Interactive cueing with walk-Mate for Hemiparetic Stroke Rehabilitation

Background: Many techniques that compensate for locomotion problems in daily life using externally controlled stimulation have recently been reported. These techniques are beneficial for effortlessly supporting patients' locomotive functions, but the users of such devices must necessarily remain dependent on them. It is possible that some individuals with gait impairment may be prevented recovering locomotive function. From a rehabilitation viewpoint, it may therefore be supposed that ideally, devices that can be used in daily life to improve the locomotive functions of the body itself should be proposed. Methods: We evaluate the effectiveness of Walk-Mate, which has been used mainly as a gait compensation device, as a gait rehabilitation training device by analyzing improvement in locomotion before, during and after rehabilitation in hemiparetic patients and comparing it with a previous gait training method. Walk-Mate generates a model walking rhythm in response to a user's locomotion in real time, and by indicating this rhythm using auditory stimuli, provides a technology that supports walking by reducing asymmetries and fluctuations in foot contact rhythm. If patients can use the system to learn a regulated walking rhythm, then it may also be expected to fulfil the functions of a gait rehabilitation training device for daily life. Results: With regard to asymmetry, significantly improvements were seen for compensatory movement during training using Walk-Mate, but improvements were not retained as rehabilitative results. Regarding fluctuations in the foot contact period, significant improvement was observed for compensatory movement during training and these significant improvements were retained as rehabilitative results. In addition, it became clear that such improvement could not be adequately obtained by the previously proposed training technique utilizing constant rhythmic auditory stimulation. Conclusions: Walk-Mate effectively compensated for locomotion problems of hemiparetic patients by improving gait rhythm both during and after training, suggesting that locomotive function can be effectively recovered in some patients. The interactive mechanism of Walk-Mate may be capable of simultaneously achieving the aims of gait compensation and gait rehabilitation training methods previously developed under individual frameworks. Walk-Mate is a promising technology for assisting the reintegration of disabled persons into society

Expression of c-myc, c-fos and CA19-9 in Human Non-Malignant and Malignant Gallbladder Tissues

Immunohistochemical study was performed on expressions of c-myc, c-fos and CA19-9 in gallbladder tissue with or without malignant lesions. A total of 81 tissues were divided into four groups including 47 carcinomas, 3 dysplasias, 17 metaplasias and 14 normal lesions. After these tissues were routinely fixed in 10% formalin solution and embedded in paraffin, 4 micrometer-thick sections were made and stained with hematoxylin-eosin to classify the type of lesions. Immunohistochemical stains were carried out for c-myc and c-fos oncoproteins, and CA19-9. The percentages of positive reaction for c-myc oncoprotein were 77%, 67%, 88% and 36%, those for c-fos oncoprotein were 83%, 66%, 35% and 7%, and those for CA19-9 were 85%, 100%, 88% and 71% in carcinoma, dysplasia, metaplasia and normal tissues, respectively. These results suggest that c-myc and c-fos oncogenes play some kind of roles in malignant transformation of the gallbladder tissues and that abnormal expression of CA19-9 is the sign of antigen reversion of carcinoma cells toward embryonic cells of the gallbladder tissue

Lectin Immunohistochemistry in Human Non-Malignant and Malignant Gallbladder Tissuses

Changes in the lectin binding pattern in non-malignant and malignant gallbladder tissues were examined using the following eight types of carbohydrate binding lectins : Ulex europaeus-1 (UEA-1), Arachis hypogaea (PNA), Griffonia simplicifolia (GS-1), Glycine maximum (SBA), Bauhinia purpurea (BPA), Dolichos biflorus (DBA), Canavalia ensiformis (Con-A), and Triticum vulgare (WGA). We used a total of 109 tissues including 31 normal tissues, 25 metaplasias, and 53 carcinomas. Lectin staining pattern was evaluated using the Hamada\u27s crieria of the following four types : apical type, cytoplasmic type with polarity, cytoplasmic type without polarity, and stromal type. Normal cases showed apical type and cytoplasmic type with polarity, while carcinoma cases revealed cytoplasmic type with or without polarity. In carcinoma cases, GS-I and DBA lectins showed higher immunohistochemical positive rate and more frequent cytoplasmic type with polarity pattern of immunohistochemical localization than the other types of lectins. These results suggest that the GS-I and DBA are the most reliable lectin marker for malignant transformation of the gallbladder tissues. Key words : Lectin, immunohistochemistry, gallbladder carcinoma

Prevalence of pathogenic germline variants in the circulating tumor DNA testing

BACKGROUND: Somatic and germline variants are not distinguishable by circulating tumor DNA (ctDNA) testing without analyzing non-tumor samples. Although confirmatory germline testing is clinically relevant, the criteria for selecting presumed germline variants have not been established in ctDNA testing. In the present study, we aimed to evaluate the prevalence of pathogenic germline variants in clinical ctDNA testing through their variant allele fractions (VAFs). METHODS: A total of consecutive 106 patients with advanced solid tumors who underwent ctDNA testing (Guardant360®) between January 2018 and March 2020 were eligible for this study. To verify the origin of pathogenic variants reported in ctDNA testing, germline sequencing was performed using peripheral blood DNA samples archived in the Clinical Bioresource Center in Kyoto University Hospital (Kyoto, Japan) under clinical research settings. RESULTS: Among 223 pathogenic variants reported in ctDNA testing, the median VAF was 0.9% (0.02-81.8%), and 88 variants with ≥ 1% VAFs were analyzed in germline sequencing. Among 25 variants with ≥ 30% VAFs, seven were found in peripheral blood DNA (BRCA2: n = 6, JAK2: n = 1). In contrast, among the 63 variants with VAFs ranging from 1 to < 30%, only one variant was found in peripheral blood DNA (TP53: n = 1). Eventually, this variant with 15.6% VAF was defined to be an acquired variant, because its allelic distribution did not completely link to those of neighboring germline polymorphisms. CONCLUSION: Our current study demonstrated that VAFs values are helpful for selecting presumed germline variants in clinical ctDNA testing

HER2 G776S mutation promotes oncogenic potential in colorectal cancer cells when accompanied by loss of APC function

Clinical cancer genome sequencing detects oncogenic variants that are potential targets for cancer treatment, but it also detects variants of unknown significance. These variants may interact with each other to influence tumor pathophysiology, however, such interactions have not been fully elucidated. Additionally, the effect of target therapy for those variants also unclarified. In this study, we investigated the biological functions of a HER2 mutation (G776S mutation) of unknown pathological significance, which was detected together with APC mutation by cancer genome sequencing of samples from a colorectal cancer (CRC) patient. Transfection of the HER2 G776S mutation alone slightly increased the kinase activity and phosphorylation of HER2 protein, but did not activate HER2 downstream signaling or alter the cell phenotype. On the other hand, the HER2 G776S mutation was shown to have strong oncogenic potential when loss of APC function was accompanied. We revealed that loss of APC function increased Wnt pathway activity but also increased RAS-GTP, which increased ERK phosphorylation triggered by HER2 G776S transfection. In addition, afatinib, a pan-HER tyrosine kinase inhibitor, suppressed tumor growth in xenografts derived from HER2 G776S-transfected CRC cells. These findings suggest that this HER2 mutation in CRC may be a potential therapeutic target

Single-molecule imaging of full protein synthesis by immobilized ribosomes

How folding of proteins is coupled to their synthesis remains poorly understood. Here, we apply single-molecule fluorescence imaging to full protein synthesis in vitro. Ribosomes were specifically immobilized onto glass surfaces and synthesis of green fluorescent protein (GFP) was achieved using modified commercial Protein Synthesis using Recombinant Elements that lacked ribosomes but contained purified factors and enzyme that are required for translation in Escherichia coli. Translation was monitored using a GFP mutant (F64L/S65T/F99S/M153T/V163A) that has a high fluorophore maturation rate and that contained the Secretion Monitor arrest sequence to prevent dissociation from the ribosome. Immobilized ribosomal subunits were labeled with Cy3 and GFP synthesis was measured by colocalization of GFP fluorescence with the ribosome position. The rate of appearance of colocalized ribosome GFP was equivalent to the rates of fluorescence appearance coupled with translation measured in bulk, and the ribosome–polypeptide complexes were stable for hours. The methods presented here are applicable to single-molecule investigation of translational initiation, elongation and cotranslational folding

Protocol for a multicentre, prospective, cohort study to investigate patient satisfaction and quality of life after immediate breast reconstruction in Japan: the SAQLA study

Introduction The aim of breast reconstruction (BR) is to improve patients' health-related quality of life (HRQOL). Therefore, measuring patient-reported outcomes (PROs) would clarify the value and impact of BR on a patient's life and thus would provide evidence-based information to help decision-making. The Satisfaction and Quality of Life After Immediate Breast Reconstruction study aimed to investigate satisfaction and HRQOL in Japanese patients with breast cancer who undergo immediate breast reconstruction (IBR). Methods and analysis This ongoing prospective, observational multicentre study will assess 406 patients who had unilateral breast cancer and underwent mastectomy and IBR, and were recruited from April 2018 to July 2019. All participants were recruited from seven hospitals: Okayama University Hospital, Iwate Medical University Hospital, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Showa University Hospital, University of Tsukuba Hospital, Osaka University Hospital and Yokohama City University Medical Center. The patients will be followed up for 36 months postoperatively. The primary endpoint of this study will be the time-dependent changes in BREAST-Q satisfaction with breast subscale scores for 12 months after reconstructive surgery, which will be collected via an electronic PRO system. Ethics and dissemination This study will be performed in accordance with the Ethical Guidelines for Medical and Health Research Involving Human Subjects published by Japan's Ministry of Education, Science and Technology and the Ministry of Health, Labour and Welfare, the modified Act on the Protection of Personal Information and the Declaration of Helsinki. This study protocol was approved by the institutional ethics committee at the Okayama University Graduate School of Medicine, Dentistry, on 2 February 2018 (1801-039) and all other participating sites. The findings of this trial will be submitted to an international peer-reviewed journal