EFSA Panel on Biological Hazards (BIOHAZ); Scientific Opinion on public health risks represented by certain composite products containing food of animal origin

This Opinion reviews the factors that affect microbial survival and growth in composite products, and in foods in general. It concludes that the main factors to be considered are: water activity, pH, temperature and duration of storage, processing, and intensity and duration of other non-thermal physical processes applied. Prevalence and concentration of the pathogens in food are important to determine the risk for consumers. The opinion presents a review of the quantitative microbiology models and databases that can be used to provide quantitative estimations of the impact of the above factors on the survival and growth of the main bacterial pathogens. In composite products, migration and diffusion of moisture and substances among the ingredients may change their physico-chemical parameters, particularly at the interfaces. Therefore, the assessment of the risk posed by composite products needs to consider the combinations of parameters most permissive to survival and growth of pathogens. Two complementary approaches are proposed for the identification and profiling of microbiological hazards in different specific composite products. The first one is based on past outbreaks and prevalence of hazards in the products and leads to the conclusion that the most frequent hazard-composite product combinations are Salmonella in cakes and bakery products. The second one consists in decision tools based on the impact on the pathogens of food composition and food processing. Categorisation of the risk for composite products requires information on their composition, processing and further handling, which can largely differ for foods belonging to the same category. Further conditions may influence the risk and should be verified, i.e. hygienic conditions during preparation of the composite products and their ingredients, shelf-life conditions, and reliability of cooking by consumers to inactivate pathogens. The decision tools developed apply to all composite products considered by the mandate, as well as to all other foods. © European Food Safety Authority, 201

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Dose-dependent biphasic leptin-induced proliferation is caused by non-specific IL-6/NF-κB pathway activation in human myometrial cells.

BACKGROUND AND PURPOSE: Leptin, an adipokine synthesized by the placenta during pregnancy, has been proposed for the management of preterm labour (PTL), as it is able to prevent in vitro uterine contractility and remodelling associated with labour onset. Another common feature of labour onset is the phenotypic switch of myometrial smooth muscle cells from a proliferative to a hypertrophic state. As proliferative effects have been demonstrated for leptin in other tissues, we aimed to investigate its ability to induce myometrial proliferation and thus to maintain uterine quiescence. EXPERIMENTAL APPROACH: We stimulated human primary myometrial smooth muscle cells with leptin in the presence or absence of receptor antagonists or signalling pathway inhibitors. KEY RESULTS: Leptin induced myometrial cell proliferation in a biphasic manner. At 6.25 ng · mL(-1), leptin-induced proliferation was mediated by the leptin receptor and required the early activation of ERK1/2. At a concentration above 25 ng · mL(-1), leptin induced direct non-specific stimulation of the IL-6 receptor, leading to NF-κB activation, and exerted anti-proliferative effects. However, at 50 ng · mL(-1), leptin re-induces proliferation via IL-6 receptor stimulation that requires STAT3 and delayed ERK1/2 activation. CONCLUSIONS AND IMPLICATIONS: These data bring new insights into leptin signalling-induced myometrial proliferation and its interrelationship with the IL-6/IL-6 receptor axis. In the light of our previous work, the present study emphasizes the potential value of leptin in the pharmacological management of PTL and it also strengthens the hypothesis that leptin might be a contributory factor in the parturition-related disorders observed in obese women

Population transcriptogenomics highlights impaired metabolism and small population sizes in tree frogs living in the Chernobyl Exclusion Zone

Abstract Background Individual functional modifications shape the ability of wildlife populations to cope with anthropogenic environmental changes. But instead of adaptive response, human-altered environments can generate a succession of deleterious functional changes leading to the extinction of the population. To study how persistent anthropogenic changes impacted local species’ population status, we characterised population structure, genetic diversity and individual response of gene expression in the tree frog Hyla orientalis along a gradient of radioactive contamination around the Chernobyl nuclear power plant. Results We detected lower effective population size in populations most exposed to ionizing radiation in the Chernobyl Exclusion Zone that is not compensated by migrations from surrounding areas. We also highlighted a decreased body condition of frogs living in the most contaminated area, a distinctive transcriptomics signature and stop-gained mutations in genes involved in energy metabolism. While the association with dose will remain correlational until further experiments, a body of evidence suggests the direct or indirect involvement of radiation exposure in these changes. Conclusions Despite ongoing migration and lower total dose rates absorbed than at the time of the accident, our results demonstrate that Hyla orientalis specimens living in the Chernobyl Exclusion Zone are still undergoing deleterious changes, emphasizing the long-term impacts of the nuclear disaster

Development and validation of an OECD reproductive toxicity test guideline with the pond snail Lymnaea stagnalis (Mollusca, Gastropoda)

The OECD test guideline development program has been extended in 2011 to establish a partial life-cycle protocol for assessing the reproductive toxicity of chemicals to several mollusk species, including the great pond snail Lymnaea stagnalis. In this paper, we summarize the standard draft protocol for a reproduction test with this species, and present inter-comparison results obtained in a 56-day prevalidation ring-test using this protocol. Seven European laboratories performed semi-static tests with cultured snails of the strain Renilys (R) exposed to nominal concentrations of cadmium chloride (from 53 to 608 mu g Cd L-1). Cd concentrations in test solutions were analytically determined to confirm accuracy in the metal exposure concentrations in all laboratories. Physico-chemical and biological validity criteria (namely dissolved oxygen content >60% ASV, water temperature 20 ± 1 degrees C, control snail survival >80% and control snail fecundity >8 egg-masses per snail over the test period) were met in all laboratories which consistently demonstrated the reproductive toxicity of Cd in snails using the proposed draft protocol. Effect concentrations for fecundity after 56 days were reproducible between laboratories (68 < EC50-56d < 124 mu g L-1) and were consistent with literature data. EC50-56d and EC10-56d values were comprised within a factor of 1.8 and 3.6, respectively, which is in the range of acceptable variation defined for reference chemicals in OECD test guidelines for invertebrates. The inter-laboratory reproducibility coefficient of variation (CV) for the Cd LC50-56d values was 8.19%. The inter-laboratory comparison of fecundity within the controls gave a CV of 29.12%, while exposure to Cd gave a CV of 25.49% based on the EC50-56d values. The OECD has acknowledged the success of this prevalidation exercise and a validation ring-test involving 14 laboratories in Europe, North- and South-America is currently being implemented using four chemicals (Cd, prochloraz, trenbolone and tributyltin). (C) 2014 Elsevier Inc. All rights reserved

Modelling the effect of lactic acid bacteria from starter- and aroma culture on growth of Listeria monocytogenes in cottage cheese

Four mathematical models were developed and validated for simultaneous growth of mesophilic lactic acid bacteria from added cultures and Listeria monocytogenes, during chilled storage of cottage cheese with freshorcultured cream dressing. The mathematical models include the effect of temperature, pH, NaCl, lactic- and sorbic acid and the interaction between these environmental factors. Growthmodels were developed by combiningnew and existing cardinal parameter values. Subsequently, the reference growth rate parameters (μref at 25 °C)were fitted to a total of 52 growth rates fromcottage cheese to improvemodel performance. The inhibitingeffect of mesophilic lactic acid bacteria from added cultures on growth of L. monocytogenes was efficiently modelled using the Jameson approach. The new models appropriately predicted the maximum population density of L. monocytogenes in cottage cheese. The developed models were successfully validated by using 25 growth rates for L. monocytogenes, 17 growth rates for lactic acid bacteria and a total of 26 growth curves for simultaneousgrowth of L. monocytogenes and lactic acid bacteria in cottage cheese. These data were used in combination with bias- and accuracy factors and with the concept of acceptable simulation zone. Evaluation of predicted growth rates of L. monocytogenes in cottage cheese with fresh- or cultured cream dressing resulted in bias-factors (Bf) of 1.07–1.10with corresponding accuracy factor (Af) values of 1.11 to 1.22. Lactic acid bacteria fromadded starter culturewere on average predicted to grow16% faster than observed (Bf of 1.16 and Af of 1.32)and growth of the diacetyl producing aromaculturewas on average predicted 9% slower than observed (Bf of 0.91 and Af of 1.17). The acceptable simulation zone method showed the new models to successfully predict maximumpopulation density of L. monocytogenes when growing together with lactic acid bacteria in cottage cheese. 11 of 13 simulations of L.monocytogenes growth were within the acceptable simulation zone,which demonstratedgood performance of the empirical inter-bacterial interaction model. The new set of models can be used to predict simultaneous growth of mesophilic lactic acid bacteria and L. monocytogenes in cottage cheese during chilled storage at constant and dynamic temperatures. The appliedmethodology is likely to be applicable for safety prediction of other types of fermented and unripened dairy productswhere inhibition by lactic acid bacteria is important for growth of pathogenic microorganism