Systematic Review of the Addition of Hip Strengthening Exercises for Adults with Patellofemoral Pain Syndrome

Patellofemoral Pain Syndrome (PFPS) is a common musculoskeletal disorder typically occurring in physically active people aged 40 years and younger, causing pain, functional deficits and lower limb weakness. Traditional treatment has been aimed at strengthening the knee, however recent research suggests the muscles around the hip also play an important role in the development and continuity of Patellofemoral Pain Syndrome. Purpose: To investigate the effectiveness of the addition of hip strengthening exercises to standard physiotherapy treatment (knee strengthening and stretching exercises) on reducing pain, and enhancing strength and function when compared to standard physiotherapy treatment alone in adults with Patellofemoral Pain Syndrome. Method: A systematic search of Cochrane, CINAHL, Embase, MEDLINE®, PEDro and SportDiscus was conducted. Studies of participants aged 18 to 44, diagnosed with Patellofemoral Pain Syndrome by a healthcare practitioner, or reporting peripatellar or retropatellar pain with common functional tasks, were included. A critical appraisal, using the Critical Appraisal Skills Program for Randomised Controlled Trials (CASP) was used to assess methodological quality. Results: Five randomised controlled trials of varying methodological quality met the inclusion criteria. The participants in these studies were aged between 18 to 40 years of age. The duration of the intervention ranged from four to six weeks consisting of 12 to 30 supervised exercise sessions. Studies used varying outcome measures for each of the three outcomes. Overall, the studies demonstrated that the addition of hip strengthening exercises to standard physiotherapy care consistently improved pain and function, but the impact on strength was variable. Conclusion: Previously, only a small number of studies have looked at the addition of hip exercises to standard physiotherapy care for treatment of Patellofemoral Pain Syndrome. While there is a growing body of evidence for the efficacy of hip strengthening exercises for Patellofemoral Pain Syndrome, this is constrained by bias towards female participants, lack of true controls in most studies, and low methodological quality of studies overall. Hip exercises added to standard physiotherapy care shows potential as a treatment method for improving outcomes of pain and function in adults with Patellofemoral Pain Syndrome

Chemical evolution of local post-starburst galaxies : implications for the mass-metallicity relation

We use the stellar fossil record to constrain the stellar metallicity evolution and star-formation histories of the post-starburst (PSB) regions within 45 local PSB galaxies from the MaNGA survey. The direct measurement of the regions’ stellar metallicity evolution is achieved by a new two-step metallicity model that allows for stellar metallicity to change at the peak of the starburst. We also employ a Gaussian process noise model that accounts for correlated errors introduced by the observational data reduction or inaccuracies in the models. We find that a majority of PSB regions (69 per cent at >1σ significance) increased in stellar metallicity during the recent starburst, with an average increase of 0.8 dex and a standard deviation of 0.4 dex. A much smaller fraction of PSBs are found to have remained constant (22 per cent) or declined in metallicity (9 per cent, average decrease 0.4 dex, standard deviation 0.3 dex). The pre-burst metallicities of the PSB galaxies are in good agreement with the mass–metallicity (MZ) relation of local star-forming galaxies. These results are consistent with hydrodynamic simulations, which suggest that mergers between gas-rich galaxies are the primary formation mechanism of local PSBs, and rapid metal recycling during the starburst outweighs the impact of dilution by any gas inflows. The final mass-weighted metallicities of the PSB galaxies are consistent with the MZ relation of local passive galaxies. Our results suggest that rapid quenching following a merger-driven starburst is entirely consistent with the observed gap between the stellar mass–metallicity relations of local star-forming and passive galaxies.Peer reviewe

Adeno-Associated Virus Neutralizing Antibodies in Large Animals and Their Impact on Brain Intraparenchymal Gene Transfer

Pre-existing neutralizing antibody (NAb) against adeno-associated virus (AAV) commonly found in primates is a major host barrier that can severely compromise in vivo gene transfer by AAV vectors. To achieve proof-of-concept success in clinical development of recombinant AAV (rAAV)-based in vivo gene therapy, it is crucial to consider the potential interference of NAb and to enroll serologically compatible study subjects. In this study, we report a large AAV NAb dataset comprising multiple large animal species and AAV serotypes and compare two NAb assays based on in vitro or in vivo transduction inhibition, respectively. Together with previously published AAV seroepidemiology studies, these data can serve as a reference for selecting suitable serotypes, study subjects of large animal species, and potentially human patients for rAAV treatment. In addition, we modeled the intrathalamus rAAV9 delivery in the presence of circulating anti-AAV9 NAb generated by either pre-immunization or passive transfer of NAb-positive large animal serum to mice. The data showed that circulating NAb may not be the sole determinant to inhibit braintransduction. Other aspects of pre-existing AAV immunity following natural infection or rAAV administration may be further studied to establish a more accurate inclusion criterion for clinical studies employing intraparenchymal rAAV9 injections

An empirical approach towards the efficient and optimal production of influenza-neutralizing ovine polyclonal antibodies demonstrates that the novel adjuvant CoVaccine HT(TM) is functionally superior to Freund's adjuvant

Passive immunotherapies utilising polyclonal antibodies could have a valuable role in preventing and treating infectious diseases such as influenza, particularly in pandemic situations but also in immunocompromised populations such as the elderly, the chronically immunosuppressed, pregnant women, infants and those with chronic diseases. The aim of this study was to optimise current methods used to generate ovine polyclonal antibodies. Polyclonal antibodies to baculovirus-expressed recombinant influenza haemagglutinin from A/Puerto Rico/8/1934 H1N1 (PR8) were elicited in sheep using various immunisation regimens designed to investigate the priming immunisation route, adjuvant formulation, sheep age, and antigen dose, and to empirically ascertain which combination maximised antibody output. The novel adjuvant CoVaccine HT™ was compared to Freund’s adjuvant which is currently the adjuvant of choice for commercial production of ovine polyclonal Fab therapies. CoVaccine HT™ induced significantly higher titres of functional ovine anti-haemagglutinin IgG than Freund’s adjuvant but with fewer side effects, including reduced site reactions. Polyclonal hyperimmune sheep sera effectively neutralised influenza virus in vitro and, when given before or after influenza virus challenge, prevented the death of infected mice. Neither the age of the sheep nor the route of antigen administration appeared to influence antibody titre. Moreover, reducing the administrated dose of haemagglutinin antigen minimally affected antibody titre. Together, these results suggest a cost effective way of producing high and sustained yields of functional ovine polyclonal antibodies specifically for the prevention and treatment of globally significant diseases.Natalie E. Stevens, Cara K. Fraser, Mohammed Alsharifi, Michael P. Brown, Kerrilyn R. Diener, John D. Haybal

Undergraduate Physiotherapy Research Project Collaboration: The exploration of the Modified Total Body Rotation Test (MTBRT) for use with older people within the community

Background – Undergraduate physiotherapy (UGP) research projects are a valuable means of exploring areas of interest. Collaborative studies can act as initial pilot studies prior to full investigation on targeted populations. Ten Cardiff University (CU) UGP students investigated various aspects of the MTBRT, an outcome measure used in the USA with Older Adults in the community. Aims/Objectives – To explore the Reliability and Validity of the MTBRT. Methods- 3 Correlation studies were undertaken over 3 years; 57 healthy CU staff and students aged between 20 – 59 years participated within the 3 reliability studies: intra-rater and inter-rater reliability of the MTBRT, and intra-rater reliability of the seated MTBRT (sMTBRT); and 7 concurrent validity studies: MTBRT v Timed Up and Go; 4 Square Step; sMTBRT; 5x Sit to Stand; Step test; COP total excursion; and Functional reach tests. Results – Intra-rater reliability was high for both MTBRT (ICC 0.903, p= 0.00) and sMTBRT (ICC 0.951, p= 0.00). Inter-rater reliability was also high (ICC 1.00, p= 0.00) for the MTBRT. For concurrent validity, correlation was moderate with TUG (r= -.559, p= 0.01), 4SST (r= -0.692, p= 0.001) and sMTBRT (r= 0.578, p= 0.009); but low with 5xSTS (r= -0.418, p= 0.084), ST (r= 0,420, p= 0.082), COPtotex (r= - 0.408, p= 0.093) and FRT (r= 0.424, p=0.08). Conclusions – Ten UGP research studies have provided pilot data exploring the reliability and validity of the MTBRT on a healthy population aged 20-59 years old. Results indicate that the measure is reliable in it standing and sitting forms. They show a moderate correlation with TUG, 4SST and sMTBRT, presently used with the older adult population and containing similar physical challenges as the MTBRT. These could now be tested with an older age population to test the MTBRT’s validity with that population

Artificial miRNAs Reduce Human Mutant Huntingtin Throughout the Striatum in a Transgenic Sheep Model of Huntington's Disease.

Huntington's disease (HD) is a fatal neurodegenerative disease caused by a genetic expansion of the CAG repeat region in the huntingtin (HTT) gene. Studies in HD mouse models have shown that artificial miRNAs can reduce mutant HTT, but evidence for their effectiveness and safety in larger animals is lacking. HD transgenic sheep express the full-length human HTT with 73 CAG repeats. AAV9 was used to deliver unilaterally to HD sheep striatum an artificial miRNA targeting exon 48 of the human HTT mRNA under control of two alternative promoters: U6 or CβA. The treatment reduced human mutant (m) HTT mRNA and protein 50-80% in the striatum at 1 and 6 months post injection. Silencing was detectable in both the caudate and putamen. Levels of endogenous sheep HTT protein were not affected. There was no significant loss of neurons labeled by DARPP32 or NeuN at 6 months after treatment, and Iba1-positive microglia were detected at control levels. It is concluded that safe and effective silencing of human mHTT protein can be achieved and sustained in a large-animal brain by direct delivery of an AAV carrying an artificial miRNA

HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn's Disease

Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.This article is freely available via Open Access. Click on Publisher URL to access the full-text

Proceedings from the Ice Hockey Summit III: Action on Concussion

Objectives The Ice Hockey Summit III provided updated scientific evidence on concussions in hockey to inform these five objectives: (1) describe sport related concussion (SRC) epidemiology, (2) classify prevention strategies, (3) define objective, diagnostic tests, (4) identify treatment and (5) integrate science and clinical care into prioritized action plans and policy. Methods Our action plan evolved from 40 scientific presentations. The 155 attendees (physicians, athletic trainers, physical therapists, nurses, neuropsychologists, scientists, engineers, coaches and officials) voted to prioritize these action items in the final Summit session. Results (1) establish a national and international hockey data base for SRCs at all levels; (2) eliminate body checking in Bantam youth hockey games; (3) expand a behavior modification program (Fair Play) to all youth hockey levels; (4) enforce game ejection penalties for fighting in Junior A and professional hockey leagues; (5) establish objective tests to diagnose concussion at point of care (POC); and (6) mandate baseline testing to improve concussion diagnosis for all age groups. Conclusions Expedient implementation of the Summit III prioritized action items is necessary to reduce the risk, severity and consequences of concussion in the sport of ice hockey

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms