Lipidomic signatures discriminate subtle hepatic changes in the progression of porcine nonalcoholic steatohepatitis.

Recently, the development of nonalcoholic steatohepatitis (NASH) in common strains of pigs has been achieved using a diet high in saturated fat, fructose, cholesterol, and cholate and deficient in choline and methionine. The aim of the present work was to characterize the hepatic and plasma lipidomic changes that accompany the progression of NASH and its reversal by switching pigs back to a chow diet. One month of this extreme steatotic diet was sufficient to induce porcine NASH. The lipidomic platform using liquid chromatography-mass spectrometry analyzed 467 lipid species. Seven hepatic phospholipids [PC(30:0), PC(32:0), PC(33:0), PC(33:1), PC(34:0), PC(34:3) and PC(36:2)] significantly discriminated the time of dietary exposure, and PC(30:0), PC(33:0), PC(33:1) and PC(34:0) showed rapid adaptation in the reversion period. Three transcripts (CS, MAT1A, and SPP1) showed significant changes associated with hepatic triglycerides and PC(33:0). Plasma lipidomics revealed that these species [FA 16:0, FA 18:0, LPC(17:1), PA(40:5), PC(37:1), TG(45:0), TG(47:2) and TG(51:0)] were able to discriminate the time of dietary exposure. Among them, FA 16:0, FA 18:0, LPC(17:1) and PA(40:5) changed the trend in the reversion phase. Plasma LDL-cholesterol and IL12P40 were good parameters to study the progression of NASH, but their capacity was surpassed by hepatic [PC(33:0), PC(33:1), and PC(34:0)] or plasma lipid [FA 16:0, FA 18:0, and LPC(17:1)] species. Taken together, these lipid species can be used as biomarkers of metabolic changes in the progression and regression of NASH in this model. The lipid changes suggest that the development of NASH also affects peripheral lipid metabolism.NEW & NOTEWORTHY A NASH stage was obtained in crossbred pigs. Hepatic [PC(33:0), PC(33:1) and PC(34:0)] or plasma [FA 16:0, FA 18:0 and LPC(17:1)] species were sensitive parameters to detect subtle changes in development and regression of nonalcoholic steatohepatitis (NASH). These findings may delineate the liquid biopsy to detect subtle changes in progression or in treatments. Furthermore, phospholipid changes according to the insult-inducing NASH may play an important role in accepting or rejecting fatty livers in transplantation.

Susceptibility Vessel Sign in Deep Perforating Arteries in Patients with Recent Small Subcortical Infarcts.

OBJECTIVES: Recent small subcortical infarcts (RSSI) are considered an acute manifestation of cerebral small vessel disease. Paramagnetic signals in perforating arteries supplying RSSI may be detected on T2*-relaxation derived sequences on MRI and is defined as susceptibility vessel sign (SVS). We aimed to study the prevalence of SVS in patients with RSSI, and explore whether its identification is related to cerebral small vessel disease markers. MATERIALS AND METHODS: We selected patients with RSSI identified on MRI during admission from a single-center stroke registry. The main demographic and clinical features, including vascular risk factors, were collected. Radiological features of RSSI and cerebral small vessel disease [white matter hyperintensities in deep and periventricular regions, enlarged perivascular spaces, lacunae, microbleeds, and brain atrophy] were described using validated qualitative scores. The presence of SVS was assessed on T2*gradient-echo or other susceptibility-weighted imaging. We compared the clinical and radiological features of patients with or without SVS in uni- and multivariate models. RESULTS: Out of 210 patients with an RSSI on an MRI, 35 (17%) showed SVS. The proportion of SVS+ patients was similar in different susceptibility imaging modalities (p=.64). Risk factor profiles and clinical course were similar in SVS+ and SVS- patients. SVS+ patients had a higher grade of deep white matter hyperintensities and brain atrophy, more lacunae (p=.001, p=.034, p=.022, respectively), and a similar degree of the rest of radiological variables, compared to SVS- patients. In the multivariate analysis, the grade of deep white matter hyperintensities was the only independent factor associated with SVS [OR 3.1 (95% CI, 1.5-6.4)]. CONCLUSIONS: SVS in patients with RSSI is uncommon and related to a higher grade of deep white matter hyperintensities. Pathophysiological mechanisms underlying the deposition of hemosiderin in the path of occluded perforating arteries are uncertain and might include endothelial dysfunction or embolic mechanisms.

Cerebral Venous Sinus Thrombosis in COVID-19 Patients: A Multicenter Study and Review of Literature.

BACKGROUND: COVID-19 infection has been known to predispose patients to both arterial and venous thromboembolic events such as deep venous thrombosis, pulmonary embolism, myocardial infarction, and stroke. A few reports from the literature suggest that Cerebral Venous Sinus Thrombosis (CVSTs) may be a direct complication of COVID-19. OBJECTIVE: To review the clinical and radiological presentation of COVID-19 positive patients diagnosed with CVST. METHODS: This was a multicenter, cross-sectional, retrospective study of patients diagnosed with CVST and COVID-19 reviewed from March 1, 2020 to November 8, 2020. We evaluated their clinical presentations, risk factors, clinical management, and outcome. We reviewed all published cases of CVST in patients with COVID-19 infection from January 1, 2020 to November 13, 2020. RESULTS: There were 8 patients diagnosed with CVST and COVID-19 during the study period at 7 out of 31 participating centers. Patients in our case series were mostly female (7/8, 87.5%). Most patients presented with non-specific symptoms such as headache (50%), fever (50%), and gastrointestinal symptoms (75%). Several patients presented with focal neurologic deficits (2/8, 25%) or decreased consciousness (2/8, 25%). D-dimer and inflammatory biomarkers were significantly elevated relative to reference ranges in patients with available laboratory data. The superior sagittal and transverse sinuses were the most common sites for acute CVST formation (6/8, 75%). Median time to onset of focal neurologic deficit from initial COVID-19 diagnosis was 3 days (interquartile range 0.75-3 days). Median time from onset of COVID-19 symptoms to CVST radiologic diagnosis was 11 days (interquartile range 6-16.75 days). Mortality was low in this cohort (1/8 or 12.5%). CONCLUSIONS: Clinicians should consider the risk of acute CVST in patients positive for COVID-19, especially if neurological symptoms develop.

Acute Stroke Care Is at Risk in the Era of COVID-19: Experience at a Comprehensive Stroke Center in Barcelona.

BACKGROUND AND PURPOSE: The purpose of the study is to analyze how the coronavirus disease 2019 (COVID-19) pandemic affected acute stroke care in a Comprehensive Stroke Center. METHODS: On February 28, 2020, contingency plans were implemented at Hospital Clinic of Barcelona to contain the COVID-19 pandemic. Among them, the decision to refrain from reallocating the Stroke Team and Stroke Unit to the care of patients with COVID-19. From March 1 to March 31, 2020, we measured the number of emergency calls to the Emergency Medical System in Catalonia (7.5 million inhabitants), and the Stroke Codes dispatched to Hospital Clinic of Barcelona. We recorded all stroke admissions, and the adequacy of acute care measures, including the number of thrombectomies, workflow metrics, angiographic results, and clinical outcomes. Data were compared with March 2019 using parametric or nonparametric methods as appropriate. RESULTS: At Hospital Clinic of Barcelona, 1232 patients with COVID-19 were admitted in March 2020, demanding 60% of the hospital bed capacity. Relative to March 2019, the Emergency Medical System had a 330% mean increment in the number of calls (158 005 versus 679 569), but fewer Stroke Code activations (517 versus 426). Stroke admissions (108 versus 83) and the number of thrombectomies (21 versus 16) declined at Hospital Clinic of Barcelona, particularly after lockdown of the population. Younger age was found in stroke admissions during the pandemic (median [interquartile range] 69 [64-73] versus 75 [73-80] years, P=0.009). In-hospital, there were no differences in workflow metrics, angiographic results, complications, or outcomes at discharge. CONCLUSIONS: The COVID-19 pandemic reduced by a quarter the stroke admissions and thrombectomies performed at a Comprehensive Stroke Center but did not affect the quality of care metrics. During the lockdown, there was an overload of emergency calls but fewer Stroke Code activations, particularly in elderly patients. Hospital contingency plans, patient transport systems, and population-targeted alerts must act concertedly to better protect the chain of stroke care in times of pandemic.

Detection and molecular characterization of porcine circovirus type 2 from piglets with porcine circovirus associated diseases in Colombia.

BACKGROUND: The porcine circovirus-associated disease (PCVAD) has been known since 1991 in Canada, but the first outbreak of PCVAD in Colombia was reported in 2007. In order to understand the molecular epidemiology of the disease and to establish the origin of the virus in the country, the study presented here intended to evaluate the presence of PCV2-associated systemic infection in piglets from different geographical regions over a period of 9-years (2002-2010). The analysis included samples collected before, during and after outbreaks of PCVAD in pigs from Colombia. The PCV2 ORF2 from the positive samples was sequenced and used to determine the genotypes of the strains and to study the dynamic of these genotypes throughout the time. RESULTS: PCV2 DNA was detected in cases related to PCV2-associated systemic infection as well as in healthy pigs with a presumable persistent infection. The analysis of the ORF2 nucleotide full length sequence of twenty-three strains allowed to divide them into two groups: PCV2a and PCV2b. At the amino acid level the main variations in the sequence of the capsid protein were found in regions located within the immunoreactive areas. CONCLUSIONS: The results of this study demonstrated for the first time, that the two subgroups: PCV2a and PCV2b have been circulating in swine from Colombia. In addition, the study showed that genotype PCV2b is present in Colombian pigs suffering from both clinical and presumable persistent infection and that the PCV2b genotype was present in the Colombian pig population even before recognition of the disease in the country and it became predominant through time.

Temporomandibular joint dysfunction in relation to tinnitus in Peruvian patients: A cross-sectional study.

Background: To determine the relationship between temporomandibular joint dysfunction (TMJD) and tinnitus in Peruvian adult patients. Material and Methods: This observational and cross-sectional study was conducted between April and May 2023, including 76 adult patients from the Otorhinolaryngology Service of Víctor Lazarte Echegaray Essalud Hospital in Trujillo (Peru). The intra- and inter-rater reliability was determined for the clinical measurement of TMJD, obtaining Kappa values above 0.995. To diagnose tinnitus, we worked with a doctor specializing in otolaryngology. Chi-square test and logistic regression were used to analyze results, considering a significance level of p<0.05. Results: A relationship was found between TMJD and tinnitus (p=0.022), increasing the frequency of this disorder as temporomandibular involvement was higher (p=0.043). There was no relation between these disorders according to gender and age, nor in hypertensive patients (p=0.131) or patients suffering from migraine (p=0.147); however, a relationship was found between TMJD and tinnitus in patients with hearing loss (p=0.046). Conclusions: TMJD is associated with tinnitus in otorhinolaryngological and hypoacusis patients. However, in hypertensive and migraine patients, and according to gender and age, no relation was found between those disorders. Key words:Tinnitus, Temporomandibular Joint Disorders, Hearing Loss, Sensorineural, Audiometry, Migraine, Hypertension, Headache.

Hepatic galectin-3 is associated with lipid droplet area in non-alcoholic steatohepatitis in a new swine model.

Non-alcoholic fatty liver disease (NAFLD) is currently a growing epidemic disease that can lead to cirrhosis and hepatic cancer when it evolves into non-alcoholic steatohepatitis (NASH), a gap not well understood. To characterize this disease, pigs, considered to be one of the most similar to human experimental animal models, were used. To date, all swine-based settings have been carried out using rare predisposed breeds or long-term experiments. Herein, we fully describe a new experimental swine model for initial and reversible NASH using cross-bred animals fed on a high saturated fat, fructose, cholesterol, cholate, choline and methionine-deficient diet. To gain insight into the hepatic transcriptome that undergoes steatosis and steatohepatitis, we used RNA sequencing. This process significantly up-regulated 976 and down-regulated 209 genes mainly involved in cellular processes. Gene expression changes of 22 selected transcripts were verified by RT-qPCR. Lipid droplet area was positively associated with CD68, GPNMB, LGALS3, SLC51B and SPP1, and negatively with SQLE expressions. When these genes were tested in a second experiment of NASH reversion, LGALS3, SLC51B and SPP1 significantly decreased their expression. However, only LGALS3 was associated with lipid droplet areas. Our results suggest a role for LGALS3 in the transition of NAFLD to NASH.

Sulfur Deprivation Modulates Salicylic Acid Responses via Nonexpressor of Pathogenesis-Related Gene 1 in Arabidopsis thaliana.

Mineral nutrients are essential for plant growth and reproduction, yet only a few studies connect the nutritional status to plant innate immunity. The backbone of plant defense response is mainly controlled by two major hormones: salicylic acid (SA) and jasmonic acid (JA). This study investigated changes in the macronutrient concentration (deficiency/excess of nitrogen, phosphorus, potassium, magnesium, and sulfur) on the expression of PR1, a well-characterized marker in the SA-pathway, and PDF1.2 and LOX2 for the JA-pathway, analyzing plants carrying the promoter of each gene fused to GUS as a reporter. After histochemical GUS assays, we determined that PR1 gene was strongly activated in response to sulfur (S) deficiency. Using RT-PCR, we observed that the induction of PR1 depended on the function of Non-expressor of Pathogenesis-Related gene 1 (NPR1) and SA accumulation, as PR1 was not expressed in npr1-1 mutant and NahG plants under S-deprived conditions. Plants treated with different S-concentrations showed that total S-deprivation was required to induce SA-mediated defense responses. Additionally, bioassays revealed that S-deprived plants, induced resistance to the hemibiotrophic pathogen Pseudomonas syringae pv. DC3000 and increase susceptibility to the necrotrophic Botrytis cinerea. In conclusion, we observed a relationship between S and SA/JA-dependent defense mechanisms in Arabidopsis.

Effectiveness of Thrombectomy in Stroke According to Baseline Prognostic Factors: Inverse Probability of Treatment Weighting Analysis of a Population-Based Registry.

BACKGROUND AND PURPOSE:  In real-world practice, the benefit of mechanical thrombectomy (MT) is uncertain in stroke patients with very favorable or poor prognostic profiles at baseline. We studied the effectiveness of MT versus medical treatment stratifying by different baseline prognostic factors. METHODS:  Retrospective analysis of 2,588 patients with an ischemic stroke due to large vessel occlusion nested in the population-based registry of stroke code activations in Catalonia from January 2017 to June 2019. The effect of MT on good functional outcome (modified Rankin Score ≤2) and survival at 3 months was studied using inverse probability of treatment weighting (IPTW) analysis in three pre-defined baseline prognostic groups: poor (if pre-stroke disability, age >85 years, National Institutes of Health Stroke Scale [NIHSS] >25, time from onset >6 hours, Alberta Stroke Program Early CT Score <6, proximal vertebrobasilar occlusion, supratherapeutic international normalized ratio >3), good (if NIHSS <6 or distal occlusion, in the absence of poor prognostic factors), or reference (not meeting other groups' criteria). RESULTS:  Patients receiving MT (n=1,996, 77%) were younger, had less pre-stroke disability, and received systemic thrombolysis less frequently. These differences were balanced after the IPTW stratified by prognosis. MT was associated with good functional outcome in the reference (odds ratio [OR], 2.9; 95% confidence interval [CI], 2.0 to 4.4), and especially in the poor baseline prognostic stratum (OR, 3.9; 95% CI, 2.6 to 5.9), but not in the good prognostic stratum. MT was associated with survival only in the poor prognostic stratum (OR, 2.6; 95% CI, 2.0 to 3.3). CONCLUSIONS:  Despite their worse overall outcomes, the impact of thrombectomy over medical management was more substantial in patients with poorer baseline prognostic factors than patients with good prognostic factors.

Factores neonatales, maternos y procedimientos invasivos asociados a sepsis neonatal tardía en el periodo 2011-2020. Revisión sistemática y metaanálisis / Neonatal, maternal and invasive procedures factors associated with late neonatal sepsis in the period 2011-2020 systematic review and meta-analysis

Objetivo: El presente trabajo se realizó con la intención de Revisar, evaluar y sintetizar literatura disponible sobre factores neonatales, maternos y procedimientos invasivos realizados en el neonato asociados a sepsis neonatal tardía durante los últimos diez años. Métodos: Las bases de datos utilizadas para la búsqueda bibliográfica fueron: Pubmed/Medline, LILACS, SciELO y Google Scholar Se seleccionaron estudios analíticos sobre investigación de factores de riesgo para sepsis neonatal tardía por etapas (título, resumen y texto completo). El riesgo de sesgo se evaluó con la Escala Newcastle Otawa. Se evaluó la heterogeneidad y se realizó un metaanálisis de efectos aleatorios para los siguientes factores de riesgo: sexo, edad gestacional, peso al nacer, Apgar a los 5 min, ruptura prematura de membranas, vía de parto, uso de catéter venoso central y ventilación mecánica. El efecto se midió con odds ratio. La certeza de la evidencia se determinó utilizando la metodología GRADE. El protocolo se registró en PROSPERO. Resultados: Se recopilaron ocho estudios de 633 registros. La heterogeneidad fue alta. 3 estudios sexo masculino OR: 1,97(0,26-14,59) p=0.03; I2 =80%, prematuridad 2 estudios OR: 2,48 (1,13-5.45); p=0.04; I2 =72%, uso de catéter venoso central 4 estudios ­ OR: 3,83 (1,07 ­ 13,71) p<0.01; I2 =89% y ventilación mecánica 4 estudios OR: 2,83 (1,42 ­ 5,68); p<0.01; I2 =86%) fueron factores independientes para el desarrollo de sepsis neonatal tardía. Los estudios tuvieron la puntuación más baja en evaluación de comparabilidad al aplicarse el riesgo de sesgo. Los resultados tuvieron certeza baja de evidencia. Interpretación: Sexo masculino, prematuridad, uso de catéter venoso central y ventilación mecánica son factores de riesgo para sepsis tardía

Objective: To review, evaluate and synthesize available literature on neonatal and maternal factors and invasive procedures associated with late neonatal sepsis during the last ten years. Methods: The databases used for the bibliographic search were: Pubmed/Medline, LILACS, SciELO, and Google Scholar. Analytical studies investigating risk factors for late neonatal sepsis by stages (title, abstract and full text) were selected. The risk of bias was assessed using the Newcastle Ottawa Scale. Heterogeneity was set, and a random-effects meta-analysis was performed for the following risk factors: gender, gestational age, birth weight, Apgar score at 5 min, premature rupture of membranes, route of delivery, use of a central venous catheter, and ventilation. Mechanics. The effect was measured with an odds ratio. The certainty of the evidence was determined using the GRADE methodology. The protocol was registered in PROSPERO. Results: Eight studies from 633 records were collected. Heterogeneity was high. Three male studies OR: 1.97(0.26-14.59) p=0.03; I2 =80%, prematurity 2 studies OR: 2.48 (1.13-5.45); p=0.04; I2 =72%, use of central venous catheter 4 studies ­ OR: 3.83 (1.07 ­ 13.71) p<0.01; I2 =89% and mechanical ventilation 4 studies OR: 2.83 (1.42 ­ 5.68); p<0.01; I2 =86%) were independent factors for the development of late neonatal sepsis. Studies had the lowest comparability assessment score when the risk of bias was applied. The results had low certainty of evidence. Interpretation: Male sex, prematurity, use of a central venous catheter, and mechanical ventilation are risk factors for late sepsis

Características fonológicas en población escolar con dislexia: Un modelo de ecuaciones estructurales / Phonological features in a school population with dyslexia: A structural equation model

Resumen Introducción: El trastorno específico del aprendizaje es una entidad nosológica del neurodesarrollo, las manifestaciones clínicas se hacen evidentes en la etapa escolar y son persistentes en el transcurso de la vida. La dislexia (DS) se caracteriza por una afectación en la comprensión y fluidez del proceso lector, asociada a déficits neurocognitivos. Objetivo: Analizar. la relación existente entre fluidez fonológica, repetición, denominación y comprensión verbal en niños con diagnóstico de DS. Método: Se empleó una muestra de N=114 personas con diagnóstico de DS escolarizados, en edades entre 7 y 16 años y un. muestreo no probabilístico. Construimos un modelo de ecuaciones estructurales (MEE) en el software RCran 4.0.4, para analizar la relación entre las variables latentes (fluidez fonológica, fluidez semántica, repetición de pseudopalabras, repetición de frases, denominación y comprensión verbal), a través de los resultados de pruebas psicométricas estandarizadas; Test de Fluencia Verbal, Test de Boston, Evaluación Neuropsicológica Infantil y Escala Weschler IV de Inteligencia. Resultados: Las covarianzas entre fluidez fonológica y todos los componentes del lenguaje (LG) fueron positivas; fluidez semántica (σxy=0,55), repetición de pseudopalabras (σxz=0,53), repetición de frases (σxw=0,64), denominación del LG (σxv=0,60), comprensión verbal (σxy=0,57), lo que indica una relación directa. En las personas con DS, a menor fluidez fonológica mayores deficiencias del LG. Conclusión: En la DS la fluidez fonológica y semántica es limitada y se relaciona de manera directa con las manifestaciones clínicas de este trastorno del neurodesarrollo (TN).

Abstract Introduction: The specific learning disorder is a nosological entity of neurodevelopment, the clinical manifestations become evident in the school stage and are persistent throughout life. Dyslexia (DS) is characterized by an impairment in the comprehension and fluency of the reading process, associated with neurocognitive deficits. Objective: To analyze the relationship between phonological fluency, repetition, naming and verbal comprehension in children diagnosed with dyslexia (DS). Method: A sample of (N=114) school patients with DS diagnosis between the ages of 7 and 16 years, selected by non-probability sampling, was used. We built a structural equation model (MEE) in RCran 4.0.4 software, to analyze the relationship between the latent variables (phonological fluency, semantic fluency, pseudoword repetition, sentence repetition, naming and verbal comprehension), through the results of standardized psychometric tests; Verbal Fluency Test, Boston Test, Child Neuropsychological Assessment and Weschler Intelligence Scale IV. Results: Covariances between phonological fluency and all language (LG) components were positive; semantic fluency (σxy=0.55), pseudoword repetition (σxz=0.53), sentence repetition (σxw=0.64), LG naming (σxv=0.60), verbal comprehension (σxy=0.57), indicating a direct relationship. In people with DS, the lower the phonological fluency the greater the language deficits. Conclusion: In DS, phonological and semantic fluency is limited and is directly related to the clinical manifestations of this neurodevelopmental disorder (TN).

Atención y funciones ejecutivas en el Trastorno Especifico del Aprendizaje / Attention and executive functions un Specific Learning Disorder

Resumen El Trastorno Especifico del Aprendizaje (TEAPZ) corresponde a una alteración de origen biológico, que se interpone en el desarrollo de habilidades académicas en lectura, escritura y cálculo, persistentes a lo largo del ciclo vital. El objetivo de este trabajo fue identificar las características de los procesos cognoscitivos de la atención y funciones ejecutivas (FE) en el TEAPZ, a través del desarrollo de una revisión sistemática de literatura, empleando la metodología propuesta por Pati y Lorusso (2018), con el objetivo de responder la siguiente pregunta de investigación: P1 ¿Cuáles son las características de la atención y de las FE en el TEAPZ? El período de búsqueda estuvo comprendido entre el año 2014 y 2021. Se revisaron las bases de datos científicas Scopus, WoS y Scielo. Se concluye que el diagnóstico del TEAPZ en el proceso cognoscitivo de la atención se asocia a dificultades en la búsqueda, rastreo visual y velocidad de procesamiento, en las FE existen déficits en la planificación, control inhibitorio y memoria de trabajo.

Abstract Specific Learning Disorder (SLD) is a disorder of biological origin, which interferes with the development of academic skills in reading, writing and arithmetic, persistent throughout the life cycle. The aim of this paper was to identify the characteristics of the cognitive processes of attention and executive functions (EF) in the TEAPZ, through the development of a systematic literature review, using the methodology proposed by Pati & Lorusso (2018), in order to answer the following research question: Q1 What are the characteristics of attention and EF in the TEAPZ? The search period was between 2014 and 2021. The scientific databases; Scopus, WoS and Scielo were reviewed. This paper concludes that the diagnosis of TEAPZ in the cognitive process of attention is associated with difficulties in search, visual tracking and processing speed, in EF there are deficits in planning, inhibitory control and working memory.

Aproximación al aprendizaje pedagógico en la discapacidad intelectual leve / An approach to pedagogical learning in mild intellectual disability

Este trabajo presenta una reflexión actualizada de métodos y estrategias eficaces para el aprendizaje del cálculo, la escritura y lectura en sujetos con discapacidad intelectual leve. Conforme con el análisis de las investigaciones abordadas, se puede concluir que, si bien los propósitos de la atención pedagógica a los sujetos con déficit intelectual vienen enmarcados bajo los principios de la educación inclusiva, se evidencia una gran diferencia entre las intenciones de la educación inclusiva y la realidad de las instituciones educativas. Así, los niños con discapacidad intelectual leve, pese a ser integrados en el aula regular, no logran recibir la atención educativa requerida para fortalecer los aprendizajes pedagógicos de lectoescritura y cálculo; situación que se relaciona con el desconocimiento, por parte de los docentes, de las estrategias pedagógicas para abordar las particularidades educativas de esta población. El resultado del análisis, evidencia la existencia de diversas técnicas; indica, al mismo tiempo, que no existe un método específico para el aprendizaje de habilidades académicas en los sujetos con deficiencias intelectuales leves, sugiere identificar el interés y la necesidad de los estudiantes para así establecer flexibilizaciones en las planeaciones pedagógicas y metodológicas del currículo que favorezcan el proceso de aprendizaje

This work presents an updated reflection of effective methods and strategies for learning calculation, writing and reading in subjects with mild intellectual disabilities. According to the analysis of the analyzed researches we can concluded that, although the purposes of pedagogical attention to subjects with intellectual deficits are framed under the principles of inclusive education, there is evidence of a great difference between the intentions of inclusive education and the reality of educational institutions. Thus, children with mild intellectual disabilities, despite being integrated into the regular classroom, do not manage to receive the educational attention required to strengthen the pedagogical learning of literacy and numeracy. A situation that is related to the ignorance, from teachers, of the pedagogical strategies to address the educational particularities of this population. The result of the analysis shows the existence of various techniques, indicates, at the same time, that there is no specific method for learning academic skills in subjects with mild intellectual deficiencies, we suggest identifying the interest and need of students in order to do so, establishing flexibilities in the pedagogical and methodological planning of the curriculum that favor the learning process.Keywords: Learning; Intellectual deficit; Intellectual disability; Inclusive education; Teaching; Reading/writing; Mathematics; Pedagogy.

An inactivated vaccine from a field strain of bovine herpesvirus-1 (BoHV-1) has high antigenic mass and induces strong efficacy in a rabbit model.

Bovine Herpesvirus-1 (BoHV-1) is a DNA virus belonging to the family Herpesviridae, subfamily Alfaherpesvirinae; it is a worldwide pathogen, causing serious economic losses in livestock. In Colombia there have been multiple isolates of BoHV-1 that have been subjected to molecular characterization, classifying most of the country isolates as BoHV-1.1. In the present study we developed and evaluated an ethyleneimine binary inactivated isolate from the native BoHV-1 strain (Córdoba-2) in a rabbit model of vaccination and infection. The vaccine was evaluated in two phases, one of immunogenicity with vaccination and a booster after 21 days, and an evaluation phase of protection against challenge with a highly virulent reference strain. The results demonstrate optimum serum-conversion, with protective neutralizing antibody titers 28 days post vaccination and optimal protection against challenge with the reference strain with decreased clinical signs of infection, protection against the onset of fever and decrease of virus excretion post challenge. In conclusion, our results show the enormous potential that an immunogenic inactivated vaccine has produced from the native BoHV-1.1 strain, which produces a high antigen mass to the vaccine to induce optimal immunity and protection, and it is a strong candidate for evaluation and possible future use in different cattle populations.

Molecular and in vitro characterization of field isolates of bovine herpesvirus-1.

Bovine Herpesvirus-1 (BoHV-1) is distributed worldwide and is a major pathogen in cattle, being the causal agent of a variety of clinical syndromes. The aim of this study was to isolate and to characterize (molecular and biological characterization) BoHV-1 from 29 immunosuppressed animals. It was possible to obtain 18 isolates, each from a different animal, such as from the respiratory and reproductive tracts. In some cases the cytopathic effect was visible 12 hours post-inoculation, and became characteristic after 36-48 hours. Biological characteristics were evaluated and compared with Iowa and Colorado-1 reference strains, and differences were found in plaque size, virus titer measured by TCID50 and PFU/mL, and one step virus curves. These results showed that some isolates had a highly virulent-like behavior in vitro, compared to the reference strains, with shorter eclipse periods, faster release of virus into the supernatants, and higher burst size and viral titer. There were no differences in glycoprotein expression of BoHV-1 isolates, measured by Western blot on monolayers. Moreover, using restriction endonucleases analysis, most of the viruses were confirmed as BoHV-1.1 and just one of them was confirmed as BoHV-1.2a subtype. These findings suggest that some wild-type BoHV-1 isolates could be useful as seeds to develop new monovalent vaccines.

DETECCIÓN Y DIFERENCIACIÓN DE Mycoplasma gallisepticum Y Mycoplasma synoviae MEDIANTE LA TÉCNICA DE PCR A PARTIR DE HISOPOS TRAQUEALES DE AVES CON SÍNTOMAS RESPIRATORIOS / Detection and Differentiation of Mycoplasma gallisepticum and Mycoplasma synoviaeby PCR from Tracheal Swabs from Birds with Respiratory Symptoms

Los micoplasmas son importantes patógenos en las aves por ser responsables de cuadros respiratorios que ocasionan grandes pérdidas económicas a la industria avícola alrededor del mundo. Existen principalmente dos especies de micoplasmas como causantes de enfermedad en aves comerciales, el Mycoplasma gallisepticum(MG) y el Mycoplasma synoviae(MS). Teniendo en cuenta su importancia y la necesidad de conocer y diferenciar las diferentes especies de micoplasmas presentes en las explotaciones avícolas, se tomaron 91 muestras de hisopos traqueales de aves con síntomas respiratorios, provenientes de igual número de granjas de pollo de engorde, ponedoras comerciales y reproductoras pesadas ubicadas en los departamentos de Cundinamarca y Boyacá, Colombia, y se determinó la presencia de MG y MS por la técnica de PCR. La prevalencia determinada fue de 39,6 % para MG y 47,3 % para MS, encontrándose diferencias estadísticamente significativas cuando se comparó la positividad a MG y MS y el tipo de explotación (p < 0,05), siendo mayor la presentación en ponedoras y reproductoras que en explotaciones de pollo de engorde. Se encontraron diferencias cuando se compararon los resultados en diferentes grupos etáreos, siendo mayor el porcentaje de positividad para MG y MS en las aves con edades entre 20 y 60 semanas tanto en ponedoras comerciales como en reproductoras, mientras que en el grupo de pollo de engorde se encontró una mayor positividad para MG en aves de cinco semanas y para MS en aves de dos semanas.

Mycoplasmas are worldwide pathogens that affect the poultry industry causing respiratory illness which cause a negative economic impact. Two mycoplasmas species are the most important in the commercial poultry: Mycoplasma gallisepticum(MG) and Mycoplasma synoviae(MS). By its importance and necessity to know and differentiate between mycoplasmas species in locals poultry houses this study used the PCR technique like a diagnosis tool, using tracheal swabs from bird with respiratory symptoms. A total of 91 samples from broilers, layers and breeders farms located in the departments of Cundinamarca and Boyacá was processed. The punctual prevalence founded in this study was 39.6 % for MG and 47.3 % for MS. Statistical differences for type of production and positive samples for MG y MS (p < 0.05) were founded, a bigger number of positive samples from layers and breeder in comparison to broilers was found. In the same way, the positive samples for the layers and breeder from the age group between 20 and 60 weeks was greater, while for the broilers group most of the positive samples were from five weeks old birds for MG and two weeks old birds for MS.

Desarrollo de u poxvirus recombinante que exprsa la glicoproteína d del herpeesvirus bovino-1 / Development of a Recombinant Poxvirus Expressing Bovine Herpesvirus-1 Glycoprotein D

El herpesvirus bovino-1 (BHV-1) es un virus de genoma DNA perteneciente a la familia Herpesviridae, el cual afecta al bovino en el que provoca un amplio espectro de manifestaciones clínicas y pérdidas económicas. El principal componente inmunogénico de su envoltura es la glicoproteína D (gD), la cual ha sido caracterizada y utilizada como inmunógeno en distintos sistemas de expresión. El objetivo de este trabajo fue generar un poxvirus recombinante (Raccoonpox [RCN]) que expresara una versión truncada de la gD del BHV-1 para ser usado como inmunógeno. Para ello, se amplificó el gen que codifica para la versión truncada de la gD, la cual se clonó en el plásmido de transferencia pTK/ IRES/tpa que posee sitios de homología a la timidinakinasa del poxvirus, un sitio interno de entrada al ribosoma (IRES) y una señal secretoria (tPA), generando el constructo pTK/gD/IRES/tpa. Para generar el RCN recombinante, se tomaron células BSC-1, se infectaron con una cepa Silvestre del RCN (CDC/V71-I-85A) a un índice de multiplicidad de infección de 0,05 y se transfectaron con el constructo pTK/gD/IRES/tpa; generándose diferentes poblaciones virales con y sin el gen de interés. Para seleccionar los virus recombinantes que expresaban el gen de interés, se realizó una selección de recombinantes negativos para timidina kinasa y positivos para la gD por tres rondas de purificación de placas en monocapas de células RAT-2 las cuales son mutantes para timidina kinasa y en presencia de bromodeoxiuridina. Los virus recombinantes se confirmaron por PCR y secuenciación de nucleótidos y se denominaron RCN-gD.

Bovine Herpesvirus-1 is a DNA virus belonging to the family Herpesviridae, which affects cattle, causing a wide spectrum of clinical manifestations and economic losses. The main immunogenic component is its envelope glycoprotein D (gD), which has been characterized and used as immunogen in different expression systems. The aim of this work was to generate a recombinant poxvirus (Raccoonpox [RCN]) expressing a truncated version of BHV-1 gD to be used as a vaccine. To do this, it was amplified the gene for a truncated version of gD which subsequently was cloned in transfer plasmid PTK/IRES/tpa which has homology to sites of poxvirus thymidine kinase, an internal site of ribosome entry (IRES) and a secretory signal (tPA), generating the construct PTK/gD/IRES/tpa. To generate the recombinant RCN, we took BSC-1 cells and we infected with a wild type RCN (CDC/V71-I-85A) at a multiplicity of infection of 0.05, then cells were transfected with the construct PTK/gD/IRES/tpa, generating different viral populations with and without the gene of interest. To select recombinant viruses expressing the gene of interest, we performed a selection of recombinant thymidine kinase negative and positive for gD by three rounds of plaque purification on RAT-2 cells monolayers which are thymidine kinase null and using bromodeoxyuridine. Recombinant viruses were recovered and confirmed by PCR and nucleotide sequencing and so called RCN-gD.

Assessing the genetic diversity and ancestry of Hartón del Valle cattle using mitochondrial DNA / Diversidad genética y ancestría del ganado Hartón del Valle mediante ADN mitocondrial / Estimação da ancestralidade e da diversidade genética no gado Hartón del Valle utilizando DNA mitocondrial

The Hartón del Valle(HV)cattleisa Criollo breed of Spanish descent that has adapted to the conditionsof the Cauca valley (Colombia). This breed is currently listed as “vulnerable” because its population has dramatically declined in the last two years. Prompted by the uncertain future of this breed and its importance as a potential resource of valuable genes. Objective: this study addressed the diversity, genetic structure and ancestry of HV cattle using mitochondrial DNA (mtDNA). Methods: a 350-bp fragment was amplified and sequenced from 72 HV animals in 9 separate farms and from animals of Brahman and Holstein breeds. To analyze the breed's ancestry, the sequences were compared with 560 sequences available in the GenBank, representing 50 Bos taurus and Bos indicus breeds. Results: in accordance with the Spanish origin of the HV breed, there was a high representation of European mtDNA (91.7%) and a low representation of African (5.5%) and Middle Eastern mtDNA (2.7%). The average haplotype diversity was 0.65 ± 0.05. The farm with the oldest ancestry was the only population in which three mitochondrial lineages were observed; unfortunately, it was recently depopulated. Proximity was observed between HV and two Columbian breeds, the Romosinuano and Costeño con Cuernos. A comparative analysis with the sequences deposited in the GenBank from numerous breeds revealed the presence of 37 haplotypes, seven of which were unique to HV. Conclusions: the following Iberian breeds were found to be most closely related to HV: Tudanca, Rubia Gallega, Negra Serrana, Murciana, Pajuna, Avileña, Garvonesa and Mertolenga. Phylogenetic analysis confirmed the Iberian ancestry and some African influence on this Latin American Criollo breed.

El Hartón del Valle (HV),es una raza adaptada a las condiciones del Valle del Cauca(Colombia) que está catalogada como “vulnerable” y cuya población ha descendido drásticamente en los últimos dos años. Objetivo: debido al futuro incierto y a la importancia como recurso potencial en la seguridad alimentaria regional se abordó el estudio de la diversidad, la estructura genética y la ancestría del HV, mediante ADN mitocondrial (ADNmt). Métodos: se amplificó y secuenció un fragmento de 350 pb en 72 animales HV, provenientes de nueve poblaciones y de controles de las razas Brahman y Holstein. Para analizar la ancestría las secuencias fueron comparadas con 560 secuencias de 50 razas Bos taurus y Bos indicus, depositadas en el GenBank. Resultados: de acuerdo con su origen español, se encontró una marcada influencia del ADNmt europeo (91.7%) y baja participación de taurinos de origen africano (5.5%) y del cercano Oriente (2.7%). La diversidad haplotípica promedio fue 0.65 ± 0.05. El hato más antiguo fue el único que mostró los tres linajes mitocondriales, sin embargo, este ha sido liquidado recientemente. Se observó proximidad entre el HV con las razas colombianas Romosinuano y Costeño con Cuernos. La comparación con las secuencias depositadas en el GenBank con diferentes razas reveló la presencia de 37 haplotipos, de los cuales siete fueron únicos en el HV. Conclusiones: las razas ibéricas más cercanas al HV fueron: Tudanca, Rubia Gallega, Negra Serrana, Murciana, Pajuna, Avileña, Garvonesa y Mertolenga. El árbol filogenético confirmó la ancestralidad ibérica y la influencia africana en las razas criollas de América Latina.

O Hartón del Valle (HV) é uma raça adaptada às condições da região pertencente ao departamento do Valle del Cauca (Colombia). A raça está catalogada como vulnerável já que sua população tem sido reduzida drasticamente nos últimos dois anos. Objetivo: devido a incerteza no futuro da raça e a sua importancia como recurso potencial na segurança alimentaria regional, abordou-se o estudo da diversidade, a estrutura genética e a ancestralidade do gado HV, utilizando DNA mitocondrial (mtDNA). Métodos: para isto, se amplificou e sequenciou um fragmento de 350 pares de bases em 72 animais provenientes de nove populações e também de controles das raças Brahman e Holandesa. Para analizar a ancestralidade das sequências, estas foram comparadas com outras 560 de 50 raças Bos taurus y Bos indicus depositadas no genebank. Resultados: de acordo com sua origem espanhola, foi encontrada uma marcada influência do DNA mitocondrial europeu (91.7%), e baixa participação de taurinos de origem africana (5.5%) e do Oriente Próximo (2.7%). A média da diversidade haplotípica foi de 0.65 ± 0.05. A população de gado HV mais antiga foi a única que apresentou as três linhagens mitocondriais encontradas; embora, esta população foi terminada recentemente. Observou-se também proximidade do gado HV com as raças colombianas da região Caribe, Romosinuano e Costeño con Cuernos. A comparação com as sequências depositadas no genebank com diferentes raças revelou a presença de 37 haplotipos, dos quais sete foram únicos no HV. Conclusões: as raças ibéricas mais aproximadas do HV foram: Tudanca, Rubia Gallega, Negra Serrana, Murciana, Pajuna, Avileña Garvonesa e Mertolenga. A árvore filogenética confirmou sua ancestralidade ibérica e a influência africana nas raças crioulas da América Latina.

Characterization of pig farms in the main swine producing regions of Colombia / Caracterización de los sistemas de producción porcina en las principales regiones porcicolas colombianas / Caracterização dos sistemas de produção de suínos nas principais regiões suínas da Colômbia

The goal of this study was to characterize intensive pig farms with inventories of 200 or more sows. Farms were located in the three major swine rearing areas of Colombia, representing 62% of the national total sow inventory. A random sample of 67 farms was evaluated, considering a 95% confidence level, 10% precision and 50% variability. A survey was applied to each farm, registering health and production indexes within each production stage, such as acclimatization, farrowing, weaning, and growing/finishing. Index differences between regions were established (p<0.05) and herd performance was analyzed to identify strengths and weaknesses of the main Colombian swine industry. Herds in the evaluated regions had a 87.6% farrowing rate, with a total of 11.7 pigs born per litter, of which 10.8 were born alive; and 10 pigs were weaned per litter, with an average production of 22.3 pigs weaned per sow/year. The average slaughter age was 166.1 days with 102.2 kg per pig. Indexes established in the present study were similar or higher compared to the ones reported for other countries. These data suggest that Colombian swine producers still have great opportunities to increase profitability if production costs decrease and the number of pigs and the amount of pork produced per year is increased.

El presente estudio tuvo como objeto caracterizar productivamente las granjas porcícolas colombianas de producción intensiva con más de 200 hembras en el pie de cría en las tres regiones con mayor influencia sobre la producción nacional lo cual representó el 62% del inventario nacional de madres. Se seleccionó aleatoriamente una muestra de 67 granjas con un nivel de confianza del 95%, una precisión del 10% y una variabilidad del 50%. Se aplicó una encuesta para estimar los principales indicadores sanitarios y de productividad en cada una de las etapas de producción: aclimatización, cría, precebo y ceba. Se establecieron las diferencias de los indicadores entre las regiones evaluadas (p<0.05) y se obtuvo una aproximación al desempeño productivo de las granjas identificando las fortalezas y debilidades de los sistemas en las regiones estudiadas. En promedio se estimó que las granjas tienen una tasa de parición del 87.6%, un promedio de 11.7 lechones nacidos totales, 10.8 lechones nacidos vivos y 10 lechones destetos por cerda; producen 22.3 lechones por cerda al año y sacrifican animales de 102 kg de peso con 166.1 días al sacrificio en promedio. Los resultados obtenidos demostraron que los indicadores de competitividad son similares a los reportados en otros países e inclusive superiores, siendo importante considerar que la porcicultura colombiana está en capacidad de disminuir costos de producción asociados al incremento en el número de cerdos y kilogramos producidos por cerda al año.

Este estudo teve como objectivo caracterizar produtivamente as empresas suínas com mais de e 200 fêmeas reprodutoras em três regiões com maior influência nacional, que representaram 62% do inventário nacional das mães. Foi seleccionada aleatoreamente uma amostra de 67 granjas com um nível de confiança de 95%, uma precisão de 10% e uma variabilidade de 50%. Um inquérito foi utilizado para estimar indicadores de saúde e produtividade em todas as fases de produção: aclimatação, cria, reprodução, pré engorda e engorda. Foram encontradas diferencias entre granjas nos indicadores entre as regiões avaliadas (p<0.05) e obteve-se uma aproximação do desempenho produtivo das granjas identificando-se os pontos fortes e fracos dos sistemas nas regiões estudadas. Em média as granjas agrícolas apresentaram uma taxa de natalidade do 87.6%, 11.7 leitões nascidos totais, 10.8 leitões nascidos vivos e 10 leitões desmamados por porca, produzidos 22.3 leitões por porca por ano e o abate foi de 102 kg com 166.1 dias. Os resultados mostraram que os indicadores da competitividade são semelhantes aos relatados em outros países e até mesmo maior, sendo importante considerar que o porco da Colômbia é capaz de reduzir os custos de produção associados ao aumento do número de leitões e kilogramas produzidos por porca ao ano.

Prevalencia serológica y aislamiento del Herpesvirus Bovino-1 (BHV-1) en hatos ganaderos de Antioquia y del Valle del Cauca / Serological prevalence and isolation of Bovine herpesvirus-1 (BHV-1) in cattle herds from Antioquia and Valle del Cauca provinces / Prevalência sorológica e isolamento do Herpesvirus Bovino-1 (BHV-1) em rebanhos bovinos de Antioquia e Valle del Cauca

El BHV-1 es un agente causante de graves pérdidas económicas. En nuestro país, ha sido reportado desde comienzos de los años 70 y aunque existe un plan de vacunación y prevención de la enfermedad, se sospecha que es uno de los principales limitantes de las explotaciones ganaderas del país. El objetivo de la presente investigación fue desarrollar un estudio serológico de la presencia del BHV-1 en dos sistemas de producción ganadera de leche y carne con antecedentes de no vacunación y posterior intento de aislamiento viral. Se realizó un estudio serológico transversal en el cual se muestrearon 316 individuos pertenecientes a 6 diferentes haciendas ganaderas, ubicadas en los departamentos de Antioquia y del Valle del Cauca. Utilizando la prueba de seroneutralización en cultivo celular, se encontró un 100% de prevalencia serológica por hato para el BHV-1 y una prevalencia general por individuos del 75.63%. La prevalencia para los hatos pertenecientes a los departamentos de Antioquia y del Valle fue del 85.51% y 69.84% respectivamente. Posteriormente, mediante inmunosupresión farmacológica, se realizó aislamiento viral en individuos que presentaron los títulos seroneutralizantes más altos, lográndose aislamientos del virus tanto de toros como de vacas y de diferentes muestras, indicando un estado de enzootia de la infección y demostrando que el BHV-1 sigue siendo uno de los agentes de mayor difusión en diferentes ámbitos ganaderos del país.

Bovine herpesvirus 1 (BHV-1) causes severe economic losses. This virus has been reported in Colombia since the early 70s, and although vaccination and prevention plans have been established, it is considered one of the major constraints for the cattle industry. Our objective was to conduct a serological survey for the presence of BHV-1 in non-vaccinated beef cattle and dairy farms. A cross-sectional serological survey, sampling 316 unvaccinated individuals from six farms located in Antioquia and Valle del Cauca provinces was conducted. The serum neutralization test showed 100% sero-prevalence of BHV-1 in each herd and 75.63% overall prevalence for individuals. The prevalence for herds in Antioquia and Valle provinces was 85.51% and 69.84% respectively. By immunosuppressive therapy, viral isolations were attempted from samples of individuals with the highest neutralizing titers, obtaining isolates from both bulls and cows, indicating an enzootic state of infection and demonstrating that BHV-1 remains one of the most widely dispersed agents in the country.

O BHV-1 é um agente que causa grandes perdas econômicas. Em nosso país, tem sido reportado desde começos dos anos 70 e embora exista um plano de vacinação e prevenção da doença, suspeita-se que é um dos principais limitantes da produção em no pais. O objetivo do presente trabalho foi desenvolver um estudo sorológico da presença do BHV-1 em dois sistemas de produção de leite e de corte com antecedentes de não vacinação e posterior intento de isolamento viral. Foi realizado um estudo sorológico transversal no qual foram mostrados 316 indivíduos pertencentes a seis fazendas localizadas nos departamentos de Antioquia e Valle del Cauca. Foi utilizada um teste de soro neutralização em cultivo celular, foi encontrado um 100% de prevalência sorológica por fazenda BHV-1 e uma prevalência geral por indivíduos do 75.63%. A prevalência para as fazenda dos departamentos de Antioquia e Valle del Cauca foi do 85.51% e 69.84%, respectivamente. Posteriormente, mediante imuno supressão farmacológica, foi realizado um isolamento viral em indivíduos que apresentaram que títulos soroneutralizantes mais altos, logrando-se isolamentos do vírus em touros e vacas e de diferentes amostras, indicando um estado de enzootia da infecção e demonstrando que o BHV-1 segue sendo um dos agentes de maior difusão em diferentes âmbitos gerados no país.