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A closed 3D printed microfluidic device for automated growth and differentiation of cerebral organoids from single-cell suspension

1 Oct

A closed 3D printed microfluidic device for automated growth and differentiation of cerebral organoids from single-cell suspension

The development of 3D organoids has provided a valuable tool for studying human tissue and organ development in vitro. Cerebral organoids, in particular, offer a unique platform for investigating neural diseases. However, current methods for generating cerebral organoids suffer from limitations such as labor-intensive protocols and high heterogeneity among organoids. To address these challenges, we present a microfluidic device designed to automate and streamline the formation and differentiation of cerebral organoids. The device utilizes microwells with two different shapes to promote the formation of a single aggregate per well and incorporates continuous medium flow for optimal nutrient exchange. In silico simulations supported the effectiveness of the microfluidic chip in replicating cellular microenvironments. Our results demonstrate that the microfluidic chip enables uniform growth of cerebral organoids, significantly reducing the hands-on time required for maintenance. Importantly, the performance of the microfluidic system is comparable to the standard 96-well plate format even when using half the amount of culture medium, and the resulting organoids exhibit substantially developed neuroepithelial buds and cortical structures. This study highlights the potential of custom-designed microfluidic technology in improving the efficiency of cerebral organoid culture.

REACT: a randomized trial to assess the efficacy and safety of clazosentan for preventing clinical deterioration due to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

13 Sep

REACT: a randomized trial to assess the efficacy and safety of clazosentan for preventing clinical deterioration due to delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

Objective: Ischemic complications account for significant patient morbidity following aneurysmal subarachnoid hemorrhage (aSAH). The Prevention and Treatment of Vasospasm with Clazosentan (REACT) study was designed to assess the safety and efficacy of clazosentan, an endothelin receptor antagonist, in preventing clinical deterioration due to delayed cerebral ischemia (DCI) in patients with aSAH.

Methods: REACT was a prospective, multicenter, randomized, double-blind, phase 3 study. Eligible patients had aSAH secured by surgical clipping or endovascular coiling, and had presented with thick and diffuse clot on admission CT scan. Patients were randomized (1:1 ratio) to 15 mg/hour intravenous clazosentan or placebo within 96 hours of the aSAH for up to 14 days, in addition to standard of care treatment including oral or intravenous nimodipine. The primary efficacy endpoint was the occurrence of clinical deterioration due to DCI up to 14 days after initiation of the study drug. The main secondary endpoint was the occurrence of clinically relevant cerebral infarction at day 16 after study drug initiation. Other secondary endpoints included clinical outcome assessed on the modified Rankin Scale (mRS) and the Glasgow Outcome Scale-Extended (GOSE) at week 12 post-aSAH. Imaging and clinical endpoints were centrally adjudicated.

Assessment of lumbar paraspinal muscle morphology using mDixon Quant magnetic resonance imaging (MRI): a cross-sectional study in healthy subjects

6 Sep

Assessment of lumbar paraspinal muscle morphology using mDixon Quant magnetic resonance imaging (MRI): a cross-sectional study in healthy subjects

Background: Lumbar paraspinal muscles (LPM) are a part of the deep spinal stabilisation system and play an important role in stabilising the lumbar spine and trunk. Inadequate function of these muscles is thought to be an essential aetiological factor in low back pain, and several neuromuscular diseases are characterised by dysfunction of LPM. The main aims of our study were to develop a methodology for LPM assessment using advanced magnetic resonance imaging (MRI) methods, including a manual segmentation process, to confirm the measurement reliability, to evaluate the LPM morphological parameters [fat fraction (FF), total muscle volume (TMV) and functional muscle volume (FMV)] in a healthy population, to study the influence of physiological factors on muscle morphology, and to build equations to predict LPM morphological parameters in a healthy population.

Methods: This prospective cross-sectional observational comparative single-centre study was conducted at the University Hospital in Brno, enrolling healthy volunteers from April 2021 to March 2023. MRI of the lumbar spine and LPM (erector spinae muscle and multifidus muscle) were performed using a 6-point Dixon gradient echo sequence. The segmentation of the LPM and the control muscle (psoas muscle) was done manually to obtain FF and TMV in a range from Th12/L1 to L5/S1. 

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