Organic residues from agricultural and forest companies in Brazil as useful substrates for cultivation of the edible mushroom Pleurotus ostreatus.

We investigated whether highly available organic residues in Brazil can be used as substrates for the production of the oyster mushroom Pleurotus ostreatus, instead of the conventional cultivation using the eucalyptus sawdust substrate. We assessed the mushroom yield on 13 substrates, of which 12 were formulated with different concentrations of organic residues and one with pure eucalyptus sawdust, and verified whether the raw material used in the substrate formula and the concentration of such alternative residues influenced their biological efficiencies. Substrates containing eucalyptus bark resulted in higher mushroom yield than those containing eucalyptus sawdust, which generally resulted in similar mushroom yield to the remaining formulas. Moreover, the raw material and the concentration of each residue affected the biological efficiency of the substrates. We show that the conventional substrate for P. ostreatus can be replaced by substrates easily accessible to producers without loss in productivity. Furthermore, that the concentration of these mixtures affects the mushroom productivity and should be considered when formulating the growth medium.

Adenovirus infection among pediatric patients with cancer and in pediatric recipients of hematopoietic stem cell: A multicenter nationwide study.

The aim was to evaluate the incidence, clinical course, and outcome of adenoviral infection (AdVI) in pediatric patients diagnosed and treated due to cancer and in pediatric recipients of hematopoietic stem cell. Over a 72-month period, all-in 5599 children with cancer: 2441 patients with hematological malignancy (HM) and 3158 with solid tumors (ST), and 971 patients after transplantation: 741 after allogeneic (allo-HSCT) and 230 after autologous (auto-HSCT) were enrolled into the study. Among cancer patients, 67 episodes of AdVI appeared in 63 (1.1%) children, including 45 (1.8%) with HM and 18 (0.6%; P < .001) with ST. Within transplanted patients, AdVIs were responsible for 88 episodes in 81 (8.3%) children (P < .001), including 78 (10.5%) patients after allo-HSCT and 3 (1.3%) after auto-HSCT. Time to develop AdVI was short, especially after allo-HSCT. The most common clinical manifestation in cancer patients was enteritis diagnosed in 63 (94.0%) cases, while among HSCT recipient asymptomatic adenoviremia was found in 36 (40.9%) cases and the most common clinical manifestation was urinary tract infection. Cancer patients with disseminated disease, as well as HSCT recipients with either asymptomatic viremia or disseminated disease, received antiviral treatment. The most commonly used first-line therapy was cidofovir. None of the cancer patients died due to AdVI, while within HSCT recipients three patients developed disseminated adenoviral disease and died despite antiviral treatment. In cancer patients, AdVIs are rare and associated with very good prognosis even without specific treatment. However, in allo-HSCT recipients, disseminated disease with fatal outcome is more likely to occur.

Hematopoietic stem cell transplantation does not increase the risk of infection-related complications for pediatric patients with Hodgkin and non-Hodgkin lymphomas: A multicenter nationwide study.

BACKGROUND: Hodgkin (HL) and non-Hodgkin lymphoma (NHL) represent a spectrum of lymphoid malignancies that are often curable with currently applied treatment regimens; however, 15%-30% of lymphoma patients still suffer from relapsed or refractory (rel/ref) disease. Although hematopoietic stem cell transplantation (HSCT) improves outcomes of second-line therapy for lymphoma in childhood, the complication rates in this group of patients, especially infectious complications (IC), remain unclear. OBJECTIVE: The aim of this population-based cohort study was a retrospective analysis of incidence, epidemiology and profile of bacterial infections (BI), invasive fungal disease (IFD), and viral infections (VI) in primary or rel/ref lymphoma patients, both HL and NHL. PATIENTS AND METHODS: We subdivided lymphoma patients into three groups: patients with primary conventional chemotherapy/radiotherapy regimens (group A), patients with rel/ref lymphoma treated with second-line chemotherapy (group B), and rel/ref lymphoma patients who underwent HSCT (group C). The medical records of the patients were biannually reported by each pediatric oncology center, and the data were analyzed centrally. RESULTS: Within 637 patients with primary lymphoma, at least one IC was diagnosed in 255 (40.0%), among 52 patients with rel/ref lymphoma 24 (46.2%) ICs were observed, and in transplanted group, 28 (57.1%) out of 49 children were diagnosed with IC (P = .151). The distribution of etiology of IC differed between the patient groups (A, B, C), with a predominance of BI in group A (85.6% vs 72.0% and 47.9%, respectively), VI in group C (9% and 16.0% vs 46.6%, respectively), and IFD in group B (5.4% vs 12.0% vs 5.5%, respectively). Overall, 500 (68.0%) episodes of bacterial IC were diagnosed in the entire group. Apart from HL patients treated with chemotherapy, in all the other subgroups of patients Gram-positives were predominant. The rate of multidrug-resistant bacteria was high, especially for Gram-negatives (41.1% in group A, 62.5% in group B, and 84.6% in group C). The infection-related mortality was comparable for each group. CONCLUSIONS: The incidence of IC was comparable during first- and second-line chemotherapy and after HSCT, but their profile was different for primary or re/ref lymphoma and depended on the type of therapy.

Multidrug-resistant bacterial infections in children undergoing haematopoietic stem cell transplantation over a 6-year period: analysis of the Polish Pediatric Group for Hematopoietic Stem Cell Transplantation.

AIMS: Multidrug-resistant (MDR) bacteria are an emerging cause of morbidity and mortality after haematopoietic stem cell transplantation (HSCT). The aim of the study was to analyse the incidence, clinical characteristics and survival from bacterial infections (BI) caused by MDR pathogens in paediatric HSCT recipients. METHODS AND RESULTS: Among 971 transplanted patients, BI were found in 416 children between the years 2012 and 2017. Overall, there were 883 bacterial episodes, which includes 85·8% after allo-HSCT and 14·2% after auto-HSCT. MDR strains were responsible for half of the total number of bacterial episodes. Over 50% of MDR pathogens were Enterobacteriaceae causing mainly gut infections or urinary tract infections. CONCLUSIONS: Regarding HSCT type, we did not find differences in the profile of MDR BI between allo- and auto-HSCT recipients. However, survival in MDR and non-MDR infections was comparable. SIGNIFICANCE AND IMPACT OF THE STUDY: The large sample size enables unique analysis and makes our data more applicable to other paediatric HSCT centres. In the absence of local epidemiological data, presented clinical characteristics of MDR-caused infections may be used to optimize the prophylactic strategies, early identification of infectious complications of MDR aetiology and thus promptly initiate adequate antibiotic therapy and further improve patients' outcome.

Incidence, course, and outcome of Clostridium difficile infection in children with hematological malignancies or undergoing hematopoietic stem cell transplantation.

Clostridium difficile infection (CDI) is one of the most common causes of nosocomial infectious diarrhea in children during anticancer therapy or undergoing hematopoietic stem cell transplantation (HSCT) in Europe. Immunosuppression in these patients is a risk factor for CDI. Malignant diseases, age, acute graft-versus-host disease (aGVHD), HLA mismatch, or use of total body irradiation may play an important role in CDI course. The aim of this study was to evaluate the incidence, course, and outcome of CDI in children treated for malignancy or undergoing HSCT. Between 2012 and 2015, a total number of 1846 patients were treated for malignancy in Polish pediatric oncological centers (PHO group) and 342 underwent transplantation (HSCT group). In PHO group, episodes of CDI occurred in 210 patients (14%). The incidence of CDI was higher in patients with hematological malignancies in comparison to that with solid tumors. Patients with acute myeloblastic leukemia had shorter time to episode of CDI than those with acute lymphoblastic leukemia. Patients over 5 years and treated for acute leukemia had more severe clinical course of disease in PHO group. In HSCT group, CDI occurred in 29 (8%) patients. The incidence of CDI was higher in patients transplanted for acute leukemia. The recurrence rate was 14.7% in PHO and 20.7% in HSCT patients. CDI incidence was highest in patients with hematological malignancies. Most of patients experienced mild CDI. Age < 5 years and diagnosis other than acute leukemia were the positive prognostic factors influencing clinical CDI course.

Suitability of Wild Boar (Sus scrofa) as a Bioindicator for Environmental Pollution with Perfluorooctanoic Acid (PFOA) and Perfluorooctanesulfonic Acid (PFOS).

Wildlife species, such as roe deer, moose, brown hare, wild boar, etc., are known to accumulate persistent environmental contaminants and thus are useful as bioindicators for environmental pollution. Wild boars become exposed to perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) from flora, fauna, water, and soil. The main exposure pathway to PFOA and PFOS is assumed to be the oral intake. From studies in domestic pigs (belonging to the same species Sus scrofa), it has been established that the oral exposure results in the liver accumulation of PFOA and PFOS. Thus, we posit that wild boars can be quantitatively used as suitable bioindicators for the presence of these substances in the environment. After the environmental pollution case in the Hessian region Sauerland in 2006, monitoring programs of individual Federal States from 2007 to 2013 showed that almost all wild boar liver samples contained PFOA and PFOS. In 2014, the analyses of PFOA and PFOS in liver of wild boars hunted in the south, north, and west of Germany showed liver concentrations at the same level among regions. Overall, an average ratio of PFOS:PFOA concentration in liver of 20.5:1 was found. To estimate the actual ratio of PFOS:PFOA in the wild boars' dietary exposure, we performed toxicokinetic modeling. According to the model, the PFOS exposure is only 2.2 times that of PFOA (because PFOS has slower elimination kinetics and higher affinity for the liver than PFOA). Overall, the determination of PFOA and PFOS in liver of wild boars indicates that both substances are ubiquitously distributed in the environment. At the same time, higher exposures were found for animals living in closer proximity to dense human populations.

Differentiation of infectious bronchitis virus vaccine strains Ma5 and 4/91 by TaqMan real-time PCR.

The aim of this study was to develop rapid molecular assays for differentiating vaccine strains Ma5 and 4/91 of the infectious bronchitis virus (IBV). Specific primers and probes for S1 and N genes were designed based on the nucleotide sequences of both vaccine strains. Cross-reactivity was not observed. Assay sensitivity was 2.373 × 103 copies of the Ma5 strain, and 3.852 x 103 copies of the 4/91 strain. Samples belonging to a known genotype demonstrated that the designed assays supported rapid and sensitive detection of Ma5 and 4/91 vaccine strains of IBV.

Bacterial infections in pediatric hematopoietic stem cell transplantation recipients: incidence, epidemiology, and spectrum of pathogens: report of the Polish Pediatric Group for Hematopoietic Stem Cell Transplantation.

BACKGROUND: Infectious complications are a significant cause of hematopoietic stem cell transplantation (HSCT) failure, especially allogeneic HSCT (allo-HSCT) because of delayed immune reconstitution and graft-versus-host disease (GVHD) occurrence. Identifying the factors responsible for bacterial infections (BI) in patients undergoing HSCT will provide much more effective empirical antimicrobial treatment in this group of patients. OBJECTIVE: The aim of this study was to evaluate the epidemiology and profile of BI in patients after HSCT in 5 centers of the Polish Pediatric Group for Hematopoietic Stem Cell Transplantation in 2012-2013. PATIENTS AND METHODS: In 308 HSCT recipients, we retrospectively analyzed 273 episodes of BI in 113 (36.7%) children aged 0.02-22 years (median age: 7 years), 92 after allo-HSCT and 22 after autologous HSCT (auto-HSCT). We assessed incidence of BI in different HSCT types by calculating the Index of Bacterial Infection (IBI) as a ratio of patients with at least 1 BI to all patients who underwent this type of HSCT in the analyzed period. We assessed the profile of BI with particular emphasis on multidrug-resistant organisms, and impact of underlying disease and of graft-versus-host disease on BI episodes. RESULTS: In the studied group, 273 episodes of BI were diagnosed, including 237 episodes after allo-HSCT and 36 after auto-HSCT. Among allo-HSCT recipients diagnosed with at least 1 BI, the IBI was 0.4 (matched sibling donor-HSCT 0.3; matched donor-HSCT 0.4; mismatched unrelated donor [MMUD]-HSCT 0.8; P = 0.027) and after auto-HSCT 0.3 per 1 transplanted patient. In patient after allo-HSCT because of myelo- or lymphoproliferative diseases and bone marrow failures, the major cause of infections was Enterobacteriaceae, while gram-positive bacteria predominated in the group with primary immunodeficiencies. In all patients after auto-HSCT, the dominant pathogen of BI were Enterobacteriaceae (P = 0.011). Time from each type of HSCT to infection caused by different pathogens did not differ significantly. CONCLUSIONS: The risk of BI does not depend on the underlying disease, but only on HSCT donor type and is the highest after MMUD-HSCT procedure. The profile of BI depends on the underlying disease and HSCT donor type, but does not depend on the occurrence of acute GVHD. Gram-negative bacteria predominated in patients with myelo- and lymphoproliferative diseases, while in patients with primary immunodeficiencies gram-positive strains were predominant.

Teenagers and young adults with cancer in Europe: from national programmes to a European integrated coordinated project.

Over 14 000 patients aged 15-24 are estimated to be diagnosed with cancer in the European Union (EU) each year. Teenagers and young adults (TYA) often fall down gaps between children's and adults cancer services. The specific challenges of providing optimal care to them are described, but we present a summary of recent progress. Progress to overcome these challenges is happening at different rates across Europe. We summarise the European national projects in this field but more recently we have seen the beginnings of European coordination. Within the EU 7th Funding Programme (FP7) European Network for Cancer Research in Children and Adolescents programme (ENCCA), a specific European Network for Teenagers and Young Adults with Cancer has held a series of scientific meetings, including professionals, patients and caregivers. This group has proposed unanswered research questions and agreed key features of a high-quality service that can improve outcomes for TYA with cancer, including the primacy of collaboration between adult and paediatric services to eliminate the gap in the management of TYA with cancer.

First-line immunosuppressive treatment in children with aplastic anemia: rabbit antithymocyte globulin.

Immunosuppressive therapy is the treatment of choice in children with acquired severe aplastic anemia (AA) and no HLA-matched family donor. The paper presents results of a multicenter study of 63 children with AA treated with rabbit antithymocyte globulin (r-ATG) and cyclosporine A as the first line treatment in the years 1996-2012. Therapeutic effects were evaluated at Days 112, 180, and 360. At Day 112, remission was achieved in 28 out of the 63 patients (44.4 %), complete remission in 10 patients (15.9 %), and partial remission in 18 (28.5 %). At Day 180, 31 patients (49.2 %) were in remission including 15 cases in complete (23.8 %), and 16 cases in partial remission (25.4 %). One year after therapy onset, 34 patients (64.9 %) were in remission including 24 patients (38.0 %) in complete and 10 (15.9 %) in partial remission. Relapse occurred in 4 patients, from 8 months up to 2 years and 2 months after remission. One child, 5 years after remission, was diagnosed with paroxysmal nocturnal hemoglobinuria. The estimated 10-year overall survival rate and 10-year event-free survival rate were 67 % and 57 %, respectively.

IL-10 promoter polymorphisms influence susceptibility to aGvHD and are associated with proportions of CD4+FoxP3+ lymphocytes in blood after hematopoietic stem cell transplantation.

Four hundred and ninety-five patients (390 and 105 grafted from unrelated and sibling (SIB) donors, respectively) and their donors were analyzed for the impact of interleukin-10 (IL-10) promoter genotype [rs18000896 (-1082 G/A), rs18000871 (-819 C/T) and rs18000872 (-592 C/A)] on the outcome of hematopoietic stem cell transplantation (HSCT). Patients having ACC haplotype were at a lower risk of acute graft versus host disease (aGvHD, grade > I) if transplanted from human leukocyte antigen (HLA) well-matched (10/10) unrelated donors (20/135 vs 39/117, P < 0.001, Pcorr = 0.002), which was not seen if patients were transplanted from either sibling (SIB) or poorly matched (<10/10) unrelated donors (MUD). In addition, GCC haplotype positive recipients of unrelated donor transplants tended to be more susceptible to aGvHD (68/199 vs 39/169, P = 0.019, Pcorr = 0.057). Multivariate logistic regression analysis in the MUD transplanted group showed that donor-recipient human leukocyte antigen (HLA) mismatch [odds ratio (OR) = 3.937, P = 0.001] and a lack of ACC haplotype in recipients (OR = 0.417, P = 0.013) played a significant role as independent risk factors of aGvHD grade > I. ACC carriers had higher proportions of FoxP3+ lymphocytes gated in CD4+ lymphocytes as compared with patients with other IL-10 haplotypes. It was seen at the time of hematological recovery (mean ± SEM: 3.80 ± 0.91% vs 2.06 ± 0.98%, P = 0.012) and 2 weeks later (5.32 ± 0.87% vs 2.50 ± 0.83%, P = 0.013); -592 C/A polymorphism was separately analyzed and it was found that AA homozygotes tended to have a higher incidence of aGvHD (8/15 vs 116/456, P = 0.034) and low proportions of FoxP3 CD4+ lymphocytes in blood (0.43 ± 0.22% vs 4.32 ± 0.71%, P = 0.051) measured 2 weeks after hematological recovery. Functional IL-10 polymorphism associated features influenced the risk of aGvHD with a positive effect of ACC on the pool of Treg in blood.

Paediatric pseudoxanthoma elasticum with cardiovascular involvement.

BACKGROUND: Pseudoxanthoma elasticum (PXE) is characterized by aberrant mineralization of connective tissues, causing considerable morbidity and mortality. The disease is typically of late onset, the skin manifestations first being noted in the teens or later. Another aberrant mineralization disorder, generalized arterial calcification of infancy (GACI), is present at birth and can demonstrate a phenotypic overlap with PXE. OBJECTIVES: A patient with PXE was noted to have skin findings as early as at 6 years of age, with cardiovascular involvement. The purpose of this study was to examine the genetic basis of this phenotypic presentation in the spectrum of PXE/GACI. METHODS: The patient's genotype was studied by sequencing ABCC6 and ENPP1, genes known to be associated with PXE and/or GACI. RESULTS: Screening of the ABCC6 gene revealed two pathogenetic mutations, p.R1141X and g.del23-29. Analysis of the ENPP1 gene failed to demonstrate the presence of mutations. CONCLUSIONS: This study demonstrates the presence of cutaneous findings of PXE in an 8-year-old paediatric patient, with cardiovascular involvement, illustrating the phenotypic spectrum of PXE.

Allelic loss of selected tumor suppressor genes in acute lymphoblastic leukemia in children.

Defect in function of tumor suppressor genes may lead to initiation/progression of leukemias. RB1, CDKN2A and TP53 gene alterations are found in acute lymphoblastic leukemia (ALL) in children. Data showing a contribution of these alterations to the pathomechanism of leukemias are contradictory and their impact on a disease course still remains undefined. The main aim of the study was to identify and the characterize of RB1, CDKN2A and TP53 allele loss in ALL children patients at diagnosis. 46 children with de novo ALL were examined. Fluorescent in situ hybridization was performed on bone marrow smear preparations. We demonstrated that at least one of three investigated deletions occurred statistically more frequently in T-lineage leukemia patients (p = 0.044); this was the most frequent in respect to RB1 gene (p = 0.054). Additionally, at least one of the examined deletions was observed statistically more frequently in patients with WBC above 20 000/µl (p = 0.043), this was the most frequent for CDKN2A gene (p = 0.066). Presented results seem to give an evidence that deletions of RB1 and CDKN2A genes may contribute to the development of hyperleukocytic type of T-lineage ALL in children, nevertheless this observation needs further investigations.

Effects of conjugated linoleic acids fed to dairy cows during early gestation on hematological, immunological, and metabolic characteristics of cows and their calves.

The aim of the present experiment was to test the stimulation ability of peripheral blood mononuclear cells (PBMC) expressed as stimulation index (SI) of newborn calves and of their dams fed a control fat supplement (CON, n=6) or 50 and 100g/d of a CLA-containing fat supplement (CLA50, n=5, and CLA100, n=6, respectively) during the preceding lactation period for 182 d after calving. The total intake of cis-9,trans-11 and trans-10,cis-12 CLA by groups CLA50 and CLA100 amounted to 4 and 8 g/d each, respectively. For this purpose, blood was collected immediately after parturition from calves before and after colostrum intake, and from cows after parturition and 21 d later. The SI was related to the fatty acid composition of erythrocyte and milk lipids and to various hematological and clinical-chemical parameters. Retrospective evaluation revealed that depletion time (i.e., the individual period elapsed between the day of terminating the feeding of the experimental diet in the preceding lactation period and the day of calving) ranged from 190 to 262 d, which corresponded to fetal exposure times of 19 to 102 d. The SI from cows increased significantly by 77 and 55%, within 21 d after calving according to the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) and Alamar Blue assays, respectively. However, feeding of 50 g of the CLA product failed to demonstrate this increase in the MTT assay. Moreover, SI was significantly lower for calves whose dams belonged to the CLA50 group, whereas stimulation ability was comparable for the PBMC from calves whose mothers were treated with CON and CLA100. Plasma metabolites (total bilirubin, total cholesterol, glucose, nonesterified fatty acids, 3-ß-hydroxybutyrate, total protein, and albumin) and hematological parameters (hematocrit, white blood cell profile) were not significantly influenced by dietary treatments of the cows in the preceding lactation period. Although the fatty acid pattern of erythrocyte lipids of cows remained uninfluenced, that of calves showed alterations due to the feeding type of their dams. For example, C16:0 increased significantly from 14.4 to 16.9% of total fatty acid methyl esters, whereas cis-9,trans-11 CLA increased slightly from 0.11 to 0.15% at the same time in calves when their mothers were fed the CLA100 instead of the CON diet. Fatty acid profile of colostrum was significantly different from that of milk after 3 wk for most of the detected fatty acids, but was not influenced by diet type. In conclusion, feeding a CLA-containing fat supplement during the preceding lactation and gestation period exerted effects on the stimulation ability of PBMC from cows and calves for the subsequent parturition. However, CLA dose effects were inconsistent and require further investigation.

Comparison of two commercial ELISA kits for serological monitoring of avian encephalomyelitis in a reproductive turkey flock.

Avian encephalomyelitis (AE) is a viral disease of poultry. Although the disease has a milder clinical course in turkeys than in chickens, reproductive flocks of turkeys are vaccinated against AE. Commercial AE ELISA kits are specifically designed for chickens, which makes it difficult to implement these tests in serological monitoring of turkey flocks. The aim of the study was to compare the AE serological results provided by two ELISA kits from different producers when testing an AE-vaccinated flock of turkey hens and their progeny. We detected differences in the sensitivity of the ELISAs for testing specific anti-AE antibody levels in turkey serum samples.

Epidural catheter replacement rates with dural puncture epidural labor analgesia compared with epidural analgesia without dural puncture: a retrospective cohort study.

BACKGROUND: Lumbar epidural analgesia (LEA) is commonly used for labor analgesia but up to 13% of epidural catheters fail and require replacement. Combined spinal-epidural analgesia is associated with a lower catheter failure rate. Few data exist regarding catheter replacement rates after dural-puncture epidural (DPE). We conducted a retrospective analysis comparing catheter failure rates between epidural and DPE techniques. METHODS: This retrospective single-center trial reviewed all labor neuraxial analgesia procedures among 18 726 women across five years, and identified 810 DPE and 2667 LEA procedures. Catheter failure rates, consisting of replacement or requirement of general anesthesia for cesarean delivery, were compared. Propensity score matching was used to balance the groups. RESULTS: Dural-puncture epidural was associated with significantly fewer catheter failures compared with LEA (74/759 vs. 49/759, odds ratio 0.64, 95% CI 0.44 to 0.93, P=0.02). Sensitivity analysis excluding cases of general anesthesia confirmed this relationship. Risk factors identified for catheter failure included age, body mass index, and nulliparity. Dural-puncture epidural was associated with a longer mean time to catheter replacement (918 min vs. 609 min, P=0.04). Kaplan-Meier and Cox multivariate analyses confirmed this relationship. There was no significant difference in the requirement for epidural analgesia supplementation, but DPE required supplementation significantly later than LEA. There was no difference in the rate of headache or epidural blood patch between groups. CONCLUSIONS: Dural-puncture epidural is associated with fewer catheter failures and replacements than LEA, without an increase in the rate of post-dural puncture headache or epidural blood patch.

Review: Bioavailability of trace elements in farm animals: definition and practical considerations for improved assessment of efficacy and safety.

Currently, the authorisation procedure of trace elements as feed additives in the European Union according to Regulation (EC) No. 1831/2003 does not consider the bioavailability of trace element sources. This manuscript provides framework conditions for in vivo experiments that aim to estimate differences in the relative bioavailability between supplements of essential trace elements. Framework conditions encompass necessary technical information on the test substance, the experimental design and diet composition as well as the suitability of status parameters that allow for relative comparisons of regression variables. This manuscript evolves recommendations for researchers to conduct solid and reliable experiments on the matter as well as decision makers to interpret the value of studies submitted with authorisation applications regarding a certain trace element supplement.

Clinical experience with Optivate®, high-purity factor VIII (FVIII) product with von Willebrand factor (VWF) in young children with haemophilia A.

Optivate® is a high-purity FVIII/VWF product. Its safety, tolerability and efficacy in subjects ≥ 12 years have been demonstrated. This study was undertaken to assess Optivate® in children with haemophilia A. Twenty-five children, including one PUP (previously untreated patient), aged 1-6 years (mean 4.67 years) were treated with Optivate® for 26 weeks. Inhibitors were assessed every 3 months and viral status at the study start and end. Prophylaxis was used by five boys and on demand by twenty. The mean number of bleeds in the study was lower compared to the same period pre-study (12.0/child vs. 16.2/child), with fewer bleeds (P < 0.05) in the prophylactic subgroup (8.0/child) compared with the on-demand sub-group (13.4/child). Fourteen major bleeds were reported, all by the on-demand sub-group. Children on prophylaxis were administered a mean of 59.4 infusions; on-demand group 35.1 infusions. A total of 998 infusions were used with a mean dose of 29.1 IU kg⁻¹, and a mean of 38.6 exposure days (ED). Children < 4 years used higher doses, and reported fewer bleeds than older children. Children's Parents/Guardians rated Optivate® as helpful or very helpful in controlling 97.5% of bleeds by the prophylactic group, and in 98.5% of the bleeds in the on-demand group. Only 5 of 101 ADRs were treatment-related events (5%), all were mild and non-serious. There were no clinically significant changes in vital signs, viral transmissions or inhibitors. In young children Optivate® was well tolerated, safe and efficacious.

Insights on the toxicity of selected rare earth elements in rainbow trout hepatocytes.

The increasing extraction of rare earth elements (REEs) for technology applications raised concerns for contamination and toxicity in the environment. The purpose of this study was to examine the toxicity of the following REEs in primary cultures of rainbow trout hepatocytes: yttrium (Y), samarium (Sm), gadolinium (Gd), terbium (Tb) and lutetium (Lu). Hepatocytes were exposed to increasing concentrations of the above elements for 24 h at 15 °C and they were analyzed for viability, metallothioneins (MT), glutathione-S-transferase (GST) and arachidonate cyclooxygenase (COX) as markers of oxidative stress and inflammation. The results revealed that the cytoxicity of REEs were as follows in decreasing order: Y > Sm > Lu > Tb > Gd in concordance with published rainbow trout mortality data. While effects on GST and COX activities were marginal, MT levels were more strongly increased with the 2 most toxic REEs (Y and Sm) and Gd, while MT levels were decreased in the least toxic ones (Tb, Lu). While cell viability followed published trout mortality data, it also followed the redox potential and the glutathione affinity constant (log k). The capacity to induce/decrease MT levels was associated with ionic radius, log k (glutathione) and electronegativity. A proposed mechanism of toxicity for REEs is presented based on the chemical properties of REEs, namely the glutathione binding constant and ionic radius, in light of the observed effects in trout hepatocytes.

Chemical analysis of materials used in pig housing with respect to the safety of products of animal origin.

Bedding, environmental enrichment materials and disinfectant powders in pig farming are meant to ensure a hygienic bedding environment or allow pigs to perform explorative behaviour. To our knowledge, no legal regulation exists, that established maximum contents for undesirable substances, such as toxic metals, dioxins or trace elements in these materials, although oral ingestion could be expected. In the present study, a total of 74 materials (disinfectant powders [n = 51], earth/peat [n = 12], biochar [n = 8], recycled manure solids [n = 3]) were analysed for their content of various toxic metals, trace elements, dioxins and polychlorinated biphenyls. The data suggest that, in some samples, trace elements like iron, copper and zinc might have been added intentionally in order to induce physiological effects (iron supply to piglets, copper and zinc as growth promoter in pigs). Moreover, some materials contained high levels of lead, cadmium or arsenic. Consequently, if farm animals repeatedly consume environmental enrichment and bedding materials or disinfectant powders in considerable amounts and these quantities are added to the daily ration, the amount of ingested undesirable substances and trace elements might exceed the maximum levels set for complete feedstuffs, and an elevated transfer into food of animal origin might occur. Future studies are required to address the possible quantitative contribution in the light of feed and food safety. Finally, the excretion of undesirable substances with manure needs to be considered due to their possible accumulation in soils.