Neurodevelopment Is Dependent on Maternal Diet: Placenta and Brain Glucose Transporters GLUT1 and GLUT3.

Glucose is the primary energy source for most mammalian cells and its transport is affected by a family of facilitative glucose transporters (GLUTs) encoded by the SLC2 gene. GLUT1 and GLUT3, highly expressed isoforms in the blood-brain barrier and neuronal membranes, respectively, are associated with multiple neurodevelopmental disorders including epilepsy, dyslexia, ADHD, and autism spectrum disorder (ASD). Dietary therapies, such as the ketogenic diet, are widely accepted treatments for patients with the GLUT1 deficiency syndrome, while ameliorating certain symptoms associated with GLUT3 deficiency in animal models. A ketogenic diet, high-fat diet, and calorie/energy restriction during prenatal and postnatal stages can also alter the placental and brain GLUTs expression with long-term consequences on neurobehavior. This review focuses primarily on the role of diet/energy perturbations upon GLUT isoform-mediated emergence of neurodevelopmental and neurodegenerative disorders.

Space Flight Enhances Stress Pathways in Human Neural Stem Cells.

Mammalian cells have evolved to function under Earth's gravity, but how they respond to microgravity remains largely unknown. Neural stem cells (NSCs) are essential for the maintenance of central nervous system (CNS) functions during development and the regeneration of all CNS cell populations. Here, we examined the behavior of space (SPC)-flown NSCs as they readapted to Earth's gravity. We found that most of these cells survived the space flight and self-renewed. Yet, some showed enhanced stress responses as well as autophagy-like behavior. To ascertain if the secretome from SPC-flown NSCs contained molecules inducing these responses, we incubated naïve, non-starved NSCs in a medium containing SPC-NSC secretome. We found a four-fold increase in stress responses. Proteomic analysis of the secretome revealed that the protein of the highest content produced by SPC-NSCs was secreted protein acidic and rich in cysteine (SPARC), which induces endoplasmic reticulum (ER) stress, resulting in the cell's demise. These results offer novel knowledge on the response of neural cells, particularly NSCs, subjected to space microgravity. Moreover, some secreted proteins have been identified as microgravity sensing, paving a new venue for future research aiming at targeting the SPARC metabolism. Although we did not establish a direct relationship between microgravity-induced stress and SPARC as a potential marker, these results represent the first step in the identification of gravity sensing molecules as targets to be modulated and to design effective countermeasures to mitigate intracranial hypertension in astronauts using structure-based protein design.

Enhancer-targeted CRISPR-Activation Rescues Haploinsufficient Autism Susceptibility Genes.

Autism Spectrum Disorder (ASD) is a highly heritable condition with diverse clinical presentations. Approximately 20% of ASD's genetic susceptibility is imparted by de novo mutations of major effect, most of which cause haploinsufficiency. We mapped enhancers of two high confidence autism genes - CHD8 and SCN2A and used CRISPR-based gene activation (CRISPR-A) in hPSC-derived excitatory neurons and cerebral forebrain organoids to correct the effects of haploinsufficiency, taking advantage of the presence of a wildtype allele of each gene and endogenous gene regulation. We found that CRISPR-A induced a sustained increase in CHD8 and SCN2A expression in treated neurons and organoids, with rescue of gene expression levels and mutation-associated phenotypes, including gene expression and physiology. These data support gene activation via targeting enhancers of haploinsufficient genes, as a therapeutic intervention in ASD and other neurodevelopmental disorders.

Survival of dental implants in oncology patients versus non-oncology patients: a 5-year retrospective study

Abstract Patients with a history of cancer are increasingly common in the dental office. Treating cancer patients requires a multidisciplinary team, which should include the dentist, in order to control the complications that occur in the oral cavity and also to recover the patient undergoing treatment in any of its types: surgical, medical, radiotherapeutic, or its possible combinations. Dental implants can be a safe and predictable treatment option for prosthetic rehabilitation. The aim of this paper is to describe in retrospect the success rate of osseointegrated implants in oncology and non-oncology patients placed by the Master of Dentistry in Oncology and Immunocompromised Patients, as well as the Master of Medicine, Surgery and Oral Implantology of the University of Barcelona Dental Hospital, between July 2011 and March 2016. 466 patients were reviewed, with a total of 1405 implants placed, considering the oncological history of the patients and the implant success rate. The total success rate in the concerned period was 96.65%. When comparing cancer patients with healthy ones, the success rate has been 93.02% in the first case, and 97.16% in the latter. According to the literature review, our results encourage implant placement in cancer patients, it is important to recognize that this is an analysis of a complex care pathway with a large number of confounding variables. However, the findings should not be considered as generalizable.

Resumo Pacientes com histórico de câncer são cada vez mais comuns no consultório odontológico. O tratamento de pacientes com câncer requer uma equipe multidisciplinar, que deve incluir o dentista, a fim de controlar as complicações que ocorrem na cavidade oral e também para tratar o paciente com qualquer uma das modalidades de tratamento: cirúrgica, médica, radioterápica ou suas possíveis combinações. Os implantes dentários podem ser uma opção de tratamento segura e previsível para reabilitação protética. O objetivo deste artigo é propor um estudo retrospectivo sobre a taxa de sucesso de implantes osseointegrados em pacientes oncológicos e não oncológicos atendidos no Mestrado em Odontologia em Pacientes Oncológicos e Imunodeprimidos, bem como no Mestrado em Medicina, Cirurgia e Implantodontia Oral do Hospital Odontológico da Universidade de Barcelona, entre julho de 2011 e março de 2016. Foram revisados 466 pacientes, com um total de 1405 implantes instalados, considerando o histórico oncológico dos pacientes e a taxa de sucesso do implante. Resultados: A taxa de sucesso total no período em questão foi de 96,65%. Na comparação entre pacientes com câncer e saudáveis, a taxa de sucesso foi de 93,02% no primeiro caso e 97,16% no segundo. Conclusão: De acordo com a revisão da literatura, nossos resultados encorajam a colocação de implantes em pacientes com câncer, é importante reconhecer que esta é uma análise complexa que requer cuidado devido ao grande número de variáveis. No entanto, os resultados não devem ser considerados de forma generalizada.

Estudio in vitro de la erosión dental asociada al chimó / In vitro study of dental erosion associated to Chimo

Antecedentes: Chimó es el nombre en Venezuela de una sustancia viscosa de color negruzco, cuyo componente principal deriva de la hoja de tabaco. Su consumo se ha asociado a alteraciones sistémicas y patologías bucales. Objetivo: Identificar in vitro la erosión dental asociada a exposición al chimó. Métodos: Se seleccionaron 30 dientes, 10 control negativo, 10 control positivo y 10 grupo experimental que se expusieron a soluciones de saliva artificial, Coca-Cola® light y chimó respectivamente, durante 20 semanas. Se analizó clínicamente la superficie y el análisis ultraestructural se efectuó con microscopio electrónico de barrido. Resultados: Clínicamente, se evidenció cambio de color en el grupo control negativo; cambio de color y superficial y pérdida de brillo en el grupo control positivo; y cambio de color y superficial en el grupo experimental (p = 0,000). El análisis ultraestructural indica que el grupo control negativo no presentó alteraciones morfológicas en la superficie del esmalte. En la escala de valores de grabado ácido utilizada, el grupo control positivo fue tipo 4 y el grupo experimental mostró estructura adamantina erosionada con imágenes similares a los patrones de grabado tipo 3-4. En cuanto a la clasificación según su gravedad, el grupo experimental correspondió al grado 1, con pérdida de esmalte sin involucrar dentina. Conclusión: En las condiciones experimentales de este estudio, el chimó produjo pérdida de la superficie del esmalte tanto clínica como ultraestructuralmente, con patrones de erosión tipos 3 y 4 de la escala de valores del grabado ácido y grado 1 según su gravedad.

Background: In Venezuela, chimó is a blackish goo derived from tobacco leaf. Its consumption has been associated with systemic and oral diseases. Purpose: To identify in vitro dental erosion associated to chimó exposure. Methods: The sample consisted of 30 teeth that were assigned 10 to the negative control group, another 10 to the positive control group, and 10 to the experimental group, which were exposed respectively to artificial saliva, Coca-Cola® light, and chimó for 20 weeks. Tooth surfaces were analyzed clinically and structurally, the latter through scanning electron microscope. Results: Clinical observations showed surface color change in the negative control group; color change and surface gloss loss in the positive control group; color and surface changes in the experimental group (p = 0.000). Ultrastructural analysis showed no enamel surface alterations in the negative control group. Acid etching scale values were 4 for the positive control group and 3-4 for the experimental group. The latter had signs of enamel erosion. In terms of severity of damage, the experimental group was type 1, that is, enamel loss without involving dentin. Conclusion: Under these experimental conditions, chimó caused clinical and ultrastructural enamel surface loss with type 3-4 erosion patterns, and type 1 severity.

Patrones EEG y clínicos de la epilepsia límbica inducida por ácido caínico en el gato / EEG and clinical patterns of limbic epilepsy induced by kainic acid in cats

Se describen los cambios EEG y conductuales en el gato tras la aplicación de ácido caínico en la amígdala. Estos cambios se manifiestan en tres fases consecutivas: a) fase inicial, b) fase convulsiva y c) fase de recuperación. En la fase inicial se observó una actividad EEG rápida en la amígdala inyectada y en el hipocampo ventral ipsolateral, la cual evolucionaba en descargas paroxísticas y dio inicio a la fase convulsiva. En esta fase los animales presentaron dos tipos de crisis límbicas: crisis locales o de tipo A y crisi propagadas o de tipo B. De manera concomitante a los cambios EEG, se presentaron diferentes manifestaciones clínicas; así, en las crisis de tipo A se presentaron mioclonías de la hemicara epsolateral al foc, movimientos masticatorios y salivación, mientras que las crisis de tipo B se acompañaron de una conducta de exploración