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.     

Post-lunch nap as a worksite intervention to promote alertness on the job.

A worksite study was conducted to examine whether a 15-min nap during a post-lunch rest period would affect subsequent alertness, performance, and nocturnal sleep in eight factory workers under a 3-week protocol. Subjects were asked to take the nap at 12:30 h on a reclining chair during the nap week, and to remain awake during the no-nap week. The order of these 2 weeks was counterbalanced between the subjects. During the third, follow-up week, each subject determined whether or not she/he would nap. Alertness on the job and nocturnal sleep were assessed using a sleep diary. Wrist activity was also recorded during sleep at night. Choice reaction time task (RT) was performed at 10:00 and 15:00 h every day of the nap week and every other day of the no-nap and follow-up weeks. Perceived alertness was significantly higher in the afternoon after nap than after no nap at the end of the week. Similar effects were observed during the follow-up week where almost half of the subjects napped. No significant differences between the three weeks were found for RT performance or nocturnal sleep. Workers' attitudes toward the nap were favourable. Although further intervention research is required, our results suggest that post-lunch napping may have the potential to promote daytime alertness at work.     

Rapid detection cytomegalovirus pneumonia in recipients of bone marrow transplant: evaluation and comparison of five survey methods for bronchoalveolar lavage fluid

To detect cytomegalovirus-associated interstitial pneumonia (CMV-IP) in recipients of BMT in its earliest stage, five CMV methods were assessed for their usefulness using bronchoalveolar lavage fluid as the test specimen. Of the 43 cases enrolled in the study, PCR was positive in 12 cases, shell vial in eight, culture in eight and cytology in three. There were no positive cases in in situ hybridization. Based on this result, the 43 cases were classified into four groups: Group 1, three cases: positive in PCR, shell vial and cytology; Group 2, five cases: positive in PCR and shell vial; Group 3, four cases: positive only in PCR; and Group 4, 31 cases: negative in all CMV tests. Cases in Group 1 were judged as having the highest risk of overt CMV-IP. They were successfully treated with a combination of ganciclovir and immunoglobulin. Group 2 was diagnosed as having active CMV infection and ganciclovir monotherapy was effective for these patients. Groups 3 and 4 were not given anti-CMV therapy, but they were free from CMV-related manifestations throughout the study. The sensitivity and specificity of each survey method for the detection of Groups 1 and 2 were 1.0 and 0.89 in PCR, 1.0 and 1.0 in shell vial, 0.88 and 1.0 in culture, and 0.38 and 1.0 in cytology. Similarly, the positive and negative predictive values were 0.67 and 1.0 in PCR, 1.0 and 1.0 in shell vial, 1.0 and 0.97 in culture, and 1.0 and 0.88 in cytology. Thus, CMV survey on bronchoalveolar fluid was thought to be useful in detecting post BMT CMV-IP in its earliest stage.     

Three-dimensional display of the bronchi using helical CT

The purpose of this study was to evaluate the clinical usefulness of three-dimensional (3D) images of the bronchi obtained using helical CT. Thirteen patients with lung cancer, one with tracheal diverticulum, and one with bronchial amyloidosis were examined. The CT scanner employed was the Toshiba Xforce. The helical CT scan cycle consisted of 20 continuous rotations, each requiring 1.5 sec, for a total scanning time of 30 sec. Scans were obtained using a 5-mm X-ray beam width, a 5-mm/1.5 sec couchtop sliding speed, and a 2-mm reconstruction interval. 3D images were reconstructed using a CEMAX VIPstation. The optimal lower and upper threshold CT values for 3D images of the bronchi were -650 and -100 HU, respectively, and 3D images clearly depicted endobronchial lesions. Cartilage crescents were also demonstrated, but longitudinal and circular mucosal folds could not be visualized. In conclusion, 3D images of the bronchi acquired using helical CT were useful in evaluating endobronchial lesions.     

Percutaneous lumbar nucleotomy

The nature of the events whereby the reactive intermediates resulting from the bioactivation of bromobenzene and furosemide induce hepatotoxicity is unknown. To examine a role for disturbances in intracellular calcium homeostasis, secondary to a depletion in cellular reduced glutathione (GSH) and reduced protein thiols (PSHs), isolated mouse hepatocytes were exposed to cytotoxic concentrations of bromobenzene or furosemide. Cytosolic calcium concentration, as well as thiol status, was determined. The incubation of hepatocytes with 3.0 mM bromobenzene, and subsequent additions (1.2 mM) of the agent every hour, resulted in significant GSH depletion. The loss of plasma membrane integrity at 1.5 h preceded both a rise in the cytosolic Ca2+ concentration and depletion of total PSH content. Furosemide (1.0 mM) produced a 70% depletion in cellular GSH content in isolated hepatocytes. The initiation of cell damage occurred concurrently with both a rise in the cytosolic Ca2+ concentration and a depletion of total PSH content 4 h following furosemide addition. Since the increase in cytosolic Ca2+ did not precede cytotoxicity, these results do not support an initiating role for Ca2+ deregulation in bromobenzene and furosemide hepatotoxicities. In addition, depletion of PSH content did not correlate with bromobenzene- or furosemide-induced cytotoxicity.     

Development of 170 GHz/500 kW gyrotron

A development of 170GHz/500kW level gyrotron was carried out as R&D work of ITER. The oscillation mode is TE_31,8. In a short pulse experiment, the maximum power of 750kW was achieved at 85kV/40A. The efficiency was 22%. In the depressed collector operation, 500kW/36%/50ms was obtained. The maximum efficiency of 40% was obtained at P_RF=470kW whereas the power decrease by the electron trapping was observed. Pulse extension was done up to 10s at P_RF=170kW with the depressed collector operation. The power was limited by the temperature increase of the output window.     

Improvements of the T-Ω method for 3-D eddy currentanalysis

An improved T-Ω method that can analyze magnetic fields produced not only by eddy currents but also by magnetizing currents is proposed. The method is applied to the analysis of 3-D eddy-current models with holes. The usefulness of the method is investigated by comparing calculated results with measured results and with results obtained by the A-Φ method. The T-Ω method has the advantage that the CPU time can be considerably reduced when most of the analyzed region is current-free and the eddy current flows two-dimensionally. The method is especially effective when the shape of the winding is simple and the distribution of magnetizing current is known beforehand. It is not effective when most of the analyzed region is current-carrying     

A 64-Mb DRAM with meshed power line

A 64-Mb dynamic RAM (DRAM) has been developed with a meshed power line (MPL) and a quasi-distributed sense-amplifier driver (qDSAD) scheme. It realizes high speed, t_RAS=50 ns (typical) at V_cc=3.3 V, and 16-b input/output (I/O). This MPL+qDSAD scheme can reduce sensing delay caused by the metal layer resistance. Furthermore, to suppress crosstalk noise, a V_SS shield peripheral layout scheme has been introduced, which also widens power line widths. This 64-Mb DRAM was fabricated with 0.4-μm CMOS technology using KrF excimer laser lithography. A newly developed memory cell structure, the tunnel-shaped stacked-capacitor cell (TSSC), was adapted to this 64-Mb DRAM     

Granular Reasoning Using Zooming In & Out: Part 2. Aristotle's Categorical Syllogism

The concept of granular computing is applied to Aristotle's categorical syllogism. Such kind of reasoning is called granular reasoning in this paper. For the purpose, two operations called zooming in & out are introduced to reconstruct granules of possible worlds.