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Xin-Mei Hu,1,* Can-Can Wang,1,* Yu Xiao,1 Yu Liu,1 Hong-Ri Huang,2 Peng Jiang,1 Ying-Kai Wang,1 Yun-Jin Lin,1 Liang-Cheng Li,3 Zhong-Quan Qi1 1Medical College, Guangxi University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Department of Research and Development, Guangxi Taimei Rensheng Biotechnology Co., Ltd, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 3School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhong-Quan Qi, Guangxi University, Da-Xue-Dong Road No. 100, Xixiangtang District, Nanning, Guangxi Zhuang Autonomous Region, 530004, People’s Republic of China, Tel +8613806001271, Email yxyyz@gxu.edu.cn Liang-Cheng Li, Xiamen University, No. 4221-115, Rm 355, Xiang’an District, Xiang’an, Xiamen Fujian Province, 361102, People’s Republic of China, Tel +8618359206906, Email lchli2013@xmu.edu.cnPurpose: In recent years, exosomes have been proved to be used to treat many diseases. However, due to the lack of uniform quality control standards for exosomes, the safety of exosomes is still a problem to be solved, especially now more and more exosomes are used in clinical trials, and its non-clinical safety evaluation is particularly important. However, there is no safety evaluation standard for exosomes at present. Therefore, this study will refer to the evaluation criteria of therapeutic biological products, adopt non-human primates to evaluate the non-clinical safety of human umbilical cord mesenchymal stem cell exosomes from the general pharmacology and immunotoxicity, aiming at establishing a safety evaluation system of exosomes and providing reference for the clinical application of exosomes in the future.Methods: 3.85 × 1012 exosomes derived from human umbilical cord mesenchymal stem cells were injected into cynomolgus monkeys intravenously. The changes of general clinical conditions, hematology, immunoglobulin, Th1/Th2 cytokines, T lymphocytes and B lymphocytes, and immune organs were observed before and within 14 days after injection.Results: The results showed that exosomes did not have obvious pathological effects on the general clinical conditions, blood, coagulation function, organ coefficient, immunoglobulin, Th1/Th2 cytokines, lymphocytes, major organs, and major immune organs (spleen, thymus, bone marrow) of cynomolgus monkeys. However, the number of granulocyte-macrophage colonies in exosomes group was significantly higher than that in control group.Conclusion: To sum up, the general pharmacological results and immunotoxicity results showed that the injection of 3.85 × 1012 exosomes may have no obvious adverse reactions to cynomolgus monkeys. This dose of exosomes is relatively safe for treatment, which provides basis research for non-clinical safety evaluation of exosomes and provides reliable research basis for future clinical application of exosomes.Keywords: exosomes, cynomolgus monkeys, safety, immunotoxicity

Ming-Ming Ma,1,* Yao-Yao Xu,2,* Li-Hua Sun,1,* Wen-Jie Cui,1 Miao Fan,3 Su Zhang,4 Lei Liu,5 Ling-Zhi Wu,6 Liu-Cheng Li7 1Department of Diagnostic Ultrasound & Echocardiography, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, People’s Republic of China; 2Department of Pharmacy, The People’s Hospital of Pingyang, Wenzhou, 325400, People’s Republic of China; 3Department of Pharmacy, The First Affiliated Hospital of Ningbo University, Ningbo, 315010, People’s Republic of China; 4Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, 310014, People’s Republic of China; 5Department of Orthopaedics, Shaoxing Hospital of Traditional Chinese Medicine, Shaoxing, 312000, People’s Republic of China; 6Department of Pharmacy, The Affiliated Hospital of Jiaxing University (The First Hospital of Jiaxing), Jiaxing, 314000, People’s Republic of China; 7Department of Pharmacy, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liu-Cheng Li, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, No. 3 Qingchun East Road, Hangzhou, 310016, People’s Republic of China, Email 3415116@zju.edu.cn Ling-Zhi Wu, The Affiliated Hospital of Jiaxing University (The First Hospital of Jiaxing), No. 1882 South Central Road, Jiaxing, 314000, People’s Republic of China, Email wulingzhi1992@163.comAbstract: Surveillance of drug safety is an important aspect in the routine medical care. Adverse events caused by real-world drug utilization has become one of the leading causes of death and an urgent issue in the field of toxicology. Cardiovascular disease is now the leading cause of fatal diseases in most countries, especially in the elderly population who often suffer from multiple diseases and need long-term multidrug therapy. Among which, statins have been widely used to lower bad cholesterol and regress coronary plaque mainly in patients with hyperlipidemia and atherosclerotic cardiovascular diseases (ASCVD). Although the real-world benefits of statins are significant, different degrees and types of adverse drug reactions (ADR) such as liver dysfunction and muscle injury, have a great impact on the original treatment regimens as well as the quality of life. This review describes the epidemiology, mechanisms, early identification and post-intervention of statin-associated liver dysfunction and muscle injury based on the updated clinical evidence. It provides systematic and comprehensive guidance and necessary supplement for the clinical safety of statin use in cardiovascular diseases.Keywords: statin, cardiovascular diseases, liver dysfunction, muscle injury, countermeasures

Qin Qian,* Yu-Zhen Wang,* Lian-Di Kan,* Jie Chen, Chen Wang, Gang Han, Liu-Cheng Li, Wei-Jian Lou Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liu-Cheng Li; Wei-Jian Lou, Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, People’s Republic of China, Tel/Fax +86-571-8600-6803, Email 3415116@zju.edu.cn; 13588708537@163.comBackground: Pediatric hypertension become an early marker of cardiovascular diseases, but their antihypertensive drug use patterns are rarely known.Purpose: To investigate the epidemiological characteristics of pediatric hypertension and the use of antihypertensive drugs in the real world in China.Methods: In this study, the demographic, diagnosis, and medication prescription data including the antihypertensive drug types and comorbidities, were analyzed. The antihypertensive drugs use were evaluated according to the Chinese guidelines for hypertension.Results: 1301 prescriptions (number of visits) containing 1880 antihypertensive medical orders were collected. The average number of antihypertensive drugs per prescription was 1.45 (± 0.75). The patients aged 16 to 18 (70.18%) accounted for the highest proportion. Kidney diseases (33.28%) were the most common comorbidities. Calcium channel blocker (CCB), angiotensin II receptor blocker (ARB), and β receptor blocker (BB) were the most used antihypertensive drugs. The most frequent monotherapy was CCB, while that of two and three drugs combination were ARB+CCB and ARB+BB+CCB, respectively. Metoprolol (11.44%), nifedipine (10.64%), amlodipine (10.59%), valsartan (6.12%) were the most commonly used antihypertensive drugs. The utilization rate of fixed compound preparations was 7.34%. However, the percentage of recommended antihypertensive drugs was just 14.20%, while the recommended drug combination was 84.93% according to the guidelines.Conclusion: For the first time ever we reported the antihypertensive prescription analysis in children in a large area of China. Our data provided new insights into the epidemiological characteristics and drug use in hypertensive children. We found that the guidelines for medication management in hypertensive children were not routinely followed. The wide use of antihypertensive drugs in children and those with weak clinical evidence raised concerns regarding its rational use. The findings could lead to more effective management of hypertension in children.Keywords: hypertensive children, antihypertensive drugs, drug combination, prescription

Jin-Bor Chen,1,2 Chiung-Chih Chang,2,3 Sin-Hua Moi,4 Lung-Chih Li1,2 1Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and School of Medicine, Kaohsiung, 833, Taiwan, Republic of China; 2College of Medicine, Chang Gung University, Taoyuan, 330, Taiwan, Republic of China; 3Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and School of Medicine, Kaohsiung, 833, Taiwan, Republic of China; 4Center of Cancer Program Development, E-Da Cancer Hospital, I-Shou University, Kaohsiung, 833, Taiwan, Republic of ChinaCorrespondence: Jin-Bor Chen, Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 123 DaPei Road, Niao Song District, Kaohsiung, 833, Taiwan, Republic of China, Tel +886-7-7317123, ext 8306, Fax +886-7-7322402, Email chenjb1019@gmail.com; jbchen@cgmh.org.twPurpose: This study aimed to compare the plasma levels of nanoparticle-based neurodegenerative biomarkers between hemodialysis (HD) participants with grossly normal cognitive function and healthy controls.Patients and Methods: A cohort of participants undergoing maintenance HD and healthy controls were enrolled for comparison between July and October 2021. The immunomagnetic reduction method was used to measure plasma neurodegenerative biomarkers Aβ1-40, Aβ1-42, tau protein, and neurofilament light chain (NfL). The clinical dementia rating (CDR) was used to evaluate cognitive function. A receiver operating characteristic curve was used to discriminate between HD participants and healthy controls.Results: There were 52 and 18 participants in the HD and healthy control groups, respectively. The mean age of the HD participants was 62 years, and that of the healthy controls was 57 years. The mean HD vintage in the HD cohort was 11.8 years. HD participants demonstrated significantly higher plasma levels of Aβ1-42, tau protein, Aβ1-42 × tau, and NfL and Aβ1-42/Aβ1-40 ratio and significantly lower plasma Aβ1-40 levels than healthy controls. The measured plasma biomarkers could not discriminate between CDR0 and CDR0.5 HD participants. The area under the curve of the study biomarkers to discriminate HD participants from healthy controls ranged from 0.987 (Aβ1-42 × tau) to 0.889 (NfL).Conclusion: The plasma levels of nanoparticle-based neurodegenerative biomarkers were higher in HD participants with grossly normal cognitive function than in healthy controls. These findings imply that neurodegenerative changes appear in HD participants. A profile of plasma neurodegenerative biomarkers could be considered a potential surrogate for evaluating long-term cognitive function in HD participants.Graphical Abstract: Keywords: Aβ proteins, cognitive function, hemodialysis, tau protein

Liu-Cheng Li,1,* Yong-Yue Han,2,* Zhi-Hui Zhang,3,4 Wen-Cheng Zhou,5,6 Hong-Mei Fang,1 Jiao Qu,7 Lian-Di Kan1 1Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, People’s Republic of China; 2School of Pharmacy, Dalian Medical University, Dalian 116044, People’s Republic of China; 3Shanghai TCM-Integrated Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200082, People’s Republic of China; 4Shanghai TCM-Integrated Institute of Vascular Anomalies, Shanghai 200082, People’s Republic of China; 5Department of Pharmacy, The First Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou 310006, People’s Republic of China; 6Department of Pharmacy, Zhejiang Provincial Hospital of Traditional Chinese Medicine, Hangzhou 310006, People’s Republic of China; 7State Key Laboratory of Pharmaceutical Biotechnology, Department of Biotechnology and Pharmaceutical Sciences, School of Life Science, Nanjing University, Nanjing 210023, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lian-Di KanDepartment of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, People’s Republic of ChinaTel +86-571-86006803Email 3198004@zju.edu.cnJiao QuState Key Laboratory of Pharmaceutical Biotechnology, Department of Biotechnology and Pharmaceutical Sciences, School of Life Science, Nanjing University, Nanjing 210023, People’s Republic of ChinaTel +86-25-89687620Email qujiao19920819@163.comAbstract: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death across the globe. Its repeated exacerbation will seriously worsen the quality of life, aggravate the patients’ symptoms, and bring a heavy burden on the patients and the society. Understanding the current status of drug therapy and the role of pharmaceutical care is essential for the management of COPD. In addition to the drugs already on the market, recent clinical trials also show that emerging novel drugs for treating COPD are being developed to prevent the symptoms, reduce the frequency of acute exacerbation, and improve the quality of life. Recent progress in new drug research should lead to novel treatment options for COPD patients in future clinical practice. The pharmaceutical care has shown significantly favourable impacts on addressing drug-related problems, supporting its vital role in the management of COPD, especially when there are a wide range of therapeutic agents. This review not only provides an overview of current treatment strategies but also further underlines the importance of new drug development and pharmaceutical care for patients with COPD.Keywords: chronic obstructive pulmonary disease, drugs, clinical trial, complications, pharmaceutical care

Since the first plasma realized in 2020, a series of key systems on HL-3 (known as HL-2M before) tokamak have been equipped/upgraded, including in-vessel components (the first wall, lower divertor, and toroidal cryogenic/water-cooling/baking/glow discharge systems, etc.), auxiliary heating system of 11 MW, and 28 diagnostic systems (to measure the plasma density electron temperature, radiation, magnetic field, etc.). Magnet field systems were commissioned firstly for divertor plasma discharges. During the 2nd experimental campaign of HL-3 tokamak, several great progresses have been achieved. Firstly, the successful operation with plasma current larger than 1 MA was achieved under a divertor configuration. Secondly, the advanced divertor concept with two distinct snowflake configurations was realized. It is found that the distribution of ion saturation current and heat flux on bottom plate becomes wide due to magnetic surface expansion, demonstrating the advantage of such configuration in the heat flux mitigation. In addition, using the combination of NBI, ECRH and LHCD, the standard sawtoothing high confinement mode of megampere plasma was firstly accessed on the HL-3. The successful commissioning of HL-3 is beneficial for the initial operation of ITER.

Glen S Hazlewood,1– 3 Deborah A Marshall,1– 3 Claire EH Barber,1– 3 Linda C Li,3 Cheryl Barnabe,1– 3 Vivian Bykerk,4,5 Peter Tugwell,6 Pauline M Hull,7 Nick Bansback3,8 1Departments of Medicine and Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Canada; 2McCaig Institute of Bone and Joint Health, University of Calgary, Calgary, Canada; 3Arthritis Research Canada, Vancouver, BC, Canada; 4Weill Cornell Medical College, Cornell University, New York, NY, USA; 5Department of Rheumatology, Hospital for Special Surgery, New York, NY, USA; 6Department of Medicine, Department of Epidemiology and Community Medicine, Canada Research Chair, University of Ottawa, Institute of Population Health, Ottawa, Canada; 7University of Calgary, Calgary, Canada; 8Faculty of Medicine, School of Population and Public Health, University of British Columbia, Vancouver, CanadaCorrespondence: Glen S HazlewoodDepartments of Medicine and Community Health Sciences, University of Calgary, 3280 Hospital Drive NW, 3AA10, Calgary AB T2N 4Z6, CanadaTel +1 403 220-5903Fax +1 403 210-3899Email gshazlew@ucalgary.caPurpose: To evaluate, in a proof-of-concept study, a decision aid that incorporates hypothetical choices in the form of a discrete-choice experiment (DCE), to help patients with early rheumatoid arthritis (RA) understand their values and nudge them towards a value-centric decision between methotrexate and triple therapy (a combination of methotrexate, sulphasalazine and hydroxychloroquine).Patients and Methods: In the decision aid, patients completed a series of 6 DCE choice tasks. Based on the patient’s pattern of responses, we calculated his/her probability of choosing each treatment, using data from a prior DCE. Following pilot testing, we conducted a cross-sectional study to determine the agreement between the predicted and final stated preference, as a measure of value concordance. Secondary outcomes including time to completion and usability were also evaluated.Results: Pilot testing was completed with 10 patients and adjustments were made. We then recruited 29 patients to complete the survey: median age 57, 55% female. The patients were all taking treatment and had well-controlled disease. The predicted treatment agreed with the final treatment chosen by the patient 21/29 times (72%), similar to the expected agreement from the mean of the predicted probabilities (68%). Triple therapy was the predicted treatment 24/29 times (83%) and chosen 20/29 (69%) times. Half of the patients (51%) agreed that completing the choice questions helped them to understand their preferences (38% neutral, 10% disagreed). The tool took an average of 15 minutes to complete, and median usability scores were 55 (system usability scale) indicating “OK” usability.Conclusion: Using a DCE as a value-clarification task within a decision aid is feasible, with promising potential to help nudge patients towards a value-centric decision. Usability testing suggests further modifications are needed prior to implementation, perhaps by having the DCE exercises as an “add-on” to a simpler decision aid.Keywords: conjoint analysis, decision tool, value concordance, methotrexate

Aileen M Davis,1–5 Marvilyn Palaganas,1 Linda C Li6,7 1Division of Health Care and Outcomes Research, 2Arthritis Community Research and Evaluation Unit, Krembil Research Institute, University Health Network, 3Department of Physical Therapy, Institute of Health Policy, 4Management and Evaluation, 5Institute of Rehabilitation Science, University of Toronto, Toronto, ON, 6Arthritis Research Canada, Richmond, 7Department of Physical Therapy, University of British Columbia, Vancouver, BC, Canada Introduction: In North America, delivery of targeted exercise and education programs by health professionals for people with hip and knee osteoarthritis (OA) poses challenges related to cost and access. Linking the wellness and health sectors could increase program availability. We evaluated if people with OA were willing to participate in programs delivered by trainers in community centers/gyms. Methods: We conducted an online survey of the general public in Canada over a period of 2 months. Participants included those aged ≥30 years with self-reported chronic OA-like knee or hip pain. We evaluated access to community/fitness centers, exercise frequency, interest in attending an evidence-based program twice a week for 6 weeks, and willingness to pay. Analyses included descriptive statistics with 95% confidence intervals and chi-square tests to evaluate factors associated with willingness to attend the program. Results: After removing duplicate records, 751 respondents completed the survey with 408 likely having hip and/or knee OA and never having received a joint replacement. These 408 respondents had an age range of 30 to ≥75 years and 86% were female. Of the 408, (63.7%) were between 45 and 64 years of age. Only two respondents reported that a community center was >1 hour away. One hundred and fifty-six (38%) reported a current membership, and 203 (50.4%) reported exercise 3 days/wk, 120 (29.8%)

© Dan Guo, Liam Barry, Sharon Szu Hua Lin, Vera Huang, and Long-Cheng Li.Small RNA programmed Argonautes are sophisticated cellular effector platforms known to be involved in a diverse array of functions ranging from mRNA cleavage, translational inhibition

Argonaute proteins are often credited for their cytoplasmic activities in which they function as central mediators of the RNAi platform and microRNA (miRNA)-mediated processes. They also facilitate heterochromatin formation and establishment of repressive

RNAa (RNA activation) is a mechanism by which small dsRNA (double-stranded RNA), termed saRNA (small activating RNA), target promoter sequences to induce gene expression. This technique represents a novel approach to gene overexpression without the use of

BACKGROUND AND OBJECTIVE: This study explored the relationships among the roles assumed by physical therapists in arthritis care and their previous participation in arthritis courses for continuing professional development (CPD). DESIGN: A cross-sectional mail survey was conducted. METHOD: A total of 600 Canadian physical therapists and 461 Dutch physical therapists practicing in orthopedics were randomly selected to participate in a mail survey. The questionnaire covered areas related to their clinical practice, previous participation in arthritis-related CPD courses, and roles in the management of osteoarthritis (OA) and rheumatoid arthritis (RA). Poisson regression was used to explore the associations between physical therapists' participation in arthritis-related CPD courses and the number of roles they assumed in OA and RA care, after adjusting for personal characteristics, arthritis caseload, and country of practice. RESULTS: The survey response rates were 47.7% in Canada and 50.5% in the Netherlands. A total of 424 participants (Canada=224, the Netherlands=200) had treated patients with OA in the previous month, and 259 participants (Canada=68, Netherlands=191) had treated patients with RA in the previous month. The most common roles reported by participants were providing traditional physical therapy interventions and providing postsurgical care. Arthritis-related CPD courses significantly increased (ie, multiplied) the expected number of roles assumed by physical therapists by a factor of 1.32 (95% confidence interval=1.11, 1.56) in OA management and 1.69 (95% confidence interval=1.34, 2.13) in RA management. LIMITATIONS: Physical therapists' roles in arthritis management were obtained through self-reporting, which might differ from their actual clinical practice. CONCLUSIONS: This exploratory analysis highlights the association between participation in arthritis-related CPD courses and the roles assumed by physical therapists in OA and RA management. Further research is needed to understand the effects of CPD activities on other areas of physical therapist practice and on patients' outcomes. [ABSTRACT FROM AUTHOR]

Previous studies have shown increased expression of acetylcholine receptor-alpha (AChR-alpha) subunit transcripts in myasthenia gravis (MG) and experimental MG (EAMG), but none examined the functional properties of this overexpression. In this study we examined the mRNA and protein expression of AChR-alpha as well as the pattern of alpha-bungarotoxin labeling in muscle tissue from EAMG mice with varying disease severity. AChR-alpha expression was increased considerably in endplates from mice with severe EAMG, but it was distinct and greatly in excess of alpha-bungarotoxin labeling. This "aberrant expression" occurred in mice with morphologic endplate damage, and the pattern of complement and immunoglobulin deposition in muscle from these mice appeared to mirror the pattern of AChR-alpha expression. The loss of functional AChR in severe MG increases transcription of AChR-alpha mRNA, but the expressed protein is "functionally inert," failing to compensate for loss of AChR. This enhanced expression of AChR may play a role in driving the ongoing autoimmune response. Muscle Nerve 40: 279-286, 2009. [ABSTRACT FROM AUTHOR]

Sitagliptin (MK-0431) is an orally active, potent, and selective dipeptidyl peptidase-4 inhibitor used for the treatment of patients with type 2 diabetes mellitus. Sitagliptin has been shown to be a substrate for P-glycoprotein in preclinical studies. Cyclosporine was used as a probe P-glycoprotein inhibitor at a high dose to evaluate the potential effect of potent P-glycoprotein inhibition on single-dose sitagliptin pharmacokinetics in healthy male subjects. Eight healthy young men received a single oral 600-mg dose of cyclosporine with a single 100-mg oral sitagliptin dose and a single oral 100-mg sitagliptin dose alone in an open-label, randomized, 2-period, crossover study. Single doses of sitagliptin with or without single doses of cyclosporine were generally well tolerated. The sitagliptin AUC0-∞ geometric mean ratio was 1.29 with a 90% confidence interval of (1.24, 1.34). The sitagliptin Cmax geometric mean ratio was 1.68 with a 90% confidence interval of (1.35, 2.08). Cyclosporine coadministration did not appear to affect apparent sitagliptin renal clearance, t1/2, or C24 h, suggesting that effects of these high doses of cyclosporine are more likely due to enhanced absorption of sitagliptin, potentially through inhibition of intestinal P-glycoprotein. These results rationalize the use of a single high-dose cyclosporine as a probe inhibitor of P-glycoprotein for compound candidates whose elimination is less dependent on CYP3A4-mediated metabolism. [ABSTRACT FROM AUTHOR]

The crystal structure and magnetic properties of polycrystalline Sr2(Fe1−xNix)MoO6 (0.0  x  0.2) synthesized via a mechanical activation route have been investigated. Rietveld refinement of the x-ray diffraction data indicates that the long-range order parameter (S) among octahedral B sites in Sr2(Fe1−xNix)MoO6 is significantly enhanced by an increasing level of Ni doping. The B-site ordering results in a decrease in the lattice dimensions and an increase in lattice tetragonal distortion. Consequently, magnetization of the Ni-doped Sr2FeMoO6 is progressively improved by an increasing level of Ni doping. The Curie temperature (Tc) in Sr2(Fe1−xNix)MoO6 is also raised systematically by Ni doping, from Tc = 411 K for x = 0 to Tc = 432 K for x = 0.20. Magnetization and Curie temperature in Sr2(Fe1−xNix)MoO6 depend almost linearly on both the level of Ni doping and B-site long-range order parameter S. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the outcomes of patients with rheumatoid arthritis (RA) receiving treatment from a rheumatology-trained primary therapist and to assess the feasibility of the research protocol.Method: The experimental (E) group received treatment from a primary therapist in addition to their overall medical care. The usual care (UC) group continued receiving usual medical care. The first 10 patients completed the Health Assessment Questionnaire, a pain visual analogue scale, and the Arthritis Community Research and Evaluation Unit RA Knowledge Questionnaire. Patients were classified as clinical responders if they showed 20% improvement in two-thirds of core measures between baseline and 6 months. Baseline assessment was performed immediately prior to randomization. All patients completed the EuroQol and a monthly health resource use questionnaire.Results: A trend towards improvement was found in the E group (n = 11) in all clinical measures at discharge (approximately 6 weeks from baseline) and 6 months from baseline. In contrast, the UC group (n = 13) showed a slight deterioration in pain (at 6 weeks) and in disease-specific knowledge (at 6 months). Three of six patients in the E group and one of four patients in the UC group met the criteria of clinical responders.Conclusions: The study suggests an improvement trend in patient outcomes after treatment from a primary therapist and that the study protocol is feasible for a full-scale clinical trial. [ABSTRACT FROM AUTHOR]

BACKGROUND AND PURPOSE: Since the release of acute low back pain management guidelines in 1994, little was known about the effect of these guidelines on clinical practice. The purpose of this study was to examine physical therapists' reported management of acute and subacute lumbar impairment. SUBJECTS: One in 10 registered physical therapists who were randomly selected from southern Ontario, Canada, (n=454) and all registered physical therapists from northern Ontario (n=331) were surveyed. METHODS: In the questionnaire, case scenarios covered 3 areas related to the management of lumbar impairment: (1) physical examination, (2) treatment and recommendations, and (3) therapists' beliefs regarding its management. RESULTS: Five hundred sixty-nine questionnaires were returned (response rate=72.5%). Only data obtained for therapists (n=274) whose weekly workload included more than 10% of people with lumbar impairment were used in the analysis. Overall, patient education, exercise, and electrotherapeutic and thermal modalities were the preferred interventions for acute lumbar impairment (symptom onset of less than 5 weeks) with or without sciatica, whereas exercise and work modification were preferred for subacute lumbar impairment (symptom onset of 5 weeks or longer). There was a trend of using electrotherapeutic and thermal modalities with uncertain effectiveness. Only 46.3% of the therapists agreed or strongly agreed that practice guidelines were useful for managing lumbar impairment. DISCUSSION AND CONCLUSION: Although the physical therapists surveyed, in general, followed the guidelines in managing acute lumbar impairment, they felt uncertain regarding the value of practice guidelines. Future research should focus on identifying effective treatment approaches and exploring the effectiveness of practice guidelines. [ABSTRACT FROM AUTHOR]

Swertia Mussotti is used as febrifuge, analgesic and to treat calculous cholecystitis, however, the underling mechanism remains unclear. This study investigates the therapeutic effect of the active fraction named iridoid and xanthone glycoside (IXG) extracted from S. mussotii on six animal models related to calculous cholecystitis and its complications, and to explore its potential target proteins. Four main compounds including swertiamarin (STR), sweroside (SRS), gentiopicroside (GPS) and mangiferin (MGR) were identified from the IXG by UHPLC-TOF-MS. The in vivo experiments results confirmed that IXG significantly decreased the level of total bilirubin (TBIL), direct bilirubin (DBIL) and cyclooxygenase-2 (COX2) in calculous cholecystitis. IXG treatment dramatically reduced the number of twists and the time of clicking foot in 2 nd phase induced by glacial acetic acid and formalin, however, no effect was showed on central pain established by hot plate test. IXG also significantly decreased the anal temperature induced by yeast and 2,4-dinitrophenol. These results indicated that IXG alleviate calculous cholecystitis and its clinical symptom. In addition, IXG suppressed the expression of Prostaglandin E2 (PGE2) in vitro. Mechanistically, COX2 was identified as the direct target of IXG in RAW264.7 cells, and downregulated the protein levels of COX2. The results confirmed that IXG ameliorates calculous cholecystitis and its clinical symptom (pain and fever) by suppressing the production of PGE2 through targeting COX2., Competing Interests: Declaration of competing interest No conflict of interest has been declared by the authors., (Copyright © 2024 Elsevier B.V. All rights reserved.)