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Cold therapy is commonly used as a procedure to relieve pain symptoms, particularly in inflammatory diseases, injuries and overuse symptoms. A peculiar form of cold therapy (or stimulation) was proposed 30 years ago for the treatment of rheumatic diseases. The therapy, called whole-body cryotherapy (WBC), consists of exposure to very cold air that is maintained at -110 degrees C to -140 degrees C in special temperature-controlled cryochambers, generally for 2 minutes. WBC is used to relieve pain and inflammatory symptoms caused by numerous disorders, particularly those associated with rheumatic conditions, and is recommended for the treatment of arthritis, fibromyalgia and ankylosing spondylitis. In sports medicine, WBC has gained wider acceptance as a method to improve recovery from muscle injury. Unfortunately, there are few papers concerning the application of the treatment on athletes. The study of possible enhancement of recovery from injuries and possible modification of physiological parameters, taking into consideration the limits imposed by antidoping rules, is crucial for athletes and sports physicians for judging the real benefits and/or limits of WBC. According to the available literature, WBC is not harmful or detrimental in healthy subjects. The treatment does not enhance bone marrow production and could reduce the sport-induced haemolysis. WBC induces oxidative stress, but at a low level. Repeated treatments are apparently not able to induce cumulative effects; on the contrary, adaptive changes on antioxidant status are elicited--the adaptation is evident where WBC precedes or accompanies intense training. WBC is not characterized by modifications of immunological markers and leukocytes, and it seems to not be harmful to the immunological system. The WBC effect is probably linked to the modifications of immunological molecules having paracrine effects, and not to systemic immunological functions. In fact, there is an increase in anti-inflammatory cytokine interleukin (IL)-10, and a decrease in proinflammatory cytokine IL-2 and chemokine IL-8. Moreover, the decrease in intercellular adhesion molecule-1 supported the anti-inflammatory response. Lysosomal membranes are stabilized by WBC, reducing potential negative effects on proteins of lysosomal enzymes. The cold stimulation shows positive effects on the muscular enzymes creatine kinase and lactate dehydrogenase, and it should be considered a procedure that facilitates athletes' recovery. Cardiac markers troponin I and high-sensitivity C-reactive protein, parameters linked to damage and necrosis of cardiac muscular tissue, but also to tissue repair, were unchanged, demonstrating that there was no damage, even minimal, in the heart during the treatment. N-Terminal pro B-type natriuretic peptide (NT-proBNP), a parameter linked to heart failure and ventricular power decrease, showed an increase, due to cold stress. However, the NT-proBNP concentrations observed after WBC were lower than those measured after a heavy training session, suggesting that the...

ObjectivesThe rRT-PCR test, the current gold standard for the detection of coronavirus disease (COVID-19), presents with known shortcomings, such as long turnaround time, potential shortage of reagents, false-negative rates around 15–20%, and expensive equipment. The hematochemical values of routine blood exams could represent a faster and less expensive alternative.MethodsThree different training data set of hematochemical values from 1,624 patients (52% COVID-19 positive), admitted at San Raphael Hospital (OSR) from February to May 2020, were used for developing machine learning (ML) models: the complete OSR dataset (72 features: complete blood count (CBC), biochemical, coagulation, hemogasanalysis and CO-Oxymetry values, age, sex and specific symptoms at triage) and two sub-datasets (COVID-specific and CBC dataset, 32 and 21 features respectively). 58 cases (50% COVID-19 positive) from another hospital, and 54 negative patients collected in 2018 at OSR, were used for internal-external and external validation.ResultsWe developed five ML models: for the complete OSR dataset, the area under the receiver operating characteristic curve (AUC) for the algorithms ranged from 0.83 to 0.90; for the COVID-specific dataset from 0.83 to 0.87; and for the CBC dataset from 0.74 to 0.86. The validations also achieved good results: respectively, AUC from 0.75 to 0.78; and specificity from 0.92 to 0.96.ConclusionsML can be applied to blood tests as both an adjunct and alternative method to rRT-PCR for the fast and cost-effective identification of COVID-19-positive patients. This is especially useful in developing countries, or in countries facing an increase in contagions.

Despite the constant presence of positive and satisfactory results in the studies analyzed, the complexity of MSC metabolism and related therapeutic effects as well as the weakness of most of the studies do not allow withdrawing definitive conclusions about the superiority of one tissue source over another, as well as about the best cell dose and the long-term durability of the effects of these procedures. Given the high potential value of these therapies in the treatment of OA, further studies accurately designed, carefully defining the type of patients to be included and pursuing minimal standard requirements in terms of follow-up, number of patients, and types of measurements should be conducted to finally assess the efficacy of MSC-based injective treatments.

Alterations in vitamin D homeostasis, mainly involving its nuclear receptor (VDR), could have a role in the pathophysiology of the spine. The association between VDR polymorphisms and spine disorders has been analyzed in different ethnic groups, focusing on the functional FokI polymorphism. However, so far, inconsistent findings were reported. The aims of this study were to evaluate, in the Italian white population, the VDR FokI polymorphism frequencies distribution in subjects with clearly defined lumbar spinal pathologies compared to asymptomatic controls and to analyze the interplay of genetic and conventional risk factors. Using a case-control design, 267 patients with spinal disorders and 220 asymptomatic controls were enrolled, evaluating their exposition to putative risk factors. Patients’ clinical assessment was performed by Magnetic Resonance Imaging. FokI polymorphism (rs2228570) was detected by PCR-RFLP. Genotypes were designated by a lowercase letter (f allele, T nucleotide) for the presence of the restriction site and by a capital letter (F allele, C nucleotide) for its absence. Family history, higher age and BMI, exposure to vibration, physical job demand, smoking habit and lower practice of leisure physical activity were associated with spinal disorders. The FF genotype and F allele represented approximately 2-fold risk factors to develop discopathies and/or osteochondrosis concomitant with disc herniation, while f allele was protective. In conclusion, the link we observed between VDR FokI variants and specific lumbar spine pathologies suggests that spinal tissue degeneration is influenced by the genetic background. Future studies should evaluate the signaling pathways involving alterations in VDR and influencing the development and/or progression of spine disorders.

Bone mass can be viewed as the net product of two counteracting metabolic processes, bone formation and bone resorption, which allow the skeleton to carry out its principal functions: mechanical support of the body, calcium dynamic deposition and haemopoiesis. Besides radiological methods, several blood and urinary molecules have been identified as markers of bone metabolic activity for estimating the rates and direction of the biological activities governing bone turnover. The advantages for the use of bone metabolism markers are that they are potentially less dangerous than radiological determinations, are more sensitive to changes in bone metabolism than radiological methods and are easily collected and analysed. The disadvantages are that they have high biological variability. Physical exercise is a known source of bone turnover and is recommended for preventing osteoporosis and bone metabolism problems. There are numerous experiments on bone metabolism markers after acute exercise, but not after long-term training and during or after a whole competition season. Moreover, few studies on bone metabolism markers have evaluated their performance in elite and top-level athletes, who have a higher bone turnover than sedentary individuals. Despite discrepant results among studies, most have shown that short exercise is insufficient for modifying serum concentrations of bone metabolism markers. Marker variations are more evident after several hours or days after exercise, bone formation markers are more sensitive than bone resorption markers, and stimulation of osteoblast and/or osteoclast functions is exercise dependent but the response is not immediate. The response depends on the type of exercise; the markers seem to be less sensitive to resistance exercise and the intensity of exercise is not discriminate. Comparisons between trained subjects and untrained controls have demonstrated the influence of exercise on bone turnover. During training, carboxy-terminal collagen cross-links (CTx), a bone resorption marker, was shown to be less sensitive than amino-terminal cross-linking telopeptide of type I collagen (NTx) and urinary pyridinolines, which were sensitive to anaerobic exercise. Whereas, the bone formation markers, bone alkaline phosphatase (BAP) and osteocalcin (OC) changed after 1 month and 2 months of an exercise programme, respectively. After 2 months, while BAP normalized, it was found to be sensitive to aerobic exercise and OC was found to be sensitive to anaerobic exercise. After prolonged training and competition, bone formation markers are found to change in sedentary subjects enrolled in a physical activity programme. Professional athletes show changes in bone formation markers depending on programme intensity, whereas bone resorption appears to stabilize. Crucial for long-term training, are the characteristics of exercise (e.g. weight-bearing, impact).

Low frequency pulsed electromagnetic field (PEMF) has proven to be effective in the modulation of bone and cartilage tissue functional responsiveness, but its effect on tendon tissue and tendon cells (TCs) is still underinvestigated. PEMF treatment (1.5 mT, 75 Hz) was assessed on primary TCs, harvested from semitendinosus and gracilis tendons of eight patients, under different experimental conditions (4, 8, 12 h). Quantitative PCR analyses were conducted to identify the possible effect of PEMF on tendon-specific gene transcription (scleraxis, SCX and type I collagen, COL1A1); the release of pro- and anti-inflammatory cytokines and of vascular endothelial growth factor (VEGF) was also assessed. Our findings show that PEMF exposure is not cytotoxic and is able to stimulate TCs' proliferation. The increase of SCX and COL1A1 in PEMF-treated cells was positively correlated to the treatment length. The release of anti-inflammatory cytokines in TCs treated with PEMF for 8 and 12 h was significantly higher in comparison with untreated cells, while the production of pro-inflammatory cytokines was not affected. A dramatically higher increase of VEGF-A mRNA transcription and of its related protein was observed after PEMF exposure. Our data demonstrated that PEMF positively influence, in a dose-dependent manner, the proliferation, tendon-specific marker expression, and release of anti-inflammatory cytokines and angiogenic factor in a healthy human TCs culture model.

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