121 research outputs found
Comparison of alternate and original forms of the Montreal Cognitive Assessment (MoCA): an Italian normative study
Objective: The Montreal Cognitive Assessment (MoCA) is a screening test widely used in clinical practice and suited for detection of Mild Cognitive Impairment. Alternate forms of the MoCA were developed to avoid \u201clearning effect\u201d in serial assessments, and the present study aimed at investigating inter-form parallelism and at providing normative values for the Italian versions of MoCAs 2 and 3. Method: Three separate convenience samples were recruited: the first (n = 78) completed three alternate MoCA versions for ascertaining inter-form parallelism; the second (n = 302) and the third (n = 413) samples were administered MoCA 2 or 3 to compute normative data. Results: A three-step procedure complemented by confirmatory factor analysis and a mixed factorial ANOVA suggested that the three MoCA versions are not strictly parallel. Multiple linear regression analysis revealed that age and education significantly influenced MoCA 2 and 3 total scores. No significant effect of sex was found. From the derived linear equation, correction grids for MoCA 2 and 3 raw scores were built and equivalent scores computed. Inferential cutoff for adjusted scores, estimated using a non-parametric technique, were 17.49 for MoCA 2 and 18.34 for MoCA 3. Correlation analysis showed strong correlations of MoCA 2 (r = 0.69, p <.001) and MoCA 3 (r = 0.61, p <.001) adjusted total scores with MMSE adjusted scores. Conclusion: The three MoCA forms are not strictly parallel. Specifically developed normative data must be adopted for using MoCA in serial cognitive assessments for clinical and research studies
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ELSA Italy
In the last 50 years, Italy has experienced a relevant transformation, starting from an emigrant nation (according to the last statistics from the Ministry of the Interior, there are more than 4.636.647 Italians still living abroad) to become an immigrant destination.
From 1970 until now, migrant citizens with regular residence permits in Italy have increased, with a rate of growth that looks almost unstoppable: at the beginning of 2017, there were more than 5,047,028 foreign nationals resident in Italy.
This numbers, added to the illegal immigrants whose numbers are difficult to define, outline a complex situation, characterized by immigrant flows from almost 200 different countries, especially Central Eastern Europe (Albania, Romania and Ukraine), Northern Africa (Morocco), China and the Indian subcontinent (Pakistan, India, and Sri Lanka).
This historically important phenomenon requires in-depth analysis in order to evaluate the effectiveness of the Italian legislation and intervention policies, and to find concrete solutions to help immigrants settling in our country
Hyperglycemia and redox status regulate RUNX2 DNA-binding and an angiogenic phenotype in endothelial cells
Angiogenesis is regulated by hyperglycemic conditions, which can induce cellular stress responses, reactive oxygen species (ROS), and anti-oxidant defenses that modulate intracellular signaling to prevent oxidative damage. The RUNX2 DNA-binding transcription factor is activated by a glucose-mediated intracellular pathway, plays an important role in endothelial cell (EC) function and angiogenesis, and is a target of oxidative stress. RUNX2 DNA-binding and EC differentiation in response to glucose were conserved in ECs from different tissues and inhibited by hyperglycemia, which stimulated ROS production through the aldose reductase glucose-utilization pathway. Furthermore, the redox status of cysteine and methionine residues regulated RUNX2 DNA-binding and reversal of oxidative inhibition was consistent with an endogenous Methionine sulfoxide reductase-A (MsrA) activity. Low molecular weight MsrA substrates and sulfoxide scavengers were potent inhibitors of RUNX2 DNA binding in the absence of oxidative stress, but acted as antioxidants to increase DNA binding in the presence of oxidants. MsrA was associated with RUNX2:DNA complexes, as measured by a sensitive, quantitative DNA-binding ELISA. The related RUNX2 protein family member, RUNX1, which contains an identical DNA-binding domain, was a catalytic substrate of recombinant MsrA. These findings define novel redox pathways involving aldose reductase and MsrA that regulate RUNX2 transcription factor activity and biological function in ECs. Targeting of these pathways could result in more effective strategies to alleviate the vascular dysfunction associated with diabetes or cancer
Drug-induced senescence bystander proliferation in prostate cancer cells in vitro and in vivo
Senescence is a distinct cellular response induced by DNA-damaging agents and other sublethal stressors and may provide novel benefits in cancer therapy. However, in an ageing model, senescent fibroblasts were found to stimulate the proliferation of cocultured cells. To address whether senescence induction in cancer cells using chemotherapy induces similar effects, we used GFP-labelled prostate cancer cell lines and monitored their proliferation in the presence of proliferating or doxorubicin-induced senescent cancer cells in vitro and in vivo. Here, we show that the presence of senescent cancer cells increased the proliferation of cocultured cells in vitro through paracrine signalling factors, but this proliferative effect was significantly less than that seen with senescent fibroblasts. In vivo, senescent cancer cells failed to increase the establishment, growth or proliferation of LNCaP and DU145 xenografts in nude mice. Senescent cells persisted as long as 5 weeks in tumours. Our results demonstrate that although drug-induced senescent cancer cells stimulate the proliferation of bystander cells in vitro, this does not significantly alter the growth of tumours in vivo. Coupled with clinical observations, these data suggest that the proliferative bystander effects of senescent cancer cells are negligible and support the further development of senescence induction as therapy
Hippocampal connectivity in Amyotrophic Lateral Sclerosis (ALS): more than Papez circuit impairment
Emerging evidence suggests that memory deficit in amyotrophic lateral sclerosis (ALS), a neurodegenerative disease with varying impairment of motor abilities and cognitive profile, may be independent from executive dysfunction. Our multimodal magnetic resonance imaging (MRI) approach, including resting state functional MRI (RS-fMRI), diffusion tensor imaging (DTI) and voxel-based morphometry (VBM), aimed to investigate structural and functional changes within and beyond the Papez circuit in non-demented ALS patients (n = 32) compared with healthy controls (HCs, n = 21), and whether these changes correlated with neuropsychological measures of verbal and non-verbal memory. We revealed a decreased functional connectivity between bilateral hippocampus, bilateral parahippocampal gyri and cerebellum in ALS patients compared with HCs. Between-group comparisons revealed white matter abnormalities in the genu and body of the corpus callosum and bilateral cortico-spinal tracts, superior longitudinal and uncinate fasciculi in ALS patients (p <.05, family-wise error corrected). Interestingly, changes of Digit Span forward performance were inversely related to RS-fMRI signal fluctuations in the cerebellum, while changes of both episodic and visual memory scores were inversely related to mean and radial diffusivity abnormalities in several WM fiber tracts, including middle cerebellar peduncles. Our findings revealed that ALS patients showed significant functional and structural connectivity changes across the regions comprising the Papez circuit, as well as more extended areas including cerebellum and frontal, temporal and parietal areas, supporting the theory of a multi-system pathology in ALS that spreads from cortical to subcortical structures
A novel role for syndecan-3 in angiogenesis.
Syndecan-3 is one of the four members of the syndecan family of heparan sulphate proteoglycans and has been shown to interact with numerous growth factors via its heparan sulphate chains. The extracellular core proteins of syndecan-1,-2 and -4 all possess adhesion regulatory motifs and we hypothesized that syndecan-3 may also possess such characteristics. Here we show that a bacterially expressed GST fusion protein consisting of the entire mature syndecan-3 ectodomain has anti-angiogenic properties and acts via modulating endothelial cell migration. This work identifies syndecan-3 as a possible therapeutic target for anti-angiogenic therapy.This work was funded by Arthritis Research-UK (Grant No. 19207) and funds from the William Harvey Research Foundation both to JRW
The in vivo properties of STX243: a potent angiogenesis inhibitor in breast cancer
The steroidal-based drug 2-ethyloestradiol-3,17-O,O-bis-sulphamate (STX243) has been developed as a potent antiangiogenic and antitumour compound. The objective of this study was to ascertain whether STX243 is more active in vivo than the clinically relevant drug 2-methoxyoestradiol (2-MeOE2) and the structurally similar compound 2-MeOE2-3,17-O,O-bis-sulphamate (STX140). The tumour growth inhibition efficacy, antiangiogenic potential and pharmacokinetics of STX243 were examined using four in vivo models. Both STX243 and STX140 were capable of retarding the growth of MDA-MB-231 xenograft tumours (72 and 63%, respectively), whereas no inhibition was observed for animals treated with 2-MeOE2. Further tumour inhibition studies showed that STX243 was also active against MCF-7 paclitaxel-resistant tumours. Using a Matrigel plug-based model, in vivo angiogenesis was restricted with STX243 and STX140 (50 and 72%, respectively, using a 10 mg kg−1 oral dose), thereby showing the antiangiogenic activity of both compounds. The pharmacokinetics of STX243 were examined at two different doses using adult female rats. The compound was orally bioavailable (31% after a single 10 mg kg−1 dose) and resistant to metabolism. These results show that STX243 is a potent in vivo drug and could be clinically effective at treating a number of oncological conditions
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Queering Peace and Security: Recommendations to the United Nations Independent Expert on Sexual Orientation and Gender Identity
Increased Vitreous Shedding of Microparticles in Proliferative Diabetic Retinopathy Stimulates Endothelial Proliferation
TRAIL inhibits angiogenesis stimulated by VEGF expression in human glioblastoma cells
Tumour growth is tightly related to new blood vessel formation, tissue remodelling and invasiveness capacity. A number of tissular factors fuel the growth of glioblastoma multiforme, the most aggressive brain neoplasm. In fact, gene array analyses demonstrated that the proapoptotic cytokine tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) inhibited mRNA expression of VEGF, along with those of matrix metalloproteinase-2 (MMP-2), its inhibitor tissue inhibitor of matrix metalloproteinases-2 (TIMP-2), as well as the tumour invasiveness-related gene secreted protein acid rich in cysteine (SPARC) in different human glioblastoma cell lines. Particularly, VEGF mRNA and protein expression and release from glioblastoma cells were also inhibited by TRAIL. The latter also exerted antimitogenic effects on human umbilical vein endothelial cells (HUVECs). With the same cells, TRAIL inhibited new vessel formation in the in vitro matrigel model, as well as it exerted powerful inhibition of blood vessel formation induced by an angiogenic cocktail administered in subcutaneous pellets in vivo in the C57 mouse. Moreover, the expression of MMP-2, its inhibitor TIMP-2 and the tumour invasiveness-related protein SPARC were effectively inhibited by TRAIL in glioblastoma cell lines. In conclusion, our data indicate that TRAIL inhibits the orchestra of factors contributing to glioblastoma biological aggressiveness. Thus, the TRAIL system could be regarded as a molecular target to exploit for innovative therapy of this type of tumour
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