The application of epiphenotyping approaches to DNA methylation array studies of the human placenta.

BACKGROUND: Genome-wide DNA methylation (DNAme) profiling of the placenta with Illumina Infinium Methylation bead arrays is often used to explore the connections between in utero exposures, placental pathology, and fetal development. However, many technical and biological factors can lead to signals of DNAme variation between samples and between cohorts, and understanding and accounting for these factors is essential to ensure meaningful and replicable data analysis. Recently, "epiphenotyping" approaches have been developed whereby DNAme data can be used to impute information about phenotypic variables such as gestational age, sex, cell composition, and ancestry. These epiphenotypes offer avenues to compare phenotypic data across cohorts, and to understand how phenotypic variables relate to DNAme variability. However, the relationships between placental epiphenotyping variables and other technical and biological variables, and their application to downstream epigenome analyses, have not been well studied. RESULTS: Using DNAme data from 204 placentas across three cohorts, we applied the PlaNET R package to estimate epiphenotypes gestational age, ancestry, and cell composition in these samples. PlaNET ancestry estimates were highly correlated with independent polymorphic ancestry-informative markers, and epigenetic gestational age, on average, was estimated within 4 days of reported gestational age, underscoring the accuracy of these tools. Cell composition estimates varied both within and between cohorts, as well as over very long placental processing times. Interestingly, the ratio of cytotrophoblast to syncytiotrophoblast proportion decreased with increasing gestational age, and differed slightly by both maternal ethnicity (lower in white vs. non-white) and genetic ancestry (lower in higher probability European ancestry). The cohort of origin and cytotrophoblast proportion were the largest drivers of DNAme variation in this dataset, based on their associations with the first principal component. CONCLUSIONS: This work confirms that cohort, array (technical) batch, cell type proportion, self-reported ethnicity, genetic ancestry, and biological sex are important variables to consider in any analyses of Illumina DNAme data. We further demonstrate the specific utility of epiphenotyping tools developed for use with placental DNAme data, and show that these variables (i) provide an independent check of clinically obtained data and (ii) provide a robust approach to compare variables across different datasets. Finally, we present a general framework for the processing and analysis of placental DNAme data, integrating the epiphenotype variables discussed here.

Prenatal stress and epigenetics.

In utero exposure to environmental stress in both animals and humans could result in long-term epigenome alterations which further lead to consequences for adaptation and development in the offspring. Epigenetics, especially DNA methylation, is considered one of the most widely studied and well-characterized mechanisms involved in the long-lasting effects of in utero stress exposure. In this review, we outlined evidence from animal and human prenatal research supporting the view that prenatal stress could lead to lasting, broad and functionally organized signatures in DNA methylation which, in turn, could mediate exposure-phenotype associations. We also emphasized the advantage of using stressor from quasi-randomly assigned experiments. Furthermore, we discuss challenges that still need to be addressed in this field in the future.

Detection and molecular characterization of porcine parvovirus in fetal tissues from sows without reproductive failure in Argentina.

Porcine parvovirus (PPV) is one of many pathogens responsible for reproductive failure in pregnant sows. Several studies have reported the appearance of new PPV strains that differ from previous isolates both genetically and antigenically. Thus, the protective effects of commercially inactivated vaccines could not be complete. In South America, the information about PPV is limited. Thus, the aim of the present study was to detect and characterize the PPV strains present in 131 mummies or stillbirths from normal deliveries in sows from a commercial swine farm of Argentina that uses the commercial vaccine. PCR results showed that 17/131 were positive to PPV. Ten of these viruses were isolated and sequenced. All viruses were related to the PPV1 sequence (NADL-2), maintaining the amino acid differences in positions 436 (S-P) and 565 (R-K). This study is the first to report the isolation of PPV in Argentina and the results suggest that PPV can cross the placenta even in vaccinated sows, thus affecting some of the fetuses and being able to cause fetal death in sows without reproductive failure. The results also suggest that vaccination only reduces clinical signs and reproductive disorders and may thus not be a perfect tool to manage PPV infection. This study provides information that needs to be studied in depth to improve strategies to prevent and control PPV infection in swine farms.

The Impact of Acute Stress Physiology on Skilled Motor Performance: Implications for Policing.

Investigations of police performance during acutely stressful situations have primarily focused on higher-order cognitive processes like attention, affect or emotion and decision-making, and the behavioral outcomes of these processes, such as errors in lethal force. However, behavioral outcomes in policing must be understood as a combination of both higher-order processes and the physical execution of motor skills. What is missing from extant police literature is an understanding of how physiological responses to acute stress contribute to observed decrements in skilled motor performance at the neuromuscular level. The purpose of the current paper is to fill this knowledge gap in the following ways: (1) review scientific evidence for the physiological (i.e., autonomic, endocrine, and musculoskeletal) responses to acutely stressful exposures and their influence on skilled motor performance in both human and animal models, (2) review applied evidence on occupationally relevant stress physiology and observed motor decrements in performance among police, and (3) discuss the implications of stress physiology for police training and identify future directions for applied researchers. Evidence is compelling that skill decay is inevitable under high levels of acute stress; however, robust evidence-informed training practices can help mitigate this decay and contribute to officer safety.

Recent Canadian efforts to develop population-level pregnancy intervention studies to mitigate effects of natural disasters and other tragedies.

The preconception, pregnancy and immediate postpartum and newborn periods are times for mothers and their offspring when they are especially vulnerable to major stressors - those that are sudden and unexpected and those that are chronic. Their adverse effects can transcend generations. Stressors can include natural disasters or political stressors such as conflict and/or migration. Considerable evidence has accumulated demonstrating the adverse effects of natural disasters on pregnancy outcomes and developmental trajectories. However, beyond tracking outcomes, the time has arrived for gathering more information related to identifying mechanisms, predicting risk and developing stress-reducing and resilience-building interventions to improve outcomes. Further, we need to learn how to encapsulate both the quantitative and qualitative information available and share it with communities and authorities to mitigate the adverse developmental effects of future disasters, conflicts and migrations. This article briefly reviews prenatal maternal stress and identifies three contemporary situations (wildfire in Fort McMurray, Alberta, Canada; hurricane Harvey in Houston, USA and transgenerational and migrant stress in Pforzheim, Germany) where current studies are being established by Canadian investigators to test an intervention. The experiences from these efforts are related along with attempts to involve communities in the studies and share the new knowledge to plan for future disasters or tragedies.

Evaluation of apoptosis markers in different cell lines infected with equine arteritis virus.

Equine arteritis virus (EAV) induces apoptosis in infected cells. Cell death caused by EAV has been studied mainly using three cell lines, BHK-21, RK-13 and Vero cells. The mechanism of apoptosis varies among cell lines and results cannot be correlated owing to differences in EAV strains used. We evaluated different markers for apoptosis in BHK-21, RK-13 and Vero cell lines using the Bucyrus EAV reference strain. Acridine orange/ethidium bromide staining revealed morphological changes in infected cells, while flow cytometry indicated the extent of apoptosis. We also observed DNA fragmentation, but the DNA ladder was detected at different times post-infection depending on the cell line, i.e., 48, 72 and 96 h post-infection in RK-13, Vero and BHK-21 cells, respectively. Measurement of viral titers obtained with each cell line indicated that apoptosis causes interference with viral replication and therefore decreased viral titers. As an unequivocal marker of apoptosis, we measured the expression of caspase-3 and caspases-8 and -9 as extrinsic and intrinsic markers of apoptosis pathways, respectively. Caspase-8 in BHK-21 cells was the only protease that was not detected at any of the times assayed. We found that Bucyrus EAV strain exhibited a distinctive apoptosis pathway depending on the cell line.

Multigenerational prenatal stress increases the coherence of brain signaling among cortico-striatal-limbic circuits in adult rats.

Prenatal stress (PNS) is a significant risk factor for the development of psychopathology in adulthood such as anxiety, depression, schizophrenia and addiction. Animal models of PNS resemble many of the effects of PNS on humans and provide a means to study the accumulated effects of PNS over several generations on brain function. Here, we examined how mild PNS delivered during the third week in utero over four consecutive generations affects behavioral flexibility and functional signaling among cortical and limbic structures. These multi-generational prenatally stressed (MGPNS) rats were not impaired on an odor-cued reversal learning task as compared to control animals. Unilateral field potential (FP) recordings from the medial prefrontal cortex, basolateral amygdala, ventral hippocampus, and striatal territories revealed widespread differences in brain signaling between these groups during the odor sampling phase of the task. The FP power was significantly lower in most structures across most frequency bands in MGPNS animals, and the relative increase in power from baseline during the task was lower for the beta band (12-30Hz) in MGPNS animals as compared to controls. The coherence of FPs between brain regions, however, was much higher in MGPNS animals among all structures and for most frequency bands. We propose that this pattern of changes in brain signaling reflects a simplification of network processing, which is consistent with reports of reduced spine density and dendritic complexity in the brains of animals receiving PNS. Our data support the proposal that recurrent ancestral stress leads to adaptations in the brain, and that these may confer adaptive behavior in some circumstances as compared to single-generation PNS.

Transfusion policy after severe postpartum haemorrhage: a randomised non-inferiority trial.

OBJECTIVE: To assess the effect of red blood cell (RBC) transfusion on quality of life in acutely anaemic women after postpartum haemorrhage. DESIGN: Randomised non-inferiority trial. SETTING: Thirty-seven Dutch university and general hospitals. POPULATION: Women with acute anaemia (haemoglobin 4.8-7.9 g/dl [3.0-4.9 mmol/l] 12-24 hours postpartum) without severe anaemic symptoms or severe comorbidities. METHODS: Women were allocated to RBC transfusion or non-intervention. MAIN OUTCOME MEASURES: Primary outcome was physical fatigue 3 days postpartum (Multidimensional Fatigue Inventory, scale 4-20; 20 represents maximal fatigue). Non-inferiority was demonstrated if the physical fatigue difference between study arms was maximal 1.3. Secondary outcomes were health-related quality of life and physical complications. Health-related quality of life questionnaires were completed at five time-points until 6 weeks postpartum. RESULTS: In all, 521 women were randomised to non-intervention (n = 262) or RBC transfusion (n = 259). Mean physical fatigue score at day 3 postpartum, adjusted for baseline and mode of delivery, was 0.8 lower in the RBC transfusion arm (95% confidence interval: 0.1-1.5, P = 0.02) and at 1 week postpartum was 1.06 lower (95% confidence interval: 0.3-1.8, P = 0.01). A median of two RBC units was transfused in the RBC transfusion arm. In the non-intervention arm, 33 women received RBC transfusion, mainly because of anaemic symptoms. Physical complications were comparable. CONCLUSIONS: Statistically, non-inferiority could not be demonstrated as the confidence interval crossed the non-inferiority boundary. Nevertheless, with only a small difference in physical fatigue and no differences in secondary outcomes, implementation of restrictive management seems clinically justified.

The equine arteritis virus isolate from the 2010 Argentinian outbreak.

A semen sample from a stallion infected during the 2010 equine arteritis virus (EAV) outbreak was received for viral isolation prior to castration of the animal. The virus was identified using a polyclonal antibody immunofluorescence test. Reverse-transcription polymerase chain reaction (RT-PCR) was used to amplify a region of the GP5 gene with primers GL105F and GL673R. The PCR products were purified and sequences of both strands were determined in a MegaBACE™1000 with inner primers CR2 and EAV32. A phylogenetic dataset was built with the previously reported sequences of five strains isolated in Argentina, together with a group of selected sequences obtained from GenBank. The unrooted neighbour-joining tree was constructed using molecular evolutionary genetic analysis (MEGA) and bootstrap analyses were conducted using 1,000 replicate datasets. Evolutionary distances were computed using the maximum composite likelihood method. A NetNGlyc server analysis at the Technical University of Denmark (www.cbs.dtu.dk/services/NetNGlyc/) was used to predict N-glycosylation in GP5 sequences. The phylogenetic analysis revealed that the new strain GLD-LP-ARG), together with other strains previously isolated, belongs to the European group EU-1 but in a different branch. The new strain shows 99% nucleotide identity with strain Al1and 98.1% with the Belgian strain 08P178. Persistently infected stallions and their cryopreserved semen constitute a reservoir of EAV, which ensures its persistence in the horse population around the world. These findings reinforce the importance of careful monitoring of persistently infected stallions, as well as semen straws, by RT-PCR or test mating, in accordance with national regulations.

ELA-DRA polymorphisms are not associated with Equine Arteritis Virus infection in horses from Argentina.

Polymorphisms at Major Histocompatibility Complex (MHC) genes have been associated with resistance/susceptibility to infectious diseases in domestic animals. The aim of this investigation was to evaluate whether polymorphisms of the DRA gene the Equine Lymphocyte Antigen is associated with susceptibility to Equine Arteritis Virus (EAV) infection in horses in Argentina. The equine DRA gene was screened for polymorphisms using Pyrosequencing® Technology which allowed the detection of three ELA-DRA exon 2 alleles. Neither allele frequencies nor genotypic differentiation exhibited any statistically significant (P-values=0.788 and 0.745) differences between the EAV-infected and no-infected horses. Fisher's exact test and OR calculations did not show any significant association. As a consequence, no association could be established between the serological condition and ELA-DRA.

Eca20 microsatellite polymorphisms in equine viral arteritis-infected horses from Argentina.

We investigated the association of equine arteritis virus (EAV) infection and three short tandem repeat (STR) polymorphisms located within or in close proximity to equine lymphocyte antigen (ELA) region. We used a case-control design as a first approach before proceeding to select candidate genes. One hundred and sixty-five Silla Argentino horses were taken in 2002 from positive serological detections of EAV in Argentina, to determine whether STR genotypes were correlated to genetic susceptibility to EVA. Allele frequency distribution did not show significant differences between both groups (P = 0.0781). However, in particular alleles, Fisher exact test and odds ratio calculations showed significant values >1 for TKY08 and LEX52, and <1 for UM011, TKY08, LEX52 and VHL20. Interestingly, TKY08 STR is located in ELA class I region.

Phylogenetic analysis of Suid Herpesvirus 1 isolates from Argentina.

Argentinean Suid Herpesvirus 1 isolates were compared with reference strains and sequences available at GenBank and phylogenetically analyzed. A short fragment of the gE gene of the immunodominant epitopes was used for preliminary grouping of isolates by phylogenetic analysis. The analysis of the partial gC gene provided more precise genetic typing and segregation into the main genotypes I and II. Results confirmed that the Argentinean genotype I isolates predominate in our country. The topology of the partial gC gene was similar to that previously reported. The Argentinean type I isolates belonged to one cluster and grouped together with NIA-3 and American and Brazilian genotype I strains. However, the results obtained by the algorithms allow inferring that the Yamagata S-81 and Mer (genotype II) strains are grouped together.

Characterization of Suid herpesvirus 1 field isolates from Argentina.

The genomic characterization of Suid herpesvirus 1 (SHV-1) isolates from Argentina was accomplished by restriction pattern analysis using the BamHI, BstEII and XhoI enzymes. Type II genome has been described only once in Argentina. This study revealed considerable homogeneity of BamHI endonuclease sites in all the strains analyzed, according to the number and size of the fragments. No deletion of BamHI fragment #7 among the Argentinean isolates suggests that these strains are wild-type. In addition, the main antigenic domain of glycoprotein E of all the Argentinean strains, as well as the reference strains and sequences available in the GenBank, were characterized. The similarity percent oscillated between 99 and 100%.

Evaluation of neutralization patterns of the five unique Argentine equine arteritis virus field strains reported.

Equine viral arteritis (EVA) is a contagious viral disease that frequently causes mild or subclinical infections in adult horses. Only one EAV serotype has been described. However, there are differences in antigenicity, pathogenicity and neutralization characteristics of virus field strains. The interaction of two viral proteins, GP5 and M, is critical for infectivity and amino acid changes in the GP5 sequences have an effect on the neutralizing phenotype, regardless the effects of other viral proteins. The objective of the present study was to evaluate the neutralization phenotypes of the 5 unique Argentine EAV strains reported and to compare them with the neutralization phenotypes of the EAV-UCD reference strain, with special emphasis on the analysis of M and GP5 proteins. The strains had a similar neutralization phenotype pattern when anti-EAV serum, derived from EAV seropositive horses, was used in the analysis. Meanwhile, low titers were observed when equine polyclonal anti-EAV reference sera were used in the assay. Argentine strains have almost the same amino acid substitutions, with the exception of LP01 strain, that mainly involves the first variable region V1, especially in neutralization sites B and C. However, they are fairly different from the EAV-UCD strain. Nevertheless, the nucleotide and amino acid differences observed among the Argentine strains LP02/R, LP02/C, LP02/P and LP-LT-ARG did not show any variations in the neutralization phenotype.

Evaluation of neutralization patterns of the five unique Argentine equine arteritis virus field strains reported / Evaluación de los patrones de neutralización de las únicas cinco cepas argentinas descritas de arteritis viral equina

Equine viral arteritis (EVA) is a contagious viral disease that frequently causes mild or subclinical infections in adult horses. Only one EAV serotype has been described. However, there are differences in antigenicity, pathogenicity and neutralization characteristics of virus field strains. The interaction of two viral proteins, GP5 and M, is critical for infectivity and amino acid changes in the GP5 sequences have an effect on the neutralizing phenotype, regardless the effects of other viral proteins. The objective of the present study was to evaluate the neutralization phenotypes of the 5 unique Argentine EAV strains reported and to compare them with the neutralization phenotypes of the EAV-UCD reference strain, with special emphasis on the analysis of M and GP5 proteins. The strains had a similar neutralization phenotype pattern when anti-EAV serum, derived from EAV seropositive horses, was used in the analysis. Meanwhile, low titers were observed when equine polyclonal anti-EAV reference sera were used in the assay. Argentine strains have almost the same amino acid substitutions, with the exception of LP01 strain, that mainly involves the first variable region V1, especially in neutralization sites B and C. However, they are fairly different from the EAV-UCD strain. Nevertheless, the nucleotide and amino acid differences observed among the Argentine strains LP02/R, LP02/C, LP02/P and LP-LT-ARG did not show any variations in the neutralization phenotype.

La arteritis viral equina (AVE) ocasiona infecciones, en su mayoría subclínicas, pero puede causar abortos y enfermedad respiratoria. Si bien se ha descrito un solo serotipo de AVE, existen diferencias en cuanto a la antigenicidad, patogenicidad y patrones de neutralización en las cepas de campo. Los ORF5 y ORF6 del virus codifican las proteínas de envoltura GP5 y M; la interacción entre estas proteínas es crítica para la infectividad. Los cambios en las secuencias de aminoácidos en la proteína GP5, especialmente en la región V1, afectan el fenotipo neutralizante, sin tener en cuenta variaciones aminoacídicas de otras proteínas virales. En este estudio evaluamos los fenotipos neutralizantes de las 5 únicas cepas de arteritis viral equina aisladas en Argentina y los comparamos con los de la cepa de referencia EAV-UCD por virus neutralización cruzada y análisis de secuencias aminoacídicas de las proteínas M y GP5. Las cepas argentinas presentaron un patrón de neutralización similar cuando se utilizaron sueros positivos del banco de sueros, mientras que fueron neutralizadas en menor medida por los sueros policlonales de referencia anti-AVE. A excepción de la cepa LP01, las cepas argentinas tienen casi las mismas sustituciones aminoacídicas en la primera región variable V1 de la proteína GP5, específicamente en los sitios neutralizantes B y C, pero difieren en gran medida respecto de la cepa de referencia EAV-UCD. Las diferencias encontradas en los aislamientos LP02/R, LP02/C, LP02/P y LT-LP-ARG no se reflejaron en variaciones en el fenotipo neutralizante.

Enriched environment promotes efficiency of compensatory movements after cerebral ischemia in rats.

Rehabilitation therapy is known to drive motor improvement in stroke patients. However, the interplay of functional recovery and compensation in postischemic motor behavior is poorly understood. This study focused on the time course of functional recovery versus motor compensation in skilled forelimb movements after cerebral ischemia in rats. Young adult male rats underwent a focal cerebral ischemia by unilateral photothrombotic lesion of the motor cortex related to the preferred forelimb. In a first set of experiments animals were exposed to small cortical lesions comprising the forelimb motor cortex (n=8) or to larger lesions additionally extending into the hind limb motor area (n=8). In a second set of experiments animals with large lesion were either housed in standard (n=10) or enriched environment (n=14). Skilled reaching was assessed for 25 to 28 days postischemia. This task allows the distinction between recovery and compensation by parallel quantitative (reaching success) and qualitative (movement pattern) analysis. The results reveal that lesion size determines the initial magnitude of motor deficits, but not the degree of chronic impairments in movement pattern in all experimental groups. Compensatory movements represent the major mechanism of functional improvement and were accompanied by a partial functional restitution. Enriched environment facilitates effective compensation in skilled reaching, while it does not promote restitution of function. In particular, rotating movements of the forelimb during reaching were permanently impaired and required functional compensation through intensified use of the upper body. We conclude an activity dependent postischemic restoration of movement success. Enriched environment provides benefit by increased motor activity mainly due to compensation. Furthermore, these findings emphasize the power of comprehensive movement analysis to gain insight into recovery processes after stroke.

Cirugía de revascularización miocárdica con y sin circulación extra corpórea / Myocardial revascularization surgery with and without extra-corporeal circulation

Introducción: Es controvertida la ventaja de la cirugía de revascularización miocárdica sin circulación extracorpórea. Objetivo: Comparar variables de evolución en cirugía de revascularización miocárdica (CRM) con y sin circulación extracorpórea. Material y métodos: Estudio retrospectivo observacional analítico. Fueron incluidos pacientes sometidos a CRM en el Hospital San Juan de Dios de La Plata desde el 1º de abril de 2000 al 30 de marzo de 2008 (n = 142). Criterios de exclusión: urgencia y edad > 70 años. Registro de variables independientes: edad (p = 0,63), género (p = 0,42), experiencia del cirujano (p = 0,08), diabetes (p = 0,98), glucemia (p = 0,14)

Introduction: The advantage of off-pump versus on-pump coronary artery bypass graft surgery (CRM) is in dispute. Objective: To compare the outcome of off-pump and on-pump coronary artery bypass graft surgery. Materials and methods: Retrospective observational analytical study. Our study included 142 patients who underwent CRM at the Hospital San Juan de Dios in La Plata between April 1, 2007 and March 30, 2008. Exclusion criteria: urgency and age >70 years. Register of independent variables: age (p = 0,63), gender (p = 0,42), surgeons experience (CX) (p = 0,08), diabetes (p = 0,98), glycemia (p = 0,14) and lactacidemia (p = 0,21) on admission to operating room, and ASA (p = 0,001). Outcome variables: glycaemia and lactacidemia at the end of surgery (LE), inotropic support time, mechanical ventilation (MV) time; postoperative hospital stay (EP); re-operation and mortality. Database EPI-Info 6.0. Statistical analysis: To compare the difference between groups: squared Ji was used and the Kruskal-Wallis test to compare numeric variables between the groups. A p < 0.05 was considered significant. Results: 116 patients with cardiopulmonary by-pass (OC) and 26 without it (CE). Complicated postoperative evolution was observed in one pump CRM: hyperglycemia (p = 0.0001) and hyperlactacidemia (p = 0.0001) at the end of the surgery, higher inotropic time support (p = 0.0001) and mortality (p = 0.04). However in the analysis of the sample, the ASA Score and the number of grafts have statistical significance; this precludes hazarding definitive conclusions.(AU)

IntroduþÒo: Existem controvérsias sobre a vantagem da cirurgia de revascularizaþÒo miocárdica sem circulaþÒo extracorpórea. Objetivo: Comparar variáveis de evoluþÒo nas cirurgias de revascularizaþÒo miocárdica (CRM) com e sem circulaþÒo extracorpórea. Material e métodos: Estudo retrospectivo observacional analítico. Foram incluídos pacientes submetidos a CRM no Hospital San Juan de Dios de La Plata entre 1º de abril de 2007 e 30 de marþo de 2008 (n = 142). Critérios de exclusÒo: urgÛncia e idade > 70 anos. Registro de variáveis independentes: idade (p = 0,63), genero (p = 0,42), experiencia do cirurgiÒo (p = 0,08), diabetes (p = 0,98), glicemia (p = 0,14) e

Cirugía de revascularización miocárdica con y sin circulación extra corpórea / Myocardial revascularization surgery with and without extra-corporeal circulation

Introducción: Es controvertida la ventaja de la cirugía de revascularización miocárdica sin circulación extracorpórea. Objetivo: Comparar variables de evolución en cirugía de revascularización miocárdica (CRM) con y sin circulación extracorpórea. Material y métodos: Estudio retrospectivo observacional analítico. Fueron incluidos pacientes sometidos a CRM en el Hospital San Juan de Dios de La Plata desde el 1° de abril de 2000 al 30 de marzo de 2008 (n = 142). Criterios de exclusión: urgencia y edad > 70 años. Registro de variables independientes: edad (p = 0,63), género (p = 0,42), experiencia del cirujano (p = 0,08), diabetes (p = 0,98), glucemia (p = 0,14) y lactacidemia (p = 21) al ingreso al quirófano, y ASA (p = 0,001) y número de puentes (p = 0,001). Variables de resultado: tiempo de apoyo inotrópico (AI), tiempo de ventilación mecánica (VM), estancia posoperatoria (EP), reoperación y mortalidad. Base de datos EPI-Info 6.0. Análisis estadístico: para comparar diferencias entre los grupos se utilizó ji al cuadrado, y para comparar variables numéricas entre los grupos, el test de Kruskal-Wallis. Se consideró significativa una p < 0,05. Resultados: 116 pacientes con derivación cardiopulmonar (DC) y 26 sin derivación cardiopulmonar. Se observó una evolución posoperatoria complicada en los casos de DC: hiperglucemia (p = 0,0001) e hiperlactacidemia (p = 0,0001) de egreso, mayor tiempo de apoyo inotrópico (p = 0,0001) y mortalidad (p = 0,04). Sin embargo, en el análisis de composición de la muestra, son significativos la puntuación ASA y el número de puentes, lo cual impide arriesgar conclusiones definitivas.

Introduction: The advantage of off-pump versus on-pump coronary artery bypass graft surgery (CRM) is in dispute. Objective: To compare the outcome of off-pump and on-pump coronary artery bypass graft surgery. Materials and methods: Retrospective observational analytical study. Our study included 142 patients who underwent CRM at the Hospital San Juan de Dios in La Plata between April 1, 2007 and March 30, 2008. Exclusion criteria: urgency and age >70 years. Register of independent variables: age (p = 0,63), gender (p = 0,42), surgeon's experience (CX) (p = 0,08), diabetes (p = 0,98), glycemia (p = 0,14) and lactacidemia (p = 0,21) on admission to operating room, and ASA (p = 0,001). Outcome variables: glycaemia and lactacidemia at the end of surgery (LE), inotropic support time, mechanical ventilation (MV) time; postoperative hospital stay (EP); re-operation and mortality. Database EPI-Info 6.0. Statistical analysis: To compare the difference between groups: squared Ji was used and the Kruskal-Wallis test to compare numeric variables between the groups. A p < 0.05 was considered significant. Results: 116 patients with cardiopulmonary by-pass (OC) and 26 without it (CE). Complicated postoperative evolution was observed in one pump CRM: hyperglycemia (p = 0.0001) and hyperlactacidemia (p = 0.0001) at the end of the surgery, higher inotropic time support (p = 0.0001) and mortality (p = 0.04). However in the analysis of the sample, the ASA Score and the number of grafts have statistical significance; this precludes hazarding definitive conclusions.

Introdução: Existem controvérsias sobre a vantagem da cirurgia de revascularização miocárdica sem circulação extracorpórea. Objetivo: Comparar variáveis de evolução nas cirurgias de revascularização miocárdica (CRM) com e sem circulação extracorpórea. Material e métodos: Estudo retrospectivo observacional analítico. Foram incluídos pacientes submetidos a CRM no Hospital San Juan de Dios de La Plata entre 1° de abril de 2007 e 30 de março de 2008 (n = 142). Critérios de exclusão: urgência e idade > 70 anos. Registro de variáveis independentes: idade (p = 0,63), genero (p = 0,42), experiencia do cirurgião (p = 0,08), diabetes (p = 0,98), glicemia (p = 0,14) e lactacidemia (p = 21), ao ingresso no quirófano, e ASA (p = 0.001) e número de pontes (p = 0,001). Variáveis de resultado: tempo de suporte inotrópico (AI), tempo de ventilação mecânica (VM), permanência hospitalar (EP), reoperação e óbitos. Base de dados EPI-Info 6.0. Análise estatística: foram utilizados, chi-quadrado para comparar diferenças entre os grupos, e o teste de Kruskal-Wallis para comparar variáveis numéricas entre os grupos; considerou-se significativa p < 0,05. Resultados: 116 pacientes com derivação cardiopulmonar (OC) e 26 sem derivação cardiopulmonar. Foi observada evolução pós-operatória complicada nos casos de DC: hiperglicemia (p = 0,0001) e hiperlactacidemia (p = 0,0001) de egresso, maior tempo de suporte inotrópico (p = 0,0001) e mortalidade (p = 0,04). Contudo, na análise de composição da amostra, sáo significativos o escore ASA e o número de pontes, o qual impede tirar conclusões definitivas.

Both pre- and post-lesion experiential therapy is beneficial in 6-hydroxydopamine dopamine-depleted female rats.

Experiential therapies, such as enriched environment (EE), have been shown to influence the neurodegenerative processes that underlie Parkinson's disease. We have previously demonstrated that EE promotes functional improvement in dopamine-depleted rats. Here we compare the influence of exposure to EE prior to versus after dopamine depletion in the 6-hydroxydopamine rat model of Parkinson's disease. Two groups of female rats were placed in an EE while two groups were housed in a standard environment (SE) for 6 weeks prior to receiving a unilateral nigrostriatal bundle infusion of the neurotoxin 6-hydroxydopamine. After the lesion, one group remained in EE, while the second EE group (Pre-Lesion EE) was moved into SE conditions. In addition, a third group of rats was now moved into EE (Post-lesion EE). A fourth group remained in SE throughout the experimental period. Rats were tested in skilled reaching and skilled walking tasks and in non-skilled motor function up to 4 weeks after lesion. The observations demonstrated beneficial effects of both pre- and post-lesion exposure to EE on skilled movement performance by promoting compensatory limb use and partial protection or restoration of skilled movement. Exposure to pre-lesion EE in particular promoted structural plasticity as indicated by increased expression of the main cytoskeletal component microtubule associated protein-2 in the lesion dorsal striatum. Continuous EE showed absence of rotational bias suggesting attenuated dopamine loss. These data indicate that enriched lifestyle before the onset of motor symptoms and rehabilitation programs after diagnosis might be beneficial in patients with Parkinson's disease.