The Effect of Nucleotide-binding Oligomerization Domain (NOD) Proteins on the Secretion of Cytokines from Macrophages

The study of Nucleotide-Binding Oligomerization Domain (NOD) Proteins is a very new area of immunology, with the gene for NOD2 having only been mapped in 2001 (Ogura et al 2001). It holds particular significance for those researching autoimmune disorders such as Blau syndrome and Crohns Disease (CD), as it has been found that a mutation in the NOD2 gene is present in a substantial proportion of CD sufferers, and having the mutation increases a person‟s susceptibility to developing the disease later in life (Economou et al 2004). This review will look at the current research surrounding the NOD proteins and what products they form, and how this can be used to further our knowledge of CD and how it can be managed. It will be specifically looking into the effects that NOD proteins in macrophages have on the secretion of various pro- and anti-inflammatory cytokines and how these can be augmented by the interaction of NOD protein signalling pathways with those of other molecules in the cell

Severity scoring of manganese health effects for categorical regression

Characterizing the U-shaped exposure response relationship for manganese (Mn) is necessary for estimating the risk of adverse health from Mn toxicity due to excess or deficiency. Categorical regression has emerged as a powerful tool for exposure-response analysis because of its ability to synthesize relevant information across multiple studies and species into a single integrated analysis of all relevant data. This paper documents the development of a database on Mn toxicity designed to support the application of categorical regression techniques. Specifically, we describe (i) the conduct of a systematic search of the literature on Mn toxicity to gather data appropriate for dose-response assessment; (ii) the establishment of inclusion/exclusion criteria for data to be included in the categorical regression modeling database; (iii) the development of a categorical severity scoring matrix for Mn health effects to permit the inclusion of diverse health outcomes in a single categorical regression analysis using the severity score as the outcome variable; and (iv) the convening of an international expert panel to both review the severity scoring matrix and assign severity scores to health outcomes observed in studies (including case reports, epidemiological investigations, and in vivo experimental studies) selected for inclusion in the categorical regression database. Exposure information including route, concentration, duration, health endpoint(s), and characteristics of the exposed population was abstracted from included studies and stored in a computerized manganese database (MnDB), providing a comprehensive repository of exposure-response information with the ability to support categorical regression modeling of oral exposure data

Nutrition issues in Codex: health claims, nutrient reference values and WTO agreements: a conference report

BACKGROUND: Codex documents may be used as educational and consensus materials for member governments. Also, the WTO SPS Agreement recognizes Codex as the presumptive international authority on food issues. Nutrient bioavailability is a critical factor in determining the ability of nutrients to provide beneficial effects. Bioavailability also influences the quantitative dietary requirements that are the basis of nutrient intake recommendations and NRVs. HEALTH CLAIMS: Codex, EFSA and some national regulatory authorities have established guidelines or regulations that will permit several types of health claims. The scientific basis for claims has been established by the US FDA and EFSA, but not yet by Codex. Evidence-based nutrition differs from evidence-based medicine, but the differences are only recently gaining recognition. Health claims on foods may provide useful information to consumers, but many will interpret the information to mean that they can rely upon the food or nutrient to eliminate a disease risk. NUTRIENT REFERENCE VALUES: NRVs are designed to provide a quantitative basis for comparing the nutritive values of foods, helping to illustrate how specific foods fit into the overall diet. The INL-98 and the mean of adult male and female values provide NRVs that are sufficient when used as targets for individual intakes by most adults. WORLD TRADE ORGANIZATION AGREEMENTS: WTO recognizes Codex as the primary international authority on food issues. Current regulatory schemes based on recommended dietary allowances are trade restrictive. A substantial number of decisions by the EFSA could lead to violation of WTO agreements

The influence of precursor on the preparation of CeO2 catalysts for the total oxidation of the volatile organic compound propane

CeO2 catalysts were prepared by a precipitation method using either (NH4)2Ce(NO3)6 or Ce(NO3)3, as CeIV or CeIII precursors respectively. The influence of the different precursors on catalytic activity was evaluated for the total oxidation of propane with water present in the feed. The catalyst prepared using the CeIV precursor was more active for propane total oxidation. The choice of precursor influenced catalyst properties such as surface area, reducibility, morphology, and active oxygen species. The predominant factor associated with the catalytic activity was related to the formation of either CeO2.nH2O or Ce2(OH)2(CO3)2.H2O precipitate species, formed prior to calcination. The formation of CeO2.nH2O resulted in enhanced surface area which was an important factor for controlling catalyst activity

The use of categorical regression in evidence integration

Exposure-response assessment methods have shifted towards more quantitative approaches, with health risk assessors exploring more statistically driven techniques. These assessments, however, usually rely on one critical health effect from a single key study. Categorical regression addresses this limitation by incorporating data from all relevant studies – including human, animal, and mechanistic studies - thereby including a broad spectrum of health endpoints and exposure levels for exposure-response analysis in an objective manner. Categorical regression requires the establishment of ordered response categories corresponding to increasingly severe adverse health outcomes, and the availability of a comprehensive database that summarizes all data on different outcomes from different studies, including the exposure or dose at which these outcomes are observed and their severity. It has found application in the risk assessment of essential nutrients and trace metals. Since adverse effects may arise from either deficient or excess exposure, the exposure-response curve is U-shaped, which provides a basis for determining optimal intake levels that minimize the joint risks of deficiency and excess. This article provides an overview of the use of categorical regression fit exposure-response models incorporating data from multiple evidence streams. An extension of categorical regression that permits the simultaneous analysis of excess and deficiency toxicity data is presented and applied to comprehensive databases on copper and manganese. Future applications of categorical regression will be able to make greater use of diverse data sets developed using new approach methodologies, which can be expected to provide valuable information on toxic responses of varying severity

Zn loading effects on the selectivity of PdZn catalysts for CO2 hydrogenation to methanol

PdZn/TiO2 catalysts have been investigated for the hydrogenation of CO2 to methanol. Varying the ratio of Pd and Zn using TiO2 as a support has a dramatic effect on catalytic performance. Chemical vapour impregnation was used to produce PdZn alloys on TiO2 and X-ray diffraction, X-ray photoelectron spectroscopy, and scanning transmission electron microscopy revealed changes in the structure at varying total PdZn molar ratios. Compared to monometallic Pd/TiO2, introducing a low loading of Zn drastically changes product selectivity. When Pd is alloyed with Zn above a total Zn/Pd = 1 molar ratio, methanol selectivity is improved. Therefore, for enhanced methanol productivity, it is crucial for the Zn loading to be higher than that required for the stoichiometric formation of the 1:1 β-PdZn alloy

Guidance for establishing and applying tolerable upper intake levels for vitamins and essential minerals:Draft for internal testing

Vitamins and essential minerals are micronutrients that are essential for the normal functioning of the human body. However, they may lead to adverse health effects if consumed in excess. The concept of a tolerable upper intake level (UL) is a science-based reference value, which was introduced to support policy-makers and other relevant actors in managing the risks of excess nutrient intake. EFSA\u2019s principles for establishing ULs for vitamins and minerals were originally developed by the Scientific Committee on Food in 2000. Since then, experience has been gained and the scientific field developed. This guidance from the EFSA Panel on Nutrition, Novel Foods and Food Allergens provides an updated framework to support EFSA\u2019s UL assessments. It covers aspects related to the planning of the risk assessment (problem formulation and definition of methods) and its implementation (evidence retrieval, appraisal, synthesis, integration, uncertainty analysis). As in the previous framework, the general principles developed for the risk assessment of chemicals in food are applied (hazard identification, hazard characterisation, intake assessment, risk characterisation). Peculiar to nutrients are their biochemical and physiological roles and the specific and selective mechanisms that maintain the systemic homoeostasis and body burden of the nutrient. These must be considered when conducting a risk assessment of nutrients. This document constitutes a draft guidance that will be applied in EFSA\u2019s assessments during a 1-year pilot phase and be revised and complemented as necessary. Before finalisation of the guidance, a public consultation will be launched

Scientific opinion on the tolerable upper intake level for selenium

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the tolerable upper intake level (UL) for selenium. Systematic reviews of the literature were conducted to identify evidence regarding excess selenium intake and clinical effects and potential biomarkers of effect, risk of chronic diseases and impaired neuropsychological development in humans. Alopecia, as an early observable feature and a well‐established adverse effect of excess selenium exposure, is selected as the critical endpoint on which to base a UL for selenium. A lowest‐observed‐adverse‐effect‐level (LOAEL) of 330 μg/day is identified from a large randomised controlled trial in humans (the Selenium and Vitamin E Cancer Prevention Trial (SELECT)), to which an uncertainty factor of 1.3 is applied. A UL of 255 μg/day is established for adult men and women (including pregnant and lactating women). ULs for children are derived from the UL for adults using allometric scaling (body weight(0.75)). Based on available intake data, adult consumers are unlikely to exceed the UL, except for regular users of food supplements containing high daily doses of selenium or regular consumers of Brazil nuts. No risk has been reported with the current levels of selenium intake in European countries from food (excluding food supplements) in toddlers and children, and selenium intake arising from the natural content of foods does not raise reasons for concern. Selenium‐containing supplements in toddlers and children should be used with caution, based on individual needs

Dietary reference values for chloride

This publication is linked to the following EFSA Supporting Publications articles: http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2019.EN-1679/full, http://onlinelibrary.wiley.com/doi/10.2903/sp.efsa.2017.e15121/full This publication is linked to the following EFSA Journal article: http://onlinelibrary.wiley.com/doi/10.2903/j.efsa.2019.5778/fullPeer reviewedPublisher PD