Effective Therapy Using Voglibose for Nonalcoholic Steatohepatitis in a Patient with Insufficient Dietary and Exercise Therapy: Exploring Other Treatment Possibilities

A 56-year-old Japanese female with a 10-year history of thyroiditis presented to our institution. The laboratory data and clinical findings suggested that the patient had complicated nonalcoholic fatty liver disease or nonalcoholic steatohepatitis (NASH) with autoimmune hepatitis according to the criteria by the application of the International Autoimmune Hepatitis score. The patient could not manage by herself so dietary- and exercise-based treatment was difficult. Accordingly, ursodeoxycholic acid and ezetimibe therapy was started and continued until the performance of a liver needle biopsy to define the diagnosis. However, no improvement in liver function was observed. In addition, pathological findings indicated that the patient had NASH. The patient was finally diagnosed as having NASH. Therefore, voglibose was added to the ursodeoxycholic acid and ezetimibe therapy, and this addition of voglibose actually took effect. The patient's serum aspartate transaminase and alanine aminotransferase levels decreased dramatically. This report is the first to document other treatment possibilities of NASH in a case when dietary therapy is difficult

Synthesis of Formation Control Systems for Multi-Agent Systems under Control Gain Perturbations

This paper proposed a linear matrix inequality (LMI)-based design method of non-fragile guaranteed cost controllers for multi-agent systems (MASs) with leader-follower structures. In the guaranteed cost control approach, the resultant controller guarantees an upper bound on the given cost function together with asymptotical stability for the closed-loop system. The proposed non-fragile guaranteed cost control system can achieve consensus for MASs despite control gain perturbations. The goal is to develop an LMI-based sufficient condition for the existence of the proposed non-fragile guaranteed cost controller.  Moreover, a design problem of an optimal non-fragile guaranteed cost controller showe that minimizing an upper bound on the given quadratic cost function can be reduced to constrain a convex optimization problem. Finally, numerical examples were given to illustrate the effectiveness of the proposed non-fragile controller for MASs

Differential determinants of physical daily activities in frail and nonfrail community-dwelling older adults

AbstractBackground/PurposeThe purpose of this study was to determine whether or not daily activities determined by average daily steps are associated with age, gender, body mass index, fear of falling, and physical functions (locomotive function, balance function, and muscle power) in community-dwelling nonfrail and frail older adults.MethodsThis is a cross-sectional study conducted in community-dwelling older adults in Japan. Based on the Timed Up and Go (TUG) test, 629 elderly adults were divided into two groups: 515 were grouped to nonfrail elderly (TUG time less than 13.5 seconds, mean age 77.0±7.2 years) and 114 to frail elderly (TUG time of 13.5 seconds or more, mean age 76.1±7.5 years). Daily physical activities were determined by average daily steps measured by pedometer and four other physical function tests (10-m walk test, single-leg standing, functional reach, and five-chair stand test) were performed along with the assessment of fear of falling.ResultsStepwise regression analysis revealed that age, gender, 10-m walk test, and single-leg standing were significant and independent determinants of the average step counts in the nonfrail elderly (R2=0.282, p<0.001), whereas fear of falling was the only significant and independent determinant of the average step counts in the frail elderly (R2=0.119, p<0.001).ConclusionThese results indicate that differential factors may be related to daily activities depending on the level of frailty in community-dwelling older adults

Enumerated sparse extraction of important surgical planning features for mandibular reconstruction

[2020 42nd Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC 2020); Montreal, Quebec, Canada, 20-24 July 2020]Because implicit medical knowledge and experience are used to perform medical treatment, such decisions must be clarified when systematizing surgical procedures. We propose an algorithm that extracts low-dimensional features that are important for determining the number of fibular segments in mandibular reconstruction using the enumeration of Lasso solutions (eLasso). To perform the multi-class classification, we extend the eLasso using an importance evaluation criterion that quantifies the contribution of the extracted features. Experiment results show that the extracted 7-dimensional feature set has the same estimation performance as the set using all 49-dimensional features

Polysaccharide-Containing Macromolecules in a Kampo (Traditional Japanese Herbal) Medicine, Hochuekkito: Dual Active Ingredients for Modulation of Immune Functions on Intestinal Peyer's Patches and Epithelial cells

A traditional Japanese herbal (Kampo) medicine, Hochuekkito (Bu-Zhong-Yi-Qi-Tang in Chinese, TJ-41) is a well-known Kampo formula, and has been found to enhance antigen-specific antibody response in not only local mucosal immune system in upper respiratory tract, but also systemic immune system through upper respiratory mucosal immune system. Although this immunopharmacological effect has been proposed to express by modulation of intestinal immune system including Peyer's patches and intestinal epithelial cells, active ingredients are not known. TJ-41 directly affected the production of bone marrow cell-proliferative growth factors from murine Peyer's patch immunocompetent cells in vitro. Among low molecular, intermediate size and macromolecular weight fractions prepared from TJ-41, only fraction containing macromolecular weight ingredients showed Peyer's patch-mediated bone marrow cell-proliferation enhancing activity. Anion-exchange chromatography and gel filtration gave 17 subfractions comprising polysaccharides and lignins from the macromolecular weight fraction of TJ-41, and some of the subfractions showed significant enhancing activities having different degrees. Some of the subfractions also expressed stimulating activity on G-CSF-production from colonic epithelial cells, and statistically significant positive correlation was observed among enhancing activities of the subfractions against Peyer's patch immunocompetent cells and epithelial cells. Among the fractions from TJ-41 oral administration of macromolecular weight ingredient fraction to mice succeeded to enhance antigen-specific antibody response in systemic immune system through upper respiratory mucosal immune system, but all the separated fractions failed to enhance the in vivo antibody response in upper respiratory tract

Red fluorescent cAMP indicator with increased affinity and expanded dynamic range

cAMP is one of the most important second messengers in biological processes. Cellular dynamics of cAMP have been investigated using a series of fluorescent indicators; however, their sensitivity was sub-optimal for detecting cAMP dynamics at a low concentration range, due to a low ligand affinity and/or poor dynamic range. Seeking an indicator with improved detection sensitivity, we performed insertion screening of circularly permuted mApple, a red fluorescent protein, into the cAMP-binding motif of PKA regulatory subunit Iα and developed an improved cAMP indicator named R-FlincA (Red Fluorescent indicator for cAMP). Its increased affinity (Kd = 0.3 μM) and expanded dynamic range (860% at pH 7.2) allowed the detection of subtle changes in the cellular cAMP dynamics at sub-μM concentrations, which could not be easily observed with existing indicators. Increased detection sensitivity also strengthened the advantages of using R-FlincA as a red fluorescent indicator, as it permits a series of applications, including multi-channel/function imaging of multiple second messengers and combinatorial imaging with photo-manipulation. These results strongly suggest that R-FlincA is a promising tool that accelerates cAMP research by revealing unobserved cAMP dynamics at a low concentration range

Auto-Luminescent Genetically-Encoded Ratiometric Indicator for Real-Time Ca2+ Imaging at the Single Cell Level

Background: Efficient bioluminescence resonance energy transfer (BRET) from a bioluminescent protein to a fluorescent protein with high fluorescent quantum yield has been utilized to enhance luminescence intensity, allowing single-cell imaging in near real time without external light illumination. Methodology/Principal Findings: We applied BRET to develop an autoluminescent Ca2+ indicator, BRAC, which is composed of Ca^[2+]-binding protein, calmodulin, and its target peptide, M13, sandwiched between a yellow fluorescent protein variant, Venus, and an enhanced Renilla luciferase, RLuc8. Adjusting the relative dipole orientation of the luminescent protein's chromophores improved the dynamic range of BRET signal change in BRAC up to 60%, which is the largest dynamic range among BRET-based indicators reported so far. Using BRAC, we demonstrated successful visualization of Ca2+ dynamics at the single-cell level with temporal resolution at 1 Hz. Moreover, BRAC signals were acquired by ratiometric imaging capable of canceling out Ca^[2+]-independent signal drifts due to change in cell shape, focus shift, etc. Conclusions/Significance: The brightness and large dynamic range of BRAC should facilitate high-sensitive Ca2+ imaging not only in single live cells but also in small living subjects

Consensus via Adaptive Gain Controllers Considering Relative Distances for Multi-Agent Systems

In this paper, for multi-agent systems (MASs) with leader-follower structures, we present a linear matrix inequality (LMI)-based design method of an adaptive gain controller considering relative distances between agents. The proposed adaptive gain controller consists of fixed gains and variable ones tuned by time-varying adjustable parameters. The objective of this paper is to derive enough conditions for the existence of the proposed adaptive gain controller which achieves consensus for each agent. The advantages of the proposed adaptive gain controller are as follows; The proposed controller can be obtained by solving LMI, and the proposed control system can achieve consensus and formation control, even if uncertainties are included in the information for relative distances. In this paper, we show that the design problem of the proposed adaptive gain controller can be reduced to the solvability of LMI. Finally, simple numerical examples are included to illustrate the effectiveness of the proposed adaptive gain controller for MASs

Exploring rare cellular activity in more than one million cells by a transscale scope

In many phenomena of biological systems, not a majority, but a minority of cells act on the entire multicellular system causing drastic changes in the system properties. To understand the mechanisms underlying such phenomena, it is essential to observe the spatiotemporal dynamics of a huge population of cells at sub-cellular resolution, which is difficult with conventional tools such as microscopy and flow cytometry. Here, we describe an imaging system named AMATERAS that enables optical imaging with an over-one-centimeter field-of-view and a-few-micrometer spatial resolution. This trans-scale-scope has a simple configuration, composed of a low-power lens for machine vision and a hundred-megapixel image sensor. We demonstrated its high cell-throughput, capable of simultaneously observing more than one million cells. We applied it to dynamic imaging of calcium ions in HeLa cells and cyclic-adenosine-monophosphate in Dictyostelium discoideum, and successfully detected less than 0.01% of rare cells and observed multicellular events induced by these cells