Acute activation of hemichannels by ethanol leads to Ca2+-dependent gliotransmitter release in astrocytes.

Multiple studies have demonstrated that acute ethanol consumption alters brain function and cognition. Nevertheless, the mechanisms underlying this phenomenon remain poorly understood. Astrocyte-mediated gliotransmission is crucial for hippocampal plasticity, and recently, the opening of hemichannels has been found to play a relevant role in this process. Hemichannels are plasma membrane channels composed of six connexins or seven pannexins, respectively, that oligomerize around a central pore. They serve as ionic and molecular exchange conduits between the cytoplasm and extracellular milieu, allowing the release of various paracrine substances, such as ATP, D-serine, and glutamate, and the entry of ions and other substances, such as Ca2+ and glucose. The persistent and exacerbated opening of hemichannels has been associated with the pathogenesis and progression of several brain diseases for at least three mechanisms. The uncontrolled activity of these channels could favor the collapse of ionic gradients and osmotic balance, the release of toxic levels of ATP or glutamate, cell swelling and plasma membrane breakdown and intracellular Ca2+ overload. Here, we evaluated whether acute ethanol exposure affects the activity of astrocyte hemichannels and the possible repercussions of this phenomenon on cytoplasmatic Ca2+ signaling and gliotransmitter release. Acute ethanol exposure triggered the rapid activation of connexin43 and pannexin1 hemichannels in astrocytes, as measured by time-lapse recordings of ethidium uptake. This heightened activity derived from a rapid rise in [Ca2+]i linked to extracellular Ca2+ influx and IP3-evoked Ca2+ release from intracellular Ca2+ stores. Relevantly, the acute ethanol-induced activation of hemichannels contributed to a persistent secondary increase in [Ca2+]i. The [Ca2+]i-dependent activation of hemichannels elicited by ethanol caused the increased release of ATP and glutamate in astroglial cultures and brain slices. Our findings offer fresh perspectives on the potential mechanisms behind acute alcohol-induced brain abnormalities and propose targeting connexin43 and pannexin1 hemichannels in astrocytes as a promising avenue to prevent deleterious consequences of alcohol consumption.

Cx43 hemichannels and panx1 channels contribute to ethanol-induced astrocyte dysfunction and damage.

BACKGROUND: Alcohol, a widely abused drug, significantly diminishes life quality, causing chronic diseases and psychiatric issues, with severe health, societal, and economic repercussions. Previously, we demonstrated that non-voluntary alcohol consumption increases the opening of Cx43 hemichannels and Panx1 channels in astrocytes from adolescent rats. However, whether ethanol directly affects astroglial hemichannels and, if so, how this impacts the function and survival of astrocytes remains to be elucidated. RESULTS: Clinically relevant concentrations of ethanol boost the opening of Cx43 hemichannels and Panx1 channels in mouse cortical astrocytes, resulting in the release of ATP and glutamate. The activation of these large-pore channels is dependent on Toll-like receptor 4, P2X7 receptors, IL-1ß and TNF-α signaling, p38 mitogen-activated protein kinase, and inducible nitric oxide (NO) synthase. Notably, the ethanol-induced opening of Cx43 hemichannels and Panx1 channels leads to alterations in cytokine secretion, NO production, gliotransmitter release, and astrocyte reactivity, ultimately impacting survival. CONCLUSION: Our study reveals a new mechanism by which ethanol impairs astrocyte function, involving the sequential stimulation of inflammatory pathways that further increase the opening of Cx43 hemichannels and Panx1 channels. We hypothesize that targeting astroglial hemichannels could be a promising pharmacological approach to preserve astrocyte function and synaptic plasticity during the progression of various alcohol use disorders.

Progressive Early-Onset Leukodystrophy Related to Biallelic Variants in the KARS Gene: The First Case Described in Latin America.

The KARS gene encodes the aminoacyl-tRNA synthetase (aaRS), which activates and joins the lysin with its corresponding transfer RNA (tRNA) through the ATP-dependent aminoacylation of the amino acid. KARS gene mutations have been linked to diverse neurologic phenotypes, such as neurosensorial hearing loss, leukodystrophy, microcephaly, developmental delay or regression, peripheral neuropathy, cardiomyopathy, the impairment of the mitochondrial respiratory chain, and hyperlactatemia, among others. This article presents the case of a Colombian pediatric patient with two pathological missense variants in a compound heterozygous state in the KARS gene and, in addition to the case report, the paper reviews the literature for other cases of KARS1-associated leukodystrophy.

Number of trials necessary to achieve performance stability in a reaching kinematics movement analysis game.

STUDY DESIGN: A cross-sectional design was used. INTRODUCTION: Motion analysis is commonly used to analyze reaching movements of individuals, but how many trials are necessary to provide stable data? PURPOSE OF THE STUDY: The purpose of this study was to determine the number of trials necessary to obtain stable kinematic variables during reaching movements in a virtual environment. METHODS: Thirty children (10.39 ± 1.68 years) and 20 adults (26.55 ± 3.12 years) participated. All participants interacted with a virtual reality evaluation game called Super Pop VR to collect their reaching kinematics. The players were instructed to pop several sets of virtual bubbles at a self-selected pace and their upper-body coordinates were recorded and reaching kinematics were computed. Two methods (sequential averaging techniques, SAT, and intraclass correlation coefficient, ICC) were carried out to assess performance stability of each kinematic variable. RESULTS: For the SAT method, children exhibited 3.11 to 5.96 trial range to achieve stability in the dominant hand and 2.7 to 5.96 trial range in the nondominant hand, whereas adults exhibited 2.65 to 6.16 trial range in the dominant hand and 3.40 to 6.05 range in the nondominant hand. For the ICC method, to reach the "excellent" value of ICC, children's dominant hand required 4.20 trials and their nondominant hand required 2.5 trials, whereas adults' dominant hand required 3.00 trials and their nondominant hand required 2.80 trials. DISCUSSION AND CONCLUSIONS: Our findings supported the importance of determining the minimum number of trials required to obtain stable movements regardless of how familiar the movement seems to participants or how sensitive the apparatus is.

HTMoL: full-stack solution for remote access, visualization, and analysis of molecular dynamics trajectory data.

Research on biology has seen significant advances with the use of molecular dynamics (MD) simulations. The MD methodology enables explanation and discovery of molecular mechanisms in a wide range of natural processes and biological systems. The need to readily share the ever-increasing amount of MD data has been hindered by the lack of specialized bioinformatic tools. The difficulty lies in the efficient management of the data, i.e., in sending and processing 3D information for its visualization. In this work, we present HTMoL, a plug-in-free, secure GPU-accelerated web application specifically designed to stream and visualize MD trajectory data on a web browser. Now, individual research labs can publish MD data on the Internet, or use HTMoL to profoundly improve scientific reports by including supplemental MD data in a journal publication. HTMoL can also be used as a visualization interface to access MD trajectories generated on a high-performance computer center directly. Furthermore, the HTMoL architecture can be leveraged with educational efforts to improve learning in the fields of biology, chemistry, and physics.

Effect of feedback from a socially interactive humanoid robot on reaching kinematics in children with and without cerebral palsy: A pilot study.

PURPOSE: To examine whether children with or without cerebral palsy (CP) would follow a humanoid robot's (i.e., Darwin) feedback to move their arm faster when playing virtual reality (VR) games. METHODS: Seven children with mild CP and 10 able-bodied children participated. Real-time reaching was evaluated by playing the Super Pop VRTM system, including 2-game baseline, 3-game acquisition, and another 2-game extinction. During acquisition, Darwin provided verbal feedback to direct the child to reach a kinematically defined target goal (i.e., 80% of average movement time in baseline). Outcome variables included the percentage of successful reaches ("% successful reaches"), movement time (MT), average speed, path, and number of movement units. RESULTS: All games during acquisition and extinction had larger "%successful reaches," faster speeds, and faster MTs than the 2 games during baseline (p < .05). CONCLUSION: Children with and without CP could follow the robot's feedback for changing their reaching kinematics when playing VR games.

Actividad ansiolítica del extracto etanólico de las hojas de Thymus vulgaris (Tomillo) en Rattus novergicus / Anxiolytic activity of Thymus vulgaris leaf ethanolic extract in Rattus novergicus

Objetivo. Demostrar que la administración vía oral del extracto etanólico de las hojas de Thymus vulgaris presenta un efecto ansiolítico en Rattus novergicus (var Wistar). Materiales y métodos. Estudio experimental. Se utilizaron 50 ratas distribuidas aleatoriamente en cinco grupos de investigación: Blanco (dieta normal con administración de agua estéril); Control positivo (dieta normal con administración de clonazepam 0.25 mg/kg); Grupo I (Extracto etanólico [EE] de Thymus vulgaris 50 mg / kg); Grupo II (EE de Thymus vulgaris 100 mg / kg) y Grupo III (EE de Thymus vulgaris 200 mg / kg). El efecto ansiolítico fue evaluado mediante el modelo de laberinto en cruz elevado, calculándose los tiempos de permanencia en brazo abierto, en brazo cerrado y los números de entrada en brazo abierto y cerrado. Resultados. Se observaron diferencias significativas en la comparación de medias de los números de entrada en el brazo abierto (p= 0.012) y en el brazo cerrado (p=0.035); sin embargo, no se evidenció diferencias significativas al comparar las medias de los grupos que recibieron Thymus vulgaris y el control negativo (p>0.05). Conclusión. El extracto etanólico de las hojas del Thymus vulgaris (a dosis de 50, 100 y 200 mg/kg) no presenta un efecto ansiolítico significativo en Rattus novergicus.

Objective. To demonstrate if oral administration of Thymus vulgaris leaves ethanolic extract has an anxiolytic effect in Rattus novergicus (Wistar var). Materials and methods. An experimental study. Fifty rats were distributed randomly in five research groups: Negative control (normal diet with distilled water oral administration); Positive control (normal diet with oral administration of clonazepam 0.25 mg / kg); Group I (Thymus vulgaris ethanolic extract [EE] 50 mg / kg); Group II (Thymus vulgaris EE 100 mg / kg) and Group III (Thymus vulgaris EE 200 mg / kg). The anxiolytic effect was evaluated by elevated plus-maze model, calculating amount of time spent as well as the total number of entries on open arm and closed arm. Results. Significant differences were observed in the comparison of means of entries in the open arm (p = 0.012) and in the closed arm (p = 0.035); however, no significant differences were found on comparison of means of groups that received Thymus vulgaris EE and negative control (p> 0.05). Conclusion. The Thymus vulgaris leaves ethanolic extract (at doses of 50, 100 and 200 mg / kg) does not show a significant anxiolytic effect in Rattus novergicus.

Effect of a Home-Based Virtual Reality Intervention for Children with Cerebral Palsy Using Super Pop VR Evaluation Metrics: A Feasibility Study.

Objective. The purpose of this pilot study was to determine whether Super Pop VR, a low-cost virtual reality (VR) system, was a feasible system for documenting improvement in children with cerebral palsy (CP) and whether a home-based VR intervention was effective. Methods. Three children with CP participated in this study and received an 8-week VR intervention (30 minutes × 5 sessions/week) using the commercial EyeToy Play VR system. Reaching kinematics measured by Super Pop VR and two fine motor tools (Bruininks-Oseretsky Test of Motor Proficiency second edition, BOT-2, and Pediatric Motor Activity Log, PMAL) were tested before, mid, and after intervention. Results. All children successfully completed the evaluations using the Super Pop VR system at home where 85% of the reaches collected were used to compute reaching kinematics, which is compatible with literature using expensive motion analysis systems. Only the child with hemiplegic CP and more impaired arm function improved the reaching kinematics and functional use of the affected hand after intervention. Conclusion. Super Pop VR proved to be a feasible evaluation tool in children with CP.

Asociación entre conocimientos de anticoncepción y embarazo no planeado: estudio de corte transversal / Association between knowledge of contraception and unplanned pregnancy: a cross-sectional study

Objetivo: medir la asociación entre el nivel de conocimientos sobre la resolución de problemas en la utilización de los métodos anticonceptivos y la presencia de embarazo no planeado en mujeres que usan métodos anticonceptivos de corta acción. Establecer la prevalencia del embarazo no planeado y describir actitudes, percepciones y características de la atención en las actividades de planificación familiar.Materiales y métodos: estudio analítico de corte transversal. Se incluyeron mujeres entre 14 y 49 años de edad, que acudieron a realizarse una prueba de embarazo a una institución de salud del sector público, de bajo nivel de complejidad, que atiende población del régimen de aseguramiento subsidiado por el Estado en la ciudad Medellín (Colombia). Antes de obtener el resultado de la prueba de embarazo se les realizó una encuesta estructurada y un test acerca de su conocimiento para resolver situaciones que pueden afectar la efectividad de los métodos de anticoncepción dependientes de la mujer.Resultados: se realizaron 471 encuestas, el 75,2 % de las mujeres no planeaban embarazarse y el 57 % tuvieron un embarazo no planeado. La mediana del nivel de conocimientos fue del 50 % (p25: 37,5 %, p75: 62,5 %). La razón de prevalencias de embarazo no planeado con nivel medio y alto de conocimientos fue 0,56 (IC 95 %: 0,34-0,92).Conclusión: el conocimiento sobre la resolución de los problemas que afectan la efectividad de los métodos anticonceptivos que dependen del buen uso de la mujer para garantizar esa efectividad se asocia a menor frecuencia de embarazo no planeado.

Objective: To measure the association between the degree of knowledge on how to solve problems associated with the use of contraceptive methods and the presence of unplanned pregnancies in women using short-acting contraception; to determine the prevalence of unplanned pregnancies; and to describe attitudes, perceptions and characteristics in relation to family planning activities.Materials and methods: Cross-sectional analytical study conducted in women between 14 and 49 years of age coming for a pregnancy test to a public, low-complexity healthcare institution in Medellín, Colombia, that provides care to a population covered under a state-subsidized healthcare system. Before delivering the result of the pregnancy test they were given a structured survey and a test to measure their knowledge for solving situations that might affect the effectiveness of contraception methods under the woman’s control.Results: Of the 471 women surveyed, 75.2 % were not planning to become pregnant and 57 % had an unplanned pregnancy. The median knowledge level was 50% (p25: 37.5%, p75: 62.5%). The prevalence ratio of unplanned pregnancy with an intermediate or high level of knowledge was 0.56 (95% CI 0.34-0.92).Conclusion: Knowledge about how to solve problems regarding contraceptive methods that depend for their effectiveness on the appropriate use by the woman is associated with a lower frequency of unplanned pregnancies.

Carga vascular y valvular en la estenosis aórtica grave con bajo flujo, bajo gradiente y fracción de eyección normal / Vascular and Valvular Load in Low-Flow/Low-Gradient Severe Aortic Stenosis and Normal Ejection Fraction

Introducción Algunos pacientes con estenosis aórtica (EAo) pueden presentar disminución del volumen sistólico (VS) y gradientes bajos a pesar de tener una fracción de eyección (Fey) normal. La disminución del área valvular aórtica (AVA) y el aumento de la carga vascular contribuyen a la disminución del VS. Objetivo Analizar la carga vascular y valvular en la EAo grave con bajo flujo, bajo gradiente y Fey normal. Material y métodos Se estudiaron 53 pacientes (70 ± 12 años) con EAo grave (AVA < 1 cm²) y Fey ≥ 50%. La carga valvular se estimó por medio del AVA y del índice de pérdida de energía (IPE). La carga vascular se evaluó mediante la elastancia arterial efectiva (Ea) y la resistencia vascular sistémica (RVS). La impedancia valvuloarterial (Zva) se calculó como una estimación de la poscarga global del VI. La Ea se calculó dividiendo la presión de fin de sístole por el VS. La presión de fin de sístole se obtuvo por tonometría. La Zva se calculó como: (presión sistólica + gradiente medio neto) / índice de VS. Los pacientes se dividieron en dos grupos según si tenían flujo normal (FN) (n = 35), definido como índice de VS > 35 ml/m², o bajo flujo (BF) (n = 18), con índice de VS ≤ 35 ml/m². Resultados Comparados con el grupo FN, los pacientes con BF tuvieron menor AVA (0,59 ± 0,18 versus 0,76 ± 0,22 cm²; p < 0,01), gradiente medio (28 ± 5 versus 45 ± 4 mm Hg; p < 0,01) e IPE (0,35 ± 0,13 versus 0,47 ± 0,16 cm²/m²; p < 0,01). Con respecto a la carga vascular, los pacientes con BF tuvieron mayor Ea (1,91 ± 0,42 versus 1,24 ± 0,33 mm Hg/ml; p < 0,00001), RVS (2.119 ± 506 versus 1.625 ± 443 mm Hg • min/L; p < 0,001) y poscarga global evaluada mediante Zva (5,45 ± 1,39 versus 3,95 ± 1,10 mm Hg/ml/m²; p < 0,001). En el análisis univariado, el VS se correlacionó con la Ea (r = -0,87, p < 0,0001), la RVS (r = -0,73, p < 0,0001) y la Zva (r = -0,71, p < 0,0001). En el análisis multivariado, la Ea fue el único predictor independiente de VS disminuido. Conclusiones En pacientes con EAo grave, la fisiopatología del BF parece estar relacionada con un aumento significativo de la carga vascular.

Background Some patients with aortic stenosis (AS) may present reduced stroke volume (SV) and low transvalvular gradients despite normal ejection fraction (EF). The reduction in the aortic valve area (AVA) and the increase in the vascular load contribute to decrease the SV. Objective To analyze the vascular and valvular load in low-flow/lowgradient severe aortic stenosis and normal ejection fraction. Material and Methods A total of 53 patients (70±12 years) with severe AS (AVA <1 cm²) and EF ≥50% were studied. Valvular load was estimated using the AVA and the energy loss index (ELI). Vascular load was evaluated by means of the effective arterial elastance (Ea) and systemic vascular resistance (SVR). Valvulo-arterial impedance (Zva) was calculated as an estimation of global left ventricular (LV) afterload. Ea was estimated as the ratio between end-systolic pressure and SV. End-systolic pressure was obtained by tonometry. Zva was calculated as: (systolic arterial pressure + mean net pressure gradient) / SV index. Patients were divided in two groups: normal flow (NF) (n=35), defined as a SV index >35 ml/m², or low flow (LF) (n=18), with a SV index ≤35 ml/m². Results Compared to NF patients, LF patients had lower AVA (0.59±0.18 versus 0.76±0.22 cm²; p<0.01), mean pressure gradient (28±5 versus 45±4 mm Hg; p<0.01) and ELI (0.35±0.13 versus 0.47±0.16 cm²/m²; p<0.01). Vascular load was greater in LF patients than in NF patients, with higher values of Ea (1.91±0.42 versus 1.24±0.33 mm Hg/ml; p<0.00001), SVR (2.119±506 versus 1.625 ± 443 mm Hg • min/L; p<0.001) and global afterload measured by Zva (5.45±1.39 versus 3.95±1.10 mm Hg/ml/m²; p<0.001). At univariate analysis, SV correlated with Ea (r= -0.87, p<0.0001), SVR (r= -0.73, p<0.0001) and Zva (r= -0.71, p<0.0001). Ea was the only independent predictor of reduced SV at multivariate analysis. Conclusions In patients with severe AS, the physiopathology of LF seems to be related to a significant increase in the vascular load.

Experiencia piloto de compostaje de barros primarios cloacales de Mar del Plata

Estudio realizado en el marco de un plan de gestión de efluentes que incluye la remodelación de la planta de pretratamiento actual de la ciudad, y la construcción de un emisario submarino. Se estudió el compostaje como alternativa de gestión del barro cloacal, evaluando el proceso durante invierno y verano, y encontrando bajas concentraciones de metales pesados en barros y lixiviados

Estudio epidemiológico analítico de los patrones de uso de alcohol y tabaco en pescadores: correlación con variables demográficas y patologías / Analytic epidemiological study of patterns of alcohol use and tobacco among fishermen

Tipo de estudio: epidemiológico transversal. Lugar:Mar del Plata, Argentina, 1989-1990. Propósito: recolección de información para futuras acciones de salud de tipo preventivo. Objetivo general: establecer una línea base del perfil de salud para espcadores argentinos. Objetivos específicos: 1)estudiar el perfil demográfico de los mismos, 2)estimar la distribución de tabaquismo y alcoholismo de acuerdo a variables seleccionadas y 3) evaluar el efecto de los factores ambientales de riesgo físico en dichos hábitos. Ambiente del estudio: consultorios ambulatorios y barcos de pesca. Diseño del estudio: muestra aleatoria sistemática de 101 pescadores y combinada aleatoria simple de propósito de 101 controles. Se formularon definiciones operacionales para cada variable. Elaboración estadística mediante métodos estanard y uso del BMDP Sofware (r). Resultados: los pescadores (expuestos) eran mayores (media: 41,25 años vs. 35.25;p < 0.05) que sus testigos. Asimismo en su mayoría estaban casados, tenían nivel de instrucción menor, pertenecían a clases sociales más bajas (IV y V del Registro General Británico basado en las ocupaciones) y habían más sujetos nacidos en Europa. Los pescadores experimentaron más años de tabaquismo y una mayor prevalencia de bronquitis crónica. Los abusadores excesivos de alcohol (34 por ciento vs 15 por ciento) eran mayores, fumaban más diariamente y tenían mayor frecuencia de accidentes laborales. A una exposición mayor a variables ambientales físicas ocupacionales marinas hubo mayor consumo de alcohol. Se presentan resultados adicionales y se discuten. Todas estas diferencias respecto la poblacion testigo fueron estadísticamente significativas. Conclusiones: las CYMAT-Condiciones y Medio Ambiente de Trabajo-influyen en los patrones de uso de tabaco y alcohol de pescadores y distintas variables demográficas afectan las asociaciones. La metodología empleada de detección se aconseja para estudios posteriores (AU)

Estudio epidemiológico analítico de los patrones de uso de alcohol y tabaco en pescadores: correlación con variables demográficas y patologías / Analytic epidemiological study of patterns of alcohol use and tobacco among fishermen

Tipo de estudio: epidemiológico transversal. Lugar:Mar del Plata, Argentina, 1989-1990. Propósito: recolección de información para futuras acciones de salud de tipo preventivo. Objetivo general: establecer una línea base del perfil de salud para espcadores argentinos. Objetivos específicos: 1)estudiar el perfil demográfico de los mismos, 2)estimar la distribución de tabaquismo y alcoholismo de acuerdo a variables seleccionadas y 3) evaluar el efecto de los factores ambientales de riesgo físico en dichos hábitos. Ambiente del estudio: consultorios ambulatorios y barcos de pesca. Diseño del estudio: muestra aleatoria sistemática de 101 pescadores y combinada aleatoria simple de propósito de 101 controles. Se formularon definiciones operacionales para cada variable. Elaboración estadística mediante métodos estanard y uso del BMDP Sofware (r). Resultados: los pescadores (expuestos) eran mayores (media: 41,25 años vs. 35.25;p < 0.05) que sus testigos. Asimismo en su mayoría estaban casados, tenían nivel de instrucción menor, pertenecían a clases sociales más bajas (IV y V del Registro General Británico basado en las ocupaciones) y habían más sujetos nacidos en Europa. Los pescadores experimentaron más años de tabaquismo y una mayor prevalencia de bronquitis crónica. Los abusadores excesivos de alcohol (34 por ciento vs 15 por ciento) eran mayores, fumaban más diariamente y tenían mayor frecuencia de accidentes laborales. A una exposición mayor a variables ambientales físicas ocupacionales marinas hubo mayor consumo de alcohol. Se presentan resultados adicionales y se discuten. Todas estas diferencias respecto la poblacion testigo fueron estadísticamente significativas. Conclusiones: las CYMAT-Condiciones y Medio Ambiente de Trabajo-influyen en los patrones de uso de tabaco y alcohol de pescadores y distintas variables demográficas afectan las asociaciones. La metodología empleada de detección se aconseja para estudios posteriores