Resveratrol and its metabolites elicit neuroprotection via high-affinity binding to the laminin receptor at low nanomolar concentrations.

Resveratrol prevents various neurodegenerative diseases in animal models despite reaching only low nanomolar concentrations in the brain after oral administration. In this study, based on the quenching of intrinsic tryptophan fluorescence and molecular docking, we found that trans-resveratrol, its conjugates (glucuronide and sulfate), and dihydro-resveratrol (intestinal microbial metabolite) bind with high affinities (Kd, 0.2-2 nm) to the peptide G palindromic sequence (near glycosaminoglycan-binding motif) of the 67-kDa laminin receptor (67LR). Preconditioning with low concentrations (0.01-10 nm) of these polyphenols, especially resveratrol-glucuronide, protected neuronal cells from death induced by serum withdrawal via activation of cAMP-mediated signaling pathways. This protection was prevented by a 67LR-blocking antibody, suggesting a role for this cell-surface receptor in neuroprotection by resveratrol metabolites.

Flavonoid quercetin and its glucuronide and sulfate conjugates bind to 67-kDa laminin receptor and prevent neuronal cell death induced by serum starvation.

Quercetin, a dietary flavonoid, has been shown to protect against various neurodegenerative diseases with mechanisms largely unknown. After oral administration, quercetin is rapidly conjugated, and the aglycone is not detectable in the plasma and brain. However, its glucuronide and sulfate conjugates are present only at low nanomolar concentrations in the brain. Since quercetin and its conjugates have limited antioxidant capability at low nanomolar concentrations, it is crucial to determine whether they induce neuroprotection by binding to high-affinity receptors. Previously we found that (-)-epigallocatechin-3-gallate (EGCG), a polyphenol from green tea, induces neuroprotection by binding to the 67-kDa laminin receptor (67LR). Therefore, in this study, we determined whether quercetin and its conjugates bind 67LR to induce neuroprotection and compared their ability with EGCG. Based on the quenching of intrinsic tryptophan fluorescence of peptide G (residues 161-180 in 67LR), we found quercetin, quercetin-3-O-glucuronide, and quercetin-3-O-sulfate bind to this peptide with a high affinity comparable to EGCG. Molecular docking using the crystal structure of 37-kDa laminin receptor precursor supported the high-affinity binding of all these ligands to the site corresponding to peptide G. A pretreatment with quercetin (1-1000 nM) did not effectively protect Neuroscreen-1 cells from death induced by serum starvation. Contrarily, a pretreatment with low concentrations (1-10 nM) of quercetin conjugates better protected these cells than quercetin and EGCG. The 67LR-blocking antibody substantially prevented neuroprotection by all these agents, suggesting the role of 67LR in this process. Collectively, these studies reveal that quercetin induces neuroprotection primarily through its conjugates via high affinity binding to 67LR.

Evaluation of Nursing School Educators' Knowledge and Attitudes Regarding Infant Sleep Safety.

AIM: The purpose of this study was to evaluate nursing educators' attitudes and knowledge regarding current American Academy of Pediatrics recommendations for a safe infant sleeping environment. METHOD: This was a cross-sectional prospective survey of all nursing programs with associate degrees or higher in the United States. Instructors teaching pediatric and obstetric didactic or clinical material at an Accreditation Commission for Education in Nursing-approved nursing school could participate. RESULTS: Of 396 educators surveyed, 70 percent identified all sudden infant death syndrome risk factors. Correct responses for individual safe sleep recommendations ranged from 99 percent for correct room temperature to 53 percent for pacifier use; 9 percent said it was safest for infants to sleep in a position other than on the back. CONCLUSION: Nursing educators need ongoing training on infant sleep safety to maintain mastery of the information that students need for competency in the workforce involving infant care.

Conocimientos, actitudes, susceptibilidad y autoeficacia frente a la infección por VIH en adolescentes de Cartagena, Colombia / Knowledge, attitudes, susceptibility and self-efficacy against HIV infection in adolescents from Cartagena, Colombia

Resumen Objetivo: Determinar los conocimientos, actitudes, susceptibilidad y autoeficacia frente a la infección por VIH en adolescentes escolarizados de la ciudad de Cartagena. Materiales y métodos: Estudio descriptivo transversal, con una población de referencia de 15.686 adolescentes de instituciones educativas oficiales matriculados en los grados 10º y 11º. Se estimó una muestra de 580 adolescentes, aplicando un muestreo multi-etapico probabilístico. Para la recolección de los datos se utilizó la Escala VIH/SIDA-65 , previo consentimiento informado. Los datos fueron procesados en el programa Microsoft Excel y analizados utilizando estadística descriptiva. Resultados: Un total de 579 adolescentes completaron satisfactoriamente el cuestionario, con un promedio de edad de 15,6 años (DE = 0,9 años), mayoritariamente de sexo femenino (65,6% (380)). El 45% (261) presenta conocimientos deficientes, 55% (318) ideas erróneas sobre la enfermedad, 69,6% (400) mostraron actitudes negativas, 46,1% (266) no se consideran susceptibles para contraer la enfermedad y 49,5% (286) mostró baja autoeficacia para la prevención de la infección. Conclusión: Los pocos conocimientos sobre el VIH y sus modos de transmisión, mezclados con ideas erróneas aumentan la probabilidad de contraer la infección entre los adolescentes, sobre todo, cuando se suman actitudes negativas, baja percepción de susceptibilidad y poca autoeficacia para la prevención.

Abstract Objective: To determine knowledge, attitudes, susceptibility and self-efficacy facing HIV infection in school adolescents in the city of Cartagena. Materials and methods: A descriptive cross-sectional study was made with a reference population of 15,686 adolescents from formal educational institutions who are enrolled in tenth and eleventh grades. A sample of 580 adolescents was estimated, and a probabilistic multi-stage sample was applied. The HIV/AIDS-65 Scale was used for data collection, previous informed consent. The data were processed using the Microsoft Excel program and were analyzed using descriptive statistics. Results: A total of 579 adolescents with an average age of 15.6 years (= 0.9 years), mainly of female sex (65.6% (380)) successfully completed the questionnaire. The 45% (261) presents deficient knowledge, 55% (318) presents misconceptions about the disease, 69.6% (400) showed negative attitudes, 46.1% (266) do not considered themselves susceptible to contract the disease and 49.5% (286) showed low self-efficacy for the prevention of the infection. Conclusion: Little knowledge about HIV and its modes of transmission, mixed with misconceptions, increases the likelihood of infection among adolescents, especially when negative attitudes, low perception of susceptibility and little self-efficacy for prevention are combined.

Neuroprotection by a novel NMDAR functional glycine site partial agonist, GLYX-13.

GLYX-13 (threonine-proline-proline-threonine-amide) is an amidated di-pyrrolidine that acts as a functional partial agonist at the glycine site on N-methyl-D-aspartate glutamate receptors (NMDARs). GLYX-13 can both increase NMDAR conductance at NR2B-containing receptors, and reduce conductance of non-NR2B-containing receptors. Here, we report that GLYX-13 potently reduces delayed (24 h) death of CA1 pyramidal neurons produced by bilateral carotid occlusion in Mongolian gerbils, when administered up to 5 h post-ischemia. GLYX-13 also reduced delayed (24 h) neuronal death of CA1, CA3, and dentate gyrus principal neurons elicited by oxygen/glucose deprivation in in-vitro hippocampal organotypic slice cultures, when applied up to 2 h post-oxygen/glucose deprivation. The glycine site full agonist D-serine completely occluded neuroprotection, indicating that GLYX-13 acts by modulating activation of this site.