Two-Month Individually Supervised Exercise Therapy Improves Walking Speed, Step Length, and Temporal Gait Symmetry in Chronic Stroke Patients: A before-after Trial.

Gait asymmetry is common after stroke and is a major risk factor for falls. In particular, temporal gait asymmetry often remains in the chronic stage of stroke. However, health insurance does not cover rehabilitation for patients with chronic stroke in many countries. Accordingly, it is undetermined whether individually supervised exercise therapy has beneficial effects on chronic hemiparetic gait. Patients with stroke (n = 25) more than 6 months after onset performed 70 min of individually supervised exercise twice weekly for 2 months in 16 sessions with qualified personnel. The intervention significantly reduced the pre-swing phase on the paretic side (mean = 91.8%, 95%CI, 84.8−98.8). In addition, there was a significant improvement in pre-swing phase symmetry in those with great asymmetry prior to the intervention (p = 0.022). Step length significantly increased after the intervention on both sides (non-paretic, p = 0.029; paretic, p = 0.0055). Walking time at both comfortable and maximum speeds was significantly shortened (comfortable, p = 0.0041; maximum, p < 0.0001). Our findings suggest that there remains scope to improve gait ability with individually supervised exercise therapy in patients with chronic stroke, whose functional recovery is often considered unlikely. This type of intervention may be a simple and effective option to improve gait parameters, including temporal asymmetry, even in patients with chronic stroke.

Coculture with hiPS-derived intestinal cells enhanced human hepatocyte functions in a pneumatic-pressure-driven two-organ microphysiological system.

Examining intestine-liver interactions is important for achieving the desired physiological drug absorption and metabolism response in in vitro drug tests. Multi-organ microphysiological systems (MPSs) constitute promising tools for evaluating inter-organ interactions in vitro. For coculture on MPSs, normal cells are challenging to use because they require complex maintenance and careful handling. Herein, we demonstrated the potential of coculturing normal cells on MPSs in the evaluation of intestine-liver interactions. To this end, we cocultured human-induced pluripotent stem cell-derived intestinal cells and fresh human hepatocytes which were isolated from PXB mice with medium circulation in a pneumatic-pressure-driven MPS with pipette-friendly liquid-handling options. The cytochrome activity, albumin production, and liver-specific gene expressions in human hepatocytes freshly isolated from a PXB mouse were significantly upregulated via coculture with hiPS-intestinal cells. Our normal cell coculture shows the effects of the interactions between the intestine and liver that may occur in vivo. This study is the first to demonstrate the coculturing of hiPS-intestinal cells and fresh human hepatocytes on an MPS for examining pure inter-organ interactions. Normal-cell coculture using the multi-organ MPS could be pursued to explore unknown physiological mechanisms of inter-organ interactions in vitro and investigate the physiological response of new drugs.

Generation of Human-Induced Pluripotent Stem Cell-Derived Functional Enterocyte-Like Cells for Pharmacokinetic Studies.

We aimed to establish an in vitro differentiation procedure to generate matured small intestinal cells mimicking human small intestine from human-induced pluripotent stem cells (iPSCs). We previously reported the efficient generation of CDX2-expressing intestinal progenitor cells from embryonic stem cells (ESCs) using 6-bromoindirubin-3'-oxime (BIO) and (3,5-difluorophenylacetyl)-L-alanyl-L-2-phenylglycine tert-butyl ester (DAPT) to treat definitive endodermal cells. Here, we demonstrate the generation of enterocyte-like cells by culturing human iPSC-derived intestinal progenitor cells on a collagen vitrigel membrane (CVM) and treating cells with a simple maturation medium containing BIO, DMSO, dexamethasone, and activated vitamin D3. Functional tests further confirmed that these iPSC-derived enterocyte-like cells exhibit P-gp- and BCRP-mediated efflux and cytochrome P450 3A4 (CYP3A4)-mediated metabolism. We concluded that hiPS cell-derived enterocyte-like cells can be used as a model for the evaluation of drug transport and metabolism studies in the human small intestine.

Direction-specific Disruption of Paretic Arm Movement in Post-stroke Patients.

OBJECTIVE: This study aimed to characterize reaching movements of the paretic arm in different directions within the reachable workspace in post-stroke patients. METHODS: A total of 12 post-stroke patients participated in this study. Each held a ball with a tracking marker and performed back-and-forth reaching movements from near the middle of the body to one of two targets in front of them located on the ipsilateral and contralateral sides of the arm performing the movement. We recorded and analyzed the trajectories of the tracking marker. The stability of arm movements was evaluated using areas and minimum Feret diameters to assess the trajectories of both the paretic and non-paretic arms. The speed of the arm movement was also calculated. RESULTS: For the paretic arm, contralateral movement was more impaired than ipsilateral movement, whereas for the non-paretic arm, no difference was observed between the directions. The maximum speed of the contralateral movement was significantly slower than that of the ipsilateral movement in both the paretic and non-paretic arms. CONCLUSION: The paretic arm shows direction-specific instability in movement toward the contralateral side of the arm.