Sulforaphane causes cell cycle arrest and apoptosis in human glioblastoma u87mg and u373mg cell lines under hypoxic conditions

Glioblastoma multiforme (GBM) is the most prevalent and aggressive primary brain tumor. The median survival rate from diagnosis ranges from 15 to 17 months because the tumor is resistant to most therapeutic strategies. GBM exhibits microvascular hyperplasia and pronounced necrosis triggered by hypoxia. Sulforaphane (SFN), an isothiocyanate derived from cruciferous vegetables, has already demonstrated the ability to inhibit cell proliferation, by provoking cell cycle arrest, and leading to apoptosis in many cell lines. In this study, we investigated the antineoplastic effects of SFN [20–80 µM for 48 h] in GBM cells under normoxic and hypoxic conditions. Cell viability assays, flow cytometry, and Western blot results revealed that SFN could induce apoptosis of GBM cells in a dose-dependent manner, under both conditions. In particular, SFN significantly induced caspase 3/7 activation and DNA fragmentation. Moreover, our results demonstrated that SFN suppressed GBM cells proliferation by arresting the cell cycle at the S-phase, also under hypoxic condition, and that these effects may be due in part to its ability to induce oxidative stress by reducing glutathione levels and to increase the phosphorylation of extracellular signal-regulated kinases (ERKs). Overall, we hypothesized that SFN treatment might serve as a potential therapeutic strategy, alone or in combination, against GBM

Tailored Torsion and Bending-Resistant Avian-Inspired Structures

The escalating demand for torsion- and bending-resistant structures paired with the need for more efficient use of materials and geometries, have led to novel bio-inspired ingenious solutions. However, lessons from Nature could be as inspiring as they are puzzling: plants and animals offer an enormous range of promising but hierarchically complex configurations. Avian bones are prominent candidates for addressing the torsional and bending issue. They present a unique intertwining of simple components: helicoidal ridges and crisscrossing struts, able to bear flexural and twisting actions of winds. Here, it is set how to harmonically move from the natural to the engineering level to formalize and analyze the biological phenomena under controlled design conditions. The effect of ridges and struts is isolated and combined toward tailored torsion and bending-resistant arrangements. Then the biological level is revisited to extrapolate the avian allometric design approach and is translated into multiscale lightweight structures at the engineering level. This study exploits the complexity of Nature and the scalability that characterizes the evolutionary design of bird bones through the design and fabrication versatility allowed by additive manufacturing technologies. This paves the way for exploring the transferability of the proposed solution at multiple engineering scales

Manganite/Alq3 interfaces investigated by impedance spectroscopy technique

With the general objective of studying interfaces between ferromagnetic materials and organic semiconductors, we report ac impedance investigations on La0.7Sr0.3MnO3 (LSMO)/tris(8-hydroxyquinoline)aluminium (Alq3)/Al and Indium Tin Oxide (ITO)/Alq3/Al heterostructures, in the frequency range between 20 Hz and 1 MHz. The comparison of the equivalent circuits deduced to fit the experimental ac responses allows isolating a specific RC contribution which can be attributed to the LSMO/Alq3 interface region. Using the information obtained from our ac measurements, we propose a model which fits the temperature dependence of the magnetoresistance in spin valves combining LSMO electrodes and Alq3 layers

Activity and analysis of costs in a dedicated weaning centre.

AIM: To analyse the diagnosis-related characteristics and the costs of treating patients with difficult/prolonged weaning from mechanical ventilation we have undertaken a retrospective observational study. METHODS: The study has considered all the patients admitted to our weaning unit of a regional Rehabilitation department during 3 consecutive periods since the opening date. Characteristics of the admitted patients and the DRG-related cares delivered have been recorded. A cost analysis has been obtained over time. RESULTS: The number of beds allocated to this unit (from 4 in the 1st period to 6 in the 2nd and 3rd periods) and the number of patients cared for (from 32 to 43 and to 65, respectively) increased over time. In particular, the COPD to non-COPD patient ratio (from 2.2 to 1.3 and to 1.0) and the DRG/patient weight (from 3.0 +/- 0.3 to 3.1 +/- 0.2 and to 3.3 +/- 0.2 point) changed significantly (p < 0.05). The daily reimbursement per patient from the public health care system only slightly increased, whereas the operating margin (reimbursement less costs) per patient significantly improved (from -304, to +17 and +55 Euro/pt/day, respectively, p < 0.05) due to a gradual restriction in the variable costs. Length of stay, mortality rate and weaning rate did not change over time. CONCLUSION: The weaning centre is a hospital area where economic burdens should be carefully evaluated. Given the actual reimbursement received on a national level for these patients, variable costs might be better spread, thus optimising the burdens without losing out on clinical outcomes

The Unfolded Protein Response in a Murine Model of Alzheimer’s Disease: Looking for Predictors

Alzheimer's disease (AD) represents the most frequent type of dementia worldwide, and aging is the most important risk factor for the sporadic form of the pathology. The endoplasmic reticulum (ER), the main cellular actor involved in proteostasis, appears significantly compromised in AD due to the accumulation of the beta-amyloid (A beta) protein and the phosphorylated Tau protein. Increasing protein misfolding activates a specific cellular response known as Unfolded Protein Response (UPR), which orchestrates the recovery of ER function. The aim of the present study was to investigate the role of UPR in a murine model of AD induced by intracerebroventricular (i.c.v.) injection of A beta 1-42 oligomers at 3 or 18 months. The oligomer injection in aged animals induced memory impairment, oxidative stress, and the depletion of glutathione reserve. Furthermore, the RNA sequencing and the bioinformatic analysis performed showed the enrichment of several pathways involved in neurodegeneration and protein regulations. The analysis highlighted the significant dysregulation of the protein kinase RNA-like ER kinase (PERK), inositol-requiring protein 1 alpha (IRE1 alpha) and activating transcription factor 6 (ATF-6). In turn, ER stress affected the PI3K/Akt/Gsk3 beta and MAPK/ERK pathways, highlighting Mapkapk5 as a potential marker, whose regulation could lead to the definition of new pharmacological and neuroprotective strategies to counteract AD

Erratum: “Seed layer technique for high quality epitaxial manganite films” [AIP Advances 6, 085109 (2016)]

No abstract available

Design and 3D printing of a modular phantom of a uterus for medical device validation

PurposeThe purpose of this study is to describe the design and validation of a three-dimensional (3D)-printed phantom of a uterus to support the development of uterine balloon tamponade devices conceived to stop post-partum haemorrhages (PPHs). Design/methodology/approachThe phantom 3D model is generated by analysing the main requirements for validating uterine balloon tamponade devices. A modular approach is implemented to guarantee that the phantom allows testing these devices under multiple working conditions. Once finalised the design, the phantom effectiveness is validated experimentally. FindingsThe modular phantom allows performing the required measurements for testing the performance of devices designed to stop PPH. Social implicationsPPH is the leading obstetric cause of maternal death worldwide, mainly in low- and middle-income countries. The proposed phantom could speed up and optimise the design and validation of devices for PPH treatment, reducing the maternal mortality ratio. Originality/valueTo the best of the authors' knowledge, the 3D-printed phantom represents the first example of a modular, flexible and transparent uterus model. It can be used to validate and perform usability tests of medical devices

Non-pharmacological treatments for pediatric refractory epilepsies

Introduction: Antiseizure medications (ASMs) are the primary treatment option for epilepsies of wide etiologies, however, about 10–20% of children do not gain sustained seizure control and in this case, it is worth investigating ‘alternative’ therapeutic approaches aside from ASMs. Nowadays, non-pharmacological strategies for epilepsy treatment encompass dietary interventions, neurostimulation-based techniques, and biobehavioral approaches. Areas covered: A search on PubMed database was conducted. Experimental and clinical studies, as well as meta-analysis and structured reviews on the latest non-pharmacological treatments for drug-resistant epilepsy (DRE) in children, were included. Special attention is given to the efficacy and tolerability outcomes, trying to infer the role novel approaches may have in the future. Expert opinion: The large heterogeneity of primary clinical outcomes and the unavoidable subjective response of each patient to treatments prevents Researchers from the identification of a single, reliable, approach to treat DRE. The understanding of fine pathophysiologic processes is giving the way to the use of alternative therapies, such as the well-known ketogenic diet, in a ‘personalized’ view of treatment. The goal is to apply the non-pharmacological treatment most suitable for the patients sake

Surface nanostructures in manganite films

Ultrathin manganite films are widely used as active electrodes in organic spintronic devices. In this study, a scanning tunnelling microscopy (STM) investigation with atomic resolution revealed previously unknown surface features consisting of small non-stoichiometric islands. Based upon this evidence, a new mechanism for the growth of these complex materials is proposed. It is suggested that the non-stoichiometric islands result from nucleation centres that are below the critical threshold size required for stoichiometric crystalline growth. These islands represent a kinetic intermediate of single-layer growth regardless of the film thickness, and should be considered and possibly controlled in manganite thin-film applications