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Background: Quercetin, a natural polyphenol with demonstrated broad-spectrum antiviral, anti-inflammatory, and antioxidant properties, has been proposed as an adjuvant for early-stage coronavirus disease 2019 (COVID-19) infection.Objective: To explore the possible therapeutic effect of quercetin in outpatients with early-stage mild to moderate symptoms of COVID-19.Methods: This was an open-label randomized controlled clinical trial conducted at the department of medicine, King Edward Medical University, Lahore, PK. Patients were randomized to receive either standard of care (SC) plus an oral quercetin supplement (500 mg Quercetin Phytosome®, 1st week, TDS: 2nd week, BDS) (n = 50, quercetin group) or SC alone (n = 50, control group).Results: After one week of treatment, patients in the quercetin group showed a speedy recovery from COVID-19 as compared to the control group, i.e., 34 patients (vs. 12 in the control group) tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (p = 0.0004), and 26 patients (vs. 12 in the control group) had their COVID-19-associated acute symptoms resolved (p = 0.0051). Patients in the quercetin group also showed a significant fall in the serum lactate dehydrogenase (LDH) mean values i.e., from 406.56 ± 183.92 to 257.74 ± 110.73 U/L, p = 0.0001. Quercetin was well-tolerated by all the 50 patients, and no side effects were reported.Conclusion: Our results, suggest the possible therapeutic role of quercetin in early-stage COVID-19, including speedy clearance of SARS-CoV-2, early resolution of the acute symptoms and modulation of the host’s hyperinflammatory response.Clinical Trial Registration:clinicaltrials.gov, identifier NCT04861298

Introduction: A group of adult septic shock patients treated with hemoperfusion (HA) with the Cytosorb® associated with CVVHD were studied to determine (a) the effects of this technique on different clinical variables; and (b) the impact of the pre CytoSorb® interval and its intensity on the outcome. Methods: The catecholamine index (CI) and the pressure-catecholamine Index (PCAI) were used to assess the amount of catecholamine administered at baseline and during the procedure, respectively. The pre-treatment time was calculated since the onset of the septic-shock related hypotension and the initiation of the first session and the intensity was assessed considering either the total volume of blood processed and the duration of the HA. Results: Overall, 51 patients with septic shock (30 m, 21 f), age 68 years (IQR 59–76) were retrospectively enrolled in the study; 26 were discharged alive form the ICU (S) and 25 died in ICU (NS); in the S group either CI and PCAI decreased significantly but in NS the CI increased and the PCAI remained stable in NS. In S, the time elapsing from the onset of symptoms and the start of Cytosorb® was shorter than in NS; the duration of the treatment and the volume of blood processed were significantly higher in S than in NS. Conclusions: In this group of septic shock patients, the earlier initiation of Cytosorb®, its longer duration and the higher volume of blood processed were associated with a better survival.

OBJECTIVES The aim of this study was to evaluate the short- to mid-term outcomes of descending thoracic aortic aneurysm (DTAA) repair from the Gore Global Registry for Endovascular Aortic Treatment (GREAT). METHODS This is a multicentre sponsored prospective observational cohort registry. The study population comprised those treated for DTAA receiving GORE thoracic aortic devices for DTAA repair between August 2010 and October 2016. Major primary outcomes were early and late survival, freedom from aorta-related mortality and freedom from aorta-related reintervention. RESULTS There were 180 (58.1%) males and 130 (41.9%) females: the mean age was 70 ± 11 years (range 18–92). The median maximum DTAA diameter was 60 mm (interquartile range 54–68.8). Technical success was achieved in all patients. Operative mortality, as well as immediate conversion to open repair, was never observed. At the 30-day window, mortality occurred in 4 (1.3%) patients, neurological events occurred in 4 (1.3%) patients (transient ischaemic attacks/stroke n = 3, paraplegia n = 1) and the reintervention rate was 4.5% (n = 14). Estimated survival was 95.6% [95% confidence interval (CI) 92.6–97.4] at 6 months, 92.7% (95% CI 89.1–95.2) at 1 year and 57.3% (95% CI 48.5–65.1) at 5 years. Freedom from aorta-related mortality was 98.3% (95% CI 96.1–99.3) at 6 months, 98.3% (95% CI 96.1–99.3) at 1 year and 92.2% (95% CI 83.4–96.4) at 5 years. Freedom from thoracic endovascular aortic repair (TEVAR)-related reintervention at 5 years was 87.2% (95% CI 81.2–91.4). CONCLUSIONS TEVAR for DTAAs using GORE thoracic aortic devices is associated with a low rate of device-related reinterventions and is effective at preventing aorta-related mortality for up to 5 years of follow-up. Clinical registration number NCT number: NCT01658787. Subject collection 161, 164.

ObjectiveWe have encountered broken or damaged polypropylene sutures (Prolene®) at the anastomotic sites during aortic reoperations. Because a surgical sealant, bovine serum albumin-glutaraldehyde (BioGlue®), was used in previous aortic surgery in some of these cases, we undertook this in vitro study to evaluate whether the use of BioGlue® was associated with breakage of polypropylene sutures at the aortic anastomosis.Materials and methodsThe broken polypropylene sutures, anastomotic sites and aortic tissue at the location of suture breakage were visually inspected and evaluated intraoperatively. Six human cadaveric aortic samples were incised circumferentially and anastomosed proximally to a valved conduit with running 4–0 polypropylene sutures (Prolene®). In the test group (n = 3), BioGlue® was applied directly to the Prolene® sutures at the anastomotic sites, while in the control group (n = 3) the anastomoses were not sealed with any surgical adhesive. The six samples were immersed in Dulbecco's phosphate buffered saline solution and mounted on a M-6 Six Position Heart Valve Durability Testing System and tested up to 120 million cycles for a 2-year period. During and upon completion of the testing, the integrity of Prolene® sutures, the anastomosis and aortic tissues was regularly assessed by visual inspection.ResultsIntraoperative findings included a stretched and thin aortic wall (some with thrombus), a small cleft between the aortic tissue and the Dacron vascular graft. An excessive amount of BioGlue® was often found around the anastomosis, with cracking material, but no signs of mechanical damage were observed in these cases. Upon visual inspection during and after in vitro testing, there was no apparent damage to the polypropylene sutures on the interior or exterior of the aortic anastomoses in any of the samples. No difference was observed in the physical integrity of the polypropylene sutures at anastomotic lines, the anastomoses and aortic tissues between the test and control samples.ConclusionsThe results of this study suggest that the use of BioGlue® was not associated with breakage of the polypropylene sutures at the anastomotic sites after aortic dissection repair.

Background: Berberine is a natural alkaloid with hypoglycemic properties. However, its therapeutic use is limited by a very low oral bioavailability. Here we developed a new oral formulation of berberine based on Sucrosomial® technology and tested its effect on insulin resistance. Methods: Sucrosomial® berberine was first tested in vitro in the hepatoma cell line Huh7 to assess its effect on proteins involved in glucose homeostasis and insulin resistance. The pharmacokinetics and efficacy on insulin resistance were then studied in C57BL/6 mice fed with standard (SD) and high-fat diet (HFD) for 16 weeks and treated daily during the last 8 weeks with oral gavage of Sucrosomial® berberine or berberine. Results: Sucrosomial® berberine did not affect Huh7 cell viability at concentrations up to 40 µM. Incubation of Huh7 with 20 µM of Sucrosomial® and control berberine induced glucokinase (GK) and the phosphorylation of 5′-adenosine monophosphate (AMP)-activated protein kinase (AMPK), both known targets for the control of insulin resistance. In vivo, we observed an 8-fold higher plasma concentration after 3 weeks of oral administration of 50 mg/kg/day of Sucrosomial® formulation compared to berberine. HFD, compared to SD, induced insulin resistance in mice as determined by oral glucose tolerance test (OGTT). The treatment with a 6.25 mg/kg/daily dose of Sucrosomial® berberine significantly reduced the area under the curve (AUC) of OGTT (73,103 ± 8645 vs. 58,830 ± 5597 mg/dL × min), while control berberine produced the same effects at 50 mg/Kg/day (51518 ± 1984 mg/dL × min). Under these conditions, the two formulations resulted in similar berberine plasma concentration in mice. Nevertheless, a different tissue distribution of metabolites was observed with a significant accumulation of reduced, demethylated and glucuronide berberine in the brain after the oral administration of the Sucrosomial® form. Glucuronide berberine plasma concentration was higher with Sucrosomial® berberine compared to normal berberine. Finally, we observed similar increases of AMPK phosphorylation in the liver in response to the treatment with Sucrosomial® berberine and berberine. Conclusions: The Sucrosomial® formulation is an innovative and effective technology to improve berberine gastrointestinal (GI) absorption with proven in vitro and in vivo activity on insulin resistance.

Purpose: To identify a new cortical vitreous segmentation protocol for non invasive standardised investigation of Neovascularisation (NV) with detection of regression of NV activity in Proliferative Diabetic Retinopathy (PDR). Design: Retrospective study. Participants: One hundred and eighty-six eyes of 93 consecutive diabetic patients (mean age: 52.6 ± 11.0 years) imaged using Topcon Triton® Swept-Source Optical Coherence Tomography Angiography (SS-OCTA) from June 2015 to January 2017. Methods: Scans were performed through the macula, optic disc and areas of possible NV in mid-peripheral retina using 6 × 6 mm and/or 9 × 9 mm raster-patterns in three segmentation protocols: Vitreo-Retinal (VRS), Outer-Vitreous (OVS) and Core-Vitreous Segmentation (CVS). Any suspicion of PDR was confirmed in all patients by Heidelberg® Widefield-Fundus-Fluorescein-Angiography (WF-FFA) and/or Optos® Ultra-WF-FFA (UWF-FFA). Inter-observer reproducibility of NV diagnosis and agreement between SS-OCTA and UWF-FFA were assessed. Primary outcome was the identification of an effective and reproducible segmentation protocol. Secondary outcome was the identification of NV regression after treatment. Results: Sensitivity-specificity reached, respectively, the value of 100 to 100 in detecting NVD, and 96.6 to 100 in detecting NVE in compared areas. SS-OCTA was able to confirm absence of blood flow within the residual NV plexus when using VRS protocol in 30 eyes in which regression of NV with absence of leakage was documented on FFA. Conclusion: Three segmentation protocols (VRS, OVS and CVS) with different but complementary characteristics, allowed a reproducible and standardised investigation of NVD and NVE. The proposed new SS-OCTA cortical vitreous segmentation protocols may be of value when identifying and assessing NV-activity (VRS, OVS and CVS) or NV-regression (VRS) in PDR and therefore, response to therapy.

Purpose: To investigate the long-term safety (primary endpoint) and effectiveness (secondary endpoint) of the somatropin biosimilar Omnitrope®. Methods: PATRO Children is an ongoing, multicenter, observational, post-marketing surveillance study. Children who received Omnitrope® for any indication were included. Adverse events (AEs) were evaluated in all study participants. Auxological data, including height standard deviation scores (HSDS) and height velocity standard deviation scores (HVSDS), were used to assess effectiveness. In this snapshot analysis, data from the Italian subpopulation up to August 2017 were reported. Results: A total of 291 patients (mean age 10.0 years, 56.0% male) were enrolled at 19 sites in Italy. The mean duration of Omnitrope® treatment was 33.1 ± 21.7 months. There were 48 AEs with a suspected relationship to the study drug (as reported by the investigator) that occurred in 35 (12.0%) patients, most commonly headache, pyrexia, arthralgia, insulin-like growth factor above normal range, abdominal pain, pain in extremity and acute gastroenteritis. There were no confirmed cases of type 1 or type 2 diabetes; however, two patients (0.7%) had impaired glucose tolerance that was considered Omnitrope® related. The mean HSDS increased from − 2.41 ± 0.73 at baseline (n = 238) to − 0.91 ± 0.68 at 6.5 years (n = 10). The mean HVSDS increased from − 1.77 ± 1.38 at baseline (n = 136) to 0.96 ± 1.13 at 6.5 years (n = 10). Conclusions: In this sub-analysis of PATRO Children, Omnitrope® appeared to have acceptable safety and effectiveness in the treatment of in Italian children, which was consistent with the earlier findings from controlled clinical trials.

The unavailability of fresh water is one of the main concerns for horticulture nowadays and it is supposed to get worse in the coming future. Some crops are more vulnerable than others to drought stress such as leafy vegetables. It is therefore essential to identify and select cultivars that can overcome this kind of abiotic stress with limited or no substantial reduction in final yield, and to do it in a fast and effective way. High throughput phenotyping combined with advances in genome sequences provide efficient and reproducible approaches that are facilitating the discovery of genes and cultivars with improved plant performance under sub-optimal conditions. Drought resistance of two different Salanova® cultivars, ‘Aquino’ (green butterhead) and ‘Barlach’ (red butterhead), was tested, by using PlantScreen™, a high-throughput non-invasive imaging platform developed at Photon Systems Instruments (PSI, Czech Republic). The two cultivars performed similarly in both control (70% soil water content) and mild drought stress conditions (40% soil water content). The results demonstrated that ‘Aquino’ grew faster in control conditions at early growth phase, while in later phase it is the red ‘Barlach’ that reached larger biomass. In drought conditions growth performance of both cultivars was rapidly compromised. However, ‘Barlach’ grew better and had improved biomass in both control and mild-drought stress conditions in comparison with ‘Aquino’. Light curve protocol was used to address light use efficiency of the two cultivars. Interestingly, we observed a rapid decline in PS II operating efficiency already three days upon mild drought stress initiation. Nevertheless, there was no obvious difference in the performances between the two cultivars. In conclusion, the results of quantitative analysis of plant growth and photosynthetic performance, allowed to set up a protocol for high-throughput image-based analysis of different morpho-physiological traits associated with the early phase of drought response.

The purpose of this work is the calibration of a numerical model for simulating the interaction of waves with a composite caisson having an internal rubble mound to dissipate incident sea wave energy. In particular, the analysis focused on the reflection coefficient and the pressure distribution at the caisson vertical walls. The numerical model is based on the Volume-Average Reynolds-Averaged Navier–Stokes (VARANS) equations. Through three closure terms (linear, nonlinear, and transition), such equations take into account some phenomena that cannot be dealt when the volume-average method is used (i.e., frictional forces, pressure force, and added mass). To reproduce properly the real phenomena, a calibration process of such terms is necessary. The reference data used in the calibration process were obtained from an experimental campaign carried out at the Hydraulics Laboratory of the University of Messina. The calibration process allowed the proper prediction of certain phenomena to be expressed as a function of different closing terms. In particular, it was estimated that the reflection coefficient and the wave loading at the frontal wall are better reproduced when all three terms are considered, while the force at the rear wall is better simulated when the effects of such terms are neglected.

Background The present clinical field trial was conducted to assess the efficacy of a broad-spectrum parasiticide spot-on formulation containing eprinomectin (Broadline®) against Thelazia callipaeda eyeworm in naturally infected cats. Methods Fifteen privately owned cats harboring at least one live adult T. callipaeda were included in the study. Cats were randomly allocated to an untreated control group of seven cats or to a Broadline®-treated group of eight cats. Cats were treated on Day 0; ocular examinations were performed at inclusion and on Days 7 and 14; eyeworms were recovered and counted on Day 14. The primary efficacy assessment was based on group comparison of number of T. callipaeda on Day 14. Results Seven days after treatment, six of eight treated cats were negative for eyeworm infection per visual examination, and on Day 14 no eyeworms were found in the treated cats while the seven untreated cats were still infected (geometric mean: 1.97). All cats had inflammatory ocular signs at inclusion; on Day 14, five of eight treated cats had recovered while all untreated control cats were still symptomatic. All collected parasites were confirmed to be T. callipaeda by morphology and molecular characterization. Conclusions A single treatment with Broadline® provided 100% efficacy against feline thelaziosis and improved related ocular inflammation signs. Graphical abstract

Following an application from Praline i Cokolada j.d.o.o. submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Croatia, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to MegaNatural (R)-BP grape seed extract and maintenance of normal blood pressure. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. MegaNatural (R)-BP, a grape seed extract standardised for total phenolics, gallic acid and the catechin and epicatechin content, is sufficiently characterised. The proposed claimed effect, maintenance of normal blood pressure (BP), is a beneficial physiological effect. Among the two human intervention studies provided from which conclusions could be drawn, one showed an effect of MegaNatural (R)-BP (300 mg/day) on BP in adults with normal and high normal BP when consumed daily for 6 weeks, whereas the second study did not show an effect of MegaNatural (R)-BP at the same daily dose consumed for 8 weeks in adults with normal and high normal blood pressure or stage 1 hypertension. The evidence provided did not establish a plausible mechanism by which the food could exert the claimed effect in vivo in humans. The evidence provided is insufficient to establish a cause and effect relationship between the consumption of MegaNatural (R) BP and maintenance of normal blood pressure. (C) 2021 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

Two commercial organosilicons, Hydrophase®, a monomeric dispersion, and Disboxan 450®, an oligomeric dispersion, were studied in pure form and applied on acrylic paint replicas. Their physico-chemical characteristics, coating properties, and interaction with acrylic paint replicas were evaluated by TG, DSC, FTIR, and contact angle measurements. Hydrophase® showed a higher interaction when used on the top of acrylic paint replicas than Disboxan 450®. No appreciable modification was detected after two years of natural ageing.

A simple and efficient method for the synthesis of 4‑organoselanyl-1H-pyrazoles has been developed, taking place under metal- and halogen-free conditions. Electrophilic species of selenium were easily generated in situ by the reaction of diorganyl diselenides with Oxone® in ethanol as solvent in an open-flask at 70 °C. These electrophilic selenium species were employed in the selenylation/cyclization of α,β-alkynyl hydrazones, giving the title compounds in moderate to excellent yields. The final species of selenium obtained from the reaction of diphenyl diselenide with Oxone® were characterized by 77Se NMR spectroscopy and high-resolution mass spectrometry (HRMS).

Aims: To determine efficacy and safety of intravenous hepatitis B immune globulin (Niuliva®, Grifols) to prevent reinfection in de novo orthotopic liver transplantation. Patients & methods: In a nonrandomized, noncontrolled and Phase III clinical trial, 15 adult patients (12 men) were treated with Niuliva from the anhepatic phase (10,000 IU/daily 1 week postsurgery) up to 6 or 12 months (5000 IU/weekly 1 month; 5000 IU/monthly thereafter). Results: No patients showed reinfection throughout the study. Niuliva was effective in maintaining antibody titers above the thresholds recommended by the European Medicines Agency (EMA) to prevent reinfection (100–150 IU/l). Four serious adverse events were reported in three patients (none related to the study product). There were no seroconversions and no deaths. Conclusion: Long-term, high-dose Niuliva administration was safe and effective to prevent graft reinfection in the tested patients.

Introduction Restorative proctocolectomy has gained acceptance in the surgical management of medically refractive ulcerative colitis and cancer prevention in familial adenomatous polyposis. Incontinence following restorative proctocolectomy occurs in up to 25% of patients overnight. The Renew® insert is an inert single-use device which acts as an anal plug. The aim of this study was to assess the acceptability, effectiveness and safety of the Renew® insert in patients who have undergone restorative proctocolectomy. The device has yet to be assessed in patients who have undergone restorative proctocolectomy. Method This was a prospective study exploring the acceptability, effectiveness and safety of the Renew® insert in improving incontinence in patients who had undergone restorative proctocolectomy. A total of 15 patients with incontinence were asked to use the Renew® insert for 14 days following their standard care. The Incontinence Questionnaire-Bowels was used pre- and posttreatment to assess response and patients were asked to report the perceived acceptability, effectiveness and safety of the device at the end of the trial. Results The device was acceptable to 8/15 (53%) of patients and was effective in 6/15 (40%). Only 2/15 (13%) of patients raised any safety concerns, and these were minor. The device was associated with a significant reduction in night seepage (P = 0.034). Conclusion In a small study, the Renew® insert can be both acceptable and effective and is also associated with few safety concerns. It is also associated with significant reductions in night-time seepage.

The additive Biosprint® contains viable cells of Saccharomyces cerevisiae MUCL 39885 and is authorised as a feed additive in sows, dairy cows, horses, piglets (weaned), cattle for fattening, minor ruminants for fattening and minor ruminants for dairy products. The applicant has requested to extend the use of the additive to cats and dogs at a minimum inclusion level of 7 × 1010 CFU/kg of complete feed. S. cerevisiae is considered by EFSA to have qualified presumption of safety status and consequently is considered safe for the target species. The additive is considered as a potential skin and eye irritant and a skin and respiratory sensitiser. Based on the results on efficacy studies provided, the FEEDAP Panel concludes that Biosprint® is efficacious when used in feeds for dogs. However, the FEEDAP Panel considered that the biological relevance of the magnitude of the effect detected is questionable. Based on the trial available, the FEEDAP Panel was unable to conclude on the efficacy of the additive when administered to cats.

Following a request from the European Commission, the Panelon Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the feed additive consisting of four bacteriophages infecting Salmonella Gallinarum B/00111 (PCM F/00069, PCM F/00070, PCM F/00071 and PCM F/00097, trade name: Bafasal®) when used as a zootechnical additive in water for drinking and liquid complementary feed for all avian species. The effects sought are the reduction of the Salmonella spp. carriage in chickens for fattening, the improvement of their performance, or both. The host strain harbours an acquired antimicrobial resistance gene. No viable cells or DNA from the host organism were found in the additive. The four phages proved to be strictly lytic and to have a machinery allowing to package a unit-length of the viral genome. The manufacturing process excludes the presence of remnants from the propagation process in the final additive. Consequently, no concerns are expected from the nature and manufacture of the product. Considering this and the results of the tolerance study with chickens for fattening, the Panelconcluded that Bafasal® is safe for all avian species. Considering the nature and manufacturing process of the additive, Bafasal® is not expected to pose a risk for consumers. The results of the subchronic oral toxicity study and genotoxicity studies provided support this conclusion. Exposure of users via inhalation is expected to be low, but Bafasal® should be considered a respiratory sensitiser. No conclusions were drawn on the irritancy of Bafasal® to skin and eyes or on its dermal sensitisation potential due to lack of data. Considering the nature and manufacturing process of the additive, Bafasal® is safe for the environment. The Panelwas not in the position to conclude on the efficacy of Bafasal® for any avian species due to insufficient data.

Following an application from Sensus B.V. (Royal Cosun), submitted for authorisation of a health claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of the Netherlands, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to Frutalose (R) and maintenance of normal defecation. The scope of the application was proposed to fall under a health claim based on newly developed scientific evidence. The Panel considers that Frutalose (R), a mixture of fructans obtained from enzymatic hydrolysis of chicory inulin, is sufficiently characterised. The claimed effect proposed by the applicant is 'contributes to regular bowel function by increasing stool frequency'. The proposed target population is 'the general healthy adult population'. Maintenance of normal defecation is a beneficial physiological effect provided that it does not result in diarrhoea. One human intervention study showed an effect of Frutalose (R) on the maintenance of normal defecation by increasing stool frequency and improving stool consistency (softer stools) when consumed daily at a dose of 15 g for 8 weeks. The results have not been replicated in other studies. There is a plausible mechanism by which Frutalose (R) could exert the claimed effect. The Panel concludes that the evidence provided is insufficient to establish a cause and effect relationship between the consumption of Frutalose (R) and maintenance of normal defecation under the proposed conditions of use. (C) 2021 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

Following a request from the European Commission, EFSA Panelon Additives and Products or Substances used in Animal Feed was asked to deliver a scientific opinion on the safety and efficacy of Bonvital® for laying hens. Bonvital® is an additive containing viable cells of Enterococcus faeciumDSM 7134 marketed in two forms, a granular and a powder form, both with a guaranteed minimum concentration of E. faeciumDSM 7134 of 1.0×1010 colony forming units (CFU)/g additive. Bonvital® in either form is intended for use in feed for laying hens at the minimum concentration of 1.0×109 CFU/kg complete feed and at the maximum concentration of 1.0×1010 CFU/kg feedingstuffs. Bonvital powder® is also proposed for use in water for drinking at the minimum concentration of 5.0×108 CFU/L. The use of Bonvital® in animal nutrition is considered safe for the target animals. The results of a tolerance trial in which hens were fed the additive at 10-fold the maximum recommended dose support this conclusion. Delivery of comparable doses of the additive via water for drinking is considered as safe for laying hens. Bonvital® at the proposed conditions of use is safe for consumers of products derived from animals fed the additive and for the environment. Bonvital® is not a dermal or ocular irritant but a potential dermal and respiratory sensitiser. Bonvital® has the potential to be efficacious in improving the hen's performance when supplemented at 1.0×109 CFU/kg feed or 5.0×108 CFU/L water for drinking.

Summary: FRAX® calculates the 10-year probability of major osteoporotic fractures (MOF), which are considered to have a greater clinical impact than other fractures. Our results suggest that, in postmenopausal women with severe osteoporosis, those treated with teriparatide had a 60% lower risk of FRAX®-defined MOF compared with those treated with risedronate. Introduction: The VERO trial was an active-controlled fracture endpoint clinical trial that enrolled postmenopausal women with severe osteoporosis. After 24 months, a 52% reduction in the hazard ratio (HR) of clinical fractures was reported in patients randomized to teriparatide compared with risedronate. We examined fracture results restricted to FRAX®-defined major osteoporotic fractures (MOF), which include clinical vertebral, hip, humerus, and forearm fractures. Methods: In total, 1360 postmenopausal women (mean age 72.1 years) were randomized to receive subcutaneous daily teriparatide (20 μg) or oral weekly risedronate (35 mg). Patient cumulative incidence of ≥ 1 FRAX®-defined MOF and of all clinical fractures were estimated by Kaplan-Meier analyses, and the comparison between treatments was based on the stratified log-rank test. Additionally, an extended Cox model was used to estimate HRs at different time points. Incidence fracture rates were estimated at each 6-month interval. Results: After 24 months, 16 (2.6%) patients in the teriparatide group had ≥ 1 low trauma FRAX®-defined MOF compared with 40 patients (6.4%) in the risedronate group (HR 0.40; 95% CI 0.23–0.68; p = 0.001). Clinical vertebral and radius fractures were the most frequent FRAX®-defined MOF sites. The largest difference in incidence rates of both FRAX®-defined MOF and all clinical fractures between treatments occurred during the 6- to 12-month period. There was a statistically significant reduction in fractures between groups as early as 7 months for both categories of clinical fractures analyzed. Conclusion: In postmenopausal women with severe osteoporosis, treatment with teriparatide was more efficacious than risedronate, with a 60% lower risk of FRAX®-defined MOF during the 24-month treatment period. Fracture risk was statistically significantly reduced at 7 months of treatment. Clinical trial information: ClinicalTrials.gov Identifier: NCT01709110 EudraCT Number: 2012-000123-41., SCOPUS: ar.j, info:eu-repo/semantics/published

An accurate description of interactions between thermal neutrons (below 4 eV) and materials is key to simulate the transport of neutrons in a wide range of applications such as criticality-safety, reactor physics, compact accelerator-driven neutron sources, radiological shielding or nuclear instrumentation, just to name a few. While the Monte Carlo transport code Geant4 was initially developed to simulate particle physics experiments, %-with a large emphasis given on modeled cross-sections for all known particles at all conceivable energies-, its use has spread to neutronics applications, requiring evaluated cross-sections for neutrons and gammas between $0$ and $20$ MeV (the so-called neutron High Precision -HP- package), as well as a proper offline or on-the-flight treatment of these cross-sections. In this paper we will point out limitations affecting Geant4 (version 10.07.p01) thermal neutron treatment and associated nuclear data libraries, by using comparisons with the reference Monte Carlo neutron transport code \tripoli, version 11, and we will present the results of various modifications of the Geant4 neutron-HP package, required to overcome these limitations. Also, in order to broaden the support of nuclear data libraries compatible with Geant4, a nuclear processing tool has been developed and validated allowing the use of the code together with ENDF-BVIII.0 and JEFF-3.3 libraries for example. These changes should be taken into account in an upcoming Geant4 release., 10 pages, 9 figures

Following a request from the European Commission, the Panelon Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of TechnoSpore® (Bacillus coagulans DSM 32016), when used as a zootechnical additive for piglets (suckling and weaned), other growing Suidae, chickens for fattening, other poultry for fattening and ornamental birds. The bacterial species present in the additive is considered suitable for the qualified presumption of safety approach to safety assessment. The identity of the active agent was established and the lack of toxigenic potential confirmed. B. coagulans DSM 32016 did not show resistance to antibiotics of human and veterinary importance, and therefore, was presumed safe for the target species, consumers of products derived from animals Fed the additive and the environment. Since the other components of the additive did not give rise to concerns, TechnoSpore® was also considered safe for the target species, consumer and the environment. The additive is not a skin/eye irritant or a skin sensitiser but should be considered a respiratory sensitiser. TechnoSpore® showed the potential to be efficacious as a zootechnical additive in weaned piglets and chickens for fattening at 1×109 CFU/kg complete feed. This conclusion was extended to suckling piglets and extrapolated to other growing Suidae at the same physiological stage and to other birds for fattening and ornamental birds at the same use level. B. coagulans DSM 32016 included in Technospore® is compatible with halofuginone and diclazuril. The Panelcould not conclude on the compatibility of the additive with monensin sodium, decoquinate, robenidine hydrochloride, lasalocid sodium, narasin, salinomycin sodium, maduramicin ammonium, nicarbazin and narasin/nicarbazin.

Scientists, extensions specialists, and growers are seeking sustainable agricultural practices that are able to cope with these objectives in order to ensure global food security and minimize environmental damage. The use of mulching films and plant biostimulants in agriculture seems to be a valid solution for tackling these rising concerns. A greenhouse experiment was conducted in order to elucidate the morpho-physiological and nutritive characteristics of lettuce (Lactuca sativa L.) in response to foliar application of a tropical plant extract (PE) biostimulant and the use of plastic mulches. Two biodegradable mulch treatments (Mater-Bi&reg, 1 and Mater-Bi&reg, 2) were compared to black polyethylene (LDPE) and bare soil. Biodegradable mulch film Mater-Bi&reg, 1 produced a comparable marketable fresh yield to the commercial standard polyethylene (LDPE), whereas Mater-Bi&reg, 2 exhibited the highest crop productivity. When averaged over biostimulant application, lettuce plants grown with biodegradable film Mater-Bi&reg, 2 exhibited superior quality traits in terms of K, Ca, total ascorbic acid, and carotenoids content. The combination of film mulching (LDPE, Mater-Bi&reg, 1 or Mater-Bi&reg, 2) with the tropical plant extract biostimulant exhibited a positive and significant synergistic effect (+30%) on yield. The PE-biostimulant induced higher values of SPAD index and total chlorophyll content when compared to untreated greenhouse lettuce. The mineral content of leaf tissues was greater by 10% and 17% (for P and Ca, respectively) when compared to the untreated lettuce (no PE application). Nitrate content was significantly reduced by 23% in greenhouse lettuce plants receiving PE as compared to the untreated control. The positive effect of Mater-Bi&reg, 2 film on the ascorbic acid content has also been highlighted when combined with the biostimulant application, where a major amplification of total ascorbic acid (+168%) was recorded in comparison to the untreated lettuce. Overall, our work can assist leafy vegetables growers in adopting good agricultural practices, such as biodegradable plastic mulches and vegetal-derived biostimulants, to improve the sustainability of greenhouse production.

Research into non-hormonal, alternative therapies is necessary for women for whom menopausal hormone therapy is contraindicated or for women who do not wish to take hormones. This review focuses on one such non-hormonal option, namely, purified and specific cytoplasmic pollen extract, or PureCyTonin (R). This extract has been evaluated in several preclinical and clinical studies, where it demonstrated its value as a safe and non-estrogenic alternative for menopause. This review presents the beneficial effects of PureCyTonin (R) in the treatment of menopausal symptoms (e.g. hot flushes) in healthy women, as well as in premenstrual syndrome. We discuss the mechanism of action of PureCyTonin (R), an SSRI-'like' therapy. The lack of estrogenic effect demonstrated in preclinical studies suggests that PureCyTonin (R) may also be a suitable option for the management of menopausal symptoms in women with breast cancer.

Zirconia-toughened alumina (ZTA) currently represents the bioceramic gold standard for load-bearing components in artificial hip joints. ZTA is long known for its high flexural strength and fracture toughness, both properties arising from a microscopic crack-tip shielding mechanism due to the stress-induced tetragonal-to-monoclinic (t&rarr, m) polymorphic transformation of zirconia. However, there have been concerns over the years regarding the long-term structural performance of ZTA since the t&rarr, m transformation also spontaneously occurs at the material&rsquo, s surface under low-temperature environmental conditions with a concomitant degradation of mechanical properties. Spontaneous surface degradation has been extensively studied in vitro, but predictive algorithms have underestimated the extent of in vivo degradation observed in retrievals. The present research focused on burst-strength assessments of &Oslash, 28 mm ZTA femoral before and after long-term in vitro hydrothermal ageing according to ISO 7206-10. An average burst strength of 52 kN was measured for pristine femoral heads. This value was ~36% lower than results obtained under the same standard conditions by other authors. A further loss of burst strength (~13% in ultimate load) was observed after hydrothermal ageing, with increased surface monoclinic content ranging from ~6% to &gt, 50%. Nevertheless, the repetitively stressed and hydrothermally treated ZTA heads exceeded the minimum burst strength stipulated by the US Food and Drug Administration (FDA) despite severe test conditions. Lastly, Raman spectroscopic assessments of phase transformation and residual stresses on the fracture surface of the femoral heads were used to clarify burst-strength fluctuations and the effect of hydrothermal ageing on the material&rsquo, s overall strength degradation.

Following a request from the European Commission, the EFSA Panelon Additives and products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of OptiPhos® PLUS (6-phytase) as a zootechnical feed additive for suckling and weaned piglets, pigs for fattening, sows, other minor pig species for fattening and other minor reproductive pig species. The additive is a preparation of 6-phytase produced by a genetically modified strain of Komagataella phaffii and has been previously assessed by the FEEDAP Panelin the context of two applications for its use in different species/categories. The Panelconcluded in those opinions that the production strain is safe, and that the use of the additive as a feed additive would raise no safety concerns for the consumers and the environment. The additive was also considered not to be skin irritant but was found to be a dermal sensitiser. The FEEDAP Panelcould not conclude on the eye irritation potential of the additive. Owing to the proteinaceous nature of the active substance, the additive is considered a respiratory sensitiser. Based on the tolerance studies provided, the Panelconcluded that the additive is safe for the target species under the conditions of use with a wide margin of safety and therefore the conclusion were extended to suckling piglets and extrapolated to other minor pig species for fattening and to other minor reproductive pig species. The FEEDAP Panelconcluded that the additive has the potential to be efficacious in weaned piglets, pigs for fattening and in sows at the level of 250 FTU/kg feed and this conclusion were extended to suckling piglets and extrapolated to other minor pig species for fattening and to other minor reproductive pig species.

© 2019 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority. Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the additional data submitted on Lancer® when used as a feed additive for weaned piglets. The FEEDAP Panel considered that uncertainty still remains on possible developmental neurotoxicity of Lancer® since it was unable to identify a no observed adverse effect level (NOAEL) for this specific endpoint applying a read-across strategy from the studies provided by the applicant. However, the FEEDAP Panel considered that the exposure to La and Ce from products of animals treated with Lancer® at 250 mg/kg feed would not add a significant contribution to the background exposure of these elements. The FEEDAP Panel concluded that the use of Lancer® in feed for weaned piglets (up to 120 days) according to the proposed conditions of use, does not represent a safety concern for the consumer and for the environment.

The gold standard of treatment in Parkinson’s disease (PD) is levodopa/carbidopa whose long-term use induces motor and non-motor fluctuations and dyskinesias. Continuous infusion of intrajejunal levodopa/carbidopa intestinal gel (Duodopa®) reduces motor and non-motor symptoms and dyskinesias, and improves the quality of life of patients. The aim of this open observational prospective study was to evaluate the impact of Duodopa® on conditions of PD patients and caregivers, and their quality of life. We enrolled 12 patients with advanced PD and their caregivers. The PD patients were assessed at baseline, 3 and 6 months after Duodopa® treatment initiation using Unified Parkinson’s Disease Rating Scale-Part III and IV (UPDRS-III and IV), Unified Dyskinesia Rating Scale (UdysRS), Beck Depression Inventory (BDI-II), Hamilton Anxiety Rating Scale (HAM-A) and Parkinson’s Disease Quality of Life Questionnaire (PDQ-39). The caregivers were assessed, at the same time as the patients, using BDI-II, HAM-A, Caregiver Burden Inventory (CBI) and SF-36 Health Status Questionnaire. Six months after Duodopa® therapy, the scores of UPDRS-III and IV, UdysRS, BDI-II, HAM-A and PDQ-39 were significantly decreased (p

The additive (trade name Biomin®DC-P) is a blend of five individual compounds (carvacrol, thymol, d-carvone, methyl salicylate and l-menthol) encapsulated with a hydrogenated vegetable oil. The additive is intended for use in feed for various poultry species at a minimum concentration of 65mg/kg complete feed and a recommended maximum level of 105mg/kg complete feed. The results of a tolerance study show that Biomin® DC-P is safe for chickens for fattening at the maximum recommended application rate of 105 mg/kg complete feed; this conclusion is extended to include chickens reared for laying and extrapolated to minor poultry species The active components of a previously evaluated additive (Biomin®DC-C) were shown to be not genotoxic; owing to the similarity on composition, this conclusion can be also applied to Biomin®DC-P. Notwithstanding the uncertainties identified in the residue study, after applying a worst-case scenario to calculate potential exposure of consumers to menthol and carvone, and since that the components of the additive are considered safe for their use as food and feed flavourings, the FEEDAP Panelconcludes that the use of the additive in animal nutrition is considered safe for consumers. The FEEDAP Panelconsidered that exposure of users by inhalation is unlikely, but cannot conclude on the effects of Biomin®DC-P on skin and eyes. The use of Biomin®DC-P is not expected to pose a risk for the environment. Biomin®DC-P has a potential to increase the growth performance of chickens for fattening when incorporated into feed at a minimum application rate of 65mg/kg complete feed; the conclusion can be extended to chickens reared for laying and extrapolated to minor poultry species reared up to the point of lay.

The Panelon Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of VevoVitall® (benzoic acid) as a zootechnical feed additive for pigs for fattening. The additive is currently authorised for pigs for fattening with the effect of ‘urinary pH decrease’ at the minimum and maximum use of 5,000 and 10,000mg/kg complete feed, respectively. The current application intends to support the use of the additive with the specific effect of ‘improvement of performance parameters’ at the minimum dose of 3,000mg additive/kg complete feed, and keeping the same other conditions as for the use already authorised. The FEEDAP Panelassessed already the safety of the product when used in pigs for fattening in 2007 and 2017. The Panelconfirms its former assessments that VevoVitall® used as a feed additive in pigs for fattening at the maximum level of 10,000mg/kg is considered as safe for pigs for fattening, consumers of food derived from pigs fed the additive and the environment. VevoVitall® does not pose a risk by inhalation to users and is not a skin sensitiser but is a skin irritant and a severe eye irritant. Based on the results of three efficacy studies, the FEEDAP Panelconcluded that VevoVitall® has the potential to increase the performance in pigs for fattening at the level of 3,000mg/kg complete feed.

Following a request from the European Commission, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of Actisaf® Sc47 for dairy cows, cattle for fattening, weaned piglets and sows when used as a zootechnical additive. Actisaf® Sc47 consists of viable cells of a strain Saccharomyces cerevisiae and is marketed in three formulations. The FEEDAP Panel considers that the three available formulations are equivalent when used to deliver the same dose of the microorganism in feed. The active agent fulfils the requirements of the qualified presumption of safety approach to the assessment of safety. Since the additive is composed of the active agent only, Actisaf® Sc47 is also presumed safe for the target animals, consumers of products derived from treated animals and the environment. Actisaf® Sc47 is not a skin irritant. In the absence of data, no conclusions can be drawn on the eye irritancy and dermal sensitisation potential of the additive. Inhalation exposure is unlikely. The additive has the potential to be efficacious in weaned piglets and sows to have benefits in piglets at the recommended dose of 5 × 109 CFU/kg feed. Insufficient evidence was provided to conclude on the efficacy of the additive in dairy cows and cattle for fattening.

The additive (trade name Biomin ® DC-C) is a blend of essential oils from oregano (Origanumvulgare L.) and from caraway seed (Carumcarvi L.) and three individual compounds (carvacrol, methyl salicylate and l-menthol) encapsulated with a hydrogenated vegetable oil. The additive is intended for use in feed for weaned piglets at a minimum concentration of 75mg/kg complete feed and a recommended maximum level of 125mg/kg complete feed. A tolerance test in which piglets were exposed to feed containing up to an intended 1,250mg additive/kg complete feed showed that additive is safe for piglets at the maximum recommended level with at least a sixfold margin of safety. The active components of the additive are not genotoxic and from the available residue study, based on the detection of five marker compounds, no measurable exposure of the consumers is foreseen; consequently, the use of the additive is considered safe for consumers of animal products. The FEEDAP Panelconsidered that exposure to users by inhalation is unlikely; in the absence of data, the Panelcannot conclude on the effects of Biomin ® DC-C on skin and eyes. The use of the additive in animal production is not expected to pose a risk for the terrestrial or aquatic environments. Based on the results of three efficacy studies in which positive benefits were seen, the additive has a potential to improve the growth performance of weaned piglets at a minimum application rate of 75mg/kg complete feed.

Stress affects the immune system and intestinal microbiota composition and can lead to imbalance between pro- and anti-inflammatory cytokines or to uncontrolled production of cytokines. The effect of emotional stress on secretory IgA levels also indicates that stress decreases mucosal integrity. Our aim was to evaluate whether a probiotic product (Lactoflorene® Plus) can prevent alterations in the immune response associated with self-reported stress and microbiota composition. Healthy adult volunteers who self-reported psychological stress were enrolled and randomised into a placebo and a probiotic group. Salivary stress markers (α-amylase, cortisol, chromogranin A) and immunological parameters (sIgA, NK cell activity, IL-8, IL-10, TNF-α) in feces and the composition of intestinal microbiota were evaluated. Administration of the product did not exert a direct effect on the salivary stress markers or NK cell activity but did reduce abdominal pain and increase faecal IgA and IL-10 levels. The probiotic product induced a moderate increase in Bifidobacterium and Lactobacillus spp., as expected, and in Faecalibacterium spp., and decreased the size of the Dialister spp. and Escherichia and Shigella populations. Administration of the product helped protect the mucosal barrier by supporting the number of short-chain fatty acid producers and decreasing the load of potentially harmful bacteria, thus reducing intestinal inflammation and abdominal discomfort. ClinicalTrials.gov: NCT03234452. Keywords: BB-12®, LA-5®, Immune response, Stress, Abdominal pain, IgA

Following a request from European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of Robenz® 66G (robenidine hydrochloride (HCl)) when used as a feed additive for chickens for fattening and turkeys for fattening. The coccidiostat Robenz® 66G is considered safe for chickens for fattening at the highest proposed level of 36 mg robenidine HCl/kg complete feed with a margin of safety of approximately 2.5. This conclusion is extrapolated to turkeys for fattening. Robenidine HCl is active against Gram‐positive but not against Gram‐negative bacteria. It is not expected that the use of robenidine HCl as a feed additive would induce resistance or cross‐resistance to antimicrobials used in human and animal therapy. The use of robenidine HCl from Robenz® 66G at the highest proposed level of 36 mg/kg complete feed in chickens and turkeys for fattening is considered safe for the consumer. The existing maximum residues limits for both avian species are confirmed. Robenidine HCl is not a skin or eye irritant and not a skin sensitiser. The risk via inhalation is considered negligible. The use of robenidine HCl from Robenz® in feed for chickens for fattening and turkeys for fattening up to 36 mg/kg complete feed does not pose a risk to either the terrestrial or the aquatic compartment. A risk for bioaccumulation cannot be excluded. The risk for secondary poisoning is not likely to occur. The FEEDAP Panel concludes that 36 mg robenidine HCl/kg complete feed from Robenz® 66G has the potential to effectively control coccidiosis of chickens for fattening under field conditions but cannot conclude on the efficacy of robenidine HCl in turkeys for fattening. The existing 5‐day withdrawal period to avoid off‐flavours in edible tissues should be maintained.

The anatomical position of the inferior epigastric artery (IEA), within the rectus sheath, subjects patients to possible IEA injury during abdominal wall surgical and interventional procedures. Pseudoaneurysm arising from IEA is very uncommon with only 16 cases reported in the literature. We present a case of an IEA false aneurysm resulting from therapeutic paracentesis for ascites in a 71-year-old patient who came to our department for abdominal pain and signs of anemization. To our knowledge, no published reports are currently available describing an IAE pseudoaneurysm successfully diagnosed with contrast-enhanced ultrasound. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40477-019-00398-x) contains supplementary material, which is available to authorized users.

The low and variable oral bioavailability of poorly water soluble drugs remains a major concern for the pharmaceutical industry. Spray congealing is an emerging technology for the production of solid dispersion to enhance the bioavailability of poorly soluble drugs by using low-melting hydrophilic excipients. The main advantages are the absence of solvents and the possibility to obtain spherical free-flowing microparticles (MPs) by a relatively inexpensive, simple, and one-step process. This review aims to fully describe the composition, structure, physico-chemical properties, and characterization techniques of spray congealed-formulations. Moreover, the influence of these properties on the MPs performance in terms of solubility and dissolution enhancement are examined. Following, an overview of the different spray congealed systems developed to increase the oral drug bioavailability is provided, with a focus on the mechanisms underpinning the bioavailability enhancement. Finally, this work gives specific insights on the main factors to be considered for the rational formulation, manufacturing, and characterization of spray congealed solid dispersions.

The iLA-activve® Novalung is a new extracorporeal device specifically designed for lung support in patients with hypercapnic and/or hypoxemic respiratory failure. To date, only low-flow applications for decompensated hypercapnic chronic obstructive pulmonary disease have been reported in the literature. Here, we briefly report three cases of iLA-activve use in patients with hypercapnic-hypoxemic acute lung failure assisted with mid-flow (up to 2.4 L/min) and different single/double venous cannulation. The main findings of our small case series were: firstly, extracorporeal blood flows over 2.0 L/min across the membrane provided clinically satisfying decarboxylation and improved oxygenation; secondly, the ratio between blood flow through the membrane and the patient’s cardiac output (CO) was a major determinant for the oxygen increase. The latter could, therefore, be a useful indicator for understanding performance in the complex and multifactorial evaluation of patients with extracorporeal veno-venous lung support.

Background The aim of this retrospective study was to evaluate the outcome of patients with intra-articular calcaneal fractures treated using a minimally invasive locking nail (Calcanail®). Methods Between January 2016 and April 2017, 15 patients (9 men and 6 women) with a calcaneal fracture were consecutively treated with Calcanail®. The Bohler angle was recorded on standard X-rays pre- and post-operatively. The articular reduction of the posterior facet was evaluated with the Goldzak index in a CT scan 3 months post-operatively. The mean age of the patients was 53 years (range, 24–78). Mean final follow-up was 18 months (range, 12–24). Results Six fractures were classified as Sanders II, 7 as Sanders III and 2 as Sanders IV. In 13 out of the 15 patients treated, the post-operative Bohler angle was of more than 20°. Goldzak index was deemed as excellent in 73.5% of the cases (11 patients), good in 20% of cases (3 patients), and poor in 6.5% (1 patient). Post-operative mean AOFAS score was 85 (range, 60–96). Conclusions The Calcanail® provides good restoration of the subtalar joint and the calcaneal angles with the advantages of a minimally invasive approach. It was effectively used in Sanders types II and III, even in the presence of poor cutaneous conditions.

l-Glutamic acid, N,N-diacetic acid, tetrasodium salt (GLDA-Na 4 ) (Kelforce ® ) is sought to be used as a zootechnical feed additive in chickens for fattening to improve the absorption of zinc from feed, reducing zinc emissions through manure and thus, affecting favourably the environment. The product has not been authorised in the European Union as a feed additive. Kelforce ® is intended to be marketed as a liquid and solid formulation, containing ≥47% and ≥30% of GLDA-Na 4 , respectively. Kelforce ® is safe for chickens for fattening at the maximum level of 1,000mg GLDA-Na 4 /kg complete feed. Based on the toxicological profile of GLDA-Na 4 and the consumer exposure to GLDA-Na 4 and to nitrilotriacetic acid trisodium salt (NTA-Na 3 ; an impurity of the additive), the use of Kelforce ® at the maximum proposed level in feed of chickens for fattening is of no concern for consumer safety. Due to its low inhalation toxicity, the exposure to GLDA-Na 4 is unlikely to pose a risk by inhalation. However, owing to the high-dusting potential of the solid formulation, a risk from such high level of dust, even if toxicologically inert, cannot be excluded. Kelforce ® is not a skin/eye irritant or skin sensitiser. No risks for the terrestrial compartment were identified at the maximum use level of the additive. Risks for the aquatic compartment cannot be excluded based on the secondary effect of the additive on green algae. In the absence of data, the Panelcannot conclude on the safety for the sediment compartment or the possible ground water contamination. The risk of bioaccumulation and secondary poisoning caused by the additive is considered very low. Owing to the inconsistent and conflicting results from the studies assessed, the Panelon Additives and Products or Substances used in Animal Feed (FEEDAP) cannot conclude on the efficacy of the additive. The Panelmade a recommendation regarding the levels of formaldehyde and cyanide in the active substance.

Trans-resveratrol (RSV) was microencapsulated in Eudragit® RS100 and RL100 resin blends. Lyophilized microspheres were characterized in the solid state for their micromeritic properties and drug loading. FT-IR, PXRD, and DSC analyzes suggested that RSV formed an intimate microcrystalline dispersion within the polymer network, also confirmed by SEM analysis. This produced a reduced degradation of RSV after storage at 40 °C, compared to the neat drug, and a protection of the drug from UV light-induced trans-cis isomerization (60% intact drug was found after 60 s irradiation at 350 nm, compared to 37% for the pure drug). Solubility and in vitro dissolution studies indicated that microencapsulation did not improve the dissolution pattern of RSV in simulated gastric and intestinal aqueous fluids. Evaluation of the in vitro antioxidant activity showed that, compared to the neat drug in aqueous solution, RSV loaded in the microspheres retained for a longer time, up to 22 days of incubation, the initial ORAC capacity. The present study thus demonstrated that Eudragit® Retard resins can be used to easily produce micro-sized solid dispersions with RSV, for potential oral administration, contributing to ameliorate the physico-chemical stability and antioxidant activity of this compound.