178,935 research outputs found
Giant cell tumor of the second metacarpal bone
No full textthis case report discusses the reconstruction after a radical resection of a giant cell tumor in an elderly woman involving the second metacarpal bone. at the presentation the tumor was in stage iii with an involvement of the trapezium and trapezoid. the patient underwent en-block resection of the second ray including trapezium and trapezoid bones. bone fusion in opposition of the first metacarpal and a cutaneous flap was performed. this treatment allowed the patient to achieve optimal functional results with pinch and grasp ability after surgery and adequate safety from recurrency. a literature review of case series describing hand localizations of tGc, and related treatments was performed. (cite this article as: reina m, liuzza f, mazzone vJ. giant cell tumor of the second metacarpal bone
Bullying and Moral Disengagement in Early Adolescence: Do Personality and Family Functioning Matter?
No full textThe present study adopted a multi-informant approach to investigate the contribution of personality and family
functioning to moral disengagement and bullying-related behaviors in early adolescence. The sample included 102 early
adolescents (53 boys and 49 girls; mean age = 12.21 years; effect size = 0.35, power = 0.95, and error probability =
5%). Behaviors during bullying situations were detected by peer nominations. Self-report measures were administered
to assess moral disengagement and family functioning, whereas a parent-report was administered to detect personality
traits. Results showed that extraversion was positively associated with bullying and moral disengagement, while
benevolence was positively associated with defending behavior. Family functioning was negatively associated with
moral disengagement. Furthermore, we found that personality and family functioning were intertwined in their
association with bullying-related behaviors and moral disengagement. In particular, a low conscientiousness, together
with a low family functioning, decreased the likelihood of defending behavior and increased the risk of bullying. High
levels of benevolence decreased outsider behavior in students with a high family functioning. Although extraversion
was positively associated with bullying and moral disengagement, findings suggested that it increased moral
disengagement only among early adolescents with low family functioning. Overall, findings underline the importance
of addressing individual and contextual variables when studying bullying and moral disengagement among early
adolescents.
Keywords: bullying, defending, outsider
Sull’ unità del pensiero italiano, par M. Antonino Mazzone, Catania, 1882
No full textd'A. F. Sull’ unità del pensiero italiano, par M. Antonino Mazzone, Catania, 1882. In: Revue internationale de l'enseignement, tome 5, Janvier-Juin 1883. p. 449
Bullying Perpetration and Victimization in Early Adolescence: Physiological Response to Social Exclusion
No full textThe present study investigated the associations between bullying perpetration and victimization and physiological reactivity to social exclusion. The participants were 28 early adolescents (17 boys and 11 girls; Mage= 11.55; SD = 1.34). Bullying perpetration and victimization were assessed by peer nominations. To elicit social exclusion, participants were first included and then excluded in a laboratory paradigm (Cyberball). Physiological reactivity (i.e., nose tip temperature) was detected through thermal infrared imaging during the computer simulation. Nose temperature variations during inclusion and exclusion were compared between each other. Results showed increasing skin temperature during exclusion, compared to inclusion, for the whole sample, indicating that being excluded affected physiological reactivity. However, victimization was associated with higher skin temperature during exclusion, compared to bullying. The present findings suggest the importance of combining behavioral and contact-free physiological measures when studying bullying perpetration and victimization by peers
Interactive effects of guilt and moral disengagement on bullying, defending, and outsider behavior
No full textWe examined the moderating effect of guilt on the associations between moral disengagement and bullying, defending and outsider behaviors in a sample of 404 students (203 boys; Mage= 11.09 years; SD = 1.48). Bullying, defending and outsider behavior were assessed through peer nominations, whereas guilt and moral disengagement were assessed by self-reports. Results showed that moral disengagement was associated with high levels of bullying and low levels of defending. Guilt was negatively associated with bullying and positively with defending. A moderating effect for guilt was also found: increasing levels of moral disengagement contributed to more bullying and outsider behavior, and to less defending, among students with low levels of guilt. The current research broadens the extant literature, showing the combined effects of guilt and moral disengagement on bullying-related behaviors
Multi-target strategy for Parkinsonian patients: the role of deep brain stimulation in the centromedian-parafascicularis complex.
No full textBrain Res Bull. 2009 Feb 16;78(2-3):113-8. doi: 10.1016/j.brainresbull.2008.08.007. Epub 2008 Sep 21.
Multi-target strategy for Parkinsonian patients: the role of deep brain stimulation in the centromedian-parafascicularis complex.
Stefani A, Peppe A, Pierantozzi M, Galati S, Moschella V, Stanzione P, Mazzone P.
SourceIRCCS Fondazione S. Lucia, Roma, Italy. [email protected]
Abstract
The intra-laminar (IL) thalamic complex, composed of centromedian (CM) and parafascicular (Pf) nucleus, is a strategic crossroad for the activity of the basal ganglia and is recently regaining its position has a putative neurosurgical target for Parkinsonian syndromes. The multi-target approach we have encouraged since the late nineties has allowed the combined implantation of a standard target (the subthalamic nucleus-STN or the internal pallidus-GPi) plus an innovative one (CM/Pf) in well-identified Parkinson's disease (PD) patients; hence, it is possible to study, in the same PD patients, the specific target-mediated effects on different clinical signs. Here, we focus on the potential usefulness of implanting the CM/Pf complex when required in the management of contra-lateral tremor (resistant to standard deep brain stimulation-DBS - in STN - , n=2) and disabling involuntary movements, partially responsive to GPi-DBS (n=6). When considering global UPDRS scores, CM/Pf-DBS ameliorate extra-pyramidal symptoms but not as strongly as STN (or GPi) does. Yet, CM/Pf acts very powerfully on tremor and contributes to the long-term management of l-Dopa-induced involuntary movements. The lack of cognitive deficits and psychic impairment associated with the improvement of their quality of life, in our small cohort of CM/Pf implanted patients, reinforces the notion of CM/Pf as a safe and attractive area for surgical treatment of advanced PD, possibly affecting not only motor but also associative functions
Design of histone methyltransferase and deacetylase modulators: applications in cancer and non-cancer diseases
No full textIn our two previous studies, we reported the discovery and the optimization of novel 1,4-dihydropyridine-based sirtuin ligands. Starting from SIRT1-activating 1,4-DHPs, bearing benzyl group at N1, we identified carbonyl group at N1 to be responsible for an increased SIRT3 activation (MC2791 (1a) and MC2789 (1u)). However, the moderate potencies of 1a and 1u prompted us to screen for more potent derivatives. We generated new series of compounds by varying their “top” or “bottom” with other substituents at C1 or C4 position of the DHP scaffold, respectively. Hence, we reported the discovery and characterization of potent and specific activators for Sirt3 and/or Sirt5. The 1,4-DHP-based activators bind to the sirtuin catalytic core independent of bound substrates and increase the enzyme’s turnover. The compounds are selective for Sirt3 or Sirt5 and show cellular activity. Overall, our results provided a scaffold for potent and specific sirtuins activation and an activation model for Sirt3 and Sirt5 as a basis for functional studies and further drug development. Additionally, HBV-infected cells treated with our potent and selective Sirt3 activator 1a, demonstrated that 1a regulates the antiviral activity of cccDNA in HepAD38 cells. The treatment of HBV-infected cells with 1a through SIRT3 stimulation led to histone H3 and/or H4 hypoacetylation and reduction in the transcription from a viral cccDNA template, accompanied by a reduction in HBV replication. Together these results indicate that the Sirt3 activator 1a can modulate the acetylation status of cccDNA-bound H3/H4 histones, thus providing a novel therapeutic approach for the treatment of chronic HBV infection.Very recently, the trend to shift towards epi-polypharmacology drugs has been taken into account in order to acquire a superior therapeutic effect and eventually reduce drug-related doses and toxicity, as well. Based on these evidence, we design and synthesize novel dual HDAC/EZH2 inhibitors to achieve higher anticancer effect by regulating sinergically the expression of a huge number of tumor suppressor genes. For our purpose, we chose the HDAC pharmacophoric model due to its wide structural variety and feasibility to accommodate on the surface binding cap a high degree of different chemical entities. In our first investigation, we combined the well-known vorinostat HDACi moiety to the already optimised pyrazole and pyrrole EZH2i scaffolds MC3629 and MC3707, respectively. The first preliminary screening of our two hybrid compounds MC4134 and MC4128 showed that only the pyrrole derivative MC4128 was able to simultaneously inhibit EZH2 and HDAC, also exhibiting an interesting isoform selectivity for HDAC6. Prompted by these findings, we decided to develop a series of dual inhibitors of EZH2 and HDAC (8a-g and 6a-g), combining the well-known HDACi moieties to the already optimised EZH2i scaffold MC3707. Therefore, according to the HDACi pharmacophoric model, we have chosen different types of spacer: the aliphatic one (Vorinostat), the benzoic one (Entinostat) and the cinnamic one (Panobinostat and Belinostat). As zinc binding group we used, in turn, a hydroxamic acid or an ortho-amino anilide. Overall, compounds 8a-g and 6a-g have been confirmed to be dual inhibitors of EZH2 and HDACs in vitro, showing an interesting selectivity profile towards HDAC isoforms. In preliminary assays in U-937 AML cells, 8c (MC4128) decreased cell viability and induced apoptosis, with increased levels of acetyl-histone H3 and acetyl-α–tubulin. Importantly, we expect that our novel HDAC/EZH2 dual inhibitors can display a potent and synergic anti-cancer activity in vivo, thus becoming an attractive therapeutic approach to fight cancer.Friedreich’s ataxia (FRDA) is an autosomal recessive neurodegenerative mitochondrial disorder caused by an unstable GAA trinucleotide (TTC) repeat expansion in the first intron of the frataxin gene (FXN). In FRDA patients, the expanded GAA·TTC repeats lead to partial transcriptional silencing resulting in expression of structurally and functionally normal frataxin, but at lower levels compared to the normal. FRDA can be considered as an epigenetic disease due to the identification of several associated epigenetic marks, including 1) increased levels of methylated histones (H3K9me2, H3K9me3, H4K20me3) in regions flanking the GAA repeats, 2) increased DNA methylation at specific CpG sites upstream of the GAA repeats and, 3) reduced acetylation of several H3 and H4 lysine residues. Due to the importance of H4K20me to genomic integrity, very recently A-196 has been discovered as the first-in-class chemical probe of Suv4-20H1 and Suv4-20H2, with an IC50= 25 nM and IC50=144 nM, respectively. Despite the in vitro potency of A-196, confirmed by biochemical and cellular assays, preliminary in vitro metabolic studies in human liver microsomes (HLM) have shown some metabolic liability and potentially low solubility, with a Clint (μL/min/mg protein) =191 and a t1/2 (min)=7.28. Prompted by these findings, a lead chemical optimisation has been carried out with the aim to ameliorate chemical and physical properties of A-196. Preliminary biological results of our final compounds (1a-m and 2c) in HEK293 cell model of FRDA showed that only compound 1b (RM02) demonstrated similar effects (or slight better) than the reference compound A-196, with a luciferase fold reactivation of 1.20. The other compounds, unfortunately, showed no increase in frataxin expression beyond that one induced by the vehicle DMSO. Preliminary data for the evaluation of the cytotoxicity (adenylate kinase scores) showed that our compounds are probable non-toxic to the cells
Analysis of irradiated Ag and Si by molecular dynamics and calculated HREM imaging
No full textIn order to clarify the limits of HREM observations of defects due to radiation damage, a simulation method has been designed which combines molecular dynamics and HREM simulation. Disorder due to ion irradiation in Si and Ag is simulated by using a molecular dynamics technique and HREM images are computed by a multislice dynamic procedure. The conditions to achieve a goad HREM visibility of such defective structures have been investigated by analyzing the effects of the physical inputs of molecular dynamics as well as the ones of the instrumental parameters of TEM observations. This analysis indicates that the structure of the damaged region is not critical. On the contrary, the fractional disorder is of paramount importance and determines the conditions leading to an appreciable contrast of the disordered region against the crystalline background
Shape and stability of heteroepitaxial metallic islands: effects of the electronic configuration
No full textThe stability of metallic islands, epitaxially grown on a metallic substrate, is Studied by the evaluation of the island total energy. Hartree-Fock calculations at semiempirical level have been used to describe the island electronic configuration with quantum mechanical detail. The functional dependence of the island energy on the elements forming the island and the substrate (i.e. Ag, Cu and Fe). on the island geometry and on its state of stress, is analyzed and discussed. A similar analysis is also carried out for the barrier experienced by adatoms at descending steps
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