RESUMO

Pannexin-1 (Panx1) hemichannel is a non-selective transmembrane channel that may play important roles in intercellular signaling by allowing the permeation of ions and metabolites, such as ATP. Although recent evidence shows that the Panx1 hemichannel is involved in controlling excitatory synaptic transmission, the role of Panx1 in inhibitory transmission remains unknown. Here, we studied the contribution of Panx1 to the GABAergic synaptic efficacy onto CA1 pyramidal neurons (PyNs) by using patch-clamp recordings and pharmacological approaches in wild-type and Panx1 knock-out (Panx1-KO) mice. We reported that blockage of the Panx1 hemichannel with the mimetic peptide 10Panx1 increases the synaptic level of endocannabinoids (eCB) and the activation of cannabinoid receptors type 1 (CB1Rs), which results in a decrease in hippocampal GABAergic efficacy, shifting excitation/inhibition (E/I) balance toward excitation and facilitating the induction of long-term potentiation. Our finding provides important insight unveiling that Panx1 can strongly influence the overall neuronal excitability and play a key role in shaping synaptic changes affecting the amplitude and direction of plasticity, as well as learning and memory processes.

Assuntos

RESUMO

Enhanced activity and overexpression of Pannexin 1 (Panx1) channels contribute to neuronal pathologies such as epilepsy and Alzheimer's disease (AD). The Panx1 channel ablation alters the hippocampus's glutamatergic neurotransmission, synaptic plasticity, and memory flexibility. Nevertheless, Panx1-knockout (Panx1-KO) mice still retain the ability to learn, suggesting that compensatory mechanisms stabilize their neuronal activity. Here, we show that the absence of Panx1 in the adult brain promotes a series of structural and functional modifications in the Panx1-KO hippocampal synapses, preserving spontaneous activity. Compared to the wild-type (WT) condition, the adult hippocampal neurons of Panx1-KO mice exhibit enhanced excitability, a more complex dendritic branching, enhanced spine maturation, and an increased proportion of multiple synaptic contacts. These modifications seem to rely on the actin-cytoskeleton dynamics as an increase in the actin polymerization and an imbalance between the Rac1 and the RhoA GTPase activities were observed in Panx1-KO brain tissues. Our findings highlight a novel interaction between Panx1 channels, actin, and Rho GTPases, which appear to be relevant for synapse stability.

Assuntos

RESUMO

OBJECTIVE: The present study examined the effectiveness of after-action reviews (AARs; also known as debriefing) in mitigating skill decay. BACKGROUND: Research on the long-term effectiveness of AARs is meager. To address this gap in the literature, we conducted an experimental study that also overcomes some research design issues that characterize the limited extant research. METHOD: Eighty-four participants were randomly assigned to an AAR or non-AAR condition and trained to operate a PC-based fire emergency simulator. During the initial acquisition phase, individuals in the AAR condition were allowed to review their performance after each practice session, whereas individuals in the non-AAR condition completed a filler task. About 12 weeks later, participants returned to the lab to complete four additional practice sessions using a similar scenario (i.e., the retention and reacquisition phase). RESULTS: The performance of participants in the AAR condition degraded more after nonuse but also recovered faster than the performance of participants in the non-AAR condition, although these effects were fairly small and not statistically significant. CONCLUSION: Consistent with the limited research on the long-term effectiveness of AARs, our findings failed to support their effectiveness as a decay-prevention intervention. Because the present study was conducted in a laboratory setting using a relatively small sample of undergraduate students, additional research is warranted. APPLICATION: Based on the results of the present study, we suggest some additional strategies that trainers might consider to support long-term skill retention when using AARs.

Assuntos

RESUMO

Cardiovascular diseases (CVD) are highly prevalent non-communicable diseases worldwide. Periodontitis may act as a non-traditional cardiovascular risk (CVR) factor, linked by a low-grade systemic inflammation mediated by C-reactive protein (CRP). Patients with periodontitis reported higher serum CRP levels; however, a CRP systemic and periodontal correlation in gingival crevicular fluid (GCF) and its CVR impact have been barely studied. We aimed to assess the association between periodontal diseases and CVR in a group of adult women, based on serum high-sensitivity CRP (hs-CRP) levels; and secondly, to determine the association between serum and GCF CRP levels. Gingival crevicular fluid and blood samples were obtained from women with periodontitis, gingivitis, and healthy controls. Serum and GCF CRP were determined by turbidimetric method and Luminex technology, respectively. Data were analyzed and adjusted by CVR factors. All women presented moderate CVR, without an evident association between serum hs-CRP levels and periodontal diseases. While serum hs-CRP concentrations did not significantly differ between groups, patients with gingivitis and periodontitis showed higher CRP levels in GCF, which positively correlated to CRP detection in serum.

Assuntos

RESUMO

Daily fine (PM2.5) and coarse (PM10-2.5) particle matter (PM) samples collected at Parque O'Higgins station in downtown Santiago de Chile have been studied to find the trends in concentration from 1998 to 2018. Elemental concentration was obtained using X-ray fluorescence (XRF). Regression models from previous studies indicate that the PM2.5 and PM10-2.5 fractions have had a continuous decrease since 1988 mostly due to several policy control measures carried out over several decades. PM2.5 has decreased from 68.3 in 1988 to 27.6 µg/m3 in 2018 (60.4%). However, if only the last 8 years are considered (2011-2018), a leveling off can be observed in PM10-2.5 and PM2.5, which points to a change in the tendency. Cluster analysis of the elements in the fine and coarse fractions were identified to evaluate trends in the contributing sources. In the fine fraction, the mass contribution of crustal elements (Si, Al, Ca, and Fe) has remained stable in the last 8 years, and mass contribution of elements (Pb, Br, and Cl) associated to anthropogenic sources (traffic, wood burning) has also remained stable in the same period. For the coarse fraction, the contribution of one group of elements associated to crustal or anthropogenic sources has remained stable, and another group has decreased in the last 8 years. The leveling off can be ascribed to decreased rainfall during the last 8 years that have promoted soil dryness and resuspension of dust facilitated by wind or vehicular traffic. Mean temperatures have increased in the last 30 years, but have not contributed directly to the leveling of the concentration.Implications: Regression models indicate that the PM2.5 (fine) and PM10-2.5 (coarse) fractions at Parque O'Higgins station in Santiago de Chile have had a continuous decrease since 1988 mostly due to several policy control measures carried out over several decades. However, in the last 8 years (2011-2018), a leveling off can be observed in PM10-2.5 and PM2.5. X-ray fluorescence (XRF) analysis was performed in the fine fractions indicating that the mass contribution of crustal elements (Ca, Al, Si, Fe) to the fine fraction has remained stable. This phenomenon can be ascribed to decreased rainfall during the last 8 years that have promoted soil dryness and resuspension of dust facilitated by wind or vehicular traffic. The crustal elements in the coarse fraction have also remained stable.

Assuntos

RESUMO

Chronic lymphocytic leukemia (CLL) cells change their metabolic program between normoxia and hypoxia, possibly affecting cytotoxic drug potency by altering mitochondria-related cell stress responses (MRCSR) including mitophagy, mitochondrial biogenesis, and mitochondrial proteostasis. We evaluated in CLL cells from nine patients, the single and multiple-combined drug potency of arsenic trioxide (ATO), valproic acid (VPA), vincristine (VCR) and MG132 as four pharmacological sensors influencing mitochondrial apoptosis, mitochondrial biogenesis, mitophagy, and mitochondrial proteostasis respectively, under normoxia and hypoxia to force hypoxia-induced metabolic reprogramming (HMR). Untreated cells from all patients remained viable under O2 levels below 0.5% for 72 h. We obtained 21 measures of drug potency and interaction at 50% effect level that we denoted drug potency signature (DPS). Using the comparative DPS between normoxia and hypoxia, two non-supervised classification algorithms discriminated CLL patients with active disease (ADT) and stable disease (NAD) and showed complete consistency with their clinical characteristics. In ADT group under hypoxia, the potency of MG132 was increased, the interaction of ATO + VPA and ATO + VPA + VCR shifted towards antagonism, and ATO + VPA + VCR + MG132 shifted towards synergism, indicating a prominent role of mitochondrial proteostasis. Classification of patients based on DPS, depended on the contrasting response of drugs under hypoxia and normoxia, owing to HMR. Using these drugs as pharmacological sensors, we linked the metabolic arrangement of CLL cells under hypoxia, to potency of drugs targeting MRCSR, and to the clinical features of individual patients, therefore providing new sources of data on disease progression, drug response and risk prognosis.

Assuntos

RESUMO

Integration of low-cost air quality sensors with the internet of things (IoT) has become a feasible approach towards the development of smart cities. Several studies have assessed the performance of low-cost air quality sensors by comparing their measurements with reference instruments. We examined the performance of a low-cost IoT particulate matter (PM10 and PM2.5) sensor in the urban environment of Santiago, Chile. The prototype was assembled from a PM10-PM2.5 sensor (SDS011), a temperature and relative humidity sensor (BME280) and an IoT board (ESP8266/Node MCU). Field tests were conducted at three regulatory monitoring stations during the 2018 austral winter and spring seasons. The sensors at each site were operated in parallel with continuous reference air quality monitors (BAM 1020 and TEOM 1400) and a filter-based sampler (Partisol 2000i). Variability between sensor units (n = 7) and the correlation between the sensor and reference instruments were examined. Moderate inter-unit variability was observed between sensors for PM2.5 (normalized root-mean-square error 9-24%) and PM10 (10-37%). The correlations between the 1-h average concentrations reported by the sensors and continuous monitors were higher for PM2.5 (R2 0.47-0.86) than PM10 (0.24-0.56). The correlations (R2) between the 24-h PM2.5 averages from the sensors and reference instruments were 0.63-0.87 for continuous monitoring and 0.69-0.93 for filter-based samplers. Correlation analysis revealed that sensors tended to overestimate PM concentrations in high relative humidity (RH > 75%) and underestimate when RH was below 50%. Overall, the prototype evaluated exhibited adequate performance and may be potentially suitable for monitoring daily PM2.5 averages after correcting for RH.

Assuntos

RESUMO

The aim of the study was threefold: (a) to test a before-school physical activity intervention (Active-Start) on academic performance, selective attention, and concentration capacity; (b) to test the effect of the Active-Start intervention on anthropometry, body composition, and physical fitness parameters; and (c) whether the physical fitness components are moderators of the effect of the Active-Start program on academic performance, selective attention, and concentration capacity in Chilean children. The Active-Start intervention was a RCT which comprised 170 children (8-10 years old) from three public schools with low socioeconomic status from the city of Santiago (Chile). The exercise intervention was delivered daily, before starting the first school-class (8:00-8:30 am) for 8 weeks. Changes in academic performance, selective attention and concentration capacity, anthropometric, body composition, and physical fitness parameters were measured. The analyses used were mixed regression models for repeated measures over time. No statistically significant changes in attention and concentration capacity were found. However, significant changes were seen in language (0.63; 95% CI 0.49-0.77) and mathematics (0.49; 95% CI 0.32-0.66) performance (P < .001). Also, improvements were seen in fat mass, fat-free mass, muscular, and cardiorespiratory fitness (all P < .05). The Johnson-Neyman technique revealed a significant relationship between the effect of intervention and attention and concentration when change in cardiorespiratory fitness was above, but not below, 3.05 and 0.70 mL/kg/min, respectively. Implementing before-school physical activity programs such as the Active-Start to enhance the cardiorespiratory fitness may benefit attention capacity and academic success among schoolchildren.

Assuntos

RESUMO

BACKGROUND/OBJECTIVE: To test the effectiveness of an 8-week before-school physical activity program to reduce bullying victimization among a group of socially disadvantaged children in the Active-Start study. METHOD: A non-blinded randomized controlled trial was conducted in three public schools classified as highly vulnerable and located in a deprived area of Santiago (Chile). A total of 5 classes participated, totaling 170 fourth grade children. The intervention was delivered before starting the first school-class (8:00-8:30 a.m.). The program lasted for 8 weeks. Primary outcome measurement on bullying victimization was assessed by the CUBE questionnaire at baseline and post-intervention. RESULTS: There was a statistically significant reduction in the probability of suffering physical bullying (OR= 0.18, 95% CI, 0.04-0.82; p= .027) and verbal bullying (OR=0.13, 95% CI, 0.02-0.97; p= .046) after the 8-week program. CONCLUSIONS: Participation in an 8-week before-school physical activity intervention implemented in schools located in a disadvantaged district in Santiago (Chile) resulted in lower levels of bullying victimization among study participants. The Active-Start program may be a feasible and potentially scalable intervention option to improve the climate and pro-sociality environment at schools.

ANTECEDENTES/OBJETIVO: Evaluar la efectividad de un programa de actividad física antes de la escuela de ocho semanas para reducir el bullying en niños en desventaja social del estudio Active-Start. MÉTODO: Se realizó un ensayo controlado aleatorio no ciego en tres escuelas públicas vulnerables y ubicadas en Santiago (Chile), con un total de cinco clases e incluyendo 170 niños de Cuarto Grado. La intervención de ocho semanas se realizó cinco veces por semana antes de comenzar la primera clase (8:00­8:30 a.m.). La medida de resultado primaria fue la victimización por bullying evaluado a través del cuestionario CUBE al inicio y después de la intervención. RESULTADOS: Hubo una reducción estadísticamente significativa en la probabilidad de sufrir bullying físico (OR= 0,18, IC 95%, 0,04-0,82; p= 0,027) y verbal (OR= 0,13, IC 95%, 0,02-0,97; p= 0,046) después del programa de ocho semanas. CONCLUSIONES: La participación en una intervención de actividad física antes de la escuela de ocho semanas implementada en escuelas ubicadas en una comuna desfavorecida en Santiago (Chile) dio lugar a niveles más bajos de victimización por bullying entre sus participantes. El programa Active-Start puede ser una opción de intervención viable y potencialmente escalable para mejorar el clima y el ambiente escolar.

RESUMO

Introducción: La Troponina I (TnI) plasmática es el biomarcador "Gold" estándar utilizado en diagnóstico de Infarto Agudo al Miocardio (IAM), indicando necrosis cardíaca. Las microvesículas extracelulares (MVEC), participan en comunicación celular, por lo que estudiar su distribución entregaría información respecto del evento isquémico, antesala del infarto. Objetivo: Estudiar las MVECs plasmáticas en pacientes con Síndrome Coronario Agudo (SCA) y compararlas con los niveles de TnI. Métodos: Plasma de 22 pacientes controles se recolectó 0-2hrs post-ingreso a urgencia. Plasma de 45 pacientes SCA se recolectó 0-2, 6-8 y 10-14hrs post ingreso, junto con la toma de muestra para estudio de TnI. Las MVECs plasmáticas fueron enriquecidas mediante kit comercial. La determinación de la concentración y tamaño MVECs se realizó por NTA (Nanoparticles Tracking Assay) usando el equipo Nanosight. Resultados: La concentración promedio de MVECs 0-2 hrs post ingreso fue 7,2 veces superior en plasma de pacientes con SCA vs controles y la moda del tamaño disminuyó en pacientes con SCA. La TnI no mostró diferencias significativas en 0-2 hrs post ingreso en el grupo estudiado. La concentración de las MVEC disminuyó significativamente después de 10-14 hrs post ingreso, mientras que la concentración promedio TnI se mantuvo invariable demostrando el aumento de MVECs previo al incremento de TnI. Conclusión. El aumento de MVECs previo al incremento de la TnI en pacientes infartados, sugiere que las MVECs aumentan en la fase previa del IAM, como respuesta al daño tisular. Actualmente, estudiamos el contenido molecular de las MVECs, para establecer un método diagnóstico del Síndrome Coronario Agudo basado en MVECs.

Background: Troponin I (TnI) is the gold standard used to establish the diagnosis of myocardial infarction (AMI), indicating the presence of myocardial necrosis. Extracellular micro vesicles are involved in cellular communication. Their distribution may provide information relating to the development of AMI in patients with acute coronary syndromes (ACS) Aim: to study plasma levels of ECMV compared to those of TnI in patients with ACS. Methods: The plasma levels of TnI and ECMV from 22 control patients coming to the emergency units was compared to plasma from 45 patients with ACS. Levels of both parameters were determined 0-2, 6-8 and 10-14 hours post admission. ECMVs were enriched by means of a commercial kit. Concentration and size of ECMV was determined by NTA (Nanoparticles tracking assay) using the Nanosight equipment. Results: Plasma concentration of ECMV was 7.2 times higher than that of TnI 0-2 hrs post admission. The mode of ECMV size was lower in patients with ACS. Concentration of ECMV had decreased significantly 10-14 hrs post admission, whereas the TnI levees remained stable. Conclusion: The increase in ECMV earlier than TnI in AMI suggests that ECMV are elevated in the pre-AMI phase, as a response to early tissue damage. A study of cellular content of ECMV, being carried out, may lead to develop a method for the early diagnosis of AMI in patients with ACS.

Assuntos