Non-Pharmacological Interventions for Treating Psoriatic Arthritis.

Background and Objective: In this review, we discuss evidence concerning the management of psoriatic arthritis (PsA) patients with non-pharmacological interventions and additionally develop physical training protocols that could be prescribed to these patients. Methods: We selected 110 articles, published on PubMed and Google Scholar databases from 1972 to date, investigating the effects of generic hygienic-dietary recommendations and training programs in PsA or psoriasis (PSO) individuals. Results: Although data in support are limited, aerobic, endurance, and strength exercises as well as complementary techniques may all be useful in preserving or improving residual functional capacity, joint flexibility, and muscle strength. Exercise may reduce systemic inflammation, pain, and fatigue and additionally control PsA comorbidities, like dysmetabolism or obesity. Conclusions: The polyhedral clinical expression of PsA underlines the need for a multidisciplinary approach combining the synergistic effects of pharmacological and non-pharmacological treatments. The latter range from preventive measures, like dietary modifications, weight loss, and cigarette smoking cessation, to personalized training protocols according to disease activity and phenotype, comorbidities, and individual tolerability. In these patients, we strongly encourage the regular practice of motor activity at progressively increasing intensity with combined supervised aerobic, strength, endurance, and stretching exercises.

Role of Serotonin in the Maintenance of Inflammatory State in Crohn's Disease.

Crohn's disease (CD) is a chronic intestinal inflammation considered to be a major entity of inflammatory bowel diseases (IBDs), affecting different segments of the whole gastrointestinal tract. Peripheral serotonin (5-HT), a bioactive amine predominantly produced by gut enterochromaffin cells (ECs), is crucial in gastrointestinal functions, including motility, sensitivity, secretion, and the inflammatory response. These actions are mediated by a large family of serotonin receptors and specialized serotonin transporter (SERT) located on a variety of cell types in the gut. Several studies indicate that intestinal 5-HT signaling is altered in patients with inflammatory bowel disease. Paraformaldehyde-fixed intestinal tissues, obtained from fifteen patients with Crohn's disease were analyzed by immunostaining for serotonin, Langerin/CD207, and alpha-Smooth Muscle Actin (α-SMA). As controls, unaffected (normal) intestinal specimens of seven individuals were investigated. This study aimed to show the expression of serotonin in dendritic cells (DCs) and myofibroblast which have been characterized with Langerin/CD207 and α-SMA, respectively; furthermore, for the first time, we have found the presence of serotonin in goblet cells. Our results show the correlation between different types of intestinal cells in the maintenance of the inflammatory state in CD linked to the recall of myofibroblasts.

Physical activity in idiopathic inflammatory myopathies: two intervention proposals based on literature review.

Idiopathic inflammatory myopathies (IIM) are rare diseases affecting skeletal muscles and leading to progressive muscle weakness and disability. Thanks to the better understanding of their pathogenesis, the management of IIM has been noteworthily implemented in recent years. Current therapeutic strategies include pharmacological and non-pharmacological interventions, among which physical exercise represents a useful option, able to ameliorate disease activity without worsening muscle inflammation. The aim of this narrative review is therefore to provide an updated overview of the benefits of physical exercise in patients with IIM and to suggest plausible training programs to be applied in patients with dermatomyositis, polymyositis, necrotizing myopathy, and inclusion body myositis. In this regard, a combined strategy mixing aerobic and resistance exercises could positively affect the pro-inflammatory and metabolic pathways occurring in skeletal muscles, while promoting muscle fiber regeneration and repair.

Cardiovascular Risk Factors and Haematological Indexes of Inflammation in Paralympic Athletes with Different Motor Impairments.

Haematological indexes of both inflammation and platelet activation have been suggested as predictive markers of cardiovascular disease (CVD), which has high prevalence in Paralympic athletes (PA). Different mechanisms could play a role in increasing CVD risk in PA with spinal cord injury (PA-SCI), lower limb amputation (PA-LLA), or upper limb impairment (PA-ULI). We compared, in 4 groups of PA competing in power, intermittent (mixed metabolism), and endurance sports, Framingham Risk Score (FRS), metabolic syndrome criteria (MetS-C), inflammation (INFLA) Score, 5 haematological indexes of platelet activation (mean platelet volume (MPV), platelet distribution width (PDW), and the ratios between MPV and platelet (MPVPR), between MPV and lymphocyte (MPVLR), and between PDW and lymphocyte (PDWLR)) and the endogenous antioxidants uric acid (UA) and bilirubin (BR). A retrospective chart review of PA from preparticipation examinations' records (London 2012 and Sochi 2014 Paralympics) was performed. We included 25 PA-SCI (13 with high and 12 with low lesion, PA-SCI-H and PA-SCI-L), 15 PA-LLA, and 10 PA-ULI. FRS and INFLA Score did not differ among groups, but PA-SCI-H had lower HDL, compared to PA-SCI-L and PA-ULI. PA-LLA had more MetS diagnostic criteria with significant higher glucose levels than other groups. PA-SCI-H had significantly lower lymphocytes' count compared to PA-LLA and higher MPV, PDW, MPVPR, MPVLR, and PDWLR. SCI-H had lower BR, haemoglobin, haematocrit, proteins, and creatinine. No interaction was found between the 3 kinds of sitting sports and the 2 groups of health conditions (PA-SCI and PA-LLA). In conclusion, PA-LLA had a higher cardiometabolic risk, whereas PA-SCI-H had a higher platelet-derived cardiovascular risk. Further larger studies are needed to investigate the relationship between indexes of inflammation/oxidation and dietary habit, body composition, and physical fitness/performance in PA with motor impairments.

Blunt thoracic trauma and cardiac injury in the athlete: contemporary management.

Commotio cordis and cardiac injuries are rare events usually following a chest blunt traumas during sports activities. Various etiologies have been identified to cause electrical (commotio cordis) and/or structural (contusion and further injuries) damage, but high-velocity tools such as baseballs or hockey pucks (also called projectiles) have been chiefly identified. Clinical consequences are challenging, varying from uncomplicated supraventricular arrhythmias to cardiac wall rupture. Ventricular fibrillation is the most remarkable outcome leading to cardiac arrest in some individuals. In this article, up-to-date epidemiological and pathophysiological issues are discussed, along with the most suitable assistance protocols of the injured athlete in the sports arena. Current knowledge about traumatic sports injuries and ensuing cardiovascular sequelae made significant steps forwards than in the past. The majority of athletes (especially the youngest ones) wearing chest protectors are usually preserved from serious outcomes and sudden cardiac death, but further technical effort is encouraged to attain more satisfactory barriers against projectile's impact. Educational campaigns among students, closer team surveillance, implementation of the sports arenas with adequate rescue devices and medical assistance remain mandatory items in contact sports activity.

Epineurial Window Is More Efficient in Attracting Axons than Simple Coaptation in a Sutureless (Cyanoacrylate-Bound) Model of End-to-Side Nerve Repair in the Rat Upper Limb: Functional and Morphometric Evidences and Review of the Literature.

End-to-side nerve coaptation brings regenerating axons from the donor to the recipient nerve. Several techniques have been used to perform coaptation: microsurgical sutures with and without opening a window into the epi(peri)neurial connective tissue; among these, window techniques have been proven more effective in inducing axonal regeneration. The authors developed a sutureless model of end-to-side coaptation in the rat upper limb. In 19 adult Wistar rats, the median and the ulnar nerves of the left arm were approached from the axillary region, the median nerve transected and the proximal stump sutured to the pectoral muscle to prevent regeneration. Animals were then randomly divided in two experimental groups (7 animals each, 5 animals acting as control): Group 1: the distal stump of the transected median nerve was fixed to the ulnar nerve by applying cyanoacrylate solution; Group 2: a small epineurial window was opened into the epineurium of the ulnar nerve, caring to avoid damage to the nerve fibres; the distal stump of the transected median nerve was then fixed to the ulnar nerve by applying cyanoacrylate solution. The grasping test for functional evaluation was repeated every 10-11 weeks starting from week-15, up to the sacrifice (week 36). At week 36, the animals were sacrificed and the regenerated nerves harvested and processed for morphological investigations (high-resolution light microscopy as well as stereological and morphometrical analysis). This study shows that a) cyanoacrylate in end-to-side coaptation produces scarless axon regeneration without toxic effects; b) axonal regeneration and myelination occur even without opening an epineurial window, but c) the window is related to a larger number of regenerating fibres, especially myelinated and mature, and better functional outcomes.

Repairing nerve gaps by vein conduits filled with lipoaspirate-derived entire adipose tissue hinders nerve regeneration.

In spite of great recent advancements, the definition of the optimal strategy for bridging a nerve defect, especially across long gaps, still remains an open issue since the amount of autologous nerve graft material is limited while the outcome after alternative tubulization techniques is often unsatisfactory. The aim of this study was to investigate a new tubulization technique based on the employment of vein conduits filled with whole subcutaneous adipose tissue obtained by lipoaspiration. In adult rats, a 1cm-long defect of the left median nerve was repaired by adipose tissue-vein-combined conduits and compared with fresh skeletal muscle tissue-vein-combined conduits and autologous nerve grafts made by the excised nerve segment rotated by 180°. Throughout the postoperative period, functional recovery was assessed using the grasping test. Regenerated nerve samples were withdrawn at postoperative month-6 and processed for light and electron microscopy and stereology of regenerated nerve fibers. Results showed that functional recovery was significantly slower in the adipose tissue-enriched group in comparison to both control groups. Light and electron microscopy showed that a large amount of adipose tissue was still present inside the vein conduits at postoperative month-6. Stereology showed that all quantitative morphological predictors analyzed performed significantly worse in the adipose tissue-enriched group in comparison to the two control groups. On the basis of this experimental study in the rat, the use of whole adipose tissue for tissue engineering of peripheral nerves should be discouraged. Pre-treatment of adipose tissue aimed at isolating stromal vascular fraction and/or adipose derived stem/precursor cells should be considered a fundamental requisite for nerve repair.

Direct muscle neurotization after end-to end and end-to-side neurorrhaphy: An experimental study in the rat forelimb model.

The need for the continuous research of new tools for improving motor function recovery after nerve injury is justified by the still often unsatisfactory clinical outcome in these patients. It has been previously shown that the combined use of two reconstructive techniques, namely end-to-side neurorrhaphy and direct muscle neurotization in the rat hindlimb model, can lead to good results in terms of skeletal muscle reinnervation. Here we show that, in the rat forelimb model, the combined use of direct muscle neurotization with either end-to-end or end-to-side neurorrhaphy to reinnervate the denervated flexor digitorum muscles, leads to muscle atrophy prevention over a long postoperative time lapse (10 months). By contrast, very little motor recovery (in case of end-to-end neurorrhaphy) and almost no motor recovery (in case of end-to-side neurorrhaphy) were observed in the grasping activity controlled by flexor digitorum muscles. It can thus be concluded that, at least in the rat, direct muscle neurotization after both end-to-end and end-to-side neurorrhaphy represents a good strategy for preventing denervation-related muscle atrophy but not for regaining the lost motor function.

Dramatic electrocardiographic changes in a junior athlete with unpredictable hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is one of the commonest causes of sudden cardiac death in young athletes. Over the last years, the Italian preparticipation screening programme strongly contributed to discriminate athletes showing borderline (grey-area) left ventricular hypertrophy or fulfilling precise diagnostic criteria for HCM, thanks to the framework of testing performed yearly before competitions. We present the case of a junior athlete in whom dramatic ECG changes suggestive for HCM became manifest during the last year training activity.

Distribution of costameric proteins in normal human ventricular and atrial cardiac muscle.

In the mature heart, the intercalated disc and costameres provide the cell-cell and cell-matrix junctions respectively. Intercalated disc is situated at the bipolar ends of the cardiomyocytes and the myofibrils are anchored at this structure. The costameres mediate integration with the extracellular matrix that covers individual cardiomyocytes laterally. Costameres are considered as "proteic machinery" that appears to comprise two protein complexes: the dystrophin-glycoprotein complex (DGC) and the vinculin-talin-integrin system. There are structural differences between atrial and ventricular myocytes, but there have been relatively few studies that have analyzed costameres and focal adhesion function in cardiac cells. Our previous study carried out only on atrial myocytes, demonstrated that the DGC and talin-vinculin-integrin complexes had a costameric distribution that, unlike skeletal muscle, it localized only on the I band. We performed a further immunohistochemical analysis extending also the evaluation to the normal human cardiac muscle fibers obtained from ventricle and interventricular septum, in order to define the distribution and the spatial relationship between the proteins of the two complexes also in the other heart districts. Immunoconfocal microscopy of cardiac tissue revealed the costameric distribution of DGC and of vinculin-talin-integrin system, the association of all tested proteins in intercalated disks, in disagreement with other Authors, and in T-tubule with irregular spokelike extensions penetrating toward the center of the cell. Moreover, our data showed that all tested proteins colocalize between each other.

Volume rendering based on magnetic resonance imaging: advances in understanding the three-dimensional anatomy of the human knee.

The choice of medical imaging techniques, for the purpose of the present work aimed at studying the anatomy of the knee, derives from the increasing use of images in diagnostics, research and teaching, and the subsequent importance that these methods are gaining within the scientific community. Medical systems using virtual reality techniques also offer a good alternative to traditional methods, and are considered among the most important tools in the areas of research and teaching. In our work we have shown some possible uses of three-dimensional imaging for the study of the morphology of the normal human knee, and its clinical applications. We used the direct volume rendering technique, and created a data set of images and animations to allow us to visualize the single structures of the human knee in three dimensions. Direct volume rendering makes use of specific algorithms to transform conventional two-dimensional magnetic resonance imaging sets of slices into see-through volume data set images. It is a technique which does not require the construction of intermediate geometric representations, and has the advantage of allowing the visualization of a single image of the full data set, using semi-transparent mapping. Digital images of human structures, and in particular of the knee, offer important information about anatomical structures and their relationships, and are of great value in the planning of surgical procedures. On this basis we studied seven volunteers with an average age of 25 years, who underwent magnetic resonance imaging. After elaboration of the data through post-processing, we analysed the structure of the knee in detail. The aim of our investigation was the three-dimensional image, in order to comprehend better the interactions between anatomical structures. We believe that these results, applied to living subjects, widen the frontiers in the areas of teaching, diagnostics, therapy and scientific research.

Behaviour of nitric oxide synthase isoforms in inflammatory human joint diseases: an immunohistochemical study.

Nitric oxide (NO) is produced by nitric oxide synthases (NOS) expressed in various human tissues and, depending on the amount of NO produced in each tissue, the physiological function of NO is determined. Since increased inducibile nitric oxide synthase (iNOS) expression and NO generation are associated with pathogenesis of idiopatic osteoarthritis of synovial tissue and data about constitutive nitric oxide isoform (cNOS) in this tissue are scarce, in this study we investigated the localization and distribution of nitric oxide isoforms in normal, acute and chronic diseased synovium. The immunohistochemical and histologic analysis was performed in human synovial tissue obtained from 10 patients with post-traumatic inflammation, 14 patients with idiopatic osteoarthritis and normal synovial specimens were obtained from 7 patients undergoing surgery for reconstruction of the anterior cruciate ligament. Immunohistochemical data showed iNOS was strongly expressed in the synovial lining layer, subsynovium and blood vessels from patients with acute and chronic inflammation pathology, on the contrary, normal joints were negative. A similar pattern of cNOS immunoreactivity was seen in synovial lining and vascular smooth muscle in the pathological samples, while in the normal joint the intensity of staining was weaker than the inflammed. These data indicate that NO is produced locally in the pathological synovial lining not only by iNOS but also by cNOS.

High-resolution CT grading of tibial stress reactions in distance runners.

OBJECTIVE: The purpose of this study was twofold: to determine whether asymptomatic distance runners exhibit cortical tibial abnormalities on CT and to determine the diagnostic accuracy of CT in athletes with medial tibial stress syndrome. MATERIALS AND METHODS: A cross-sectional study with high-resolution CT of both tibiae was performed on 41 subjects: 20 asymptomatic distance runners, 11 distance runners with unilateral or bilateral pain due to medial tibial stress syndrome (14 painful tibiae), and 10 volunteers not involved in a sport. The group was composed of 13 women and 28 men, ranging in age from 18 to 26 years. A total of 82 tibiae, 14 painful and 68 painless, were evaluated. On the basis of CT findings, tibiae were classified in three groups, and correlation between CT classification and symptoms was made. RESULTS: Among distance runners, the presence of CT abnormalities was found in 14 (100%) of 14 painful tibiae in patients with medial tibial stress syndrome and in 8 (16.6%) of 48 painless tibiae. The difference was statistically significant (p < 0.001, Fisher's exact test). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of CT in diagnosing medial tibial stress syndrome were 100%, 88.2%, 63.6%, 100%, and 90.2%, respectively. CONCLUSION: High-resolution CT has high diagnostic accuracy in depicting medial tibial stress syndrome. Cortical abnormalities can also be seen in some asymptomatic distance runners.

CT and MR imaging findings in athletes with early tibial stress injuries: comparison with bone scintigraphy findings and emphasis on cortical abnormalities.

PURPOSE: To prospectively compare computed tomography (CT), magnetic resonance (MR) imaging, and bone scintigraphy in athletes with clinically suspected early stress injury of tibia. MATERIALS AND METHODS: Medical ethics committee approval and informed consent were obtained. A total of 42 patients experiencing tibial pain due to early stress injuries were evaluated. Eight patients had bilateral involvement; thus, 50 tibiae were evaluated. All patients underwent initial radiography that was negative for injury. MR imaging, CT, and bone scintigraphy were performed in all patients within 1 month of onset of symptoms. Ten asymptomatic volunteers served as the control group. Location of stress injuries, types of bone alterations, and presence of periosteal and bone marrow edema were evaluated. Sensitivity, specificity, accuracy, and positive and negative predictive values of MR imaging and CT were assessed, as was sensitivity of bone scintigraphy. McNemar test was used to detect statistically significant differences. RESULTS: Sensitivity of MR imaging, CT, and bone scintigraphy was 88%, 42%, and 74%, respectively. Specificity, accuracy, and positive and negative predictive values were 100%, 90%, 100%, and 62%, respectively, for MR imaging and 100%, 52%, 100%, and 26%, respectively, for CT. Significant difference in detection of early tibial stress injuries was found between MR imaging and both CT and bone scintigraphy (McNemar test; P < .001 and P = .008, respectively). CONCLUSION: MR imaging is the single best technique in assessment of patients with suspected tibial stress injuries; in some patients with negative MR imaging findings, CT can depict osteopenia, which is the earliest finding of fatigue cortical bone injury.

Ultrastructural changes of corpora cavernosa in men with erectile dysfunction and chronic renal failure.

Erectile dysfunction (ED) is a common and often distressing side effect of renal failure. Uremic men of different ages report a high variety of sexual problems, including sexual hormonal pattern alterations, reduced or loss of libido, infertility, and impotence, thereby influencing their well-being. The pathogenic mechanisms include physiologic, psychologic, and organic causes. To determine the contribution of morphologic factors to impotence we studied the ultrastructure of the corpora cavernosa in 20 patients with end-stage renal disease who were treated with chronic dialysis and compared the findings with 6 individuals with no clinical history of impotence. Our results indicated that in male uremic patients with sexual disturbances there were major changes in smooth muscle cells. This was characterized by reduction of dense bodies in the cytoplasm, thick basement membranes, and increased interstitial collagen fibers with resultant reduction of cell-to-cell contact. In addition, there was thickening and lamination of basement membranes of endothelial cells and increased accumulation of collagen between nerve fibers. These alterations were more evident in patients with longer time on dialysis and were independent of type of primary renal disease. We hypothesize that ED in dialysis patients is not related to the primary disease but to the uremic state.