Analysis of signal components < 500 Hz in brain organoids coupled to microelectrode arrays: A reliable test-bed for preclinical seizure liability assessment of drugs and screening of antiepileptic drugs.

Brain organoids with three-dimensional structure and tissue-like function are highly demanded for brain disease research and drug evaluation. However, to our knowledge, methods for measuring and analyzing brain organoid function have not been developed yet. This study focused on the frequency components of an obtained waveform below 500 Hz using planner microelectrode array (MEA) and evaluated the response to the convulsants pentylenetetrazol (PTZ) and strychnine as well as the antiepileptic drugs (AEDs) perampanel and phenytoin. Sudden and persistent seizure-like firing was observed with PTZ administration, displaying a concentration-dependent periodic activity with the frequency component enhanced even in one oscillation characteristic. On the other hand, in the administration of AEDs, the frequency of oscillation decreased in a concentration-dependent manner and the intensity of the frequency component in one oscillation also decreased. Interestingly, at low doses of phenytoin, a group of synchronized bursts was formed, which was different from the response to the perampanel. Frequency components contained information on cerebral organoid function, and MEA was proven useful in predicting the seizure liability of drugs and evaluating the effect of AEDs with a different mechanism of action. In addition, frequency component analysis of brain organoids using MEA is an important analysis method to perform in vitro to in vivo extrapolation in the future, which will help explore the function of the organoid itself, study human brain developments, and treat various brain diseases.

Laparoscopic Heller myotomy and Dor fundoplication for the treatment of achalasia. Assessment in relation to morphologic type.

BACKGROUND: The significance of laparoscopic Heller myotomy and Dor fundoplication (LHD) for the treatment of achalasia in relation to the severity of the lesion has not been sufficiently assessed. METHODS: Of patients who were diagnosed with achalasia from August 1994 to February 2004, 55 individuals who underwent LHD served as subjects. The therapeutic effects of LHD were assessed in terms of operation time, intraoperative complications, postoperative hospital stay, and symptom improvement in relation to morphologic type (spindle type, Sp; flask type, Fk; and sigmoid type, Sig). Degree of symptomatic improvement was classified into four grades: excellent, good, fair, and poor. RESULTS: Breakdown of morphologic type was as follows: Sp, n = 29; Fk, n = 18; and Sig, n = 8. Excluding one patient for whom conversion to open surgery was required, median average operation time for 54 patients was 160 min. As to intraoperative complications, esophageal mucosal perforation was seen in nine of the 55 patients (16%); however, conversion to open surgery could be avoided by suturing the affected area. Moreover, intraoperative bleeding of at least 100 g was seen in five of the 55 patients (9%), with one Fk patient requiring conversion to open surgery and transfusion. Median postoperative hospital stay was 8 days. Degree of dysphagia relief was excellent in 45 patients (83%), good in eight patients (15%), and fair in one patient (2%). Excellent improvement was obtained in 90%, 88%, and 50% in Sp, Fk, and Sig patients, respectively. Reflux esophagitis was seen in two patients, and was treated with a proton pump inhibitor. CONCLUSIONS: The results of the present study suggest that classification of morphologic type is a useful parameter in predicting postoperative outcome in achalasia. In order to achieve excellent symptomatic relief, surgery for achalasia should be recommended for but not limited to Sp and Fk types.

Assessment of posterior cruciate ligament graft performance using robotic technology.

We used the information on in situ forces provided by robotics to compare two methods of posterior cruciate ligament graft fixation. Twenty porcine knees were studied using robotic technology to determine and repeat intact, deficient, and reconstructed knee motion under 110 N of posterior tibial loading at 30 degrees, 60 degrees, and 90 degrees of knee flexion. Reconstruction was performed using a bone-patellar tendon-bone graft with the distal end of the graft placed in the posterolateral aspect of the posterior cruciate ligament tibial insertion. Specimens were separated into two groups based on the femoral fixation site: the proximal or anterior aspect of the femoral insertion. Repetition of knee motion allowed measurement of the force in the intact posterior cruciate ligament and graft using the principle of superposition. The forces in the graft and the intact ligament provided additional information to evaluate graft performance. Force in the intact posterior cruciate ligament was significantly greater at 90 degrees than at 30 degrees and 60 degrees of knee flexion. The forces in both graft types were significantly lower than those of the posterior cruciate ligament, but the force in the anteriorly placed graft was significantly greater at 90 degrees than at 30 degrees and 60 degrees of knee flexion, similar to the intact posterior cruciate ligament. Thus, the anteriorly placed graft had a more physiologic increase in tension with knee flexion, when the joint provided less restraint.