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Background: The COVID-19 pandemic led to profound changes in the organization of health care systems worldwide. Aims: We sought to measure the global impact of the COVID-19 pandemic on the volumes for mechanical thrombectomy, stroke, and intracranial hemorrhage hospitalizations over a three-month period at the height of the pandemic (1 March–31 May 2020) compared with two control three-month periods (immediately preceding and one year prior). Methods: Retrospective, observational, international study, across 6 continents, 40 countries, and 187 comprehensive stroke centers. The diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases at participating centers. Results: The hospitalization volumes for any stroke, intracranial hemorrhage, and mechanical thrombectomy were 26,699, 4002, and 5191 in the three months immediately before versus 21,576, 3540, and 4533 during the first three pandemic months, representing declines of 19.2% (95%CI, −19.7 to −18.7), 11.5% (95%CI, −12.6 to −10.6), and 12.7% (95%CI, −13.6 to −11.8), respectively. The decreases were noted across centers with high, mid, and low COVID-19 hospitalization burden, and also across high, mid, and low volume stroke/mechanical thrombectomy centers. High-volume COVID-19 centers (−20.5%) had greater declines in mechanical thrombectomy volumes than mid- (−10.1%) and low-volume (−8.7%) centers (p < 0.0001). There was a 1.5% stroke rate across 54,366 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.9% (784/20,250) of all stroke admissions. Conclusion: The COVID-19 pandemic was associated with a global decline in the volume of overall stroke hospitalizations, mechanical thrombectomy procedures, and intracranial hemorrhage admission volumes. Despite geographic variations, these volume reductions were observed regardless of COVID-19 hospitalization burden and pre-pandemic stroke/mechanical thrombectomy volumes. © 2021 World Stroke Organization.

OBJECTIVE: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods. METHODS: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. RESULTS: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] -11.7 to -11.3, p < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI -13.8 to -12.7, p < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI -13.7 to -10.3, p = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2-9.8, p < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions. CONCLUSIONS: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months. © 2021 American Academy of Neurology.

Since its introduction approximately 20 years ago, the Challenge-Hindrance Stress Model (CHM) has been widely accepted both among academic and practitioner audiences. The model posits that workplace stressors can be grouped into two categories. Hindrance stressors will interfere with performance or goals, while challenge stressors contribute to performance opportunities. These two categories of stressors are theorized to exhibit differential relationships with strain, with hindrance stressors being more consistently linked to psychological, physical, or behavioral strain compared to challenge stressors. Despite the popularity of this model, recent evidence suggests that the proposed differential relationship hypothesis has not consistently held true for all types of strain. Thus, a reexamination or modification of this paradigm is clearly warranted. In the present review, we describe existing evidence surrounding the CHM and describe the rationale for a shifting paradigm. We outline recent advances in research using the CHM, such as novel moderators and mediators, the need to explicitly measure challenge and hindrance appraisal and differentiate between hindrance and threat appraisal, the dynamic nature of these appraisals over time, and the recognition that a single stressor could be appraised simultaneously as both a challenge and a hindrance. Finally, we provide recommendations and future research directions for scholars examining stress and stress management through a CHM lens, including recommendations related to study design, the measurement of stressors, the integration of CHM with other models of stress, and interventions for stress management.

Objective: We seek to evaluate the opinions of nurses and doctors in Japan regarding EULAR recommendations for nurses' roles in the management of chronic inflammatory arthritis.Methods: This is a cross-sectional survey within Japan. We randomly selected nurses and doctors engaged in consultation of patients with rheumatoid arthritis (RA) and assessed their agreement and opinions on the feasibility of implementing EULAR recommendations, including potential barriers.Results: 431 nurses and 128 doctors completed the questionnaire. For both nurses and doctors, levels of feasibility showed statistically significant lower results compared with those of agreement for all items. When compared between nurses and doctors, agreement showed no statistically significant differences, while nurses' answers were statistically significant lower for feasibility. Insufficient time, staff and knowledge, lack of established procedures and facilities, and lack of an education system for nurses were cited as barriers to the feasibility of implementing EULAR recommendations.Conclusions: This is the first survey within Japan evaluating opinions regarding EULAR recommendations for nurses' roles. We found that while agreement was high, feasibility was generally believed to be low. We recommend further research and collaboration between medical professionals in order to implement these recommendations in Japan.

Background Rheumatoid arthritis (RA) is a chronic disease with periods of flare-ups and remissions, affecting daily life. Therefore, this disease requires lifelong management and support by the patients social circle and health professionals (HP). Objectives The aim of this study was to follow up the history of patients with RA, and demonstrate an improved understanding at each point in their disease trajectory, whilst encouraging them to cope, and enabling HP to optimize support provided. Methods We conducted two 30minute interviews with patients with RA. Interview questions included the patients perspective of their disease and disease information, effects on daily life, as well as psychological considerations using the Corbin and Strauss Chronic Illness Trajectory Framework approach [1]. This study was approved by the ethics committee of our hospital and informed consent was obtained. Results The first case; An unmarried 68 year old female living alone. The patients mother also suffered from RA. The patient was vaguely aware of the hereditary nature of RA (pretrajectory phase) and did not result in a big shock to her and she accepted her the diagnosis relatively smoothly (trajectory onset phase). She was prescribed initially prescribed methotrexate but this proved infective and infliximab was commenced. Remission was achieved and at that time she was satisfied with her relationship with her primary physician (stable phase). Two years after beginning infliximab, she developed chest pain. However, her primary physician did not explore the problem and advised her that she had depression. She began to distrust him (unstable). She asked for infliximab to be stopped and requested her care be transferred to B university hospital where her mother was being treated. However, she was refused treatment due to the non-severity of her condition. She was unable to come to terms with refusal, and her physical and mental state deteriorated (downward phase). Her mother advised the patient to go to D hospital, where she was put on Etanercept achieving remission with no complications (comeback phase). At D Hospital; (1) her condition and the need for treatment were clearly explained to her, and she was able to actively participate in shared decision making; and (2) she was given access to support from Health Professionals (HP) such as nurses, who offered a patient centered approach listening to her concerns and advising her appropriately whilst offering general psychological support. A further 4 patients were interviewed. We will show the key phases of trajectories of their illnesses, the patients opinions about sharing their information with HP through interviewing, and the possibility of behavior change in the patients journeys. Conclusion This study shows that a patient centered approach taking into account the stages of the illness trajectory benefits patients perceptions of their disease and ability to cope with their condition. It also highlights the importance of having the support of ones social circle, particularly at challenging times. Making a thorough record of the patients disease and QOL trajectory allows the patient to understand their disease process and associated life changes, and assist health professionals to provide the optimal support and resolve problems when they arise. This preliminary study focuses on understanding the value of different phases of the trajectory of illness and sheds more light on the relationship between patients and HP and how the disease process and patients perspectives of their disease can facilitate mutual trust and smooth future treatment. References [1] Corbin JM. Sch Inq Nurs Pract 1998;12: 341. Disclosure of Interests MIE FUSAMA: None declared, Susan Oliver: None declared, Hideko Nakahara: None declared, Yvonne van Eijk-Hustings Grant/research support from: UCB, Speakers bureau: Cellgene, Yuriko Kuroe: None declared

Background:The course of rheumatoid arthritis (RA) differs from patient to patient, and each patient has a unique story. The disease condition affects psychological and social aspects, greatly affecting the quality of life. The disease course is unpredictable, and each patient’s story can be seen as a lifelong journey, full of ups and downs. Therefore, it is crucial to know what kind of support is required during the course of their life.Objectives:The aim of this study is to examine the life story of patients with RA and clarify a common situation in their stories in order to consider what kind of support is needed.Methods:This is a qualitative study using life story interview for patients with RA in Japan. Interview included disease history, patients’ behaviors, effects on daily life, the patients’ perspectives regarding psychological considerations and useful support. Data were analyzed using content analysis. This study was approved by the ethics committee and informed consent was obtained.Results:Eight patients participated in this study. They were all females and the average age was 57 years old. As a result of the categorization, we extracted the following eight situations: (1) Emergence of symptom; patients thought joint pain would go away, however, the symptom did not improve and began to affect their daily life and work, (2) Choose a hospital to visit; pain and anxiety have continued and decided to visit a hospital, (3) Encounter with their doctors; patients expected their doctor to relieve their pain, while they were afraid of being told that they were suffering from a serious disease. (4) Diagnosis of RA; patients were shocked when diagnosed and anxious about what would happen and wondered why they had such a disease, (5) Choice of treatment; patients were afraid of the side effects. They wanted to make a decision discussing with their doctor, but they could not understand the explanation about drugs well and, therefore, followed the doctor’s opinion. (6) Change of treatment; a biological agent was often recommended. Patients were also worried about side effects and the financial burden. (7) Remission or stable phase; they felt better mentally too, however, they often felt anxiety about disease flare, side effect of drugs and financial burden, and (8) Flare and remission; patients felt shocked and disappointed when RA flared, and then, they noticed that patients with RA had alternating periods of relapse and remission and they had to live with RA.These interviews revealed repeated worsening and improvement of symptoms and many similar repeated psychological reactions such as anxiety, shock, denial, conflict, acceptance, giving up and relief. To cope with these fluctuating disease and mental conditions, patients were supported by educational and psychological assistance, timely consultations, social life help from nurses and support from their family. The patients considered a trusting relationship with their doctors is necessary. The patients had also realized through their experience the importance of enhancing their own abilities, such as decision-making, prevention of infections and self-management skills. Moreover, they noticed that it is important to have their own goals including hobbies and work.Conclusion:This study elucidated the common behaviors of patients with RA, the impact of RA on their psychological state and daily and social life, and the required support. The psychological condition and daily and social life also had a great influence on medical behavior. Therefore, psychosocial support and establishment of trust between healthcare professionals and patients are crucial. In addition, improving patients’ self-management skills including self-efficacy and empowerment is also necessary. As patients with RA often feel anxious in various situations and expect nurses’ support, nurses should listen to patients, pay attention to their concerns and anxieties, and show a solution-oriented attitude. In order for patients to feel at ease in their Patient Journey, nurses should sail with them while maintaining a patient-centered perspective.Disclosure of Interests:None declared

Background:The role of rheumatology nurses is considered important for the implementation of T2T [1]. For nurses’ contribution to implementation of the T2T strategy, it is necessary to explore the nurses’ opinion on their roles in real clinical practice.Objectives:The aim of this study is to evaluate what is required for nurses to implement T2T in real clinical practice in Japan.Methods:Registered nurses engaged in rheumatic care in clinical practice in Japan were enrolled. Focus group interviews were conducted exploring ‘What is necessary for RA nurses to implement T2T’using semi-structured interviews. Data analysis was used with Krippendorff’s content analysis method.Results:24 nurses (all females) from 10 hospitals were enrolled in this study. The results of the qualitative analysis were categorized in 10 main categories, derived from 37 subcategories based on 64 different codes: (1) provide basic knowledge of RA, (2) provide knowledge of RA drugs, (3) provide knowledge and skills of self-monitoring, (4) enhance self-efficacy and support self-management, (5) support decision-making, (6) psychological and social support, (7) understand the diversity and feelings of patients and their families, (8) support based on individual needs, (9) ensure continuing educational opportunities for nurses to enable the provision of high quality care, (10) collaborate with multidisciplinary teams.These categories are mostly covered in the contents of the 2018 updated EULAR recommendations for the role of nurses except “evidence-based rheumatic care”, “telehealth” and “comprehensive participation in disease management”.Conclusion:These findings indicate the areas of exploration including further educational and training needs, attitudes and the professional scope for nurses to extend their roles to provide greater value to patient care.In Japan, evidence-based RA nursing and telehealth systems have not yet been established. In addition, therapeutic intervention by nurses and nurse-led clinic are not permitted. Our results might reflect this situation and possibly elucidates the gap between EULAR’s evidence-based recommendations and opinions of Japanese nurses working in daily clinical practice. As evidence-based nursing is considered to be crucial from both cost-effectiveness and improvement of patients QOL, this result also might shed light on what we need for future better rheumatic nursing in Japan.References:[1]van Eijk- Hustings Y, et al. Ann Rheum Dis 2012;71: 13–19.Disclosure of Interests:MIE FUSAMA: None declared, Miyabi Uda: None declared, Harumi Matsumura: None declared, Yvonne van Eijk-Hustings Grant/research support from: grand from sanofi and UCB, Consultant of: fee from amgen, Susan Oliver: None declared, Hideko Nakahara: None declared

Background Patients with rheumatoid arthritis (RA) who achieved clinical remission sometimes have synovitis detected by joint ultrasonography (US) (1). This residual synovitis has been shown to be predictive of insidious radiographic progression, flares after tapering or cessation of DMARDs. Since it is difficult to examine all joints by US in daily clinical practice, several joint combinations have been proposed for optimal and/or feasible assessments of joint inflammation in patients with RA. Objectives To find the minimum number of paired joint set for US to predict clinically significant residual synovitis. Methods A comprehensive US assessment of joints was performed in 109 RA patients who achieved DAS28-CRP remission or low disease activity. Totally 40 (20 pairs) of joints including metacarpophalangeal (MCP) 1 to 5, proximal interphalangeal (PIP) 1 to 5, wrist, elbow, shoulder, knee, ankle, metatarsophalangeal (MTP) 1 to 5 joints were evaluated according to the EULAR recommendation (2). Residual synovitis was defined as synovial hypertrophy with grey scale (GS) score greater than 1 or GS score 1 with any power Doppler (PD) signal, using semi quantitative scoring system (scale 0 to 3). Results 73 of 109 patients (67%) had at least one residual synovitis, and 39 of 73 patients (53.4%) had residual synovitis at least two different joints. As shown in table 1, residual synovitis at wrist and knee joints were found in 54.8% and 53.4% of 73 patients respectively, while for residual synovitis of another joints were less than 20% of patients. Solitary residual synovitis was most frequent in wrist and knee joints. By adding and combining joints which frequently found to have residual synovitis, we found that combination of wrist, knee, ankle, elbow, MCP1, and MCP2 joints (6 pairs) could detect residual synovitis in 94.5% of patients (table 2). Using the fact that one patients can have more than one residual synovitis at different joints and the tendency of residual synovitis to be found at some particular joints, we might find minimum pairs set of joint ultrasonography to detect residual ultrasound-defined synovitis. This could minimise the efforts needed to perform thorough joint US, while keeping the sensitivity high enough to detect any residual synovitis. Conclusions Patients achieved DAS28-CRP remission often had residual synovitis. The residual synovitis had tendency to be distributed at wrist, knee, ankle, elbow, MCP1, and MCP2, joints frequently used in activities of daily life. We propose this combination of joints as the minimum paired joint set to predict ultrasonographic remission. References [1] Foltz V, et al. Arthritis & Rheumatology2012;64:67–76. [2] Backhaus M, et al. Ann Rheum Dis2001;60:641–649. Disclosure of Interest None declared

Background Biologics are effective for improving disease activity in patients with rheumatoid arthritis (RA). However, improved disease activity of RA alone does not always lead to high patient satisfaction. Objectives We evaluate which factors among items of disease activity and health status are correlated with improvement of patient satisfaction in patients with RA treated with biological agent. Methods Patients with RA who were planning to be treated with tocilizumab (TCZ) were enrolled in this study. Satisfaction, disease activity, and health status were assessed at week 0 and week 24 of TCZ therapy. Disease activity was evaluated using SJC, TJC, PGA, EGA and CDAI. Pain was also assessed using Visual Analogue Scale (VAS). Satisfaction and health status were assessed using the patient satisfaction score and the 5 components of the Arthritis Impact Measurement Scale 2 (AIMS-2). Multiple linear regression analysis was used to assess the correlation between changes in satisfaction, disease activity and health status adjusted for CDAI at weed 0. Also, Wilcoxon signed rank test was used to evaluate effect of TCZ on satisfaction, disease activity, and health status. Results Nineteen patients (male/female: 4/15) were evaluated. Patients’ data at baseline were as follows: mean of age (51.3), disease duration (7.6 years), SJC (12.2), TJC (9.6), PGA (47.9 mm), EGA (51.4 mm), CRP (2.9 mg/dl) and CDAI (10.2), respectively. SJC, TJC, PGA, CDAI and RA-pain showed a statistically significant decrease at week 24 compared to the baseline (p After adjusting for CDAT at week 0, the change in satisfaction from week 0 to week 24 showed statistically significant correlation with changes in PGA and pain-VAS (all p-values Conclusions Satisfaction was correlated with pain, PGA and psychological state in patients with RA treated with tocilizumab. On the other hand, satisfaction was not correlated with TJC, SJC and EGA. In other words, it appears that patient satisfaction is more closely linked with how symptoms are experienced physically and mentally. Further research into specific factors influencing the patients’ experience could shed more light on conditions for improving patients’ satisfaction and QOL. Disclosure of Interest None declared

Background Patients with rheumatoid arthritis (RA) often suffer from psychological concerns.1 There is a lack of psychology specialists in many hospitals and clinics. According to EULAR, nurses should undertake a significant portion of providing psychological support to patients.2 However, in Japan nurses involved in clinical practice often do not have sufficient time and opportunity to receive adequate education on psychological support. Objectives The aim of this study is to evaluate nurses’ understanding of basic psychological concepts and the efficacy of a short psychology workshop for nurses in RA clinical care. Methods A clinical psychotherapist provided a lecture on psychological support once for a period of 30 min, followed by 1 hour of role-play groupwork. The lecture focused on basic psychological support including concepts of “listening”, “acceptance”, “empathy”, “open question”, “closed question” and “patient-centred perspective”. Group work focused on applying the aforementioned concepts. Nurses were asked before and after workshop regarding their understanding and opinions on the necessity and feasibility of psychological support, as well as their motivation for implementation. Nurses’ opinions were evaluated on a 1–7 rating scale (1=not at all, 7=full). Client Satisfaction Questionnaire-8 (CSQ-8J) was utilised to assess satisfaction with the workshop. Data analyses were performed with Wilcoxon signed rank test. Results 53 nurses (M/F: 1/52) participated in this study. The average of ages, clinical experience and clinical experience in RA care were 45.5 years old, 21.0 and 7.9 years, respectively. Nurses’ opinions regarding the necessity and feasibility of psychological support in general, as well as their motivation for providing psychological support statistically significantly increased post-workshop (necessity: p=0.0052, feasibility: p Nurses’ answers regarding their current application of these concepts in clinical practice were as follows: mean ±SD; listening: 5.15±1.20, empathy: 5.06±1.18, acceptance: 4.71±1.18, open question: 4.80±1.31, closed question: 4.49±1.47. The understanding of these concepts was statistically significantly higher after the workshop (p Conclusions This is the first report evaluating the effectiveness of brief psychological workshops for nurses in rheumatic care in Japan. This preliminary study demonstrated that even a brief workshop appears effective for assisting and encouraging nurses in providing psychological support to patients. Further studies of training methods and of nurses’ application of the skills acquired in such training are ongoing. References [1] Hyrich K, et al. Ann Rheum Dis2006;65:895–8. [2] van Eijk-Hustings Y, et al. Ann Rheum Dis2012;71:13–9. Disclosure of Interest None declared

Objectives To study the residual Power Doppler (PD) signals for assessing synovitis in CRP negative patients with rheumatoid arthritis (RA) treated with biologics. Methods Biologics treated RA patients who were maintained normal CRP for more than 6months (34 TNF inhibitors, 37 Tocilizumab, 23 Abatacept) were assessed by ultrasonography. Residual PD signals were assessed in MCP, PIP, and wrist joints with both hands. We assumed patients who had any PD signals in assessed joints were “residual PD signals”. Results All treated patients with biologics maintained normal CRP for a half year (n=94). 35.1% of patients treated with biologics had positive PD signals. The remission rates of DAS28-ESR, CDAI, and Boolean were 68.7%, 62.8%, and 48.9% respectively. 28.1% of patients who achieved DAS28-ESR remission had residual PD signals, 22.0% in CDAI, and 21.7% in Boolean. 23.8% of patients treated by TNF inhibitors who achieved DAS28-ESR remission had residual PD signals, 34.6% in Tocilizumab, and 20.0% in Abatacept. In case of setting the DAS28-ESR remission less than 3.0, 30.2% of patients who achieved DAS28-ESR remission had residual PD signals, 29.0% in less than 2.0, and 12.5% in less than 1.5. The patients who have no tender or swollen joints and the excellent patient oriented global health assessment (VAS score was zero) had fewer residual PD signals (23.4% vs 58.6% in tender joints, 26.7% vs 66.7% in swollen joints, and 13.3% vs 44.4% in patient VAS). Conclusions The patients who achieved clinical remission had residual PD signals. Patients with Tocilizumab induced remission had more residual PD signals compared with TNF inhibitor or Abatacept induced remission. More strict criteria of clinical remission may reduce residual PD signals in patients treated by Tocilizumab. Disclosure of Interest None declared

Background Subcutaneous injection of biologic agents gives more freedom and independence for patients with rheumatoid arthritis (RA) than intravenous injection. Despite this, patients with RA sometimes select intravenous injections due to concerns over self-injection, such as injection anxiety, including pain, and lack of confidence in giving a self-injection [1]. It is reported that one in five people are estimated to experience injection anxiety [2]. Therefore, an understanding of subcutaneous injection pain and anxiety and support for anxiety of patients with RA are important for appropriate usage of subcutaneous biologics. Objectives The aim is to evaluate pain and anxiety caused by adalimumab (ADA) subcutaneous injection and assess the effectiveness of nurses9 care. Methods Patients with RA using ADA self-injections were enrolled. Pain was assessed in 4 categories: general, needle insertion, drug injection, needle removal. Pain was evaluated using Visual Analogue Scale (VAS) scale. Effectiveness of support by nurses was also assessed using self-questionnaires and free-format comments. Statistical analyses were performed utilizing Wilcoxon9s signed rank test and Spearman9s rank correlation coefficient. Results Twenty patients (Male: Female, 4: 16) completed the questionnaire. Average age and disease duration were 68 and 12.6 years, respectively. Mean ± SD of Pain VAS were 34.9±28.1 mm (General), 30.3±30.6 mm (needle insert), 42.5±35.6mm (drug injection) and 11.8±18.4mm (needle removal). There were no statistically significant differences between general pain and needle insertion (p=0.631), or general pain and drug injection (p=0.121). However, statistically significant differences were found between general pain and needle removal (p=0.001). Moreover, there were statistically significant differences between needle insertion and removal (p=0.003), and drug injection and needle removal (p=0.00048). General pain showed statistically significant correlation with needle insertion pain (r=0.653, p=0.0018) and drug injection pain (r=0.615, p=0.004). However, general pain was not correlated with needle removal pain (r=0.137, p=0.565). Patients with RA answered that support by nurses was effective for relieving pain (30%), reduction of anxiety (35%) and improving treatment motivation (50%). According to the patients, nurses helped raise motivation by explaining that treatment prevents the progression of RA and allows many patients to feel better and have less pain. Interaction with nurses appears to be effective in reducing injection pain and anxiety and improving motivation for self-injection treatment. Conclusions These data indicate that needle insertion and drug injection pain have great influences on general pain. Support by nurses is likely to reduce injection anxiety and pain, resulting in higher motivation toward self-injection treatment. References Keininger D, et al. Health Qual Life Outcomes. 2011 Jan 13; 9:2. Nir Y, et al. Am J Trop Med Hyg 2003, 68: 341–4. Disclosure of Interest None declared

The aim of this study was to investigate the differences between rats and hamsters, Two of the most widely used experimental animals, with respect to the effects of microsomal membrane solubilization on the inhibition of liver 11β-hydroxysteroid dehydrogenase (11β-HSDI) enzyme by bile acids. Liver microsome fractions were prepared, and the 11β-HSDI enzymatic activity was measured using cortisone as a substrate. The substrate and various concentrations of bile acids were added to the assay mixtures. After incubation, the products were extracted and analyzed using high-performance liquid chromatography. To investigate the effect of detergent on the inhibitory effects of bile acids, we conducted inhibition tests using Triton X-100-solubilized animal liver microsomes. When solubilized microsomes were used, all bile acids inhibited 11β-HSDI from rats and hamsters to various degrees. 7α-Hydroxycholanoic acids (cholic acid and chenodeoxycholic acid) in particular had strong inhibitory activities. In hamsters, 7β-hydroxycholanoic acid (ursodeoxycholic acid) was the strongest inhibitor among the bile acids tested, although its effect was not very strong. When nonsolubilized microsomes were used, deoxycholic acid did not inhibit but rather enhanced the enzymatic activity in both animals. Microsomal content of cholesterol and phospholipids are significantly different between rats and hamsters. Species differences in bile acid inhibition of nonsolubilized microsomes might be reflected not only by structural difference of bile acids, which affect membrane solubilization and enzyme activity directly, but also species difference in microsomal membrane lipid content.

To evaluate the improvement of health status in patients with rheumatoid arthritis (RA) treated with tocilizumab. Thirty-nine patients were treated with 8 mg/kg tocilizumab every 4 weeks for 24 weeks. Disease activity was assessed by Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI). Improvement of health status was assessed by Arthritis Impact Measurement Scale 2 (AIMS-2) and Short Form-36 (SF-36). Tocilizumab improved CDAI and SDAI significantly at week 4 compared with at baseline. In the components of AIMS-2, “physical score”, “symptom” and “affect” improved significantly at week 4 compared with at baseline, while “social interaction” did not improve significantly during 24 weeks of tocilizumab therapy. Similarly in SF-36, “bodily pain”, “general health”, “vitality” and “mental health” improved significantly at week 4. The most correlative component of AIMS-2 with CDAI was “symptom”, while “social interaction” did not correlate with CDAI during tocilizumab treatment. The time-course diversity in improvement of health status should be considered to provide proper healthcare when treated with tocilizumab.

Summary Myostatin (MSTN) has been implicated in metabolic adaptation to physiological stimuli, such as physical exercise, which is linked to improved glucose homeostasis. The aim of the present study was to evaluate the influence of exercise on the expression of MSTN, MSTN receptors (ActRIIB and ALK4) and follistatin (FS) in the muscle and fat of streptozotocin-induced diabetic rats. Control and diabetic rats were randomly assigned to a swimming training group (EC and ED, respectively) and a sedentary group (SC and SD, respectively). Exercising animals swam for 45 min at 0900 and 1700 hours, 5 day/week, for 4 weeks. The mRNA expression of MSTN, ActRIIB, ALK4 and FS mRNA was quantified by real-time reverse transcription–polymerase chain reaction. Expression of MSTN and FS mRNA increased in the muscle and subcutaneous fat of SD compared with SC rats. Expression of ActRIIB mRNA was increased in the muscle, mesenteric fat and brown adipose tissue (BAT) of SD compared with SC rats, whereas ALK4 mRNA expression was only increased in the BAT of SD compared with SC rats. After training, MSTN and ActRIIB expression was lower in the BAT of EC compared with SC rats. Expression of MSTN mRNA increased in the mesenteric fat of ED compared with SD rats, whereas FS mRNA expression decreased in the muscle, mesenteric and subcutaneous fat and BAT. Lower ALK4 mRNA expression was noted in the BAT of ED compared with SD rats. These results indicate that MSTN, its receptors and FS expression change in both the muscle and fat of diabetic rats and that the expression of these factors can be modulated by exercise in diabetes.

A female patient with rheumatoid arthritis (RA) suffered from Mycobacterium avium (M. avium) infection during tocilizumab treatment. Tocilizumab was discontinued and she was treated with a recommended chemotherapy, resulting in improvement of M. avium. Tocilizumab retreatment did not aggravate M. avium infection, and radiographic abnormalities improved over 1 year after cessation of the recommended therapy. Tocilizumab may be one candidate for intractable RA patients with M. avium if any biologic is required.

We report the nanoscopic properties of a BaTiO3 single crystal. Atomic Force Microscopy and Piezoresponse Force Microscopy measurements show that there is no relationship between domain boundary and surface one-lattice-height (4 angstrom) steps of 200nm thick BaTiO3 single crystal. Both a-c domain boundary and c-c domain boundary are with no relationship between surface one-lattice-height steps of BaTiO3.

Interleukin-6 overproduction is pathologically involved in adult onset Still's disease (AOSD). We successfully treated a man with refractory AOSD utilizing tocilizumab. Tocilizumab was discontinued after 15 doses due to intestinal bleeding, but the efficacy was sustained over 21 months. Tocilizumab was readministered safely upon recurrence and showed similar efficacy over 6 years. Corticosteroid and NSAIDs could be discontinued and intestinal bleeding was no more observed. Tocilizumab can be a therapeutic option for AOSD.

A simple distributed antenna system via simultaneous transmission using an anti-multipath modulation scheme, in which a phase variation is imposed on the symbol of a differential phase-shift keying modulation, is proposed for intended radio area formation. Based on multiray Rice channel models corresponding to linear deployment, focusing on the cell borders, fundamental error rate characteristics are revealed through simulation results, and a preferred configuration and deployment with an appropriate delay insertion plan are discussed. The proposed system achieves reliable transmission throughout a united radio area with the aid of diversity effects. Seamless transmission has been actually verified by field tests. By using downward-tilted directional base antennas, the system can extend the communication area at will while subduing outside emissions. The field tests have also shown that two-channel alternate linear deployment is realizable. Furthermore, these features remain for such fast-fading situations as not only high-speed vehicles on millimeter-wave bands but also practical baseband distribution using separate local oscillators with different carrier frequency offsets and phase noises.

Objectives:To understand the acute phase responses to surgical intervention in patients with rheumatoid arthritis (RA) treated with the anti-interleukin (IL)6 receptor antibody, tocilizumab.Methods:In a retrospective 1:1 pair-matched case-control study, 22 tocilizumab-treated RA cases and 22 cases treated with conventional disease-modifying antirheumatic drugs (DMARDs) and matched for type of surgery, age and sex were evaluated for body temperature every day, and blood C-reactive protein (CRP) levels and white blood cell (WBC), neutrophil and lymphocyte counts on days −1, 1, 3 and weeks 1 and 2 after joint surgery. Safety issues were also monitored.Results:No complications of infection or delay of wound healing occurred in either patient group. Tocilizumab partially, but significantly, suppressed the increase in body temperature on postoperative days 1 and 2, compared with DMARDs (average (SD) maximum increase in temperature was 0.45 (0.1)°C in the tocilizumab group and 0.78 (0.1)°C in the DMARD group; pConclusions:Within this small number of cases, safe operations on patients were performed during tocilizumab treatment. Tocilizumab suppressed fever and increase of CRP after surgery, whereas there was no influence on the transition in number of leukocytes. This characteristic postoperative response should be considered during tocilizumab treatment.

To evaluate whether the psychological state is related to the Boolean-based definition of patient global assessment (PGA) remission in patients with rheumatoid arthritis (RA).Patients with RA who met the criteria of swollen joint count (SJC) ≤ 1, tender joint count (TJC) ≤ 1 and C-reactive protein (CRP) ≤ 1 were divided into two groups, PGA remission group (PGA ≤ 1 cm) and non-remission group (PGA1 cm). Anxiety was evaluated utilizing the Hospital Anxiety and Depression Scale-Anxiety (HADS-A), while depression was evaluated with HADS-Depression (HADS-D) and the Center for Epidemiologic Studies Depression Scale (CES-D). Comparison analyses were done between the PGA remission and non-remission groups in HADS-A, HADS-D and CES-D.Seventy-eight patients met the criteria for SJC ≤ 1, TJC ≤ 1 and CRP ≤ 1. There were no significant differences between the PGA remission group (n = 45) and the non-remission group (n = 33) in age, sex, disease duration and Steinbrocker's class and stage. HADS-A, HADS-D and CES-D scores were significantly lower in the PGA remission group.Patients with RA who did not meet the PGA remission criteria despite good disease condition were in a poorer psychological state than those who satisfied the Boolean-based definition of clinical remission. Psychological support might be effective for improvement of PGA, resulting in the attainment of true remission.

In the treatment of rheumatic diseases such as rheumatoid arthritis (RA) or systemic onset juvenile idiopathic arthritis (soJIA), new therapies targeting pro-inflammatory cytokines have been developed. IL-6 is a pleiotropic cytokine with a wide range of biological activities including a pro-inflammatory mediator activity. Overproduction of IL-6 has been reported to be pathologically involved in the rheumatic diseases and, therefore, blockade of IL-6 actions may improve the disease. Tocilizumab, a humanized monoclonal antibody against human interleukin-6 receptor (IL-6R), inhibits IL-6 binding to IL-6R and specifically interferes with IL-6 actions. Castleman's disease is an atypical lymphoproliferative disorder caused by the overproduction of IL-6. Tocilizumab therapy improves immunological and hematological abnormalities as well as systemic inflammatory symptoms including wasting. This translational study also confirmed the pathological significance of IL-6 in the disease. RA is a representative autoimmune inflammatory disease characterized by bone and cartilage destruction in multiple joints. Since IL-6 also plays pathological roles in RA, tocilizumab therapy has been introduced to the patients with refractory disease and has shown a strong therapeutic effect. Besides Castleman's disease and RA, tocilizumab has been shown to be effective for patients with soJIA and Crohn's disease. Tocilizumab treatment is generally well tolerated and safe. Therefore, tocilizumab can be a promising therapeutic agent for the rheumatic diseases in which IL-6 overproduction is pathologically involved.

Chemical studies of the transactinide elements ( Z ≥ 104) at JAERI (Japan Atomic Energy Research Institute) are reviewed and prospects for extending the studies are briefly considered. Aqueous chemistry of element 104, rutherfordium (Rf), and element 105, dubnium (Db), produced in the 248 Cm( 18 O, 5 n ) 261 Rf and 24 m( 19 F, 5 n ) 262 Db reactions, respectively, has been studied by ion-exchange chromatography on an atom-at-a-time basis. Characteristic ion-exchange behavior of Rf and Db in acidic solution is discussed.

The IUPAC/IUPAP Joint Working Party (JWP) on the priority of claims to the discovery of new elements 113???116 and 118 has reviewed the relevant literature pertaining to several claims. In accordance with the criteria for the discovery of elements previously established by the 1992 IUPAC/IUPAP Transfermium Working Group (TWG), and reinforced in subsequent IUPAC/IUPAP JWP discussions, it was determined that the Dubna-Livermore collaborations share in the fulfillment of those criteria both for elements Z = 114 and 116. A synopsis of experiments and related efforts is presented.

The present status of heavy element nuclear chemistry research at JAERI (Japan Atomic Energy Research Institute) is reviewed. Production of the transactinide nuclei 261Rf and 262Db via the reactions of 248Cm(18O,5n) and 248Cm(19F, 5n), respectively, at the JAERI tandem accelerator is reported. Study of the aqueous chemistry of Rf is being carried out with a newly developed rapid ion-exchange separation apparatus. Anion-exchange behavior of Rf in acidic solution is briefly discussed. Recent experimental results on decay studies of neutron-deficient actinide nuclei using the gas-jet coupled JAERI-ISOL are given. We also discuss characteristics of nuclear deformation properties at scission in symmetric and asymmetric fission of actinides. Prospects for studies in the near future are briefly considered.

The present status of transactinide nuclear chemistry research at JAERI (Japan Atomic Energy Research Institute) is reviewed. Successful production of the transactinide nuclei, 261Rf and 262Db in the reactions of 248Cm(18O,5n) and 248Cm(19F,5n), respectively, at the JAERI tandem accelerator is reported. Aqueous chemistry of element 104, Rf, is being performed with a newly developed rapid ion-exchange separation apparatus. Anion-exchange behaviour of Rf in acidic solutions is outlined. Research plans for the near future are briefly discussed.

The IUPAC/IUPAP Joint Working Party (JWP) on the priority of claims to the discovery of new elements has reviewed the relevant literature pertaining to several claims. In accordance with the criteria for the discovery of elements previously established by the 1992 IUPAC/IUPAP Transfermium Working Group (TWG), and reiterated by the 1999 and 2003 IUPAC/IUPAP JWPs, it was determined that the 1996 and 2002 claims by the Hofmann et al. research collaborations for the discovery of the element with atomic number 112 at Gesellschaft für Schwerionenforschung (GSI) share in the fulfillment of those criteria. A synopsis of Z = 112 experiments and related efforts is presented. A subsequent report will address identification of higher-Z elements including those of odd atomic number.

The transactinide nuclides261Rf and262Db have been successfully produced in the248Cm(18O,5n) reaction at 99 MeV and in the248Cm(19F,5n) reaction at 100, 103, and 106 MeV, respectively, at the JAERI tandem accelerator. The on-line ion exchange experiments with an automated fast and repetitive liquid chromatography separation system were performed in the HNO3/HF system using Rf homologues89mZr and167,165Hf produced in the89Y(p,n) and152Gd(18O,xn) reactions, respectively. The radiotracers88Zr,175Hf, and234Th were also prepared and the distribution coefficients on ion exchange resins were measured systematically in 1-11 M HCl and 1-14 M HNO3with the batch method. It was found that anion exchange experiments of Rf in 8 M HNO3and 9 M HCl provided information useful to extract the ionic radius of Rf and to verify the influence of relativistic effects.

BACKGROUND Lymphangioleiomyomatosis is a rare disease, histologically characterized by an abnormal proliferation of smooth muscle around the lymphatics. Lung is the most common site of involvement, and patients usually present with dyspnea, chest pain, and cough. Chylous pleural effusion and ascites occasionally appear during the course of the disease. There are only a few reports on the cytologic findings in this disease. To our knowledge, the cytologic findings of chylous pleural effusion and chyloascites have not been reported before. CASE A 23-year-old female presented with chylothorax, chyloascites and a retroperitoneal mass. Cytologic examination of chylous pleural effusion and chyloascites revealed numerous cohesive and thick clusters of cells with a high nuclear/cytoplasmic ratio, oval nuclei and slightly increased chromatin content. Mitosis and necrosis were not observed. Exploratory laparotomy and transbronchial lung biopsy were performed, and the histologic diagnosis was lymphangioleiomyomatosis involving the retroperitoneal lymph nodes, uterine fundus and lungs. Immunohistochemistry showed that the characteristic clusters in chylous fluids were positive for alpha-smooth muscle actin. CONCLUSION A diagnosis of lymphangioleiomyomatosis is possible from cytologic findings of effusions with the aid of clinical findings.

A new series of 3,4-dihydro-2H-1,4-benzoxazine derivatives, where various substituents were introduced into one of the geminal dimethyl groups at the 2 position, were synthesized and their potassium channel-activating activity was evaluated. Introduction of a hydroxyl group, as in compound 5, resulted in good solubility in water and a long duration of action compared with the parent compound 1. Introduction of a nitrato group, as in compound 8, produced typical nitrate activity such as exhibited by nitroglycerine in addition to potassium channel-activating activity. X-ray structural analysis of compound 5 showed that the sum of the bond angles around the N atom at the 4 position was 357.8 degrees, suggesting that the N atom had an approximately sp2-like planar bond configuration.

Monolayers of europium complexes on water surface have been directly visualized in the gas-liquid expanded region at different temperatures using Brewster angle microscopy (BAM). The film texture with network patterns of the complex (C18)2 Eu(DBM)4 and hs evolution with time and temperature of the subphase were examined. The average linear cell dimension and the polygon areas have been analyzed as a function of time and the temperature. The mechanism of the domain growth is qualitatively discussed.

s / Osteoarthritis and Cartilage 21 (2013) S9–S62 S48 markers measured (Figure 1C). This phenotype represented the sole AF cell type identified thus far. Conclusions: We generated the first human annulus fibrosis cell lines and present an detailed characterization of their phenotype in comparison to our novel nucleus pulposus cell lines. The distinct migratory behavior of isolated immortal AF clones, in contrast to that of cell pools, suggests that distinct phenotype may be preferentially immortalized and, by inference, that functionally different subtypes may exist in AF cell population. Our future investigations will focus on integrin expression, in relation to culturing them on defined (e.g. fibronectin, collagen) surfaces, as such conditions were suggested to mimic AF-like conditions. ĂThis research forms part of the Project P2.01 IDiDAS of the research program of the BioMedical Materials institute, cofunded by the Dutch Ministry of Economic Affairs, Agriculture and Innovation. 77 THE TRANSCRIPTION FACTOR MOHAWK PLAYS AN IMPORTANT ROLE FOR MAINTAINING HUMAN ACL HOMEOSTASIS AND LIGAMENT/ TENDON DIFFERENTIATION OF MESENCHYMAL STEM CELLS K. Otabe, H. Nakahara, A. Hasegawa, F. Ayabe, T. Matsukawa, M.K. Lotz, H. Asahara. The Scripps Res. Inst., La Jolla, CA, USA Background/Purpose: Mohawk homeobox (MKX) has been demonstrated as a tendon and ligament specific transcriptional factor. MKX knock-out mice showed hypoplastic tendons throughout the body, due to reduced type I collagen production in tendon cells. However, in mature human tendon or ligament tissues, the function of MKX has not been fully understood. The aims of this study are to characterize the expression of MKX in normal human knee joints and osteoarthritis (OA) affected knee joints and to investigate the role of MKX in human ligament homeostasis and in ligament/tenogenic differentiation of mesenchymal stem cells. Methods: Human ACL specimens were obtained from the knee joints at autopsy within 24-48 hours postmortem with approval of the Scripps Human Subjects Committee. 7 normal donors (mean SD age 33.6 11.7 years) and 8 donors with OA (mean SD age 77.5 11.5 years) were analyzed. All cartilage surfaces were graded macroscopically. ACL degeneration was assessed macroscopically and histologically using quantitative scoring systems. ACL tissues were analyzed for the expression of MKX by immunohistochemistry and quantitative RT-PCR assays. Primary cultured human ACL cells were stimulated with IL-1b to examine whether this pro-inflammatory cytokine modulates MKX expression. Moreover, in order to examine the function of MKX in ECM production and differentiation in these cells, we performedMKX knockdown by MKX specific siRNA. To examine the function of MKX in ECM production and differentiation in human bone marrow mesenchymal stem cells (BMMSC) (n1⁄46 from 2 donors), we performed over-expression of MKX by adenoviral vector and analyzed gene and protein levels of COL1a1, and tenascin b (TNXb), important ECM components of ACL. Results: The expression of MKX mRNA was remarkably decreased during OA development. In addition, the expression of COL1a1 was also decreased in the OA group. Immunohistochemistry revealed that the percentage of MKX positive cells was significantly reduced in OA group. In primary cultured human ACL cells, the expression of MKX was significantly reduced by the treatment of IL-1b. The expression of ECM genes COL1a1 and TNXb and transcription factor Scleraxis (SCX), which is a specific regulator of the tendon/ligament lineage, were downregulated by IL-1b treatment. On the other hand, SOX9, which is involved in the modulation of chondrocyte like phenotype, was upregulated by IL-1b treatment. The expression of COL1a1 and TNXbwere decreased by MKX specific siRNA treatment, while SOX9 was increased. By contrast, the expression of COL1a1 and TNXb were increased by overexpression of MKX in BMMSCs. Conclusion: To our knowledge, this is the first report to investigate the MKX expression and function in human ligaments. The present findings demonstrate that the ACL in OA-affected joints are deficient in MKX expression and this is associated with reduced ECM production. Reduced MKX in OA may be due to inflammatory stimuli such as IL-1b. In cultured ACL cells, and in mesenchymal stem cells MKX promotes the maintenance and induction of tenocyte phenotype. Thus, MKX is a key factor that is required for maintenance of ligament structure and

Thallium-201 ( 201 Tl) is widely used in the diagnosis of malignant tumours. However, its use in predicting the response to radiation therapy for head and neck cancer has not been established. Nineteen patients with histologically proven head and neck cancer were studied. 201 Tl single photon emission tomographic (SPET) images were obtained 15 min (early) and 4 h (delayed) post-injection of the radionuclide. For a semi-quantitative assessment, regions of interest were drawn over the lesions and normal soft tissue. Lesion-to-normal tissue uptake ratios of 201 Tl activity were measured from mean counts-per-voxel obtained on both the early and delayed scans, representing the early index (EI) and delayed index (DI) respectively. Subsequently, a retention index (RI) was calculated using the formula: RI = (DI - EI) x 100/ (EI). The patients were classified into two groups according to the effect of radiotherapy: a partial response or complete response group (PR-CR group) and a no change group (NC group). In the analysis of primary lesions, both the delayed and retention indexes of the PR-CR group were significantly higher than those of the NC group. However, the early index was not significantly different between the two groups. In the metastatic lymph nodes, only the retention index was significantly different between the two groups. Our results demonstrate that 201 Tl SPET and a 201 Tl index can be used to predict the response to radiotherapy for primary head and neck cancer and lymph node metastases. The retention index is a useful parameter for estimating the effects of radiotherapy.

Dendritic ice crystals were grown in air of 1.0 × 105 Pa at about −15°C and the formation mechanism of side branches was experimentally investigated. As a result, when bulk supersaturation is constant, side branches are not formed though the ruggedness is formed along the sides of primary branches. On the other hand, when bulk supersaturation varies with time, the side branches are formed.

To establish the most effective radiation dose for treatment of Graves ophthalmopathy (GO).A combination of 10 Gy (n = 15) or 24 Gy (n = 16) of radiation and corticosteroids was used to treat 31 patients with GO. Magnetic resonance (MR) images obtained before treatment showed swollen extraocular muscles with prolonged T2 relaxation times in all patients.Before therapy, T2 relaxation time of extraocular muscle was 79.6 msec (95% confidence interval, 76.3, 82.9) in the 24-Gy group and 77.4 msec (95% confidence interval, 74.6, 80.1) in the 10-Gy group (P = .32). After therapy, T2 relaxation time was 62.8 msec (95% confidence interval, 61.2, 64.4) in the 24-Gy group and 68.9 msec (95% confidence interval, 66.8, 71.1) in the 10-Gy group. In the 24-Gy group, there was a significant decrease in T2 relaxation times (P = .001) and clinical response to initial treatment was better. At 1- and 3-month follow-up, the resistance rate was lower in the 24-Gy group.In treatment of GO, 24 Gy of radiation is a more effective dose than 10 Gy when combined with systemic corticosteroids.

Background Pulmonary hypertension (PH) is defined as an increase in mean pulmonary arterial pressure (PAPm) greater than or equal to 25 mmHg at rest as assessed by right heart catheterization (RHC), but RHC is not routinely performed for the diagnosis of PH in a “real world” setting in Japan. Objectives The aim of this study is to assess the change of frequency of RHC for the diagnosis of PH among patients with connective tissue diseases in our hospital, and to know if the decision to prescribe pulmonary hypertension drugs is affected by whether we perform RHC. Methods Clinical records of admitted patients describe both the main diseases which were constantly followed by physicians and the actual diseases which were the reasons for admission. We analyzed the clinical records retrospectively of who was admitted to the wards of our rheumatology section for 10 years from Aug 1, 2005 to July 31, 2015. These 10 years were divided into two periods: the first half is from Aug 1, 2005 to July 31, 2010 (period A) and the latter half is from Aug 1, 2010 to July 31, 2015 (period B). We checked echocardiography, RHC and prescription for PH drugs. PH drugs include prostacyclin pathway agonists, endothelin receptor antagonists, and nitric oxide-cGMP enhancers. Results We reviewed clinical records of 5,428 patients for ten years and we found 57 patients with the diagnosis of PH either in the section of main diseases or actual diseases. We used the label “tentative pulmonary hypertension (tentative PH)” for patients who showed peak tricuspid regurgitation gradient in thoracic echocardiography of more than or equal to 30 mmHg. Among the tentative PH patients, those whose PAPm were confirmed by RHC were labeled “true pulmonary hypertension (true PH)”. Forty patients among the 57 selected patients were categorized as having tentative PH and their original diseases were 20 with systemic sclerosis, 4 with Sjogren9s syndrome, 3 with mixed connective tissue disease, and 2 with systemic lupus erythematosus, and so on. Among these 40 patients, 25 belonged to period A and 15 belonged to period B. RHC was performed for 9 patients (36.0%) in period A and true PH was diagnosed in 5 of those 9 patients (55.6%). Also RHC was performed for 12 patients (80.0%) in period B and 7 patients were found to have true PH (58.3%). In period A, 60% of true PH patients (3/5) and 60% of tentative PH patients (12/20) took PH drugs, and in period B, 71.4% of true PH patients (5/7) and 37.5% of tentative PH patients (3/8) took PH drugs. Conclusions The frequency of RHC increased from 36% in the first half period to 80% in the latter half period in our hospital. In addition, the use of PH drugs did not depend on the confirmation of PH by RHC, particularly in the first half period. In Japan rheumatologists, including doctors at our hospital have a tendency to prescribe PH drugs without RHC data, but recently this tendency is changing. This tendency to not always perform RHC may be partly explained by the content of the guidelines from the Ministry of Health, Welfare and Labor in Japan. Acknowledgement The authors thank Ms. Ayumi Kondou for her excellent secretarial assistance. Disclosure of Interest None declared

Background Biologics are effective for improving disease activity in patients with rheumatoid arthritis (RA). We also reported the efficacy of biologicals on health status [1]. However, efficacy of biologics on psychological status, self-efficacy and patient satisfaction in RA patients is not well evaluated. Objectives We evaluated improvement of health status, psychological status, self-efficacy and patient satisfaction in patients with RA treated with biologics. Methods The patients with RA who were planning to be treated with the biologics (adalimumab (ADA), tocilizumab (TCZ) and abatacept (ABT)) were enrolled. Disease activity was evaluated using SJC, TJC, PGA and CDAI. Psychological status was examined using the Hospital Anxiety and Depression Scale-Depression (HADS-D) and Anxiety (HADS-A). Self-efficacy and health status including patient satisfaction were assessed using the General Self-Efficacy Scale (GSES) and the Arthritis Impact Measurement Scale 2 (AIMS-2), respectively. Comparison analysis was performed between the baseline and 24 weeks after biological therapy. To further investigate the items related to satisfaction, correlation analysis was performed between patient satisfaction and disease activity and health status including psychological status. Data analyses were performed utilizing Wilcoxon rank-sum test and Spearman correlation analysis. Results Twenty-six patients (male/female: 7/19) (ADA: 8, TCZ: 9, ABT: 9) were evaluated. Patients9 characteristics were as follows: median (interquartile range) age of 57 (49.2 - 75.0) years and duration of 2.9 (0.8 - 5.5) years. SJC, TJC, PGA and CDAI showed statistically significant improvement at week 24 compared to the baseline (p Patient satisfaction showed statistically significant correlation with SJC (r=0.686, p Conclusions Biologics were effective in improving psychological status, patient satisfaction and self-efficacy as well as disease activity and health status. For further improving patient satisfaction, psychological support and social assistance by health professionals9 team in addition to appropriate treatment may be required. References Fusama M, et al. Mod Rheumatol 2013; 23: 276–83. Disclosure of Interest None declared

Background The clinical benefits of biologics to patients with rheumatoid arthritis (RA) have been demonstrated in various clinical trials. However, patient satisfaction in patients treated with biologics is not well evaluated. Objectives We evaluated patient satisfaction and health status in patients with RA treated with biologics. Methods The patients with RA who were planning to be treated with IL-6 inhibitor (tocilizumab; TCZ) (IL-6 group) and TNF inhibitor (adalimumab: ADA, infliximab; IFX, etanercept; ETN) (TNF group) were enrolled. Disease activity was evaluated using swollen joint counts (SJC), tender joint counts (TJC) and patient global assessment (PGA), and Clinical Disease Activity Index (CDAI). Patient satisfaction was evaluated utilizing patient satisfaction scores of the Arthritis Impact Measurement Scale 2 (AIMS-2). Satisfaction was measured before and after 6-months of treatment with each of the biologics, and the results were compared. Statistical analysis was performed utilizing Wilcoxon rank-sum test and t-test. Results Patients with RA (n=85) were evaluated in this study. 48 patients were treated with TCZ, and 47 patients were treated with anti-TNF agents (ADA: 17, IFX:17, ETN:13).Patients characteristics were as follows as follows: mean±SD of age (55.6±11.9 years old) and duration (7.29±8.83 years), male/female (16/79). Both at baseline and at 6 months after treatment, there was no statistically significant differences in SJC, TJC, PGA, EGA and CDAI between TCZ group and TNF group. All these evaluations showed statistically significant improvement after 6 months of treatment in each group.As for health status, all 5 components of AIMS-2 showed statistically significant improvement at 6 months compared to the baseline in TNF groups. In IL-6 group, “physical”, “symptom”, “affect” and “role” improved significantly at 6 months (p Conclusions Patient satisfaction and health status except social interaction were improved by TNF inhibitor or IL-6 inhibitor. To solve the problems related to social function, understandings and social support for patients by health professionals may be required. Disclosure of Interest None declared

The prion protein (PrP) displays some unusual features in its biogenesis. In cell-free systems it can be synthesized as either an integral transmembrane protein spanning the membrane twice, with both amino and carboxyl domains in the lumen of the endoplasmic reticulum, or as a fully translocated polypeptide. A charged, extracytoplasmic region, termed the Stop Transfer Effector (STE) sequence, has been shown to direct the nascent translocating chain to stop at the adjoining hydrophobic domain to generate the first membrane-spanning region (TM1). However, the determinants of the second translocation event in the biogenesis of the transmembrane form have not been identified previously. Moreover, the relationship of transmembrane and fully translocated forms of PrP has not been well understood. Here, we report progress in resolving both of these issues. Using protein chimeras in cell-free translation systems and Xenopus oocytes, we identify the sequence which directs nascent PrP to span the membrane a second time, with its carboxyl-terminal domain in the endoplasmic reticulum lumen. Surprisingly, PrP carboxyl-terminal domain translocation does not appear to be directed by an internal signal or signal-anchor sequence located downstream of TM1, as would have been expected from studies of other multispanning membrane proteins. Rather, carboxyl-terminal domain translocation appears to be another consequence of the action of STE-TM1, that is, the same sequence responsible for generating the first membrane-spanning region. Studies of an STE-TM1-containing protein chimera in Xenopus oocytes demonstrate that most of these chains upon completion of their translation, initially span the membrane twice, with a topology similar to that of transmembrane PrP, but are carbonate-extractable. These chains have the transmembrane orientation only transiently and chase into a fully translocated form. These results support a model in which a metastable "transmembrane" intermediate, residing within the aqueous environment of the translocation channel, can be converted into either the integrated transmembrane or the fully translocated form of PrP, perhaps directed by trans-acting factor (s). Such a model may explain why stable the transmembrane isoform of PrP has not been observed in normal cells and how nascent PrP might be directed to alternate pathways of folding.

A surface photovoltage (SPV) technique has been applied to construct a taste sensor by combining modified LB (Langmuir-Blodgett) methods to immobilize taste-sensitive membranes. The contactless approach of the SPV method provides a simple sensing system with considerable patterning flexibility. Several kinds of artificial lipid membranes are monolithically integrated on a semiconductor surface as taste-sensitive materials and the surface potential change caused by the reactions with taste substances is detected by scanning a light beam along the semiconductor surface. First it is shown that the uniformly oriented lipid membranes exhibit different responses to five taste substances, with high sensitivity and fast response rate. Then, a preliminary experimental result to identify commercial drinks is demonstrated.