Postnatal administration of allopregnanolone modifies glutamate release but Not BDNF content in striatum samples of rats prenatally exposed to ethanol

Ethanol consumption during pregnancy may induce profound changes in fetal CNS development. We postulate that some of the effects of ethanol on striatal glutamatergic transmission and neurotrophin expression could be modulated by allopregnanolone, a neurosteroid modulator of GABA A receptor activity. We describe the acute pharmacological effect of allopregnanolone (65 μg/kg, s.c.) administered to juvenile male rats (day 21 of age) on the corticostriatal glutamatergic pathway, in both control and prenatally ethanol-exposed rats (two ip injections of 2.9 g/kg in 24% v/v saline solution on gestational day 8). Prenatal ethanol administration decreased the K+-induced release of glutamate regarding the control group. Interestingly, this effect was reverted by allopregnanolone. Regarding BDNF, allopregnanolone decreases the content of this neurotrophic factor in the striatum of control groups. However, both ethanol alone and ethanol plus allopregnanolone treated animals did not show any change regarding control values. We suggest that prenatal ethanol exposure may produce an alteration of GABA A receptors which blocks the GABA agonist-like effect of allopregnanolone on rapid glutamate release, thus disturbing normal neural transmission. Furthermore, the reciprocal interactions found between GABAergic neurosteroids and BDNF could underlie mechanisms operating during the neuronal plasticity of fetal development.Fil: Yunes, Roberto Miguel Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Medicas; ArgentinaFil: Estrella, Cecilia R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: García Menéndez, Sebastián Marcelo Manuel. Universidad Nacional de Cuyo. Facultad de Ciencias Medicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Lara, Hernán E.. Universidad de Chile; ChileFil: Cabrera Kreiker, Ricardo Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin

Discovery, optimization, and target identification of novel coumarin derivatives as HIV-1 reverse transcriptase-associated ribonuclease H inhibitors

Despite significant advances in antiretroviral therapy, acquired immunodeficiency syndrome remains as one of the leading causes of death worldwide. New antiretroviral drugs combined with updated treatment strategies are needed to improve convenience, tolerability, safety, and antiviral efficacy of available therapies. In this work, a focused library of coumarin derivatives was exploited by cell phenotypic screening to discover novel inhibitors of HIV-1 replication. Five compounds (DW-3, DW-4, DW-11, DW-25 and DW-31) showed moderate activity against wild-type and drug-resistant strains of HIV-1 (IIIB and RES056). Four of those molecules were identified as inhibitors of the viral RT-associated RNase H. Structural modification of the most potent DW-3 and DW-4 led to the discovery of compound 8a. This molecule showed increased potency against wild-type HIV-1 strain (EC = 3.94 ± 0.22 μM) and retained activity against a panel of mutant strains, showing EC values ranging from 5.62 μM to 202 μM. In enzymatic assays, 8a was found to inhibit the viral RNase H with an IC of 12.3 μM. Molecular docking studies revealed that 8a could adopt a binding mode similar to that previously reported for other active site HIV-1 RNase H inhibitors.Natural Science Foundation of China (NSFC Nos. 81973181, 81903453), Shandong Provincial Key research and development project (Nos. 2019JZZY021011), Shandong Provincial Natural Science Foundation (ZR2019BH011, ZR2020YQ61, ZR2020JQ31), Foreign cultural and educational experts Project (GXL20200015001), Qilu Young Scholars Program of Shandong University, the Taishan Scholar Program at Shandong Province, and KU Leuven (GOA 10/014). Work in Madrid was supported by the Spanish Ministry of Science and Innovation (grant PID2019-104176RB-I00/AEI/10.13039/501100011033), and an institutional grant of Fundación Ramón Areces (Madrid, Spain)

Novel indolylarylsulfone derivatives as covalent HIV-1 reverse transcriptase inhibitors specifically targeting the drug-resistant mutant Y181C

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are widely used in combination therapies against HIV-1. However, emergent and transmitted drug resistance compromise their efficacy in the clinical setting. Y181C is selected in patients receiving nevirapine, etravirine and rilpivirine, and together with K103N is the most prevalent NNRTI-associated mutation in HIV-infected patients. Herein, we report on the design, synthesis and biological evaluation of a novel series of indolylarylsulfones bearing acrylamide or ethylene sulfonamide reactive groups as warheads to inactivate Cys181-containing HIV-1 RT via a Michael addition reaction. Compounds I-7 and I-9 demonstrated higher selectivity towards the Y181C mutant than against the wild-type RT, in nucleotide incorporation inhibition assays. The larger size of the NNRTI binding pocket in the mutant enzyme facilitates a better fit for the active compounds, while stacking interactions with Phe227 and Pro236 contribute to inhibitor binding. Mass spectrometry data were consistent with the covalent modification of the RT, although off-target reactivity constitutes a major limitation for further development of the described inhibitors.by grants PID2019-104176RB-I00/AEI/10.13039/501100011033) (Spanish Ministry of Science and Innovation) and 2019AEP001 (CSIC), as well as an institutional grant of Fundación Ramón Areces (awarded to the CBMSO)

Bariatric surgery in women in reproductive age: recommendations from the “Diabetes and Pregnancy” and “Diabetes and Obesity” working committees from the Argentine Society of Diabetes

El incremento de la obesidad en el mundo, a edades más tempranas, ha tenido un impacto negativo especialmente en las mujeres en edad reproductiva. Se ven afectadas tanto la fertilidad como la tasa de embarazos de riesgo, de niños con bajo peso al nacer, pretérmino e índice de cesáreas. La cirugía bariátrica como alternativa de tratamiento de la obesidad ha mejorado la fertilidad, pero el trastorno malabsortivo que provoca modifica la absorción de nutrientes en la madre y en el feto. El diagnóstico de diabetes gestacional se dificulta dado que la prueba de tolerancia oral a la glucosa estaría contraindicada en estos casos. El objetivo de estas recomendaciones es proveer herramientas para el control y seguimiento de mujeres en edad reproductiva sometidas a cirugía bariátrica.Worldwide increased obesity prevalence at early ages particularly affects women of reproductive ages. Both fertility and risk pregnancy rates are affected, of low birth weight infants, prematures and cesarean section rates have been modified considerably. Bariatric surgery is a validated tool to improve fertility but nutrient malabsorption as a consequence of surgery could affect mother and fetus nutrition and development. Gestational diabetes diagnosis turns difficult in this group of obese patients after bariatric surgery since oral glucose tolerance testing would be contraindicated in these cases. The aim of these recommendations was to offer tools for a good control and follow up of women at reproductive age.Fil: Gutt, Susana. Hospital Italiano de Buenos Aires; ArgentinaFil: Rovira, Gabriela. Universidad de Buenos Aires. Facultad de Medicina. Sede Hospital Britanico Bs.as; ArgentinaFil: Jawerbaum, Alicia Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Espinoza, Frank. Instituto Cardiovascular Lezica; ArgentinaFil: Mociulsky, Juliana. Clínica de Nutrición y Salud Dr. Cormillot; ArgentinaFil: Sucani, Stella. Provincia de Misiones. Hospital Escuela de Agudos Dr. Ramon Madariaga; ArgentinaFil: Kojdamanian, Verónica. Centro de Educación, Prevención y Asistencia al paciente diabético; ArgentinaFil: Aguirre Ackermann, Marianela. Centro Integral de Endocrinología y Nutrición; ArgentinaFil: Álvarez, María Graciela. Centro de Estudio y Tratamiento de la Obesidad Severa; ArgentinaFil: Camaño, Alejandro. Centro Médico de Especialidades y Diagnósticos Privado para la Salud; ArgentinaFil: Glatstein, Liliana. Centro Médico San Andrés; ArgentinaFil: Lifszyc, Paula. Hospital Carlos G. Durand; ArgentinaFil: Gómez Martin, Carolina. Centro Integral de Endocrinología y Diabetes; ArgentinaFil: Mendes, Patricio. Maternidad San Lucas; ArgentinaFil: Menéndez, Estrella. Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno; ArgentinaFil: Yuma, María. Hospital Italiano de Buenos Aires; ArgentinaFil: Bertona, Celina. Universidad Nacional de Cuyo; ArgentinaFil: Cafaro, Lilia. Obesidad y Cirugía Mini Invasiva; ArgentinaFil: Fuentes, Susana. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad En Red El Cruce Dr. Nestor Carlos Kirchner Samic; ArgentinaFil: Salzberg, Susana. Instituto Centenario; ArgentinaFil: Basualdo, Natalia. Hospital Materno Infantil Ramón Sardá; ArgentinaFil: González, Sandra . Cínica IMA; ArgentinaFil: Villarroel Parra, Beatriz. Hospital de Agudos Dalmacio Vélez Sarsfield; Argentina. Sanatorio Santa Isabel; ArgentinaFil: Musso, Carla. Fundacion Favaloro; Argentin

Minimally Invasive Autopsy Practice in COVID-19 Cases: Biosafety and Findings

Postmortem studies are crucial for providing insight into emergent diseases. However, a complete autopsy is frequently not feasible in highly transmissible diseases due to biohazard challenges. Minimally invasive autopsy (MIA) is a needle-based approach aimed at collecting samples of key organs without opening the body, which may be a valid alternative in these cases. We aimed to: (a) provide biosafety guidelines for conducting MIAs in COVID-19 cases, (b) compare the performance of MIA versus complete autopsy, and (c) evaluate the safety of the procedure. Between October and December 2020, MIAs were conducted in six deceased patients with PCR-confirmed COVID-19, in a basic autopsy room, with reinforced personal protective equipment. Samples from the lungs and key organs were successfully obtained in all cases. A complete autopsy was performed on the same body immediately after the MIA. The diagnoses of the MIA matched those of the complete autopsy. In four patients, COVID-19 was the main cause of death, being responsible for the different stages of diffuse alveolar damage. No COVID-19 infection was detected in the personnel performing the MIAs or complete autopsies. In conclusion, MIA might be a feasible, adequate and safe alternative for cause of death investigation in COVID-19 cases

Reverse Transcriptase: From Transcriptomics to Genome Editing

Reverse transcriptases (RTs) are enzymes that can generate a complementary strand of DNA (cDNA) from RNA. Coupled with PCR, RTs have been widely used to detect RNAs and to clone expressed genes. Classical retroviral RTs have been improved by protein engineering. These enzymes and newly characterized RTs are key elements in the development of next-generation sequencing techniques that are now being applied to the study of transcriptomics. In addition, engineered RTs fused to a CRISPR/Cas9 nickase have recently shown great potential as tools to manipulate eukaryotic genomes. In this review, we discuss the properties and uses of wild type and engineered RTs in biotechnological applications, from conventional RT-PCR to recently introduced prime editing.Ministry of Science and Innovation of Spain (grant BIO2016‐76716‐R (AEI/FEDER, UE)), and Consejo Superior de Investigaciones Científicas (2019AEP001). S.M.‐A. is a predoctoral fellow of the Ministry of Science and Innovation of Spain (BES‐2017‐079836). An institutional grant to CBMSO of Fundación Ramón Arece

Dificultades de aprendizaje en Educación Superior: un reto para la comunidad universitaria

El número de estudiantes con Dificultades del Aprendizaje que accede a entornos universitarios está aumentando, lo que pone en relieve la importancia de realizar adaptaciones que se correspondan con las necesidades de este nuevo alumnado. Con el objetivo de analizar las barreras percibidas por estos estudiantes, se realiza una revisión sistemática a través de la base de datos Web of Science, sin restricción de fecha, utilizando un concepto amplio de dificultades de aprendizaje y combinado los siguientes descriptores: learning disabilities, highereducation, university, barriers. Se seleccionan, examinan y comparan un total de 23 artículos. Del análisis realizado se desprende que, si bien se están realizando esfuerzos por elaborar adaptaciones de calidad que se correspondan con las demandas de los estudiantes con Dificultades del Aprendizaje, las barreras aún parecen ser más numerosas que los sistemas de apoyo implantados. Las implicaciones a corto y largo plazo se analizan en la discusión

Revista de psicología y educación

Título, resumen, palabras clave en español e inglesResumen basado en el de la publicaciónSe analizan las propiedades psicométricas del Cuestionario de Conocimiento Autorregulatorio (CEA) en estudiantes universitarios (CEA-U). En base a un diseño de medidas repetidas (dos medidas con un intervalo temporal de seis meses) se ha aplicado el instrumento de evaluación a una amplia muestra de estudiantes de las titulaciones de psicología y educación. La validez y la fiabilidad de la escala se estudió por una doble vía : la validez estructural y la predictiva; así como la fiabilidad por consistencia interna y test-retest. Se muestra en los resultados al CEA-U como un instrumento válido y fiable para su utilización con estudiantes universitarios.ES