TNF-Alpha in the Locomotor System beyond Joints: High Degree of Involvement in Myositis in a Rabbit Model

The importance of TNF-alpha in arthritis is well documented. It may be that TNF-alpha is also markedly involved in muscle inflammation (myositis). An animal model where this can be investigated is needed. A newly developed rabbit myositis model involving pronounced muscle overuse and local injections of substances having proinflammatory effects was therefore used in the present study. The aim was to investigate the patterns of TNF-alpha expression in the developing myositis and to evaluate the usefulness of this myositis model for further TNF-alpha research. Human rheumatoid arthritis (RA) synovial tissue was examined as a reference. TNF-alpha immunoexpression and TNF-alpha mRNA, visualized via in situ hybridization, were detected in cells in the inflammatory infiltrates of the affected muscle (soleus muscle). Coexistence of TNF-alpha and CD68 immunoreactions was noted, suggesting that the TNF-alpha reactive cells are macrophages. Expression of TNF-alpha mRNA was also noted in muscle fibers and blood vessel walls in areas with inflammation. These findings demonstrate that TNF-alpha is highly involved in the myositis process. The model can be used in further studies evaluating the importance of TNF-alpha in developing myositis

Asymptomatic Achilles tendon pathology is associated with a central fat distribution in men and a peripheral fat distribution in women: a cross sectional study of 298 individuals

<p>Abstract</p> <p>Background</p> <p>Adiposity is a modifiable factor that has been implicated in tendinopathy. As tendon pain reduces physical activity levels and can lead to weight gain, associations between tendon pathology and adiposity must be studied in individuals without tendon pain. Therefore, the purpose of this study was to determine whether fat distribution was associated with asymptomatic Achilles tendon pathology.</p> <p>Methods</p> <p>The Achilles tendons of 298 individuals were categorised as normal or pathological using diagnostic ultrasound. Fat distribution was determined using anthropometry (waist circumference, waist hip ratio [WHR]) and dual-energy x-ray absorptiometry.</p> <p>Results</p> <p>Asymptomatic Achilles tendon pathology was more evident in men (13%) than women (5%) (p = 0.007). Men with tendon pathology were older (50.9 ± 10.4, 36.3 ± 11.3, p < 0.001), had greater WHR (0.926 ± 0.091, 0.875 ± 0.065, p = 0.039), higher android/gynoid fat mass ratio (0.616 ± 0.186, 0.519 ± 0.142, p = 0.014) and higher upper-body/lower body fat mass ratio (2.346 ± 0.630, 2.022 ± 0.467, p = 0.013). Men older than 40 years with a waist circumference >83 cm had the greatest prevalence of tendon pathology (33%). Women with tendon pathology were older (47.4 ± 10.0, 36.0 ± 10.3, p = 0.008), had less total fat (17196 ± 3173 g, 21626 ± 7882 g, p = 0.009), trunk fat (7367 ± 1662 g, 10087 ± 4152 g, p = 0.003) and android fat (1117 ± 324 g, 1616 ± 811 g, p = 0.005). They had lower central/peripheral fat mass ratios (0.711 ± 0.321 g, 0.922 ± 0.194 g, p = 0.004) than women with normal tendons. Women with tendon pathology were more often menopausal (63%, 13%, p = 0.002).</p> <p>Conclusions</p> <p>Men with Achilles tendon pathology were older and had a central fat distribution. Women with tendon pathology were older and had a peripheral fat distribution. An interaction between age and waist circumference was observed among men.</p

The Acceptability Among Health Researchers and Clinicians of Social Media to Translate Research Evidence to Clinical Practice: Mixed-Methods Survey and Interview Study

Background: Establishing and promoting connections between health researchers and health professional clinicians may help translate research evidence to clinical practice. Social media may have the capacity to enhance these connections. Objective: The aim of this study was to explore health researchers’ and clinicians’ current use of social media and their beliefs and attitudes towards the use of social media for communicating research evidence. Methods: This study used a mixed-methods approach to obtain qualitative and quantitative data. Participation was open to health researchers and clinicians. Data regarding demographic details, current use of social media, and beliefs and attitudes towards the use of social media for professional purposes were obtained through an anonymous Web-based survey. The survey was distributed via email to research centers, educational and clinical institutions, and health professional associations in Australia, India, and Malaysia. Consenting participants were stratified by country and role and selected at random for semistructured telephone interviews to explore themes arising from the survey. Results: A total of 856 participants completed the questionnaire with 125 participants declining to participate, resulting in a response rate of 87.3%. 69 interviews were conducted with participants from Australia, India, and Malaysia. Social media was used for recreation by 89.2% (749/840) of participants and for professional purposes by 80.0% (682/852) of participants. Significant associations were found between frequency of professional social media use and age, gender, country of residence, and graduate status. Over a quarter (26.9%, 229/852) of participants used social media for obtaining research evidence, and 15.0% (128/852) of participants used social media for disseminating research evidence. Most participants (95.9%, 810/845) felt there was a role for social media in disseminating or obtaining research evidence. Over half of the participants (449/842, 53.3%) felt they had a need for training in the use of social media for professional development. A key barrier to the professional use of social media was concerns regarding trustworthiness of information. Conclusions: A large majority of health researchers and clinicians use social media in recreational and professional contexts. Social media is less frequently used for communication of research evidence. Training in the use of social media for professional development and methods to improve the trustworthiness of information obtained via social media may enhance the utility of social media for communicating research evidence. Future studies should investigate the efficacy of social media in translating research evidence to clinical practice

Lifestyle and metabolic factors in relation to shoulder pain and rotator cuff tendinitis: A population-based study

<p>Abstract</p> <p>Background</p> <p>Shoulder pain is a common health problem. The purpose of this study was to assess the associations of lifestyle factors, metabolic factors and carotid intima-media thickness with shoulder pain and chronic (> 3 months) rotator cuff tendinitis.</p> <p>Methods</p> <p>In this cross-sectional study, the target population consisted of subjects aged 30 years or older participating in a national Finnish Health Survey during 2000-2001. Of the 7,977 eligible subjects, 6,237 (78.2%) participated in a structured interview and clinical examination. Chronic rotator cuff tendinitis was diagnosed clinically. Weight-related factors, C-reactive protein and carotid intima-media thickness were measured.</p> <p>Results</p> <p>The prevalence of shoulder joint pain during the preceding 30 days was 16% and that of chronic rotator cuff tendinitis 2.8%. Smoking, waist circumference and waist-to-hip ratio were related to an increased prevalence of shoulder pain in both genders. Metabolic syndrome, type 2 diabetes mellitus and carotid intima-media thickness were associated with shoulder pain in men, whereas high level of C-reactive protein was associated with shoulder pain in women. Increased waist circumference and type 1 diabetes mellitus were associated with chronic rotator cuff tendinitis in men.</p> <p>Conclusions</p> <p>Our findings showed associations of abdominal obesity, some other metabolic factors and carotid intima-media thickness with shoulder pain. Disturbed glucose metabolism and atherosclerosis may be underlying mechanisms, although not fully supported by the findings of this study. Prospective studies are needed to further investigate the role of lifestyle and metabolic factors in shoulder disorders.</p

Deciphering the pathogenesis of tendinopathy: a three-stages process

Our understanding of the pathogenesis of "tendinopathy" is based on fragmented evidences like pieces of a jigsaw puzzle. We propose a "failed healing theory" to knit these fragments together, which can explain previous observations. We also propose that albeit "overuse injury" and other insidious "micro trauma" may well be primary triggers of the process, "tendinopathy" is not an "overuse injury" per se. The typical clinical, histological and biochemical presentation relates to a localized chronic pain condition which may lead to tendon rupture, the latter attributed to mechanical weakness. Characterization of pathological "tendinotic" tissues revealed coexistence of collagenolytic injuries and an active healing process, focal hypervascularity and tissue metaplasia. These observations suggest a failed healing process as response to a triggering injury. The pathogenesis of tendinopathy can be described as a three stage process: injury, failed healing and clinical presentation. It is likely that some of these "initial injuries" heal well and we speculate that predisposing intrinsic or extrinsic factors may be involved. The injury stage involves a progressive collagenolytic tendon injury. The failed healing stage mainly refers to prolonged activation and failed resolution of the normal healing process. Finally, the matrix disturbances, increased focal vascularity and abnormal cytokine profiles contribute to the clinical presentations of chronic tendon pain or rupture. With this integrative pathogenesis theory, we can relate the known manifestations of tendinopathy and point to the "missing links". This model may guide future research on tendinopathy, until we could ultimately decipher the complete pathogenesis process and provide better treatments

Drug Repurposing: The Anthelmintics Niclosamide and Nitazoxanide Are Potent TMEM16A Antagonists That Fully Bronchodilate Airways

There is an unmet need in severe asthma where approximately 40% of patients exhibit poor β-agonist responsiveness, suffer daily symptoms and show frequent exacerbations. Antagonists of the Ca2+-activated Cl− channel, TMEM16A, offers a new mechanism to bronchodilate airways and block the multiple contractiles operating in severe disease. To identify TMEM16A antagonists we screened a library of ∼580,000 compounds. The anthelmintics niclosamide, nitazoxanide, and related compounds were identified as potent TMEM16A antagonists that blocked airway smooth muscle depolarization and contraction. To evaluate whether TMEM16A antagonists resist use- and inflammatory-desensitization pathways limiting β-agonist action, we tested their efficacy under harsh conditions using maximally contracted airways or airways pretreated with a cytokine cocktail. Stunningly, TMEM16A antagonists fully bronchodilated airways, while the β-agonist isoproterenol showed only partial effects. Thus, antagonists of TMEM16A and repositioning of niclosamide and nitazoxanide represent an important additional treatment for patients with severe asthma and COPD that is poorly controlled with existing therapies. It is of note that drug repurposing has also attracted wide interest in niclosamide and nitazoxanide as a new treatment for cancer and infectious disease. For the first time we identify TMEM16A as a molecular target for these drugs and thus provide fresh insights into their mechanism for the treatment of these disorders in addition to respiratory disease

Adiposity and its metabolic consequences contribute to Achilles tendinopathy

Pain in the Achilles tendon commonly affects active individuals but is also seen in sedentary people. This thesis shows that the accumulation of excess body fat, abnormal blood lipids and glucose metabolism were associated with Achilles tendinopathy. Targeting these lifestyle factors may improve treatment outcomes for tendon injury