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.     

Upflow anaerobic sludge blanket (UASB) treatment of supernatant of cow manure by thermal pre-treatment.

Upflow anaerobic sludge blanket (UASB) methane fermentation treatment of cow manure that was subjected to screw pressing, thermal treatment and subsequent solid-liquid separation was studied. Conducting batch scale tests at temperatures between 140 and 180 degrees C, the optimal temperature for sludge settling and the color suppression was found to be between 160-170 degrees C. UASB treatment was carried out with a supernatant obtained from the thermal treatment at the optimal conditions (170 degrees C for 30 minutes) and polymer-dosed solid-liquid separation. In the UASB treatment with a COD(Cr) loading of 11.7 kg/m3/d and water temperature of 32.2 degrees C, the COD(Cr) level dropped from 16,360 mg/L in raw water to 3,940 mg/L in treated water (COD(Cr), removal rate of 75.9%), and the methane production rate per COD(Cr) was 0.187 Nm3/kg. Using wastewater thermal-treated at the optimal conditions, also a methane fermentation treatment with a continuously stirred tank reactor (CSTR) was conducted (COD(Cr) in raw water: 38,000 mg/L, hydraulic retention time (HRT): 20 days, 35 degrees C). At the COD(Cr) loading of 1.9 kg/m3/d, the methane production rate per COD(Cr), was 0.153 Nm3/kg. This result shows that UASB treatment using thermal pre-treatment provides a COD(Cr), loading of four times or more and a methane production rate of 1.3 times higher than the CSTR treatment.     

Reliability investigation of 0.07-/spl mu/m InGaAs-InAlAs-InP HEMT MMICs with pseudomorphic In/sub 0.75/Ga/sub 0.25/As channel

The authors have investigated the reliability performance of G-band (183 GHz) monolithic microwave integrated circuit (MMIC) amplifiers fabricated using 0.07-/spl mu/m T-gate InGaAs-InAlAs-InP HEMTs with pseudomorphic In/sub 0.75/Ga/sub 0.25/As channel on 3-in wafers. Life test was performed at two temperatures (T/sub 1/ = 200 /spl deg/C and T/sub 2/ = 215 /spl deg/C), and the amplifiers were stressed at V/sub ds/ of 1 V and I/sub ds/ of 250 mA/mm in a N/sub 2/ ambient. The activation energy is as high as 1.7 eV, achieving a projected median-time-to-failure (MTTF) /spl ap/ 2 /spl times/ 10/sup 6/ h at a junction temperature of 125 /spl deg/C. MTTF was determined by 2-temperature constant current stress using /spl Delta/G/sub mp/ = -20% as the failure criteria. The difference of reliability performance between 0.07-/spl mu/m InGaAs-InAlAs-InP HEMT MMICs with pseudomorphic In/sub 0.75/Ga/sub 0.25/As channel and 0.1-/spl mu/m InGaAs-InAlAs-InP HEMT MMICs with In/sub 0.6/Ga/sub 0.4/As channel is also discussed. The achieved high-reliability result demonstrates a robust 0.07-/spl mu/m pseudomorphic InGaAs-InAlAs-InP HEMT MMICs production technology for G-band applications.     

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.     

Thermal stability of reinforced Nb3Sn composite superconductor under cryocooled conditions

Several types of reinforced Nb₃Sn wires have been developed to prevent reduction of superconducting properties by applying a strong electromagnetic force. To fabricate a cryocooled magnet using those reinforced wires, we experimentally measured the minimum quench energy (MQE) under cryocooled conditions of some reinforced Nb₃Sn wires. As a result, it became clear that thermal stability expressed as MQE was controlled by the temperature margin between the temperature of the operating condition and the transition temperature from superconductivity to normal. Using the FEM analysis, it was realized that the cause of the decline in thermal stability for the reinforced wires was the low thermal conductivity of the reinforced materials.     

Three-dimensional pin power reconstruction for the axially heterogeneous region in BWR

A three-dimensional pin power reconstruction method was proposed and verified by applying to the axially heterogeneous region problem of the BWR core calculation. Because the production assembly calculation has been carried out by two-dimensional deterministic calculation methods like current coupling collision probability or the method of characteristics, it has been difficult to predict the detailed three-dimensional heterogeneous pin power distribution of the axially heterogeneous region. Consequently, only radial intranodal homogeneous power distributions have been considered, and axial intranodal homogeneous power distributions have not been considered in the estimation of linear-heat-generation-ratio at common BWR core calculations.     

Expression of V642 APP mutant causes cellular apoptosis as Alzheimer trait-linked phenotype

APP is a transmembrane precursor of beta-amyloid. In dominantly inherited familial Alzheimer's disease (FAD), point mutations V6421, V642F and V642G have been discovered in APP695. Here we show that expression of these mutants (FAD-APPs) causes a clone of COS cells to undergo apoptosis associated with DNA fragmentation. Apoptosis by the three FAD-APPs was the highest among all possible V642 mutants; normal APP695 had no effect on apoptosis, suggesting that apoptosis by APP mutants in this system is phenotypically linked to the FAD trait. FAD-APP-induced apoptosis was sensitive to bcl-2 and most probably mediated by heteromeric G proteins. This study presents a model system allowing analysis of the mechanism for FAD-APP-induced cytotoxicity.     

Synthesis and characterization of chitosan/poly(acrylic acid) polyelectrolyte complex

Polyelectrolyte complex based on chitosan and acrylic acid monomer by photoinitiated free‐radical polymerization in the absence of crosslinker showed a large transition in swelling in response to changes in pH of surrounding medium. Their ability to swell arises from polyelectrolyte interactions and molecular structure of the complex. The main properties of interest that related to the molecular structure, swelling volumes, glass transition temperature, and elastic modulus of the complex were investigated. The effect of water content, the only variable in the sample component, played an important role in molecular structure of the complex and as a consequence, the extent of intermolecular linkage, especially amide bonds which in turn governed the degree of swelling of the polyelectrolyte complex in this study. The decreased degree of swelling and higher temperature shift of glass transition temperature was found with increased water content, whereas increased modulus of elasticity of dry complex was found in lower water content of synthesis component. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 83: 1025–1035, 2002     

XIII. Yeast sequencing reports. Cloning and sequencing of the NES24 gene of Saccharomyces cerevisiae

We have cloned NES24 using a temperature-sensitive nes24-1 mutant as a host and sequenced a 3162 bp XhoI-EcoRI DNA fragment containing the NES24 gene. Computer analysis revealed that this segment contains a 1806 bp open reading frame which is needed for complementation of the nes24-1 mutation. We found SUP8 in the region upstream of the NES24 gene, placing the NES24 gene on chromosome XIII. A protein homology search indicated that NES24 encodes a new protein. The disruption of the NES24 gene resulted in temperature-sensitive growth. The sequence has been deposited in DDBJ/EmBL/GenBank data bases under Accession Number D15052.