A co-ultramicronized palmitoylethanolamide/luteolin composite mitigates clinical score and disease-relevant molecular markers in a mouse model of experimental autoimmune encephalomyelitis

Background: Persistent and/or recurrent inflammatory processes are the main factor leading to multiple sclerosis (MS) lesions. The composite ultramicronized palmitoylethanolamide, an endogenous N-acylethanolamine, combined with the flavonoid luteolin, PEALut, have been found to exert neuroprotective activities in experimental models of spinal and brain injury and Alzheimer disease, as well as a clinical improvement in human stroke patients. Furthermore, PEALut enhances the expression of different myelin proteins in oligodendrocyte progenitor cells suggesting that this composite might have protective effects in MS experimental models. Methods: The mouse model of experimental autoimmune encephalomyelitis (EAE) based on active immunization with a fragment of myelin oligodendrocyte glycoprotein (MOG35-55) was used. The daily assessment of clinical score and the expression of serum amyloid A (SAA1), proinflammatory cytokines TNF-\u3b1, IL-1\u3b2, IFN-\u3b3, and NLRP3 inflammasome, as well as TLR2, Fpr2, CD137, CD3-\u3b3, and TCR-\u3b6 chain, heterodimers that form T cell surface glycoprotein (TCR), and cannabinoid receptors CB1, CB2, and MBP, were evaluated in the brainstem and cerebellum at different postimmunization days (PIDs). Results: Vehicle-MOG35-55-immunized (MOG35-55) mice developed ascending paralysis which peaked several days later and persisted until the end of the experiment. PEALut, given intraperitoneally daily starting on day 11 post-immunization, dose-dependently improved clinical score over the range 0.1-5 mg/kg. The mRNA expression of SAA1, TNF-\u3b1, IL-1\u3b2, IFN-\u3b3, and NLRP3 were significantly increased in MOG35-55 mice at 14 PID. In MOG35-55 mice treated with 5 mg /kg PEALut, the increase of SAA1, TNF- \u3b1, IL-1\u3b2, and IFN-\u3b3transcripts at 14 PID was statistically downregulated as compared to vehicle-MOG35-55 mice (p < 0.05). The expression of TLR2, Fpr2, CD137, CD3-\u3b3, TCR-\u3b6 chain, and CB2 receptors showed a significant upregulation in vehicle-MOG35-55 mice at 14 PID. Instead, CB1 and MBP transcripts have not changed in expression at any time. In MOG/PEALut-treated mice, TLR2, Fpr2, CD137, CD3-\u3b3, TCR-\u3b6 chain, and CB2 mRNAs were significantly downregulated as compared to vehicle MOG35-55 mice. Conclusions: The present results demonstrate that the intraperitoneal administration of the composite PEALut significantly reduces the development of clinical signs in the MOG35-55 model of EAE. The dose-dependent improvement of clinical score induced by PEALut was associated with a reduction in transcript expression of the acute-phase protein SAA1, TNF-\u3b1, IL-1\u3b2, IFN-\u3b3, and NLRP3 proinflammatory proteins and TLR2, Fpr2, CD137, CD3-\u3b3, TCR-\u3b6 chain, and CB2 receptors

Intelligenza, personalit\ue0, coscienza in "Una vita". Svevo e Taine

Il saggio presenta una lettura del primo romanzo di Svevo alla luce delle categorie filosofiche e psicologiche di Taine, prendendo in esame in particolare le nozioni di percezione, coscienza e personalit\ue0 nel De l\u2019Intelligence. Rispetto alla psicologia di origine sensistica degli Id\ue9ologues che presiedeva alla narrazione di Stendhal (uno dei modelli di Una vita), la rivoluzione epistemologica di Taine induce non solo mutamenti profondi di ordine narrativo e strutturale, ma influisce sui ruoli del narratore e del personaggio, e sulla costruzione dell\u2019identit\ue0 romanzesc

Cosmic voids uncovered -- first-order statistics of depressions in the biased density field

Cosmic voids are the major volume component in the matter distribution of the Universe. They posses great potential for constraining dark energy as well as for testing theories of gravity. Nevertheless, in spite of their growing popularity as cosmological probes, a gap of knowledge between cosmic void observations and theory still persists. In particular, the void size function models proposed in literature have been proven unsuccessful in reproducing the results obtained from cosmological simulations in which cosmic voids are detected from biased tracers of the density field, undermining the possibility of using them as cosmological probes. The goal of this work is to cover this gap. In particular, we make use of the findings of a previous work in which we have improved the void selection procedure, presenting an algorithm that redefines the void ridges and, consequently, their radius. By applying this algorithm, we validate the volume conserving model of the void size function on a set of unbiased simulated density field tracers. We highlight the difference in the internal structure between voids selected in this way and those identified by the popular VIDE void finder. We also extend the validation of the model to the case of biased tracers. We find that a relation exists between the tracer used to sample the underlying dark matter density field and its unbiased counterpart. Moreover, we demonstrate that, as long as this relation is accounted for, the size function is a viable approach for studying cosmology with cosmic voids.Comment: 11 pages, 6 figures, 3 tables, submitted to MNRA

Cosmological exploitation of the size function of cosmic voids identified in the distribution of biased tracers

Cosmic voids are large underdense regions that, together with galaxy clusters, filaments and walls, build up the large-scale structure of the Universe. The void size function provides a powerful probe to test the cosmological framework. However, to fully exploit this statistics, the void sample has to be properly cleaned from spurious objects. Furthermore, the bias of the mass tracers used to detect these regions has to be taken into account in the size function model. In our work we test a cleaning algorithm and a new void size function model on a set of simulated dark matter halo catalogues, with different mass and redshift selections, to investigate the statistics of voids identified in a biased mass density field. We then investigate how the density field tracers' bias affects the detected size of voids. The main result of this analysis is a new model of the size function, parameterised in terms of the linear effective bias of the tracers used, which is straightforwardly inferred from the large-scale two-point correlation function. This represents a crucial step to exploit the method on real data catalogues. The proposed size function model has been accurately calibrated on mock catalogues, and used to validate the possibility to provide forecasts on the cosmological constraints, namely on the matter density contrast, $\Omega_{\rm M}$, and on the normalisation of the linear matter power spectrum, $\sigma_8$, at different redshifts.Comment: 17 pages, 11 figures, 4 tables, accepted by MNRA

Sal y salud, el punto de vista del consumidor argentino obtenido por la técnica de grupos focales

The consumption of high levels of salt (NaCl) is associated with hypertension, and possible development of cardiovascular and cerebrovascular diseases. The aim of this study was to explore consumers’ understanding of salt in their daily diet, their perceptions and knowledge about health implications and actions to reduce salt intake. Four focus groups were conducted (31 participants): one with university students, two with working adults and one older woman’s group. Some participants were not aware of salt content of food whereas others demonstrated an awareness of salt in food, the role of salt as a preservative, affecting taste and health implications. Reducing consumption of salt tended to be a reactive event when personal/family health events took place rather than a proactive behaviour. Participants tended to consider their own consumption of salt as low/moderate but those who they lived with were perceived to have a high intake based only on table salt. The three adult focus groups expressed concerns about adding salt. Alternatives to salt such as seasonings/spices could be used as strategies to reduce its consumption. At the population level campaigns involving schools and mass media were suggested. Only university students raised the need to involve the food industry and food processors in reducing salt consumption

Curcumin Prevents Acute Neuroinflammation and Long-Term Memory Impairment Induced by Systemic Lipopolysaccharide in Mice

Systemic lipopolysaccharide (LPS) induces an acute inflammatory response in the central nervous system (CNS) (\u201cneuroinflammation\u201d) characterized by altered functions of microglial cells, the major resident immune cells of the CNS, and an increased inflammatory profile that can result in long-term neuronal cell damage and severe behavioral and cognitive consequences. Curcumin, a natural compound, exerts CNS anti-inflammatory and neuroprotective functions mainly after chronic treatment. However, its effect after acute treatment has not been well investigated. In the present study, we provide evidence that 50 mg/kg of curcumin, orally administered for 2 consecutive days before a single intraperitoneal injection of a high dose of LPS (5 mg/kg) in young adult mice prevents the CNS immune response. Curcumin, able to enter brain tissue in biologically relevant concentrations, reduced acute and transient microglia activation, pro-inflammatory mediator production, and the behavioral symptoms of sickness. In addition, short-term treatment with curcumin, administered at the time of LPS challenge, anticipated the recovery from memory impairments observed 1 month after the inflammatory stimulus, when mice had completely recovered from the acute neuroinflammation. Together, these results suggest that the preventive effect of curcumin in inhibiting the acute effects of neuroinflammation could be of value in reducing the long-term consequences of brain inflammation, including cognitive deficits such as memory dysfunction

Caracterização dos sistemas produtivos de bovinos leiteiros do município de Rondon do Pará, mesorregião Sudeste paraense.

Este trabalho caracteriza as propriedades leiterias de Rondon do Pará (04º46?45?S/48°04?00?W), Mesorregião Sudeste Paraense, estado do Pará, para auxiliar nas ações institucionais e políticas públicas, e dar suporte ao desenvolvimento da cadeia produtiva do leite. Os dados foram coletados em entrevistas realizadas em 55 propriedades leiteiras, em 2012, por pesquisadores da Embrapa Amazônia Oriental e alunos do Programa de Pós Graduação em Ciência Animal - UFPA/Embrapa Amazônia Oriental/UFRA. Inicialmente foram selecionadas cinco propriedades, cuja atividade leiteira é a principal fonte de sustento familiar, com auxílio de profissionais de instituições de extensão privadas e públicas. Posteriormente, outras propriedades foram recrutadas por meio da técnica de bola de neve, onde os produtores recomendavam outros, de mesmo perfil e dispostos a participar da pesquisa. As informações foram obtidas por técnicas de Diagnóstico Rápido Participativo (DRP), com entrevista livre e aplicação de questionário semiestruturado, com possibilidades dos produtores discorrerem sobre suas experiências, a partir do foco principal proposto, e permitir respostas livre e espontâneas. As questões foram agrupadas em nove partes: identificação da propriedade e proprietário; caracterização da propriedade; discriminação da exploração leiteira na propriedade; máquinas e equipamentos; instalações e benfeitorias rurais; sanidade do rebanho; procedimento de ordenha e manejo do rebanho; produção, comercialização e mão de obra; e informações adicionais. Os dados foram tabulados em planilha no programa Microsoft Excel 2010, para posterior análise. A produção leiteira do município estudado apresenta condições precárias, o que demonstra a necessidade da melhoria das instalações zootécnicas e manejo animal e principalmente assistência eficiente em relação às boas práticas na ordenha, bem como melhoria do sistema nutricional. O clima afeta, negativamente, a produção de forragem no decorrer do ano, fato que aliado à baixa adoção de tecnologias, reduz a produtividade média dos bovinos leiteiros das pequenas propriedades rurais