Neuromuscular training to enhance sensorimotor and functional deficits in subjects with chronic ankle instability: A systematic review and best evidence synthesis

<p>Abstract</p> <p>Objective</p> <p>To summarise the available evidence for the efficacy of neuromuscular training in enhancing sensorimotor and functional deficits in subjects with chronic ankle instability (CAI).</p> <p>Design</p> <p>Systematic review with best evidence synthesis.</p> <p>Data Sources</p> <p>An electronic search was conducted through December 2009, limited to studies published in the English language, using the Pubmed, CINAHL, Embase, and SPORTDiscus databases. Reference screening of all included articles was also undertaken.</p> <p>Methods</p> <p>Studies were selected if the design was a RCT, quasi RCT, or a CCT; the patients were adolescents or adults with confirmed CAI; and one of the treatment options consisted of a neuromuscular training programme. The primary investigator independently assessed the risk of study bias and extracted relevant data. Due to clinical heterogeneity, data was analysed using a best-evidence synthesis.</p> <p>Results</p> <p>Fourteen studies were included in the review. Meta-analysis with statistical pooling of data was not possible, as the studies were considered too heterogeneous. Instead a best evidence synthesis was undertaken. There is limited to moderate evidence to support improvements in dynamic postural stability, and patient perceived functional stability through neuromuscular training in subjects with CAI. There is limited evidence of effectiveness for neuromuscular training for improving static postural stability, active and passive joint position sense (JPS), isometric strength, muscle onset latencies, shank/rearfoot coupling, and a reduction in injury recurrence rates. There is limited evidence of no effectiveness for improvements in muscle fatigue following neuromuscular intervention.</p> <p>Conclusion</p> <p>There is limited to moderate evidence of effectiveness in favour of neuromuscular training for various measures of static and dynamic postural stability, active and passive JPS, isometric strength, muscle onset latencies, shank/rearfoot coupling and injury recurrence rates. Strong evidence of effectiveness was lacking for all outcome measures. All but one of the studies included in the review were deemed to have a high risk of bias, and most studies were lacking sufficient power. Therefore, in future we recommend conducting higher quality RCTs using appropriate outcomes to assess for the effectiveness of neuromuscular training in overcoming sensorimotor deficits in subjects with CAI.</p

Genetic and pharmacological inhibition of CDK9 drives neutrophil apoptosis to resolve inflammation in zebrafish in vivo

Neutrophilic inflammation is tightly regulated and subsequently resolves to limit tissue damage and promote repair. When the timely resolution of inflammation is dysregulated, tissue damage and disease results. One key control mechanism is neutrophil apoptosis, followed by apoptotic cell clearance by phagocytes such as macrophages. Cyclin-dependent kinase (CDK) inhibitor drugs induce neutrophil apoptosis in vitro and promote resolution of inflammation in rodent models. Here we present the first in vivo evidence, using pharmacological and genetic approaches, that CDK9 is involved in the resolution of neutrophil-dependent inflammation. Using live cell imaging in zebrafish with labelled neutrophils and macrophages, we show that pharmacological inhibition, morpholino-mediated knockdown and CRISPR/cas9-mediated knockout of CDK9 enhances inflammation resolution by reducing neutrophil numbers via induction of apoptosis after tailfin injury. Importantly, knockdown of the negative regulator La-related protein 7 (LaRP7) increased neutrophilic inflammation. Our data show that CDK9 is a possible target for controlling resolution of inflammation

‘Medusa head ataxia’: the expanding spectrum of Purkinje cell antibodies in autoimmune cerebellar ataxia. Part 3: Anti-Yo/CDR2, anti-Nb/AP3B2, PCA-2, anti-Tr/DNER, other antibodies, diagnostic pitfalls, summary and outlook

Serological testing for anti-neural autoantibodies is important in patients presenting with idiopathic cerebellar ataxia, since these autoantibodies may indicate cancer, determine treatment and predict prognosis. While some of them target nuclear antigens present in all or most CNS neurons (e.g. anti-Hu, anti-Ri), others more specifically target antigens present in the cytoplasm or plasma membrane of Purkinje cells (PC). In this series of articles, we provide a detailed review of the clinical and paraclinical features, oncological, therapeutic and prognostic implications, pathogenetic relevance, and differential laboratory diagnosis of the 12 most common PC autoantibodies (often referred to as ‘Medusa head antibodies’ due to their characteristic somatodendritic binding pattern when tested by immunohistochemistry). To assist immunologists and neurologists in diagnosing these disorders, typical high-resolution immunohistochemical images of all 12 reactivities are presented, diagnostic pitfalls discussed and all currently available assays reviewed. Of note, most of these antibodies target antigens involved in the mGluR1/calcium pathway essential for PC function and survival. Many of the antigens also play a role in spinocerebellar ataxia. Part 1 focuses on anti-metabotropic glutamate receptor 1-, anti-Homer protein homolog 3-, anti-Sj/inositol 1,4,5-trisphosphate receptor- and anti-carbonic anhydrase-related protein VIII-associated autoimmune cerebellar ataxia (ACA); part 2 covers anti-protein kinase C gamma-, anti-glutamate receptor delta-2-, anti-Ca/RhoGTPase-activating protein 26- and anti-voltage-gated calcium channel-associated ACA; and part 3 reviews the current knowledge on anti-Tr/delta notch-like epidermal growth factor-related receptor-, anti-Nb/AP3B2-, anti-Yo/cerebellar degeneration-related protein 2- and Purkinje cell antibody 2-associated ACA, discusses differential diagnostic aspects and provides a summary and outlook

Mechanisms of the noxious inflammatory cycle in cystic fibrosis

Multiple evidences indicate that inflammation is an event occurring prior to infection in patients with cystic fibrosis. The self-perpetuating inflammatory cycle may play a pathogenic part in this disease. The role of the NF-κB pathway in enhanced production of inflammatory mediators is well documented. The pathophysiologic mechanisms through which the intrinsic inflammatory response develops remain unclear. The unfolded mutated protein cystic fibrosis transmembrane conductance regulator (CFTRΔF508), accounting for this pathology, is retained in the endoplasmic reticulum (ER), induces a stress, and modifies calcium homeostasis. Furthermore, CFTR is implicated in the transport of glutathione, the major antioxidant element in cells. CFTR mutations can alter redox homeostasis and induce an oxidative stress. The disturbance of the redox balance may evoke NF-κB activation and, in addition, promote apoptosis. In this review, we examine the hypotheses of the integrated pathogenic processes leading to the intrinsic inflammatory response in cystic fibrosis

Potential therapeutic applications of microbial surface-activecompounds

Numerous investigations of microbial surface-active compounds or biosurfactants over the past two decades have led to the discovery of many interesting physicochemical and biological properties including antimicrobial, anti-biofilm and therapeutic among many other pharmaceutical and medical applications. Microbial control and inhibition strategies involving the use of antibiotics are becoming continually challenged due to the emergence of resistant strains mostly embedded within biofilm formations that are difficult to eradicate. Different aspects of antimicrobial and anti-biofilm control are becoming issues of increasing importance in clinical, hygiene, therapeutic and other applications. Biosurfactants research has resulted in increasing interest into their ability to inhibit microbial activity and disperse microbial biofilms in addition to being mostly nontoxic and stable at extremes conditions. Some biosurfactants are now in use in clinical, food and environmental fields, whilst others remain under investigation and development. The dispersal properties of biosurfactants have been shown to rival that of conventional inhibitory agents against bacterial, fungal and yeast biofilms as well as viral membrane structures. This presents them as potential candidates for future uses in new generations of antimicrobial agents or as adjuvants to other antibiotics and use as preservatives for microbial suppression and eradication strategies

Hand-held dynamometry in patients with haematological malignancies: measurement error in the clinical assessment of knee extension strength

BACKGROUND: Hand-held dynamometry is a portable and inexpensive method to quantify muscle strength. To determine if muscle strength has changed, an examiner must know what part of the difference between a patient's pre-treatment and post-treatment measurements is attributable to real change, and what part is due to measurement error. This study aimed to determine the relative and absolute reliability of intra and inter-observer strength measurements with a hand-held dynamometer (HHD). METHODS: Two observers performed maximum voluntary peak torque measurements (MVPT) for isometric knee extension in 24 patients with haematological malignancies. For each patient, the measurements were carried out on the same day. The main outcome measures were the intraclass correlation coefficient (ICC +/- 95%CI), the standard error of measurement (SEM), the smallest detectable difference (SDD), the relative values as % of the grand mean of the SEM and SDD, and the limits of agreement for the intra- and inter-observer ;3 repetition average; and the ;highest value of 3 MVPT; knee extension strength measures. RESULTS: The intra-observer ICCs were 0.94 for the average of 3 MVPT (95%CI: 0.86-0.97) and 0.86 for the highest value of 3 MVPT (95%CI: 0.71-0.94). The ICCs for the inter-observer measurements were 0.89 for the average of 3 MVPT (95%CI: 0.75-0.95) and 0.77 for the highest value of 3 MVPT (95%CI: 0.54-0.90). The SEMs for the intra-observer measurements were 6.22 Nm (3.98% of the grand mean (GM) and 9.83 Nm (5.88% of GM). For the inter-observer measurements, the SEMs were 9.65 Nm (6.65% of GM) and 11.41 Nm (6.73% of GM). The SDDs for the generated parameters varied from 17.23 Nm (11.04% of GM) to 27.26 Nm (17.09% of GM) for intra-observer measurements, and 26.76 Nm (16.77% of GM) to 31.62 Nm (18.66% of GM) for inter-observer measurements, with similar results for the limits of agreement. CONCLUSION: The results indicate that there is acceptable relative reliability for evaluating knee strength with a HHD, while the measurement error observed was modest. The HHD may be useful in detecting changes in knee extension strength at the individual patient level