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.     

Frequency of Upward Lightning Hits to Wind Turbines in Winter

In recent years, frequent damage to wind turbines by winter lightning has been reported in the region along the Sea of Japan. It is a serious finding that lightning hits concentrate on wind turbines in this region. The authors investigated the increase rate of the frequency of lightning hits on wind turbines due to wind turbine construction by using LLS (lightning location system) data. As a result, an experimental formula to estimate the increase rate of the frequency of lightning hits on wind turbines as a function of parameters related to the construction conditions, namely the height of wind turbines, the height above sea level, and the latitude, is proposed.     

Extraction of Trivalent Rare Earths and Minor Actinides from Nitric Acid with N,N,N’,N’-Tetradodecyldiglycolamide (TDdDGA) by Using Mixer-Settler Extractors in a Hot Cell

Single-stage batch experiments to reveal the extraction properties of N,N,N’,N’-tetradodecyldiglycolamide (TDdDGA) for Y, La, Eu, Nd, and Am in nitric acid were carried out. The distribution ratios of Y, Eu, Nd, and Am exceeded 10 when the nitric acid concentration was 1–2 mol/dm³ (M), and the distribution ratio of La was 5.5 when the nitric acid concentration was 2 M. A continuous counter-current experiment using 0.1 M TDdDGA diluted with n-dodecane was performed using mixer-settler extractors installed in a hot cell. Nitric acid with a concentration of 2.1 M containing minor actinides (MAs: Am and Cm), rare earths (REs: Y, La, Nd, and Eu), and other fission products (Sr, Cs, Zr, Mo, Ru, Rh, and Pd) was fed to the extractor. TDdDGA effectively extracted MAs and REs from the feed, while other fission products were barely extracted. The extracted MAs and REs were back-extracted by bringing them in contact with 0.02 M nitric acid, and they were collected as the MA–RE fraction. The results indicated that more than 98% of Am and Cm in the feed were recovered in the MA–RE fraction. The proportions of Y, La, Nd, and Eu in the MA–RE fraction were 94.0%, 99.9%, 99.9%, and 86.9%, respectively.     

Adaptation to climate change and conservation of biodiversity using green infrastructure

In recent years, we have experienced mega‐flood disasters in Japan due to climate change. In the last century, we have been building disaster prevention infrastructure (artificial levees and dams, referred to as “grey infrastructure”) to protect human lives and assets from floods, but these hard protective measures will not function against mega‐floods. Moreover, in a drastically depopulating society such as that in Japan, farmland abandonment prevails, and it will be more difficult to maintain grey infrastructure with a limited tax income. In this study, we propose the introduction of green infrastructure (GI) as an adaptation strategy for climate change. If we can use abandoned farmlands as GI, they may function to reduce disaster risks and provide habitats for various organisms that are adapted to wetland environments. First, we present a conceptual framework for disaster prevention using a hybrid of GI and conventional grey infrastructure. In this combination, the fundamental GI, composed of forests and wetlands in the catchment (GI‐1) and additional multilevel GIs such as flood control basins that function when floodwater exceeds the planning level (GI‐2) are introduced. We evaluated the flood attenuation function (GI‐1) of the Kushiro Wetland using a hydrological model and developed a methodology for selecting suitable locations of GI‐2, considering flood risk, biodiversity and the distribution of abandoned farmlands, which represent social and economic costs. The results indicated that the Kushiro Wetland acts as a large natural reservoir that attenuates the hydrological peak discharge during floods and suitable locations for introducing GI‐2 are concentrated in floodplain areas developing in the downstream reaches of large rivers. Finally, we discussed the network structure of GI‐1 as a hub and GI‐2 as a dispersal site for conservation of the Red‐crowned Crane, one of the symbolic species of Japan.     

Stabilizing effect of the cyclodextrins additive to spray-dried particles of curcumin/polyvinylpyrrolidone on the supersaturated state of curcumin

Although curcumin is considered to have various therapeutic effects, its use as a functional food or supplement is restricted owing to its low water solubility and bioavailability. To increase the solubility of curcumin in water, the use of polyvinylpyrrolidone (PVP) and vinylpyrrolidone-vinyl acetate copolymers with a pyrrolidone skeleton was noted to be promising. In particular, the bi-component formulations of curcumin/PVP prepared through spray drying exhibited an amorphous state in powder X-ray diffraction observations and temporally increased the apparent solubility of curcumin to over 5000 times that of untreated curcumin; nevertheless, after 24 h, the solubility decreased owing to the unstable supersaturated state of curcumin. The addition of α-cyclodextrin (α-CyD) in the bi-component curcumin/PVP formulation helped maintain the supersaturated state of curcumin, whereas the addition of β- and γ-CyD led to the collapse of the supersaturated state. The addition of α-CyD can likely help inhibit the nucleation and crystal growth of curcumin, through the interaction among the solubilized units of curcumin/PVP and α-CyD.     

Simulation of the mechanical behavior of inclined jointed rock masses during tunnel construction using Discontinuous Deformation Analysis (DDA)

In this paper, the mechanical behavior of inclined jointed rock masses during tunneling is considered. Such rock masses can be considered as an assembly of discrete blocks with the discontinuities having a significant influence on the mechanical behavior. To simulate this situation, a discrete numerical analysis method, Discontinuous Deformation Analysis (DDA), is applied. The DDA results show the existence of stress arching in the rock masses during tunneling. This stress arching is the primary influence on the stress distribution and surface subsidence. In addition, the stress arching is affected by the dip angle of the jointed rock masses. Moreover, the DDA results are in good agreement with experiments, explaining the reason for the asymmetrical vertical stress and surface subsidence obtained in laboratory tests. These results suggest that DDA can be applied to model the tunneling behavior of complicated discontinuous rock masses.     

Simultaneous bipedal locomotion based on haptics for teleoperation

ABSTRACT

This paper proposes a novel, simultaneous bipedal locomotion method using haptics for remote operation of biped robots. In general, traditional biped walking methods require very high computational power and advanced controllers to perform the required task. However, in this proposed method, a master exoskeleton attached to the human’s lower body is used to obtain the trajectory and haptic information to generate the trajectory of the slave biped robot in real time. Lateral motion of the center of mass of the biped is constrained in this experiment. Also, it is considered that no communication delay is presented in between the two systems in this experiment, and they are not discussed in this paper. Since a direct motion transmission is used in the proposed method, this method is quite straight forward and a simultaneous walking can be realized at the same time with high performance. Also, it does not require an exact dynamic model of the biped or specific method to plan the trajectory. The gait pattern of the biped is directly determined by that of the human. Also, the operator can feel the remote environment through the exoskeleton robot. Results obtained from the experiments validate the proposed method.     

Oxidative Stress and Its Significant Roles in Neurodegenerative Diseases and Cancer

Reactive oxygen and nitrogen species have been implicated in diverse pathophysiological conditions, including inflammation, neurodegenerative diseases and cancer. Accumulating evidence indicates that oxidative damage to biomolecules including lipids, proteins and DNA, contributes to these diseases. Previous studies suggest roles of lipid peroxidation and oxysterols in the development of neurodegenerative diseases and inflammation-related cancer. Our recent studies identifying and characterizing carbonylated proteins reveal oxidative damage to heat shock proteins in neurodegenerative disease models and inflammation-related cancer, suggesting dysfunction in their antioxidative properties. In neurodegenerative diseases, DNA damage may not only play a role in the induction of apoptosis, but also may inhibit cellular division via telomere shortening. Immunohistochemical analyses showed co-localization of oxidative/nitrative DNA lesions and stemness markers in the cells of inflammation-related cancers. Here, we review oxidative stress and its significant roles in neurodegenerative diseases and cancer.     

A Basic Study of User Utility Maximizing Content Retrieval from Information Networks

This paper proposes some basic methods of content search yielding high user utility or user's satisfaction from numerous information sources scattered over large‐scale networks. In these methods, the search policy is decided by the estimated user utility gain and/or current user utility for each search action, and the most favorable combination of information sources and search content items is selected so as to enlarge the total user utility of the entire search activity. In addition, we evaluate the efficiency of the methods by computer simulations, in which we specify the network topology, user utility functions, probabilities of existence of the search content items in each information source, and so on, apply the proposed methods and other methods for comparison, and compare their aggregate utility gains as an estimation index. The proposed methods are found to achieve good performance in general and an index value about 2.45 times that of ordinary search is observed in an extreme simulation scenario. We discuss the pros and cons of the proposed methods for all the simulation scenarios.