Biomechanical Analysis of Human Gait When Changing Velocity and Carried Loads: Simulation Study with OpenSim.

Walking is one of the main activities of daily life and gait analysis can provide crucial data for the computation of biomechanics in many fields. In multiple applications, having reference data that include a variety of gait conditions could be useful for assessing walking performance. However, limited extensive reference data are available as many conditions cannot be easily tested experimentally. For this reason, a musculoskeletal model in OpenSim coupled with gait data (at seven different velocities) was used to simulate seven carried loads and all the combinations between the two parameters. The effects on lower limb biomechanics were measured with torque, power, and mechanical work. The results demonstrated that biomechanics was influenced by both speed and load. Our results expand the previous literature: in the majority of previous work, only a subset of the presented conditions was investigated. Moreover, our simulation approach provides comprehensive data that could be useful for applications in many areas, such as rehabilitation, orthopedics, medical care, and sports.

Influence of Backpack Carriage and Walking Speed on Muscle Synergies in Healthy Children.

Four to five muscle synergies account for children's locomotion and appear to be consistent across alterations in speed and slopes. Backpack carriage induces alterations in gait kinematics in healthy children, raising questions regarding the clinical consequences related to orthopedic and neurological diseases and ergonomics. However, to support clinical decisions and characterize backpack carriage, muscle synergies can help with understanding the alterations induced in this condition at the motor control level. In this study, we investigated how children adjust the recruitment of motor patterns during locomotion, when greater muscular demands are required (backpack carriage). Twenty healthy male children underwent an instrumental gait analysis and muscle synergies extraction during three walking conditions: self-selected, fast and load conditions. In the fast condition, a reduction in the number of synergies (three to four) was needed for reconstructing the EMG signal with the same accuracy as in the other conditions (three to five). Synergies were grouped in only four clusters in the fast condition, while five clusters were needed for the self-selected condition. The right number of clusters was not clearly identified in the load condition. Speed and backpack carriage altered nearly every spatial-temporal parameter of gait, whereas kinematic alterations reflected mainly hip and pelvis adaptations. Although the synergistic patterns were consistent across conditions, indicating a similar motor pattern in different conditions, the fast condition required fewer synergies for reconstructing the EMG signal with the same level of accuracy.

Whole Genome Expression Profiling of Semitendinosus Tendons from Children with Diplegic and Tetraplegic Cerebral Palsy.

Cerebral palsy (CP) is the most common movement disorder in children, with a prevalence ranging from 1.5 to 4 per 1000 live births. CP is caused by a non-progressive lesion of the developing brain, leading to progressive alterations of the musculoskeletal system, including spasticity, often leading to the development of fixed contractures, necessitating tendon lengthening surgery. Total RNA-sequencing analysis was performed on semitendinosus tendons from diplegic and tetraplegic CP patients subjected to tendon lengthening surgery compared to control patients undergoing anterior cruciate ligament reconstructive surgery. Tetraplegic CP patients showed increased expression of genes implicated in collagen synthesis and extracellular matrix (ECM) turnover, while only minor changes were observed in diplegic CP patients. In addition, tendons from tetraplegic CP patients showed an enrichment for upregulated genes involved in vesicle-mediated transport and downregulated genes involved in cytokine and apoptotic signaling. Overall, our results indicate increased ECM turnover with increased net synthesis of collagen in tetraplegic CP patients without activation of inflammatory and apoptotic pathways, similar to observations in athletes where ECM remodeling results in increased tendon stiffness and tensile strength. Nevertheless, the resulting increased tendon stiffness is an important issue in clinical practice, where surgery is often required to restore joint mobility.

Recent developments in muscle synergy analysis in young people with neurodevelopmental diseases: A Systematic Review.

The central nervous system simplifies motor control by sending motor commands activating groups of muscles, known as synergies. Physiological locomotion can be described as a coordinated recruitment of four to five muscle synergies. The first studies on muscle synergies in patients affected by neurological diseases were on stroke survivors. They showed that synergies can be used as biomarkers for motor impairment as they vary in patients with respect to healthy people. Likewise, muscle synergy analysis has been applied to developmental diseases (DD). The need for a comprehensive view of the present findings is crucial for comparing results achieved so far and promote future directions in the field. In the present review, we screened three scientific databases and selected thirty-six papers investigating muscle synergies extracted from locomotion in children affected by DD. Thirty-one articles investigate how cerebral palsy (CP) influences motor control, the currently exploited method in studying motor control in CP and finally the effects of treatments in these patients in terms of synergies and biomechanics; two articles investigate how muscle synergies vary in Duchenne muscular dystrophy (DMD), and three other articles assess other developmental pathologies, such as chronic and acute neuropathic pain. For CP, most of the studies demonstrate that the number of synergies is lower and that the synergy composition varies in the affected children with respect to normal controls. Still, the predictability of treatment's effects and the etiology of muscle synergy variation are open questions, as it has been reported that treatments minimally modify synergies, even if they improve biomechanics. The application of different algorithms in extracting synergies might bring about more subtle differences. Considering DMD, no correlation was found between non-neural muscle weakness and muscle modules' variation, while in chronic pain a decreased number of synergies was observed as a possible consequence of plastic adaptations. Even if the potential of the synergistic approach for clinical and rehabilitation practices is recognized, there is not full consensus on protocols nor widely accepted guidelines for the systematic clinical adoption of the method in DD. We critically commented on the current findings, on the methodological issues and the relative open points, and on the clinical impact of muscle synergies in neurodevelopmental diseases to fill the gap for applying the method in clinical practice.

Blood Thiol Redox State in Chronic Kidney Disease.

Thiols (sulfhydryl groups) are effective antioxidants that can preserve the correct structure of proteins, and can protect cells and tissues from damage induced by oxidative stress. Abnormal levels of thiols have been measured in the blood of patients with moderate-to-severe chronic kidney disease (CKD) compared to healthy subjects, as well as in end-stage renal disease (ESRD) patients on haemodialysis or peritoneal dialysis. The levels of protein thiols (a measure of the endogenous antioxidant capacity inversely related to protein oxidation) and S-thiolated proteins (mixed disulphides of protein thiols and low molecular mass thiols), and the protein thiolation index (the molar ratio of the S-thiolated proteins to free protein thiols in plasma) have been investigated in the plasma or red blood cells of CKD and ESRD patients as possible biomarkers of oxidative stress. This type of minimally invasive analysis provides valuable information on the redox status of the less-easily accessible tissues and organs, and of the whole organism. This review provides an overview of reversible modifications in protein thiols in the setting of CKD and renal replacement therapy. The evidence suggests that protein thiols, S-thiolated proteins, and the protein thiolation index are promising biomarkers of reversible oxidative stress that could be included in the routine monitoring of CKD and ESRD patients.

Antioxidants in smokers.

Cigarette smoke (CS) is likely the most common preventable cause of human morbidity and mortality worldwide. Consequently, inexpensive interventional strategies for preventing CS-related diseases would positively impact health systems. Inhaled CS is a powerful inflammatory stimulus and produces a shift in the normal balance between antioxidants and oxidants, inducing oxidative stress in both the respiratory system and throughout the body. This enduring and systemic pro-oxidative state within the body is reflected by increased levels of oxidative stress and inflammation biomarkers seen in smokers. Smokers might benefit from consuming antioxidant supplements, or a diet rich in fruit and vegetables, which can reduce the CS-related oxidative stress. This review provides an overview of the plasma profile of antioxidants observable in smokers and examines the heterogeneous literature to elucidate and discuss the effectiveness of interventional strategies based on antioxidant supplements or an antioxidant-rich diet to improve the health of smokers. An antioxidant-rich diet can provide an easy-to-implement and cost-effective preventative strategy to reduce the risk of CS-related diseases, thus being one of the simplest ways for smokers to stay in good health for as long as possible. The health benefits attributable to the intake of antioxidants have been observed predominantly when these have been consumed within their natural food matrices in an optimal antioxidant-rich diet, while these preventive effects are rarely achieved with the intake of individual antioxidants, even at high doses.

Plasma Protein Carbonyls as Biomarkers of Oxidative Stress in Chronic Kidney Disease, Dialysis, and Transplantation.

Accumulating evidence indicates that oxidative stress plays a role in the pathophysiology of chronic kidney disease (CKD) and its progression; during renal replacement therapy, oxidative stress-derived oxidative damage also contributes to the development of CKD systemic complications, such as cardiovascular disease, hypertension, atherosclerosis, inflammation, anaemia, and impaired host defence. The main mechanism underlying these events is the retention of uremic toxins, which act as a substrate for oxidative processes and elicit the activation of inflammatory pathways targeting endothelial and immune cells. Due to the growing worldwide spread of CKD, there is an overwhelming need to find oxidative damage biomarkers that are easy to measure in biological fluids of subjects with CKD and patients undergoing renal replacement therapy (haemodialysis, peritoneal dialysis, and kidney transplantation), in order to overcome limitations of invasive monitoring of CKD progression. Several studies investigated biomarkers of protein oxidative damage in CKD, including plasma protein carbonyls (PCO), the most frequently used biomarker of protein damage. This review provides an up-to-date overview on advances concerning the correlation between plasma protein carbonylation in CKD progression (from stage 1 to stage 5) and the possibility that haemodialysis, peritoneal dialysis, and kidney transplantation improve plasma PCO levels. Despite the fact that the role of plasma PCO in CKD is often underestimated in clinical practice, emerging evidence highlights that plasma PCO can serve as good biomarkers of oxidative stress in CKD and substitutive therapies. Whether plasma PCO levels merely serve as biomarkers of CKD-related oxidative stress or whether they are associated with the pathogenesis of CKD complications deserves further evaluation.

Guided Growth of the Proximal Femur for the Management of Hip Dysplasia in Children With Cerebral Palsy.

BACKGROUND: Progressive hip displacement is one of the most common and debilitating deformities seen in children with cerebral palsy (CP). The aim of this study was to evaluate the results of temporary medial hemiepiphysiodesis of the proximal femur (TMH-PF) using a transphyseal screw to control hip migration during growth in children with CP. METHODS: This was a retrospective study of children with CP and hip dysplasia, age 4 to 11 years and GMFCS levels III-V. There were 28 patients with 56 hips that underwent TMH-PF surgery between 2007 and 2010. Clinical and radiologic evaluation was performed preoperatively, at 6, 12, and 60 months following the index surgery. Acetabular index (AI), neck-shaft angle (NSA) and migration percentage (MP) were measured. All complications were recorded. RESULTS: All radiographic measurements were significantly improved at the final follow-up. Positive correlations were found between NSA, MP, and AI. Multiple regression analysis revealed that MP, time from surgery, and age were influenced by the decrease of the NSA. The femoral physis grew off the screw in 9 hips within 36 months. The screw head broke during attempted screw exchange in 1 hip. The remain cases (4 hips) were treated by placing a second screw parallel to the existing one. Finally, progressive subluxation occurred in 3 hips when the physis grew off the screw and were treated by skeletal reconstruction. CONCLUSIONS: TMH-PF was effective in controlling progressive subluxation of the hip in the majority of cases, obviating the need for major reconstructive surgery in these children with CP. LEVEL OF EVIDENCE: Level IV.

Effect of plano-valgus foot posture on midfoot kinematics during barefoot walking in an adolescent population.

BACKGROUND: Plano-valgus is a common alteration of the paediatric foot, characterized by valgus hindfoot, foot pronation and drop of the medial longitudinal arch. Despite their importance in the diagnosis and classification of plano-valgus foot condition, little information is available on functional alterations of the major joints spanning the medial longitudinal arch - i.e. midtarsal and tarso-metatarsal. Aim of the study was to provide objective description of the alterations in plano-valgus midfoot joints with respect to those in an age-matched normally-developed feet population. METHODS: Twenty adolescents (13.3 ± 0.8 years) with bilateral plano-valgus feet underwent clinical examination and were gait-analysed via a validated 4-segment foot model. This allowed to measure static foot posture, kinematics of the main foot joints, and medial longitudinal arch deformation during walking at comfortable speed. Range of motion and temporal profiles of joint rotations were compared to those from a control population of age-matched adolescents with normally-developed feet. RESULTS: The plano-valgus midtarsal joint was more dorsiflexed, everted and abducted than that in the control group, and showed reduced sagittal-plane RoM (plano-valgus = 15.9 degrees; control = 22.2 degrees; P <  0.01). The tarso-metarsal joint was more plantarflexed and adducted, and showed larger frontal-plane RoM. The MLA showed larger RoM and was lower throughout the stance phase of the gait cycle. CONCLUSION: Significant postural and kinematic alterations are present at the midtarsal and tarso-metarsal joints of adolescents with plano-valgus feet. Objective identification and quantification of plano-valgus foot alterations, via non-invasive gait-analysis, is relevant to improving the diagnosis of this condition and to evaluating the effect of conservative treatments and of surgical corrections by different techniques.

The Role of Taylor Spatial Frame in the Treatment of Blount Disease.

BACKGROUND: Alteration of the posteromedial part of the proximal tibia is the main characteristic of Blount's disease and if left untreated, leg alignment and normal development of the lower limbs may be compromised. AIM: To report treatment outcomes in children with Blount's disease using the Taylor Spatial Frame (TSF). MATERIALS AND METHODS: From January 2007 to December 2014, 16 young children (24 tibia) with a mean age of 7.5 years (range of 3-14 yrs) and severe Blount's disease were treated using TSF. Preoperative long standing radiographs were performed and anatomic medial proximal tibial angle (MPTA), diaphyseal-metaphyseal tibial angle (Drennan), femoro-tibial angle and leg length discrepancy (LLD) were measured. RESULTS: Post-operative improvement of all measurements was observed. MPTA increased from a mean of 71.8° (58° - 79°) to 92.5° (90° - 95°), the Drennan decreased from 16.6° (14° - 18°) to 3.6° (0° - 6°), the F-T angle changed from 15.4° (10° - 25°) of varus to 5.9° (2° - 10°) of valgus and the LLD decreased from 208 mm (150-320) to 69 mm (0- +120). Mean follow-up was 45.6 months. According to Paley's criteria pin track infection was present in 6 tibiae, while in 5 patients software changes were necessary. Recurrence was observed in 3 patients (triplets). Complete restoration of the mechanical axis was obtained at the end of the treatment. CONCLUSIONS: In the last decades, different surgical treatments have been proposed for Blount's disease (tension band plate, staples, osteotomies using external or internal fixation). External fixation using the TSF allows gradual safe correction of multiplanar deformities and is a well-tolerated technique by patients with Blount's disease.

Intra-Articular Cytokine Levels in Adolescent Patients after Anterior Cruciate Ligament Tear.

The treatment of anterior cruciate ligament (ACL) injuries in children and adolescents is challenging. Preclinical and clinical studies investigated ACL repairing techniques in skeletally immature subjects. However, intra-articular bioenvironment following ACL tear has not yet been defined in skeletally immature patients. The aim of this study was to measure cytokine concentrations in the synovial fluid in adolescent population. Synovial levels of IL-1ß, IL-1ra, IL-6, IL-8, IL-10, and TNF-α were measured in 17 adolescent patients (15 boys) with ACL tears who underwent ACL reconstruction including acute (5), subacute (7), and chronic (5) phases. Femoral growth plates were classified as "open" in three patients, "closing" in eight, and "closed" in six. Eleven patients presented an ACL tear associated with a meniscal tear. The mean Tegner and Lysholm scores (mean ± SD) of all patients were 8 ± 1 and 50.76 ± 26, respectively. IL-8, TNF-α, and IL-1ß levels were significantly greater in patients with "open" physes. IL-1ra and IL-1ß levels were significantly higher in patients with ACL tear associated with a meniscal tear. Poor Lysholm scores were associated with elevated IL-6 and IL-10 levels. IL-10 levels positively correlated with IL-6 and IL-8 levels, whereas TNF-α concentration negatively correlated with IL-6 levels. Skeletally immature patients with meniscal tears and open growth plates have a characteristic cytokine profile with particularly elevated levels of proinflammatory cytokines including IL-8, TNF-α, and IL-1ß. This picture suggests that the ACL tear could promote an intra-articular catabolic response in adolescent patients greater than that generally reported for adult subjects. The study lacks the comparison with synovial samples from healthy skeletally immature knees due to ethical reasons. Overall, these data contribute to a better knowledge of adolescent intra-articular bioenvironment following ACL injuries.

Plasma Protein Carbonylation in Haemodialysed Patients: Focus on Diabetes and Gender.

Patients with end-stage renal disease (ESRD) undergoing haemodialysis (HD) experience oxidative/carbonyl stress, which is postulated to increase after the HD session. The influence of diabetes mellitus and sex on oxidation of plasma proteins in ESRD has not yet been clarified despite that diabetic nephropathy is the most common cause of ESRD in developed and developing countries and despite the increasingly emerging differences between males and females in epidemiology, pathophysiology, clinical manifestations, and outcomes for several diseases. Therefore, this study aimed to evaluate the possible effect of type 2 diabetes mellitus, gender, and dialysis filter on plasma level of protein carbonyls (PCO) in ESRD patients at the beginning and at the end of a single HD session. Results show that mean post-HD plasma PCO levels are significantly higher than mean pre-HD plasma PCO levels and that the type of dialysis filter and dialysis technique are unrelated to plasma PCO levels. The mean level of plasma PCO after a HD session increases slightly but significantly in nondiabetic ESRD patients compared to diabetic ones, whereas it increases more markedly in women than in men. These novel findings suggest that women with ESRD are more susceptible than men to oxidative/carbonyl stress induced by HD.

Total Hip Arthroplasty in an Inveterate Femoral Neck Fracture in a Patient with Congenital Insensitivity to Pain with Anhidrosis.

Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare disorder characterized by autonomic and sensory nerves malfunction with insensitivity to both deep and superficial painful stimuli, inability to sweat and produce tears, and mild to moderate mental retardation with self-mutilating behavior. Related consequences of inveterate musculoskeletal injuries represent a major issue for these patients, since pain cannot act as a protection mechanism. For the same reason, the patients are at risk during postoperative rehabilitation, which should be taken into account when selecting an orthopaedic implant. To our knowledge, only one case of total hip arthroplasty has been reported in the literature to date. A 21-year-old Caucasian male patient affected with CIPA arrived at our attention complaining about a functional limitation of the left hip. No history of trauma was reported. The X-rays showed an inveterate femoral neck fracture with a severe necrosis and resorption of the femoral head. We decided to perform a total hip arthroplasty with a cemented stem and a cemented dual mobility cup. The postoperative course and rehabilitation were satisfactory, with excellent clinical results, measured with the Harris Hip Score at 1 year.

Assessment of glutathione/glutathione disulphide ratio and S-glutathionylated proteins in human blood, solid tissues, and cultured cells.

Glutathione (GSH) is the major non-protein thiol in humans and other mammals, which is present in millimolar concentrations within cells, but at much lower concentrations in the blood plasma. GSH and GSH-related enzymes act both to prevent oxidative damage and to detoxify electrophiles. Under oxidative stress, two GSH molecules become linked by a disulphide bridge to form glutathione disulphide (GSSG). Therefore, assessment of the GSH/GSSG ratio may provide an estimation of cellular redox metabolism. Current evidence resulting from studies in human blood, solid tissues, and cultured cells suggests that GSH also plays a prominent role in protein redox regulation via S -glutathionylation, i.e., the conjugation of GSH to reactive protein cysteine residues. A number of methodologies that enable quantitative analysis of GSH/GSSG ratio and S-glutathionylated proteins (PSSG), as well as identification and visualization of PSSG in tissue sections or cultured cells are currently available. Here, we have considered the main methodologies applied for GSH, GSSG and PSSG detection in biological samples. This review paper provides an up-to-date critical overview of the application of the most relevant analytical, morphological, and proteomics approaches to detect and analyse GSH, GSSG and PSSG in mammalian samples as well as discusses their current limitations.

Gait analysis on force treadmill in children: comparison with results from ground-based force platforms.

Gait analysis (GA) typically includes surface electromyographic (sEMG) recording from several lower limb muscles, optoelectronic measurement of joint rotations, and force recordings from ground-based platforms. From the latter two variables, the muscle power acting on the lower limb joints can be estimated. Recently, gait analysis on a split-belt force treadmill (GAFT) was validated for the study of adult walking. It showed high reliability of spatiotemporal, kinematic, dynamic, and sEMG parameters, matching those obtainable with GA on the basis of ground walking. GAFT, however, still needs validation in children. Potential differences with respect to adult GAFT relate to (a) possible high signal-to-noise ratio, given the lower forces applied; (b) higher differences between treadmill and over-ground walking; and (c) limited compliance with the experimental setup. This study aims at investigating whether GAFT provides results comparable with those obtainable from ground walking in children and consistent with results from GAFT in adults. GAFT was applied to three groups of healthy children aged 5-6 years (n=6), 7-8 years (n=6), and 9-13 years (n=8) walking at the same average speed spontaneously adopted overground. The results were compared with those obtained from another study applying GA to an age-matched and speed-matched sample of 47 children, and with those obtained from GAFT in adults. The reliability (as indicated by the SD) of both spatiotemporal and dynamic parameters was higher in GAFT compared with GA. In the 5-6-, 7-8-, and 9-13-year-old groups, at average speeds of 0.83, 1.08, and 1.08 m/s, step length was shorter by 9.19, 3.57, and 2.30% compared with GA in controls at comparable speeds, respectively. For the youngest group, a lower power generation from the plantar flexors (peak power: 1.35±0.32 vs. 2.11±1.02 W/kg) and a slightly more flexed posture of the hip, knee, and ankle joints were observed during GAFT compared with GA in controls. The other gait parameters were very similar between the GAFT and the GA groups. The shortening of step length during GAFT, relative to GA at superimposable speed, was on average of all children 6.8%, in line with the 8% decrease found in adults. The profiles of sEMG and joint rotations, and all of the weight-standardized joint power parameters, matched those recorded in adults. The entire experimental session lasted about 1 h. All children complied with the experimental setting and easily completed the requested tests. In conclusion, GAFT seems to be a promising alternative to conventional GA in children.

Plasma protein-bound di-tyrosines as biomarkers of oxidative stress in end stage renal disease patients on maintenance haemodialysis.

BACKGROUND: Patients with end-stage renal disease (ESRD) undergoing haemodialysis (HD) experience enhanced oxidative stress and systemic inflammation, which are risk factors for cardiovascular disease, the most common cause of excess morbidity and mortality for these patients. Different pathways producing different types of oxidative stress occur in ESRD. The purpose of our study was to determine the effect of HD on plasma levels of protein-bound dityrosine (di-Tyr), a biomarker of protein oxidation. METHODS: Protein-bound di-Tyr formation was measured by size exclusion HPLC coupled to fluorescence detector. Clinical laboratory parameters were measured by standardized methods. RESULTS: In most ESRD patients, a single HD session decreased significantly the plasma protein-bound di-Tyr level, although the mean post-HD level remained significantly greater than the one in healthy people. Furthermore, pre-HD plasma protein-bound di-Tyr level was positively correlated with pre-HD serum creatinine and albumin concentrations. No significant correlation was found between plasma protein-bound di-Tyr level and serum concentration of C-reactive protein, a biomarker of systemic inflammation. CONCLUSIONS: This study demonstrates that a single HD session does not increase, rather partially decreases, oxidative pathways producing di-Tyr in the haemodialyzed patient. GENERAL SIGNIFICANCE: The choice of the most pertinent biomarkers of oxidative stress is critical for the development of novel treatments for ESRD. However, the relative importance of oxidative stress and inflammation in ESRD remains largely undetermined, and several questions concerning oxidative stress and inflammation remain poorly defined. These results could stimulate further studies on the use of plasma protein-bound di-Tyr as a long-lasting oxidative stress biomarker in ESRD.

Protein Carbonylation in Human Smokers and Mammalian Models of Exposure to Cigarette Smoke: Focus on Redox Proteomic Studies.

SIGNIFICANCE: Oxidative stress is one mechanism whereby tobacco smoking affects human health, as reflected by increased levels of several biomarkers of oxidative stress/damage isolated from tissues and biological fluids of active and passive smokers. Many investigations of cigarette smoke (CS)-induced oxidative stress/damage have been carried out in mammalian animal and cellular models of exposure to CS. Animal models allow the investigation of many parameters that are similar to those measured in human smokers. In vitro cell models may provide new information on molecular and functional differences between cells of smokers and nonsmokers. Recent Advances: Over the past decade or so, a growing number of researches highlighted that CS induces protein carbonylation in different tissues and body fluids of smokers as well as in in vivo and in vitro models of exposure to CS. CRITICAL ISSUES: We review recent findings on protein carbonylation in smokers and models thereof, focusing on redox proteomic studies. We also discuss the relevance and limitations of these models of exposure to CS and critically assess the congruence between the smoker's condition and laboratory models. FUTURE DIRECTIONS: The identification of protein targets is crucial for understanding the mechanism(s) by which carbonylated proteins accumulate and potentially affect cellular functions. Recent progress in redox proteomics allows the enrichment, identification, and characterization of specific oxidative protein modifications, including carbonylation. Therefore, redox proteomics can be a powerful tool to gain new insights into the onset and/or progression of CS-related diseases and to develop strategies to prevent and/or treat them. Antioxid. Redox Signal. 26, 406-426.

Thiol oxidation and di-tyrosine formation in human plasma proteins induced by inflammatory concentrations of hypochlorous acid.

In this study, we assessed the oxidative damage occurring in plasma proteins when human blood was exposed to inflammatory concentrations of hypochlorous acid (HOCl). We used specific thiol labelling and Western blot analyses to determine protein thiol oxidation, as well as analytical gel filtration HPLC coupled to fluorescence detection to explore formation of high molecular weight (HMW) protein aggregates. Thiol-containing proteins oxidized by HOCl were identified by redox proteomics. Mass spectrometry (MS) analysis was performed to elucidate the protein composition of HMW aggregates. α1-antitrypsin, transthyretin, and haptoglobin showed thiol oxidation at HOCl concentrations higher than those causing complete oxidation of albumin. At the highest HOCl concentrations, formation of carbonylated and di-tyrosine cross-linked HMW protein aggregates also occurred. MS analysis identified fibrinogen, complement C3 and apolipoprotein A-I as components of HMW protein aggregates. These results could be relevant for human diseases characterized by inflammatory conditions in which myeloperoxidase and HOCl are involved. BIOLOGICAL SIGNIFICANCE: In this study we evaluated the oxidative damage occurring on plasma proteins when reconstituted human blood was exposed to inflammatory concentrations of hypochlorous acid (HOCl). Pathophysiological concentrations of HOCl are able to induce different modifications on plasma proteins such as carbonylation, sulfhydryl oxidation and formation of high molecular weight (HMW) protein aggregates characterized by di-tyrosine fluorescence. There are two relevant aspects emerging from this paper. The first one consists on identifying low abundant proteins undergoing sulfhydryl oxidation by biotin-maleimide derivatization followed by MALDI-TOF mass spectrometry. This approach suggests three low-abundant proteins undergoing HOCl-induced oxidation: transthyretin, α1-antitrypsin, and haptoglobin. In addition, we analysed HMW protein aggregates forming after HOCl exposure. These aggregates are characterized by carbonylation, intra- and/or intermolecular di-tyrosine bridges. After their isolation from SDS-PAGE gel electrophoresis, using electrospray tandem mass spectrometry coupled to reversed-phase nanoscale capillary liquid chromatography, we identified some protein constituents of these HMW aggregates such as α, ß, γ fibrinogen chains, apolipoprotein A-I and complement C3. In particular, our work highlights how fibrinogen is an important constituent of HOCl-induced HMW protein aggregates validating the mass spectrometry result with additional experiments. Further investigations are required in order to evaluate the possibility to use carbonylated and di-Tyr cross-linked HMW protein aggregates as (early) biomarkers for disease progression in inflammatory conditions in which myeloperoxidase and HOCl are involved.

Knee arthrodesis by the Ilizarov method in the treatment of total knee arthroplasty failure.

BACKGROUND: Currently, the main indication for knee arthrodesis is septic failure of a total knee arthroplasty (TKA). The purpose of this study was to evaluate the results of knee arthrodesis by circular external fixation performed in the treatment of TKA failure in which revision arthroplasty was not indicated. METHODS: The study involved 19 patients who underwent knee arthrodesis by the Ilizarov method. Clinical and functional assessments were performed, including Knee Society Score (KSS). A postoperative clinical and radiographic evaluation was conducted every three months until the end of the treatment. Postoperative complications and eventual leg shortening were recorded. RESULTS: KSS results showed a significant improvement with respect to the preoperative condition. Of the 16 patients in the final follow-up, 15 patients (93.7%) achieved complete bone fusion. Major complications occurred in patients treated for septic failure of TKA and most occurred in patients over 75years of age; the mean final leg shortening was four centimeters. CONCLUSION: In our experience, the Ilizarov method is effective for performing a knee arthrodesis in the case of extensive bone loss. At the same time, it is possible to correct the associated leg deformities or limb length difference. In addition, only the Ilizarov method provides a mechanical stimulus for bone formation and improves the quality of the bone and of the microcirculation, which enhances the host response against infection. Despite these attributes, knee arthrodesis by the Ilizarov method must be considered a 'salvage procedure' in cases of severe outcomes from knee surgery in which revision arthroplasty is not indicated.

Can we prevent hip dislocation in children with cerebral palsy? Effects of postural management.

BACKGROUND: Hip dislocation is common in children with cerebral palsy (CP). At birth they do not have musculoskeletal deformities but they develop over time due to the combined effects of the movement disorder and impaired gross motor function. Early detection and treatment of a hip at risk is needed to modify the natural of hip development in CP. AIM: The aim of this study was to determine the effect of postural management treatment on hip displacement's progression in children CP. DESIGN: Prospective comparative non-randomized study. SETTING: Rehabilitative outpatient unit. POPULATION: Fifty-one children with CP were studied; the treated group (N.=30) was compared to a control group (N.=21). METHODS: The treated group followed a two year's long combined treatment program consisting a neurodevelopment treatment (NDT) two times a week and a 5 hours daily siège moulé postural program. The control group underwent only NDT twice a week for two years. Hip radiographs were measured with the migration percentage (MP) method at baseline, at 1 and 2 years of follow-up. RESULTS: A significant difference has been observed in the MP (%) trend (P<0.001) between treatment and control groups. At 2 years, there was a marked worsening (MP from 23.0 to 37.7) in the control group, compared to the stability (from 28.8 to 26.8) in the treatment group. CONCLUSIONS: This study supports the evidence that conservative postural management of hip deformity is useful to prevent the natural progression of hip dislocation. CLINICAL REHABILITATION IMPACT: Hip radiographic follow up program together with NDT and postural management program is useful to modify the natural progression of hip dislocation in children with CP.