Attempt to Make the Upper-Limb Item of Objective Fugl-Meyer Assessment Using 9-Axis Motion Sensors.

The Fugl-Meyer Assessment (FMA) has been used as a functional assessment of upper-limb function in stroke patients. This study aimed to create a more objective and standardized evaluation based on an FMA of the upper-limb items. A total of 30 first-ever stroke patients (65.3 ± 10.3 years old) and 15 healthy participants (35.4 ± 13.4 years old) admitted to Itami Kousei Neurosurgical Hospital were included. A nine-axis motion sensor was attached to the participants, and the joint angles of 17 upper-limb items (excluding fingers) and 23 FMA upper-limb items (excluding reflexes and fingers) were measured. From the measurement results, we analyzed the time-series data of each movement and obtained the correlation between the joint angles of each part. Discriminant analysis showed that 17 and 6 items had a concordance rate of ≥80% (80.0~95.6%) and <80% (64.4~75.6%), respectively. In the multiple regression analysis of continuous variables of FMA, a good regression model was obtained to predict the FMA with three to five joint angles. The discriminant analysis for 17 evaluation items suggests the possibility of roughly calculating FMA scores from joint angles.

A Combination of Cryopreservation and Kneading Maintains the Usability of Mohs Paste.

Mohs paste is useful for controlling exudates from wounds and infections and is used to treat patients with inoperable skin tumors. Unfortunately, Mohs paste is difficult to preserve because its viscosity and stickiness increase dramatically immediately after preparation, resulting in decreased usability. In this study, the combined use of cryopreservation and kneading was shown to improve long-term storage of Mohs paste. At 25°C, Mohs pastes solidified rapidly, and viscosity reached approximately 700 Pa·s 5 h after preparation. In contrast, cryopreservation at -20°C attenuated hardening of Mohs pastes, and kneading also decreased viscosity. The viscosity of Mohs pastes cotreated with cryopreservation and kneading after 7 months of storage was <70 Pa·s. In addition, tissue invasion with these stored pastes was similar to freshly prepared Mohs paste. Results suggest that the combination of cryopreservation and kneading permits Mohs paste to be stored over extended periods, which may increase the utility of the paste for clinical use.

Establishment of DNA methylation patterns of the Fibrillin1 (FBN1) gene in porcine embryos and tissues.

DNA methylation in transcriptional regulatory regions is crucial for gene expression. The DNA methylation status of the edges of CpG islands, called CpG island shore, is involved in tissue/cell-type-specific gene expression. Haploinsufficiency diseases are caused by inheritance of one mutated null allele and are classified as autosomal dominant. However, in the same pedigree, phenotypic variances are observed despite the inheritance of the identical mutated null allele, including Fibrillin1 (FBN1), which is responsible for development of the haploinsufficient Marfan disease. In this study, we examined the relationship between gene expression and DNA methylation patterns of the FBN1 CpG island shore focusing on transcriptionally active hypomethylated alleles (Hypo-alleles). No difference in the DNA methylation level of FBN1 CpG island shore was observed in porcine fetal fibroblast (PFF) and the liver, whereas FBN1 expression was higher in PFF than in the liver. However, Hypo-allele ratio of the FBN1 CpG island shore in PFF was higher than that in the liver, indicating that Hypo-allele ratio of the FBN1 CpG island shore likely correlated with FBN1 expression level. In addition, oocyte-derived DNA hypermethylation in preimplantation embryos was erased until the blastocyst stage, and re-methylation of the FBN1 CpG island shore was observed with prolonged in vitro culture of blastocysts. These results suggest that the establishment of the DNA methylation pattern within the FBN1 CpG island shore occurs after the blastocyst stage, likely during organogenesis. In conclusion, Hypo-allele ratios of the FBN1 CpG island shore correlated with FBN1 expression levels in porcine tissues.

Evaluation of starch granules based on hydroxypropylcellulose as a substitute for excipient lactose.

BACKGROUND: The improvement in flowability and adhesion of starch powder (SP) is essential for using starch as an excipient for lactose intolerant patients. In this study, we attempted to evaluate the usefulness of hydroxypropylcellulose with molecular weight 80,000 (HPC-80) in the preparation of the starch granules (SG) as a substitute for excipient lactose. METHODS: Hydroxypropylcellulose with molecular weight 30,000 (HPC-30) and HPC-80 were used as binders to prepare the SG, and defined as HPC-30-SG and HPC-80-SG, respectively. Mean particle size (D50) was measured according to the Method, Optical Microscopy of Particle Size Determination in Japanese Pharmacopoeia, Eighteenth Edition, and storage stability were evaluated by measuring of the physical properties after vortexing the granules for 180 s (physical impact). The product loss rate was calculated from the weight change of the various excipients before and after the one dose packaging (ODP). RESULTS: The D50 of SP (30 µm) was smaller than that of the lactose powder (115 µm). The granulation with 0.75-3% HPC-30 and HPC-80 increased the particle size of SP, and the D50 in 1.5% HPC-30-SG (255 µm) and HPC-80-SG (220 µm) were higher than that of lactose. The excipient was removed from the heat seal of the ODP, and upon visual inspection, a large amount of starchy material was observed to be adhering to the paper in the SP. On the other hand, the low recovery rate in SP was attenuated by the granulation with HPC-30 and HPC-80. In the both HPC-30 and HPC-80, the improvement in recovery rate reached a plateau at 1.5%, and the levels of recovery rate was similar to that of lactose. The recovery rate in the 0.75-3% HPC-30-SG and 0.75% HPC-80-SG were decreased by the physical impact, however, the recovery rate and amount of 1.5% and 3% HPC-80-SG were not affected by the physical impact, and these levels were similar to that of lactose. CONCLUSIONS: The use of HPC-80 as a binder of SG was found to produce a higher quality granule product than conventional HPC-based SG. This finding is useful in streamlining the preparation of starch-based powdered medicine in clinical applications.

Comparison of tendon and muscle belly vibratory stimulation in the treatment of post-stroke upper extremity spasticity: a retrospective observational pilot study.

Previous studies have reported the effects of vibratory stimulation (VS) therapy in reducing upper extremity spasticity after stroke. However, the effective location of the VS in patients with stroke remains unclear. This study aimed to determine the VS location that is most effective in reducing post-stroke finger and wrist flexor spasticity. We enrolled 27 consecutive patients with stroke and upper extremity spasticity in this retrospective observational study. The participants received stretching, tendon vibration, and muscle belly vibration for 5 min over a period of 3 days. To evaluate spasticity, we assessed the Modified Ashworth Scale score before and immediately after each treatment and immediately after voluntary finger flexion. Participants who received tendon vibration showed greater improvement in flexor tone in the fingers than participants who received stretching and muscle belly vibration (P < 0.05 and < 0.001, respectively). Participants who underwent VS showed no significant improvement in the wrist flexor tone compared to those who underwent stretching. Our results suggest that the tendon may be the most effective location for treating spasticity of the finger flexor muscles and that VS may not significantly improve spasticity of the wrist flexors more than stretching.

Incorporation of human iPSC-derived stromal cells creates a pancreatic cancer organoid with heterogeneous cancer-associated fibroblasts.

The aggressiveness of pancreatic ductal adenocarcinoma (PDAC) is affected by the tumor microenvironment (TME). In this study, to recapitulate the PDAC TME ex vivo, we cocultured patient-derived PDAC cells with mesenchymal and vascular endothelial cells derived from human induced pluripotent stem cells (hiPSCs) to create a fused pancreatic cancer organoid (FPCO) in an air-liquid interface. FPCOs were further induced to resemble two distinct aspects of PDAC tissue. Quiescent FPCOs were drug resistant, likely because the TME consisted of abundant extracellular matrix proteins that were secreted from the various types of cancer-associated fibroblasts (CAFs) derived from hiPSCs. Proliferative FPCOs could re-proliferate after anticancer drug treatment, suggesting that this type of FPCO would be useful for studying PDAC recurrence. Thus, we generated PDAC organoids that recapitulate the heterogeneity of PDAC tissue and are a potential platform for screening anticancer drugs.

Retrospective comparison between definitive stereotactic body radiotherapy and radical surgery for 538 patients with early-stage non-small cell lung cancer in a single institution.

Introduction: Survival information for stereotactic body radiotherapy (SBRT) and surgery for stage I non-small cell lung cancer (NSCLC) was examined. Methods: Stage I NSCLC patients who underwent surgery or SBRT between 2012 and 2016 were retrospectively enrolled in this single-institution study. Using the Kaplan--Meier method and Cox regression model, overall survival (OS) was estimated and compared. Results: Among 538 enrolled patients, compared to the surgery group (443), the SBRT group (95) had more complications (P = 0.01), worse performance status (P = 0.001), and were older (P < 0.001). Three-year OS was 70.5% post SBRT and 90.1% postsurgery. The 3-year cancer-specific survival (CSS) and disease-free survival (DFS) post SBRT and postsurgery were 92.7% vs. 92.3% and 61.1% vs 79.3%, respectively. Three-year locoregional and distant control rates post SBRT and postsurgery were 85.6% vs. 90.1% and 82.5% vs. 86.4%, respectively. Multivariate analysis using the Cox model, including age, T-stage, CCI, and C/T ratio and treatment, showed the surgery group's OS to be significantly superior to that of the SBRT group (HR of SBRT per surgery: 1.90, 95%CI: 1.12-3.21, P = 0.017). No significant differences were observed in rates of adverse events. Conclusion: Although OS was better in the surgery group, no differences in CSS existed. This analysis suggests the need for future studies that compare specific radical surgeries and SBRT in a prospective and randomized setting.

Stereotactic Body Radiotherapy for a Sacral Metastasis Clarified by Diffusion-Weighted Whole-Body Imaging With Background Body Signal Suppression in a Patient With Castration-Resistant Prostate Cancer.

Diffusion-weighted whole-body imaging with background body signal suppression (DWIBS) is an emerging extended modality of diffusion-weighted imaging for screening malignant lesions in the body. A 70-year-old male was diagnosed with advanced-stage prostate adenocarcinoma with distant metastasis. After hormone therapy, the disease progressed to castration-resistant prostate cancer (CRPC). Serum prostate-specific antigen (PSA) levels increased during androgen deprivation therapy with low serum testosterone levels. 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) and technetium-99m methylene bone scintigraphy (BS) did not reveal obvious distant metastases; however, we were able to identify distant metastases by DWIBS. We herein report a case in which stereotactic body radiotherapy (SBRT) was performed on target lesions detected by DWIBS and successfully suppressed disease progression.

Radiotherapeutic Outcomes for Localized Primary Rectal Mucosa-Associated Lymphoid Tissue Lymphoma: A Consecutive Case Series of Three Patients.

Gastrointestinal malignant lymphoma is uncommon and accounts for a small proportion of all gastrointestinal neoplasms. Primary rectal extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALToma) is a rare type of intestinal lymphoma. Here, we report about three patients (two females, one male) with localized rectal MALToma who were treated with external beam radiation therapy (EBRT). The median age of the patients was 59 years (range: 50-67 years). Chemotherapy or eradication therapy was not performed before EBRT. All patients received a radiation dose of 30 Gy in 15 fractions using X-ray photon beams. Pathological examination confirmed complete remission of rectal MALToma after EBRT in all patients. At approximately five years after EBRT, none of the patients showed any evidence of recurrence of rectal MALToma. The use of EBRT resulted in excellent disease control, and no severe radiation-induced toxicity was observed. These results suggest that EBRT is a useful treatment modality for primary rectal MALToma.

Generation of human induced pluripotent stem cell-derived liver buds with chemically defined and animal origin-free media.

Advances in organoid technology have broadened the number of target diseases and conditions in which human induced pluripotent stem cell (iPSC)-based regenerative medicine can be applied; however, mass production of organoids and the development of chemically defined, animal origin-free (CD-AOF) media and supplements are unresolved issues that hamper the clinical applicability of these approaches. CD-AOF media and supplements ensure the quality and reproducibility of culture systems by lowering lot-to-lot variations and the risk of contamination with viruses or toxins. We previously generated liver organoids from iPSCs, namely iPSC-liver buds (iPSC-LBs), by mimicking the organogenic interactions among hepatocytes, endothelial cells (ECs), and mesenchymal cells (MCs) and recently reported the mass production of iPSC-LBs derived entirely from iPSCs (all iPSC-LBs), which should facilitate their large-scale production for the treatment of liver failure. However, in previous studies we used media originating from animals for differentiation except for the maintenance of undifferentiated iPSCs. Therefore, we developed a CD-AOF medium to generate all iPSC-LBs. We first developed a CD-AOF medium for hepatocytes, ECs, and stage-matched MCs, i.e., septum transversum mesenchyme (STM), in 2D cultures. We next generated all iPSC-LBs by incubating individual cell types in ultra-low attachment micro-dimple plates. The hepatic functions of all iPSC-LBs generated using the CD-AOF medium were equivalent to those of all iPSC-LBs generated using the conventional medium both in vitro and in vivo. Furthermore, we found that this CD-AOF medium could be used in several cell culture settings. Taken together, these results demonstrate the successful development of a CD-AOF medium suitable for all iPSC-LBs. The protocol developed in this study will facilitate the clinical applicability of all iPSC-LBs in the treatment of liver diseases.