Diagnostic accuracy of cell-free DNA in maternal blood in detecting chromosomal anomalies in twin pregnancies: systematic review and meta-analysis.

OBJECTIVES: To report the diagnostic accuracy of cell-free DNA (cfDNA) in maternal blood in detecting chromosomal anomalies in twin pregnancies. METHODS: Medline, Embase and Cochrane databases were searched. The inclusion criteria were twin pregnancies undergoing cfDNA screening for Trisomies 13, 18, 21, monosomy X0 and other sex chromosomal anomalies (SCA). The index test was represented by a positive results of cfDNA test. The reference standard was represented by the karyotype results (obtained either pre or postnatally) or, in case of negative cfDNA result, by a normal neonatal phenotype. The quality of the studies was assessed using the revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2). Summary estimates of sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-) and diagnostic odds ratio (DOR), with the corresponding 95% Confidence Intervals (95% CI), were computed using the bivariate random-effects model. RESULTS: Thirty-five studies were included. cfDNA had an overall high accuracy in detecting Trisomy 21 in twin pregnancies with a sensitivity of 98.8% (95% CI 96.5-100), a specificity of 100% (95% CI 99.9-100). Sensitivity and specificity were of 94.9% (95% CI 75.6-99.1) and 100 (95% CI 99.9-100) for Trisomy 18, and 84.6% (95% C% 54.6-98.1) and 100% (95% CI 99.9-100) for Trisomy 13 . We could not compute the diagnostic accuracy of cfDNA in detecting monosomy X0 in twins, while cfDNA had a sensitivity of 100% (95% CI 71.5-100) and a specificity of 99.8% (95% CI 99.7-99.9) in detecting other SCA (11 cases). The accuracy of cfDNA in detecting Trisomy 21, 18 and 13 was similar in dichorionic and monochorionic twin pregnancies. CONCLUSION: cfDNA has a high diagnostic accuracy in detecting Trisomy 18 and 21 in twin pregnancies, irrespective of chorionicity. Accuracy in the detection of Trisomy 13 and SCA was limited by the small number of affected cases and the difficulties in the confirmation of false negative cases in case of SCA and requires confirmation in larger studies. This article is protected by copyright. All rights reserved.

Developing an improved optical biosensing system based on gold nanoparticles acting as interferometric enhancers in Lactoferrin detection.

We report for the first time the whole development of a biosensing system based on the Interferometric Optical Detection Method (IODM) enriched with gold nanoparticles (AuNPs), acting as interferometric enhancers for improving the performance of immunoassays. For this purpose, the Lactoferrin sandwich immunoassay model was employed. We describe in detail the entire value chain from the AuNPs production, its functionalization, and characterization with anti-Lactoferrin (anti-LF), the biosensing response of these conjugates as well as their corresponding calculation of the kinetic constants, performance comparison of the readout interferometric signals versus Scanning Electron Microscopy (SEM) and the percentage of the sensing surface covered. Finally, a Lactoferrin sandwich immunoassay was carried out and correlated with Enzyme-Linked ImmunoSorbent Assay (ELISA), and the Limit of Detection and sensitivity figures were obtained. As a result, we demonstrate how the AuNPs act as interferometric amplifiers of the IODM for improving the biosensing response, opening the possibility of being applied in multiple biological detection applications.

Adaptaciones de la dispensación hospitalaria a pacientes con hemofilia durante la pandemia COVID-19 en España y su influencia en la adherencia / Adaptations of hospital dispensing to haemophilia patients during the COVID-19 pandemic in Spain and its influence on adherence

Introducción: El estado de alarma decretado por la pandemia del virus SARS COV-2 del 14 de marzo hasta el 21 de junio, ha supuesto un desafío para el área de pacientes externos de los Servicios de Farmacia. Nos centramos en los pacientes con hemofilia que se administran factores de la coagulación de forma crónica para prevenir hemorragias.Objetivos: Analizar durante este periodo el porcentaje de pacientes que han recogido su medicación, han mantenido la adherencia al tratamiento y las barreras encontradas para ello. Cuantificar el número y gravedad de episodios hemorrágicos (EH) sufridos y su relación con la pandemia. Analizar la prevalencia y gravedad de COVID en hemofílicos.Métodos: Uno objetivo, utilizando los registros del hospital y otro subjetivo, mediante encuesta oral durante la consulta de atención farmacéutica presencial o telemática.Resultados: El 80% de los pacientes retiraron medicación durante el periodo de estudio, un 30% en domicilio. El último mes las dispensaciones a domicilio se acompañaron de consulta telemática.Un 24% de pacientes disminuyó su adherencia respecto al 2019. Las principales causas fueron dificultad para acudir al hospital, y percepción de no necesitar tratamiento ante la inactividad.No se registraron más EH o ingresos por causas imputables a la pandemia.No hubo ningún enfermo COVID-19 grave y la incidencia de pacientes con síntomas leves fue similar a la población general.Conclusión: La mayoría de los pacientes con hemofilia pudieron acceder a su medicación. La adherencia se redujo. Los EH no aumentaron por causas atribuibles a la pandemia. La incidencia de COVID-19 fue similar a la población. (AU)

Introduction: The state of alarm decreed by the SARS COV-2 virus pandemic from March 14th to June 21st, has meant a challenge for the outpatient area of the pharmacy services. We focus on hemophilia patients who are chronically administered clotting factors to prevent bleeding.Objectives: To analyse during this period the percentage of patients who have collected their medication, maintained adherence to treatment and the barriers encountered in doing so. To quantify the number and severity of haemorrhagic episodes (HD) suffered and their relationship with the pandemic. Analyse the prevalence and severity of COVID in haemophiliacs.Methods: One objective, using hospital records, and one subjective, using an oral survey during the face-to-face or telematic pharmaceutical care consultation.Results: 80% of patients withdrew medication during the study period, 30% at home. In the last month, home deliveries were accompanied by telematic consultation.24% of patients decreased their adherence with respect to 2019. The main causes were difficulty in going to hospital, and perception of not needing treatment in the face of inactivity.There were no more HD or admissions for reasons attributable to the pandemic.There were no serious COVID-19 patients and the incidence of patients with mild symptoms was similar to the general population.Conclusion: Most haemophilia patients were able to access their medication. Adherence was reduced. HD did not increase due to causes attributable to the pandemic. The incidence of COVID-19 was similar to the population. (AU)

Developing an Optical Interferometric Detection Method based biosensor for detecting specific SARS-CoV-2 immunoglobulins in Serum and Saliva, and their corresponding ELISA correlation.

The standard rapid approach for the diagnosis of coronavirus disease 2019 (COVID-19) is the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. The detection of specific anti-SARS-CoV-2 immunoglobulins is crucial for screening people who have been exposed to the virus, whether or not they presented symptoms. Recent publications report different methods for the detection of specific IgGs, IgMs, and IgAs against SARS-CoV-2; these methods mainly detect immunoglobulins in the serum using conventional techniques such as rapid lateral flow tests or enzyme-linked immunosorbent assay (ELISA). In this article, we report the production of recombinant SARS-CoV-2 spike protein and the development of a rapid, reliable, cost-effective test, capable of detecting immunoglobulins in serum and saliva samples. This method is based on interferometric optical detection. The results obtained using this method and those obtained using ELISA were compared. Owing to its low cost and simplicity, this test can be used periodically for the early detection, surveillance, detection of immunity, and control of the spread of COVID-19.

Exome sequencing of early-onset patients supports genetic heterogeneity in colorectal cancer.

Colorectal cancer (CRC) is a complex disease that can be caused by a spectrum of genetic variants ranging from low to high penetrance changes, that interact with the environment to determine which individuals will develop the disease. In this study, we sequenced 20 early-onset CRC patients to discover novel genetic variants that could be linked to the prompt disease development. Eight genes, CHAD, CHD1L, ERCC6, IGTB7, PTPN13, SPATA20, TDG and TGS1, were selected and re-sequenced in a further 304 early onset CRC patients to search for rare, high-impact variants. Although we found a recurring truncating variant in the TDG gene shared by two independent patients, the results obtained did not help consolidate any of the candidates as promising CRC predisposing genes. However, we found that potential risk alleles in our extended list of candidate variants have a tendency to appear at higher numbers in younger cases. This supports the idea that CRC onset may be oligogenic in nature and may show molecular heterogeneity. Further, larger and robust studies are thus needed to unravel the genetics behind early-onset CRC development, coupled with novel functional analyses and omic approaches that may offer complementary insight.

Chemical restraint of coatis by the association of Detomidine, Tiletamine and Zolazepam, in allometrically scaled dosages / [Contenção farmacológica de quatis pela associação de detomidina, tiletamina e zolazepam, em doses calculadas por extrapolação alométrica]

Ten free-living adult coatis (two males and eight females) were chemically restrained with "ZAD-50", a concentrated formulation prepared with the dehydrated content of a Zoletil/50® vial diluted with 0.25mL of 1% atropine, 0.265mL of Dormiun-V®, and 2.2mL of distilled water, being exactly 3.0mL. The formula was administered to each animal previously captured and physically contained with a net. The loss of righting reflex (RR) occurred at 2.3±0.8 minutes post-injection (MPI), with anesthesia beginning at 4.4±2.7 MPI. Myorelaxant and analgesia were considered excellent at all moments of the evaluation. Conscious reactions were observed at 78.7±22.2 MPI, the return of the RR occurred at 101 ± 18 MPI, and normal ambulation was acquired at 137.0±31.0 MPI. The mean values ​​of physiological parameters measured every 10 minutes between 10 and 50 MPI were 152.2 heartbeats per minute for heart rate, 66.4 respiratory movements per minute for respiratory rate, 39.2oC for rectal temperature, 86.2% for SpO2 and 14.6 mmHg for systolic blood pressure. In the same times, the EEG registered sinus rhythm. No adverse reactions were observed, and the assessed vital parameters remained compatible with the state of chemical restraint.(AU)

Dez quatis adultos de vida livre (dois machos e oito fêmeas) foram contidos empregando-se a formulação denominada "ZAD-50". A fórmula foi preparada a partir do conteúdo desidratado de um frasco de Zoletil/50® diluído em 0,25mL de atropina a 1%, 0,265mL de Dormiun-V® e 2,2mL de água destilada, obtendo-se volume final de 3,0mL. A associação foi administrada, por via intramuscular, a cada animal capturado e contido fisicamente com puçá, em dose calculada por meio de extrapolação alométrica interespecífica. A perda da reação postural de endireitamento (RPE) ocorreu aos 2,3±0,8 minutos pós-injeção (MPI), observando-se início da anestesia aos 4,4±2,7 MPI. Miorrelaxamento e analgesia foram considerados excelentes em todos os momentos da avaliação. Reações conscientes foram observadas aos 78,7±22,2 MPI, o retorno da RPE ocorreu aos 101±18 MPI, e os animais voltaram à ambulação normal aos 137,0±31,0 MPI. Os valores médios dos parâmetros fisiológicos mensurados a cada 10 minutos entre 10 e 50 MPI foram 152,2 batimentos por minuto para frequência cardíaca, 66,4 movimentos por minuto para frequência respiratória, 39,2oC para temperatura retal, 86,2% para saturação parcial de oxigênio e 14,6mmHg para pressão arterial sistólica. Nesses tempos, observou-se ritmo sinusal no eletrocardiograma, e não foram observadas reações adversas.(AU)

Sub-clustering in skeletal class III malocclusion phenotypes via principal component analysis in a southern European population.

The main aim of this study was to generate an adequate sub-phenotypic clustering model of class III skeletal malocclusion in an adult population of southern European origin. The study design was conducted in two phases, a preliminary cross-sectional study and a subsequent discriminatory evaluation by main component and cluster analysis to identify differentiated skeletal sub-groups with differentiated phenotypic characteristics. Radiometric data from 699 adult patients of southern European origin were analyzed in 212 selected subjects affected by class III skeletal malocclusion. The varimax rotation was used with Kaiser normalization, to prevent variables with more explanatory capacity from affecting the rotation. A total of 21,624 radiographic measurements were obtained as part of the cluster model generation, using a total set of 55 skeletal variables for the subsequent analysis of the major component and cluster analyses. Ten main axes were generated representing 92.7% of the total variation. Three main components represented 58.5%, with particular sagittal and vertical variables acting as major descriptors. Post hoc phenotypic clustering retrieved six clusters: C1:9.9%, C2:18.9%, C3:33%, C4:3.77%, C5:16%, and C6:16%. In conclusion, phenotypic variation was found in the southern European skeletal class III population, demonstrating the existence of phenotypic variations between identified clusters in different ethnic groups.

Allergooncology: an expanding research area.

The relationship between allergic diseases and cancer is a very controversial topic, widely discussed in the last decades. Many studies have demonstrated inverse association between allergy and cancer, but others have reached neutral conclusions or have indicated a positive role of allergy in the development of cancer. However, either inhibiting or favoring, many cells and molecules relevant in the allergic process play a role in tumorigenesis. On the one hand, activated immune cells, like classically activated macrophages "M1", activated dendritic cells, IL-33 and amphiregulin stimulated Innate Lymphoid Cells (ILC2), Th1, IFN-γ producing T CD8+ and B lymphocytes have inhibitory effects on tumorigenesis and tumor progression. On the other hand, tolerogenic immune cells, like alternatively activated macrophages "M2" (M2a, M2b and M2c), tolerogenic dendritic cells, ILC3, T regulatory and B regulatory lymphocytes, while inhibiting allergic sensitization and response, appear to favour carcinogenesis. Furthermore, M2 subtypes macrophages (M2a, M2b), IL-25 stimulated ILC2 and Th2 lymphocytes have a role both in inducing allergic reactions and in favouring cancer progression. In addition, mast cells, pivotal cells in allergy, have a different effect of tumorigenesis based on their location - they can promote cancer progression or inhibit it. Finally, eosinophils have shown a prevalent tumoricidal function mediated by α-defensins, TNF-α, granzymes A and IL-18. Better understanding the role of various cells on carcinogenesis can help in developing new strategies (diagnostic, therapeutic and of follow up) against tumor.

Relación entre automanejo y síntomas depresivos en personas con diabetes e hipertensión / Relationship between self-management and depressive symptoms in persons with diabetes and hypertension / Relação entre automanejo e sintomas depressivos em pessoas com diabetes e hipertensão

Resumen Introducción: Las personas con diabetes e hipertensión experimentan con mayor frecuencia sintomatología depresiva, lo cual contribuye a un inadecuado automanejo de la enfermedad, que implica tareas como: la toma de la medicación, asistir a las consultas médicas, el conocimiento de signos y síntomas, además de la toma de decisiones. Objetivo: Por lo anterior, el objetivo de este trabajo es identificar la relación entre automanejo en general y sus dimensiones con síntomas depresivos en personas con diabetes e hipertensión. Método: Estudio transversal-correlacional con n=205 pacientes con diagnóstico de diabetes (100) e hipertensión (105). Muestreo no probabilístico por conveniencia. Se utilizó la estadística descriptiva y r de Pearson. Se aplicaron los instrumentos Partners in Health (PIH) y The Patient Health Questionnaire (PHQ-8). Resultados: Se encontró correlación estadísticamente significativa entre la sintomatología depresiva y el automanejo (r=-0.308 ρ<0.001). Discusión y Conclusiones: Se concluye que la sintomatología depresiva se relaciona con el automanejo de la enfermedad de la siguiente manera: a mayor automanejo menor sintomatología de depresión, o a mayor sintomatología depresiva menor automanejo; dicha relación confirma que ambas variables se afectan mutuamente y/o mantienen una relación estrecha.

Abstract Introduction: Persons with diabetes and hypertension frequently suffer from depression as well, a situation which contributes to an inadequate management of the condition in terms of medication, medical consultations, signs, and decision making. Objective: To identify the relationship between general self-management and depression symptoms in persons with diabetes and hypertension. Method: This is a transversal and correlational study with a sample of 205 patients, 100 with a main diagnosis of diabetes, and 105 with a main diagnosis of hypertension. The sampling process was non-probabilistic and by convenience. Descriptive statistics, including Pearson's r were calculated. The Partners in Health (PIH) and Patient Health Questionnaire (PHQ-8) instruments were administered. Results: A statistically significant correlation between depression symptoms and diabetes and hypertension self-management was found (r=-0.308 ρ<0.001). Discussion and conclusions: Depression symptoms were related to how diabetes and hypertension are self-managed in a way that, the more self-management, the less depression symptoms, or the more depression symptoms, the less self-management.

Resumo Introdução: As pessoas com diabetes e hipertensão experimentam com maior frequência a sintomatologia depressiva, o qual contribui a um inadequado automanejo da doença, que envolve tarefas como: a toma da medicação, assistir às consultas médicas, o conhecimento de signos e sintomas, além da toma de decisões. Objetivo: Pelo anterior, o objetivo deste trabalho é identificar a relação entre automanejo em geral e suas dimensões com sintomas depressivos em pessoas com diabetes e hipertensão. Método: Estudo transversal-correlacional com n=205 pacientes com diagnóstico de diabetes (100) e hipertensão (105). Amostragem não probabilística por conveniência. Utilizou-se a estatística descritiva e r de Pearson. Aplicaram-se os instrumentos Partners in Health (PIH) e The Patient Health Questionnaire (PHQ-8). Resultados: Encontrou-se correlação estatisticamente significativa entre a sintomatologia depressiva e o automanejo (r=-0.308 ρ<0.001). Discussão e Conclusões: Conclui-se que a sintomatologia depressiva relaciona-se com o automanejo da doença da seguinte maneira: a maior automanejo, menor sintomatologia de depressão, ou a maior sintomatologia depressiva, menor automanejo; esta relação confirma que ambas variáveis afetam-se mutuamente e/ou mantem uma relação estreita.

Utilidad de mediciones objetivas para la programación en implantes cocleares / Use of objective measures for cochlear implant programming

RESUMEN Introducción: La programación adecuada de los implantes cocleares permiten lograr niveles de estimulación auditivos óptimos. Se realiza de forma individualizada, siendo la detección del umbral de confort ideal un desafío. Se ha descrito la utilidad de los potenciales auditivos del tronco encefálico eléctrico (ePEATC) y el reflejo eléctrico estapedial (eREE) para este propósito. Objetivo: Determinar la posibilidad de realizar ePEATC y eREE en pacientes adultos y pediátricos con implantes cocleares, y evaluar cambios en la programación de los implantes cocleares luego de las mediciones objetivas. Material y método: Se realizó un estudio prospectivo, descriptivo, de pacientes con implante coclear marca MED-EL®, separando los pacientes en dos grupos: el grupo adulto (n =5) y el grupo pediátrico (n =5). Todos los pacientes incluidos presentaron más de 6 meses de encendido del implante. Se evaluaron variables epidemiológicas y tiempo de encendido del implante. Se realizó una otoscopía, prueba básica de funcionamiento del implante, y las mediciones objetivas eléctricas (ePEATC, eREE). Con estos resultados se ajustó el umbral de confort. Resultados: El tiempo promedio de encendido del implante en el grupo adulto fue de 27 meses, y 30 meses en el grupo pediátrico. El ePEATC requiere más tiempo y cooperación al compararlo con eREE. Luego de estas evaluaciones objetivas, fue necesario el ajuste del umbral de confort en tres pacientes adultos, y en dos pacientes pediátricos. Fue necesario realizar una audiometría de campo libre para estimar el umbral de confort en dos pacientes pediátricos que no presentaron respuesta en eREE. Conclusión: Fue posible realizar estas mediciones objetivas en pacientes adultos y pediátricos, siendo mejor tolerado y requiriendo menos tiempo, el eREE.

ABSTRACT Introduction: Mapping a cochlear implant allows for adjusting ideal electrical stimulation limits. It is an individualized process and detecting the most comfortable loudness level can be challenging. The use of electrically evoked auditory brainstem response (ePEATC) and electrically evoked stapedius reflex thresholds (eREE) have been considered for this purpose. Aim: To determine the feasibility of performing ePEATC and eREE on adult and pediatric patients with a cochlear implant, and to evaluate changes in programming following these objective measures. Material and method: A prospective, descriptive study was completed, of patients with MED-EL® cochlear implants, separating patients into two groups: adults (n=5) and children (n=5). All of the patients included had their implants activated for 6 months or longer. Epidemiological variables and duration of implant activation were evaluated. Otoscopy, a basic implant functioning evaluation, and objective measures (ePEATC, eREE) were performed. With these results, comfortable loudness levels were adjusted. Results: Average duration of implant activation was 27 months and 30 months, for adults and children respectively. Performing ePEATC required more time and cooperation as compared to eREE. Following the objective measures, adjustment of the comfortable loudness levels was required for three adult and two pediatric patients. Sound field audiometry was necessary for two pediatric patients in order to estimate the comfortable loudness levels because the eREE responses were absent. Conclusions: It is feasible to perform these objective measures for both adult and pediatric patients, with eREE requiring less time and being better tolerated by patients.

Kounis Syndrome as First Manifestation of Allergic Sensitization.

Mast cells are abundant in the heart, among myocardial fibers, around coronary arteries, within arterial intima and intramural vessels, and in atherosclerotic plaques. Their mediators can be released during anaphylaxis and be responsible for acute coronary syndrome. This condition has been described as Kounis syndrome (KS). We report three cases of acute myocardial ischemia, which fulfill the definition for KS. In Cases 1 and 2, the association of intense chest pain with acute urticaria after an allergenic contact (wasp sting and betalactam antibiotic administration, respectively) was suspected to be an attack of angina related to an allergic reaction. No signs of an allergic reaction were observed in Case 3, but only the history of a wasp sting suggested its relationship to loss of consciousness and heart ischemia when hypersensitivity to venom was ascertained. These cases strongly recommend measurement of anaphylactic biomarkers, such as tryptase, during acute coronary syndromes to detect the possible involvement of an allergic reaction. Conversely, measurement of cardiac biomarkers during anaphylaxis, even without obvious signs of myocardial ischemia, might identify patients at risk of myocardial injury.

Chemically Modified Variants of Fenofibrate with Antiglioblastoma Potential.

Anticancer effects of a common lipid-lowering drug, fenofibrate, have been described in the literature for a quite some time; however, fenofibrate has not been used as a direct anticancer therapy. We have previously reported that fenofibrate in its unprocessed form (ester) accumulates in the mitochondria, inhibits mitochondrial respiration, and triggers a severe energy deficit and extensive glioblastoma cell death. However, fenofibrate does not cross the blood brain barrier and is quickly processed by blood and tissue esterases to form the PPARα agonist fenofibric acid, which is practically ineffective effective in triggering cancer cell death. To address these issues, we have made several chemical modifications in fenofibrate structure to increase its stability, water solubility, tissue penetration, and ultimately anticancer potential. Our data show that, in comparison to fenofibrate, four new compounds designated here as PP1, PP2, PP3, and PP4 have improved anticancer activity in vitro. Like fenofibrate, the compounds block mitochondrial respiration and trigger massive glioblastoma cell death in vitro. In addition, one of the lead compounds, PP1, has improved water solubility and is significantly more stable when exposed to human blood in comparison to fenofibrate. Importantly, mice bearing large intracranial glioblastoma tumors demonstrated extensive areas of tumor cell death within the tumor mass following oral administration of PP1, and the treated mice did not show any major signs of distress, and accumulated PP1 at therapeutically relevant concentrations in several tissues, including brain and intracranial tumors.

Author Correction: nr3c1 null mutant zebrafish are viable and reveal DNA-binding-independent activities of the glucocorticoid receptor.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Una radiografía con sorpresa: osteopoiquilosis / An X-ray with a suprise: osteopoikilosis

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Helminth egg excretion in horses kept under tropical conditions-Prevalence, distribution and risk factors.

Increasing levels of anthelmintic resistance observed in equine cyathostomin parasites have led to recommendations of selective anthelmintic treatment strategies to lower the selection pressure favoring resistant populations. This principle is based on determining strongyle fecal egg counts from all herd members, and treating those exceeding a predetermined treatment cutoff. However, epidemiological information is lacking from horses kept under tropical conditions, where parasite burdens may be of a different composition and magnitude compared to those of horses kept under temperate climate conditions. The aim of the present work was to characterize the strongylid fauna in horses kept in tropical Camagüey, Cuba and identify risk factors associated with strongylid and ascarid egg counts. A total of 396 horses from eight different establishments were included in the study. Coprocultures revealed that Strongylus vulgaris and cyathostomins, sensu lato, were detected in all of those establishments. Prevalence and mean value of strongylid eggs per gram of feces were 97% and 1436, respectively. Eggs of Parascaris spp. were observed in 10% of horses. A multivariate mixed linear model identified sex (p=0.022), month (p=0.044), operation type (p=0.037) and time since last deworming (p<0.001) to be significantly associated in with the magnitude of strongylid fecal egg counts. A multivariate logistic regression identified horses less than two years of age (p=0.010) and horses not receiving anthelmintic treatment (p<0.001) to be significantly more likely to harbor Parascaris spp. parasites. The high magnitude and prevalence of strongylid fecal egg counts observed and the common occurrence of S. vulgaris suggest that strongylid parasite burdens are substantially different from those typically observed in managed equines kept under more temperate conditions.

nr3c1 null mutant zebrafish are viable and reveal DNA-binding-independent activities of the glucocorticoid receptor.

Glucocorticoids (GCs) play important roles in developmental and physiological processes through the transcriptional activity of their cognate receptor (Gr). Using CRISPR/Cas9 technology, we established a zebrafish null Gr mutant line and compared its phenotypes with wild type and a zebrafish line with partially silenced gr (gr s357/s357 ). Homozygous gr -/- larvae are morphologically inconspicuous and, in contrast to GR -/- knockout mice, viable through adulthood, although with reduced fitness and early life survival. Mutants gr -/- are fertile, but their reproductive capabilities fall at around 10 months of age, when, together with cardiac and intestinal abnormalities already visible at earlier stages, increased fat deposits are also observed. Mutants show higher levels of whole-body cortisol associated with overstimulated basal levels of crh and pomca transcripts along the HPI axis, which is unresponsive to a mechanical stressor. Transcriptional activity linked to immune response is also hampered in the gr -/- line: after intestinal damage by dextran sodium sulphate exposure, there are neither inflammatory nor anti-inflammatory cytokine gene responses, substantiating the hypothesis of a dual-action of the GC-GR complex on the immune system. Hence, the zebrafish gr mutant line appears as a useful tool to investigate Gr functions in an integrated in vivo model.