Generation of homogeneous midbrain organoids with in vivo-like cellular composition facilitates neurotoxin-based Parkinson\u27s disease modeling

Recent studies have demonstrated the generation of midbrain-like organoids (MOs) from human pluripotent stem cells. However, the low efficiency of MO generation and the relatively immature and heterogeneous structures of the MOs hinder the translation of these organoids from the bench to the clinic. Here we describe the robust generation of MOs with homogeneous distribution of midbrain dopaminergic (mDA) neurons. Our MOs contain not only mDA neurons but also other neuronal subtypes as well as functional glial cells including astrocytes and oligodendrocytes. Furthermore, our MOs exhibit mDA neuron-specific cell death upon treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, indicating that MOs could be a proper human model system for studying the in vivo pathology of Parkinson\u27s disease (PD). Our optimized conditions for producing homogeneous and mature MOs might provide an advanced patient-specific platform for in vitro disease modeling as well as for drug screening for PD

A Novel Surgical Method for Treating Symptomatic Incomplete Atypical Femoral Fracture using Percutaneous Elastic Intramedullary Nailing

Purpose: To introduce the principles and procedure of percutaneous elastic intramedullary nailing (PEIN) as a treatment for symptomatic incomplete atypical femoral fracture (SIAFF). Methods: From October 2014 to April 2019, 6 cases of SIAFF were treated with PEIN. Two pre-bent 4-mm stainless-steel nails were used to apply compressive force to the fracture site. The antegrade method was used for proximal fractures and the retrograde method for middle and distal femoral fractures. The femoral bowing angle in the coronal and sagittal planes, and the time required for callus formation and union, were evaluated on plain radiographs in both planes. Thigh pain, tenderness, and complications were also assessed. Results: The mean operating time was 65.00 ± 22.64 min. No case progressed to complete atypical fracture. In one case, fracture occurred around the point of nail entry after the patient fell from a chair on postoperative day 7. The incomplete fracture lines were united in 5 cases, after excluding one case with a complication. The time taken to confirm endocortical callus formation, fracture line disappearance, and clinical union was 2.11 ± 0.53, 6.45 ± 4.10, and 6.45 ± 3.65 months, respectively. Conclusions: PEIN is a quick, simple but effective treatment for SIAFF that considers the fracture mechanism and is applicable to cases with severe femoral bowing. Level of evidence: Level IV, case series