Rejected

Mesenchymal stem cell (MSC) therapies have been used as cell-based treatments for decades, owing to their anti-inflammatory, immunomodulatory, and regenerative properties. With high expectations, many ongoing clinical trials are investigating the safety and efficacy of MSC therapies to treat arthritic diseases. Studies on osteoarthritis (OA) have shown positive clinical outcomes, with improved joint function, pain level, and quality of life. In addition, few clinical MSC trials conducted on rheumatoid arthritis (RA) patients have also displayed some optimistic outlook. The largely positive outcomes in clinical trials without severe side effects establish MSCs as promising tools for arthritis treatment. However, further research is required to investigate its applicability in clinical settings. This review discusses the most recent advances in clinical studies on MSC therapies for OA and RA.

Aging is associated with changes in hormones, slowing of metabolism, diminished physiological processes, chronic inflammation and high exposure to oxidative stress factors, generally described as the biological cost of living. Lifestyle interventions of diet and exercise can improve the quality of life during aging and lower diet-related chronic disease. The endocannabinoid system (ECS) has important effects on systemic metabolism and physiological systems, including the central and peripheral nervous systems. Exercise can reduce the loss of muscle mass and improve strength, and increase the levels of endocannabinoids (eCB) in brain and blood. Although the ECS exerts controls on multiple systems throughout life it affords benefits to natural aging. The eCB are synthesized from polyunsaturated fatty acids (PUFA) and the primary ones are produced from arachidonic acid (n-6 PUFA) and others from the n-3 PUFA, namely eicosapentaenoic and docosahexaenoic acids. The eCB ligands bind to their receptors, CB1 and CB2, with effects on appetite stimulation, metabolism, immune functions, and brain physiology and neuroplasticity. Dietary families of PUFA are a primary factor that can influence the types and levels of eCB and as a consequence, the downstream actions when the ligands bind to their receptors. Furthermore, the association of eCB with the synthesis of oxylipins (OxL) is a connection between the physiological actions of eCB and the lipid derived immunological OxL mediators of inflammation. OxL are ubiquitous and influence neuroinflammation and inflammatory processes. The emerging actions of eCB on neuroplasticity, well-being and pain are important to aging. Herein, we present information about the ECS and its components, how exercise and diet affects specific eCB, their role in neuroplasticity, neuroinflammation, pain, mood, and relationship to OxL. Poor nutrition status and low nutrient intakes observed with many elderly are reasons to examine the role of dietary PUFA actions on the ECS to improve health.

Neurostimulation techniques for the treatment of chronic low back pain (LBP) have been rapidly evolving; however, questions remain as to which modalities provide the most efficacious and durable treatment for intractable axial symptoms. Modalities of spinal cord stimulation, such as traditional low-frequency paresthesia based, high-density or high dose (HD), burst, 10-kHz high-frequency therapy, closed-loop, and differential target multiplexed, have been limitedly studied to determine their efficacy for the treatment of axial LBP. In addition, stimulation methods that target regions other than the spinal cord, such as medial branch nerve stimulation of the multifidus muscles and the dorsal root ganglion may also be viable treatment options. Here, current scientific evidence behind neurostimulation techniques have been reviewed with a focus on the management of chronic axial LBP.

Infrared (IR) inhibition can selectively block peripheral sensory nerve fibers, a potential treatment for autonomic-dysfunction-related diseases (e.g., neuropathic pain and interstitial cystitis). Lowering the IR inhibition threshold can increase its translational potentials. Infrared induces inhibition by enhancing potassium channel activation. We hypothesized that the IR dose threshold could be reduced by combining it with isotonic ion replacement. We tested the IR inhibition threshold on the pleural-abdominal connective of . Using a customized chamber system, the IR inhibition was applied either in normal saline or in isotonic ion-replaced saline, which could be high glucose saline, high choline saline, or high glucose/high choline saline. Each modified saline was at a subthreshold concentration for inhibiting neural conduction. We showed that isotonically replacing ions in saline with glucose and/or choline can reduce the IR threshold and temperature threshold of neural inhibition. Furthermore, the size selectivity of IR inhibition was preserved when combined with high glucose/high choline saline. The present work of IR inhibition combined with isotonic ion replacement will guide further development of a more effective size-selective IR inhibition modality for future research and translational applications.

An analytical review of the methods of cancer patients' rehabilitation with peripheral polyneuropathy induced by cytostatics (PNPIC) was carried out. Studies from electronic databases were investigated: Scopus, Web of Science, MedLine, World Health Organization, The Cochrane Central Register of Controlled Trials, ScienceDirect, US National Library of Medicine National Institutes of Health, PubMed Cancer, eLIBRARY, CyberLeninka. Despite the improvement of anticancer therapy and an increase in patients' life expectancy, the emerging peripheral polyneuropathy remains an urgent problem, since it significantly affects both the patients' life quality and the selection of adequate therapy. The frequency of detection of PNPIC is 90%, after discontinuation of treatment; symptoms of damaged peripheral nerve fibers remain in 30% of patients. The clinical symptoms of PNPIC are varied and most often include numbness in the extremities and / or increased sensitivity to thermal or mechanical stimuli, neuropathic pain. Currently, to prevent PNPIC, treatment is being modified with a reduction in the duration of courses and doses of cytostatics, and interruption of treatment. Official guidelines do not recommend any prophylaxis other than the possible use of duloxetine or a topical gel containing baclofen, amitriptyline, and ketamine. Over the past few years, there has been no significant progress in the prevention and treatment of PNPIC. The most common drug treatment method in clinical practice is the prescription of vitamins B. Among the non-drug treatment methods of PNPIC, the authors used acupuncture, electro-acupuncture, manual therapy, massage, gymnastics, yoga, sensorimotor training, general vibration therapy, percutaneous electro-neuro-stimulation, electro-analgesia, local cryotherapy, hydrotherapy, low-intensity alternating magnetic radiation. The studies included in the review are heterogeneous in design and protocol, number of patients, and time points for assessing outcomes. In connection with the existing differences, it is not possible to carry out a comparative analysis of the results of these rehabilitation types and to give an unambiguous answer about their effectiveness. As the analysis has shown, peripheral PNPIC is well known all over the world, however, the search for methods of its treatment is far from complete.

Chronic pain is often associated with functional limitations that have a huge impact on patients' lives. However, despite being relatively common, chronic musculoskeletal pain is still viewed by some as a symptom of another disease rather than its own condition, and is therefore poorly addressed. This is compounded by other challenges in the field, including education gaps for both healthcare professionals and patients, a lack of universal and comprehensive assessment tools, poor societal perceptions of chronic pain, and the current stigma around the use of opioids. Here, we review the current chronic musculoskeletal pain management landscape in the United States and offer professional insight into emerging methods that can be used to improve patient outcomes, in particular, the achievement of meaningful functional goals. This perspective incorporates our combined multidisciplinary (psychiatry, psychology, nursing, physical therapy, and general medicine) experience and insights. We believe that chronic pain is a multifactorial experience and treatment requires an integrated, multidisciplinary approach from a range of healthcare providers. For the best patient outcomes, this team should work together to assess and treat the patient as a whole, addressing their pain and also providing education, empowerment, and support to enable patients to set and achieve meaningful functional goals that will provide real improvement in their quality of life. We believe that the healthcare community should elevate the conversation around chronic musculoskeletal pain management beyond that of just pain, to encompass the meaningful benefits that improvement in functional outcomes brings to patients.

Atopic dermatitis (AD) is a chronic, relapsing, inflammatory condition marked by pruritus and traditionally treated with topical corticosteroids (TCS) and topical calcineurin inhibitors (TCI). Crisaborole 2% ointment (a topical phosphodiesterase-4 inhibitor) is a newer topical agent for the treatment of AD. Crisaborole is indicated for treating mild-to-moderate AD and evidence from phase 3 and phase 4 trials show that crisaborole is an effective agent with a well-tolerated side effect profile for children >2 years of age. The most common side effects are pain and paresthesia at the application site. Treatments with tolerable safety profiles such as crisaborole may provide an alternative to patients with TCS phobia. The role of crisaborole in AD therapy may become clearer as multiple phase 4 trials are currently underway and their results are poised to answer more questions, including its safety profile for patients as young as 3 months of age, potential use as a steroid-sparing agent, and direct comparisons to TCS and TCI, which are the current mainstay treatments of mild-to-moderate AD.

Osteoarthritis (OA) is one of the major causes of chronic pain in dogs. However, the pathogenesis of OA has not been fully understood in dogs. The objective of this study was to comprehensively investigate the mRNA expression levels of proinflammatory cytokines, inflammatory mediators, nerve growth factor and its receptor, and matrix metalloproteinases in the synovium of dogs with spontaneous OA as well as to elucidate their relationships with the severity of synovitis. Dogs that were diagnosed with stifle OA on the basis of radiographic findings were included, and the degree of synovitis was observed using stifle arthroscopy. The dogs were assigned to two different groups depending on their synovitis scores: the low-grade group (score of 1 or 2; n = 8) and high-grade group (score of 3 to 5; n = 18). The dogs showing no evidence of orthopedic disease were included in the control group (n = 6). Synovial tissue samples were collected from the sites at which synovitis scores were assessed using arthroscopy. Total RNA was extracted from the collected synovial tissue, and cDNA was synthesized. Subsequently, RT-qPCR were performed using canine-specific primer sets for IL1B, IL6, CXCL8, TNF, TGFB1, PTGS2, PTGES, MMP3, MMP13, NGF, NTRK1, and PTGER4. Expression levels of IL1B, IL6, CXCL8, and MMP13 were significantly higher in the high-grade group than in the control group. In addition, expression levels of IL1B, CXCL8, TNF, and PTGS2 were significantly higher in the high-grade group than in the low-grade group. Expression levels of IL1B, IL6, CXCL8, TNF, PTGS2, and PTGER4 showed significant positive correlation with synovitis score. In conclusion, all mRNA expression levels in the synovial membrane varied according to the degree of synovitis in dogs with spontaneous OA. Thus, this study may partially elucidate the pathogenesis of synovitis in dogs with spontaneous OA.

Lumbar spondylolysis, caused by stress fracture of the pars interarticularis may lead to a bony defect or spondylolisthesis. In adolescents, its surgical treatment employs the smiley face rod method for direct reduction of pseudoarthrotic spondylolysis and spondylolisthesis. Clinical outcomes of this treatment have been occasionally described; however, implant removal has not been discussed previously. We present a patient with lumbar spondylolysis with grade 1 slip at the 5th lumbar vertebra (L5) per the Meyerding classification. A 14-year-old boy presented with chronic severe lower back pain. Since conservative therapy did not resolve pain or enable resuming sports activities, the smiley face rod repair was performed 7 months after the initial treatment. Anterior slippage of the L5 was surgically reduced. The patient wore a brace for 3 months postoperatively, and partial bone fusion was noted 6 months postoperatively. He resumed his sports activity 8 months postoperatively, and absolute bone fusion was confirmed 18 months postoperatively. Implant removal was performed 3 years postoperatively. Grade 1 slip was corrected with absolute bone fusion, and long-term follow-up revealed good results in terms of healing and rehabilitation. Smiley face rod method that allows for implant removal after bone fusion is suitable for adolescents.