关键词： Brain organoid   Stem cell   Neurological disease   Disease modeling   3D culture  

摘要： Neurological disorders are challenging to study given the complexity and species-specific features of the organ system. Brain organoids are three dimensional structured aggregates of neural tissue that are generated by self-organization and differentiation from pluripotent stem cells under optimized culture conditions. These brain organoids exhibit similar features of structural organization and cell type diversity as the developing human brain, creating opportunities to recapitulate disease phenotypes that are not otherwise accessible. Here we review the initial attempt in the field to apply brain organoid models for the study of many different types of human neurological disorders across a wide range of etiologies and pathophysiologies. Forthcoming advancements in both brain organoid technology as well as analytical methods have significant potentials to advance the understanding of neurological disorders and to uncover opportunities for meaningful therapeutic intervention.

摘要： Spine injuries have substantial impact on quality of life, especially when neurologic injury is present, with significant associated healthcare costs. Most spine injuries occur within the thoracolumbar spine, with burst fractures representing a notable proportion. Unstable burst fractures with neurologic deficits come with difficult evaluation and management decisions. Treatment of these injuries has substantially evolved over the last 2 decades. Options for operative management include anterior, posterior, and combined anterior-posterior approaches. Posterior approaches allow for stabilization of fractures, but come with challenges of performing an adequate decompression in the setting of neurologic deficit. Anterior approaches allow for direct decompression, but traditional approaches have noteworthy complications. Growth of minimally invasive spine surgery has helped to mitigate some risks associated with traditional open approaches. Minimally invasive anterior decompression with percutaneous posterior stabilization represents a reasonable management option in unstable thoracolumbar burst fractures with neurologic deficit. © 2021

关键词： axonal sprouting   conditioned medium   ischemic stroke   mesenchymal stem cells   synaptic plasticity  

摘要： The transplantation of mesenchymal stem cells (MSCs) is of main approaches in regenerative therapy for stroke. Due to the potential tumorigenicity and low survival rate of transplanted cells, focuses have been shifted from cell replacement to their paracrine effects. Therefore, stem cell-conditioned medium (CM) therapy has emerged as an alternative candidate. Here, we investigated the effect of CM derived from human embryonic MSCs on experimental ischemic stroke. Wistar rats underwent ischemic stroke by the right middle cerebral artery occlusion (MCAO). CM was infused either one time (1 hr post-MCAO) or three times (1, 24, and 48 hr post-MCAO) through guide cannula into the left lateral ventricle. Neurological functions were evaluated using Bederson's test and modified Neurological Severity Score on Days 1, 3, and 7 following MCAO. Infarction volumes and cerebral edema were measured on Days 3 and 7. growth-associated protein-43, synaptophysin, cAMP response element-binding protein, and phosphorylated-cAMP response element-binding protein levels were also assessed in peri-ischemic cortical tissue on Day 7 postsurgery. Our results indicated that three times injections of CM could significantly reduce body weight loss, mortality rate, infarct volumes, cerebral edema, and improve neurological deficits in MCAO rats. Moreover, three injections of CM could restore decreased levels of synaptic markers in MCAO rats up to its normal levels observed in the sham group. Our data suggest that using the CM obtained from embryonic stem cells-MSCs could be a potent therapeutic approach to attenuate cerebral ischemia insults which may be partly mediated through modulation of synaptic plasticity.

关键词： Diabetic ketoacidosis   Hypophosphatemia   Phosphate  

摘要： Insulin treatment for diabetic ketoacidosis occasionally results in hypophosphatemia, which is often mild and does not require treatment. However, we experienced a case in which intravenous insulin administration resulted in myocardial injury and altered consciousness despite mild hypophosphatemia. Phosphate replacement therapy resulted in a marked improvement in symptoms. As overlapping conditions that result in hypophosphatemia can cause severe complications after insulin therapy for diabetic ketoacidosis, even in patients with mild hypophosphatemia, physicians should pay more attention to changes in phosphate levels in patients undergoing treatment for diabetic ketoacidosis.

关键词： Pediatrics   terminal care   DNAR orders  

摘要： Context. For parents, family, or clinicians of children with rare life-threatening conditions, there is little information regarding likely symptoms, illness trajectory, and end-of-life care. Objectives. This descriptive analysis of a bereaved cohort recruited in the charting the territory study describes patient characteristics, symptoms, use of medications, discussion of resuscitation orders, and care provided preceding and during the end of life. Methods. Of the 275 children enrolled in the Charting the Territory study, 54 died between 2009 and 2014. Baseline demographic information, symptoms, interventions, and medical information were collected via chart review, interviews, and surveys. Results. Fifty-one of the 54 children had complete medical records. Of the seven symptoms evaluated, children were found to have an increase in median symptoms from baseline (n = 2) to time of death (n = 3). Opioids were used in the last 48 hours of life in 29 (56.9%) children, whereas only eight (15.7%) were receiving opioids at baseline. Do Not Attempt Resuscitation orders were in place at baseline in 17 (33.3%) children, increasing to 33 (64.7%) at time of death. Death occurred in a hospice setting in 16 (31.4%) children. Conclusion. Although much emphasis on pediatric palliative care has been on supportive treatment and symptom management, when faced with a lack of sound understanding of a rare illness, the mode of care can often be reactive and based on critical needs. By developing greater knowledge of symptoms and illness trajectory, both management and care can be more responsive and anticipatory, thereby helping ease illness burden and suffering. (C) 2020 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved. Key Words

关键词： Out-of-hospital cardiac arrest   Emergency medical services   Advanced cardiac life support   Endotracheal intubation   Supraglottic airway   Mechanical ventilation   Return of spontaneous circulation  

摘要： Background: Out-of-hospital cardiac arrest (OHCA) studies have focused on the benefits and harms of placing an intra-arrest advanced airway, but few studies have evaluated the benefits and harms after successful placement. We hypothesize that increased time in the tumultuous prehospital environment after intra-arrest advanced airway placement results in reduced patient survival. Methods: This was a secondary analysis of adult, non-traumatic, OHCA patients with an advanced airway placed in the PRIMED trial. The exposure variable was the time interval between successful advanced airway placement and Emergency Department (ED) arrival. The outcome was cerebral performance category (CPC) 1 or 2 at hospital discharge. Multivariable logistic regression, adjusted for Utstein variables and resuscitation-associated time intervals, was used to estimate adjusted odds ratios (aOR). Results: The cohort of complete cases included 4779 patients. The median time exposed to a prehospital advanced airway was 27 min (IQR 20-35). The total prehospital time was 39.4 min (IQR 32.3-48.1). An advanced airway was placed intra-arrest in 3830 cases (80.1%) and post-return of spontaneous circulation (post-ROSC) in 949 cases (19.9%). Overall, 486 (10.2%) of the cohort achieved the CPC outcome, but this was higher in the post-ROSC (21.7%) versus intra-arrest (7.5%) cohort. CPC was not associated with the time interval from advanced airway placement to ED arrival in the intra-arrest airway cohort (aOR 0.98, 95%CI 0.94-1.01). Conclusions: In OHCA patients who receive an intra-arrest advanced airway, longer time intervals exposed to a prehospital advanced airway are not associated with reduced patient survival.

关键词： Genetic murine models   Interval timing   Peak interval procedure   Neurodegenerative disorders   Neurodevelopmental disorders  

摘要： How timing behavior is altered in different neurodevelopmental and neurodegenerative disorders is a contemporary research question. Genetic murine models (GMM) that offer high construct validity also serve as useful tools to investigate this question. But the literature on timing behavior of different GMMs largely remains to be consolidated. The current paper addresses this gap by reviewing studies that have been conducted with GMMs of neurodevelopmental (e.g. ADHD, schizophrenia, autism spectrum disorder), neurodegenerative disorders (e.g., Alzheimer's disease, Huntington's disease) as well as circadian and other mutant lines. The review focuses on those studies that specifically utilized the peak interval procedure to improve the comparability of findings both within and between different disease models. The reviewed studies revealed timing deficits that are characteristic of different disorders. Specifically, Huntington's disease models had weaker temporal control over the termination of their anticipatory responses, Alzheimer's disease models had earlier timed responses, schizophrenia models had weaker temporal control, circadian mutants had shifted timed responses consistent with shifts in the circadian periods. The differences in timing behavior were less consistent for other conditions such as attention deficit and hyperactivity disorder and mutations related to intellectual disability. We discuss the implications of these findings for the neural basis of an internal stopwatch. Finally, we make methodological recommendations for future research for improving the comparability of the timing behavior across different murine models.