Clinical reporting following the quantification of cerebrospinal fluid biomarkers in Alzheimer's disease: An international overview

Introduction: The current practice of quantifying cerebrospinal fluid (CSF) biomarkers as an aid in the diagnosis of Alzheimer's disease (AD) varies from center to center. For a same biochemical profile, interpretation and reporting of results may differ, which can lead to misunderstandings and raises questions about the commutability of tests. Methods: We obtained a description of (pre-)analytical protocols and sample reports from 40 centers worldwide. A consensus approach allowed us to propose harmonized comments corresponding to the different CSF biomarker profiles observed in patients. Results: The (pre-)analytical procedures were similar between centers. There was considerable heterogeneity in cutoff definitions and report comments. We therefore identified and selected by consensus the most accurate and informative comments regarding the interpretation of CSF biomarkers in the context of AD diagnosis. Discussion: This is the first time that harmonized reports are proposed across worldwide specialized laboratories involved in the biochemical diagnosis of AD

Rôles,impacts et services issus des élevages en Europe. Synthèse du rapport d’expertise scientifique collective

L’élevage, secteur majeur pour l’économie de nombreux territoires et structurant beaucoup de paysages ruraux européens, fait l’objet de controverses, depuis au moins une décennie, notamment du fait des dommages environnementaux qu’il engendre. Dans un tel contexte, il est apparu nécessaire d’étayer les débats en faisant le point sur l’état des connaissances scientifiques relatives aux rôles, impacts et services environnementaux, économiques et sociaux issus des élevages européens et leurs produits. Pour ce faire, les ministères français en charge de l’Environnement et de l’Agriculture ainsi que l’Agence de l’environnement et de la maîtrise de l’énergie (Ademe) ont sollicité l’Inra pour réaliser une expertise scientifique collective (ESCo) abordant conjointement les multiples conséquences sur les milieux et le climat, l’emploi et le travail, les marchés et certains enjeux sociaux et culturels, de la production et de la consommation humaine de produits d’origine animale (bovins, ovins, caprins, porcins et avicoles). L’analyse de ces diverses dimensions s’appuie sur les démarches d’évaluation rapportées dans la littérature scientifique internationale. Abordées, dans un premier temps, de manière analytique et globale, les connaissances ont ensuite été mobilisées par « bouquet de services » au sein de territoires contrastés. Les relations entre les différents impacts ou services permettent d’identifier des compromis et des leviers d’action envisageables pour les systèmes d’élevage. Livestock production is a sector of major economic importance that defines many European rural areas. It has become the focus of controversy over the past decade or more, particularly with regard to the environmental impacts it causes. In this context, it seemed useful to support this debate with a critical review of the state of scientific knowledge on the role, impacts, and services – environmental, economic, and social – associated with European livestock production. Accordingly, the French ministries responsible for Agriculture and the Environment, in cooperation with the French Environment and Energy Management Agency (ADEME), requested INRA to undertake a collective scientific assessment addressing the many consequences – for the environment and the climate, for employment and labor, for markets, and for a variety of social and cultural issues – related to the production and human consumption of animal products (cattle, sheep, goats, pigs, and poultry). Analysis of these diverse dimensions was based on assessment methods utilized and described in the international scientific literature. Using a broad, analytical overview as a starting point, the review proceeded by identifying the "service bundles" associated with livestock production in contrasting areas

Recurrent attacks of acute hepatic porphyria: major role of the chronic inflammatory response in the liver

Acute intermittent porphyria (AIP) is an inherited disorder of heme metabolism characterized by life-threatening acute neurovisceral attacks due to the induction of hepatic -aminolevulinic acid synthase 1 (ALAS1) associated with hydroxymethylbilane synthase (HMBS) deficiency. Hemin represses ALAS1 and restores metabolic equilibrium. The main issue in the medical care of AIP patients is the occurrence of debilitating recurrent attacks. Chronically ill patients require repeated hemin infusions and develop secondary hemochromatosis and have a poorer quality of life. To decipher the mechanisms underlying recurrence in AIP patients, we studied the metabolic pathways altered by chronic hemin administration. A follow-up study was conducted between 1974 and 2015 and included 602 French AIP patients, of whom 46 had recurrent AIP. Moreover, we studied the hepatic transcriptome, serum proteome, liver macrophage polarization and oxidative and inflammatory profiles of Hmbs-/- mice chronically treated by hemin and extended the investigations to 5 human explanted livers. The introduction of hemin into the pharmacopeia has coincided with a 4.4-fold increase in the prevalence of chronic patients. We show that repeated hemin infusions trigger a high level heme oxygenase 1 (HO1) response, induce a pro-oxidative iron accumulation and a complex pattern of liver inflammation with macrophage infiltration. Conclusion: chronically heme-treated AIP patients may present with symptoms of an inflammatory disease responsible for an adaptive HO1 induction that could deplete the free heme pool inducing ALAS1. Hemin remains the most effective treatment but should be restricted to patients with severe forms of AIP to prevent chronic damage

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

En Sibérie dans les années vingt, deux séances de chamanes toungouses

In Siberia, in the 1920s, two meetings of tungus shamans Laurence Delaby presents two translations of shamanic meetings taken from articles published in Soviet reviews reflecting the anti-religious struggle in the pre-war period. The author, I.M. Suslov, a specialist of Tungus shamanism reports (with the political atmosphere of the time) some facts that he himself observed in the basin of the river Ienissei.Laurence Delaby présente deux traductions de séances chamaniques extraites d'articles parus dans des revues soviétiques reflétant la lutte anti-religieuse des années d'avant-guerre. Leur auteur, I.M. Suslov, un spécialiste du chamanisme toungouse, y expose, avec la coloration politique de l'époque, des faits qu'il a observés lui-même dans le bassin du Iénisséi.Delaby Laurence, Suslov I. M. En Sibérie dans les années vingt, deux séances de chamanes toungouses. In: Cahiers de sociologie économique et culturelle, n°8, 1987. pp. 103-112

Rheological behavior of compatibilized and non-compatibilized PA6/EPM blends

The rheological properties of PA-6/EPM polymer blends, non-compatibilized and compatibilized with grafted ethylene propylene rubber (EPM-g-MA), have been investigated. Linear and non-linear (relaxation both in shear and extension) experiments were realized. Stress relaxation experiments coupled with scanning electron microscopy (SEM) analysis showed the existence of one relaxation time and non-deformed droplets for the immiscible blend, and two relaxation times and deformed droplets for the compatibilized ones, the second relaxation being more pronounced for higher compatibilizer contents. These results clearly indicate that, despite the high viscosity and elasticity ratios, if high amounts of compatibilizer are added to the blend, interfacial slip is suppressed and a high-enough adhesion between the phases is achieved for the high-viscosity dispersed phase to be deformed

Effects of forage quantity and access-time restriction on feeding behaviour, feed efficiency, nutritional status, and dairy performance of dairy cows fed indoors

International audienceOptimising feed is a key challenge for dairy livestock systems, as forage stock shortages are increasingly frequent and feed is the biggest operating cost. The aim of this experiment was to evaluate the effects of reducing forage quantity and access time on dairy performance and animal nutritional status during indoor feeding. Twenty-seven Montbéliarde and Holstein cows were randomly allocated to three groups of nine cows balanced by breed, parity, days in milk, and milk yield. The three groups were given 3.9 kg DM/day of second-cut hay and 4.5 kg/day of concentrate and either i) ad libitum access to first-cut hay (Ad Libitum group; AL), ii) 10.5 kg/day of first-cut hay (Quantity-restricted group; QR), or iii) 10.5 kg/day of first-cut hay but with access time restricted to only 2 h in the morning and 2 h in the afternoon (Quantity-and-Time-restricted group; QTR). Milk yield, composition and coagulation properties, cow nutritional status (weight, body condition score, blood metabolites) and cow activities were recorded. The AL group ingested 10 % more feed than the QR group and 16 % more feed than the QTR group. Organic matter digestibility was lower in the AL group than in the QR and QTR groups whereas feed efficiency did not differ. Milk yield was not significantly different among the three groups. Compared to the QR and QTR groups, the AL group had significantly higher milk fat (35.9 vs 32.9 and 32.8 g/kg of milk) and milk protein content (29.5 vs 27.7 and 28.5 g/kg of milk). QR and QTR cows mobilised their body fat, resulting in a lower final body condition score, and tended to have a lower blood non-esterified fatty acid concentration than the AL group. QTR cows showed greater body fat mobilisation, but their final corrected BW was not different from AL cows. Access-time restriction did not impact fat and protein content but led to decreased casein, lactose contents and casein-to-whey protein ratio. The forage savings achieved through this feed management practice could prove economically substantial when forage prices increase. This practice can be of interest in grassland systems to overcome certain climatic hazards without having to resort to purchases or to increase the farm's forage autonomy