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Novel strategies have been proposed for articular cartilage damage occurring during osteoarthritis (OA) and -among these- Extracorporeal Shock Wave Therapy (ESWT), intra-articular injections of Platelet-Rich Plasma (PRP) or Hyaluronic Acid (HA) revealed encouraging results. To investigate the possible mechanisms responsible for those clinical benefits, we established primary cultures of human chondrocytes derived from cartilage explants and measured the in vitro effects of ESW, PRP and HA therapies. After molecular/morphological cell characterization, we assessed those effects on the functional activities of the chondrocyte cell cultures, at the protein and molecular levels. ESWT significantly prevented the progressive dedifferentiation that spontaneously occurs during prolonged chondrocyte culture. We then attested the efficiency of all such treatments to stimulate the expression of markers of chondrogenic potential such as SOX9 and COL2A, to increase the Ki67 proliferation index as well as to antagonize the traditional marker of chondrosenescence p16INK4a (known as Cdkn2a). Furthermore, all our samples showed an ESW- and HA-mediated enhancement of migratory and anti-inflammatory activity onto the cytokine-rich environment characterizing OA. Taken together, those results suggest a regenerative effect of such therapies on primary human chondrocytes in vitro. Moreover, we also show for the first time that ESW treatment induces the surface expression of major hyaluronan cell receptor CD44 allowing the increase of COL2A/COL1A ratio upon HA administration. Therefore, this work suggests that ESW-induced CD44 overexpression enhances the in vitro cell susceptibility of human chondrocytes to HA, presumably favouring the repair of degenerated cartilage.

Our previous study in patients with cerebellar ataxias of different causes showed significant benefit of riluzole after 8 weeks. We aimed to confirm these results in patients with spinocerebellar ataxia or Friedreich's ataxia in a 1-year trial. Patients with spinocerebellar ataxia or Friedreich's ataxia (2:1 ratio) from three Italian neurogenetic units were enrolled in this multicentre, double-blind, placebo-controlled trial, and randomly assigned to riluzole (50 mg orally, twice daily) or placebo for 12 months. The randomisation list was computer-generated and a centralised randomisation system was implemented. Participants and assessing neurologists were masked to treatment allocation. The primary endpoint was the proportion of patients with improved Scale for the Assessment and Rating of Ataxia (SARA) score (a drop of at least one point) at 12 months. An intention-to-treat analysis was done. This trial is registered at ClinicalTrials.gov, number NCT01104649. Between May 22, 2010, and Feb 25, 2013, 60 patients were enrolled. Two patients in the riluzole group and three in the placebo group withdrew their consent before receiving treatment, so the intention-to-treat analysis was done on 55 patients (19 with spinocerebellar ataxia and nine with Friedreich's ataxia in the riluzole group, and 19 with spinocerebellar ataxia and eight with Friedreich's ataxia in the placebo group). The proportion with decreased SARA score was 14 (50%) of 28 patients in the riluzole group versus three (11%) of 27 in the placebo group (OR 8·00, 95% CI 1·95–32·83; p=0·002). No severe adverse events were recorded. In the riluzole group, two patients had an increase in liver enzymes (less than two times above normal limits). In two participants in the riluzole group and two participants in the placebo group, sporadic mild adverse events were reported. Our findings lend support to the idea that riluzole could be a treatment for cerebellar ataxia. Longer studies and disease-specific trials are needed to confirm whether these findings can be applied in clinical practice. Agenzia Italiana del Farmaco.

Anterior cruciate ligament (ACL) injury represents one of the main disorders affecting players, especially in contact sports. Even though several approaches based on artificial intelligence have been developed to allow the quantification of ACL injury risk, their applicability in training sessions compared with the clinical scale is still an open question. We proposed a machine-learning approach to accomplish this purpose. Thirty-nine female basketball players were enrolled in the study. Leg stability, leg mobility and capability to absorb the load after jump were evaluated through inertial sensors and optoelectronic bars. The risk level of athletes was computed by the Landing Error Score System (LESS). A comparative analysis among nine classifiers was performed by assessing the accuracy, F1-score and goodness. Five out nine examined classifiers reached optimum performance, with the linear support vector machine achieving an accuracy and F1-score of 96 and 95%, respectively. The feature importance was computed, allowing us to promote the ellipse area, parameters related to the load absorption and the leg mobility as the most useful features for the prediction of anterior cruciate ligament injury risk. In addition, the ellipse area showed a strong correlation with the LESS score. The results open the possibility to use such a methodology for predicting ACL injury.

In vitro models of human tenocytes derived from healthy as well as from ruptured tendons were established, characterized and used at very early passage (P1) to evaluate the effects of Extracorporeal Shock Wave Treatment (ESWT). The molecular analysis of traditional tenocytic markers, including Scleraxis (Scx), Tenomodulin (Tnm), Tenascin-C (Tn-C) and Type I and III Collagens (Col I and Col III), permitted us to detect in our samples the simultaneous expression of all these genes and allowed us to compare their levels of expression in relationship to the source of the cells and treatments. In untreated conditions, higher molecular levels of Scx and Col I in tenocytes from pathological compared to healthy samples have been detected, suggesting--in the cells from injured tendon--the natural trigger of an early differentiation and repairing program, which depends by Scx and requires an increase in collagen expression. When ESWT (at the dose of 0.14 mJ/mm(2)) was applied to cultured tenocytes explanted from injured source, Scx and Col I were significantly diminished compared to healthy counterpart, indicating that such natural trigger maybe delayed by the treatment, in order to promote cellular repair. Herein, we show for the first time that ESWT enhances in vitro functional activities of ruptured tendon-derived tenocytes, such as proliferation and migration, which could probably contributes to tendon healing in vivo.

Spinal pain is recognized as the most common cause of disability, work absenteeism and need of healthcare services worldwide. Although many strategies have been developed for conservative treatment of spinal pain, its increasing prevalence diagnosis highlights the need for new treatments. Oxygen-ozone (O2-O3) therapy is considered to be an alternative therapy due to its analgesic and anti-inflammatory effects. This retrospective study evaluated the effects of O2-O3 intramuscular paravertebral injections in 76 patients with chronic neck pain or low back pain, in terms of pain and disability reduction, quality of life improvement, and analgesic drug intake. Patients were evaluated before, at the end of the treatment, and at 1, 3 and 6 months after the last treatment, using Numeric Rating Scale, Neck Disability Index or Oswestry Disability Index, and Short Form-12 Health Survey. There were significant beneficial effects of O2-O3 therapy in reducing pain and disability reduction and improving quality of life during the 6-month follow-up period. O2-O3 therapy was associated with a reduction in analgesic drug intake at each assessment. Our results allow us not only to support treatment with O2-O3 intramuscular paravertebral injections as a safe and beneficial treatment for chronic low back pain, but also to consider it as a valuable conservative therapy for patients with chronic neck pain.

Facet joint osteoarthritis is the most prevalent source of facet joint pain and represents a significant cause of low back pain. Oxygen-ozone therapy has been shown to have positive results in acute and chronic spinal degeneration diseases and it could be a safe and efficacious alternative to traditional facet joint conservative treatments. This review article explains the interventional facet joint management with ultrasound-guided oxygen-ozone therapy, providing an anatomy/sonoanatomy overview of lumbar facet joints and summarizing the potential mechanism of action of oxygen-ozone in the treatment of facet joint osteoarthritis, not yet fully understood.

The possibility of measuring predictive factors to discriminate athletes at higher risk of anterior cruciate ligament (ACL) injury still represents an open research question. We performed an observational study with thirteen female basketball players who performed monopodalic jumps and single-leg squat tests. One of them suffered from an ACL injury after the first test session. Data gathered from twelve participants, who did not suffer from ACL injury, were used for a reliability analysis. Parameters related to leg stability, load absorption capability and leg mobility showed good-to-excellent reliability. Path length, root mean square of the acceleration and leg angle with respect to the vertical axis revealed themselves as possible predictive factors to identify athletes at higher risk. Results confirm that six months after reconstruction represents the correct time for these athletes to return to playing. Furthermore, the training of leg mobility and load absorption capability could allow athletes to reduce the probability of new injuries.

Purpose The aim of this study was to investigate whether the effects of extracorporeal shock wave therapy (ESWT) could affect the behavior of primary cultured human tenocytes over a 12-day period. Methods In this controlled laboratory study, primary human tenocytes were established from semitendinosus tendons collected from 3 patients undergoing arthroscopic anterior cruciate ligament (ACL) reconstruction. Cell viability, overall cell morphology, cell proliferation, and collagen synthesis following ESWT have been evaluated. Results ESWT significantly interferes with the overall cell morphology, by impairing dedifferentiation of the cells. Furthermore, a shock wave-mediated growth-promoting effect was measured by the MTT (tetrazolium) colorimetric assay and by the proliferation marker Ki67. Lastly, a significant increase in collagen (mainly type I) synthesis by ESWT-tenocytes compared with control cells was found. Conclusions Shock wave treatment promoted cell growth and collagen synthesis of primary cultured human tenocytes. The clinical benefits of ESWT may be ascribed to an increased efficiency of tendon repair after injury.

Extracorporeal shockwave therapy (ESWT) represents a form of \"mechanotherapy\" that operates by delivering acoustic waves to biological tissues [...].Extracorporeal shockwave therapy (ESWT) represents a form of \"mechanotherapy\" that operates by delivering acoustic waves to biological tissues [...].

Neuroinflammation is an emerging therapeutic target in chronic degenerative and autoimmune diseases, such as osteoarthritis (OA) and rheumatoid arthritis. Mast cells (MCs) play a key role in the homeostasis of joints and the activation of MCs induces the release of a huge number of mediators, which fuel the fire of neuroinflammation. Particularly, synovial MCs release substances which accelerate the degradation of the extra-cellular matrix causing morphological joint changes and cartilage damage and inducing the proliferation of synovial fibroblasts, angiogenesis, and the sprouting of sensory nerve fibers, which mediate chronic pain. Palmitoylethanolamide (PEA) is a well-known MCs modulator, but in osteoarthritic joints, its levels are significantly reduced. Adelmidrol, a synthetic derivate of azelaic acid belonging to the ALIAmides family, is a PEA enhancer. Preclinical and clinical investigations showed that the intra-articular administration of Adelmidrol significantly reduced MC infiltration, pro-inflammatory cytokine release, and cartilage degeneration. The combination of 1% high molecular weight hyaluronic acid and 2% Adelmidrol has been effectively used for knee osteoarthritis and, a significant improvement in analgesia and functionality has been recorded.