, Brotzu Hospital, in the management of elderly patients with GIST related emergencies.Methods: This study was carried out on 12 patients with gastrointestinal stromal tumors who presented to in an emergency situation during the period from January 2010 to December 2013. All patients' data, clinical presentations, surgical procedures, complications, and survival data were collected and analyzed.Results: Between 2010 and 2013, 12 patients (8 males and 4 females), with a mean age of 70 years (range: 65-79 years) were admitted with different emergency presentations of clinically and radiologically suspected GISTs. The incidence of proximal obstruction was 41.7% of all gastric GIST cases, resulting acute gastrointestinal bleeding and perforation in 41.7% and 16.6% respectively. The mean length of hospitalization was 9.1 +/- 2.3 days and there were no posterative complications or mortalities. At a mean follow-up of 21 months, 11 patients (91.6%) were alive and disease free.Discussions: Although GISTs are uncommon among elderly, their incidence is increasing especially in their emergency presentation and surgeon should be prepared to treat this condition following the principles of GIST surgery as stated by the GIST consensus conference.Conclusions: In conclusion our data demonstrate that age itself does not affect the outcome of surgical treatment of GISTs in emergency situation. (C) 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved

The molecular basis of herpesviruses as oncolytic agents.

Herpes simplex viruses (HSVs) have entered clinical trials as oncolytic agents. The following properties make them good candidates. It is a mild pathogen; drugs (Aciclovir) are available to control viral infection; the large genome is amenable to genetic engineering, they can be rendered cancer-specific by deletion of genes, envelope glycoproteins allow the insertion of heterologous ligands to achieve modification of the natural tropism. Genetically modified HSVs have been thoroughly tested in humans. New generation recombinants retargeted to cancer-specific heterologous receptors have been generated and are presently evaluated in pre-clinical settings. They will be reviewed along with the molecular bases of cancer specificity and the strategies for the enhancement of oncolytic potential of HSV recombinants

Rethinking herpes simplex virus: the way to oncolytic agents.

Oncolytic viruses infect, replicate in and kill cancer cells. HSV has emerged as a most promising candidate because it exerts a generally moderate pathogenicity in humans; it is amenable to attenuation and tropism retargeting; the ample genome provides space for heterologous genes; specific antiviral therapy is available in a worst case scenario. The first strategy to convert HSV into an oncolytic agent consisted in deletion of the γ(1) 34.5 gene which counteracts the protein kinase R (PKR) response, and of the UL39 gene which encodes the large ribonucleotide reductase subunit. Tumor specificity resided in low PKR activity, and high deoxyribonucleotides content of cancer cells. These highly attenuated viruses have been and presently are in clinical trials with encouraging results. The preferred route of administration has been intratumor or in tissues adjacent to resected tumors. Although the general population has a high seroprevalence of antibodies to HSV, studies in animals and humans demonstrate that prior immunity is not an obstacle to systemic routes of administration, and that oncolytic HSV (o-HSVs) do populate tumors. As the attenuated viruses undergo clinical experimentation, the research pipeline is developing novel, more potent and highly tumor-specific o-HSVs. These include viruses which overcome tumor heterogeneity in PKR level by insertion of anti-PKR genes, viruses which reinforce the host tumor clearance capacity by encoding immune cytokines (IL-12 or granulocyte-macrophage colony-stimulating factor), and non-attenuated viruses fully retargeted to tumor specific receptors. A strategy to generate o-HSVs fully retargeted to human epidermal growth factor receptor-2 (HER-2) or other cancer-specific surface receptors is detailed

Decompressive craniectomy may cause diagnostic challenges to asses brain death by computed tomography angiography.

Background: According to Italian legislation to diagnose brain death (BD) after the initial documentation of the clinical signs, repetition of clinical testing and confirmation of the loss of bioelectrical activity of the brain (EEG) is required. However, when EEG is unreliable it is necessary to demonstrate cerebral circulatory arrest (CCA). Accepted imaging techniques to demonstrate CCA include: cerebral angiography, cerebral scintigraphy, transcranial Doppler (TCD) and computed tomography angiography (CTA). This latter technique, due to its large availability, low invasivity and easy and fast acquisition is widely used over the country. Nevertheless its diagnostic reliability is affected by some limitations in patients with decompressive craniectomy. Methods and Results: Here we report two cases of brain injury with clinical signs of BD and at the same time, opacification of intracranial arteries on CTA and a pattern consistent with flow arrest on the corresponding insonable arteries on TCD. Conclusion: The discrepancy between CTA and TCD results points out a methodology limitation that could be overcome by updating Italian legislation according to other European Countries legislation