Sutureless fixation of amniotic membrane for therapy of ocular surface disorders

Amniotic membrane is applied to the diseased ocular surface to stimulate wound healing and tissue repair, because it releases supportive growth factors and cytokines. These effects fade within about a week after application, necessitating repeated application. Generally, amniotic membrane is fixed with sutures to the ocular surface, but surgical intervention at the inflamed or diseased site can be detrimental. Therefore, we have developed a system for the mounting of amniotic membrane between two rings for application to a diseased ocular surface without surgical intervention (sutureless amniotic membrane transplantation). With this system, AmnioClip, amniotic membrane can be applied like a large contact lens. First prototypes were tested in an experiment on oneself for wearing comfort. The final system was tested on 7 patients in a pilot study. A possible influence of the ring system on the biological effects of amniotic membrane was analyzed by histochemistry and by analyzing the expression of vascular endothelial growth factor-A (VEGF-A), hepatocyte growth factor (HGF), fibroblast growth factor 2 (FGF 2) and pigment epithelium-derived factor (PEDF) from amniotic membranes before and after therapeutic application. The final product, AmnioClip, showed good tolerance and did not impair the biological effects of amniotic membrane. VEGF-A and PEDF mRNA was expressed in amniotic membrane after storage and mounting before transplantation, but was undetectable after a 7-day application period. Consequently, transplantation of amniotic membranes with AmnioClip provides a sutureless and hence improved therapeutic strategy for corneal surface disorders

Induction of vascular endothelial growth factor-A165a in human retinal and endothelial cells in response to glyoxal

Low-density lipoprotein (LDL) apheresis is effective and safe for patients with diabetes, proteinuria, and dyslipidemia. Diabetes mellitus is accompanied by ocular microvascular complications like retinal neovascularization or diabetic macular edema. These are leading causes of blindness and can be mediated by abnormal vessel growth and increased vascular permeability due to elevated levels of vascular endothelial growth factor (VEGF) in diabetic patients. In this study, we established methods to study the expression of different VEGF isoforms in human retinal and endothelial cells. The VEGF-A165a isoform is much higher expressed in retinal cells, compared to endothelial cells. Stimulation with glyoxal as a model of oxidative stress under diabetic conditions lead to a pronounced induction of VEGF-A165a in human retinal and endothelial cells. These data suggest that diabetes and oxidative stress induce VEGF-A isoforms which could be relevant in regulating the ingrowths of novel blood vessels into the retina in diabetic patients

The Transition between Telomerase and ALT Mechanisms in Hodgkin Lymphoma and Its Predictive Value in Clinical Outcomes

International audienceBackground: We analyzed telomere maintenance mechanisms (TMMs) in lymph node samples from HL patients treated with standard therapy. The TMMs correlated with clinical outcomes of patients. Materials and Methods: Lymph node biopsies obtained from 38 HL patients and 24 patients with lymphadenitis were included in this study. Seven HL cell lines were used as in vitro models. Telomerase activity (TA) was assessed by TRAP assay and verified through hTERT immunofluorescence expression; alternative telomere lengthening (ALT) was also assessed, along with EBV status. Results: Both TA and ALT mechanisms were present in HL lymph nodes. Our findings were reproduced in HL cell lines. The highest levels of TA were expressed in CD30−/CD15− cells. Small cells were identified with ALT and TA. Hodgkin and Reed Sternberg cells contained high levels of PML bodies, but had very low hTERT expression. There was a significant correlation between overall survival (p < 10−3), event-free survival (p < 10−4), and freedom from progression (p < 10−3) and the presence of an ALT profile in lymph nodes of EBV+ patients. Conclusion: The presence of both types of TMMs in HL lymph nodes and in HL cell lines has not previously been reported. TMMs correlate with the treatment outcome of EBV+ HL patients

RENEB accident simulation exercise

Purpose: The RENEB accident exercise was carried out in order to train the RENEB participants in coordinating and managing potentially large data sets that would be generated in case of a major radiological event. Materials and methods: Each participant was offered the possibility to activate the network by sending an alerting email about a simulated radiation emergency. The same participant had to collect, compile and report capacity, triage categorization and exposure scenario results obtained from all other participants. The exercise was performed over 27 weeks and involved the network consisting of 28 institutes: 21 RENEB members, four candidates and three non-RENEB partners. Results: The duration of a single exercise never exceeded 10 days, while the response from the assisting laboratories never came later than within half a day. During each week of the exercise, around 4500 samples were reported by all service laboratories (SL) to be examined and 54 scenarios were coherently estimated by all laboratories (the standard deviation from the mean of all SL answers for a given scenario category and a set of data was not larger than 3 patient codes). Conclusions: Each participant received training in both the role of a reference laboratory (activating the network) and of a service laboratory (responding to an activation request). The procedures in the case of radiological event were successfully established and tested

Safety of extended uses of UV-treated baker's yeast as a Novel Food pursuant to Regulation (EU) 2015/2283

In 2014, the EFSA NDA Panel&nbsp;concluded that UV-treated baker's yeast containing up to 3.5 Mio IU of vitamin D/100 g, is safe under the proposed conditions of use for yeast-leavened breads, rolls and fine bakery wares, and food supplements. Following a request from the European Commission, the EFSA Panel&nbsp;on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on an application for an extension of the use of UV-treated baker's yeast as a novel food (NF) pursuant to Regulation (EU) 2015/2283. In this extension of use, the applicant proposed a broad range of food categories to which the NF can be added. On the basis of the proposed uses and maximum use levels, the Panel&nbsp;estimated the potential exposure to vitamin D from the NF and the potential combined exposure to vitamin D including also exposure from the background diet and food supplements. The Panel&nbsp;notes that the upper level (UL) for one age group, i.e. children aged 4-10 years, is exceeded by 4%, when summing up the highest P95 estimate for the background diet (including food supplements) and the highest P95 estimate for vitamin D from the NF under the proposed uses and maximum use levels. The Panel&nbsp;notes, however, the highly conservative approach for estimating the potential intake of vitamin D from the NF, given that the applicant has proposed 34 FoodEx2 level 2 food categories. Thus, the Panel&nbsp;considers that the UL for children aged between 4 and 10 years is highly unlikely to be exceeded. The Panel&nbsp;concludes that the NF is safe under the proposed conditions of use

Safety of hydrothermally treated kernels from edible Jatropha curcas L. (Chuta) as a novel food pursuant to Regulation (EU) 2015/2283

[EN] Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on hydrothermally treated kernels from edible Jatropha curcas (Chuta) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Although Jatropha curcas is generally considered a toxic plant due to the presence of phorbol esters (PEs), edible varieties exist in Central America. The applicant has developed a breeding programme for an edible cultivar and proposes the kernels from this cultivar as an NF as whole kernels or fragments thereof to be used as a snack or as a food ingredient. Procedures are in place to avoid commingling with non-edible kernels, with the last steps being the analytical control of PEs concentrations in all produced batches. The Panel considers that the production process of the NF is sufficiently described and that the information provided on the composition of the NF is sufficient for its characterisation. Components of the NF were tested for genotoxicity applying the standard in vitro test battery and no genotoxic concerns have been identified. In a conservative scenario for exposure to PEs from the NF, it was assumed that all kernels contain PEs at the level of detection of the analytical method. When comparing the estimated maximum exposure to PEs with a reference point from a subchronic study in pigs, a margin of exposure ≥ 900 is obtained, which is considered sufficiently large. The presence of anti-nutritional factors does not pose safety concerns as they are within the ranges found in vegetables. The Panel concludes that the NF is safe under the proposed conditions of useSIThe Panel wishes to thank the Working Group on Compendium of Botanicals, Eirini Kouloura and Petra Gergelova for the support provided to this scientific outpu

Safety of zinc l-carnosine as a Novel food pursuant to Regulation (EU) 2015/2283 and the bioavailability of zinc from this source in the context of Directive 2002/46/EC on food supplements

Requestor: European Commission Question number: EFSA-Q-2020-00263 Correspondence: [email protected] reviewedPublisher PD

Safety of freeze-dried mycelia of Antrodia camphorata as a novel food pursuant to regulation (EU) 2015/2283

Requestor: European Commission Question number: EFSA-Q-2019-00759 Correspondence: [email protected] reviewedPublisher PD

Safety of dried fruits of Synsepalum dulcificum as a novel food pursuant to Regulation (EU) 2015/2283

Following a request from the European Commission, the EFSA Panel&nbsp;on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on dried fruits of Synsepalum dulcificum as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF is pitted and dried (by lyophilisation) fruits of S.&nbsp;dulcificum. The NF contains the glycoprotein miraculin (≤ 2.5%) which causes sour and acidic foods to taste sweet. The fruits have a documented history of consumption in Africa and products thereof can be found in different markets worldwide. Information on the production process and the composition of the NF is sufficient and does not raise safety concerns. The applicant proposes to use the NF as or in food supplements for the adult population, excluding pregnant and lactating women, at a maximum daily amount of 0.9 g. Taking into account these conditions of use, the Panel&nbsp;considers that the consumption of the NF is not nutritionally disadvantageous. The provided genotoxicity studies do not raise concerns for genotoxicity of the NF. The Panel&nbsp;concludes that the only dose tested in a 90-day oral toxicity study of 2,000 mg/kg body weight (bw) per day was not associated with adverse effects. By applying an uncertainty factor of 200, the Panel&nbsp;concludes that the NF is safe at an intake level of 10 mg/kg bw per day, corresponding to a maximum daily intake of 0.7 g of the NF for the target population, rather than 0.9 g/day as proposed by the applicant

Safety of calcium fructoborate as a novel food pursuant to Regulation (EU) 2015/2283

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on calcium fructoborate as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF, produced by chemical synthesis, contains a maximum of 2.9% of boron and on average 4.7% calcium and 84.2% fructose. It is intended to be marketed as food supplements targeting the general adult population, excluding pregnant and lactating women, at a maximum level of 220 mg/day (maximum boron intake of 6.4 mg per day). The combined intake of boron from the background diet and the NF is in the range of 9.6-9.9 mg/day (corresponding to up to 0.14 mg/kg body weight (bw) per day given a default bw of 70 kg). This is in the range of the acceptable daily intake (ADI) of 0.16 mg/kg bw per day. Under conditions mimicking the gastrointestinal (GI) environment, the NF is fully hydrolysed and the Panel considered boron toxicity relevant for the safety assessment. The Panel considers that there is no concern with respect to genotoxicity of the NF. The effect induced by the NF in a 13-week rat study is consistent with toxicological findings induced by treatment with boron compounds in animal studies. Epididymides-to-brain weight ratio was identified as the most relevant endpoint and the reference point derived was the lowest model averaged BMDL10 value of 529 mg/kg bw per day. This corresponds to 14.8 mg/kg bw per day of boron, which is higher than the critical no observed adverse effect level (NOAEL) (9.6 mg boron/kg bw per day) used for establishing the ADI of 0.16 mg/kg bw per day for boron. The Panel therefore applied the present ADI for boron in the assessment of the NF. The Panel concludes that the NF, calcium fructoborate, is safe under the proposed uses and use levels.Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on calcium fructoborate as a novel food (NF) pursuant to Regulation (EU) 2015/2283. The NF, produced by chemical synthesis, contains a maximum of 2.9% of boron and on average 4.7% calcium and 84.2% fructose. It is intended to be marketed as food supplements targeting the general adult population, excluding pregnant and lactating women, at a maximum level of 220 mg/day (maximum boron intake of 6.4 mg per day). The combined intake of boron from the background diet and the NF is in the range of 9.6–9.9 mg/day (corresponding to up to 0.14 mg/kg body weight (bw) per day given a default bw of 70 kg). This is in the range of the acceptable daily intake (ADI) of 0.16 mg/kg bw per day. Under conditions mimicking the gastrointestinal (GI) environment, the NF is fully hydrolysed and the Panel considered boron toxicity relevant for the safety assessment. The Panel considers that there is no concern with respect to genotoxicity of the NF. The effect induced by the NF in a 13-week rat study is consistent with toxicological findings induced by treatment with boron compounds in animal studies. Epididymides-to-brain weight ratio was identified as the most relevant endpoint and the reference point derived was the lowest model averaged BMDL10 value of 529 mg/kg bw per day. This corresponds to 14.8 mg/kg bw per day of boron, which is higher than the critical no observed adverse effect level (NOAEL) (9.6 mg boron/kg bw per day) used for establishing the ADI of 0.16 mg/kg bw per day for boron. The Panel therefore applied the present ADI for boron in the assessment of the NF. The Panel concludes that the NF, calcium fructoborate, is safe under the proposed uses and use levels