Zolpidem therapy in dystonia

Although there are some newly developed options to treat dystonia, its medical treatment is not always satisfactory. Zolpidem, an imidazopyridine agonist with a high affinity on benzodiazepine subtype receptor BZ1 (ω1), was found to improve clinical symptoms of dystonia in a limited number of case reports. To investigate what subtype of dystonia is responsive to the therapy, we conducted an open label study to assess the efficacy of zolpidem (5–20 mg) in 34 patients suffering from miscellaneous types of dystonia using the Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS). Patients were entered into the study if they had been refractory to other medications as evaluated by BFMDRS (no change in the previous two successive visits). After zolpidem therapy, the scores in the patients as a whole were decreased from 7.2 ± 7.9 to 5.5 ± 5.0 (P = 0.042). Patients with generalized dystonia, Meige syndrome/blepharospasm, and hand dystonia improved in the scale by 27.8, 17.8, and 31.0%, respectively, whereas no improvement was found in cervical dystonia patients. Overall response rate among patients were comparable to that of trihexyphenidyl. Zolpidem may be a therapeutic option for generalized dystonia, Meige syndrome, and hand dystonia including musician’s. Drowsiness was the dose-limiting factor

Efficacy of Zolpidem for Dystonia: A Study Among Different Subtypes

Although there are some newly developed options to treat dystonia, its medical treatment is not always satisfactory. Zolpidem, an imidazopyridine agonist with a high affinity on benzodiazepine subtype receptor BZ1 (ω1), was found to improve clinical symptoms of dystonia in a limited number of case reports. To investigate what subtype of dystonia is responsive to the therapy, we conducted an open label study to assess the efficacy of zolpidem (5–20 mg) in 34 patients suffering from miscellaneous types of dystonia using the Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS). Patients were entered into the study if they had been refractory to other medications as evaluated by BFMDRS (no change in the previous two successive visits). After zolpidem therapy, the scores in the patients as a whole were decreased from 7.2 ± 7.9 to 5.5 ± 5.0 (P = 0.042). Patients with generalized dystonia, Meige syndrome/blepharospasm, and hand dystonia improved in the scale by 27.8, 17.8, and 31.0%, respectively, whereas no improvement was found in cervical dystonia patients. Overall response rate among patients were comparable to that of trihexyphenidyl. Zolpidem may be a therapeutic option for generalized dystonia, Meige syndrome, and hand dystonia including musician’s. Drowsiness was the dose-limiting factor

Improvement of responsivity of Unified Power Flow Controller in digital control system

The Unified Power Flow Controller (UPFC) can flexibly manage power flow and maintain line voltage. The UPFC consists of two inverters in parallel side and series side. In parallel side, the reactive power can be compensated to improve the power factor. In series side, the voltage drop can be compensated to maintain proper line voltage. It is necessary for the operation in both sides to output the current and the voltage quickly and accurately. As the method for the UPFC control, the deadbeat control is applied. The deadbeat control is able to realize a quick response of the current and voltage control for only a sampling period compared with the general PI control. A principle and simulation results are presented in this paper.2013 International Conference on Electrical Machines and Systems, ICEMS 2013; Busan; South Korea; 26 October 2013 through 29 October 201

A Strategic Protocol to Improve the Process and Outcomes of Two-stage Revision Total Hip Arthroplasty

Two-stage revision total hip arthroplasty (THA) is the most commonly used treatment approach for deep prosthetic infection. However, in this approach the interval between the first and second stage tends to be prolonged. We devised a strategic protocol for improving the infection eradication rate and shortening the interval between the stages in two-stage revision THA. This study analyzed a series of 14 patients (14 hips) from 2008 to 2012, who were treated using an antibiotic-loaded acrylic cement (ALAC) spacer at the first stage and re-implantation at the second stage. The ALAC included vancomycin and amikacin for most of the cases. Patients with MRSA infection were additionally administered intravenous vancomycin in combination with either oral rifampicin or trimethoprim-sulfamethoxazole. The average interval between the stages was 54.2 days overall, and 58.7 days for cases with MRSA infection. Our infection eradication rate was 100%, with no reported recurrence of infection. The presence of MRSA tended to be associated with a longer interval between the two stages. Our protocol for two-stage revision THA was associated with a high eradication rate of infection and a shortened interval between the stages

Content-based CT image retrieval system using deep learning: Preliminary assessment of its accuracy for classifying lesion patterns and retrieving similar cases among patients with diffuse lung diseases

Practical image retrieval systems must fully use image databases. We investigated the accuracy of our content-based computer tomography (CT) image retrieval system (CB-CTIRS) for classifying lesion patterns and retrieving similar cases in patients with diffuse lung diseases. The study included 503 individuals, with 328 having diffuse lung disease and 175 having normal chest CT scans. Among the former, we randomly selected ten scans that revealed one of five specific patterns [consolidation, ground-glass opacity (GGO), emphysema, honeycombing, or micronodules: two cases each]. Two radiologists separated the squares into six categories (five abnormal patterns and one normal pattern) to create a reference standard. Subsequently, each square was entered into the CB-CTIRS, and the F-score used to classify squares was determined. Next, we selected 15 cases (three per pattern) among the 503 cases, which served as the query cases. Three other radiologists graded the similarity between the retrieved and query cases using a 5-point grading system, where grade 5 = similar in both the opacity pattern and distribution and 1 = different therein. The F-score was 0.71 for consolidation, 0.63 for GGO, 0.74 for emphysema, 0.61 for honeycombing, 0.15 for micronodules, and 0.67 for normal lung. All three radiologists assigned grade 4 or 5 to 67.7% of retrieved cases with consolidation, emphysema, or honeycombing, and grade 2 or 3 to 67.7% of the retrieved cases with GGO or micronodules. The retrieval accuracy of CB-CTIRS is satisfactory for consolidation, emphysema, and honeycombing but not for GGO or micronodules

The Cytoplasmic Region of Plasmodium falciparum SURFIN4.2 Is Required for Transport from Maurer’s Clefts to the Red Blood Cell Surface

Background: Plasmodium, the causative agent of malaria, exports many proteins to the surface of the infected red blood cell (iRBC) in order to modify it toward a structure more suitable for parasite development and survival. One such exported protein, SURFIN4.2, from the parasite of human malignant malaria, P. falciparum, was identified in the trypsin-cleaved protein fraction from the iRBC surface, and is thereby inferred to be exposed on the iRBC surface. SURFIN4.2 also localize to Maurer’s clefts?parasite-derived membranous structures established in the RBC cytoplasm and tethered to the RBC membrane?and their role in trafficking suggests that they are a pathway for SURFIN4.2 transport to the iRBC surface. It has not been determined the participation of protein domains and motifs within SURFIN4.2 in transport from Maurer’s clefts to the iRBC surface; and herein we examined if the SURFIN4.2 intracellular region containing tryptophan-rich (WR) domain is required for its exposure on the iRBC surface. Results: We generated two transgenic parasite lines which express modified SURFIN4.2, with or without a part of the intracellular region. Both recombinant SURFIN4.2 proteins were exported to Maurer’s clefts. However, only SURFIN4.2 possessing the intracellular region was efficiently cleaved by surface treatment of iRBC with proteinase K. Conclusions: These results indicate that SURFIN4.2 is exposed on the iRBC surface and that the intracellular region containing WR domain plays a role on the transport from Maurer’s clefts to the iRBC membrane

Peptide barcoding for one-pot evaluation of sequence–function relationships of nanobodies

遊離型抗体の構造活性相関解析を迅速に評価可能とする新手法を開発. 京都大学プレスリリース. 2021-11-08.Optimisation of protein binders relies on laborious screening processes. Investigation of sequence–function relationships of protein binders is particularly slow, since mutants are purified and evaluated individually. Here we developed peptide barcoding, a high-throughput approach for accurate investigation of sequence–function relationships of hundreds of protein binders at once. Our approach is based on combining the generation of a mutagenised nanobody library fused with unique peptide barcodes, the formation of nanobody–antigen complexes at different ratios, their fine fractionation by size-exclusion chromatography and quantification of peptide barcodes by targeted proteomics. Applying peptide barcoding to an anti-GFP nanobody as a model, we successfully identified residues important for the binding affinity of anti-GFP nanobody at once. Peptide barcoding discriminated subtle changes in KD at the order of nM to sub-nM. Therefore, peptide barcoding is a powerful tool for engineering protein binders, enabling reliable one-pot evaluation of sequence–function relationships

Japan and the European Union in the global economy. Bruegel Blueprint 22, 9 April 2014

This book is the final output of a strategic European Union-Japan research partnership, which we initiated in order to deepen our understanding of two major economies facing similar challenges and opportunities. This publication brings together scholars from Kobe University and Bruegel along with selected outside contributors from Japan and the EU from government and leading policy institutions