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.     

Self-reflective segmentation of human bodily motions using recurrent neural networks

For realizing a naturalistic collaboration between the human and the robot, we have to establish the intention sharing from the series of motion data that are observed and exchanged between the human and the machine. In a word, this is a problem to detect "meanings" out of the digitized data stream. In this paper, we propose a novel approach based on semiosis, and present a method of interpreting bodily motions using recurrent neural networks called Elman networks. We made some experiments using the raw data acquired while a human performs a simple task of fetching objects by stretching and folding his/her arm, and demonstrate that the network can learn invariant features of the generalized motion concepts, classify the motion by referring to self-organized memory structure, and understand a task structure of the observed human bodily motion. These capabilities are essential for machine intelligence to establishing the human-robot shared autonomy, a new style of human-machine collaboration proposed in the area of robotics.     

An early phase II trial combining cisplatin and carboplatin in advanced non-small cell lung cancer

We conducted an early phase II trial in advanced non-small cell lung cancer (NSCLC) to evaluate response efficacy of a combination of Cisplatin (CDDP) and Carboplatin (CBDCA). The twenty-six patients in the study had had no previous treatment. They received a sequential administration of 300 mg/m2 CBDCA and 80 mg/m2 CDDP with approximately 3,500 ml of hydration on day 1 every 4 weeks. All patients were evaluable for response and toxicity. Ten (38.5%) of all assessable patients achieved a partial response (95% confidence interval, 19.8-57.2%). Response rates for patients with stage III A, III B and IV- disease were 40.0 (2/5), 70.0 (7/10) and 9.1% (1/11), respectively. Response rates for patients with squamous cell carcinoma, adenocarcinoma and large cell carcinoma were 35.7 (5/14), 45.5 (5/11) and 0.0% (0/1), respectively. The median survival time (MST) of all patients was 11 months. The MST for patients with stage III disease was 14 months; for those with stage IV disease it was 7 months. The MST for responding patients was 15 months and for not responding patients 5 months. Major toxicities were hematologic and gastrointestinal, and the dose-limiting factor was thrombocytopenia. This combination chemotherapy was effective against NSCLC with tolerable toxicities. Further trials are warranted to determine the efficacy of the combination chemotherapy.     

Premixed flame propagating into a narrow channel at a high speed, part 2: Transient behavior of the properties of the flowing gas inside the channel

The behavior of a premixed flame propagating from a chamber into a narrow channel at a high speed was examined using high speed and instantaneous schlieren photography, ion current measurement with electrostatic probes, and temperature measurement with an optical method. From detailed measurements of flames passing through the channel, flame extinguishment in the channel, no matter whether transient or not, was found to occur due to quenching of the reacting gas by rapid turbulent mixing with cold fresh mixture at the downstream of the contraction region and by heat transfer to the cold channel walls. Extinguishment must occur when these heat losses exceed the heat released by the chemical reaction of the flowing mixture.     

Mechanical stretch induces hypertrophic responses in cardiac myocytes of angiotensin II type 1a receptor knockout mice

Many lines of evidence have suggested that angiotensin II (AngII) plays an important role in the development of cardiac hypertrophy through AngII type 1 receptor (AT1). To determine whether AngII is indispensable for the development of mechanical stress-induced cardiac hypertrophy, we examined the activity of mitogen-activated protein kinase (MAPK) family and the expression of the c-fos gene as hypertrophic responses after stretching cultured cardiac myocytes of AT1a knockout (KO) mice. When cardiac myocytes were stretched by 20% for 10 min, extracellular signal-regulated protein kinases (ERKs) were strongly activated in KO cardiomyocytes as well as wild type (WT) myocytes. Both basal and stimulated levels of ERKs were higher in cardiomyocytes of KO mice than in those of WT mice. Activation of another member of the MAPK family, p38(MAPK), and expression of the c-fos gene were also induced by stretching cardiac myocytes of both types of mice. An AT1 antagonist attenuated stretch-induced activation of ERKs in WT cardiomyocytes but not in KO cardiomyocytes. Down-regulation of protein kinase C inhibited stretch-induced ERK activation in WT cardiomyocytes, whereas a broad spectrum tyrosine kinase inhibitor (genistein) and selective inhibitors of epidermal growth factor receptor (tyrphostin, AG1478, and B42) suppressed stretch-induced activation of ERKs in KO cardiac myocytes. Epidermal growth factor receptor was phosphorylated at tyrosine residues by stretching cardiac myocytes of KO mice. These results suggest that mechanical stretch could evoke hypertrophic responses in cardiac myocytes that lack the AT1 signaling pathway possibly through tyrosine kinase activation.     

Effect of dietary fatty acid composition on the biosynthesis of unsaturated fatty acids in rat liver microsomes

A study was made of the influence of semisynthetic diets of low and high unsaturation on the fatty acid composition and desaturation-chain elongation enzymatic activity of the liver microsomal fractions of male Sprague-Dawley rats of different ages. Groups of rats were fed 5 or 20% coconut oil (CO), or a 5 or 20% mixture of corn and menhaden oils (3∶7) (CME) from weaning to 100 wk of age. Growth rate and food consumption were measured during this period in which animals were sacrificed at 36, 57, 77 and 100 wk of age. Both the level and composition of the dietary fat supplements produced marked effects on the fatty acid composition of the liver microsomal lipids. In general, the fatty acid composition of the microsomal fractions reflected that of the dietary fat and was more unsaturated with the higher level of fat fed. The rate of conversion of linoleic to arachidonic acid in assays performed in vitro with liver microsomal preparations from animals of the different groups also showed marked differences. The 6-desaturase-chain elongation activity was higher in the 5% than 20% group and corresponded to the essential fatty acid (EFA) status of the animals in these groups as represented by the triene-tetraene ratio of the microsomal lipid. The relationship of the 6-desaturase activity to fatty acid composition of the microsomal lipid indicated that if varied directly with the level of 20∶3ω9, 18∶1 and 16∶1 and was inhibited by arachidonic acid. The activity of the 6-desaturase enzyme system was lowest in the liver microsomal fraction obtained from the animals fed the CME diets and appeared to be suppressed by the high levels of 20∶5 and 22∶6 that accumulated in the microsomal lipid. Accordingly, the levels of arachidonic acid were lower in the microsomal lipid of these groups than those of the corresponding CO groups in spite of a greater abundance of linoleic acid in the diet. The data suggest that the activity of the 6-desaturase-chain elongation system is regulated by the fatty acid composition of the microsomal lipid as influenced by the composition of the dietary fat.     

A novel radial orientation treatment of nematic liquid crystals using magnetic field lines with permanent magnet and applying the assisted electric field

Recently, there has been considerable research on optical devices, such as liquid crystal (LC) lenses and special optical plates, using LCs. In such devices, relatively small LC cells are frequently used, or unique LC orientations are required. As an LC orientation process, we focused on the LC director's orientation induced by the magnetic force line distribution of a small neodymium magnet. We propose a simple method for obtaining radial orientation, which is rather difficult to obtain using the ordinary rubbing method. The initial orientation in the LC cell is a vertical orientation cell with almost zero azimuth anchoring. With the proposed method, the reorientation process is performed with an assisting electric field and a small permanent magnet, unlike the conventional magnetic field orientation process that requires a large electromagnet. Furthermore, a polymer stabilization treatment is used to fix the obtained radial orientation pattern in the LC cell. After the treatment, the applying voltage can control the tilt angle of the director in weak polymer treatment, and a completely fixed orientation pattern can be obtained that in strong.     

Sensor Fusion System Using Recurrent Fuzzy Inference

In robotic and manufacturing systems, it is difficult to measure the state of systems accurately because of many uncertain factors and noise, and it is very important to estimate the state of systems. We must measure the phenomena of systems by multiple sensors and estimate the state of systems by acquiring information of sensors. However, we can not acquire all of sensor information synchronically, because each sensor has particular sensor information and measuring time. For estimating the state of systems by multiple sensors, a multi-sensor fusion system fusing various sensory information is needed. In this paper, we propose a Recurrent Fuzzy Inference (RFI) with recurrent inputs and apply it to a multi-sensor fusion system for estimating the state of systems. The membership functions of RFI are expressed by Radial Basis Function (RBF) with insensitive ranges. The shape of the membership functions can be adjusted by a learning algorithm. The learning algorithm is based on the steepest descent method and incremental learning which can add new fuzzy rules. The effectiveness of the multi-sensor fusion system using RFI will be shown through a numerical experiment of moving robot and estimation of surface roughness in grinding process.     

Interactive aesthetic curve segments

To meet highly aesthetic requirements in industrial design and styling, we propose a new category of aesthetic curve segments. To achieve these aesthetic requirements, we use curves whose logarithmic curvature histograms (LCH) are represented by straight lines. We call such curves aesthetic curves. We identify the overall shapes of aesthetic curves depending on the slope of LCH α, by imposing specific constraints to the general formula of aesthetic curves. For interactive control, we propose a novel method for drawing an aesthetic curve segment by specifying two endpoints and their tangent vectors. We clarify several characteristics of aesthetic curve segments.     

Drug-induced pneumonitis caused by sulfamethoxazole, trimethoprim during treatment of Pneumocystis carinii pneumonia in a patient with refractory ulcerative colitis

We recently treated a patient with intractable ulcerative colitis complicated with Pneumocystis carinii pneumonia in whom sulfamethoxazole/trimethoprim caused pneumonitis. The pneumonitis was difficult to differentiate from worsening of the infection or the appearance of another opportunistic infection. The patient's history of sulfasalazine (sulfonamide)-induced pneumonitis made diagnosis possible. The CD4/CD8 ratio of lymphocyte subsets in bronchoalveolar lavage fluid was decreased at the diagnosis of Pneumocystis carinii pneumonia and this ratio had increased when drug-induced pneumonitis was diagnosed. Topical administration of beclomethasone dipropionate by enema was a safe and effective for the treatment of such a compromised patient with active colitis.