Spinocerebellar ataxia type 1 (SCA1) is a dominant neurodegenerative disease caused by the expression of mutant ataxin-1 containing an expanded polyglutamine tract. Ataxin-1 is a nuclear protein that localizes to punctate inclusions similar to neuronal nuclear inclusions seen in many polyglutamine expansion disease proteins. We demonstrate that ataxin-1 localization to inclusions and inclusion dynamics within the nucleus are RNA and transcription dependent, but not dependent on the polyglutamine tract. Ataxin-1 nuclear inclusions are distinct from other described nuclear bodies but recruit the mRNA export factor, TAP/NXF1, in a manner that is enhanced by cell heat shock. By FRAP protein dynamic studies in live cells, we found that wild-type, but not mutant, ataxin-1 was capable of nuclear export. These results suggest that the normal role of ataxin-1 may be in RNA processing, perhaps nuclear RNA export. Thus, nuclear retention of mutant ataxin-1 may be an important toxic gain of function in SCA1 disease.

Background: The Functional Movement Screen (FMS) is used to predict individuals at heightened risk of injury within sports such as American Football. However, the relationship between the FMS and injury within football (a.k.a. soccer) has yet to be quantified. The current literature does not allude to whether the FMS has a role in predicting injury within this sport specific group. Objective: To evaluate the association between the 7 FMS tasks and the incidence of non-contact injury amongst football players from a professional English football club over one season. Methods: 135 footballers between the ages of 8 and 21 years from one professional football club's academy were used. Players performed the FMS and then were observed throughout the study period to record and establish injury incidence in rates per 1000 training and match hours. Results: The deep squat (p=0.0128) and trunk stability push-up (p=0.0621) were significant predictors of non-contact injury. Players with a trunk stability push up score of 3 had a statistically significant lower risk of injury than those with a score of 1. There was a similar trend for players with a trunk stability push up score of 2, but this was not statistically significant. Total FMS score was not statistically significantly related to injury. Conclusion: There appears to be only statistically significant associations between 2 of the 7 FMS components and non-contact injury incidence within youth players from one professional football clubs' academy. Further investigations need to be conducted to see whether these results reflect the academy football population within the English academy programme.

Prosthetics increase the risk of deep surgical site infections in procedures intended to restore function. In orthopaedics, prosthetic joint infections can lead to repetitive surgeries, amputation, or worse. Biofilm formation both in vitro and in vivo involves stages of attachment, accumulation, and maturation. The level of maturation affects susceptibility to antibiotics, the immune system, and the success of surgical interventions. A review of the literature indicates that orthopedic publications are less likely to mention biofilm. We have reviewed animal models of infection to assess in vivo models of prosthetic infection. Although most prosthetic infections seem to originate from local skin microbiota, clinically representative biofilm inocula are unusual. Biofilm-related end points are more widely adopted, but studies rarely include both quantification of adherent microbial burden and imaging of the in vivo biofilm. Failure to differentiate between planktonic and biofilm infections can skew research away from needed chronic disease models. In this review, we address prosthetic joint infections as an important model for chronic biofilm infection research, identify critical requirements for in vivo models of chronic infection, and propose that resistance to the terminology of biofilm research exists within both research and regulation, which could limit progress toward important orthopaedic targets.

Prosthetic joint infection (PJI) is a rare but devastating complication of joint arthroplasty. Biofilm formation around the prosthesis confers tolerance to antibiotics so that treatment is challenging. Most animal models of PJI use planktonic bacteria to establish the infection which fails to reproduce the pathology of chronic infection. We aimed to establish a rat model of Staphylococcus aureus PJI in male Sprague–Dawley rats using biofilm inocula and demonstrate its tolerance to frontline antibiotics. Pilot studies indicated that infection could be introduced to the knee joint by a biofilm‐coated pin but that handling the prosthetic without disturbing the biofilm was difficult. We, therefore, developed a pin with a slotted end and used a miniature‐biofilm reactor to develop mature biofilm in this niche. These biofilm‐laden pins consistently produced infection of the bone and joint space. Treatment with high dose cefazolin, 250 mg/kg, starting the day of surgery reduced or cleared pin‐adherent bioburden within 7 days, however when escalation from 25 to 250 mg/kg cefazolin treatment was delayed for 48 h, rats were unable to clear the infection. To track infections, we used bioluminescent bacteria, however, the bioluminescent signal did not accurately track the degree of infection in the bone and joint space as the signal did not penetrate the bone. In conclusion, we demonstrate that using a custom prosthetic pin, we can generate biofilm in a specific niche using a novel bioreactor setup and initiate a rat PJI that rapidly develops tolerance to supra‐clinical doses of cefazolin.

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