Molecular Targeted Therapy for the Bone Loss Secondary to Pyogenic Spondylodiscitis Using Medications for Osteoporosis: A Literature Review

Pyogenic spondylodiscitis can cause severe osteolytic and destructive lesions in the spine. Elderly or immunocompromised individuals are particularly susceptible to infectious diseases; specifically, infections in the spine can impair the ability of the spine to support the trunk, causing patients to be bedridden, which can also severely affect the physical condition of patients. Although treatments for osteoporosis have been well studied, treatments for bone loss secondary to infection remain to be elucidated because they have pathological manifestations that are similar to but distinct from those of osteoporosis. Recently, we encountered a patient with severely osteolytic pyogenic spondylodiscitis who was treated with romosozumab and exhibited enhanced bone formation. Romosozumab stimulated canonical Wnt/β-catenin signaling, causing robust bone formation and the inhibition of bone resorption, which exceeded the bone loss secondary to infection. Bone loss due to infections involves the suppression of osteoblastogenesis by osteoblast apoptosis, which is induced by the nuclear factor-κB and mitogen-activated protein kinase pathways, and osteoclastogenesis with the receptor activator of the nuclear factor-κB ligand-receptor combination and subsequent activation of the nuclear factor of activated T cells cytoplasmic 1 and c-Fos. In this study, we review and discuss the molecular mechanisms of bone loss secondary to infection and analyze the efficacy of the medications for osteoporosis, focusing on romosozumab, teriparatide, denosumab, and bisphosphonates, in treating this pathological condition.     

Multifaceted Mechanisms of Action of Metformin Which Have Been Unraveled One after Another in the Long History

While there are various kinds of drugs for type 2 diabetes mellitus at present, in this review article, we focus on metformin which is an insulin sensitizer and is often used as a first-choice drug worldwide. Metformin mainly activates adenosine monophosphate-activated protein kinase (AMPK) in the liver which leads to suppression of fatty acid synthesis and gluconeogenesis. Metformin activates AMPK in skeletal muscle as well, which increases translocation of glucose transporter 4 to the cell membrane and thereby increases glucose uptake. Further, metformin suppresses glucagon signaling in the liver by suppressing adenylate cyclase which leads to suppression of gluconeogenesis. In addition, metformin reduces autophagy failure observed in pancreatic β-cells under diabetic conditions. Furthermore, it is known that metformin alters the gut microbiome and facilitates the transport of glucose from the circulation into excrement. It is also known that metformin reduces food intake and lowers body weight by increasing circulating levels of the peptide hormone growth/differentiation factor 15 (GDF15). Furthermore, much attention has been drawn to the fact that the frequency of various cancers is lower in subjects taking metformin. Metformin suppresses the mechanistic target of rapamycin (mTOR) by activating AMPK in pre-neoplastic cells, which leads to suppression of cell growth and an increase in apoptosis in pre-neoplastic cells. It has been shown recently that metformin consumption potentially influences the mortality in patients with type 2 diabetes mellitus and coronavirus infectious disease (COVID-19). Taken together, metformin is an old drug, but multifaceted mechanisms of action of metformin have been unraveled one after another in its long history.     

The World robot summit disaster robotics category – achievements of the 2018 preliminary competition

The World Robot Summit is a robot Olympics and aims to be held in a different country every four years from 2020. The concept of the Plant Disaster Prevention challenge is daily inspections, checks, and emergency response in industrial plants, and in this competition, robots must carry out these types of missions in a mock-up plant. The concept of the Tunnel Disaster Response and Recovery challenge is emergency response to tunnel disasters, and is a simulation competition whereby teams compete to show their ability to deal with disasters, by collecting information and removing debris. The Standard Disaster Robotics challenge assesses, in the form of a contest, the standard performance levels of a robot that are necessary for disaster prevention and emergency response. The World Robot Summit Preliminary Competition was held at Tokyo Big Sight in October 2018, and 36 teams participated in the Disaster Robotics Category. UGVs and UAVs contended the merits of new technology for solving complex problems, using core technologies such as mobility, sensing, recognition, performing operations, human interface, autonomous intelligence etc., as well as system integration and implementation of strategies for completing missions, gaining high-level results.     

Crosslinked acrylic pressure‐sensitive adhesives. II. Effect of humidity on the crosslinking reaction

The effect of humidity during storage on the crosslinking reactions of isocyanate groups was investigated with attenuated total reflectance Fourier transform infrared spectroscopy with pressure‐sensitive adhesives composed of poly[ethyl acrylate‐co‐(2‐ethylhexyl acrylate)‐co‐(2‐hydroxyethyl methacrylate)] as a base resin and polyisocyanate as a crosslinker. A peak‐resolving analysis of the amide II region revealed four bands. According to an analysis of the Fourier transform infrared spectra of the model compounds, these four bands were assigned to free urethane linkages, hydrogen‐bonded urethane linkages, free urea linkages, and hydrogen‐bonded urea linkages. As expected, storage under humid conditions led to the formation of free and hydrogen‐bonded urea linkages corresponding to the promotion of isocyanate consumption. Peak resolution of the amide II region was found to be a reasonable way of monitoring urethane and urea linkages during crosslinking reactions. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 3039–3045, 2003     

Reduction mechanism of tioglycolic acid on keratin fibers using microspectrophotometry and FT-Raman spectroscopy

In order to investigate the reduction mechanism of thioglycolic acid (TG) on the keratin fibers, cross-sectional samples of white human hair treated with TG were prepared. The heterogeneous reaction between TG and keratin fibers involving the diffusion of TG into human hair was analyzed at the molecular level using microspectrophotometry and FT-Raman spectroscopy. The diffusion of TG into human hair clearly increased by increasing the treatment time and by raising pH. The TG relative concentration and the disconnected relative concentration of disulfide (–SS–) groups at various depths of the hair samples with pH 9.0 were in good agreement, indicating that the reaction rate (the disconnection of –SS– groups) was faster than the diffusion rate of TG into human hair. From these experiments, we demonstrated that TG diffuses gradually beyond the cuticle region, and toward the inside of the cortex region along with the disconnection of –SS– groups.     

Changes in the gaseous H2S barrier properties of damaged silicate coated nylon 6 films

The damage imposed on SiO _x deposited nylon 6 films as a result of abrasion with a cotton cloth and Gelboflex testing was examined by evaluating the rate at which copper plates, which were enveloped by the damaged films, were corroded by H₂S. Abrasion with a cotton cloth caused some micro-cracking of the SiO _x layer and the permeation rate of H₂S approached that of the uncoated nylon 6 film. Damage to the SiO _x layer by twisting and crushing progressed gradually with the number of Gelboflex test cycles and correspondingly the corrosion rate of the copper plates increased. Comparison of the corrosion rates of the copper plates kept in the pouches made of various commercial films with those obtained for the damaged SiO _x deposited nylon 6 films showed a clear relationship between the H₂ permeation rate of the films and the corrosion rate of the copper plates by H₂S.     

Effects of Neodymium Concentration on Optical Characteristics of Polycrystalline Nd:YAG Laser Materials

A neodymium-doped yttrium-aluminum garnet (Y₃A1₅O₁₂, YAG) (Nd:YAG) ceramic that contained 0.3–4.8 at.% neodymium additives and exhibited nearly the same optical properties as those of a single crystal was fabricated by a solid-state reaction method using high-purity powders. Although the integrated absorption intensity of the ²H_9/2+⁴F_5/2 bands simply increased as the neodymium concentration in the YAG ceramics decreased, the fluorescence intensity of the 2.4 at.% Nd:YAG ceramic was the strongest among Nd:YAG ceramics with various neodymium concentrations and a 0.9 at.% Nd:YAG single crystal. An oscillation experiment was performed on a continuous-wave (cw) laser with a diode-laser exciting system using those ceramics and the single crystal. The oscillation threshold and slope efficiency in that analysis were 309 mW and 28%, respectively, for the 1.1 at.% Nd:YAG ceramics and 356 mW and 40%, respectively, for the 2.4 at.% Nd:YAG ceramics. The lasing characteristics of the ceramics in the present work were superior to those of a 0.9 at.% Nd:YAG single crystal that was fabricated by the Czochralski (Cz) method.     

A low-resistance self-aligned T-shaped gate for high-performancesub-0.1-μm CMOS

This paper describes the high performance of T-shaped-gate CMOS devices with effective channel lengths in the sub-0.1-μm region. These devices were fabricated by using selective W growth, which allows low-resistance gates smaller than 0.1 μm to be made without requiring fine lithography alignment. We used counter-doping to scale down the threshold voltage while still maintaining acceptable short-channel effects. This approach allowed us to make ring oscillators with a gate-delay time as short as 21 ps at 2 V with a gate length of 0.15 μm. Furthermore, we experimentally show that the high circuit speed of a sub-0.1-μm gate length CMOS device is mainly due to the PMOS device performance, especially in terms of its drivability