Mast Cell Cytokines IL-1, IL-33, and IL-36 Mediate Skin Inflammation in Psoriasis: A Novel Therapeutic Approach with the Anti-Inflammatory Cytokines IL-37, IL-38, and IL-1Ra.

Psoriasis (PS) is a skin disease with autoimmune features mediated by immune cells, which typically presents inflammatory erythematous plaques, and is associated with many comorbidities. PS exhibits excessive keratinocyte proliferation, and a high number of immune cells, including macrophages, neutrophils, Th1 and Th17 lymphocytes, and mast cells (MCs). MCs are of hematopoietic origin, derived from bone marrow cells, which migrate, mature, and reside in vascularized tissues. They can be activated by antigen-provoking overexpression of proinflammatory cytokines, and release a number of mediators including interleukin (IL)-1 and IL-33. IL-1, released by activated keratinocytes and MCs, stimulates skin macrophages to release IL-36-a powerful proinflammatory IL-1 family member. IL-36 mediates both innate and adaptive immunity, including chronic proinflammatory diseases such as psoriasis. Suppression of IL-36 could result in a dramatic improvement in the treatment of psoriasis. IL-36 is inhibited by IL-36Ra, which binds to IL-36 receptor ligands, but suppression can also occur by binding IL-38 to the IL-36 receptor (IL-36R). IL-38 specifically binds only to IL-36R, and inhibits human mononuclear cells stimulated with IL-36 in vitro, sharing the effect with IL-36Ra. Here, we report that inflammation in psoriasis is mediated by IL-1 generated by MCs-a process that activates macrophages to secrete proinflammatory IL-36 inhibited by IL-38. IL-37 belongs to the IL-1 family, and broadly suppresses innate inflammation via IL-1 inhibition. IL-37, in murine models of inflammatory arthritis, causes the suppression of joint inflammation through the inhibition of IL-1. Therefore, it is pertinent to think that IL-37 can play an inhibitory role in inflammatory psoriasis. In this article, we confirm that IL-38 and IL-37 cytokines emerge as inhibitors of inflammation in psoriasis, and hold promise as an innovative therapeutic tool.

Integrated Rehabilitation Approach with Manual and Mechanic-Acoustic Vibration Therapies for Urinary Incontinence.

This study aims to verify whether an integrated rehabilitation protocol comprising neuromuscular manual therapy and focused mechanical-acoustic vibrations can significantly reduce pelvic floor dysfunctions in women affected by stress, urge, or mixed urinary incontinence. Sixty-two women were treated with a combination of neuromuscular manual therapy and mechanical-acoustic vibrations at the level of superficial pelvic floor muscle groups. The results were analyzed before the beginning and after the end of the study protocol with the myometric measuring device MyotonPRO, the Pelvic Floor Disability Index (PFDI-20), and the Pelvic Floor Impact Questionnaire (PFIQ-7). Two patients withdrew from the study after the first visit. The 60 remaining patients showed significant improvements of myometric parameters, with the percentage variations ranging from +8.5% to +20.7% for the muscle logarithmic decrement, from -11.2 to -13.9% for muscle frequency, and from -4.8% to -12.3% for muscle stiffness. There has been a reduction of 56% in the perceived disability induced by urinary incontinence, measured with the PFDI-20, and 43% reduction in the impact of the problem on daily living, measured with the PFIQ-7. We conclude that a combination of neuromuscular manual therapy and mechanical-acoustic vibrations effectively reduces pelvic symptoms in patients affected by urinary incontinence, with minimal invasiveness.

The use of adaptive neuro-stimulation for rebalancing posture and muscular tone in a soccer team.

BACKGROUND: Posture and somatic structure could positively influence athletic gestures for their biomechanical implications. Working on neuromuscular activity, offers the possibility of intervention on postural control. The aim of this study was to demonstrate the possibility of interacting with the human body system through the spinal reflex pathway, starting from the stimulation of cutaneous receptors. METHODS: Twenty soccer players were recruited: all were male aged 25.5±10.6 years. Patients were divided using a single-blind criterion into two groups, each containing ten subjects. The experimental group was treated with 2 pre-set programs 4 times a week with an adaptive neuro-stimulation (ANS) able to interact with cutaneous receptors through an ENF Physio® device with a range of electrical frequency of about 15-350 Hz; the placebo-controlled group received the treatment with the device switched off. Patients performed a myometric evaluation with the MyotonPRO® system and a postural one with the Rarog software at T0 before the treatment and at T1 after the four-week treatment. RESULTS: After our intervention, we identified an improvement in muscular tone, in particular in the hamstring muscles (17.69%, right P<0.01 / left P<0.05) and a rebalancing of the principal bone points in the postural system (shoulder 71%, P<0.05, hips 65.6%, P=0.056, sagittal AP and frontal LL center of gravity, respectively 40%, P<0.05 and 52.7%, P=0.01). CONCLUSIONS: In conclusion, we could hypothesize the usefulness of an ANS to act on these parameters. ANS could be used not only for treatment of injuries but also in the field of prevention.

Bioprogressive Paradigm in Physiotherapeutic and Antiaging Strategies: A Review.

This review updates the knowledge on the use of bioprogressive philosophy in current rehabilitation paradigms, focusing on age-related ailments and antiaging strategies. It is a holistic approach that combines aspects of biology and function into the realm of rehabilitation therapy. The bioprogressive philosophy, with assistance of modern technological developments, such as microgravity-producing devices and techniques, enables personalized and targeted therapeutic approach that seems the most effective in rehabilitation and prevention of neuro-myo-sensory disorders that compromise the homeostatic body harmony, particularly in old age. The review defines the aging, discusses the most common physical dysfunctions, linked to posture, balance, or gait, and gives cues to modern antiaging rehabilitative approaches. The emphasis is put on the proprio-neuromuscular facilitation, a combination of stretch technique that steps into the bioprogressive approach, as currently the best method in the world of physical rehabilitation.

Contralateral effect of short-duration unilateral neuromuscular electrical stimulation and focal vibration in healthy subjects.

BACKGROUND: The "contralateral effect" phenomenon refers to the strength gain in the opposite, untrained homonymous muscle following unilateral training. Previous studies showed that neuromuscular electrical stimulation (NMES) of the right quadriceps facilitated maximal voluntary strength and efferent neural drive of the left knee extensors, while no previous study investigated the contralateral effect elicited by focal muscle vibration. AIM: The aim of this study was to investigate whether quadriceps NMES and focal vibration, when applied unilaterally, have the same potential to enhance the contralateral muscle strength and the associated neural drive. DESIGN: Randomized controlled experimental study. SETTING: University laboratory. POPULATION: Healthy subjects. METHODS: Subjects completed several maximal voluntary contractions (MVCs) of the left quadriceps (tested muscle) while the right quadriceps (treated muscle) received no conditioning stimulation (control condition), NMES or focal vibration. Paired supramaximal stimuli were delivered to the left quadriceps during and immediately after the MVCs to assess voluntary activation. The EMG activity of vastus lateralis, vastus medialis, and rectus femoris muscles of the left quadriceps was also concomitantly recorded. RESULTS: MVC torque and voluntary activation of the left quadriceps increased during contralateral NMES and vibration. A remarkable inter-individual variability was observed in the contralateral effect of NMES and vibration. In fact, MVC and voluntary activation increases were particularly evident in subjects "responders" to both treatments (who showed NMES-elicited increases in MVC and voluntary activation of 22.5% and 15.8%, respectively, and vibration-elicited increases of 13.1% and 10.7%, respectively). Moreover, we found that the increases in voluntary activation and EMG activity elicited by NMES were higher than those elicited by focal vibration. We also found that voluntary activation increases were higher in subjects presenting lower baseline levels of voluntary activation. CONCLUSIONS: The short-duration unilateral application of quadriceps NMES and focal vibration increased MVC torque and efferent neural drive of the contralateral homologous muscle in healthy subjects. CLINICAL REHABILITATION IMPACT: As the two physical therapy modalities can be useful to maximize motor unit recruitment contralaterally to the side of application, they could be incorporated in rehabilitation protocols when unilateral voluntary contractions are uncomfortable, painful or not feasible.