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.     

Effect of the ACAT inhibitor, HL-004, on cholesterol metabolism in macrophages

The effects of a novel acyl-CoA: cholesterol acyltransferase (ACAT) inhibitor, HL-004, on cholesterol metabolism were examined in mice peritoneal macrophages. Cholesteryl ester-rich foam cells were induced by incubating macrophages with acetylated LDL. HL-004 prevented the accumulation of cholesteryl ester in the presence of the cholesterol acceptor, HDL. In the absence of HDL, HL-004 generated large amounts of free cholesterol in the cell. Moreover, HL-004 stimulated the efflux of cholesterol from preestablished foam cells in the presence of HDL. These results suggest that the inhibition of foam cell formation and the stimulation of foam cell regression by HL-004 are attributed to intracellular ACAT inhibition, and that HL-004 would be expected to exhibit an antiatherosclerotic effect through direct action on arterial wall.     

Motivational bases of the public goods problem.

Compared 2 motivational bases for not contributing to a public good, desire to "free ride" (or greed) and fear of being a "sucker," among 110 Japanese undergraduates. It was hypothesized that these 2 types of motivation would be activated under different situations. When a public good was provided conjunctively, fear would have a strong effect but greed would not; when a public good was disjunctively provided, greed would have a strong effect but fear would not. In addition, it was predicted that the greater mutual trust existing among friends would make them contribute more than strangers would in the conjunctive condition but would make no difference in the disjunctive condition. Three types of production rules, in which a public good was conjunctively, disjunctively, or additively produced on the basis of members' contributions, were experimentally created. Half of the groups in each condition consisted of total strangers, and the other half consisted of friends. The hypotheses were supported when the size of the public good (bonus points) was relatively large. Also, Ss responded similarly in the conjunctive condition and in the additive condition. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mechanochemically synthesized ZIF-8 nanoparticles blended into 6FDA-TrMPD membranes for C3H6/C3H8 separation

The mixed matrix membranes (MMMs) consisting zeolitic-imidazolate framework-8 (ZIF-8) nanoparticles in a polymer have been of considerable interest in separation applications. The fillers used are mostly synthesized using the solvothermal method. In this study, the ZIF-8 nanoparticles were synthesized using a solvent-less and salt-free mechanochemical method and were added to 6FDA-TrMPD polyimide to prepare MMMs. The single gas permeation of C₃H₆ and C₃H₈ through the MMMs was investigated. The C₃H₆ permeability and C₃H₆/C₃H₈ ideal selectivity of a 20 wt% mechano-synthesized ZIF-8/6FDA-TrMPD MMM were 70% and 32% higher than those of the neat polymer membrane at 0.1 MPa and 308 K, respectively. The C₃H₆/C₃H₈ separation performance of the mechano-synthesized ZIF-8 MMM was similar to that of the conventional solvothermal-synthesized ZIF-8 MMM. This separation performance was in good agreement with the Maxwell model. Temperature and pressure dependence analyses confirmed that the mechano-synthesized ZIF-8 nanoparticles acted as molecular sieves in the MMMs for the C₃H₆ and C₃H₈ permeation.     

Analysis of Speaker Adaptation Algorithms for HMM-Based Speech Synthesis and a Constrained SMAPLR Adaptation Algorithm

In this paper, we analyze the effects of several factors and configuration choices encountered during training and model construction when we want to obtain better and more stable adaptation in HMM-based speech synthesis. We then propose a new adaptation algorithm called constrained structural maximum a posteriori linear regression (CSMAPLR) whose derivation is based on the knowledge obtained in this analysis and on the results of comparing several conventional adaptation algorithms. Here, we investigate six major aspects of the speaker adaptation: initial models; the amount of the training data for the initial models; the transform functions, estimation criteria, and sensitivity of several linear regression adaptation algorithms; and combination algorithms. Analyzing the effect of the initial model, we compare speaker-dependent models, gender-independent models, and the simultaneous use of the gender-dependent models to single use of the gender-dependent models. Analyzing the effect of the transform functions, we compare the transform function for only mean vectors with that for mean vectors and covariance matrices. Analyzing the effect of the estimation criteria, we compare the ML criterion with a robust estimation criterion called structural MAP. We evaluate the sensitivity of several thresholds for the piecewise linear regression algorithms and take up methods combining MAP adaptation with the linear regression algorithms. We incorporate these adaptation algorithms into our speech synthesis system and present several subjective and objective evaluation results showing the utility and effectiveness of these algorithms in speaker adaptation for HMM-based speech synthesis.     

Microdosimetric specification of the radiation quality of a d(48.5)+Be fast neutron therapy beam produced by a superconducting cyclotron

The proportional counter microdosimetric technique has been employed to quantify variations in the quality of a d(48.5)+Be fast neutron beam passing through a homogeneous water phantom. Single event spectra have been measured as a function of spatial location in the water phantom and field size. The measured spectra have been separated into component spectra corresponding to the gamma, recoil proton and alpha plus heavy recoil ion contribution to the total absorbed dose. The total absorbed dose normalized to the "monitor units" used in daily clinical use has been calculated from the measured spectra and compared to the data measured with calibrated ion chambers. The present measurements agree with the ion chamber data to within 5%. The RBE of the neutron beam is assumed to be proportional to the microdosimetric parameter y* for the dose ranges pertinent to fractionated neutron therapy. The relative variations in y*, assumed to be representative of variations in the RBE are mapped as a function of field size and spatial location in the phantom. A variation in the RBE of about 4% for points within and 8% for points outside a 10 cm x 10 cm field is observed. The variations in the RBE within the beam are caused by an increase in the gamma component with depth. An increase in the RBE of about 4% is observed with increasing field size which is attributed to a change in the neutron spectrum. Compared to the uncertainties in the prescribed dose, associated with uncertainties in the clinically used RBE, variation in the RBE between various tissues, and other dosimetric uncertainties caused by factors such as patient inhomogeneities, patient setup errors, patient motion, etc., the measured spatial RBE variations are not considered significant enough to be incorporated into the treatment planning scheme.     

Proteome of human endometrium: Identification of differentially expressed proteins in proliferative and secretory phase endometrium

Purpose: To exploit the potential of proteomics to identify and study additional yet‐unidentified important proteins present in human endometrium. Experimental design: The proteome of human endometrium would be established using 2‐DE and MALDI and the data analyzed to identify differential protein expression in the proliferative and secretory phase of the menstrual cycle using PDQuest software and MALDI. Results: In the present work, 2‐DE of human endometrium protein led to the resolution of over 200 spots. Subsequent MALDI analysis of 215 spots allowed the identification of 194 proteins. A total of 57 out of the 215 spots were found to be differentially expressed, out of which 49 could be identified using MALDI. These differentially expressed proteins included structural proteins, molecular chaperones, signaling proteins, metabolic proteins, proteins related to immunity, RNA biogenesis, protein biosynthesis and others. The differential expressions of seven representative proteins in secretory and proliferative phase endometrium tissue were confirmed by immunoblot analysis. Conclusion and clinical relevance: This study establishes the 2‐D proteome of human endometrium represented by 194 identified protein spots. The present data provides an important clue towards determining the function of these proteins with respect to endometrium related diseases.     

Order-disorder transition and its effect on microwave quality factor Q in Ba(Zn1/3Nb2/3)O3 system

Influences of composition deviation from stoichiometry and heat treatment on crystal phases and Q factor in Ba(Zn_1/3Nb_2/3)O₃(BZN) were studied. The structural order and the crystal phases strongly depended on the slight composition deviation from stoichiometric BZN. The maximum Q factor was obtained at the vicinity of the stoichiometric BZN. In the other regions, non-stoichiometric disordered BZN or ordered BZN with secondary phase were formed, and their Q factors were found to be low. For the stoichiometric BZN, the order-disorder phase transition occurred between 1300 and 1400^°C. The crystal-structural ordering of the stoichiometric BZN was improved by post-annealing at below its transition temperature, conserving the density and the grain size. However, no significant Q factor improvement was found. The Q factor of the stoichiometric BZN strongly depends on the density and grain size not on the crystal-structural order. These results suggest that the ceramic microstructure such as the pore and grain boundary, the secondary phase and lattice defect caused by non-stoichiometry affect the variation of the Q factor in BZN system than the crystal-structural ordering.     

Degradation behavior of moduli in extruded pure magnesium during low- to giga-scale cyclic tension fatigue

The mechanical properties of extruded pure magnesium during cyclic tension fatigue in the low- to giga-scale regime at room temperature have been investigated using ultrasonic reflection methods with longitudinal and shear waves. The acoustic velocities and calculated Young’s and shear moduli decreased by a large percentage with an increase in the number of cycles in all cycle modes due to growth of grain boundary voids. The eventual degradation of the properties was largest during giga-cycle fatigue, in which the moduli decreased by ～9%. The elastic behavior depended on the drive stress and the number of cycles rather than on fatigue time. Longitudinal and shear wave propagation characteristics and investigations of a grain boundary before and after fatigue using electron backscatter diffraction based on field-emission scanning electron microscopy and focused ion beam transmission electron microscopy revealed that the largest boundary void gap width was less than several nanometers (almost closed). The Poisson’s ratio and bulk modulus were affected notably by the void gap, in which the threshold corresponds to the longitudinal wave amplitude. Other damage phase data were determined using scanning electron microscopy, Vickers hardness, and surface roughness tests under progressive fatigue; these results also indicated slight grain boundary degradation.