KRASG12D inhibition reprograms the microenvironment of early and advanced pancreatic cancer to promote FAS-mediated killing by CD8+ T cells.

The KRASG12D mutation is present in nearly half of pancreatic adenocarcinomas (PDAC). We investigated the effects of inhibiting the KRASG12D mutant protein with MRTX1133, a non-covalent small molecule inhibitor of KRASG12D, on early and advanced PDAC and its influence on the tumor microenvironment. Employing 16 different models of KRASG12D-driven PDAC, we demonstrate that MRTX1133 reverses early PDAC growth, increases intratumoral CD8+ effector T cells, decreases myeloid infiltration, and reprograms cancer-associated fibroblasts. MRTX1133 leads to regression of both established PanINs and advanced PDAC. Regression of advanced PDAC requires CD8+ T cells and immune checkpoint blockade (ICB) synergizes with MRTX1133 to eradicate PDAC and prolong overall survival. Mechanistically, inhibition of KRASG12D in advanced PDAC and human patient derived organoids induces FAS expression in cancer cells and facilitates CD8+ T cell-mediated death. Collectively, this study provides a rationale for a synergistic combination of MRTX1133 with ICB in clinical trials.

Preoperative oral practices and incidence of postoperative complications in hospital medical-surgical procedures: A meta-analysis

Background: Oral decay prior to a hospital medical-surgical procedure is a risk factor for the development of postoperative complications. However, perioperative oral practices as a protective factor have not been studied. This review aims to evaluate the effectiveness of perioperative oral practices in the reduction of risk of developing postoperative complications in in-hospital medical surgical procedures. Material and methods: This review and meta-analysis was conducted according to Cochrane guidelines. Medline, Scopus, Scielo, and Cochrane were consulted. Articles of the previous 10 years concerning adult patients undergoing perioperative oral practices prior to hospital medical-surgical procedures, were included. Data of the type of perioperative oral practice, type of postoperative complication and measures of effect on the development of complications were extracted. Results: Of a pool of 1470 articles, 13 were included for systematic review and 10 for meta-analysis. The most common perioperative oral procedures were focalized approach (FA), referred to only the elimination of infectious foci in the oral cavity and comprehensive approach (CA), referred to a integral approach of the patient's oral health, both of which were mainly performed in oncologic surgeries, both were effective in the reduction of postoperative complications (RR=0.48, [95% CI 0.36 - 0.63]). The most reported postoperative complication was postoperative pneumonia. Conclusions: Perioperative oral management proved to be a protective factor against the development of postoperative complications. (AU)

Oncogenic Kras G12D specific non-covalent inhibitor reprograms tumor microenvironment to prevent and reverse early pre-neoplastic pancreatic lesions and in combination with immunotherapy regresses advanced PDAC in a CD8 + T cells dependent manner.

Pancreatic ductal adenocarcinoma (PDAC) is associated with mutations in Kras, a known oncogenic driver of PDAC; and the KRAS G12D mutation is present in nearly half of PDAC patients. Recently, a non-covalent small molecule inhibitor (MRTX1133) was identified with specificity to the Kras G12D mutant protein. Here we explore the impact of Kras G12D inhibition by MRTX1133 on advanced PDAC and its influence on the tumor microenvironment. Employing different orthotopic xenograft and syngeneic tumor models, eight different PDXs, and two different autochthonous genetic models, we demonstrate that MRTX1133 reverses early PDAC growth, increases intratumoral CD8 + effector T cells, decreases myeloid infiltration, and reprograms cancer associated fibroblasts. Autochthonous genetic mouse models treated with MRTX1133 leads to regression of both established PanINs and advanced PDAC. Regression of advanced PDAC requires CD8 + T cells and immune checkpoint blockade therapy (iCBT) synergizes with MRTX1133 to eradicate PDAC and prolong overall survival. Mechanistically, inhibition of mutant Kras in advanced PDAC and human patient derived organoids (PDOs) induces Fas expression in cancer cells and facilitates CD8 + T cell mediated death. These results demonstrate the efficacy of MRTX1133 in different mouse models of PDAC associated with reprogramming of stromal fibroblasts and a dependency on CD8 + T cell mediated tumor clearance. Collectively, this study provides a rationale for a synergistic combination of MRTX1133 with iCBT in clinical trials.

Herramientas de evaluación de actividades de la vida diaria instrumentales en población adulta: revisión sistemática / Tools for the evaluation of daily life activities instrumental in adults: systematic review

Introducción: La transición al modelo biopsicosocial implica que las herramientas de evaluación se adapten a esta nueva visión de la salud. Las herramientas usadas en Chile para medir la funcionalidad en las actividades de la vida diaria instrumentales (AVDI) son las mismas desde los años 50, por lo que se requiere hacer una revisión de la literatura a fin de conocer nuevas metodologías de evaluación en la materia. Objetivo: Identificar las herramientas de evaluación en AVDI, qué ítems son considerados, metodología de puntuación (rangos, puntajes, categorización de resultados), tiempo y contexto de aplicación, creadores de las herramientas y propiedades psicométricas de los mismos. Diseño: Revisión sistemática. Fuentes de datos: PubMed, BIREME y Epistemonikos. Se realizaron tres búsquedas: dos el 2018 (marzo y septiembre) y una el 2020 (diciembre). Selección de estudios: Estudios observacionales (estudios de cohorte y estudios de corte transversal) y revisiones sistemáticas que contemplaron la valoración de AVDI en mayores de 18 años, en inglés o español, publicados desde 1998 y de libre acceso. Extracción de datos: Se realizó lectura de títulos y resúmenes como primer filtro, y posteriormente el texto completo. Una vez seleccionados los estudios que cumplen con los criterios de inclusión, se les aplicó la pauta "Strengthening The Reporting of Observational studies in Epidemiology (STROBE)" y la pauta "Critical Appraisal Skills Programme Spanish (CASPe)" para evaluar la calidad metodológica. Se estableció, a través de un consenso de las investigadoras, que cada estudio seleccionado debía cumplir con al menos 13 de los 22 ítems de la pauta STROBE. Resultados: De los 27.606 artículos encontrados, 15 cumplieron con los criterios de inclusión y el punto de corte establecido de la pauta. Sólo un artículo era en idioma español y 14 en inglés; y fueron publicados principalmente en EE.UU. y España. De los 20 instrumentos encontrados en los artículos seleccionados, el 60% corresponde a la "Escala Lawton y Brody", el 10% a la de "The Performance Assessment of Self-Care Skills (PASS)" y el porcentaje restante otras herramientas. Conclusiones: A nivel internacional se han creado nuevas herramientas de evaluación de AVDI en respuesta a necesidades locales, dificultando la posibilidad de ser generalizadas a otros contextos sin contar previamente con un proceso de validación transcultural y estadística que resguarde la confiabilidad de su aplicación y data. La "Escala de Lawton y Brody", pese a las limitaciones ni sesgos, sigue siendo un patrón de oro a nivel internacional.

Background: The transition to the biopsychosocial model implies that the assessment tools are adapted to this new vision of health. In Chile, the evaluations to measure functionality on Instrumental Activities of Daily Living (IADL), have been the same since the 1950s, so a review of the literature is required to know new evaluation tools in the matter. Aim: To identify the evaluation tools that exist to assess the functionality in AVDI, what items are considered, scoring methodology (rank, score, categorization of results), time and in which contexts they are applied, assessment creators and psychometric properties. Design: Systematic review. Data sources: PubMed, BIREME and Epistemonikos. Three searches were carried out: two in 2018 (March and September) and one in 2020 (December). Study selection: Observational studies (cohort studies and cross-sectional studies) and Systematic Reviews that contemplated the assessment of IADL in people over 18 years of age, in English or Spanish, published since 1998 and open access. Data extraction: Titles and abstracts were read as a first filter, followed by the full text. Once the studies that met the inclusion criteria had been selected, the "Strengthening The Reporting of Observational studies in Epidemiology (STROBE)" and "Critical Appraisal Skills Programme Spanish (CASPe)" guideline was applied to assess methodological quality. It was established, through a consensus of the researchers, that each selected study had to comply with at least 13 of the 22 items of STROBE guideline. Results: Of the 27.606 articles found, 15 met the inclusion criteria and the established cut-off point of the guideline. One article was written in Spanish and 14 in English, which were carried out mainly in the United States and Spain (3 out of 15 respectively). Of the 20 instruments found in the selected articles, 60% correspond to "Lawton & Brody Scale", 10% to "The Performance Assessment of Self-Care Skills (PASS)" and the remaining percentage other tools. Conclusions: At an international level, new IADL assessment tools have been created in response to local needs, making it difficult to generalize to other contexts without previously having a cross-cultural and statistical validation process that safeguards the reliability of its application and data. The "Lawton s Brody Scale", despite its limitations and biases, remains an international gold standard.

Surgical Outcome in Extratemporal Epilepsies Based on Multimodal Pre-Surgical Evaluation and Sequential Intraoperative Electrocorticography.

OBJECTIVE: to present the postsurgical outcome of extratemporal epilepsy (ExTLE) patients submitted to preoperative multimodal evaluation and intraoperative sequential electrocorticography (ECoG). SUBJECTS AND METHODS: thirty-four pharmaco-resistant patients with lesional and non-lesional ExTLE underwent comprehensive pre-surgical evaluation including multimodal neuroimaging such as ictal and interictal perfusion single photon emission computed tomography (SPECT) scans, subtraction of ictal and interictal SPECT co-registered with magnetic resonance imaging (SISCOM) and electroencephalography (EEG) source imaging (ESI) of ictal epileptic activity. Surgical procedures were tailored by sequential intraoperative ECoG, and absolute spike frequency (ASF) was calculated in the pre- and post-resection ECoG. Postoperative clinical outcome assessment for each patient was carried out one year after surgery using Engel scores. RESULTS: frontal and occipital resection were the most common surgical techniques applied. In addition, surgical resection encroaching upon eloquent cortex was accomplished in 41% of the ExTLE patients. Pre-surgical magnetic resonance imaging (MRI) did not indicate a distinct lesion in 47% of the cases. In the latter number of subjects, SISCOM and ESI of ictal epileptic activity made it possible to estimate the epileptogenic zone. After one- year follow up, 55.8% of the patients was categorized as Engel class I-II. In this study, there was no difference in the clinical outcome between lesional and non lesional ExTLE patients. About 43.7% of patients without lesion were also seizure- free, p = 0.15 (Fischer exact test). Patients with satisfactory seizure outcome showed lower absolute spike frequency in the pre-resection intraoperative ECoG than those with unsatisfactory seizure outcome, (Mann- Whitney U test, p = 0.005). CONCLUSIONS: this study has shown that multimodal pre-surgical evaluation based, particularly, on data from SISCOM and ESI alongside sequential intraoperative ECoG, allow seizure control to be achieved in patients with pharmacoresistant ExTLE epilepsy.

Efectos de las Técnicas Manuales Orofaciales en la Disminución del Dolor Cervical. Una Revisión Bibliográfica / Effects of Orofacial Manual Techniques in the Reduction of Cervical Pain. A Bibliographic Review

Introducción: La prevalencia anual de dolor cervical oscila entre un 16,7% y un 75,1%, durando alrededor de 6 meses o más en el 14% de los casos, desencadenando en restricción del movimiento y dolor principalmente. Esto podría deberse a la relación entre la cabeza, columna cervical y estructuras relacionadas a la articulación temporomandibular (ATM). El objetivo de esta investigación es describir a través de la evidencia científica el efecto de las técnicas manuales orales en la disminución del dolor cervical. Métodos: Se incluyeron ensayos clínicos aleatorizados y revisiones sistemáticas encontrados en las bases de datos PubMed, Cochrane y PEDro. Realizando la extracción de datos a través de una tabla estructurada para cada tipo de estudio. Resultados: De 10 estudios seleccionados, 3 corresponden a revisiones sistemáticas y 7 a ensayos clínicos, donde la disminución del dolor cervical fue significativa al aplicar la terapia manual con ejercicios por sobre la terapia manual por sí sola. Por otro lado, las técnicas orofaciales fueron beneficiosas al combinarlas con terapia manual en comparación con un tratamiento habitual. No se encontraron diferencias significativas al aplicar ejercicios de Maitland y movilizaciones en comparación con ejercicios de flexibilidad, fortalecimiento, ejercicios de Mulligan y movilizaciones. Conclusión: Los resultados son debatibles, ya que la terapia manual por sí sola o combinada con ejercicios es la técnica más efectiva no solo en la disminución del dolor cervical, también en la mejoría de la calidad de vida.

Introduction: The annual prevalence of cervical pain ranges from 16.7% to 75.1%, lasting about 6 months or more in 14% of cases, triggering mainly movement restriction and pain. This could be due to the relationship between the head, cervical spine and structures related to the temporomandibular joint (TMJ). The objective of this research is to describe through scientific evidence the effect of oral techniques in reducing cervical pain. Methods: Randomized clinical trials and systematic reviews found in the PubMed, Cochrane and PEDro databases were included. Data extraction was done through a structured table for each type of study. Results: Out of 10 selected studies, 3 correspond to systematic reviews and 7 to clinical trials, where the decrease in neck pain was significant when applying manual therapy with exercises over manual therapy alone. On the other hand, orofacial techniques were beneficial when combined with manual therapy compared to an usual treatment. No significant differences were found when applying Maitland exercises and mobilizations compared to flexibility, strengthening, Mulligan exercises, and mobilizations (p<0.05). Conclusion: The results are debatable, as manual therapy alone or combined with exercises is the most effective technique not only in reducing neck pain, but also in improving quality of life.

Motor Coordination Disorders Evaluated through the Grid Test and Changes in the Nigral Nrf2 mRNA Expression in Rats with Pedunculopontine Lesion.

Neurotoxic lesion of the pedunculopontine nucleus (PPN) is known to cause subtle motor dysfunctions. However, motor coordination during advance on a discontinuous and elevated surface has not been studied. It is also not known whether there are changes in the mRNA expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in nigral tissue. METHODS: The effects of the unilateral neurotoxic lesion of the PPN in motor coordination evaluated through grid test and Nrf2 mRNA expression in nigral tissue were evaluated. Two experimental designs (ED) were organized: ED#1 behavioral study (7 and 30 days after PPN lesion) and ED#2 molecular biology study (24 h, 48 h and 7 days) after PPN lesion. RESULTS: ED#1-The number of faults made with left limbs, were significant higher in the lesioned groups (p < 0.01) both 7 and 30 days post-lesion. The number of failures made by the right limbs, was also significantly higher (p < 0.05) vs. control groups. ED#2-Nrf2 mRNA expression showed an increase 24 h after PPN injury (p < 0.01), followed by a peak of expression 48 h post injury (p < 0.001). CONCLUSIONS: Disorders of motor coordination associated with PPN injury are bilateral. The increased Nrf2 mRNA expression could represent an adaptive response to oxidative stress in the nigral tissue following pontine injury.

New Aspects of VEGF, GABA, and Glutamate Signaling in the Neocortex of Human Temporal Lobe Pharmacoresistant Epilepsy Revealed by RT-qPCR Arrays.

In the epilepsy spectrum, temporal lobe epilepsy (TLE) is the most common and devastating focal and symptomatic epilepsy form in adults, where more than 30% of patients develop pharmacoresistance. It is not fully understood how the gene expression contributes to establishing an epileptic phenotype. Cerebrovascular remodeling directed by VEGF (vascular endothelial growth factor) signaling might modulate the synaptic neurotransmission in the epileptic brain. To address this question, the gene expression was profiled in biopsies of the temporal cortex from diagnosed patients with pharmacoresistant TLE that underwent surgical resection to seizure control. One hundred sixty-eight genes related to VEGF signaling and GABA and glutamate neurotransmissions were evaluated. Genes related to downstream signaling -phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinases (MAPK), and Janus-activated kinase/signal transducer and activator of transcription (JAK/STAT) pathways- and neurotransmitters metabolism were evaluated too. Thirty-nine genes were upregulated. The genes encoding for G protein q polypeptide, serine racemase, gephyrin, and glutamate/cystine antiporter system xCT appeared as novel upregulated genes in the pharmacoresistant TLE. ClueGO, a Cytoscape plugin, was used to build a gene network associated using Gene Ontology (GO) terminology. Enrichment analysis by ClueGO retrieves that positive regulation of endothelial cell proliferation, nerve development, and neuronal apoptosis were over-represented categories. In conclusion, VEGF signaling is confirmed as a relevant mediator in the pharmacoresistant TLE. In addition, the enrichment analysis applied to differentially expressed genes suggests new pharmacological targets to be assessed in the treatment of pharmacoresistant TLE. Results make up an approximation to better understand the epileptic brain and complement the available data.

Relation of Structural and Functional Changes in Auditory and Visual Pathways after Temporal Lobe Epilepsy Surgery.

Auditory and visual pathways may be affected as a consequence of temporal lobe epilepsy surgery because of their anatomical relationships with this structure. The purpose of this paper is to correlate the results of the auditory and visual evoked responses with the parameters of tractography of the visual pathway, and with the state of connectivity between respective thalamic nuclei and primary cortices in both systems after the surgical resection of the epileptogenic zone in drug-resistant epileptic patients. Tractography of visual pathway and anatomical connectivity of auditory and visual thalamus-cortical radiations were evaluated in a sample of eight patients. In general, there was a positive relationship of middle latency response (MLR) latency and length of resection, while a negative correlation was found between MLR latency and the anatomical connection strength and anatomical connection probability of the auditory radiations. In the visual pathway, significant differences between sides were found with respect to the number and length of tracts, which was lower in the operated one. Anatomical connectivity variables and perimetry (visual field defect index) were particularly correlated with the latency of P100 wave which was obtained by quadrant stimulation. These results demonstrate an indirect functional modification of the auditory pathway and a direct traumatic lesion of the visual pathway after anterior temporal lobectomy in patients with drug resistant epilepsy.

Oxidative Stress in Patients with Drug Resistant Partial Complex Seizure.

Oxidative stress (OS) has been implicated as a pathophysiological mechanism of drug-resistant epilepsy, but little is known about the relationship between OS markers and clinical parameters, such as the number of drugs, age onset of seizure and frequency of seizures per month. The current study’s aim was to evaluate several oxidative stress markers and antioxidants in 18 drug-resistant partial complex seizure (DRPCS) patients compared to a control group (age and sex matched), and the results were related to clinical variables. We examined malondialdehyde (MDA), advanced oxidation protein products (AOPP), advanced glycation end products (AGEs), nitric oxide (NO), uric acid, superoxide dismutase (SOD), glutathione, vitamin C, 4-hydroxy-2-nonenal (4-HNE) and nitrotyrosine (3-NT). All markers except 4-HNE and 3-NT were studied by spectrophotometry. The expressions of 4-HNE and 3-NT were evaluated by Western blot analysis. MDA levels in patients were significantly increased (p ≤ 0.0001) while AOPP levels were similar to the control group. AGEs, NO and uric acid concentrations were significantly decreased (p ≤ 0.004, p ≤ 0.005, p ≤ 0.0001, respectively). Expressions of 3-NT and 4-HNE were increased (p ≤ 0.005) similarly to SOD activity (p = 0.0001), whereas vitamin C was considerably diminished (p = 0.0001). Glutathione levels were similar to the control group. There was a positive correlation between NO and MDA with the number of drugs. The expression of 3-NT was positively related with the frequency of seizures per month. There was a negative relationship between MDA and age at onset of seizures, as well as vitamin C with seizure frequency/month. We detected an imbalance in the redox state in patients with DRCPS, supporting oxidative stress as a relevant mechanism in this pathology. Thus, it is apparent that some oxidant and antioxidant parameters are closely linked with clinical variables.

Long-Term Electroclinical and Employment Follow up in Temporal Lobe Epilepsy Surgery. A Cuban Comprehensive Epilepsy Surgery Program.

The purpose of this paper is to present a long- term electroclinical and employment follow up in temporal lobe epilepsy (TLE) patients in a comprehensive epilepsy surgery program. Forty adult patients with pharmacoresistant TLE underwent detailed presurgical evaluation. Electroencephalogram (EEG) and clinical follow up assessment for each patient were carried out. The occurrence of interictal epileptiform activity (IEA) and absolute spike frequency (ASF) were tabulated before and after 1, 6, 12, 24 and 72 months surgical treatment. Employment status pre- to post-surgery at the last evaluated period was also examined. Engel scores follow-up was described as follows: at 12 months 70% (28) class I, 10% (4) class II and 19% (8) class III-IV; at 24 months after surgery 55.2% (21) of the patients were class I, 28.9% (11) class II and 15.1% (6) class III-IV. After one- year follow up 23 (57.7%) patients were seizure and aura-free (Engel class IA). These figures changed to 47.3%, and 48.6% respectively two and five years following surgery whereas 50% maintained this condition in the last follow up period. A decline in the ASF was observed from the first year until the sixth year after surgery in relation to the preoperative EEG. The ASF one year after surgery allowed to distinguish "satisfactory" from "unsatisfactory" seizure relief outcome at the last follow up. An adequate social functioning in terms of education and employment in more than 50% of the patients was also found. Results revealed the feasibility of conducting a successful epilepsy surgery program with favorable long term electroclinical and psychosocial functioning outcomes in a developing country as well.

Tyrosine Hydroxylase, Vesicular Monoamine Transporter and Dopamine Transporter mRNA Expression in Nigrostriatal Tissue of Rats with Pedunculopontine Neurotoxic Lesion.

BACKGROUND: The degeneration of the pedunculopontine nucleus (PPN) precedes the degeneration of the nigral cells in the pre-symptomatic stages of Parkinson's disease (PD). Although the literature recognizes that a lesion of the PPN increases the vulnerability of dopaminergic cells, it is unknown if this risk is associated with the loss of capability of handling the dopaminergic function. METHODS: In this paper, the effects of a unilateral neurotoxic lesion of the PPN in tyrosine hydroxylase (TH), vesicular monoamine transporter 2 (VMAT2) and dopamine transporter (DAT) mRNA expression in nigrostriatal tissue were evaluated. Three experimental groups were organized: non-treated rats, NMDA-lesioned rats and Sham-operated rats. RESULTS: Seven days after the PPN lesion, in nigral tissue, TH mRNA expression was higher in comparison with control groups (p < 0.05); in contrast, VMAT2 mRNA expression showed a significant decrease (p < 0.01). DAT mRNA expression showed a significant decrease (p < 0.001) in the striatal tissue. Comparing nigral neuronal density of injured and control rats revealed no significant difference seven days post-PPN injury. CONCLUSIONS: Findings suggest that the PPN lesion modifies the mRNA expression of the proteins associated with dopaminergic homeostasis at nigrostriatal level. It could represent vulnerability signals for nigral dopaminergic cells and further increase the risk of degeneration of these cells.

Follow-Up of Peripheral IL-1ß and IL-6 and Relation with Apoptotic Death in Drug-Resistant Temporal Lobe Epilepsy Patients Submitted to Surgery.

Increasing amounts of evidence support the role of inflammation in epilepsy. This study was done to evaluate serum follow-up of IL-1ß and IL-6 levels, as well as their concentration in the neocortex, and the relationship of central inflammation with NF-κB and annexin V in drug-resistant temporal lobe epileptic (DRTLE) patients submitted to surgical treatment. Peripheral and central levels of IL-1ß and IL-6were measured by ELISA in 10 DRTLE patients. The sera from patients were taken before surgery, and 12 and 24 months after surgical treatment. The neocortical expression of NF-κB was evaluated by western blotting and annexin V co-localization with synaptophysin by immunohistochemistry. The neocortical tissues from five patients who died by non-neurological causes were used as control. Decreased serum levels of IL-1 and IL-6 were observed after surgery; at this time, 70% of patients were seizure-free. No values of IL-1 and IL-6 were detected in neocortical control tissue, whereas cytokine levels were evidenced in DRTLE. Increased NF-κB neocortex expression was found and the positive annexin V neurons were more obvious in the DRTLE tissue, correlating with IL-6 levels. The follow-up study confirmed that the inflammatory alterations disappeared one year after surgery, when the majority of patients were seizure-free, and the apoptotic death process correlated with inflammation.

Motor dysfunction and alterations in glutathione concentration, cholinesterase activity, and BDNF expression in substantia nigra pars compacta in rats with pedunculopontine lesion.

Pedunculopontine nucleus (PPN) has been considered a critically important region in the regulation of some of the physiological functions that fail during the progression of Parkinson's disease (PD). In this paper, the effects of unilateral neurotoxic lesion of the PPN [through the injection of N-methyl-d-aspartate (NMDA) solution (concentration: 0.1M; volume: 0.5µL)] in motor execution and gait disorders and the changes in cellular and molecular indicators in rat nigral tissue were evaluated. The motor execution was assessed using the beam test (BT) and the gait disorders by footprint test. Glutathione (GSH) concentrations, acetyl cholinesterase enzymatic activity (AChE EA), and brain-derived neurotrophic factor (BDNF) mRNA expression in nigral tissue were analyzed. NMDA-lesioned rats showed fine motor dysfunction with a significant increase in the slow (p≤0.01) and fast movement (p≤0.01) time and in path deviation (p≤0.01) on the smaller diameter beams. Moreover, NMDA-lesioned rats exhibited an imprecise path with moments of advances and setbacks, alternating with left and right deviations, suspensions, and inverted positions. Footprint test revealed slight gait disorders, which were manifested by a reduction in the left and right stride lengths, the intra-step distance, and the support area (p≤0.01). Biochemical studies showed that 48h after the PPN neurotoxic injury, the GSH concentrations and BDNF expression were significantly increased (p≤0.01). These variables returned to normal values 7days after the PPN lesion; the AChE EA showed a significant increase at this time. These functional changes in nigral tissue could be a plastic responses associated with early PD.

Percepción de estudiantes sobre el proceso enseñanza aprendizaje en la asignatura de Enfermería Pediátrica / Students' perception about teaching- learning process in the Pediatric Nursing subject

Introducción: El análisis del proceso enseñanza-aprendizaje constituye una línea de investigación necesaria en aras de definir el carácter de las relaciones que se establecen entre profesores y alumnos.Objetivo: Valorar la percepción de los estudiantes sobre el proceso enseñanza-aprendizaje en la asignatura de Enfermería Pediátrica durante el curso 2014-2015. Material y Métodos: Se realizó un estudio observacional descriptivo de corte transversal entre los meses de septiembre a julio del curso 2014-2015 con los estudiantes de 3er y 5to años de Enfermería. Resultados: La mayor cantidad de estudiantes que participaron en el estudio correspondió al 5to año con un predominio del sexo femenino, la calidad de la docencia por la mayoría de los estudiantes fue valorada de buena, así como la preparación de los profesores, en la exploración de los aspectos negativos resaltaron en mayor porciento la bibliografía desactualizada y la cantidad de contenido a estudiar y el poco tiempo para hacerlo así como las actividades docentes en horario de la tarde, resaltando como aspecto positivo el trabajo de los tutores en los diferentes servicios. Conclusiones: Los estudiantes valoran de forma positiva el papel de los profesores en el proceso docente-educativo con el consecuente reconocimiento de la utilidad de la asignatura para la formación de los mismos. No obstante, aún existen deficiencias en el logro de los nodos interdisciplinarios por parte de algunos profesores(AU)

Introduction: The analysis of the teaching - learning process constitutes a line of necessary research with the aim of defining the professor –students relationships nature. Objective: To value the students perception about teaching learning process in Pediatric Nursing subject, during 2014-2015 course.Material and Methods: Was performed a cross-section, descriptive and observational study from September to July of 2014-2015 course, with the students of 3rd and 5th year of Nursing.Results: The biggest quantity of students that participated in the study corresponded to the course 5th year with a prevalence of the feminine sex, teaching quality was valued as good for mostly of the students, as well as professors preparation, regarding negative aspects stood out in the biggest percent the outdated bibliography, the amount of content to be studied and the shortage of time to do it as well as the educational activities during the afternoon, standing out as a positive issue the work done by the tutors in the different services. Conclusions: Students value positively the role of professors in the educational process and also recognize the usefulness of the subject in their formation. However, there are still lacks in the achievement of interdisciplinary node by some professors(AU)

Sarcoma histiocítico primario del sistema nervioso central. Reporte de caso y revisión de la literatura / Primary histiocytic sarcoma of the central nervous system. A case report and review of the literature

La afectación primaria del sistema nervioso central por un sarcoma histiocítico es extremadamente infrecuente, con apenas 17 casos publicados y un comportamiento clínico agresivo. Presentamos el caso de una mujer de 46 años cuyas imágenes de resonancia magnética mostraron masa tumoral intraparenquimatosa temporoparietal derecha con desplazamiento de la línea media y edema vasogénico asociado. El tumor fue resecado parcialmente, resultó ser un sarcoma histiocítico. La paciente falleció a los 3 meses de ser realizado el diagnóstico. La necropsia demostró un severo edema cerebral y recrecimiento del tumor sin afectación del resto de los órganos. El diagnóstico estuvo basado en las características microscópicas del tumor, complementado con un panel inmunohistoquímico amplio, que resulta vital para confirmar el origen histiocítico y excluir otras lesiones malignas (AU)

Primary histiocytic sarcoma of the central nervous system is not only an extremely rare tumour, with only 17 published cases to date, but also a very aggressive one. We report the case of a 46 year old woman, who was seen on magnetic resonance to have a right intracerebral parietal temporal tumour with displacement of the midline and associated vasogenic oedema. The tumour was partially resected and seen to be a histiocytic sarcoma. The patient died 3 months after the diagnosis. Necropsy showed severe brain oedema and tumour regrowth but no involvement of other organs. Diagnosis was based on the microscopic characteristics of the tumour as well as an immunohistochemical panel, essential for the confirmation of its histiocytic origin and for the differential diagnosis with other malignant lesions (AU)

Hotspots of Community Change: Temporal Dynamics Are Spatially Variable in Understory Plant Composition of a California Oak Woodland.

Community response to external drivers such climate and disturbance can lead to fluctuations in community composition, or to directional change. Temporal dynamics can be influenced by a combination of drivers operating at multiple spatial scales, including external landscape scale drivers, local abiotic conditions, and local species pools. We hypothesized that spatial variation in these factors can create heterogeneity in temporal dynamics within landscapes. We used understory plant species composition from an 11 year dataset from a California oak woodland to compare plots where disturbance was experimentally manipulated with the removal of livestock grazing and a prescribed burn. We quantified three properties of temporal variation: compositional change (reflecting the appearance and disappearance of species), temporal fluctuation, and directional change. Directional change was related most strongly to disturbance type, and was highest at plots where grazing was removed during the study. Temporal fluctuations, compositional change, and directional change were all related to intrinsic abiotic factors, suggesting that some locations are more responsive to external drivers than others. Temporal fluctuations and compositional change were linked to local functional composition, indicating that environmental filters can create subsets of the local species pool that do not respond in the same way to external drivers. Temporal dynamics are often assumed to be relatively static at the landscape scale, provided disturbance and climate are continuous. This study shows that local and landscape scale factors jointly influence temporal dynamics creating hotspots that are particularly responsive to climate and disturbance. Thus, adequate predictions of response to disturbance or to changing climate will only be achieved by considering how factors at multiple spatial scales influence community resilience and recovery.