108 research outputs found
Lâorganisation du temps libre : les foyers du soldat en Italie
LâItalie entre en guerre le 24 mai 1915, presque dix mois aprĂšs les autres puissances. Auparavant, ni lâarmĂ©e ni lâĂtat nâĂ©tudient un Ă©ventuel plan dâaction pour le temps libre des combattants. Si les autoritĂ©s civiles et militaires Ă©taient pleinement convaincues que la guerre serait de courte durĂ©e, la principale raison de cette carence trouve son origine dans la traditionnelle passivitĂ© des pouvoirs publics en matiĂšre dâassistance aux classes dĂ©favorisĂ©es, y compris concernant leur temps li..
Bergamot (Citrus bergamia Risso) fruit extracts and identified components alter expression of interleukin 8 gene in cystic fibrosis bronchial epithelial cell lines
<p>Abstract</p> <p>Background</p> <p>Cystic fibrosis (CF) airway pathology is a fatal, autosomal, recessive genetic disease characterized by extensive lung inflammation. After induction by TNF-α, elevated concentrations of several pro-inflammatory cytokines (i.e. IL-6, IL-1ÎČ) and chemokines (i.e. IL-8) are released from airway epithelial cells. In order to reduce the excessive inflammatory response in the airways of CF patients, new therapies have been developed and in this respect, medicinal plant extracts have been studied. In this article we have investigated the possible use of bergamot extracts (<it>Citrus bergamia </it>Risso) and their identified components to alter the expression of IL-8 associated with the cystic fibrosis airway pathology.</p> <p>Methods</p> <p>The extracts were chemically characterized by <sup>1</sup>H-NMR (nuclear magnetic resonance), GC-FID (gas chromatography-flame ionization detector), GC-MS (gas chromatography-mass spectrometry) and HPLC (high pressure liquid chromatography). Both bergamot extracts and main detected chemical constituents were assayed for their biological activity measuring (a) cytokines and chemokines in culture supernatants released from cystic fibrosis IB3-1 cells treated with TNF-α by Bio-Plex cytokine assay; (b) accumulation of IL-8 mRNA by real-time PCR.</p> <p>Results</p> <p>The extracts obtained from bergamot (<it>Citrus bergamia </it>Risso) epicarps contain components displaying an inhibitory activity on IL-8. Particularly, the most active molecules were bergapten and citropten. These effects have been confirmed by analyzing mRNA levels and protein release in the CF cellular models IB3-1 and CuFi-1 induced with TNF-α or exposed to heat-inactivated <it>Pseudomonas aeruginosa</it>.</p> <p>Conclusions</p> <p>These obtained results clearly indicate that bergapten and citropten are strong inhibitors of IL-8 expression and could be proposed for further studies to verify possible anti-inflammatory properties to reduce lung inflammation in CF patients.</p
A versatile clearing agent for multi-modal brain imaging
Extensive mapping of neuronal connections in the central nervous system
requires high-throughput um-scale imaging of large volumes. In recent years,
different approaches have been developed to overcome the limitations due to
tissue light scattering. These methods are generally developed to improve the
performance of a specific imaging modality, thus limiting comprehensive
neuroanatomical exploration by multimodal optical techniques. Here, we
introduce a versatile brain clearing agent (2,2'-thiodiethanol; TDE) suitable
for various applications and imaging techniques. TDE is cost-efficient,
water-soluble and low-viscous and, more importantly, it preserves fluorescence,
is compatible with immunostaining and does not cause deformations at
sub-cellular level. We demonstrate the effectiveness of this method in
different applications: in fixed samples by imaging a whole mouse hippocampus
with serial two-photon tomography; in combination with CLARITY by
reconstructing an entire mouse brain with light sheet microscopy and in
translational research by imaging immunostained human dysplastic brain tissue.Comment: in Scientific Reports 201
A follow up study on the efficacy of metadoxine in the treatment of alcohol dependence
BACKGROUND: We carried out a three months follow-up study on the efficacy of metadoxine in a cohort of alcoholics admitted to the Alcohol misuse Long-term Treatment (ALT) Unit â University of Pisa (Italy). We analyzed the clinical data, psychometric tests and blood tests of 160 alcoholics on admission and after 3 months of treatment. We compared 58 pts treated with metadoxine (MET) with 102 pts who did not receive (NULL) any drug as an adjunct to the psycho-educational interventions provided by the ALT Unit. RESULTS: At follow-up, the patients in treatment with metadoxine showed a significant improvement in the rate of complete abstinence (44.8% vs. 21.6%; chi square: 8.45, df = 1, p < 0.0037). Furthermore, the number of drop-outs at three months of treatment was also significantly lower in the MET than in the NULL group (17% vs. 57%; chi square of 23.22, df = 1, p < 0.001). CONCLUSION: Our findings support the use of metadoxine in the management of alcohol dependence. However, randomized clinical trials are necessary to confirm and replicate them. This study raises the importance of identifying new pharmacological compounds effective on the outcome of alcoholism in order to help patients to best adhere to treatment programs and to prevent the development of mental and physical complications due to chronic and heavy use of alcohol
Constitutional mismatch repair deficiencyâassociated brain tumors: report from the European C4CMMRD consortium
Abstract
Background
Malignant brain tumors (BT) are among the cancers most frequently associated with constitutional mismatch repair deficiency (CMMRD), a rare childhood cancer predisposition syndrome resulting from biallelic germline mutations in mismatch repair genes. This study analyzed data from the European "Care for CMMRD" (C4CMMRD) database to describe their clinical characteristics, treatments, and outcome with the aim of improving its diagnosis/treatment.
Methods
Retrospective analysis of data on patients with CMMRD and malignant BT from the C4CMMRD database up to July 2017.
Results
Among the 87 registered patients, 49 developed 56 malignant BTs: 50 high-grade gliomas (HGG) (with giant multinucleated cells in 16/21 histologically reviewed tumors) and 6 embryonal tumors. The median age at first BT was 9.2 years [1.1â40.6], with nine patients older than 18. Twenty-seven patients developed multiple malignancies (including16 before the BT). Most patients received standard treatment, and eight patients immunotherapy for relapsed HGG. The 3- and 5-year overall survival (OS) rates were 30% (95% CI: 19â45) and 22% (95% CI: 12â37) after the first BT, with worse prognosis for HGG (3-year OS = 20.5%). Six patients were alive (median follow-up 2.5 years) and 43 dead (38 deaths, 88%, were BT-related). Other CMMRD-specific features were cafĂ©-au-lait macules (40/41), multiple BTs (5/15), developmental brain anomalies (11/15), and consanguinity (20/38 families).
Conclusions
Several characteristics could help suspecting CMMRD in pediatric malignant BTs: giant cells on histology, previous malignancies, parental consanguinity, café-au-lait macules, multiple BTs, and developmental brain anomalies. The prognosis of CMMRD-associated BT treated with standard therapies is poor requiring new therapeutic up-front approaches
Biological and chemo-diverse characterization of Amazonian (Ecuador) Citrus petitgrains
Six Amazonian petitgrains samples from C. nobilis Lour., C. aurantium L., C. limon L. and mixture of Citrus spp.(Rutaceae), named CN, CA, CL1, CL2, C1 and C2, were chemically characterized by GC-MS and 13C NMR and evaluated for antioxidant acitivity (DPPH and b-carotene bleaching tests), for antimicrobial properties (disk diffusion method) and for antifungal capacity (agar vapour assay). CN, C1, C2 samples evidenced the most interesting results: CN (g-terpinene/linalool chemotype: 14.3%/41.6%, with a considerable amount of thymol: 9.0%), and C1 (linalool, 18.3%; sabinene, 11.6%; thymol, 5.5%), showed relevant antioxidant activity with both DPPH (IC50=3.52 and 5.48 mg/ml, respectively) and b-carotene (IC50=0.387and 0.491 mg/ml, respectively). Antibacterial properties of CN and C1 against P. mirabilis (MIC=0.61 mg/ml for both)and B. subtilis (MIC=0.61 and 0.44 mg/ml, respectively) were most probably due to thymol.C2 (geranial: 34.7%, neral: 33.1%) evidenced a valuable bioactivity against Candida albicans (MIC=0.44 mg/ml).The 50% growth inhibition (IC50) of the dermatophytes T. mentagrophytes and N. cajetani was reached with amounts ofC1, C2 and CN less than 4 ml/plate. Bioactivity of Amazonian Citrus spp. CN, C1 and C2 essential oils suggests their potential use as food preservatives or additives in cosmeceuticals as preventive against dermatophytic fungal infections
Phenotypic and genetic spectrum of epilepsy with myoclonic atonic seizures
Objective: We aimed to describe the extent of neurodevelopmental impairments andidentify the genetic etiologies in a large cohort of patients with epilepsy with myoclonicatonic seizures (MAE).Methods: We deeply phenotyped MAE patients for epilepsy features, intellectualdisability, autism spectrum disorder, and attention-deficit/hyperactivity disorderusing standardized neuropsychological instruments. We performed exome analysis(whole exome sequencing) filtered on epilepsy and neuropsychiatric gene sets toidentify genetic etiologies.Results: We analyzed 101 patients with MAE (70% male). The median age of seizureonset was 34 months (range = 6-72 months). The main seizure types were myoclonicatonic or atonic in 100%, generalized tonic-clonic in 72%, myoclonic in 69%, absencein 60%, and tonic seizures in 19% of patients. We observed intellectual disability in62% of patients, with extremely low adaptive behavioral scores in 69%. In addition,24% exhibited symptoms of autism and 37% exhibited attention-deficit/hyperactivitysymptoms. We discovered pathogenic variants in 12 (14%) of 85 patients, includingfive previously published patients. These were pathogenic genetic variants inSYNGAP1 (n = 3), KIAA2022 (n = 2), and SLC6A1 (n = 2), as well as KCNA2,SCN2A, STX1B, KCNB1, and MECP2 (n = 1 each). We also identified three newcandidate genes, ASH1L, CHD4, and SMARCA2 in one patient each.Significance: MAE is associated with significant neurodevelopmental impairment.MAE is genetically heterogeneous, and we identified a pathogenic genetic etiologyin 14% of this cohort by exome analysis. These findings suggest that MAE is a manifestationof several etiologies rather than a discrete syndromic entity
Les mises en guerre de l'Ătat
Ă partir de lâĂ©tĂ© 1914, les sociĂ©tĂ©s europĂ©ennes paraissent brutalement saisies par la guerre et, ce faisant, saisies par lâĂtat. Câest en son nom que des millions dâhommes vont sâaffronter, sous lâuniforme, et que sâopĂšre une gigantesque « mobilisation » des corps, des esprits et des ressources, pour reprendre le terme de lâĂ©poque toujours employĂ© par les historiens et les historiennes. Cent ans plus tard, alors que tous les Ătats ayant fait la guerre ont engagĂ© de vastes programmes de commĂ©moration, le moment semblait particuliĂšrement opportun pour comprendre comment lâĂtat parvient Ă faire la guerre et ce que la guerre fait Ă lâĂtat. Lâemprise de lâĂtat est-elle immĂ©diate, progressive, continue ou discontinue ? ConnaĂźt-elle des phases dâessoufflement, des ratĂ©s ? Sâaccompagne-t-elle de phĂ©nomĂšnes parallĂšles de « dĂ©prise » ? Loin de toute gĂ©nĂ©ralitĂ© ou de toute extrapolation hasardeuse, est-il possible de repĂ©rer des formes de rĂ©sistance ou dâĂ©vitement ? Interroger le processus de nationalisation des sociĂ©tĂ©s europĂ©ennes, tel est lâun des enjeux de cet ouvrage pluridisciplinaire, largement ouvert dans lâespace et dans le temps autour du point de rĂ©fĂ©rence de 1914. ComposĂ© dâenquĂȘtes bien circonscrites, lâouvrage sâinscrit dans une histoire sociale de la guerre, et permet de questionner ce qui semble une Ă©vidence, au moins en France : la spectaculaire capacitĂ© de lâĂtat Ă mobiliser, presque du jour au lendemain, une sociĂ©tĂ© tout entiĂšre.From the summer of 1914, European societies seem brutally seized by war and, as a consequence, seized by the State. In the name of the State, millions of men enrolled in the armed forces are to fight one another. Bodies, minds and resources are subjected to a gigantic "mobilization", a contemporary word still used by historians. A hundred years later, when all the warring States, as well as the States that were born from the conflict, are launching ambitious commemorative programs, the moment seems well chosen to study how the State wages war and, in return, how war transforms the State. As part of this vast topic, this international and multidisciplinary (history, political science, sociology) conference will address the invention of the War State, from the perspective of all the processes through which the event has â or does not have â an impact on the organisation, actions and conduct of the public power. The aim is to identify potential changes or limited adjustments, but always within situations of transition born from the conflict. Is the intensification of the State's hold on society immediate or gradual, continuous or discontinuous? Are there slower phases, failures? Is it paralleled with a loss of influence in other areas? Is it possible to detect forms of resistance or avoidance, while refraining from all generalizations and risky extrapolations? Questioning the process of nationalisation of European societies is one of the challenges of this multidisciplinary work, which is widely open in space and time around the 1914 key date. Composed of well-defined surveys, the book falls within a social perspective of war, and allows us to question what seems obvious, at least in France: the spectacular capacity of the State to mobilize, almost overnight, an entire society
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