Humanized anti-interleukin-6-receptor antibody (tocilizumab) monotherapy is more effective in slowing radiographic progression in patients with rheumatoid arthritis at high baseline risk for structural damage evaluated with levels of biomarkers, radiography, and BMI: data from the SAMURAI study

Our aim was to assess the ability of tocilizumab monotherapy to reduce progressive structural joint damage in rheumatoid arthritis patients at high risk of progression. This study was a subanalysis from a prospective 1-year, multicenter, X-ray-reader-blinded, randomized controlled trial of tocilizumab [Study of Active Controlled Monotherapy Used for Rheumatoid Arthritis, an IL-6 Inhibitor (SAMURAI) trial]. All patients were categorized into two or three groups according to four independent predictive markers for progressive joint damage [urinary C-terminal crosslinking telopeptide (uCTX-II), urinary pyridinoline/deoxypyridinoline (uPYD/DPD) ratio, body mass index (BMI), and joint-space narrowing (JSN) score at baseline]. One-year progression of joint destruction was assessed in high-risk versus low-risk groups receiving tocilizumab monotherapy and compared with patients receiving conventional disease-modifying antirheumatic drugs (DMARDs) (n = 157 and 145, respectively). In patients at high risk of progression of erosion as estimated by high uCTX-II, uPYD/DPD, or low BMI, and at high risk of progression of JSN as estimated by low BMI or high JSN score, the 52-week changes in radiological erosion and JSN, respectively, were significantly less in patients treated with tocilizumab monotherapy compared with those receiving DMARDs for each type of risk factor. In patients at low risk, those receiving tocilizumab also progressed less than those on DMARDs, although the difference did not reach statistical significance. Tocilizumab monotherapy is more effective in reducing radiological progression in patients presenting with risk factors for rapid progression than in low-risk patients. Patients at high risk for progression may benefit more from tocilizumab treatment

Administration of oxygen ultra-fine bubbles improves nerve dysfunction in a rat sciatic nerve crush injury model

Ultra-fine bubbles (<200 nm in diameter) have several unique properties and have been tested in various medical fields. The purpose of this study was to investigate the effects of oxygen ultra-fine bubbles (OUBs) on a sciatic nerve crush injury (SNC) model rats. Rats were intraperitoneally injected with 1.5 mL saline, OUBs diluted in saline, or nitrogen ultra-fine bubbles (NUBs) diluted in saline three times per week for 4 weeks in four groups: (1) control, (sham operation + saline); (2) SNC, (crush + saline); (3) SNC+OUB, (crush + OUB-saline); (4) SNC+NUB, (crush + NUB-saline). The effects of the OUBs on dorsal root ganglion (DRG) neurons and Schwann cells (SCs) were examined by serial dilution of OUB medium in vitro. Sciatic functional index, paw withdrawal thresholds, nerve conduction velocity, and myelinated axons were significantly decreased in the SNC group compared to the control group; these parameters were significantly improved in the SNC+OUB group, although NUB treatment did not affect these parameters. In vitro, OUBs significantly promoted neurite outgrowth in DRG neurons by activating AKT signaling and SC proliferation by activating ERK1/2 and JNK/c-JUN signaling. OUBs may improve nerve dysfunction in SNC rats by promoting neurite outgrowth in DRG neurons and SC proliferation.Matsuoka H., Ebina K., Tanaka H., et al. Administration of oxygen ultra-fine bubbles improves nerve dysfunction in a rat sciatic nerve crush injury model. International Journal of Molecular Sciences 19, 1395 (2018); https://doi.org/10.3390/ijms19051395

Basic Reseach on the Simulation of "Sensibility Information Processing"

We have studied the information processing of human sensibility from various approaches. In an approach from information retrieval theory, we constructed a "sensibility information retrieval system" which extracts words expressing human feelings from a novel and analyzes the chronological structure of the novel. Novels are thus classified into those with increasing-sadness, those with happy-endings, etc. In an approach from psychology, we constructed a model which simulates the process of evoking emotion. Words expressing feelings are classified, and the influence of past experiences and the effects on future actions are investigated by experiments. In an approach from business management, we point out that the study of sensibility information has a good applicability in the decision making system of an organization because the feelings of its members are crucial in making decisions. In particular, we emphasize that a "good morale" among organizational members is essential in avoiding serious accidents. From a device approach, we study the signal processing of electrical data trains using a modulated laser diode, and propose a potential application to the microwave phase shifter with small variations in amplitude

Comparison of postmenopausal endogenous sex hormones among Japanese, Japanese Brazilians, and non-Japanese Brazilians

<p>Abstract</p> <p>Background</p> <p>Differences in sex hormone levels among populations might contribute to the variation in breast cancer incidence across countries. Previous studies have shown higher breast cancer incidence and mortality among Japanese Brazilians than among Japanese. To clarify the difference in hormone levels among populations, we compared postmenopausal endogenous sex hormone levels among Japanese living in Japan, Japanese Brazilians living in the state of São Paulo, and non-Japanese Brazilians living in the state of São Paulo.</p> <p>Methods</p> <p>A cross-sectional study was conducted using a control group of case-control studies in Nagano, Japan, and São Paulo, Brazil. Participants were postmenopausal women older than 55 years of age who provided blood samples. We measured estradiol, estrone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), testosterone and free testosterone by radioimmunoassay; bioavailable estradiol by the ammonium sulfate precipitation method; and sex hormone-binding globulin (SHBG) by immunoradiometric assay. A total of 363 women were included for the present analyses, comprising 185 Japanese, 44 Japanese Brazilians and 134 non-Japanese Brazilians.</p> <p>Results</p> <p>Japanese Brazilians had significantly higher levels of estradiol, bioavailable estradiol, estrone, testosterone and free testosterone levels, and lower SHBG levels, than Japanese. Japanese Brazilians also had significantly higher levels of bioavailable estradiol, estrone and DHEAS and lower levels of SHBG and androstenedione than non-Japanese Brazilians. Levels of estradiol, testosterone and free testosterone, however, did not differ between Japanese Brazilians and non-Japanese Brazilians. These differences were observed even after adjustment for known breast cancer risk factors. We also found an increase in estrogen and androgen levels with increasing body mass index, but no association for most of the other known risk factors.</p> <p>Conclusions</p> <p>We found higher levels of estrogens and androgens in Japanese Brazilians than in Japanese and levels similar to or higher than in non-Japanese Brazilians. Our findings may help explain the increase in the incidence and mortality rate of breast cancer among Japanese Brazilians.</p

Stable Supply of Mineral Resources and Environmental Problems

There are many factors which can become obstacles against the stable supply of mineral resources, and unstable supply causes serious disruptions in both the economy and industry. In Information Technology (IT) industries, some rare metals used as high function materials are immediately needed for import. For instance, small condensers for mobile phones or laptop personal computers require powdered tantalum. Recently, this powdered tantalum is in short supply as the demand for I.T. products increases rapidly. This shortage causes a steep rise in price and the market shifts to speculation. Shortages are the most serious problem in Japan, worse than high prices, because we consume 20-25% of the world\u27s products, that is, lack of resources affects not only the economy but also technology. Since supply conditions for each metal are different, it is impossible to simply discuss the reason why shortages occur. For the base metals that have a long history of use like copper, iron, lead and zinc, it is relatively easy to clarify their market mechanism, while for most rare metals it is difficult to discuss the relation between supply and demand. In the IT industry, munition industry or space development, new materials are continuously developed from many rare metals, and market mechanisms are always changed by these new materials. In such conditions, the gap in environmental safeguards among countries becomes a serious problem because it highlights the difference of ability in price competition. Developed countries generally load more expenses than developing countries for environmental safeguards, therefore, developing countries have more advantages than developed countries. As a result, many metal mines in developed countries must be closed, and maldistribution of rare metals becomes worse; price manipulation would be easier by monopoly or oligopoly. On the other hand, developing countries make global environmental problems worse because of their resource extractions. In this paper, the basic conditions for a stable supply are considered first, and then shortages, which are caused by environmental problems, is considered

Optimal Intravascular Ultrasound-Guided Percutaneous Coronary Intervention in Patients With Multivessel Disease

BACKGROUND: Intravascular ultrasound (IVUS) was only rarely used in landmark trials comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with multivessel disease. OBJECTIVES: The authors aimed to evaluate clinical outcomes after optimal IVUS-guided PCI in patients undergoing multivessel PCI. METHODS: The OPTIVUS (OPTimal IntraVascular UltraSound)-Complex PCI study multivessel cohort was a prospective multicenter single-arm study enrolling 1, 021 patients undergoing multivessel PCI, including left anterior descending coronary artery using IVUS, aiming to meet the prespecified criteria (OPTIVUS criteria: minimum stent area > distal reference lumen area [stent length ≥28mm], and minimum stent area >0.8 × average reference lumen area [stent length <28mm]) for optimal stent expansion. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE) (death/myocardial infarction/stroke/any coronary revascularization). The predefined performance goals were derived from the CREDO-Kyoto (Coronary REvascularization Demonstrating Outcome study in Kyoto) PCI/CABG registry cohort-2 fulfilling the inclusion criteria in this study. RESULTS: In this study, 40.1% of the patients met OPTIVUS criteria in all stented lesions. The cumulative 1-year incidence of the primary endpoint was 10.3% (95% CI: 8.4%-12.2%), which was significantly lower than the predefined PCI performance goal of 27.5% (P < 0.001), and which was numerically lower than the predefined CABG performance goal of 13.8%. The cumulative 1-year incidence of the primary endpoint was not significantly different regardless of meeting or not meeting OPTIVUS criteria. CONCLUSIONS: Contemporary PCI practice conducted in the OPTIVUS-Complex PCI study multivessel cohort was associated with a significantly lower MACCE rate than the predefined PCI performance goal, and with a numerically lower MACCE rate than the predefined CABG performance goal at 1 year

Local microbleeding facilitates IL-6– and IL-17–dependent arthritis in the absence of tissue antigen recognition by activated T cells

Local microbleeding induces the accumulation of Th17 cells and the development of IL-17– and IL-6–dependent arthritis in the absence of cognate antigen recognition by CD4+ T cells

Exchange of “signature” calls in captive belugas (Delphinapterus leucas)

Belugas (Delphinapterus leucas) produce echolocation clicks, burst pulses, and whistles. The sounds of 3 captive belugas were recorded using 2 hydrophones at the Port of Nagoya Public Aquarium. There were stable individual differences in the pulse patterning of one type of pulsed sounds (PS1 call), suggesting that belugas use these as “signature” calls. Eighty-eight percent of PS1 calls initiated PS1 calls from other animals within 1 s. PS1 calls repeated by the same individual occurred primarily when other belugas did not respond within 1 s of the first call. Belugas delayed successive PS1 calls when other belugas responded with a PS1 call within 1 s. There was no clear temporal pattern for whistles. It appears that the time limit for responding to calls is 1 s after the initial call. If other individuals do not respond to the PS1 call of a beluga within 1 s, belugas tend to repeat the call and wait for a response. The results of this study suggest that the belugas exchange their individual signatures by using PS1 calls, in a manner similar to that of signature whistles used by bottlenose dolphins