Treatment with Bumped Kinase Inhibitor 1294 Is Safe and Leads to Significant Protection against Abortion and Vertical Transmission in Sheep Experimentally Infected with Toxoplasma gondii during Pregnancy.

Previous studies on drug efficacy showed low protection against abortion and vertical transmission of Toxoplasma gondii in pregnant sheep. Bumped kinase inhibitors (BKIs), which are ATP-competitive inhibitors of calcium-dependent protein kinase 1 (CDPK1), were shown to be highly efficacious against several apicomplexan parasites in vitro and in laboratory animal models. Here, we present the safety and efficacy of BKI-1294 treatment (dosed orally at 100 mg/kg of body weight 5 times every 48 h) initiated 48 h after oral infection of sheep at midpregnancy with 1,000 TgShSp1 oocysts. BKI-1294 demonstrated systemic exposure in pregnant ewes, with maximum plasma concentrations of 2 to 3 µM and trough concentrations of 0.4 µM at 48 h after each dose. Oral administration of BKI-1294 in uninfected sheep at midpregnancy was deemed safe, since there were no changes in behavior, fecal consistency, rectal temperatures, hematological and biochemical parameters, or fetal mortality/morbidity. In ewes infected with a T. gondii oocyst dose lethal for fetuses, BKI-1294 treatment led to a minor rectal temperature increase after infection and a decrease in fetal/lamb mortality of 71%. None of the lambs born alive in the treated group exhibited congenital encephalitis lesions, and vertical transmission was prevented in 53% of them. BKI-1294 treatment during infection led to strong interferon gamma production after cell stimulation in vitro and a low humoral immune response to soluble tachyzoite antigens but high levels of anti-SAG1 antibodies. The results demonstrate a proof of concept for the therapeutic use of BKI-1294 to protect ovine fetuses from T. gondii infection during pregnancy.

Urinary BPA measurements in children and mothers from six European member states: Overall results and determinants of exposure.

For the first time in Europe, both European-wide and country-specific levels of urinary Bisphenol A (BPA) were obtained through a harmonized protocol for participant recruitment, sampling and quality controlled biomarker analysis in the frame of the twin projects COPHES and DEMOCOPHES. 674 child-mother pairs were recruited through schools or population registers from six European member states (Belgium, Denmark, Luxembourg, Slovenia, Spain and Sweden). Children (5-12 y) and mothers donated a urine sample. Information on socio-demographic characteristics, life style, dietary habits, and educational level of the parents was provided by mothers. After exclusion of urine samples with creatinine values below 300 mg/L or above 3000 mg/L, 653 children and 639 mothers remained for which BPA was measured. The geometric mean (with 95% confidence intervals) and 90th percentile were calculated for BPA separately in children and in mothers and were named "European reference values". After adjustment for confounders (age and creatinine), average exposure values in each country were compared with the mean of the "European reference values" by means of a weighted analysis of variance. Overall geometric means of all countries (95% CI) adjusted for urinary creatinine, age and gender were 2.04 (1.87-2.24) µg/L and 1.88 (1.71-2.07) µg/L for children (n=653) and mothers (n=639), respectively. Multiple regression analysis was used to identify significant environmental, geographical, personal or life style related determinants. Consumption of canned food and social class (represented by the highest educational level of the family) were the most important predictors for the urinary levels of BPA in mothers and children. The individual BPA levels in children were significantly correlated with the levels in their mothers (r=0.265, p<0.001), which may suggest a possible common environmental/dietary factor that influences the biomarker level in each pair. Exposure of the general European population was well below the current health-based guidance values and no participant had BPA values higher than the health-based guidance values.

Presence of anti-Leishmania infantum antibodies in sheep (Ovis aries) in Spain.

Sandflies are the primary transmission vector for Leishmania spp parasite in endemic regions. The role of other animals, different from the dog, is under discussion in the leishmaniosis endemic countries. A limited number of reports have been published on the possible role of livestock in European countries for Leishmania maintenance and diffusion. The aim of the present study was to perform a serosurvey on sheep in areas of Spain that are endemic for zoonotic leishmaniosis and establish the possible role of sheep regarding Leishmania infantum infection in endemic areas. Three hundred and two serum samples were obtained from sheep and were evaluated for serological survey to detect L. infantum by using the in-house ELISA technique. Twenty-eight out of the 302 samples included in this study, were positive for L. infantum antibodies (9.27%). In the present study, a significant association was found between adult age and seropositivity (p = 0.006) and female gender and seropositivity (p = 0.02). This association has not been previously described in other European studies related to L. infantum infection in sheep. Our study reveals that domestic sheep in a European Mediterranean country are exposed to L. infantum. To our knowledge, this study demonstrates the presence of seropositive sheep in different regions of Spain for the first time. Further epidemiological studies focus on evaluating the rural cycle of this parasite to know if livestock could act as a potential reservoir are needed.

Use of a local anaesthetic and antiseptic wound formulation for the treatment of lambs naturally infected with Orf virus.

Contagious ecthyma (CE) is a worldwide highly contagious zoonotic viral skin disease of sheep and goats. Treatment for Orf virus (ORFV) infection usually involves topical and oral antibiotics. An anaesthetic and antiseptic topical gel (Multisolfen® or Tri-Solfen®; MS®, Medical Ethics, Australia) has been documented as an efficacious therapy for lesions from mucosal and epithelial viral infections in ruminants. The present study tested a new treatment protocol of MS® for CE therapy on-farm in 150 lambs naturally infected with ORFV. Lambs were divided into three cohorts of 50 lambs each (C, D and E). Cohort C was treated with MS® 3 times with an interval of 3 days between treatments, cohort D was treated daily with hypochlorous acid, whilst cohort E served as untreated controls. The lambs were examined clinically every two days, weight measured weekly, with whole blood and sterile swabs from ORFV lesions collected for haematological analysis and specific ORFV PCR. Cohort C presented fewer lambs displaying ORFV-associated lesions than other cohorts at different times of the experiment. Further, lesions treated with MS® were milder compared with other cohorts. However, following cessation of therapy, most of the lambs again developed ORFV-associated lesions. No differences between cohorts were observed in weight, haematological and PCR results. These findings suggest that topical treatment with MS® is effective for CE in field conditions, especially in the first stages of the clinical course, although treatment with MS® may need to be extended a minimum of 4 weeks.

Sensitive Instrumental Method for Quantitative Determination of High-Brominated Flame Retardants in Human Serum Samples.

BACKGROUND: High-brominated flame retardants (BFRs) can be released into the environment from consumer products, such as electric and electronic equipment, and enter the human body by different pathways. Because of their toxicity and the regulations, it is very relevant to know their levels and trends in human samples. However, chromatographic serum analysis of some of these compounds represents nowadays a challenge in the general population. OBJECTIVE: To optimize and validate an instrumental method based on gas chromatography coupled to mass spectrometry, which, together with a simple sample preparation procedure, allows the analysis of decabromodiphenyl ether (BDE-209), decabromodiphenyl ethane (DBDPE), and tetrabromobisphenol A-bis(2,3-dibromopropyl ether) (TBBPA-DBPE) in human serum samples from the general population. METHOD: To minimize the high degradation during instrumental analysis, GC parameters such as injection volumes, carrier flow rates, and column lengths were assessed and optimized. This instrumental approach in combination with solid-phase extraction (SPE) followed by multilayer silica gel column purification allowed satisfactory analysis using only 1 mL of serum. RESULTS: The performance of the complete method was evaluated at three spiking levels, 0.01, 0.05, and 0.2 ng/mL. Recoveries in the range 87-108% were obtained whereas the relative standard deviation in interday measurements, were, in general, lower than 19%. Limits of detection were in the range of 0.0045-0.0070 ng/mL. The optimized procedure was successfully applied to the determination of the investigated pollutants in real human samples of general population. CONCLUSIONS: The proposed method could contribute to the inclusion of these environmental pollutants in human biomonitoring (HBM) studies, increasing the knowledge of levels and trends in the general population. HIGHLIGHTS: GC-MS parameters optimization to minimize instrumental analytes degradation. Successful application to human serum samples from the general population. Tetrabromobisphenol A bis(2,3-dibromopropyl ether) human serum levels are reported for the first time.

Use of a Local Anaesthetic/Antiseptic Formulation for the Treatment of Lambs Experimentally Infected with Orf Virus.

Contagious ecthyma is a highly transmissible eruptive viral disease of the skin and mucosa of sheep and goats distributed worldwide. The treatment of orf lesions is usually based on the use of antiseptics and antibiotics for the management of presumptive secondary infections, increasing risks of antimicrobial resistance. The wound dressing formulation Tri-Solfen® (TS) containing two local anaesthetics (lignocaine and bupivacaine), adrenaline and an antiseptic (cetrimide) in a gel formulation has been demonstrated to reduce suffering and enhance recovery in cattle and buffalo with oral and skin lesions due to foot-and-mouth disease virus infection and reduced the orf viral load in lambs. In the present study, experimental infection with the orf virus was conducted in 50 newborn lambs and 25 animals were treated after the presence of the first lesions with TS and repeated three days later. Daily clinical examination, haematological, serological, biomolecular and post-mortem analyses were conducted during 34 days after treatment. Results indicated that treatment had no effect on weight gain and clinical progression of the lesions. It was determined that seroconversion after experimental infection occurs 34 days after infection and suggested that the deep basal epithelial location of the orf lesions may have prevented the therapy from having altered the clinical course.

Anaemia in Ruminants Caused by Plant Consumption.

Plant toxicology has affected animals throughout evolution. Plants have adapted themselves to the environment. This adaptation has led to the development of defensive strategies to avoid being consumed. Plants have several chemical compounds, which can cause deleterious effects on people or animals that consume them, causing a wide variety of clinical signs. Plants from various latitudes, both cultivated for human and animal feeding or decorative purpose and even wild growth plants are able to generate anaemia in ruminants. Coumarins or ptaquiloside predispose bleeding and haemorrhages, causing a haemorrhagic disease in affected animals. In this group, some important fodder plants, such sweet clover (Genus Melilotus spp.), or other weeds distributed worldwide, such as bracken fern (Pteridium aquilinum) of giant fennel (Ferula communis), are included. On the other hand, sulfur-containing chemicals (e.g., n-propyl disulfate and S-propyl cysteine sulfoxides (SMCOs)) may cause severe direct damage to the erythrocyte and their membrane, leading to their destruction and causing haemolytic anaemia in the animal. This review presents the most frequent intoxication by plants causing anaemia in ruminants. Toxic compounds, clinical signs, diagnosis and possible treatments are also presented.

Comparative Study of the Use of Doxycycline and Oxytetracycline to Treat Anaplasmosis in Fattening Lambs.

Lamb icteric carcasses condemnation due to Anaplasma ovis is causing relevant economic losses. A comparative study was developed on the effects of different antibiotics to treat ovine anaplasmosis in fattening lambs. A total of 100 A. ovis naturally infected lambs were selected and randomly divided into four groups of 25 lambs: Group ID, treated with injectable doxycycline; Group OD, oral doxycycline; Group O, injectable oxytetracycline; and Group C, untreated animals for the control group. Clinical, haematological, and molecular analyses were performed before the treatment and 12 and 45 days after the beginning of the treatments, and carcass condemnation was followed after slaughter. The A. ovis bacterial load was high before the treatments in the four groups and decreased significantly 45 days after treatment in the ID and O Groups (p < 0.001). The parameters that were related to haemolysis showed similar results. At the abattoir, 15 out of the 47 examined carcasses were condemned; 7 of C Group, 6 of OD Group, 2 of O Group, and 0 of ID Group. It can be concluded that injectable doxycycline and oxytetracycline significantly reduce A. ovis bacterial load in blood and carcass condemnation at the abattoir. Further studies are needed in order to confirm these encouraging findings.

Squamous cell carcinoma of the vagina and cervix in sheep - case report.

This report describes the clinical and histopathological characteristics of a squamous cell carcinoma infiltrating the cervix and the vaginal wall, producing reproductive symptoms and subnormal fertility in an adult ewe. Necropsy showed a large (15-cm-long) neoplastic mass infiltrating the vaginal wall and the cervix. Histopathological examination revealed atypical squamous epithelial cords invading the basal membrane and dermis, round anaplastic cells, focal areas of necrosis, keratinisation of isolated cells, and pronounced infiltration by mononuclear cells around the cords. No squamous cell carcinoma of such localisation has been reported from sheep before. In humans, this tumour is the most common gynaecological malignancy in the world.

Absence of SARS-CoV-2 Antibodies in Natural Environment Exposure in Sheep in Close Contact with Humans.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the zoonotic causative agent of coronavirus disease 2019 (COVID-19) that has caused a pandemic situation with millions of infected humans worldwide. Among domestic animals, there have been limited studies regarding the transmissibility and exposure to the infection in natural conditions. Some animals are exposed and/or susceptible to SARS-CoV-2 infection, such as cats, ferrets and dogs. By contrast, there is no information about the susceptibility of ruminants to SARS-CoV-2. This study tested the antibody response in 90 ovine pre-pandemic serum samples and 336 sheep serum samples from the pandemic period (June 2020 to March 2021). In both cases, the animals were in close contact with a veterinary student community composed of more than 700 members. None of the serum samples analyzed was seroreactive based on an enzyme-linked immunosorbent assay (ELISA) using the receptor-binding domain (RBD) of the spike antigen. In this sense, no statistical difference was observed compared to the pre-pandemic sheep. Our results suggest that it seems unlikely that sheep could play a relevant role in the epidemiology of SARS-CoV-2 infection. This is the first study to report the absence of evidence of sheep exposure to SARS-CoV-2 in natural conditions.

Prevalence of Salmonella enterica subsp. diarizonae serotype 61:k:1:5:(7) in nasal secretions and stool of sheep flocks with and without cases of chronic proliferative rhinitis.

Salmonella enterica subsp. diarizonae serotype 61: k: 1,5, (7) (SED) is a microorganism well adapted to sheep; however, it has also been described producing chronic proliferative rhinitis (CPR) in ovine. CPR causes a proliferative inflammation of the ventral nasal turbinates that may totally obstruct the nasal cavity. The main objective of the present study was to investigate the prevalence of SED in nostrils and stool of sheep without CPR clinical signs in commercial sheep farms of Spain with and without previous clinical cases of CPR. Five samplings were performed in 10 commercial sheep farms for one year. Samples from nostrils and faeces were taken from four animals without CPR visible clinical signs that belonged to four different age ranges at each farm visit. The prevalence of positive animals was 45.3 %, and the number of positive samples in nostrils was higher than in faeces (38.5 % vs 22.5 %). Only on one farm was no positive result obtained in the entire study. In almost all positive farms, sheep belonging to the youngest age ranges accounted for more than 50 % of positive isolates. Finally, farms with a previous diagnosis of CPR were 1.784 times more likely to have an animal with positive isolation than farms without a previous diagnosis. This could suggest that the infection pressure in the farm might favour the occurrence of clinical cases of the disease. However, further studies will be necessary to unravel why this saprophytic bacterium is able to cross the epithelial barrier causing severe rhinitis in certain animals.

Impact of Stress on Health and Final Weight in Fattening Lambs.

In order to determine whether the stress level had any influence on the health and final weight of Rasa Aragonesa fattening lambs, stress markers were measured throughout the fattening period in 80 feedlot lambs (group F) and in 40 lambs finished on the farm of birth (group C). The highest values of the stress indicators-neutrophil-to-lymphocyte-ratio (N/L), non-esterified fatty acids (NEFA), serum cortisol and fecal cortisol metabolites (FCM)-were recorded after the road transportation of group F to the feedlot. No differences between the groups were identified at the end of the adaptation period, but at the end of the fattening, statistically significant higher values for NEFA and serum cortisol were determined in group F. However, statistically significant differences between the groups were not found in the percentage of lambs with clinical signs of illness and ovine respiratory complex (ORC) lesions or in the final weight of the lambs. Independent of the location at which the lambs were fattened, those with FCM values at the beginning of the study (at the time of weaning) in the highest quartile developed a higher percentage of clinical signs of illness (45.5% vs. 32.1%, p > 0.05) and ORC lesions (45.5% vs. 10.7%, p < 0.01), and their average final weight was lower (24.36 kg vs. 27.40 kg, p = 0.001) than those with values in the lowest quartile. Stress experienced by lambs prior to finishing seems to be relevant for their further development, and FCM concentration at the time of weaning could be used as an indicator of health and productive performance of the lambs during the fattening period, regardless of finishing location.

The Relevance of Caseous Lymphadenitis as a Cause of Culling in Adult Sheep.

Four hundred and ninety-eight culled sheep received at the Ruminant Clinical Service of the Veterinary Faculty of Zaragoza, Spain, were examined in life and after humanitarian sacrifice in order to reach the final diagnosis of the cause of culling and to evaluate the presence of caseous lymphadenitis (CLA) lesions. One hundred and forty-seven of the 498 studied animals (29.52%) showed CLA compatible lesions that were subsequently confirmed by Corynebacterium pseudotuberculosis isolation. One hundred and seven of the 147 CLA affected animals presenting the visceral clinical form of the disease (72.79%), while only 32 animals were affected by the superficial form (21.77%). In addition, eight animals were found to be affected in both the visceral and the superficial presentations (5.44%). Eighty-four of the 147 CLA-affected animals (57.14%) did not show any concurrent disease, considering, in this case, CLA the main cause of culling (84/498: 16.87%). In the superficial presentation, the retropharyngeal lymph node, as a sole lesion, was the most frequently affected (13/32: 40.63%). Further, in the visceral form of the disease, 85.06% of the affected animals had the lesions located in the respiratory system (91/107: 85.06%). CLA was revealed as an important cause of culling in sheep production.

Management of Risk Factors Associated with Chronic Oral Lesions in Sheep.

Oral disorders constitute a significant cause of weight loss in sheep. In a study of disorders of the oral cavity of 36,033 sheep from 60 meat sheep flocks in Spain, we looked for management risk factors associated with chronic oral lesions. Mandibular and maxillary disorders were assessed as an external manifestation of oral lesions by palpation, searching for tissue swellings, fistulae, or open wounds. The prevalence of flocks containing sheep with jaw disorders was 98.3%, with an average individual prevalence of 5.5%. The majority of lesions were located in in the mid-region of the mandible, and the most relevant risk factor was increasing age. Use of acidic diets based on silage and inclusion of hard foods, such as maize straw or hay, was associated with the occurrence of jaw inflammation. It was concluded that hard diets containing plant material with edges and sharp areas, plus acidic foods including silage, are more likely to cause lesions of the gingiva, enabling entry of pathogens to the oral mucosa that eventually establish locally in bony tissues, usually as mandibular osteomyelitis. It was also observed that mineral supplementation appears to prevent the occurrence of these lesions.

Impact of a Topical Anaesthesia Wound Management Formulation on Pain, Inflammation and Reduction of Secondary Infections after Tail Docking in Lambs.

We examined several procedures for surgical tail docking; with and without general anaesthesia (GA), including the use of a topical wound gel formulation to provide pain relief (PR) and improve healing after surgery, containing local anaesthetics lignocaine and bupivacaine, with cetrimide and adrenalin. Forty-four lambs were recruited into four equal cohorts: Groups A and C, the tail was excised with a scalpel without anaesthesia or stitches; Groups B and D, the tail was surgically excised and stitched under GA; Groups C and D wounds were immediately sprayed with PR. Behavioural observations identified that Groups A and C displayed significantly less pain-related behaviours than Groups B and D shortly after the procedure, especially if treated with PR. Similarly, the mean of days when animals showed no signs of wound infection was longer in the groups not undergoing stitching. Finally, treatment with PR appeared to reduce the cortisol response and avoided the elevation of serum amyloid A in lambs where the tail was excised without general anaesthesia. In conclusion, surgical tail-docking without GA but where wounds are immediately sprayed with PR, appears as an affordable and more welfare-appropriate method for conducting tail docking in lambs.

Anaplasmosis Outbreak in Lambs: First Report Causing Carcass Condemnation.

In spring and summer 2020, six outbreaks of condemnation of jaundiced lamb carcasses were diagnosed in different farms in Aragón region, Spain. Anaplasma ovis was identified in all affected farms. Four hundred and ninety-two lambs from two affected farms were more closely examined. Clinical examination, haematologies, biochemistries, histopathology and microbiological and molecular analyses were performed. After slaughter, 34.84% of the lambs showed jaundiced carcasses and 79.64% presented splenomegaly at the abattoir. All tested lambs with icteric carcasses showed positive A. ovis PCR, although 72.72% of the unaffected lambs also tested positive. However, the bacterial load was significantly higher in the animals that showed jaundiced carcasses (Cq: 25.00 vs 26.16; p = 0.004). Moreover, all the tested lambs that showed severe anaemia were PCR positive. On the contrary, the PCR negative lambs did not show anaemia. Lambs that presented icteric carcasses displayed severe regenerative anaemia with significantly lower erythrocyte count (7.18 vs. 11.97), haematocrit (26.89 vs. 34.82) and haemoglobin (8.50 vs. 11.10) than unaffected lambs. Reticulocyte count (18.80 vs. 5.65) was also significantly increased in affected animals. This article describes a new disorder caused by Anaplasma ovis that is producing significant economic losses associated with the carcass condemnation of apparently healthy lamb.

[Education for health. Nutrition and gastronomy in the Autonomous Cities of Melilla and Ceuta]. / Educación para la salud. Nutrición y gastronomía en las ciudades autónomas de Melilla y Ceuta.

INTRODUCTION: The aim of this research was to analyze overweigh and obesity among student population of childhood and primary education levels, in a first stage at the city of Melilla (2005), and two years later in Ceuta. From an administrative point of view both cities depend on the Ministry of Education and Culture, alike the Spanish education centers in foreign countries. This research begun gathering anthropometric measures of students and surveys about gastronomic and dietary habits of their families, with the objective of detecting and modifying those that were not healthy, and foster the adoption of healthy habits among students, who could influence their families through their cooperation and engagement. Once students adopted healthy nutritive behaviors, those were complemented with physical activity. To achieve these aims, the following steps were taken: - Education on health for teachers through CEPs. - Include in the scholar curriculum a new matter: Education for Health and Non-Competitive Physical Exercise, as part of the existing programs Education for Citizenship and Physical Education. - Develop extracurricular activities together with parents and students: cooking workshops and physical exercise. - Implement at the childhood and primary schools a program of Healthy Breakfasts: during a quarter breakfasts composed by fresh fruit, whole meal bread toast with virgin olive oil, and sugar free yoghourt were delivered. Vending machines of juices and industrial baking were forbidden at educational centers. - Analyze and correct the menus delivered at school canteens.

INTRODUCCIÓN: Se trató de analizar la situación de sobrepeso y obesidad de la población escolar en el nivel educativo de Infantil y Primaria, primero en la ciudad de Melilla (2005) y, dos años más tarde, en la de Ceuta, dependientes administrativamente, lo mismo que los centros españoles en el extranjero, del Ministerio de Educación y Cultura (MEC). El estudio comenzó con la toma de medidas antropométricas y encuestas sobre los hábitos alimentarios y gastronómicos de los escolares y sus familias con la finalidad de detectar y modificar aquellos que no fuesen saludables y fomentar la adopción de hábitos saludables en los escolares y, a través de ellos, influir en sus familias, buscando su colaboración e implicación en este aprendizaje, complementándolo con la práctica de la actividad física. Para ello se realizaron las siguientes actuaciones: ­ Formación de profesores a través de los CEP en educación para la salud. ­ Introducir en el currículum escolar las materias Educación para la Salud y Ejercicio Físico no Competitivo dentro de los contenidos de las materias de Educación para la Ciudadanía y Educación Física, respectivamente. ­ Desarrollar actividades extraescolares conjuntas con alumnos y padres de talleres de cocina y actividad física. ­ Implantar en los centros educativos de Infantil y Primaria (CEIP) el consumo de desayunos saludables. Se distribuyeron durante un trimestre desayunos en los centros de Infantil y Primaria consistentes en: fruta fresca, tostada de pan integral con aceite de oliva virgen y yogur natural no azucarado. Se prohibieron las máquinas expendedoras de zumos y bollería en los centros educativos. ­ Analizar y corregir los menús de los comedores escolares.

Effects of chlorpyrifos on cell death and cellular phenotypic specification of human neural stem cells.

Chlorpyrifos (CPF) is an organophosphate pesticide widely used in agriculture, whose traditional and well-known mechanism of action is the inhibition of the enzyme Acetylcholinesterase (AChE). Subacute exposures to CPF have been associated with alterations different from the inhibition of AChE. Because of the vulnerability of the developing nervous system, prenatal and early postnatal exposures are of special concern. Human neural stem cells (hNSC) provide the opportunity to study early stages of neural development and may be a valuable tool for developmental neurotoxicology (DNT). In the current work, the cell line hNS1 was used as a model system with the aim of validating this cell line as a reliable testing method. To evaluate the effects of CPF on early developmental stages, hNS1 cells were exposed to different concentrations of the pesticide and cell death, proliferation and cell fate specification were analyzed under differentiation conditions. Since hNS1 cells responded to CPF in a similar way to other human cell lines, we consider it may be a valid model for DNT chemical assessment. CPF induced apoptotic cell death only at the highest doses tested, suggesting that it is not toxic for the specific developmental stage here addressed under short term exposure. In addition, the higher doses of CPF promoted the generation of astroglial cells, without affecting neurogenesis.

Associations of multiple exposures to persistent toxic substances with the risk of hyperuricemia and subclinical uric acid levels in BIOAMBIENT.ES study.

Hyperuricemia is becoming a serious public health issue, which is highly influenced by environmental factors, although there is still controversial information on the potential influence of the exposure to Persistent Toxic Substances (PTSs) in the general population. In this study we aimed to assess the association. PTS exposure with uric acid homeostasis in a sample of the Spanish population. Participants were recruited during 2009-2010 in all the main geographical areas of Spain. Exposure to 34 PTSs was estimated by chemical analyses of serum levels of 6 Polychlorinated Biphenyls (PCBs, n = 950), 13 Organochlorine Pesticides (OCPs, n = 453), 6 Perfluoroalkyl Substances (PFAs, n = 755), 7 Polybrominated Diphenyl Ethers (PBDEs, n = 365), urinary Cadmium (n = 926), and Lead in whole blood (n = 882). The two study outcomes were defined as the prevalence of hyperuricemia in the study population and uric acid levels, the latter only in individuals with no previous diagnosis of hyperuricemia. Statistical analyses were performed by means of binomial logistic regression and linear regression, and mixture effects were screened using Weighted Quantile Sum Regression (WQS). Serum concentrations of γ-HCH, o,p´-DDE, PCB-138, PCB-153, PFOA, and urinary Cadmium were associated with an increased risk of hyperuricemia, while PBDE-153 showed an inverse association with the effect. Furthermore, exposure to Cadmium, PCB-138, and to PCB-153 was positively associated with uric acid levels. Results were consistent after lipid adjustment or standardization. WQS analyses revealed a major contribution of PCB-153 within the PCB mixture on both the risk of hyperuricemia and uric acid levels. Sensitivity analyses were performed by adjusting for dietary habits, fasting glucose and estimated glomerular filtration rate. Overall, we found novel associations between human exposure to mixtures of PTSs and disturbances in uric acid homeostasis. However, we cannot completely rule out potential residual confounding effect or reversed-causality related to the cross-sectional design.

Differential contribution of animal and vegetable food items on persistent organic pollutant serum concentrations in Spanish adults. Data from BIOAMBIENT.ES project.

Diet is considered the main source of Persistent Organic Pollutant (POP) exposure in the general population, although there are still several gaps of knowledge regarding the differential contribution of main food groups. The aim of this study was to identify dietary patterns that contribute to human exposure to organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and Perfluoroalkyl Substances (PFASs). Study population (n=1880, 18-65years old) was recruited during 2009-2010 in all the main geographical areas of Spain. For this work, exposure was estimated by chemical analyses of serum levels of 6 PCBs (n=1880), 13 OCPs (n=934), and 6 (PFASs) in a subsample of 755 (n=755). Dietary habits and covariates were gathered via self-administered questionnaires. Data analyses were performed by means of multivariable linear regression and weighted quantile sum regression. Both the consumption of animal-based and plant-based food were positively associated with the individual concentrations of p,p´-DDE, hexachlorobenzene, and PCB-congeners -138, -153, and-180. The contribution of animal-based products was 2.1-4.0× stronger except in p,p´-DDE, to which both patterns had similar contributions. In PFASs only animal food was positively associated with the exposure levels. The main animal-based contributors to PCB exposure were fish (49-64%) and eggs (19-36%), while OCP concentrations were mainly influenced by dairy products (32-48%) and fish (47-48%). PFOA and PFHxS were mainly explained by cold-meat (34-37%), fish (25-26%), and eggs (19-21%), while PFOS and PFDA were primarily influenced by fish consumption (44-77%). In the case of plant-based items, fruits (25-82%) and vegetables (18-63%) accounted for the majority of the variability of PCB and OCP concentrations. Our results highlight the relevance of dietary POP exposure as well as the need for the consideration of nutritional interventions in public health programs aiming to reduce POP exposure in the general population.