Distraction Arthroplasty for Basal Thumb Osteoarthritis: 10-Year Follow-Up.

PURPOSE: Trapeziectomy has frequently been used to treat basal thumb osteoarthritis. However, complications, such as shortening of the thumb ray and reduced mobility and strength, can occur. The aim of this study was to present a 10-year follow-up of distraction arthroplasty without trapeziectomy. METHODS: Fifteen patients were followed for a mean of 121 months (range, 121-124 months). Subjective outcomes were evaluated with the Disabilities of the Arm, Shoulder, and Hand questionnaire, while the pain intensity was assessed with a Visual Analog Scale both before surgery and at the end of follow-up. Objective outcomes were obtained using the Kapandji score and an assessment of grip and pinch strength. Preoperative and final postoperative x-rays were obtained to evaluate metacarpal subsidence and progression of trapezial-metacarpal joint arthritis. RESULTS: The Visual Analog Scale score was reduced from 9.4 ± 0.5 before surgery to 2.5 ± 1 at follow-up. The mean Disabilities of the Arm, Shoulder, and Hand questionnaire score was 75.6 ± 12.6 before surgery and 16.9 ± 4 at 10 years. Hand grip strength of the operated side (26 ± 5.5 kg) achieved 95% of functionality compared to the opposite side, while key pinch strength (6.4 ± 1.6 kg) reached 93%. A Kapandji opposition score of 10 points was found in 12 patients, a score of 9 was found in 1, and a score of 8 was found in 2. CONCLUSIONS: Distraction arthroplasty of the trapeziometacarpal joint ensures good results in long-term follow-up, when performed in patients with stage I-II basal thumb osteoarthritis. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Rupture of the Patellar Tendon After Platelet-Rich Plasma Treatment: A Case Report.

INTRODUCTION: Rupture of the patellar tendon is becoming more and more frequent, even in sports activities overloading the extensor mechanism of the knee. Platelet-rich plasma (PRP) treatment has been recently introduced in treatment for several knee- and sport-related injuries including muscle strain cartilage defect and tendinopathies. The aim of this case report is to present a case of rupture of the patellar tendon occurred after injections of PRP. CASE REPORT: A case of a 40-year-old male soccer player sustaining a patellar tendon rupture after a series of 4 PRP injections. At surgery, a complete rupture in the middle of the patellar tendon was found, with severe degenerative changes of the tendon tissue. This case questions the actual efficacy and safety of PRP in severe degenerative tendinopathies.

Resveratrol protects against homocysteine-induced cell damage via cell stress response in neuroblastoma cells.

Recent findings underscore that some natural compounds are responsible for specific biochemical effects, i.e., the activation of redox-sensitive intracellular pathways and modulation of different stress proteins, such as heat shock proteins and sirtuins. Resveratrol, a natural polyphenol widely present in plants, has been shown to display various beneficial effects, including neuroprotection, in several pathological conditions. In the present study, by using differentiated SH-SY5Y neuroblastoma cells, we investigated the potential protective effects of resveratrol against homocysteine-induced neurotoxicity. We observed that homocysteine (100 µM) decreased cell viability while at the same time significantly increasing intracellular reactive oxygen species and DNA fragmentation. Cell pretreatment with resveratrol concentrations ranging from 1 to 5 µM elicited protective effects through the reduction of oxidative stress and genotoxic damage. In addition, we observed that resveratrol produced significant changes in the expression of both Hsp70 and sirtuin 1 (SIRT1). After homocysteine treatment in the presence of resveratrol, SIRT1 protein was found abundantly not only in the cytosol but also in the nucleus, as demonstrated by confocal laser scanning microscopy. The results of this study suggest that resveratrol is a potential protective agent against homocysteine-induced neurotoxicity and that beneficial effects are accompanied by changes in cell stress response. Taken together, these features contribute to our knowledge of underlying mechanisms involved in resveratrol-induced cell survival.

Heat shock proteins and hormesis in the diagnosis and treatment of neurodegenerative diseases.

Modulation of endogenous cellular defense mechanisms via the vitagene system represents an innovative approach to therapeutic intervention in diseases causing chronic tissue damage, such as in neurodegeneration. The possibility of high-throughoutput screening using proteomic techniques, particularly redox proteomics, provide more comprehensive overview of the interaction of proteins, as well as the interplay among processes involved in neuroprotection. Here by introducing the hormetic dose response concept, the mechanistic foundations and applications to the field of neuroprotection, we discuss the emerging role of heat shock protein as prominent member of vitagene network in neuroprotection and redox proteomics as a tool for investigating redox modulation of stress responsive vitagenes. Hormetic mechanisms are reviewed as possibility of targeted therapeutic manipulation in a cell-, tissue- and/or pathway-specific manner at appropriate points in the neurodegenerative disease process.

Mutant huntingtin regulates EGF receptor fate in non-neuronal cells lacking wild-type protein.

Huntingtin (htt) is a scaffold protein localized at the subcellular level and is involved in coordinating the activity of several protein for signaling and intracellular transport. The emerging properties of htt in intracellular trafficking prompted us to study the role of mutant htt (polyQ-htt) in the intracellular fate of epidermal growth factor receptor (EGFR), whose activity seems to be strictly regulated by htt. In particular, to evaluate whether protein trafficking dysfunction occurs in non-neuronal cells in the absence of functional htt, we monitored the EGFR protein in fibroblasts from homozygotic HD patients and their healthy counterpart. We found that polyQ-htt controls EGFR degradation and recycling. Lack of wild-type htt caused alteration of the ubiquitination cycle, formation of EGFR-incorporating high-molecular weight protein aggregates and abnormal EGFR distribution in endosomes of the degradation and recycling pathways after EGF stimulation. PolyQ-htt-induced alteration of EGFR trafficking affected cell migration and proliferation, at least in part, through inhibition of ERK signaling. To our knowledge the data here reported represent the first signaling and phenotypic characterization of polyQ-htt involvement in the modulation of growth factor stimulation in non-neuronal cells.

Anterior cruciate ligament injury in elite football players: video analysis of 128 cases.

BACKGROUND: The purpose of this study was to evaluate with video analysis the circumstances and the mechanism leading to ACL injury in a high-level population of athletes participating in the main European football championships. METHODS: Video analysis of 128 competitive matches with ACL injury events was performed through Wyscout.com® from August 2009 to January 2020. Details regarding situation, events and injured players were obtained. The type of trauma was assessed on the basis of the game phase, player's action, traumatic mechanism, type of maneuver, contact type, speed of the action and the position of the center of gravity. RESULTS: Of the injuries, 67.2% occurred without direct contact (39.1% non-contact and 28.1% indirect contact) and more than 50% occurred in the first 30 minutes of the match; 31.2% of injuries occurred during ball recovery and 63% in the offensive half; 62.5% of the trauma occurred in a valgus-external rotation maneuver and 35.1% during a deceleration phase with an eccentric contraction of the quadriceps. The referee whistled a foul in 20.6% of cases. CONCLUSIONS: Video-analysis may be helpful either to better understand the situations leading to ACL injury or to set up preventive strategies in order to reduce ACL injury in football. Most of the injuries occur during the first thirty minutes after entering the field. It therefore seems unlikely that fatigue will play an important role. Valgus external rotation, eccentric muscular contraction, loss of the center of gravity, attempting to recover the ball are the most frequent scenario.

Surgical Treatment of a Voluminous Median Nerve Lipofibromatous Hamartoma Involving Distal Forearm: A Case Report.

CASE: Lipofibromatous hamartoma (LFH) is a rare benign tumor of the peripheral nerves, which often affects upper extremity. There is no consensus regarding management of these lesions. We report a case of median nerve LFH in the volar forearm of a 24-year-old man with carpal tunnel syndrome symptoms. Clinically, the mass appeared tender to palpation, ill-defined and soft, located on the volar aspect of the left forearm. Open epineurotomy and neurolysis of the median nerve were performed with full recovery at 1 year. CONCLUSION: Surgical approach may be resolutive in patients with large masses refractory to conservative treatment.

Dose response biology of resveratrol in obesity.

Obesity is a major health problem throughout the world, and it is increasing both in prevalence and severity. Pharmaceutical approaches developed for the treatment of obesity, despite short-term benefits, often are associated with rebound weight gain after the cessation of drug use and serious side effects deriving from the medication can occur. Resveratrol has been well recognized as an anti-obesity substance for its lipid-lowering function as well as calorie-restriction effect. This polyphenol induces hormetic dose responses in a wide range of biological models, affecting numerous endpoints of biomedical and therapeutic significance. From an hormetic standpoint, we will discuss the potential relevance of resveratrol in the management of obesity and related comorbid conditions, emphasizing its ability to control simultaneously various pathological mechanisms associated with obesity.

Osteoporosis and alzheimer pathology: Role of cellular stress response and hormetic redox signaling in aging and bone remodeling.

Alzheimer's disease (AD) and osteoporosis are multifactorial progressive degenerative disorders. Increasing evidence shows that osteoporosis and hip fracture are common complication observed in AD patients, although the mechanisms underlying this association remain poorly understood. Reactive oxygen species (ROS) are emerging as intracellular redox signaling molecules involved in the regulation of bone metabolism, including receptor activator of nuclear factor-κB ligand-dependent osteoclast differentiation, but they also have cytotoxic effects that include lipoperoxidation and oxidative damage to proteins and DNA. ROS generation, which is implicated in the regulation of cellular stress response mechanisms, is an integrated, highly regulated, process under control of redox sensitive genes coding for redox proteins called vitagenes. Vitagenes, encoding for proteins such as heat shock proteins (Hsps) Hsp32, Hsp70, the thioredoxin, and the sirtuin protein, represent a systems controlling a complex network of intracellular signaling pathways relevant to life span and involved in the preservation of cellular homeostasis under stress conditions. Consistently, nutritional anti-oxidants have demonstrated their neuroprotective potential through a hormetic-dependent activation of vitagenes. The biological relevance of dose-response affects those strategies pointing to the optimal dosing to patients in the treatment of numerous diseases. Thus, the heat shock response has become an important hormetic target for novel cytoprotective strategies focusing on the pharmacological development of compounds capable of modulating stress response mechanisms. Here we discuss possible signaling mechanisms involved in the activation of vitagenes which, relevant to bone remodeling and through enhancement of cellular stress resistance provide a rationale to limit the deleterious consequences associated to homeostasis disruption with consequent impact on the aging process.

Cellular stress response, redox status, and vitagenes in glaucoma: a systemic oxidant disorder linked to Alzheimer's disease.

Amyloid deposits, constituted of amyloid beta (Aß) aggregates, are a characteristic feature of several neurodegenerative diseases, such as Alzheimer's, mild cognitive impairment and Parkinson's disease. They also have been recently implicated in the pathogenesis of retinal damage, as well as age-related macular degeneration and glaucoma. Glaucoma is a progressive optic neuropathy characterized by gradual degeneration of neuronal tissue due to retinal ganglion cell loss, associated to visual field loss over time resulting in irreversible blindness. Accumulation of Aß characterizes glaucoma as a protein misfolding disease, suggesting a pathogenic role for oxidative stress in the pathogenesis of retinal degenerative damage associated to glaucoma. There is a growing body of evidence demonstrating a link between Alzheimer's disease and glaucoma. Further, several heat shock proteins (HSPs) members have been implicated both in neurodegenerative diseases and glaucomatous apoptosis. To maintain redox homeostasis vitagenes, as integrated mechanisms, operate actively to preserve cell survival under condition of stress. Vitagenes encode for sirtuin, thioredoxin and HSPs. The present study was designed to investigate cellular stress response mechanisms in the blood of patients with glaucoma, compared to control subjects. Levels of vitagenes HSP-72, heme oxygenase-1, as well as F2-isoprostanes were significantly higher in the blood of patients with glaucoma than in controls. Furthermore, in the same experimental group increased expression of Trx and sirtuin 1 were measured. Our results sustain the importance of redox homeostasis disruption in the pathogenesis of glaucoma and highlights the opportunity that new therapies that prevents neurodegeneration through non-immunomodulatory mechanisms might be synergistically associated with current glaucoma therapies, thus unraveling important targets for novel cytoprotective strategies.