Consensus paper on postural dysfunction: recommendations for prevention, diagnosis and therapy.

Good fundamentals of posture and balance are essential for the efficient performance of both simple daily tasks and more complex movement patterns. In particular, postural balance is the ability to keep the body in equilibrium and to regain balance after the shift of body segments: postural control mechanisms of integration of the visual, vestibular and foot afferential channels contribute to this. This document provides recommendations based on scientific evidence, clinical practice, and consensus between experts concerning the prevention, diagnosis, and treatment of postural dysfunction at the three stages of life as the developmental age, adult age, and old age > 65 years and follows the "National Guidelines on Classification and Measuring of Posture and its Dysfunctions" per the Italian Ministry of Health (December 2017). The paper answers four main questions: i) "Which measures can be adopted to prevent postural dysfunctions?" ii) "What can we do in order to make a correct diagnosis of postural dysfunction?" iii) "What are the correct treatment programs for postural dysfunctions?" iv) Which professional competencies and experiences are useful for preventing, diagnosing and treating postural dysfunctions? By the Consensus of the Experts and the scientific evidence, emerge that the approach to postural dysfunctions requires a multidisciplinary and interdisciplinary team. Furthermore, rehabilitation treatment interventions must be specific to the age groups that have been indicated, to consider the integration of the main systems and subsystems of postural control that change with age.

Idiopathic facial palsy: umbrella review of systematic reviews and meta-analyses.

Idiopathic facial palsy is the most common disease of the VII cranial nerve. There are many treatments to facilitate recovery from this condition: pharmacological, surgical, rehabilitative, but the effectiveness of some of these treatments, especially the latter, is still under discussion. The purpose of this umbrella review of systematic reviews is to analyse the literature in order to investigate the different rehabilitation interventions in patients suffering from idiopathic facial palsy. A scientific literature search was carried out from January 2009 until August 2019, using Mesh the terms "facial palsy", "Bell's Palsy", "idiopathic facial nerve palsy", combined with "rehabilitation" and "therapy". Initially all the systematic reviews and meta-analyses of the last 10 years concerning rehabilitation treatments for the recovery of injured functions in facial palsy were included. Given the heterogeneity of the studies in the literature, which do not differentiate the different causes of facial palsy, all the causes of idiopathic facial palsy were included in the review. The research resulted in 94 published systematic reviews but only 6 were considered in respect to the inclusion criteria. All studies agree on the lack of high-quality scientific work to be able to say that Bell's physiotherapy treatments for facial palsy are effective, in particular with regard to recovery times during the rehabilitation process. Future studies are needed, in order to highlight the therapeutic implications of the different rehabilitation methods, with standardized protocols, in patients suffering from facial palsy of different aetiology.

Extracorporeal shockwaves as regenerative therapy in orthopedic traumatology: a narrative review from basic research to clinical practice.

Extracorporeal Shock Wave Therapy (ESWT), after its first medical application in the urological field for lithotripsy, nowadays represents a valid therapeutical tool also for many musculoskeletal diseases, as well as for regenerative medicine applications. This is possible thanks to its mechanisms of action, which in the non-urological field are not related to mechanical disruption (as for renal stones), but rather to the capacity, by mechanotransduction, to induce neoangiogenesis, osteogenesis and to improve local tissue trophism, regeneration and remodeling, through stem cell stimulation. On the basis of these biological assumptions, it becomes clear that ESWT can represent a valid therapeutic tool also for all those pathological conditions that derive from musculoskeletal trauma, and are characterized by tissue loss and/or delayed healing and regeneration (mainly bone and skin, but not only). As a safe, repeatable and non–invasive therapy, in many cases it can represent a first–line therapeutic option, as an alternative to surgery (for example, in bone and skin healing disorders), or in combination with some other treatment options. It is hoped that with its use in daily practice also the muscle–skeletal field will grow, not only for standard indications, but also in post–traumatic sequelae, in order to improve recovery and shorten healing time, with undoubted advantages for the patients and lower health service expenses.

Clinical application of shock wave therapy in musculoskeletal disorders: part II related to myofascial and nerve apparatus.

Shock waves have been widely recognized in literature as a biological regulator; accordingly we carried out a review on the effect of shock waves on the mesenchymal cells in their various expressions: bone, muscle, ligament and tendon tissue. To date, the application of Shock Wave Therapy (SWT) in musculoskeletal disorders has been primarily used in the treatment of tendinopathies (proximal plantar fasciopathy, lateral elbow tendinopathy, calcific tendinopathy of the shoulder, and patellar tendinopathy, etc.) and bone defects (delayed and non-union of bone fractures, avascular necrosis of femoral head, etc.). Although the mechanism of their therapeutic effects is still unknown, the majority of published papers have shown the positive and beneficial effects of using SWT as a treatment for musculoskeletal disorders, with a success rate ranging from 65% to 91%, while the complications are low or negligible. The purpose of this paper is to present the published data on the clinical application of SWT in the treatment of myofascial and nerve disorders. With the help of the relevant literature, in this paper we outline the indications and success rates of SWT, as well as the adequate SWT parameters (e.g., rate of impulses, energy flux density) defined according to the present state of knowledge.

CLINICAL APPLICATION OF SHOCK WAVE THERAPY IN MUSCULOSKELETAL DISORDERS: PART I.

The shock wave has been widely recognized in literature as a biological regulator; therefore we carried out a review on the activity performed by shock waves on the bone-myofascial tissue system. To date, the application of Shock Wave Therapy (SWT) in musculoskeletal disorders has been primarily used in the treatment of tendinopathies (proximal plantar fasciopathy, lateral elbow tendinopathy, calcific tendinopathy of the shoulder, and patellar tendinopathy, etc.) and bone defects (delayed- and non-union of bone fractures, avascular necrosis of femoral head, etc.). Although the mechanism of their therapeutic effects is still unknown, the majority of published papers have shown positive and beneficial effects of using SWT as a treatment for musculoskeletal disorders, with a success rate ranging from 65 to 91%, while the complications are low or negligible. The purpose of this paper is to inform the reader about the published data on the clinical application of SWT in the treatment of musculoskeletal disorders. In this paper, with the help of a literature review, indications and success rates for SWT in the treatment of musculoskeletal disorders are outlined, while adequate SWT parameters (e.g., rate of impulses, energy flux density, etc.) are defined according to the present state of knowledge. Given the abundance of the argument, it seems appropriate to subdivide the review into two parts, the first concerning the evidence of Extracorporeal Shock Wave Therapy (ESWT) on bone disorders, the second concerning findings on tendon and muscle treatment.

Role of TNF in mast cell neuroinflammation and pain.

Inflammatory mediators, such as cytokines, chemokines and arachidonic acid compounds, lead to vascular permeability and dilation and increase sensitization and pain receptors. Proinflammatory cytokines, including tumor necrosis factor, are involved in the etiology of clinical neurological disorders. These cytokines activate nuclear factor-κB (NF-κB) which leads to the activation of different inflammatory genes. TNF implicated in neurological disorders has an important role in the activation of microglia and astrocytes. The inhibition of TNF may lead to the decrease of microglia activation and can be useful for therapeutic intervention. TNF, at the site of nerve injury may activate mast cells (MCs) which mediate pathologic events such as headache and pain. TNF is the only cytokine stored in mast cells and can be rapidly released along with biogenic amines after MC stimulation. Activation of MCs leads to NF-κB and AP1 generation with release of many cytokines including TNF, IL-33 and IL-1. In this paper we discuss the role of TNF in MC activation, mediating pain and neurological disorders.

IMMUNOMODULATORY EFFECTS OF VITAMIN D ON SKIN INFLAMMATION.

Vitamin D has a major role in calcium absorption and maintenance of healthy bones. Vitamin D is also involved in cancer, cardiovascular system, allergic diseases, immune regulation and immune disor¬ders. Irradiation of food as well as animals produces vitamin D and more than 90% of previtamin D3 synthesis in the skin occurs in the epidermis. Vitamin D receptor has been found in many cells including T and B lymphocytes, macrophages, mast cells, NK cells and Tregs, and it selectively binds with high affinity to its ligand. Vitamin D binds its receptor VDR, resulting in transcription of a number of genes playing a role in inhibition of MAPK. Its effect may be also mediated by the direct activation of PKC. Vitamin D has the ability to suppress inflammatory cytokines such as TNF, IL-1, IFN-gamma and IL-2; while it increases the generation of anti-inflammatory cytokines IL-4 and IL-10. In B cells, vitamin D3 have also been shown to suppress IgE antibody class switch partly through the inhibition of NF-kB. Here we discuss the relationship between vitamin D, immunity and skin disorders.

CROSSTALK BETWEEN VITAMIN B AND IMMUNITY.

Vitamin B1 (thiamin) is considered to be the oldest vitamin and in 1936 R.R. Williams and colleagues determined its chemical structure and were able to synthesize this vitamin. Vitamin B1 influences pro-apoptotic proteins, mitochondrial membrane potential, cytochrome C release, protein kinases, p38-MAPK, suppresses oxidative stress-induced NF-kappaB and has anti-inflammatory properties. Deficiency of vitamin B1 may cause beriberi, dysfunction of the nervous system, neuroinflammation, T cell infiltration, chemokine CCL2 activation, over expression of proinflammatory cytokines, such as IL-1, TNF, IL-6, and arachidonic acid products, and induces expression of CD40 by the microglia and CD40L by astrocytes which provoke the death of neurons. Here we report the relationship between vitamin B complex and immunity.

Can vitamin a mediate immunity and inflammation?

Vitamins are natural components of foods and are organic compounds distinct from fat, carbohydrates and proteins. Vitamin A is the generic descriptor for compounds with the qualitative biological activity of retinol. Unlike beta-carotene, vitamin A is not an antioxidant and its benefit is related to possible boosting of immune reactions. The effect of vitamin A on immune function is wide-reaching and its deficiency appears to affect immunity in several ways. Innate and adaptive immune responses are affected in some way by lack of vitamin A. Retinoids seem to act on differentiation of lymphocytes, antibody production, phagocytosis of macrophages, NK, Treg, and T helper cell activity. In addition, in humans, signs of a vitamin A deficiency also include the dysregulation of cytokine/chemokine generation and release. However, excess of vitamin A has been demonstrated to have toxic effects in most species studied. Here we summarize some important effects of vitamin A in immunity and inflammation.

Italian survey on the use of anti-inflammatory drugs in osteoarthritis.

Osteoarthritis (OA) is the most common painful arthritic disease in adults, causes severe disability and worsens the quality of life of the patients. The aim of this survey, carried out on 147 Italian orthopedic doctors who attended an ISIAT (International Symposium Intra Articular Treatment) educational course in Barcelona, was to investigate some aspects of daily clinical practice in the management of OA: the most used pharmacological treatments, compliance to the most important Guidelines, the advantages of COXIBs in this setting and pharmacoeconomic aspects. The main results of this survey are: a) inflammation has become the main target in OA; b) Guidelines are a useful and valid tool for daily clinical practice; c) acetaminophen is no longer a valid therapeutical option for OA patients; d) anti-inflammatory drugs (NSAIDs and COXIBs) have a primary role in the management of OA, due to their dual activity (anti-inflammatory and analgesic); e) selectivity of COXIBs for COX-2 is very important; f) within the COXIB class, the therapeutic value of etoricoxib has been widely recognized, especially in terms of safety and cost/benefit ratio.

Impact of mast cells on multiple sclerosis: inhibitory effect of natalizumab.

Mast cells (MCs) derive from a distinct precursor in the bone marrow and are predominantly found in tissues at the interface between the host and the external environment where they can secrete mediators without overt degranulation. Mast cells mature under local tissue microenvironmental factors and are necessary for the development of allergic reactions, through crosslinking of their surface receptors for IgE (FcεRI), leading to degranulation and the release of vasoactive, pro-inflammatory and nociceptive mediators that include histamine, pro-inflammatory and anti-inflammatory cytokines and proteolytic enzymes. Multiple sclerosis (MS) is an autoimmune disease characterized by inflammatory demylination within the central nervous system. MCs are involved in the pathogenesis of MS by generating various vasoactive mediators and cytokines and participate in the destruction of the myelin sheath and the neuronal cells. The process of the development of demyelinating plaques in MS is probably linked with the rupture of the blood-brain barrier by MC products. The effects of natalizumab, which is a very effective drug in reducing the annualized relapse rate and other relapse-based endpoints, are discussed. Here, we report the relationship between MCs and MS.

Role of mast cells in atherosclerosis: a classical inflammatory disease.

Atherosclerosis is an inflammatory disease and hyperlipidaemia is one of the main risk factors for aging, hypertension and diabetes. Variance in plasma LDL cholesterol concentration may be associated with differences in cardiovascular disease risk and high levels of lipids are associated with increased risk of developing atherosclerosis. Macrophages, which generate pro-inflammatory cytokines, mainly interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-alpha), are deeply involved in atherosclerosis, as well as mast cells which generate several cytokines, including IL-6 and IFN-gamma, and chemokines such as eotaxin, MCP-1 and RANTES involved in monocyte recruitment and differentiation in the arterial wall. In addition, mast cells participate in lipid retention and vascular cell remodeling, and are mediators of innate and adaptive immunity during atherosclerosis. Mast cells which accumulate in the human arterial intima and adventitia during atherosclerotic plaque progression, release vasoactive and angiogenic compounds, and pro-inflammatory mediators, such as arachidonic acid metabolites, histamine, cytokines/chemokines, platelet activating factor (PAF) and proteolytic enzymes. Mast cells can be activated by pro-inflammatory stimuli, including cytokines, hypercholesterolemia, and hyperglycemia, and trigger the endothelial expression of adhesion molecules such as P-selection, vascular cell adhesion molecule-1 (VCAM-1) and chemokines which mediate the recruitment and adhesion of leukocytes. The participation of mast cells in atherosclerosis is still an enigma and it may be of therapeutic interest to clarify this process.

Nerve growth factor interactions with mast cells.

Neuropeptides are involved in neurogenic inflammation where there is vasodilation and plasma protein extravasion in response to this stimulus. Nerve growth factor (NGF), identified by Rita Levi Montalcini, is a neurotrophin family compound which is important for survival of nociceptive neurons during their development. Therefore, NGF is an important neuropeptide which mediates the development and functions of the central and peripheral nervous system. It also exerts its proinflammatory action, not only on mast cells but also in B and T cells, neutrophils and eosinophils. Human mast cells can be activated by neuropeptides to release potent mediators of inflammation, and they are found throughout the body, especially near blood vessels, epithelial tissue and nerves. Mast cells generate and release NGF after degranulation and they are involved in iperalgesia, neuroimmune interactions and tissue inflammation. NGF is also a potent degranulation factor for mast cells in vitro and in vivo, promoting differentiation and maturation of these cells and their precursor, acting as a co-factor with interleukin-3. In conclusion, these studies are focused on cross-talk between neuropeptide NGF and inflammatory mast cells.

Corticotropin-releasing hormone, microglia and mental disorders.

Microglia derive from mononuclear myeloid progenitors and are a major glial complement of the central nervous system. When microglia are activated they secrete inflammatory cytokines and toxic mediators which amplify the inflammatory response. In addition, the microglia inflammatory products are implicated in the neuronal destruction usually observed in various neurodegenerative diseases. Microglia cells express corticotropin releasing hormone (CRH) receptors, and activation of microglia by CRH releases bioactive molecules which have a biological effect in the brain and regulate several neurological diseases. CRH plays a pivotal role in stress responses and is a key mediator of the hypothalamic-pituitary-adrenocortical system. CRH is expressed in human mast cells, leading to autocrine effects and participates in inflammatory response together with neuropeptides, and stimulates mast cells. IL-33-activated mast cells release vascular endothelial growth factor in response to CRH and act synergistically to increase vascular permeability. CRH also up-regulates IL-18 expression by increasing intracellular reactive oxygen in microglia cells. Here we report the relationship between CRH, microglia and mental disorders.

Relationship between serotonin and mast cells: inhibitory effect of anti-serotonin.

Serotonin (5-HT) is an important neurotransmitter that acts in both central and peripheral nervous system, and has an impact on cell proliferation, migration and apoptosis. 5HT exerts its effects via several receptors. Treatment with anti-5-HT receptors diminish the severity of contact allergy in experimental animals, an effect mediated by mast cells; while an agonist reduces the stress level and relieves pruritus in patients with atopic dermatitis. Mast cells are important for both innate and adaptive immunity and they are activated by cross-linking of FceRI molecules, which are involved in the binding of multivalent antigens to the attached IgE molecules, resulting in a variety of responses including the immediate release of potent inflammatory mediators. Serotonin is present in murine mucosal mast cells and some authors reported that human mast cells may also contain serotonin, especially in subjects with mastocytosis. Here we report the interrelationship between mast cells, serotonin and its receptor inhibitor.

Interrelationship between IL-3 and mast cells.

It is well established that mast cells, which are found in the tissues in the proximity of small blood vessels and post-capillary venules, play a key role in the early phase of IgE-mediated allergic reactions. A greatly expanded understanding of the biology of IL-3 has emerged since the early 1980s. IL-3 is a specific factor that stimulates the growth of hematopoietic stem and progenitor cells of a variety of lineages and can promote the proliferation of certain classes of lymphocytes distinct from those that are dependent on IL-2. IL-3 has been identified among the most important cytokines for regulation of mast cell growth and differentiation, migration and effector function activities of many hematopoietic cells. IL-3 termed multi colony-stimulating-factor (multi-CSF) or mast cell growth factor (MCGF) is a haematopoietic growth factor which stimulates the formation of colonies for erythroid, megakaryocytic, granulocytic and monocytic lineages. It is predominantly produced by activated T cells, natural killer (NK) cells and mast cells and supports the growth-promoting effects of SCF on mast cell precursors. IL-3 causes severe hypersensivity reactions and plays a pivotal role in exacerbating the inflammatory response in vivo. Here we report the interrelationship between IL-3 and mast cells.