Publications by authors named "Sarah Fernandes"

Objective: Trigeminal schwannoma (TS), though a rare and benign tumor, becomes a significant surgical challenge due to its intricate location. This study aims to detail the long-term functional outcomes and tumor control post-surgical resection.

Method: We analyzed a multicentric retrospective cohort of 39 patients operated on for a TS in five tertiary centers between January 1993 and July 2022.

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Article Synopsis
  • Age-related neurodegenerative diseases, such as Alzheimer's, currently have no cure and limited treatment options, making them particularly difficult to manage.
  • Human stem cell-derived brain organoids offer a promising method to study Alzheimer's disease by mimicking human brain structure and pathology, which may help reveal how the disease affects neural cells and cognitive function.
  • This review examines the strategies for using brain organoids in Alzheimer's research while also discussing the challenges faced when studying age-related brain disorders with these models.
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Astrocytes, the most abundant glial cell type in the brain, are underrepresented in traditional cortical organoid models due to the delayed onset of cortical gliogenesis. Here we introduce a new glia-enriched cortical organoid model that exhibits accelerated astrogliogenesis. We demonstrated that induction of a gliogenic switch in a subset of progenitors enabled the rapid derivation of astroglial cells, which account for 25-31% of the cell population within 8-10 weeks of differentiation.

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Objective: Systematically review randomized controlled trials on the efficacy of cognitive training on executive functions in healthy older people.

Measures: The outcome measures were related to inhibitory control, working memory, and cognitive flexibility.

Results: Thirty-one trials were included in the systematic review and thirteen trials in the meta-analysis.

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Recent advances in genetics, molecular biology, and stem cell biology have accelerated our understanding of neuropsychiatric disorders, like autism spectrum disorder (ASD), major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ). This progress highlights the incredible complexity of both the human brain and mental illnesses from the biochemical to the cellular level. Contributing to the complexity of neuropsychiatric disorders are their polygenic nature, cellular and brain region interconnectivity, and dysregulation of human-specific neurodevelopmental processes.

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Brain organoids are proving to be physiologically relevant models for studying human brain development in terms of temporal transcriptional signature recapitulation, dynamic cytoarchitectural development, and functional electrophysiological maturation. Several studies have employed brain organoid technologies to elucidate human-specific processes of brain development, gene expression, and cellular maturation by comparing human-derived brain organoids to those of non-human primates (NHPs). Brain organoids have been established from a variety of NHP pluripotent stem cell (PSC) lines and many protocols are now available for generating brain organoids capable of reproducibly representing specific brain region identities.

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Differentiation of human pluripotent stem cells to small brain-like structures known as brain organoids offers an unprecedented opportunity to model human brain development and disease. To provide a vascularized and functional in vivo model of brain organoids, we established a method for transplanting human brain organoids into the adult mouse brain. Organoid grafts showed progressive neuronal differentiation and maturation, gliogenesis, integration of microglia, and growth of axons to multiple regions of the host brain.

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Cardiomyocytes derived from human embryonic stem cells (hESC-CMs) can improve the contractility of injured hearts.We hypothesized that mesodermal cardiovascular progenitors (hESC-CVPs), capable of generating vascular cells in addition to cardiomyocytes, would provide superior repair by contributing to multiple components of myocardium. We performed a head-to-head comparison of hESC-CMs and hESC-CVPs and compared these with the most commonly used clinical cell type, human bone marrow mononuclear cells (hBMMNCs).

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Background: Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) were recently shown to be capable of electromechanical integration following direct injection into intact or recently injured guinea pig hearts, and hESC-CM transplantation in recently injured hearts correlated with improvements in contractile function and a reduction in the incidence of arrhythmias. The present study was aimed at determining the ability of hESC-CMs to integrate and modulate electrical stability following transplantation in a chronic model of cardiac injury.

Methods And Results: At 28 days following cardiac cryoinjury, guinea pigs underwent intracardiac injection of hESC-CMs, noncardiac hESC derivatives (non-CMs), or vehicle.

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Inhibition of cardiac late Na(+) current (I(Na,L)) decreases sodium-dependent calcium overload in diseased hearts. Because INa,L is small in the absence of disease, its inhibition is not expected to significantly alter function of the normal heart. To test this hypothesis, we determined the effects of GS-458967 (GS967), a novel selective inhibitor of I(Na,L) (IC(50) = 0.

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Transplantation studies in mice and rats have shown that human embryonic-stem-cell-derived cardiomyocytes (hESC-CMs) can improve the function of infarcted hearts, but two critical issues related to their electrophysiological behaviour in vivo remain unresolved. First, the risk of arrhythmias following hESC-CM transplantation in injured hearts has not been determined. Second, the electromechanical integration of hESC-CMs in injured hearts has not been demonstrated, so it is unclear whether these cells improve contractile function directly through addition of new force-generating units.

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Poor cell retention and limited cell survival after grafting are major limitations of cell therapy. Recent studies showed that the use of matrices as vehicles at the time of cell injection can significantly improve cell engraftment by providing an appropriate structure and physical support for the injected cells. Properly designed matrices can also promote the organization of the cells into a functioning cardiac-like tissue and enhance integration between the host and the engrafted tissue.

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Introduction: Early randomized clinical trials of autologous bone marrow cardiac stem cell therapy have reported contradictory results highlighting the need for a better evaluation of protocol designs. This study was designed to quantify and compare whole body and heart cell distribution after intracoronary or peripheral intravenous injection of autologous bone marrow mononuclear cells in a porcine acute myocardial infarction model with late reperfusion.

Methods: Myocardial infarction was induced using balloon inflation in the left coronary artery in domestic pigs.

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Cell-based therapies have great potential for the treatment of cardiovascular diseases. Recently, using a transgenic mouse model Roell et al. reported that cardiac engraftment of connexin43 (Cx43)-overexpressing myoblasts in vivo prevents post-infarct arrhythmia, a common cause of death in patients following heart attack.

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Background: Small scale clinical trials suggested the feasibility and the efficacy of autologous myoblast transplantation to improve ventricular function after myocardial infarction. However, these trials were hampered by unexpected episodes of life-threatening ventricular tachyarrhythmias (VT). We investigated cardiac electrical stability after myoblast transplantation to the myocardium.

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Over the past decade, numerous nonviral cationic vectors have been synthesized. They share a high density of positive charges and efficiency for gene transfer in vitro. However, their positively charged surface causes instability in body fluids and cytotoxicity, thereby limiting their efficacy in vivo.

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