Babesia microti-like en un perro inmunocompetente

La babesiosis canina es una enfermedad infecciosa de distribución mundial causada por parásitos intraeritrocitarios transmitidos por garrapatas. Si bien ha sido tradicionalmente asumido que sólo dos de las 73 especies de babesias identificadas causan enfermedad en la especie canina, Babesia canis y Babesia gibsoni, recientes publicaciones demuestran que una tercera especie (Babesia microti-like) también puede parasitar a perros. Este último parásito, genéticamente relacionado con Babesia microti, es el origen de una enfermedad endémica entre la población canina del noroeste de España. Este trabajo presenta un caso no experimental de esta forma de Babesia microti-like en un perro cocker spaniel de 9 años, sin antecedentes de inmunodeficiencia ni de esplenectomía, que se presenta en la clínica veterinaria con signos de hipertermia, hemoglobinuria, escalofríos y apatía. Una muy intensa parasitemia (24%), junto con trombopenia y una acusada anemia hemolítica regenerativa fueron los hallazgos más caractéristicos. En la extensión de sangre periférica se visualizaron múltiples merozoitos intraeritrocitarios (parasitemia de un 24%) de pequeño tamaño (1-2 um) y presentación única en cada hematíe. Cuarenta y ocho horas después del comienzo de los síntomas, y tras tratamiento específico con dipropionato de imidocarb el perro evolucionó hacia la curación

Random Forest-Based Prediction of Stroke Outcome

[Abstract] We research into the clinical, biochemical and neuroimaging factors associated with the outcome of stroke patients to generate a predictive model using machine learning techniques for prediction of mortality and morbidity 3-months after admission. The dataset consisted of patients with ischemic stroke (IS) and non-traumatic intracerebral hemorrhage (ICH) admitted to Stroke Unit of a European Tertiary Hospital prospectively registered. We identified the main variables for machine learning Random Forest (RF), generating a predictive model that can estimate patient mortality/morbidity according to the following groups: (1) IS + ICH, (2) IS, and (3) ICH. A total of 6022 patients were included: 4922 (mean age 71.9 ± 13.8 years) with IS and 1100 (mean age 73.3 ± 13.1 years) with ICH. NIHSS at 24, 48 h and axillary temperature at admission were the most important variables to consider for evolution of patients at 3-months. IS + ICH group was the most stable for mortality prediction [0.904 ± 0.025 of area under the receiver operating characteristics curve (AUC)]. IS group presented similar results, although variability between experiments was slightly higher (0.909 ± 0.032 of AUC). ICH group was the one in which RF had more problems to make adequate predictions (0.9837 vs. 0.7104 of AUC). There were no major differences between IS and IS + ICH groups according to morbidity prediction (0.738 and 0.755 of AUC) but, after checking normality with a Shapiro Wilk test with the null hypothesis that the data follow a normal distribution, it was rejected with W = 0.93546 (p-value < 2.2e−16). Conditions required for a parametric test do not hold, and we performed a paired Wilcoxon Test assuming the null hypothesis that all the groups have the same performance. The null hypothesis was rejected with a value < 2.2e−16, so there are statistical differences between IS and ICH groups. In conclusion, machine learning algorithms RF can be effectively used in stroke patients for long-term outcome prediction of mortality and morbidity.This study was partially supported by grants from the Spanish Ministry of Science and Innovation (SAF2017-84267-R), Xunta de Galicia (Axencia Galega de Innovación (GAIN): IN607A2018/3), Instituto de Salud Carlos III (ISCIII) (PI17/00540, PI17/01103), Spanish Research Network on Cerebrovascular Diseases RETICS-INVICTUS PLUS (RD16/0019) and by the European Union FEDER program. T. Sobrino (CPII17/00027), F. Campos (CPII19/00020) are recipients of research contracts from the Miguel Servet Program (Instituto de Salud Carlos III). General Directorate of Culture, Education and University Management of Xunta de Galicia (ED431G/01,252 ED431D 2017/16), “Galician Network for Colorectal Cancer Research" (Ref. ED431D 2017/23), Competitive Reference Groups (ED431C 2018/49), Spanish Ministry of Economy and Competitiveness via funding of the unique installation BIOCAI (UNLC08-1E-002, UNLC13-13–3503), European Regional Development Funds (FEDER).Xunta de Galicia; IN607A2018/3Xunta de Galicia; ED431G/01,252Xunta de Galicia; ED431D 2017/1

Association of Systemic Lupus Erythematosus Clinical Features with European Population Genetic Substructure

Systemic Lupus Erythematosus (SLE) is an autoimmune disease with a very varied spectrum of clinical manifestations that could be partly determined by genetic factors. We aimed to determine the relationship between prevalence of 11 clinical features and age of disease onset with European population genetic substructure. Data from 1413 patients of European ancestry recruited in nine countries was tested for association with genotypes of top ancestry informative markers. This analysis was done with logistic regression between phenotypes and genotypes or principal components extracted from them. We used a genetic additive model and adjusted for gender and disease duration. Three clinical features showed association with ancestry informative markers: autoantibody production defined as immunologic disorder (P = 6.8×10(-4)), oral ulcers (P = 6.9×10(-4)) and photosensitivity (P = 0.002). Immunologic disorder was associated with genotypes more common in Southern European ancestries, whereas the opposite trend was observed for photosensitivity. Oral ulcers were specifically more common in patients of Spanish and Portuguese self-reported ancestry. These results should be taken into account in future research and suggest new hypotheses and possible underlying mechanisms to be investigated. A first hypothesis linking photosensitivity with variation in skin pigmentation is suggested

Análisis de la expresión de genes de respuesta inmune durante el desarrollo ontogénico de paralarvas de pulpo Octopus vulgaris criadas en cautividad

El pulpo común es una especie de gran importancia comercial, considerada como una especie emergente en acuicultura. En este trabajo se analizó el nivel de expresión de los genes inmunes TLR, C1q, Galectina, PGRP, LITAF, SERPIN, PRDX y Caspasa 3 mediante PCR cuantitativa (q-PCR) en embriones y paralarvas de O. vulgaris de edades 0, 10, 20 y 34 días. Adicionalmente, se infectaron paralarvas de 22 días con bacterias patógenas vivas Vibrio lentus y V. splendidus a 1h, 4h y 24h. El estudio del desarrollo del sistema inmune de estas paralarvas ayudará a identificar factores claves para la supervivencia y cultivo del pulpo común. Durante el desarrollo ontogénico, los embriones mostraron el menor nivel de expresión de PGRP, Caspasa 3 y PRDX. Por el contrario, C1q, Galectina y LITAF se observaron visiblemente expresados. C1q, TLR y SERPIN fueron los genes que presentaron mayor nivel de expresión en Pa0D. A partir de Pa10D se observó un notable incremento en la expresión de C1q, Galectina, PGRP y LITAF. La expresión de Caspasa3 se incrementó gradualmente desde Em. V. lentus y V. splendidus inducen un notable incremento de la expresión de C1q y PRDX entre 1h y 4h post infección. Sin embargo, durante las primeras horas de infección se observó una disminución de la expresión de Galectina, TLR, PGRP y LITAF. Particularmente la infección por V. lentus produjo una disminución de la expresión de SERPIN. Los resultados obtenidos sugieren que la capacidad del sistema inmune de reconocer patógenos y evitar infecciones es significativamente activo desde los estadíos de paralarvas recién eclosionadas. Sin embargo, se observó un aumento significativo de los genes seleccionados a partir de Pa10D.The common octopus is a species of high commercial interest and nowadays is considered as an emergent species in aquaculture. The mRNA expression level of immune-related genes (TLR, C1q, Galectin, PGRP, LITAF, SERPIN, PRDX and Caspase 3) was analyzed by Real time qPCR on embryos and paralarvae of O. vulgaris at age of 0, 10, 20 and 34 days. Additionally, paralarvae of 22 days were challenged with live Vibrio lentus and V. splendidus during a time course (1 h, 4 h and 24 h). This analysis will allow a better understanding of the developmental of immune system of these paralarvae, which will help to identify key factors for survival and culture of the common octopus. Regarding ontogeny, Em showed the lowest expression of PGRP, Caspase 3 and PRDX. In contrast, C1q, Galectin and LITAF were visibly expressed. C1q, TLR and SERPIN were highly expressed in Pa0D. A notably increase in the expression of C1q, Galectin, PGRP and LITAF began from Pa10D. Caspase 3 expression was gradually increased from Em. V. lentus and V. splendidus induced a notable expression of C1q and PRDX at 1 h and 4 h post infection (p. i.). Nevertheless, they markedly suppress the activation of Galectin, TLR, PGRP and LITAF during the first hours p.i.. Particularly, V. lentus suppressed the expression of SERPIN. The present results suggest that the ability of immune system to recognize pathogens and avoid infections is a priority in recently hatched paralarvae. However, a noticeable increase of gene expression was observed from Pa10D.0,000

Intra- and extra-hospital improvement in ischemic stroke patients: influence of reperfusion therapy and molecular mechanisms

Neuroprotective treatments in ischemic stroke are focused to reduce the pernicious effect of excitotoxicity, oxidative stress and inflammation. However, those cellular and molecular mechanisms may also have beneficial effects, especially during the late stages of the ischemic stroke. The objective of this study was to investigate the relationship between the clinical improvement of ischemic stroke patients and the time-dependent excitotoxicity and inflammation. We included 4295 ischemic stroke patients in a retrospective study. The main outcomes were intra and extra-hospital improvement. High glutamate and IL-6 levels at 24 hours were associated with a worse intra-hospital improvement (OR:0.993, 95%CI: 0.990-0.996 and OR:0.990, 95%CI: 0.985-0.995). High glutamate and IL-6 levels at 24 hours were associated with better extra-hospital improvement (OR:1.13 95%CI, 1.07-1.12 and OR:1.14, 95%CI, 1.09-1.18). Effective reperfusion after recanalization showed the best clinical outcome. However, the long term recovery is less marked in patients with an effective reperfusion. The variations of glutamate and IL6 levels in the first 24 hours clearly showed a relationship between the molecular components of the ischemic cascade and the clinical outcome of patients. Our findings suggest that the rapid reperfusion after recanalization treatment blocks the molecular response to ischemia that is associated with restorative processes

Lack of replication of higher genetic risk load in men than in women with systemic lupus erythematosus

Introduction: We aimed to replicate a recent study which showed higher genetic risk load at 15 loci in men than in women with systemic lupus erythematosus (SLE). This difference was very significant, and it was interpreted as indicating that men require more genetic susceptibility than women to develop SLE. Methods: Nineteen SLE-associated loci (thirteen of which are shared with the previous study) were analyzed in 1,457 SLE patients and 1,728 healthy controls of European ancestry. Genetic risk load was calculated as sex-specific sum genetic risk scores (GRS(s)). Results: Our results did not replicate those of the previous study at either the level of individual loci or the global level of GRS(s). GRS(s) were larger in women than in men (4.20 ± 1.07 in women vs. 3.27 ± 0.98 in men). This very significant difference (P < 10(-16)) was more dependent on the six new loci not included in the previous study (59% of the difference) than on the thirteen loci that are shared (the remaining 41%). However, the 13 shared loci also showed a higher genetic risk load in women than in men in our study (P = 6.6 × 10(-7)), suggesting that heterogeneity of participants, in addition to different loci, contributed to the opposite results. Conclusion: Our results show the lack of a clear trend toward higher genetic risk in one of the sexes for the analyzed SLE loci. They also highlight several limitations of assessments of genetic risk load, including the possibility of ascertainment bias with loci discovered in studies that have included mainly women

Transcriptomics of In Vitro Immune-Stimulated Hemocytes from the Manila Clam Ruditapes philippinarum Using High-Throughput Sequencing

The Manila clam (Ruditapes philippinarum) is a worldwide cultured bivalve species with important commercial value. Diseases affecting this species can result in large economic losses. Because knowledge of the molecular mechanisms of the immune response in bivalves, especially clams, is scarce and fragmentary, we sequenced RNA from immune-stimulated R. philippinarum hemocytes by 454-pyrosequencing to identify genes involved in their immune defense against infectious diseases

Sediment mobilization and seawater warming affect ecophysiology of the clam polititapes rhomboides

Poster.-- Poster.-- VIII International Symposium on Marine Science, Las Palmas de Gran Canaria, 6-8 July 2022High-energy hydrodynamic events associated to currents and waves may disturb bivalve mollusks´ ecophysiology, especially those buried in the the sea bed due to sediment mobilization. Evidences of massive mortality for the clam Polititapes rhomboides (banded carpet shell clam) in Galicia (NW Spain) have been associated to warm water temperatures and high wave magnitudes above climatic averages and the presence of rickettsias (intracellular prokaryotic colonies) in gills (Villalba et al. 1999; Darriba et al. 2019; Villacieros-Robineau et al. 2021)Project PID2019-106008RB-C21 financed by MCIN/AEI/10.13039/501100011033N

Immune and physiological responses of clams (Polititapes rhomboides) under sediment mobilization and seawater warming conditions

Poster.-- 4th Congress of the International Society of Fish & Shellfish Immunology, December 12-15, 2022, Bode, NorwayHigh-energy hydrodynamic events associated with currents and waves may disturb bivalve mollusks' ecophysiology, especially those buried in the sea bed where the bottom boundary layer dynamics may mobilize and resuspend the surface sediments. Evidence of massive mortality for the clam Polititapes rhomboides (banded carpet shell clam) in 2010 in Galicia (NW Spain) has been associated to warm water temperatures and high wave magnitudes above climatic averages and the presence of rickettsias (intracellular prokaryotic colonies) in gills. To monitor in the laboratory the environmental conditions observed in 2010, clams were subjected to intense sediment mobilization (four cycles of sediment remobilization, each followed by a calm period) and seawater warming (from 15°C to 18°C). Immune system, behavioral, and ecophysiological clams' responses were then evaluated. Nitric oxide (NO) production increased synergistically with seawater warming and sediment remobilization. Taking into account the four cycles of sediment remobilization, clams responded by increasing NO production as early as the first cycle in what we could call an acute effect. However, the most striking effect was the increased NO response after a second stimulation (the following sediment remobilization cycles), suggesting that clams achieve a kind of alertness the first time they are exposed to a stimulus through a mechanism possibly related to "trained immunity". Seawater warming and sediment mobilization presented also synergistic effects causing the lowest valve opening amplitude. Besides, sediment remobilization caused abrupt decrease in clearance rates of clams suggesting that reduced valve opening during this stage may have altered filtration processes of phytoplankton uptake. Metabolic rate as oxygen consumption showed a synergistic increase with both abiotic stressors. Considering the NO response and the ecophysiology data we could suggest that clams respond to stress increasing metabolism to obtain energy (ATP) and oxygen consumption by aerobic respiration. ATP production involves the generation of reactive oxygen species (ROS) including NO as by-products. The anti-oxidant system can balance the ROS production but this could be drastically altered (disruption of cytoskeleton and apoptotic cell death) if ROS production is greater and faster than the antioxidant system can regulate, which seems not to be the case for this particular experimentProject PID2019-106008RB-C21 financed by MCIN/AEl/10.13039/501100011033N