Analysis of Plasma-Derived Exosomal MicroRNAs as Potential Biomarkers for Canine Idiopathic Epilepsy.

Epilepsy is one of the most prevalent complex neurological diseases in both the canine and human species, with the idiopathic form as its most common diagnosis. MicroRNAs (miRNAs) are small, noncoding RNA molecules that play a role in gene regulation processes and appear to be a promising biological target for convulsion control. These molecules have been reported as constituents of the internal content of exosomes, which are small extracellular vesicles released by cells. In this study, exosome samples were isolated from the plasma of 23 dogs, including 9 dogs with epilepsy responsive to treatment, 6 dogs with drug-resistant epilepsy, and 8 control dogs. Plasma exosomes were then characterized by electron transmission microscopy, nanoparticle tracking analysis, and dot blotting. Afterwards, the microRNA-enriched RNA content of exosomes was isolated, and miRNA quantification was performed by quantitative real-time PCR. Seven circulating miRNAs that have been previously described in the literature as potential diagnostic or prognostic biomarkers for epilepsy were evaluated. We observed significant differences in miR-16 (p < 0.001), miR-93-5p (p < 0.001), miR-142 (p < 0.001), miR-574 (p < 0.01), and miR-27 (p < 0.05) levels in dogs with refractory epilepsy compared to the control group. In drug-sensitive epileptic dogs, miR-142 (p < 0.01) showed significant differences compared to healthy dogs. Moreover, distinct levels of miR-16 (p < 0.05), miR-93-5p (p < 0.01), miR-132 (p < 0.05), and miR-574 (p < 0.05) were also found between drug-sensitive and drug-resistant epileptic dogs. Our results present plasma-circulating exosomes as an advantageous source of epileptic biomarkers, highlighting the potential of miRNAs as prognostic and diagnostic biomarkers of canine idiopathic epilepsy.

Design and Implementation of a Prototype Seismogeodetic System for Tectonic Monitoring.

This manuscript describes the design, development, and implementation of a prototype system based on seismogeodetic techniques, consisting of a low-cost MEMS seismometer/accelerometer, a biaxial inclinometer, a multi-frequency GNSS receiver, and a meteorological sensor, installed at the Doñana Biological Station (Huelva, Spain) that transmits multiparameter data in real and/or deferred time to the control center at the University of Cadiz. The main objective of this system is to know, detect, and monitor the tectonic activity in the Gulf of Cadiz region and adjacent areas in which important seismic events occur produced by the interaction of the Eurasian and African plates, in addition to the ability to integrate into a regional early warning system (EWS) to minimize the consequences of dangerous geological phenomena.

Effect of a Ketogenic Medium Chain Triglyceride-Enriched Diet on the Fecal Microbiota in Canine Idiopathic Epilepsy: A Pilot Study.

Ketogenic diets have been successfully used in people and dogs with idiopathic epilepsy. This study examined the effect of a ketogenic medium chain triglycerides (MCT)- enriched diet administered for one month on the fecal microbiota of epileptic (n = 11) (six with drug-sensitive epilepsy, DSE; five with drug-refractory epilepsy, DRE) and non-epileptic beagle dogs (n = 12). A significant reduction after diet in the relative abundance of bacteria from the Actinobacteria phylum was observed in all dogs. Epileptic dogs showed a higher relative abundance of Lactobacillus compared with non-epileptic dogs at baseline but these differences disappeared after diet. Epileptic dogs also showed a significantly higher abundance of Negativicutes and Selenomonadales after dietary intervention. Baseline microbiota patterns were similar in non-epileptic beagles and dogs with DSE but significantly different from dogs with DRE. In non-epileptic and DSE groups, the MCT diet decreased the relative abundance of Firmicutes and increased that of Bacteroidetes and Fusobacteria, but the opposite effect was observed in dogs with DRE. These results suggest that the MCT diet effect would depend on individual baseline microbiota patterns and that ketogenic diets could help reduce gut microbiota differences between dogs with DRE and DSE.

Enhanced thrombin generation detected with ST-Genesia analyzer in patients with newly diagnosed multiple myeloma.

The issue of how to identify newly diagnosed multiple myeloma (NDMM) patients requiring thromboprophylaxis remains unsolved. Several changes in thrombin generation (TG)-derived parameters have been described in multiple myeloma (MM) patients recently. Assessment of prothrombotic risk with a fully automated TG analyzer could reduce interlaboratory variability. Our objective was to determine whether ST-Genesia® could reveal a hypercoagulable state in NDMM compared to healthy controls. We conducted a multicenter observational study of NDMM requiring initial treatment to compare TG parameters obtained with ST-Genesia® analyzer and ST-ThromboScreen® reagent with a control group. Clinical data were obtained from medical records and blood samples were collected before initial anti-myeloma therapy. A thrombophilia panel was performed in all patients. Compared to age- and sex-matched controls (n = 83), NDMM patients (n = 83) had significantly higher peak height, higher velocity index, shorter time-to-peak and lower percentage of endogenous thrombin potential (ETP) inhibition after adding thrombomodulin (TM) (ETP%inh). NDMM on prophylactic low molecular weight heparin (LMWH) showed reduced both peak height and velocity index compared to NDMM who had not yet started VTE prophylaxis, similar to that of controls. Moreover, partial correction of ETP%inh was observed in MM patients on LMWH. The presence of a thrombophilia did not modify the TG phenotype. Untreated NDMM patients showed an enhanced TG, regardless of their thrombophilia status. They generate a higher peak of thrombin, take less time to produce it, and exhibit resistance to TM inhibition. Our findings suggest that standard prophylactic dose of LMWH may reduce TG at levels of healthy controls.

Gut Microbiota in Canine Idiopathic Epilepsy: Effects of Disease and Treatment.

Epilepsy is one of the most common neurological disorders in humans and dogs. The structure and composition of gut microbiome associated to this disorder has not yet been analyzed in depth but there is evidence that suggests a possible influence of gut bacteria in controlling seizures. The aim of this study was to investigate the changes in gut microbiota associated to canine idiopathic epilepsy (IE) and the possible influence of antiepileptic drugs (AEDs) on the modulation of this microbiota. Faecal microbiota composition was analyzed using sequencing of bacterial 16S rRNA gene in a group of healthy controls (n = 12) and a group of epileptic dogs both before (n = 10) and after a 30-day single treatment with phenobarbital or imepitoin (n = 9). Epileptic dogs showed significantly reduced abundance of GABA (Pseudomonadales, Pseudomonadaceae, Pseudomonas and Pseudomona_graminis) and SCFAs-producing bacteria (Peptococcaceae, Ruminococcaceae and Anaerotruncus) as well as bacteria associated with reduced risk for brain disease (Prevotellaceae) than control dogs. The administration of AEDs during 30 days did not modify the gut microbiota composition. These results are expected to contribute to the understanding of canine idiopathic epilepsy and open up the possibility of studying new therapeutic approaches for this disorder, including probiotic intervention to restore gut microbiota in epileptic individuals.

Incidence and clinical profile of venous thromboembolism in hospitalized COVID-19 patients from Madrid region.

BACKGROUND: COVID-19 related in-hospital venous thromboembolism (VTE) incidence is high but data reported vary significantly. Some studies show that up to half of the events are diagnosed early after admission. OBJECTIVES: To study symptomatic VTE incidence in acute COVID-19 hospitalized patients and to describe timing of VTE diagnosis. METHODS: Multicenter cohort of 5966 patients hospitalized with acute COVID-19. Multicenter Registry of 844 hospitalized patients with acute COVID-19 and associated acute VTE. RESULTS: By the time of cohort data collection, 68 patients (1.14%) were still hospitalized, 19.8% had died, and 5.4% required ICU. During a median follow-up of 6 days (IQR, 4-12), 183 patients (3.07%; 95% CI, 2.64-3.55) presented a symptomatic VTE event. The cumulative incidences of VTE at 7, 14 and 21 days in wards [2.3% (95% CI, 1.9-2.7), 3.6% (95% CI, 3.0-4.3), and 4.3% (95% CI, 3.5-5.1)] were similar to the ones reported in ICU [2.2% (95% CI, 1.0-4.4), 2.9% (95% CI, 1.5-5.3), and 4.1% (95% CI, 2.2-6.8)], but at 30 and 60 days were higher in ICU [6.9% (95% CI, 4.2-10.5), and 12.8% (95% CI, 8.1-18.5)] than in wards. Eighty-eight VTE events (48%) were diagnosed early, within 48 h of admission. VTE was not associated with death (HR, 0.79; 95% CI, 0.55-1.12). CONCLUSIONS: Incidence of symptomatic VTE in our COVID-19 cohort is consistent with that of other real-life studies recently published. Early VTE events are, along with COVID-19, the reason for admission rather than an in-hospital complication.

Detection of owner-perceived emotional eating in companion dogs: A regression modelling approach.

BACKGROUND: Emotional eating has been largely demonstrated in humans and laboratory rodents, but a recent survey conducted by the authors revealed that dog owners have also detected this phenomenon in their pets. However, due to the lack of diagnostic tools, veterinarians and researchers might encounter serious difficulties in detecting emotional eating in clinical settings. The present study aimed to explore different variables associated with owner perceived-emotional eating in companion dogs with the ultimate goal of designing a tool that could facilitate its detection. METHODS: The mentioned survey included information on feeding habits, eating behaviour, temperament and emotional state of the dogs, as well as a specific question for assessing the owners' perception on emotional eating. From these data (n = 1137), a stochastic model based on binary logistic regression was used to design a regression model. RESULTS AND CONCLUSION: The final model (r2 = 0.179, p < 0.001) included a constant and nine variables and, of these, five did act as risk factors whereas the rest were considered as protective factors, in line with a congruent clinical perception. These variables could make up an easy-to-respond nine-item checklist to be answered by dog owners that could help veterinarians identify those companion dogs susceptible to emotional eating.

Perception of Canine Welfare Concerns among Veterinary Students, Practitioners, and Behavior Specialists in Spain.

Veterinarians are well placed to supervise and ensure canine welfare. However, the perception of animal welfare among veterinarians may vary depending on the level of training and professional practice, including the specialization in animal behavior and welfare. The aim of this study was to survey the perception of canine welfare among veterinarians, including students, practitioners, and behavior specialists. A scale-based questionnaire including 12 issues affecting canine welfare was adapted from Yeates and Main and distributed to first-year (n=50) and fifth-year veterinary students (n=50), as well as veterinary practitioners (n=260) and specialists in behavioral medicine (n=50). For each issue, respondents were asked to rate how much they perceived each issue to affect canine welfare (on a scale of 0 to 4). A General Linear Model test was used to assess the effect of the studied group on scores. "Physical abuse or cruelty" was the highest-scoring problem in all groups and "breed-related conditions" was the lowest. In general, specialists in behavioral medicine assigned significantly higher scores to most items, particularly "behavioral problems" and "lack of sufficient company." In contrast, fifth-year students assigned significantly lower scores to most items. This study shows that situations clearly affecting canine welfare represent an important concern for veterinarians, both undergraduates and professionals. However, the level of professional experience and specialization might influence the perception of more subtle examples of poor welfare. Raising awareness regarding canine welfare, including concern for breed- or behavior-related problems, should be emphasized within university programs.

Asociación de nefropatía por cambios mínimos y policitemia en un paciente muy anciano / Association of minimal-change disease and polycythaemia in a very elderly patient

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Do endothelial cells belong to the primitive stem leukemic clone in CML? Role of extracellular vesicles.

The expression of BCR-ABL in hematopoietic stem cells is a well-defined primary event in chronic myeloid leukemia (CML). Some reports have described the presence of BCR-ABL on endothelial cells from CML patients, suggesting the origin of the disease in a primitive hemangioblastic cell. On the other hand, extracellular vesicles (EVs) released by CML leukemic cells are involved in the angiogenesis modulation process. In the current work we hypothesized that EVs released from BCR-ABL(+) cells may carry inside the oncogene that can be transferred to endothelial cells leading to the expression of both BCR-ABL transcript and the oncoprotein. EVs from K562 cells and plasma of newly diagnosed CML patients were isolated by ultracentrifugation. RT-PCR analysis detected the presence of BCR-ABL RNA in the EVs isolated from both K562 cells and plasma of CML patients. The incorporation of these EVs into endothelial cells was demonstrated by flow cytometry and fluorescence microscopy showed that after 24h of incubation most EVs were incorporated. BCR-ABL transcripts were detected in all experiments on endothelial cells incubated with EVs from both sources. The presence of BCR-ABL on endothelial cells incubated with Philadelphia(+) EVs was also confirmed by Western blot assays. In summary, endothelial cells acquire BCR-ABL RNA and the oncoprotein after incubation with EVs released from Ph(+) positive cells (either from K562 cells or from plasma of newly diagnosed CML patients). This results challenge the hypothesis that endothelial cells may be part of the Philadelphia(+) clone in CML.

Plasma ß-amyloid peptides in canine aging and cognitive dysfunction as a model of Alzheimer's disease.

Aging dogs naturally demonstrate cognitive impairment and neuropathology that model early Alzheimer's disease (AD). In particular, there is evidence that canine cognitive dysfunction syndrome (CDS) in aged dogs is accompanied by cortical deposition of Aß peptides and neurodegeneration. Plasma Aß levels have been examined in humans as putative biomarkers for AD, but to date, no similar studies have been conducted for canine dementia. The aim of the present study was to assess plasma Aß1-42 and Aß1-40 levels in a blind study using pet dogs that were either successfully aging or exhibiting CDS. The severity of cognitive impairment was assessed using an owner-based questionnaire. On average, young dogs presented significantly higher plasma levels of Aß1-42 and Aß1-40 than aged, cognitively unimpaired dogs. Notably, among aged dogs, the levels of Aß1-42 and the Aß42/40 ratio were significantly higher in those showing mild cognitive impairment than in either cognitively unimpaired or severely affected dogs. These results suggest that increased plasma Aß1-42 levels and Aß42/40 ratio could be a biomarker for canine cognitive dysfunction, which is considered an excellent natural model of early AD.

Serotonin transporter activity in platelets and canine aggression.

Several studies have suggested an inhibitory action of the serotonergic system in the regulation of canine aggression, but the role of the serotonin (5-HT) transporter (5-HTT) has not been investigated. Platelet 5-HT uptake has been proposed as a peripheral marker of brain 5-HTT. The aim of the study was to investigate the relationship between platelet 5-HTT activity and canine aggression by measuring the rate of 5-HT uptake mediated by 5-HTT in platelets and serum concentrations of 5-HT in both aggressive (n=14) and non-aggressive dogs (n=17). Aggressive dogs showed significantly higher 5-HT uptake by 5-HTT in platelets and lower serum concentrations of 5-HT, compared with the control group. These results suggested an association between an alteration in the serotonergic system and canine aggression, possibly mediated by an increased 5-HT transport.

A comprehensive study of dog bites in Spain, 1995-2004.

Dog bites in humans are a complex problem embracing public health and animal welfare. To prevent dog bites it is necessary to have comprehensive epidemiological data that allow the identification of associated risk patterns. This study was aimed at investigating the problem posed by dog bites in Spain. The epidemiology of medically attended dog bite-related incidents reported in Aragón was analysed from 1995 to 2004. Bite incidents were mostly associated with: (1) low-population areas (71.3/100,000 inhabitants); (2) males and children, particularly those aged 5-9; (3) single injuries directed to the head and neck area in children and to the extremities in adults; (4) young, male, medium to large, owned dogs that were known to the victim; (5) summer months, and (6) specific circumstances such as human interference with knocked down and fighting dogs. In the light of these risk patterns, a wide range of specific preventive measures could be proposed.