Late-onset Parkinsonism in NFκB/c-Rel-deficient mice.

Activation of the nuclear factor \u3baB/c-Rel can increase neuronal resilience to pathological noxae by regulating the expression of pro-survival manganese superoxide dismutase (MnSOD, now known as SOD2) and Bcl-xL genes. We show here that c-Rel-deficient (c-rel(-/-)) mice developed a Parkinson's disease-like neuropathology with ageing. At 18 months of age, c-rel(-/-) mice exhibited a significant loss of dopaminergic neurons in the substantia nigra pars compacta, as assessed by tyrosine hydroxylase-immunoreactivity and Nissl staining. Nigral degeneration was accompanied by a significant loss of dopaminergic terminals and a significant reduction of dopamine and homovanillic acid levels in the striatum. Mice deficient of the c-Rel factor exhibited a marked immunoreactivity for fibrillary \u3b1-synuclein in the substantia nigra pars compacta as well as increased expression of divalent metal transporter 1 (DMT1) and iron staining in both the substantia nigra pars compacta and striatum. Aged c-rel(-/-) mouse brain were characterized by increased microglial reactivity in the basal ganglia, but no astrocytic reaction. In addition, c-rel(-/-) mice showed age-dependent deficits in locomotor and total activity and various gait-related deficits during a catwalk analysis that were reminiscent of bradykinesia and muscle rigidity. Both locomotor and gait-related deficits recovered in c-rel(-/-) mice treated with l-3,4-dihydroxyphenylalanine. These data suggest that c-Rel may act as a regulator of the substantia nigra pars compacta resilience to ageing and that aged c-rel(-/-) mice may be a suitable model of Parkinson's disease

Late-onset Parkinsonism in NFκB/c-Rel-deficient mice

Activation of the nuclear factor κB/c-Rel can increase neuronal resilience to pathological noxae by regulating the expression of pro-survival manganese superoxide dismutase (MnSOD, now known as SOD2) and Bcl-xL genes. We show here that c-Rel-deficient (c-rel(-/-)) mice developed a Parkinson's disease-like neuropathology with ageing. At 18 months of age, c-rel(-/-) mice exhibited a significant loss of dopaminergic neurons in the substantia nigra pars compacta, as assessed by tyrosine hydroxylase-immunoreactivity and Nissl staining. Nigral degeneration was accompanied by a significant loss of dopaminergic terminals and a significant reduction of dopamine and homovanillic acid levels in the striatum. Mice deficient of the c-Rel factor exhibited a marked immunoreactivity for fibrillary α-synuclein in the substantia nigra pars compacta as well as increased expression of divalent metal transporter 1 (DMT1) and iron staining in both the substantia nigra pars compacta and striatum. Aged c-rel(-/-) mouse brain were characterized by increased microglial reactivity in the basal ganglia, but no astrocytic reaction. In addition, c-rel(-/-) mice showed age-dependent deficits in locomotor and total activity and various gait-related deficits during a catwalk analysis that were reminiscent of bradykinesia and muscle rigidity. Both locomotor and gait-related deficits recovered in c-rel(-/-) mice treated with l-3,4-dihydroxyphenylalanine. These data suggest that c-Rel may act as a regulator of the substantia nigra pars compacta resilience to ageing and that aged c-rel(-/-) mice may be a suitable model of Parkinson's disease

Tsunami risk communication and management: Contemporary gaps and challenges

Very large tsunamis are associated with low probabilities of occurrence. In many parts of the world, these events have usually occurred in a distant time in the past. As a result, there is low risk perception and a lack of collective memories, making tsunami risk communication both challenging and complex. Furthermore, immense challenges lie ahead as population and risk exposure continue to increase in coastal areas. Through the last decades, tsunamis have caught coastal populations off-guard, providing evidence of lack of preparedness. Recent tsunamis, such as the Indian Ocean Tsunami in 2004, 2011 Tohoku and 2018 Palu, have shaped the way tsunami risk is perceived and acted upon. Based on lessons learned from a selection of past tsunami events, this paper aims to review the existing body of knowledge and the current challenges in tsunami risk communication, and to identify the gaps in the tsunami risk management methodologies. The important lessons provided by the past events call for strengthening community resilience and improvement in risk-informed actions and policy measures. This paper shows that research efforts related to tsunami risk communication remain fragmented. The analysis of tsunami risk together with a thorough understanding of risk communication gaps and challenges is indispensable towards developing and deploying comprehensive disaster risk reduction measures. Moving from a broad and interdisciplinary perspective, the paper suggests that probabilistic hazard and risk assessments could potentially contribute towards better science communication and improved planning and implementation of risk mitigation measures

Rapid production of human liver scaffolds for functional tissue engineering by high shear stress oscillation-decellularization

The development of human liver scaffolds retaining their 3-dimensional structure and extra-cellular matrix (ECM) composition is essential for the advancement of liver tissue engineering. We report the design and validation of a new methodology for the rapid and accurate production of human acellular liver tissue cubes (ALTCs) using normal liver tissue unsuitable for transplantation. The application of high shear stress is a key methodological determinant accelerating the process of tissue decellularization while maintaining ECM protein composition, 3D-architecture and physico-chemical properties of the native tissue. ALTCs were engineered with human parenchymal and non-parenchymal liver cell lines (HepG2 and LX2 cells, respectively), human umbilical vein endothelial cells (HUVEC), as well as primary human hepatocytes and hepatic stellate cells. Both parenchymal and non-parenchymal liver cells grown in ALTCs exhibited markedly different gene expression when compared to standard 2D cell cultures. Remarkably, HUVEC cells naturally migrated in the ECM scaffold and spontaneously repopulated the lining of decellularized vessels. The metabolic function and protein synthesis of engineered liver scaffolds with human primary hepatocytes reseeded under dynamic conditions were maintained. These results provide a solid basis for the establishment of effective protocols aimed at recreating human liver tissue in vitro

Clinical features and comorbidity pattern of HCV infected migrants compared to native patients in care in Italy: A real-life evaluation of the PITER cohort

Background: Direct-acting antivirals are highly effective for the treatment of hepatitis C virus (HCV) infection, regardless race/ethnicity. We aimed to evaluate demographic, virological and clinical data of HCV-infected migrants vs. natives consecutively enrolled in the PITER cohort. Methods: Migrants were defined by country of birth and nationality that was different from Italy. Mann-Whitney U test, Chi-squared test and multiple logistic regression were used. Results: Of 10,669 enrolled patients, 301 (2.8%) were migrants: median age 47 vs. 62 years, (p < 0.001), females 56.5% vs. 45.3%, (p < 0.001), HBsAg positivity 3.8% vs. 1.4%, (p < 0.05). Genotype 1b was prevalent in both groups, whereas genotype 4 was more prevalent in migrants (p < 0.05). Liver disease severity and sustained virologic response (SVR) were similar. A higher prevalence of comorbidities was reported for natives compared to migrants (p < 0.05). Liver disease progression cofactors (HBsAg, HIV coinfection, alcohol abuse, potential metabolic syndrome) were present in 39.1% and 47.1% (p > 0.05) of migrants and natives who eradicated HCV, respectively. Conclusion: Compared to natives, HCV-infected migrants in care have different demographics, HCV genotypes, viral coinfections and comorbidities and similar disease severity, SVR and cofactors for disease progression after HCV eradication. A periodic clinical assessment after HCV eradication in Italians and migrants with cofactors for disease progression is warranted

Tsunami risk communication and management: Contemporary gaps and challenges

Supplementary data: The following is the Supplementary data to this article: Acrobat PDF file (2MB) available at: https://ars.els-cdn.com/content/image/1-s2.0-S2212420921007329-mmc1.pdfCopyright © 2022 The Authors. Very large tsunamis are associated with low probabilities of occurrence. In many parts of the world, these events have usually occurred in a distant time in the past. As a result, there is low risk perception and a lack of collective memories, making tsunami risk communication both challenging and complex. Furthermore, immense challenges lie ahead as population and risk exposure continue to increase in coastal areas. Through the last decades, tsunamis have caught coastal populations off-guard, providing evidence of lack of preparedness. Recent tsunamis, such as the Indian Ocean Tsunami in 2004, 2011 Tohoku and 2018 Palu, have shaped the way tsunami risk is perceived and acted upon. Based on lessons learned from a selection of past tsunami events, this paper aims to review the existing body of knowledge and the current challenges in tsunami risk communication, and to identify the gaps in the tsunami risk management methodologies. The important lessons provided by the past events call for strengthening community resilience and improvement in risk-informed actions and policy measures. This paper shows that research efforts related to tsunami risk communication remain fragmented. The analysis of tsunami risk together with a thorough understanding of risk communication gaps and challenges is indispensable towards developing and deploying comprehensive disaster risk reduction measures. Moving from a broad and interdisciplinary perspective, the paper suggests that probabilistic hazard and risk assessments could potentially contribute towards better science communication and improved planning and implementation of risk mitigation measures.COST (European Cooperation in Science and Technology); Royal Society, UK (grant number CHL\R1\180173); Severo Ochoa Centers of Excellence Program (CEX 2018-000797-S) funded by MCIN/ AEI /10.13039/501100011033; Lloyd's Tercentenary Research Foundation, the Lighthill Risk Network, and the Lloyd's Register Foundation-Data Centric Engineering Programme of the Alan Turing Institute

L'Italia come modello per l'Europa e per il mondo nelle politiche sanitarie per il trattamento dell'epatite cronica da HCV

The World Health Organization foresees the elimination of HCV infection by 2030. In light of this and the curre nt, nearly worldwide, restriction in direct-acting agents (DAA) accessibility due to their high price, we aimed to evaluate the cost-effectiveness of two alternative DAA treatment policies: Policy 1 (universal): treat all patients, regardless of the fibrosis stage; Policy 2 (prioritized): treat only priori tized patients and delay treatment of the remaining patients until reaching stage F3. T he model was based on patient’s data from the PITER cohort. We demonstrated that extending HC V treatment of patients in any fibrosis stage improves health outcomes and is cost-effective