Positive Impact of Physical Exercise for Managing Stereotypies in Dogs

Stereotypies in dogs are repetitive behavioral patterns that occur always in the same sequence but do not play any role. This altered behavior may thus take over the animal’s life, changing its sleep patterns and eating habits. The drive to adopt the specific behavior becomes increasingly stronger, to the extent that the animal may sometimes even mutilate parts of its own body, such as the tail and limbs. The overall approach to the problem through retraining of owners, environmental modification and enrichment and proper use of psychotropics proved necessary for restoring the patients’ balance. However, it was also necessary to introduce a physical exercise routine with a canine motorized treadmill and/or daily walks. Although exercise itself may contribute to increased anxiety in the animal, the potential benefits justify considering its introduction for managing dogs with stereotypies.Fil: Ostrovsky, G.. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Alvarez, F.. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Risso, Analia Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET- La Plata. Instituto de Genética Veterinaria "Ing. Fernando Noel Dulout". Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Instituto de Genética Veterinaria; ArgentinaFil: Pellegrino, Francisco Javier. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Marchionni, M.. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Aversa, D.. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Corrada, Yanina Alejandra. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Algebraic Comparison of Partial Lists in Bioinformatics

The outcome of a functional genomics pipeline is usually a partial list of genomic features, ranked by their relevance in modelling biological phenotype in terms of a classification or regression model. Due to resampling protocols or just within a meta-analysis comparison, instead of one list it is often the case that sets of alternative feature lists (possibly of different lengths) are obtained. Here we introduce a method, based on the algebraic theory of symmetric groups, for studying the variability between lists ("list stability") in the case of lists of unequal length. We provide algorithms evaluating stability for lists embedded in the full feature set or just limited to the features occurring in the partial lists. The method is demonstrated first on synthetic data in a gene filtering task and then for finding gene profiles on a recent prostate cancer dataset

DRD4 genotype predicts longevity in mouse and human

Longevity is influenced by genetic and environmental factors. The brain's dopamine system may be particularly relevant, since it modulates traits (e.g., sensitivity to reward, incentive motivation, sustained effort) that impact behavioral responses to the environment. In particular, the dopamine D4 receptor (DRD4) has been shown to moderate the impact of environments on behavior and health. We tested the hypothesis that the DRD4 gene influences longevity and that its impact is mediated through environmental effects. Surviving participants of a 30-year-old population-based health survey (N = 310; age range, 90-109 years; the 90+ Study) were genotyped/resequenced at the DRD4 gene and compared with a European ancestry-matched younger population (N = 2902; age range, 7-45 years). We found that the oldest-old population had a 66% increase in individuals carrying the DRD4 7R allele relative to the younger sample (p = 3.5 × 10(-9)), and that this genotype was strongly correlated with increased levels of physical activity. Consistent with these results, DRD4 knock-out mice, when compared with wild-type and heterozygous mice, displayed a 7-9.7% decrease in lifespan, reduced spontaneous locomotor activity, and no lifespan increase when reared in an enriched environment. These results support the hypothesis that DRD4 gene variants contribute to longevity in humans and in mice, and suggest that this effect is mediated by shaping behavioral responses to the environment.Fil: Grady, Deborah L.. University of California. College of Medicine. Department of Biological Chemistry; Estados UnidosFil: Thanos, Panayotis K.. National Institute on Alcohol Abuse and Alcoholism. Laboratory of Neuroimaging; Estados Unidos. Brookhaven National Laboratory. Medical Department. Behavioral Neuropharmocology and Neuroimaging Laboratory; Estados Unidos. Stony Brook University. Department of Psychology; Estados UnidosFil: Corrada, Maria M.. University of California. Department of Neurology; Estados UnidosFil: Barnett Jr., Jeffrey C.. Brookhaven National Laboratory. Medical Department. Behavioral Neuropharmocology and Neuroimaging Laboratory; Estados UnidosFil: Ciobanu, Valentina. University of California. College of Medicine. Department of Biological Chemistry; Estados UnidosFil: Shustarovich, Diana. Brookhaven National Laboratory. Medical Department. Behavioral Neuropharmocology and Neuroimaging Laboratory; Estados UnidosFil: Napoli, Anthony. Brookhaven National Laboratory. Medical Department. Behavioral Neuropharmocology and Neuroimaging Laboratory; Estados UnidosFil: Moyzis, Alexandra G.. University of California. College of Medicine. Department of Biological Chemistry; Estados UnidosFil: Grandy, David. Oregon Health Sciences University. Physiology and Pharmacology; Estados UnidosFil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; ArgentinaFil: Wang, Gene-Jack. Brookhaven National Laboratory. Medical Department. Behavioral Neuropharmocology and Neuroimaging Laboratory; Estados UnidosFil: Kawas, Claudia H.. University of California. Department of Neurology; Estados UnidosFil: Chen, Chuansheng. University of California. Department of Psychology and Social Behavior; Estados UnidosFil: Dong, Qi. Beijing Normal University. National Key Laboratory of Cognitive Neuroscience and Learning; ChinaFil: Wang, Eric. University of California. College of Medicine. Department of Biological Chemistry; Estados Unidos. Aria Diagnostics Inc.; Estados Unidos. University of California. Institute of Genomics and Bioinformatics; Estados UnidosFil: Volkow, Nora D.. National Institute on Alcohol Abuse and Alcoholism. Laboratory of Neuroimaging; Estados Unidos. Brookhaven National Laboratory. Medical Department. Behavioral Neuropharmocology and Neuroimaging Laboratory; Estados Unidos. National Institute on Drug Abuse; Estados UnidosFil: Moyzis, Robert K.. University of California. College of Medicine. Department of Biological Chemistry; Estados Unidos. Beijing Normal University. National Key Laboratory of Cognitive Neuroscience and Learning; China. University of California. Institute of Genomics and Bioinformatics; Estados Unido

In vitro and in vivo assessment of skim milk with and without egg yolk on canine spermatozoa incubated at 4ºC

The aims of this study were to assess and compare the effect of skim milk with (MEY) and without (SMI) egg yolk on canine spermatozoa incubated at 4ºC in vitro and to evaluate the efficacy of MEY in vivo. Also, the effect of semen cooled storage before freezing was also evaluated in vitro. The ejaculates of 10 dogs were collected, pooled, centrifuged, and divided into 4 aliquots and diluted in one of the following 4 diluents: Prostatic fluid (PRO), commercial diluent (COM), SMI, or MEY. Extended samples were stored at 4°C and evaluated daily for 6 days. Percentage of total (P 0.1) bitches from each group became pregnant and whelped normally. MEY extended semen samples were cooled for 2, 24, or 48 h at 4°C, and a second dilution was performed prior to freezing and thawing. Post-thaw total and forward sperm motility decreased with increasing cooled storage (P < 0.05), although no significant differences in total or forward motility, normal acrosomes, positive endosmosis, live spermatozoa, or positive endosmosis were found between 2 and 24 h storage. These in vitro and in vivo results show that MEY can be considered a simple, inexpensive, and efficient diluent for canine semen chilling. Furthermore, MEY could be successfully frozen after 1 day of cooled storage.Facultad de Ciencias Veterinaria

Visual memory predicts Alzheimer’s disease more than a decade before diagnosis

BackgroundRecent studies have suggested that AD may reflect a chronic process that begins many years before the clinical expression of dementia. The current study examines premorbid Benton Visual Retention Test (BVRT) and Wechsler Adult Intelligence Scale-vocabulary (WAIS-voc) test scores in order to determine whether long-term deficits in these tests can predict the development of AD decades later in the Baltimore Longitudinal Study of Aging (BLSA).MethodParticipants are volunteers from the BLSA, a multidisciplinary study of normal aging conducted by the National Institute on Aging. A total of 1,425 BLSA participants who were older than 60 years were included in the analyses. Cox proportional hazards models were used to estimate the relative risk of developing AD associated with BVRT and WAIS-voc scores at different time periods up to 20 years before the diagnosis of AD.ResultsThe relative risks for 6 or more BVRT errors vs less than 6 errors at 1 to 3, 3 to 5, 5 to 10, and 10 to 15 years before the diagnosis of AD were 5.69, 2.11, 1.76, and 1.83 (p &lt; 0.05). The relative risk for 15 or more years before diagnosis was not significant (p &gt; 0.10). WAIS-voc scores were not significantly associated with the risk of AD in any time period.ConclusionsA greater number of errors on the BVRT is associated with an increased risk of AD up to 15 years later. Poor visual memory performance may represent an early expression of AD years before diagnosis. This result suggests the need to continue to revise views on the natural history of AD and the possibility of an increased window of opportunity for preventive treatment before definitive diagnosis

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

In vitro and in vivo assessment of skim milk with and without egg yolk on canine spermatozoa incubated at 4ºC

The aims of this study were to assess and compare the effect of skim milk with (MEY) and without (SMI) egg yolk on canine spermatozoa incubated at 4ºC in vitro and to evaluate the efficacy of MEY in vivo. Also, the effect of semen cooled storage before freezing was also evaluated in vitro. The ejaculates of 10 dogs were collected, pooled, centrifuged, and divided into 4 aliquots and diluted in one of the following 4 diluents: Prostatic fluid (PRO), commercial diluent (COM), SMI, or MEY. Extended samples were stored at 4°C and evaluated daily for 6 days. Percentage of total (P 0.1) bitches from each group became pregnant and whelped normally. MEY extended semen samples were cooled for 2, 24, or 48 h at 4°C, and a second dilution was performed prior to freezing and thawing. Post-thaw total and forward sperm motility decreased with increasing cooled storage (P < 0.05), although no significant differences in total or forward motility, normal acrosomes, positive endosmosis, live spermatozoa, or positive endosmosis were found between 2 and 24 h storage. These in vitro and in vivo results show that MEY can be considered a simple, inexpensive, and efficient diluent for canine semen chilling. Furthermore, MEY could be successfully frozen after 1 day of cooled storage.Facultad de Ciencias Veterinaria

Simultaneous isolation of intact brain cells and cell-specific extracellular vesicles from cryopreserved Alzheimer’s disease cortex

BackgroundThe neuronal and gliaI populations within the brain are tightly interwoven, making isolation and study of large populations of a single cell type from brain tissue a major technical challenge. Concurrently, cell-type specific extracellular vesicles (EVs) hold enormous diagnostic and therapeutic potential in neurodegenerative disorders including Alzheimer's disease (AD).New methodPostmortem AD cortical samples were thawed and gently dissociated. Following filtration, myelin and red blood cell removal, cell pellets were immunolabeled with fluorescent antibodies and analyzed by flow cytometry. The cell pellet supernatant was applied to a triple sucrose cushion for brain EV isolation.ResultsNeuronal, astrocyte and microglial cell populations were identified. Cell integrity was demonstrated using calcein AM, which is retained by cells with esterase activity and an intact membrane. For some experiments cell pellets were fixed, permeabilized, and immunolabeled for cell-specific markers. Characterization of brain small EV fractions showed the expected size, depletion of EV negative markers, and enrichment in positive and cell-type specific markers.Comparison with existing methods and conclusionsWe optimized and integrated established protocols, aiming to maximize information obtained from each human autopsy brain sample. The uniqueness of our method lies in its capability to isolate cells and EVs from a single cryopreserved brain sample. Our results not only demonstrate the feasibility of isolating specific brain cell subpopulations for RNA-seq but also validate these subpopulations at the protein level. The accelerated study of EVs from human samples is crucial for a better understanding of their contribution to neuron/glial crosstalk and disease progression