Phenotypic Expression and Outcomes in Patients with the p.Arg301Gln GLA Variant in Anderson-Fabry Disease.

The p.Arg301Gln variant in the α -galactosidase A gene (GLA) has been poorly described in the literature. The few reports show controversial information, with both classical and nonclassical Anderson-Fabry Disease (AFD) presentation patterns. The aim of this study was to analyze the penetrance, clinical phenotype, and biochemical profile of an international cohort of patients carrying the p.Arg301Gln genetic variant in the GLA gene. This was an observational, international, and retrospective cohort case series study of patients carrying the p.Arg301Gln variant in the GLA gene associated with AFD disease. Forty-nine p.Arg301Gln GLA carriers, 41% male, were analyzed. The penetrance was 63% in the entire cohort and 1.5 times higher in men. The mean age of symptoms onset was 41 years; compared to women, men presented symptoms earlier and with a shorter delay to diagnosis. The typical clinical triad-cornea verticillate, neuropathic pain, and angiokeratomas-affected only 20% of the cohort, with no differences between genders. During follow-up, almost 20% of the patients presented some type of nonfatal cardiovascular and renal event (stroke, need for dialysis, heart failure, and arrhythmias requiring intracardiac devices), predominantly affecting men. Residual levels were the most common finding of α-GAL A enzyme activity, only a few women had a normal level; a small proportion of men had undetectable levels. The incidence of combined outcomes including all causes of death was 33%, and the cumulative incidence of all-cause mortality was 9% at the follow-up. Patients carrying the p.Arg301Gln GLA variant have a high penetrance, with predominantly cardiorenal involvement and clinical onset of the disease in middle age. Only a small proportion showed the classic clinical presentation of AFD. As in other X-linked diseases, males were more affected by severe cardiovascular and renal events. This genotype-phenotype correlation could be useful from a practical clinical point of view and for future decision making.

Molecular Pharmacology of Gelsemium Alkaloids on Inhibitory Receptors.

Indole alkaloids are the main bioactive molecules of the Gelsemium genus plants. Diverse reports have shown the beneficial actions of Gelsemium alkaloids on the pathological states of the central nervous system (CNS). Nevertheless, Gelsemium alkaloids are toxic for mammals. To date, the molecular targets underlying the biological actions of Gelsemium alkaloids at the CNS remain poorly defined. Functional studies have determined that gelsemine is a modulator of glycine receptors (GlyRs) and GABAA receptors (GABAARs), which are ligand-gated ion channels of the CNS. The molecular and physicochemical determinants involved in the interactions between Gelsemium alkaloids and these channels are still undefined. We used electrophysiological recordings and bioinformatic approaches to determine the pharmacological profile and the molecular interactions between koumine, gelsemine, gelsevirine, and humantenmine and these ion channels. GlyRs composed of α1 subunits were inhibited by koumine and gelsevirine (IC50 of 31.5 ± 1.7 and 40.6 ± 8.2 µM, respectively), while humantenmine did not display any detectable activity. The examination of GlyRs composed of α2 and α3 subunits showed similar results. Likewise, GABAARs were inhibited by koumine and were insensitive to humantenmine. Further assays with chimeric and mutated GlyRs showed that the extracellular domain and residues within the orthosteric site were critical for the alkaloid effects, while the pharmacophore modeling revealed the physicochemical features of the alkaloids for the functional modulation. Our study provides novel information about the molecular determinants and functional actions of four major Gelsemium indole alkaloids on inhibitory receptors, expanding our knowledge regarding the interaction of these types of compounds with protein targets of the CNS.

New Benzodihydrofuran Derivatives Alter the Amyloid ß Peptide Aggregation: Strategies To Develop New Anti-Alzheimer Drugs.

Alzheimer's disease is a neurodegenerative disorder that is the leading cause of dementia in elderly patients. Amyloid-ß peptide (1-42 oligomers) has been identified as a neurotoxic factor, triggering many neuropathologic events. In this study, 15 chalcones were synthesized employing the Claisen-Schmidt condensation reaction, starting from a compound derived from fomannoxine, a natural benzodihydrofuran whose neuroprotective activity has been proven and reported, and methyl aromatic ketones with diverse patterns of halogenated substitution. As a result, chalcones were obtained, with good to excellent reaction yields from 50 to 98%. Cytotoxicity of the compounds was assessed, and their cytoprotective effect against the toxicity associated with Aß was evaluated on PC-12 cells. Out of the 15 chalcones obtained, only the 4-bromo substituted was cytotoxic at most tested concentrations. Three synthesized chalcones showed a cytoprotective effect against Aß toxicity (over 37%). The 2,4,5-trifluoro substituted chalcone was the most promising series since it showed a cytoprotective impact with more than 60 ± 5% of recovery of cellular viability; however, 3-fluoro substituted compound also exhibited important values of recovery (50 ± 6%). The fluorine substitution pattern was shown to be more effective for cytoprotective activity. Specifically, substitution with fluorine in the 3,5-positions turned out to be particularly effective for cytoprotection. Furthermore, fluorinated compounds inhibited the aggregation rate of Aß, suggesting a dual effect that can be the starting point of new molecules with therapeutic potential.

TG2 promotes amyloid beta aggregates: Impact on ER-mitochondria crosstalk, calcium homeostasis and synaptic function in Alzheimer's disease.

Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by cognitive impairment that increasingly affects the elderly. AD's main features have been related to cellular and molecular events, including the aberrant aggregation of the amyloid beta peptide (Aß), Ca2+ dyshomeostasis, and increased mitochondria-associated membranes (MAMs). Transglutaminase type 2 (TG2) is a ubiquitous enzyme whose primary role is the Ca2+-dependent proteins transamidation, including the Aß peptide. TG2 activity has been closely related to cellular damage and death. We detected increased TG2 levels in neuronal cells treated with Aß oligomers (AßOs) and hippocampal slices from J20 mice using cellular and molecular approaches. In this work, we characterized the capacity of TG2 to interact and promote Aß toxic aggregates (AßTG2). AßTG2 induced an acute increase in intracellular Ca2+, miniature currents, and hiperexcitability, consistent with an increased mitochondrial Ca2+ overload, IP3R-VDAC tethering, and mitochondria-endoplasmic reticulum contacts (MERCs). AßTG2 also decreased neuronal viability and excitatory postsynaptic currents, reinforcing the idea of synaptic failure associated with MAMs dysregulation mediated by TG2. Z-DON treatment, TG2 inhibitor, reduced calcium overload, mitochondrial membrane potential loss, and synaptic failure, indicating an involvement of TG2 in a toxic cycle which increases Aß aggregation, Ca2+ overload, and MAMs upregulation. These data provide novel information regarding the role TG2 plays in synaptic function and contribute additional evidence to support the further development of TG2 inhibitors as a disease-modifying strategy for AD.

Co-designed metaoptoelectronic deep learning.

A metaoptical system is co-designed with electronic hardware to implement deep learning image recognition. The optical convolution block includes a reflective metasurface to perform one layer of a deep neural network. The optical and digital components are jointly optimized to perform an image classification task attaining 65% accuracy, which is close to the 66% accuracy of a fully-digital network where the optical block is replaced by a digital convolution layer.

Understanding the Role of ATP Release through Connexins Hemichannels during Neurulation.

Neurulation is a crucial process in the formation of the central nervous system (CNS), which begins with the folding and fusion of the neural plate, leading to the generation of the neural tube and subsequent development of the brain and spinal cord. Environmental and genetic factors that interfere with the neurulation process promote neural tube defects (NTDs). Connexins (Cxs) are transmembrane proteins that form gap junctions (GJs) and hemichannels (HCs) in vertebrates, allowing cell-cell (GJ) or paracrine (HCs) communication through the release of ATP, glutamate, and NAD+; regulating processes such as cell migration and synaptic transmission. Changes in the state of phosphorylation and/or the intracellular redox potential activate the opening of HCs in different cell types. Cxs such as Cx43 and Cx32 have been associated with proliferation and migration at different stages of CNS development. Here, using molecular and cellular biology techniques (permeability), we demonstrate the expression and functionality of HCs-Cxs, including Cx46 and Cx32, which are associated with the release of ATP during the neurulation process in Xenopus laevis. Furthermore, applications of FGF2 and/or changes in intracellular redox potentials (DTT), well known HCs-Cxs modulators, transiently regulated the ATP release in our model. Importantly, the blockade of HCs-Cxs by carbenoxolone (CBX) and enoxolone (ENX) reduced ATP release with a concomitant formation of NTDs. We propose two possible and highly conserved binding sites (N and E) in Cx46 that may mediate the pharmacological effect of CBX and ENX on the formation of NTDs. In summary, our results highlight the importance of ATP release mediated by HCs-Cxs during neurulation.

Identification of Structural Determinants of the Transport of the Dehydroascorbic Acid Mediated by Glucose Transport GLUT1.

GLUT1 is a facilitative glucose transporter that can transport oxidized vitamin C (i.e., dehydroascorbic acid) and complements the action of reduced vitamin C transporters. To identify the residues involved in human GLUT1's transport of dehydroascorbic acid, we performed docking studies in the 5 Å grid of the glucose-binding cavity of GLUT1. The interactions of the bicyclic hemiacetal form of dehydroascorbic acid with GLUT1 through hydrogen bonds with the -OH group of C3 and C5 were less favorable than the interactions with the sugars transported by GLUT1. The eight most relevant residues in such interactions (i.e., F26, Q161, I164, Q282, Y292, and W412) were mutated to alanine to perform functional studies for dehydroascorbic acid and the glucose analog, 2-deoxiglucose, in Xenopus laevis oocytes. All the mutants decreased the uptake of both substrates to less than 50%. The partial effect of the N317A mutant in transporting dehydroascorbic acid was associated with a 30% decrease in the Vmax compared to the wildtype GLUT1. The results show that both substrates share the eight residues studied in GLUT1, albeit with a differential contribution of N317. Our work, combining docking with functional studies, marks the first to identify structural determinants of oxidized vitamin C's transport via GLUT1.

Neuroprotective Properties of Eudesmin on a Cellular Model of Amyloid-ß Peptide Toxicity.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive impairment and memory loss. One of the hallmarks in AD is amyloid-ß peptide (Aß) accumulation, where the soluble oligomers of Aß (AßOs) are the most toxic species, deteriorating the synaptic function, membrane integrity, and neuronal structures, which ultimately lead to apoptosis. Currently, there are no drugs to arrest AD progression, and current scientific efforts are focused on searching for novel leads to control this disease. Lignans are compounds extracted from conifers and have several medicinal properties. Eudesmin (Eu) is an extractable lignan from the wood of Araucaria araucana, a native tree from Chile. This metabolite has shown a range of biological properties, including the ability to control inflammation and antibacterial effects. OBJECTIVE: In this study, the neuroprotective abilities of Eu on synaptic failure induced by AßOs were analyzed. METHODS: Using neuronal models, PC12 cells, and in silico simulations we evaluated the neuroprotective effect of Eu (30 nM) against the toxicity induced by AßOs. RESULTS: In primary cultures from mouse hippocampus, Eu preserved the synaptic structure against AßOs toxicity, maintaining stable levels of the presynaptic protein SV2 at the same concentration. Eu also averted synapsis failure from the AßOs toxicity by sustaining the frequencies of cytosolic Ca2+ transients. Finally, we found that Eu (30 nM) interacts with the Aß aggregation process inducing a decrease in AßOs toxicity, suggesting an alternative mechanism to explain the neuroprotective activity of Eu. CONCLUSION: We believe that Eu represents a novel lead that reduces the Aß toxicity, opening new research venues for lignans as neuroprotective agents.

Probióticos: una mirada al mecanismo de acción y aplicaciones clínicas en Pediatría

Introducción: Los probióticos son microorganismos vivos que brindan beneficios al huésped mediante diversos mecanismos de acción. Han sido fuente de estudio en diversas patologías pediátricas, mostrando algunos resultados prometedores. Objetivo: Elaborar una revisión de la literatura sobre los mecanismos de acción y la evidencia actual que tienen los probióticos sobre la salud infantil. Materiales y métodos: Se realizó una revisión narrativa de la literatura con estrategia de búsqueda sistemática de la literatura con términos MESH acerca de los mecanismos de acción de los probióticos y su uso. Se incluyeron metaanálisis, revisiones sistemáticas y ensayos clínicos aleatorizados. Resultados: Los probióticos son una nueva herramienta terapéutica usada para mejorar la salud infantil. Se ha encontrado efecto benéfico en diarrea, en enterocolitis necrosante con una disminución significativa de la mortalidad y se ha mostrado evidencia significativa en las horas de llanto en cólico del lactante. Conclusión: Se requieren más estudios en otro tipo de enfermedades como estreñimiento y en algunos procesos alérgicos e inflamatorios. Los ensayos revisados ofrecen un panorama prometedor, pero la elección de un probiótico debe ser personalizado de acuerdo con la edad, enfermedad, cepa y dosis, dado que cada uno de ellos tiene múltiples mecanismos de acción que impactan de manera diferente en la eficacia clínica.

Introduction: Prebiotics are living microorganisms that provide benefits to the host through various mechanisms of action. They have been a source of study in various pediatric pathologies showing some promising results. Objective: To prepare a review on the mechanisms of action and current evidence that prebiotics have on child health. Materials and methods: A narrative review of the literature was carried out with a systematic literature search strategy with MESH terms about the mechanisms of action of probiotics and their use. Meta-analyzes, systematic reviews, and randomized clinical trials were included. Results: Probiotics are a new therapeutic tool used to improve children's health. A beneficial effect has been found in diarrhea, in necrotizing enterocolitis with a significant decrease in mortality and significant evidence has been shown in the hours of crying in colic in infants. Conclusion: The trials reviewed offer a promising picture, but the choice of a probiotic must be customized according to the age, disease, bacterial strain and dose, since each one has different action mechanisms and clinical effectiveness. More studies are required in some allergic and inflammatory diseases.

The Impact of Treated Wastewater Irrigation on the Metabolism of Barley Grown in Arid and Semi-Arid Regions.

The use of treated wastewater (TWW) for irrigation has gained global attention since it reduces pressure on groundwater (GW) and surface water. This study aimed to evaluate the effect of TWW on agronomic, photosynthetic, stomatal, and nutritional characteristics of barley plants. The experiment with barley was established on two bands: one band was irrigated with GW and the other with TWW. The evaluation was performed 25, 40, 60, 90, and 115 days after sowing (DAS). Results showed that irrigation with TWW increased (p < 0.01) grain yield by 54.3% and forage yield by 39.4% compared to GW irrigation. In addition, it increased plant height (PH) (p = 0.013), chlorophyll concentration index (CCI) (p = 0.006), and leaf area index (LAI) (p = 0.002). TWW also produced a positive effect (p < 0.05) in all the photosynthetic efficiency parameters evaluated. Barley plants irrigated with TWW had lower stomatal density (SD) and area (SA) (p < 0.001) than plants irrigated with GW. Plants irrigated with TWW had a higher P concentration (p < 0.05) in stems and roots and K concentration in leaves than plants irrigated with GW. We concluded that the use of TWW induced important biochemical, physiological, and agronomic changes in barley plants. Hence, the use of TWW may be a sustainable alternative for barley production in arid and semi-arid regions. This study was part of a government project, which aimed to develop a new metropolitan irrigation district with TWW. This study may contribute to the sustainability of water resources and agricultural practices in northern Mexico.

Modulation of GABAA receptors and of GABAergic synapses by the natural alkaloid gelsemine.

The Gelsemium elegans plant preparations have shown beneficial activity against common diseases, including chronic pain and anxiety. Nevertheless, their clinical uses are limited by their toxicity. Gelsemine, one of the most abundant alkaloids in the Gelsemium plants, have replicated these therapeutic and toxic actions in experimental behavioral models. However, the molecular targets underlying these biological effects remain unclear. The behavioral activity profile of gelsemine suggests the involvement of GABAA receptors (GABAARs), which are the main biological targets of benzodiazepines (BDZs), a group of drugs with anxiolytic, hypnotic, and analgesic properties. Here, we aim to define the modulation of GABAARs by gelsemine, with a special focus on the subtypes involved in the BDZ actions. The gelsemine actions were determined by electrophysiological recordings of recombinant GABAARs expressed in HEK293 cells, and of native receptors in cortical neurons. Gelsemine inhibited the agonist-evoked currents of recombinant and native receptors. The functional inhibition was not associated with the BDZ binding site. We determined in addition that gelsemine diminished the frequency of GABAergic synaptic events, likely through a presynaptic modulation. Our findings establish gelsemine as a negative modulator of GABAARs and of GABAergic synaptic function. These pharmacological features discard direct anxiolytic or analgesic actions of gelsemine through GABAARs but support a role of GABAARs on the alkaloid induced toxicity. On the other hand, the presynaptic effects of the alkaloid provide an additional mechanism to explain their beneficial effects. Collectively, our results contribute novel information to improve understanding of gelsemine actions in the mammalian nervous system.

The Stimulatory Effects of Intracellular α-Synuclein on Synaptic Transmission Are Attenuated by 2-Octahydroisoquinolin-2(1H)-ylethanamine.

α-Synuclein (αSyn) species can be detected in synaptic boutons, where they play a crucial role in the pathogenesis of Parkinson's Disease (PD). However, the effects of intracellular αSyn species on synaptic transmission have not been thoroughly studied. Here, using patch-clamp recordings in hippocampal neurons, we report that αSyn oligomers (αSynO), intracellularly delivered through the patch electrode, produced a fast and potent effect on synaptic transmission, causing a substantial increase in the frequency, amplitude and transferred charge of spontaneous synaptic currents. We also found an increase in the frequency of miniature synaptic currents, suggesting an effect located at the presynaptic site of the synapsis. Furthermore, our in silico approximation using docking analysis and molecular dynamics simulations showed an interaction between a previously described small anti-amyloid beta (Aß) molecule, termed M30 (2-octahydroisoquinolin-2(1H)-ylethanamine), with a central hydrophobic region of αSyn. In line with this finding, our empirical data aimed to obtain oligomerization states with thioflavin T (ThT) and Western blot (WB) indicated that M30 interfered with αSyn aggregation and decreased the formation of higher-molecular-weight species. Furthermore, the effect of αSynO on synaptic physiology was also antagonized by M30, resulting in a decrease in the frequency, amplitude, and charge transferred of synaptic currents. Overall, the present results show an excitatory effect of intracellular αSyn low molecular-weight species, not previously described, that are able to affect synaptic transmission, and the potential of a small neuroactive molecule to interfere with the aggregation process and the synaptic effect of αSyn, suggesting that M30 could be a potential therapeutic strategy for synucleinopathies.

Design framework for metasurface optics-based convolutional neural networks.

Deep learning using convolutional neural networks (CNNs) has been shown to significantly outperform many conventional vision algorithms. Despite efforts to increase the CNN efficiency both algorithmically and with specialized hardware, deep learning remains difficult to deploy in resource-constrained environments. In this paper, we propose an end-to-end framework to explore how to optically compute the CNNs in free-space, much like a computational camera. Compared to existing free-space optics-based approaches that are limited to processing single-channel (i.e., gray scale) inputs, we propose the first general approach, based on nanoscale metasurface optics, that can process RGB input data. Our system achieves up to an order of magnitude energy savings and simplifies the sensor design, all the while sacrificing little network accuracy.

Boldine Attenuates Synaptic Failure and Mitochondrial Deregulation in Cellular Models of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common cause of senile dementia worldwide, characterized by both cognitive and behavioral deficits. Amyloid beta peptide (Aß) oligomers (AßO) have been found to be responsible for several pathological mechanisms during the development of AD, including altered cellular homeostasis and synaptic function, inevitably leading to cell death. Such AßO deleterious effects provide a way for identifying new molecules with potential anti-AD properties. Available treatments minimally improve AD symptoms and do not extensively target intracellular pathways affected by AßO. Naturally-derived compounds have been proposed as potential modifiers of Aß-induced neurodysfunction and cytotoxicity based on their availability and chemical diversity. Thus, the aim of this study was to evaluate boldine, an alkaloid derived from the bark and leaves of the Chilean tree Peumus boldus, and its capacity to block some dysfunctional processes caused by AßO. We examined the protective effect of boldine (1-10 µM) in primary hippocampal neurons and HT22 hippocampal-derived cell line treated with AßO (24-48 h). We found that boldine interacts with Aß in silico affecting its aggregation and protecting hippocampal neurons from synaptic failure induced by AßO. Boldine also normalized changes in intracellular Ca2+ levels associated to mitochondria or endoplasmic reticulum in HT22 cells treated with AßO. In addition, boldine completely rescued the decrease in mitochondrial membrane potential (ΔΨm) and the increase in mitochondrial reactive oxygen species, and attenuated AßO-induced decrease in mitochondrial respiration in HT22 hippocampal cells. We conclude that boldine provides neuroprotection in AD models by both direct interactions with Aß and by preventing oxidative stress and mitochondrial dysfunction. Additional studies are required to evaluate the effect of boldine on cognitive and behavioral deficits induced by Aß in vivo.

Phenotypic characterization and predictive analysis of p.Asp47Asn LDL receptor mutation associated with Familial Hypercholesterolemia in a Chilean population.

BACKGROUND: Familial hypercholesterolemia (FH) is an inherited disorder mainly caused by mutations in the LDL receptor (LDL-R) and characterized by elevation of low-density lipoprotein cholesterol (LDL-C) levels and premature cardiovascular disease. OBJECTIVE: In this study, we evaluated the clinical phenotype of the p.Asp47Asn, described as an uncertain pathogenic variant, and its effect on the structure of LDL-R and ligand interactions with apolipoproteins. METHODS: 27 children and adolescents with suspected FH diagnosis were recruited from a pediatric endocrinology outpatient clinic. Blood samples were collected after 12 h fasting for lipid profile analysis. DNA sequencing was performed for six FH-related genes by Ion Torrent PGM platform and copy number variation by MLPA. For index cases, a familial cascade screening was done restricted to the same mutation found in the index case. In silico analysis were developed to evaluate the binding capacity of LDL-R to apolipoproteins B100 and E. RESULTS: Lipid profile in children and adolescents demonstrated higher LDL-C levels in p.Asp47Asn carriers compared to the wild type genotype. In silico analysis predicted a reduction in the binding capacity of the ligand-binding modules LA1-2 of p.Asp47Asn LDL-R for ApoB100 and ApoE, which was not produced by local structural changes or folding defects but as a consequence of a decreased apparent affinity for both apolipoproteins. CONCLUSION: The clinical phenotype and the structural effects of p.Asp47Asn LDL-R mutation suggest that this variant associates to FH.

Inhibition of the Glycine Receptor alpha 3 Function by Colchicine.

Colchicine is a plant alkaloid that is widely used as a therapeutic agent. It is widely accepted that colchicine reduces the production of inflammatory mediators mainly by altering cytoskeleton dynamics due to its microtubule polymerization inhibitory activity. However, other lines of evidence have shown that colchicine exerts direct actions on the function of ion channels, which are independent of cytoskeleton alterations. Colchicine is able to modify the function of several pentameric ligand-gated ion channels, including glycine receptors (GlyRs). Previous electrophysiological studies have shown that colchicine act as an antagonist of GlyRs composed by the α 1 subunit. In addition, it was recently demonstrated that colchicine directly bind to the α 3 subunit of GlyRs. Interestingly, other studies have shown a main role of α 3GlyRs on chronic inflammatory pain. Nevertheless, the functional effects of colchicine on the α 3GlyR function are still unknown. Here, by using electrophysiological techniques and bioinformatics, we show that colchicine inhibited the function of the α 3GlyRs. Colchicine elicited concentration-dependent inhibitory effects on α 3GlyRs at micromolar range and decreased the apparent affinity for glycine. Single-channel recordings show that the colchicine inhibition is associated with a decrease in the open probability of the ion channel. Molecular docking assays suggest that colchicine preferentially bind to the orthosteric site in the closed state of the ion channel. Altogether, our results suggest that colchicine is a competitive antagonist of the α 3GlyRs.

Gabapentin Inhibits Multiple Steps in the Amyloid Beta Toxicity Cascade.

Oligomeric ß-amyloid peptide (Aß) is one of the main neurotoxic agents of Alzheimer's disease (AD). Oligomers associate to neuronal membranes, forming "pore-like" structures that cause intracellular calcium and neurotransmitter dyshomeostasis, leading to synaptic failure and death. Through molecular screening targeting the C terminal region of Aß, a region involved in the toxic properties of the peptide, we detected an FDA approved compound, gabapentin (GBP), with neuroprotective effects against Aß toxicity. At micromolar concentrations, GBP antagonized peptide aggregation over time and reduced the Aß absorbance plateau to 28% of control. In addition, GBP decreased Aß association to membranes by almost half, and the effects of Aß on intracellular calcium in hippocampal neurons were antagonized without causing effects on its own. Finally, we found that GBP was able to block the synaptotoxicity induced by Aß in hippocampal neurons, increasing post-synaptic currents from 1.7 ± 0.9 to 4.2 ± 0.7 fC and mean relative fluorescence intensity values of SV2, a synaptic protein, from 0.7 ± 0.09 to 1.00 ± 0.08. The results show that GBP can interfere with Aß-induced toxicity by blocking multiple steps, resulting in neuroprotection, which justifies advancing toward additional animal and human studies.

Validation of a novel equation to predict lower-limb muscle mass in young soccer players: a brief communication / Validación de una nueva ecuación para predecir la masa muscular de los miembros inferiores en jugadores jóvenes de fútbol: una comunicación breve

Lower-limbs appendicular muscle mass is a key body composition trait related to health and performance. Considering the relevance of lower-limbs appendicular muscle mass in soccer players, the assessment and monitoring of this variable with a low-cost tool would be of great value in order to improve performance through training and nutritional interventions. This study aimed to develop a multiple regression model in order to validate, through dual-energy X-ray absorptiometry, a novel equation to predict lower-limbs appendicular muscle mass in young soccer players using anthropometric variables. Forty-two soccer players of the Chilean National Team (age, 17.1±1.3 years; body mass, 70.0±6.8 kg; height, 175.0±6.6 cm) underwent anthropometrically and body composition assessments. Forward stepwise linear regression was used to develop the equation to estimate the lower-limb appendicular muscle mass. The estimated results were compared with measurements by dual-energy X-ray absorptiometry. The best predictor model to estimate lower-limbs appendicular muscle mass was (kg): (-21.268 + (0.087*height) - (0.853*middle thigh circumference) - (0.329*middle thigh skinfold) + (1.136*corrected middle thigh circumference) + (0.306*calf circumference)) (R2= 0.83). The lower-limbs appendicular muscle mass estimated by the equation and measured by DXA were similar (14.71±1.72 kg vs 14.76±1.89 kg, respectively), and have a good concordance according to Bland-Altman method (mean difference: 0.049 kg; 95 % IC: -1.481 to 1.578 kg) and Lin's concordance correlation coefficient (0.91; 95 % CI: 0.85 - 0.96) methods. In conclusion, the predictive equation is a valid, easy to calculate, and a low-cost tool to predict lower-limbs appendicular muscle mass in young soccer players.

La masa muscular de los miembros inferiores es un factor antropométrico clave relacionado a la salud y el rendimiento deportivo. Considerando la relevancia de este factor en jugadores de fútbol, la medición y monitoreo de esta variable a través de herramientas prácticas de bajo costo puede ser de gran utilidad para lograr objetivos relacionados a mejorar el rendimiento a través del entrenamiento e intervenciones nutricionales. El objetivo de este estudio fue desarrollar un modelo de regresión lineal con el objetivo de validar una nueva ecuación predictiva de la masa muscular de miembros inferiores en jugadores jóvenes de fútbol. Cuarenta y dos jugadores jóvenes de fútbol pertenecientes a la Selección Nacional Chilena (17,1±1,3 años; 70,0±6,8 kg; 175,0±6,6 cm) fueron sometidos a evaluaciones antropométricas y de composición corporal. La regresión lineal de pasos hacia adelante fue utilizada para desarrollar la ecuación para estimar la masa muscular de miembros inferiores. Los resultados estimados fueron comparados con medición de absorciometría de rayos X de doble energía (DEXA). El mejor modelo predictor de masa muscular de miembros inferiores (kg) fue: (-21,268 + (0,087*talla) - (0,853*circunferencia de muslo medio) - (0,329*pliegue de muslo medio) + (1,136*circunferencia de muslo medio corregida) + (0,306*circunferencia de pantorrilla)) (R2= 0,83). La masa muscular estimada por la ecuación y la medida por DEXA fue similar (14,71±1,72 kg vs 14,76±1,89 kg, respectivamente), y tuvo una buena concordancia acorde al método Bland-Altman (diferencia promedio: 0,049 kg; 95 % IC: -1,481 to 1,578 kg) y el coeficiente de correlación de concordancia de Lin (0,91; 95 % CI: 0,85 - 0,96). En conclusión, la ecuación predictiva desarrollada en este estudio es una herramienta válida, fácil de calcular y de bajo costo que permite estimar la masa muscular de miembros inferiores en futbolistas jóvenes.