Oral plus vaginal alpha-lipoic acid in women at risk for preterm delivery

Objective: The etiology of preterm labor is multifactorial. An inflammatory response is always involved with the activation of NF-kB that determines synthesis and release of inflammatory molecules, implicated in fetal membrane activation, cervical modifications, abdominal pain and spontaneous uterine contractions. There is a close relationship between preterm birth and cervical shortening in the second quarter of pregnancy. We evaluated the benefits of alpha-lipoic acid administration on women considered at risk of preterm delivery due to the presence of symptoms (pelvic pain and uterine contractions) or reduced cervical length. Patients and Methods: This prospective observational study was carried out at the Gynecology and Obstetrics Unit of Palermo University Hospital (Palermo, Italy), from October 2015 to April 2016. The inclusion criteria were: women aged 18-35, with gestational age between 24 and 33 weeks of amenorrhea, pregnancy at risk of preterm delivery due to cervical length between 35-25 mm (in presence of symptoms) or < 30 and > 15 mm (if asymptomatic), intact membranes and negative for vaginosis. Patients were treated daily with alpha lipoic acid orally (300 mg, twice a day for 30 days) and vaginally (10 mg, once a day for 10 days), or untreated (controls). Patients were evaluated at the baseline (T 0), after 7 days, after 30 days, and at 34 weeks of gestation considering: maternal characteristics, symptomology and cervical length. Results: Among 60 analyzed women, 50 were treated orally and vaginally with alpha-lipoic acid, whereas 10 did not undergo any therapy. In the treated group, 10 patients were asymptomatic and 40 symptomatic. The symptoms disappeared in 37 patients. In the untreated group, 4 women were symptomatic and 6 asymptomatic. At the end all women were symptomatic. Mean cervical length showed a reduction in the untreated group compared to the treated group. Conclusions: The vaginal/oral-combined administration with alpha-lipoic acid showed effectiveness in reducing symptoms and preventing cervical shortening in our set of patients. No adverse effects were detected during the treatment

An explorative study setting a national supportive system of near-miss management for the Italian industrial sector

Initiatives, projects, and programmes for Occupational Safety and Health (OSH) management benefit from supportive systems to develop and properly last over time. National OSH systems were born to enforce the law by applying national regulations. In the last years, most countries have started to take preventative actions to improve workers’ health and safety conditions. Assistance initiatives are growing fast, and new roles and profiles are arising to keep up with changes. Nowadays, national OSH actors usually perform both supervisory and supporting activities. This is widely applied in Italy where several bodies promote and support companies in taking part in OSH initiatives. In Italy, a collaborative project for near-miss management is under development by the Italian National Institute for Insurance against Accidents at Work (INAIL, i.e., in Italian, “Istituto Nazionale Assicurazione Infortuni sul Lavoro”). The project aims at increasing awareness of the relevance of near-miss monitoring. This paper studies the environment setting for this project, so bodies that will have an active role in its implementation and daily management. A focus group with INAIL’s experts and researchers from two Italian universities has enabled to identify key actors and their role in the project’s development and to select the most viable scenarios. This work provides a methodological approach to study other national supportive OSH systems and also detects Italian best practices replicable in other countries

Sustainable Occupational Safety and Health Interventions: A Study on the Factors for an Effective Design

Effective interventions are a priority in continuously changing occupational environments, particularly in companies struggling to manage health and safety in the workplace. Practitioners may consider practical solutions for Occupational Safety and Health (OSH) improvement as a panacea for all major problems. However, they may overlook a range of other factors that affect the success of such solutions. The way in which a solution is developed, designed, implemented, and evaluated determines its impact. Participatory interventions are one way of ensuring better results. Consequently, this study proposes a way of establishing sustainable, effective, and efficient interventions by defining the required processes and actively involving responsible actors (i.e., who, when, and how). A national OSH intervention for introducing a near-miss management system, funded by the Italian National Institute for Insurance against Accidents at Work (INAIL), is used as a reference because its development process includes an accurate design stage. Based on this intervention, a multistep design process is built to answer how (how the intervention will persist by defining the context, processes, and scenarios), who (who will be the responsible actors actively participating), and when (when actors will be involved) questions. The design process established for the intervention, although within a specific context, provides clues to discriminant factors that would enable effectiveness in general interventions, and the proposed system for near- miss management generates insights that may be generalizable to other OSH interventions developed in different environments

Nonsense-mediated decay mechanism is a possible modifying factor of clinical outcome in nonsense cd39 beta thalassemia genotype

Nonsense-mediated mRNA decay (NMD) is a surveillance system to prevent the synthesis of non-functional proteins. In β-thalassemia, NMD may have a role in clinical outcome. An example of premature translation stop codons appearing for the first time is the β-globin cd39 mutation; when homozygous, this results in a severe phenotype. The aim of this study was to determine whether the homozygous nonsense cd39 may have a milder phenotype in comparison with IVS1,nt110/cd39 genotype. Genotypes have been identified from a cohort of 568 patients affected by β-thalassemia. These genotypes were compared with those found in 577 affected fetuses detected among 2292 prenatal diagnoses. The nine most common genotypes, each with an incidence rate of 1.5% or over, and together accounting for 80% of genotype frequencies, underwent statistical analysis. Genotype prevalence was calculated within the overall group. Results are expressed as proportions with 95% confidence intervals; P≤0.05 was considered statistically significant. A binomial distribution was assumed for each group; z-tests were used to compare genotype frequencies observed in the patient group with frequencies in the affected fetus group. In the absence of selecting factors, prevalence of these two genotypes was compared between a cohort of 568 β-thalassemia patients (PTS) and 577 affected fetuses (FOET) detected during the same period. IVS1,nt110/cd39 was significantly more prevalent in FOET than PTS (P<0.0001), while there was no significant difference in prevalence of cd39/cd39 in FOET compared with PTS (P=0.524). These results suggest a cd39 genotype NMD mechanism may be associated with improved clinical outcomes in thalassemia major

Tubular composite scaffolds produced via Diffusion Induced Phase Separation (DIPS) as a shaping strategy for anterior cruciate ligaments reconstruction

Injuries of tendons and ligaments are common, especially among the young population. Anterior cruciate ligament (ACL) injuries do not heal due to its limited vascularization and hence, surgical intervention is usually required. The ideal scaffold for ligament tissue engineering (TE) should be biocompatible and possess mechanical and functional characteristics comparable to the native ACL. The Diffusion Induced Phase Separation (DIPS) technique allows the preparation of homogenous porous tubular scaffold with micro-pores using a rather simple procedure. Composites based on biodegradable polymers and bioglass have attracted much attention in tissue reconstruction and repair because of their biological and physicochemical advantages. In this work a new approach in ACL TE will be proposed focussing on the development of a suitable technique for in vitro seeding of lapine ACL fibroblasts into tubular-shaped instructive Poly-lactic-acid (PLLA) scaffolds, supplemented or not with bioglass (BG) 1393, produced via DIPS. Tubular composite scaffold (diameters: 1.2 and 2 mm, +/- BG) were obtained through a dip coating around a cylindrical support followed by a DIPS. An 8%wt PLLA/dioxane solution was prepared with 5%wt of BG-1393 as filler. Preliminary in vitro cell culture trials were carried out by seeding lapine ACL fibroblasts inside the scaffolds (2 cm as length) employing different seeding strategies in order to find the best way that allows to obtain a homogeneous fibroblast distribution inside the tubes. (1) First trials consisted in the inoculating of the cell suspension inside the tubes and maintaining them in dynamical culture. (2) The second one was done by suspending the cells in a fibrin gel polymerized within the tubes by using of thrombin. (3) The third approach was carried out by using cell spheroids (three-dimensional self-assembled cell agglomerates). Cell attachment, viability and morphology were examined by live-death and Hematoxylin/Eosin stainings after 1, 7, 14 d and vimentin immunolabelings (7 d). Scanning electron microscopical analysis revealed that the internal surface of the tubes was homogeneously structured with micropores sized around 5 µm and a mean thickness of the wall of 60 µm. The results showed cell adhesion to the wall of the tubes with all seeding techniques applied even though with fibrin gel it was more homogenous. Furthermore, colonized areas expanded with culture time and the majority of cell survived irrespectively of seeding techniques. (1) In inoculation phase, many cells left the scaffold and attached on the plate. Even after the dynamic culture (rotating device) most cells covered only half the tube inner surface. (2) In the second trial, a fibrin gel was used to achieve a homogenous cell distribution during seeding. In the early stage (48 h) cells remained captured inside the fibrin, but after 7 d they become elongated and migrated from the fibrin to the inner tube surface forming a compact cell layer. So, the fibrin appears helpful to achieve an immediate high cell seeding efficiency and an almost homogeneous cell distribution inside the tubes. (3) Although using the spheroid technique the scaffold internal surface was not homogeneously colonized with cells, after 7 d cell migration to the inner scaffold surface from the attaching spheroids could be observed. In longitudinal sections cells were elongated like typical ligament fibroblasts parallel to the longitudinal tube axis. Therefore, it can be affirmed that employment of tubular scaffolds produced by DIPS could be a promising approach of ligament TE. In the future, it would be interesting to evaluate the effectiveness of seeding by combining the spheroids and the fibrin gel

Potential roles of extracellular vesicles in brain cell-to-cell communication

Potential roles of extracellular vesicles in brain cell-to-cell communication Extracellular vesicles (EVs) are released into thè extracellular space from both cancer and normal brain cells, and are probably able to modify thè phenotypic properties of receiving cells1. EVs released from astrocytes and neurons contain FGF2 and VEGF2'3 and induce a 'blood-brain barrier' (BBB) phenotype in cultured brain capillary endothelial cells (BCECs, unpublished results), On thè other hand, EVs from G26/24 oligodendroglioma induce apoptosis in neurons and astrocytes4-5. These effects are probably due to Fas Ligand and TRAIL, present in G26/24 vesicles4-5. Moreover, G26/24 EVs contain extracellular matrix remodeling proteases (such as ADAMTS)6, H1.0 histone protein, and H1.0 mRNA7. In particular, we previously hypothesized that G26/24 cells, and tumor cells in generai, can escape differentiation cues, and continue to proliferate by eliminating proteins, such as thè H1° linker histone (and its mRNA)7, which could otherwise block proliferation. To study vesicle release in a System that can better resemble in vivo conditions, astrocytes and BCECs were cultured on poly-L-lactic acid (PLLA) scaffolds and tested for their ability to grow and survive on this three-dimensional structures. We analyzed in parallel thè celi growth in 2D and 3D culture systems and observed thè differences in celi morphology by fluorescence analysis: threedimensional scaffolds have thè ability to guide celi growth, provide support, encourage celi adhesion and proliferation. Astrocytes8 and BCECs (unpublished results) adapted well to these porous matrices, not only remaining on thè surface, but also penetrating inside thè scaffolds. EVs released by astrocytes in these scaffolds are probably exosomes, as suggested by transmission electron microscopy pictures, and by thè presence of intracellular structures resembling multivesicular bodies. This 3D celi culture System could be further enriched to host different brain celi types, in order to set, for example, an in vitro model of BBB, that may be useful for drug delivery studies, and for thè formulation of new therapeutic strategies for thè treatment of neurological diseases. References [1] Schiera, G., Di Liegro, C.M., Di Liegro I. Int J Mol Sci. 2017, 18(12). pii: E2774. [2] Schiera, G., Proia, P., Alberti, C., Mineo, M., Savettieri, G., Di Liegro, I., 2007. J Celi Mol Med. 2007, 111(6), 1384-94. [3] Proia, P., Schiera, G., Mineo, M., Ingrassia, A.M. Santoro, G., Savettieri, G., Di Liegro, I. Int J Mol Med. 2008, 21(1), 63-7. [4] D'Agostino, S., Salamene, M., Di Liegro, I., Vittorelli, ML, Int J Oncol. 2006, 29(5), 1075-85. [5] Lo Cicero, A., Schiera, G., Proia, P., Saladino, P., Savettieri, G., Di Liegro, C.M., Di Liegro, I. Int J Oncol. 2011,39(6): 1353-7. [6] Lo Cicero, A., Majkowska, I., Nagase, H., Di Liegro, I., Troeberg, L., Matrix Biol. 2012, 31(4), 229-33. [7] Schiera, G., Di Liegro, C.M., Saladino, P., Pitti, R., Savettieri, G., Proia, P., Di Liegro, I. Int J Oncol. 2013, 43(6), 1771-6. [8] Carfì Pavia, F., Di Bella, M.A., Brucato, V., Blanda, V., Zummo, F., Vitrano, I., Di Liegro, C.M., Ghersi, G., Di Liegro, I., Schiera, G. Mol Med Rep. 2019 [Epub ahead of print]. [9] Di Bella MA, Zummo F., Carfì Pavia F., Brucato V., Di Liegro I., Schiera G. 2017, In: Microscopy and Imaging Science: practical approaches to applied research and education, pp 260-264. Ed: A. Méndez-Vilas Publisher, Formatex Research Center (Spain), ISBN-13, 978-84-942134-9-6

Uso de cannabis y desarrollo de esquizofrenia: ¿cuáles son los vínculos?

El cannabis es la droga más utilizada por personas con esquizofrenia. Sin embargo, la relación entre el consumo de cannabis y el desarrollo de esquizofrenia aún no ha sido completamente aclarada. Esta comunicación corta pretende destacar algunos vínculos estudiados entre el consumo de cannabis y el desarrollo de esquizofrenia. Los autores resumen algunos de los principales hallazgos de varias investigaciones realizadas sobre este tema, incluyendo estudios sobre la sustancia blanca del cerebro, el circuito de recompensa cerebral, la fisiopatología del hipocampo, el volumen cerebral, la edad de inicio de la psicosis, las características del uso de cannabis y los rasgos de personalidad, la genética, la neuroquímica, así como la respuesta al estrés. Los autores concuerdan con la noción de que hay dos hipótesis más convincentes sobre el vínculo entre el cannabis y la esquizofrenia: 1. Cannabis como causa contribuyente y, 2. Vulnerabilidad compartida. Los autores hacen hincapié en que el consumo de cannabis no provoca por sí mismo un trastorno psicótico; sin embargo, tanto el uso temprano como el uso intensivo del mismo son más probables en individuos con una vulnerabilidad a la psicosis. El uso del cannabis es posiblemente el factor de riesgo medioambiental más modificable de la esquizofrenia, por lo que es necesaria una advertencia de salud pública de que el consumo de cannabis puede aumentar el riesgo de trastornos psicóticos