Impaired astrocytic synaptic function by peripheral cholesterol metabolite 27-hydroxycholesterol.

Astrocytes represent the most abundant cell type in the brain, where they play critical roles in synaptic transmission, cognition, and behavior. Recent discoveries show astrocytes are involved in synaptic dysfunction during Alzheimer's disease (AD). AD patients have imbalanced cholesterol metabolism, demonstrated by high levels of side-chain oxidized cholesterol known as 27-hydroxycholesterol (27-OH). Evidence from our laboratory has shown that elevated 27-OH can abolish synaptic connectivity during neuromaturation, but its effect on astrocyte function is currently unclear. Our results suggest that elevated 27-OH decreases the astrocyte function in vivo in Cyp27Tg, a mouse model of brain oxysterol imbalance. Here, we report a downregulation of glutamate transporters in the hippocampus of CYP27Tg mice together with increased GFAP. GLT-1 downregulation was also observed when WT mice were fed with high-cholesterol diets. To study the relationship between astrocytes and neurons, we have developed a 3D co-culture system that allows all the cell types from mice embryos to differentiate in vitro. We report that our 3D co-cultures reproduce the effects of 27-OH observed in 2D neurons and in vivo. Moreover, we found novel degenerative effects in astrocytes that do not appear in 2D cultures, together with the downregulation of glutamate transporters GLT-1 and GLAST. We propose that this transporter dysregulation leads to neuronal hyperexcitability and synaptic dysfunction based on the effects of 27-OH on astrocytes. Taken together, these results report a new mechanism linking oxysterol imbalance in the brain and synaptic dysfunction through effects on astrocyte function.

Inflammatory, metabolic, and sex-dependent gene-regulatory dynamics of microglia and macrophages in neonatal hippocampus after hypoxia-ischemia.

Neonatal hypoxia-ischemia (HI) is a major cause of perinatal death and long-term disabilities worldwide. Post-ischemic neuroinflammation plays a pivotal role in HI pathophysiology. In the present study, we investigated the temporal dynamics of microglia (CX3CR1GFP/+) and infiltrating macrophages (CCR2RFP/+) in the hippocampi of mice subjected to HI at postnatal day 9. Using inflammatory pathway and transcription factor (TF) analyses, we identified a distinct post-ischemic response in CCR2RFP/+ cells characterized by differential gene expression in sensome, homeostatic, matrisome, lipid metabolic, and inflammatory molecular signatures. Three days after injury, transcriptomic signatures of CX3CR1GFP/+ and CCR2RFP/+ cells isolated from hippocampi showed a partial convergence. Interestingly, microglia-specific genes in CX3CR1GFP/+ cells showed a sexual dimorphism, where expression returned to control levels in males but not in females during the experimental time frame. These results highlight the importance of further investigations on metabolic rewiring to pave the way for future interventions in asphyxiated neonates.

Endoscopia bajo sueño inducido en la apnea obstructiva del sueño (DISE). Estudio comparativo entre las clasificaciones NOHLy VOTE / Drug Induced Sleep Endoscopy (DISE). A comparative study between NOHL and VOTE classifications

Introducción y objetivo: Varias clasificaciones han sido propuestas para expresar los resultados de la endoscopia bajo sueño inducido (DISE) en la apnea obstructiva del sueño (AOS), pero ninguna está globalmente aceptada. El objetivo del estudio es analizar las clasificaciones más utilizadas: NOHL y VOTE, para valorar cuál de ellas aporta más ventajas.Método: Se diseñó un estudio de cohortes prospectivo de 100 pacientes a los que se les realizó una DISE por AOS. Tres otorrinolaringólogos evaluaron de forma ciega los videos de las DISE y codificaron los resultados de acuerdo a las escalas NOHL y VOTE, anotando qué hallazgos determinaban la indicación de cirugía.Resultados: Según el investigador principal, en un 64% se indicó cirugía de un solo nivel, de estos, el paladar fue el más predominante, en el 26% se indicó cirugía multinivel y en un 10% se desestimó cirugía. La concordancia global para expresar los resultados de la DISE según las escalas NOHL y VOTE, en cuanto al grado de obstrucción es moderada / regular a nivel de la epiglotis (k = 0,467) y baja en el resto de estructuras (k = 0,097).Discusión: A pesar de que el grado de acuerdo interobservador es similar en ambas escalas, para VOTE es ligeramente superior.Conclusiones: La DISE es una prueba segura, reproducible y fácil de realizar. Recomendamos el uso de la escala VOTE porque ha demostrado tener un grado de acuerdo interobservador superior, es la escala más utilizada en la literatura y la recomendada en los documentos de consenso. (AU)

Introduction and objective: There is no standardized method to express DISE results. Several classifications have been proposed, but none are globally accepted. The objective of this study is to analyze the most used classifications: NOHL and VOTE to assess which of them provides more advantages. Method: A prospective cohort study of 100 patients who underwent DISE was carried out. Three otolaryngologists blindly evaluated the DISE videos and coded the results according to the NOHL and VOTE scales and at what level surgery was indicated. Results: According to the main researcher, in 64% of patients, surgery of only one level was indicated, being the palate the predominant level, followed by a 26% where multilevel surgery was indicated, and in 10% no surgery was indicated. The global agreement to express the DISE results according to the NOHL, VOTE scales regarding the degree of obstruction is moderate / regular at the level of the epiglottis (k = 0.467) and low in the rest of the structures (k = 0.097). Discussion: Although the degree of interobserver agreement is similar in both scales, for VOTE it is slightly higher. Conclusions: DISE is a safe, reproducible and easy to perform test. We recommend the use of the VOTE scale because it has been demonstrated to have a higher degree of interobserver agreement, it is not only the most widely used scale, but also recommended in consensus documents. (AU)

Utilización de recursos hospitalarios en pacientes con infección/colonización por Enterobacterias Productoras de Carbapenemasas / Utilization of hospital resources in patients with carbapenemase-producing enterobacteriaceae infection or colonization

Objetivo: Describir la casuística de los pacientes con cultivo positivo para Enterobacterias Productoras de Carbapenemasas (EPC), la complejidad de sus patologías y el consumo de recursos hospitalarios. Método: Estudio observacional retrospectivo en pacientes con diagnóstico de infección/colonización por EPC (2013-2018) en el Hospital Universitario Fundación Alcorcón. Estudio descriptivo de los pacientes y análisis de los recursos consumidos utilizando los Grupos de Diagnóstico Relacionado y la estancia media (EM). Resultados: Se analizan 119 pacientes con edad media de 76,9 años, siendo la localización más frecuente en orina (58,8%) y la carbapenemasa más habitual en enterobacterias la OXA-48 (79,8%). La EM de estos pacientes y el peso medio (PM) fue significativamente superior al de las altas hospitalarias en este período (p<0,05). Conclusiones: Los pacientes que asocian un diagnóstico de EPC incrementan el consumo de recursos hospitalarios triplicando los días de estancia y la complejidad del proceso atendido (aumento del 50% en el PM).(AU)

Objective: Describe case-mix of patients with positive culture for Carbapenemase-Producing Enterobacteriaceae (CPE), complexity of their pathologies and hospital resources consumption. Method: Retrospective observational study in patients with diagnosis of CPE infection/colonization (2013-2018) at Alcorcon University Hospital Foundation. Patient descriptive study and resource consumption analysis using Diagnosis Related Groups (DRG ́s) and mean length of stay (LOS). Results: 119 patients were analyzed. The average age was 76.9 years, the most frequent location was urine (58.8%) and OXA-48 the most common carbapenemase in the enterobacteriaceae (79.8%). The mean LOS of these patients and the DRG relative weight was higher than the patients treated during this period (p<0.05). Conclusions: Patients with diagnosis of CPE associate a greater consumption of hospital resources tripling the LOS and increasing 50% relative weight of DRG.(AU)

Risk of musculoskeletal disorders in pepper cultivation workers.

Agricultural workers have an increased risk of musculoskeletal disorders, mainly due to the manual nature of the work. This study assesses the level of physical well-being in pepper cultivation workers in Almería (Spain). The objective was to analyze pepper cultivation tasks performed in the Almería-type greenhouse, using the OWAS (Ovako Working Posture Assessment System) and RULA (Rapid Upper Limb Assessment) methods. The OWAS results showed a normal posture percentage of 53 %, a medium risk of 30 %, a high risk of 16 %, and a very high risk of 1 %. The body areas most affected were the back and legs. The RULA assessment found high risk/action levels, with 50 % of the postures corresponding to level 3, 35 % to level 4, and 15 % to level 2. Improvements are therefore proposed; these include: redesigning tasks, mechanization, training, team development, and improving the workers' physical condition. The OWAS and RULA data may have overestimated the results, as workers do not appear to be limited in performing tasks and do not normally request sick leave.

Approach for Assessing the Prevalence of Psychosocial Risks of Workers in the Greenhouse Construction Industry in South-Eastern Spain.

This paper shows the prevalence of psychosocial risks for workers in the greenhouse construction industry in south-eastern Spain. Method: The assessment of the workers' psychosocial risks was carried out through simple random sampling, which uses a questionnaire containing 13 variables characterizing the companies, 14 variables characterizing the workers, and 15 questions proposed by the Mini Psychosocial Factors (MPFs) risk assessment method. A descriptive analysis and multiple correspondence analysis were performed on the sample data. Results: Greenhouse construction businesses in south-eastern Spain can generally be classified as small companies with an average annual turnover below EUR 2.0 million (69.3%), an average of 22.8 workers with an average age of 39.84 years old, most of whom are married, with an average of 1.76 children. The prevalence of workers at high risk was 2.9%, while 45.1% were at medium-high risk. Of the 12 psychosocial factors assessed using the MPF method, 7 of them presented a high level of worker risk: Mobbing (3.2%), Relationships (1.6%), Recognition (1.6%), Autonomy (12.9%), Emotional (8.0%), Control (4.8%), and Demands (3.2%). Lastly, the variables were grouped into four clusters, showing that larger companies are correlated with a medium (workers over 40 years of age or less than 25 years of age) to high (workers under 25 years of age) risk level in several of the psychosocial factors assessed for workers who are Spanish nationals, while in smaller companies, the workers are usually middle aged (between 25 and 40 years old) and from Eastern Europe or Africa, presenting either a low or high level of risk depending on the psychosocial factors and tasks performed. Impact of the results: The study reveals a lack of prevention management regarding psychosocial risks. Therefore, it is necessary to carry out new prevention programmes that optimise the psychosocial conditions of the workers, involving the workers, employers, and other social agents.

High levels of 27-hydroxycholesterol results in synaptic plasticity alterations in the hippocampus.

Alterations in brain cholesterol homeostasis in midlife are correlated with a higher risk of developing Alzheimer's disease (AD). However, global cholesterol-lowering therapies have yielded mixed results when it comes to slowing down or preventing cognitive decline in AD. We used the transgenic mouse model Cyp27Tg, with systemically high levels of 27-hydroxycholesterol (27-OH) to examine long-term potentiation (LTP) in the hippocampal CA1 region, combined with dendritic spine reconstruction of CA1 pyramidal neurons to detect morphological and functional synaptic alterations induced by 27-OH high levels. Our results show that elevated 27-OH levels lead to enhanced LTP in the Schaffer collateral-CA1 synapses. This increase is correlated with abnormally large dendritic spines in the stratum radiatum. Using immunohistochemistry for synaptopodin (actin-binding protein involved in the recruitment of the spine apparatus), we found a significantly higher density of synaptopodin-positive puncta in CA1 in Cyp27Tg mice. We hypothesize that high 27-OH levels alter synaptic potentiation and could lead to dysfunction of fine-tuned processing of information in hippocampal circuits resulting in cognitive impairment. We suggest that these alterations could be detrimental for synaptic function and cognition later in life, representing a potential mechanism by which hypercholesterolemia could lead to alterations in memory function in neurodegenerative diseases.

Surgical Trauma in Mice Modifies the Content of Circulating Extracellular Vesicles.

Surgical interventions rapidly trigger a cascade of molecular, cellular, and neural signaling responses that ultimately reach remote organs, including the brain. Using a mouse model of orthopedic surgery, we have previously demonstrated hippocampal metabolic, structural, and functional changes associated with cognitive impairment. However, the nature of the underlying signals responsible for such periphery-to-brain communication remains hitherto elusive. Here we present the first exploratory study that tests the hypothesis of extracellular vesicles (EVs) as potential mediators carrying information from the injured tissue to the distal organs including the brain. The primary goal was to investigate whether the cargo of circulating EVs after surgery can undergo quantitative changes that could potentially trigger phenotypic modifications in the target tissues. EVs were isolated from the serum of the mice subjected to a tibia surgery after 6, 24, and 72 h, and the proteome and miRNAome were investigated using mass spectrometry and RNA-seq approaches. We found substantial differential expression of proteins and miRNAs starting at 6 h post-surgery and peaking at 24 h. Interestingly, one of the up-regulated proteins at 24 h was α-synuclein, a pathogenic hallmark of certain neurodegenerative syndromes. Analysis of miRNA target mRNA and corresponding biological pathways indicate the potential of post-surgery EVs to modify the extracellular matrix of the recipient cells and regulate metabolic processes including fatty acid metabolism. We conclude that surgery alters the cargo of circulating EVs in the blood, and our results suggest EVs as potential systemic signal carriers mediating remote effects of surgery on the brain.

The impact of damage-associated molecular patterns on the neurotransmitter release and gene expression in the ex vivo rat carotid body.

NEW FINDINGS: What is the central question of this study? Are carotid bodies (CBs) modulated by the damage-associated molecular patterns (DAMPs) and humoral factors of aseptic tissue injury? What are the main findings and their importance? DAMPs (HMGB1, S100 A8/A9) and blood plasma from rats subjected to tibia surgery, a model of aseptic injury, stimulate the release of neurotransmitters (ATP, dopamine) and TNF-α from ex vivo rat CBs. All-thiol HMGB1 mediates upregulation of immune-related biological pathways. These data suggest regulation of CB function by endogenous mediators of innate immunity. ABSTRACT: The glomus cells of carotid bodies (CBs) are the primary sensors of arterial partial O2 and CO2 tensions and moreover serve as multimodal receptors responding also to other stimuli, such as pathogen-associated molecular patterns (PAMPs) produced by acute infection. Modulation of CB function by excessive amounts of these immunomodulators is suggested to be associated with a detrimental hyperinflammatory state. We have hypothesized that yet another class of immunomodulators, endogenous danger-associated molecular patterns (DAMPs), released upon aseptic tissue injury and recognized by the same pathogen recognition receptors as PAMPs, might modulate the CB activity in a fashion similar to PAMPs. We have tested this hypothesis by exposing rat CBs to various DAMPs, such as HMGB1 (all-thiol and disulfide forms) and S100 A8/A9 in a series of ex vivo experiments that demonstrated the release of dopamine and ATP, neurotransmitters known to mediate CB homeostatic responses. We observed a similar response after incubating CBs with conditioned blood plasma obtained from the rats subjected to tibia surgery, a model of aseptic injury. In addition, we have investigated global gene expression in the rat CB using an RNA sequencing approach. Differential gene expression analysis showed all-thiol HMGB1-driven upregulation of a number of prominent pro-inflammatory markers including Il1α and Il1ß. Interestingly, conditioned plasma had a more profound effect on the CB transcriptome resulting in inhibition rather than activation of the immune-related pathways. These data are the first to suggest potential modulation of CB function by endogenous mediators of innate immunity.

Blocking Astrocytic GABA Restores Synaptic Plasticity in Prefrontal Cortex of Rat Model of Depression.

A decrease in synaptic plasticity and/or a change in excitation/inhibition balance have been suggested as mechanisms underlying major depression disorder. However, given the crucial role of astrocytes in balancing synaptic function, particular attention should be given to the contribution of astrocytes in these mechanisms, especially since previous findings show that astrocytes are affected and exhibit reactive-like features in depression. Moreover, it has been shown that reactive astrocytes increase the synthesis and release of GABA, contributing significantly to tonic GABA inhibition. In this study we found decreased plasticity and increased tonic GABA inhibition in the prelimbic area in acute slices from the medial prefrontal cortex in the Flinders Sensitive Line (FSL) rat model of depression. The tonic inhibition can be reduced by either blocking astrocytic intracellular Ca2+ signaling or by reducing astrocytic GABA through inhibition of the synthesizing enzyme MAO-B with Selegiline. Blocking GABA synthesis also restores the impaired synaptic plasticity in the FSL prefrontal cortex, providing a new antidepressant mechanism of Selegiline.

Musculoskeletal Risks: RULA Bibliometric Review.

The objective of this study was to reveal RULA method applications in terms of the knowledge, country, year and journal categories. The search was performed using the "Web of Science Core Collection". The period from 1993 to April 2019 was selected. Eight hundred nine results were obtained, of which 226 were used. The largest number of publications was determined to be in the fields of industry and health and social assistance, which coincides with the OWAS and Standardized Nordic Questionnaire methods. By country, the USA stands out for its greater number of research studies and categories that are encompassed. By date, 2016 was the year when more studies were carried out, again coinciding with the Standardized Nordic Questionnaire. By journal, "Work-A Journal of Prevention Assessment and Rehabilitation" is highlighted, as it is for the REBA method as well. It was concluded that RULA can be applied to workers in different fields, usually in combination with other methods, while technological advancement provides benefits for its application.

An Overview of REBA Method Applications in the World.

The objective of this work is to review literature, worldwide, in which the Rapid Entire Body Assessment (REBA) ergonomic assessment method was applied and count the number of times that REBA was applied together with other methods and subsequent incidence. The database used was the "Web of Science-Core Collection". Only scientific articles and bibliographic reviews were included, analysing a total of 314 documents and selecting only 91. The use of the REBA method is indicated in terms of knowledge, country, year and journal sectors. It was most used in the knowledge areas of "Manufacturing" (24.18%), "Agriculture, forestry and fishing" (21.98%) and in "Other activities" (19.78%). One of the benefits of REBA is that it evaluates different body parts: upper limbs (arm, forearm and wrist), lower extremities, trunk and neck. It is a useful method to identify the forced postures adopted by workers to thus develop improvement measures if necessary. It is concluded that REBA method use has increased over the last decade, probably due to the digitization of knowledge. It is almost always applied in combination with other methods, and its use can be a positive indicator of company sustainability.

The Guatemalan Construction Industry: Approach of Knowledge Regarding Work Risks Prevention.

In the present work, the results are presented for the characterization of work risk prevention in the Guatemalan construction industry. This characterization has been carried out using a simple random sampling technique, employing a questionnaire that was structured into 3 groups of variables: 1. General company data; 2. Prevention and management activities regarding health and safety in the company and on the worksite; and 3. Health and safety in the contractor companies. Following the sampling phase, the data were introduced in a database format, and a preliminary analysis was performed on the studied variables, followed by a descriptive analysis and a multiple correspondence analysis. The main findings of the study emphasize that companies in the Guatemalan construction sector are characterized as dedicating most of their activity (52.0%) indistinctly between civil engineering work, building construction and other specialized construction, mainly working as contractors (47.5%). These are "medium-sized" companies, employing an average of 81.1 on-site workers, having an average of 6.8 on-site work crews, and grossing an average turnover of 1.29 million euros annually. Likewise, it found that the larger construction companies adopt better prevention and management measures for worksite health and safety the larger companies are correlated with a high awareness of experiencing worksite accidents, while medium-sized companies have medium-level awareness. Companies with fewer workers manage workplace risk prevention worse, with low accident risk awareness. This correlation between these indicative variables of company size and workplace risk management and prevention is clearly reflected in the four company "clusters" that have been identified as having homogenous characteristics using the multiple correspondence analysis technique. Companies in the Guatemalan construction sector should make a greater effort to improve manager and worker training regarding workplace risk prevention to increase the effectiveness of company prevention management.

Disrupted Neuroglial Metabolic Coupling after Peripheral Surgery.

Immune-related events in the periphery can remotely affect brain function, contributing to neurodegenerative processes and cognitive decline. In mice, peripheral surgery induces a systemic inflammatory response associated with changes in hippocampal synaptic plasticity and transient cognitive decline, however, the underlying mechanisms remain unknown. Here we investigated the effect of peripheral surgery on neuronal-glial function within hippocampal neuronal circuits of relevance to cognitive processing in male mice at 6, 24, and 72 h postsurgery. At 6 h we detect the proinflammatory cytokine IL-6 in the hippocampus, followed up by alterations in the mRNA and protein expression of astrocytic and neuronal proteins necessary for optimal energy supply to the brain and for the reuptake and recycling of glutamate in the synapse. Similarly, at 24 h postsurgery the mRNA expression of structural proteins (GFAP and AQP4) was compromised. At this time point, functional analysis in astrocytes revealed a decrease in resting calcium signaling. Examination of neuronal activity by whole-cell patch-clamp shows elevated levels of glutamatergic transmission and changes in AMPA receptor subunit composition at 72 h postsurgery. Finally, lactate, an essential energy substrate produced by astrocytes and critical for memory formation, decreases at 6 and 72 h after surgery. Based on temporal parallels with our previous studies, we propose that the previously reported cognitive decline observed at 72 h postsurgery in mice might be the consequence of temporal hippocampal metabolic, structural, and functional changes in astrocytes that lead to a disruption of the neuroglial metabolic coupling and consequently to a neuronal dysfunction.SIGNIFICANCE STATEMENT A growing body of evidence suggests that surgical trauma launches a systemic inflammatory response that reaches the brain and associates with immune activation and cognitive decline. Understanding the mechanisms by which immune-related events in the periphery can influence brain processes is essential for the development of therapies to prevent or treat postoperative cognitive dysfunction and other forms of cognitive decline related to immune-to-brain communication, such as Alzheimer's and Parkinson's diseases. Here we describe the temporal orchestration of a series of metabolic, structural, and functional changes after aseptic trauma in mice related to astrocytes and later in neurons that emphasize the role of astrocytes as key intermediaries between peripheral immune events, neuronal processing, and potentially cognition.

Musculoskeletal disorders: OWAS review.

The prevention of musculoskeletal disorders (MSD) is very important in the world. Governments and companies are the most interested. The objective of the present work is to review the literature on the applications of the OWAS method in the diverse sectors or fields of knowledge and countries from its publication to March 2017. The use of OWAS method has been classified by categories of knowledge, by country and by year. The search was made by selecting only the main collection of the Web of Science. This was selected by the option "Advanced search" using the term OWAS (ts=OWAS) for the time period of 1900 to 2017. A total of 166 results were found, consisting of conference papers and articles in scientific journals. In conclusion, the OWAS has been applied mainly in two sectors: "Manufacturing industries" and "Healthcare and Social assistance activities". This method needs to be complemented with other indirect or direct methods. Also, whenever the OWAS has been used, whether individually or together with other methods, musculoskeletal disorders risks have been detected, this perhaps being an indicator to review the evaluation parameters because overestimating the risk.

Running Opposes the Effects of Social Isolation on Synaptic Plasticity and Transmission in a Rat Model of Depression.

Stress, such as social isolation, is a well-known risk factor for depression, most probably in combination with predisposing genetic factors. Physical exercise on the other hand, is depicted as a wonder-treatment that makes you healthier, happier and live longer. However, the published results on the effects of exercise are ambiguous, especially when it comes to neuropsychiatric disorders. Here we combine a paradigm of social isolation with a genetic rat model of depression, the Flinders Sensitive Line (FSL), already known to have glutamatergic synaptic alterations. Compared to group-housed FSL rats, we found that social isolation further affects synaptic plasticity and increases basal synaptic transmission in hippocampal CA1 pyramidal neurons. These functional synaptic alterations co-exist with changes in hippocampal protein expression levels: social isolation in FSL rats reduce expression of the glial glutamate transporter GLT-1, and increase expression of the GluA2 AMPA-receptor subunit. We further show that physical exercise in form of voluntary running prevents the stress-induced synaptic effects but do not restore the endogenous mechanisms of depression already present in the FSL rat.

Acute and Long-Term Effects of Brief Sevoflurane Anesthesia During the Early Postnatal Period in Rats.

The possibility that exposure to general anesthetics during early life results in long-term impairment of neural function attracted considerable interest over the past decade. Extensive laboratory data suggest that administration of these drugs during critical stages of central nervous system development can lead to cell death, impaired neurogenesis, and synaptic growth as well as cognitive deficits. These observations are corroborated by several recent human epidemiological studies arguing that such cognitive impairment might also occur in humans. Despite the potential public health importance of this issue, several important questions remain open. Amongst them, how the duration of anesthesia exposure impact on outcome is as yet not fully elucidated. To gain insight into this question, here we focused on the short- and long-term impact of a 30-min-long exposure to clinically relevant concentrations of sevoflurane in rat pups at 2 functionally distinct stages of the brain growth spurt. We show that this treatment paradigm induced developmental stage-dependent and brain region-specific acute but not lasting changes in dendritic spine densities. Electrophysiological recordings in hippocampal brain slices from adult animals exposed to anesthesia in the early postnatal period revealed larger paired-pulse facilitation but no changes in the long-term potentiation paradigm when compared with nonanesthetized controls. 5-bromo-2-deoxyuridine pulse and pulse-chase experiments demonstrated that neither proliferation nor differentiation and survival of hippocampal progenitors were affected by sevoflurane exposure. In addition, behavioral testing of short- and long-term memory showed no differences between control and sevoflurane-exposed animals. Overall, these results suggest that brief sevoflurane exposure during critical periods of early postnatal development, although it does not seem to exert major long-term effects on brain circuitry development, can induce subtle changes in synaptic plasticity and spine density of which the physiological significance remains to be determined.

Anti-Human Immunodeficiency Virus Activity of Thiol-Ene Carbosilane Dendrimers and Their Potential Development as a Topical Microbicide.

The concept of a "microbicide" was born out of the lack of a vaccine against HIV and the difficulty of women in ensuring the use of preventive prophylaxis by their partners, especially in developing countries. Approaches using polyanionic carbosilane dendrimers have shown promise in the development of new microbicides. We have developed and evaluated two anionic carbosilane dendrimers with sulfonate and carboxylate terminal groups, G2-STE16 and G2-CTE16. Both dendrimers showed high biosafety in human epithelial cell lines derived from the vagina and in primary blood human cells (PBMCs). The dendrimers not only have a greater capacity to block the entry of different X4- and R5-HIV-1 isolates into epithelial cells but also prevent the HIV-1 infection of activated PBMCs. The treatment of epithelial cells with different carbosilane dendrimers did not produce changes in the activation or proliferation of PBMCs or in the expression of CD4, CCR5 or CXCR4. Computational modeling showed significantly higher affinities for the complexes G2-STE16/gp120 and G2-CTE16/gp120. Moreover, no irritation or vaginal lesions were detected in female BALB/c mice after vaginal administration of the dendrimers. Summing up, G2-STE16 and G2-CTE16 are easy to synthesize and compatible with functional groups, and the purification steps are easy and short. Our results have clearly demonstrated that these dendrimers have high potency as a topical microbicide against HIV-1 infection.

Adaptación fonética y validación del método de valoración perceptual de la voz CAPE- V al español / Validation of the Spanish adaptation of the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V)

Objetivo: Con el propósito de promocionar un abordaje estándar para la evaluación y documentación de las calificaciones perceptuales de la calidad vocal se desarrolló el método CAPE-V (Consensus Auditory-Perceptual Evaluation of Voice). Originalmente diseñado en el idioma inglés, no existe una adaptación del mismo para ser usado en hispanohablantes. El propósito del presente trabajo es proponer una adaptación del protocolo al español y examinar la fiabilidad y la validez empírica de dicha versión. Método: Con el fin de adaptar el protocolo al español, se proponen seis frases de acuerdo a los requerimientos fonéticos del CAPE-V. Se llevó a cabo una validación instrumental de forma prospectiva. La validez de la versión en español del CAPE-V se investigó mediante la determinación de la fiabilidad intra- e interobservador y mediante la comparación de las calificaciones obtenidas mediante el CAPE-V con las obtenidas mediante el GRABS. Resultados: Los coeficientes de fiabilidad interobservador fluctuaron entre el 0,93 para la severidad global y el 0,54 para la intensidad, mientras que la fiabilidad intraobservador varió entre el 0,98 para la severidad global y el 0,85 para la intensidad. La comparación entre las calificaciones obtenidas mediante el método GRABS y el CAPE-V obtuvo resultados entre el 0,86 para la severidad global y el 0,61 para la calidad aérea. Conclusiones: El presente estudio apoya el uso de la versión en español del CAPE-V dada su validez y fiabilidad (AU)

Objective: The Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) was developed.to promote a standardised approach to evaluating and documenting auditory perceptual judgments of vocal quality. This tool was originally developed in English language and its Spanish version is still inexistent. The aim of this study was to develop a Spanish adaptation of CAPE-V and to examine the reliability and empirical validity of this Spanish version. Method: To adapt the CAPE-V protocol to the Spanish language, we proposed 6 phrases phonetically designed according to the CAPE-V requirements. Prospective instrument validation was performed. The validity of the Spanish version of the CAPE-V was examined in 4 ways: intra-rater reliability, inter-rater reliability and CAPE-V versus GRABS judgments. Results: Inter-rater reliability coefficients for the CAPE-V ranged from 0.93 for overall severity to 0.54 for intensity; intra-rater reliability ranged from 0.98 for overall severity to 0.85 for intensity. The comparison of judgments between GRABS and CAPE-V ranged from 0.86 for overall severity to 0.61 for breathiness. Conclusions: The present study supports the use of the Spanish version of CAPE-V because of its validity and reliability (AU)