Time for return to sport following total hip arthroplasty: a meta-analysis.

INTRODUCTION: Total Hip Arthroplasty (THA) is being increasingly undertaken in younger and more active patients, with many of these patients wanting to return to sport (RTS) after surgery. However, the percentage of patients RTS and time at which they are able to get back to sport following surgery remains unknown. The objective of this meta-analysis was to determine the time patients RTS after THA. METHODS: A search was performed on PUBMED, MEDLINE, EMBASE, and the Cochrane Library for trials on THA and RTS, in the English language, published from the inception of the database to October 2020. All clinical trials reporting on to RTS following THA were included. Data relating to patient demographics, methodological quality, RTS, clinical outcomes and complications were recorded. The PRISMA guidelines were used to undertake this study. RESULTS: The initial literature search identified 1720 studies. Of these, 11 studies with 2297 patients matched the inclusion criteria. 3 studies with 154 patients demonstrated an overall pooled proportion of 40.0% (95% CI, 32.5-47.9%) of patients RTS between 2 and 3 months after surgery. 4 studies with 242 patients demonstrated an overall pooled proportion of 76.9% (95% CI, 71.5-82.0) of patients RTS by 6 months after surgery. Pooled proportion analysis from 7 trials with 560 patients demonstrated 93.9% (95% CI, 82.7-99.5%) of patients RTS between 6 and 12 months after surgery. CONCLUSIONS: Pooled proportion analysis showed increasingly more patients were able to RTS after THA over the first 1 year after surgery. There remains marked inter and intra-study variations in time for RTS but the pooled analysis shows that over 90% of patients were able to RTS at 6-12 months after THA. These finding will enable more informed discussions between patients and healthcare professionals about time for RTS following THA.

Nanopatterned Titanium Implants Accelerate Bone Formation In Vivo.

Accelerated de novo formation of bone is a highly desirable aim of implants targeting musculoskeletal injuries. To date, this has primarily been addressed by biologic factors. However, there is an unmet need for robust, highly reproducible yet economic alternative strategies that strongly induce an osteogenic cell response. Here, we present a surface engineering method of translating bioactive nanopatterns from polymeric in vitro studies to clinically relevant material for orthopedics: three-dimensional, large area metal. We use a titanium-based sol-gel whereby metal implants can be engineered to induce osteoinduction both in vitro and in vivo. We show that controlled disordered nanotopographies presented as pillars with 15-25 nm height and 100 nm diameter on titanium dioxide effectively induce osteogenesis when seeded with STRO-1-enriched human skeletal stem cells in vivo subcutaneous implantation in mice. After 28 days, samples were retrieved, which showed a 20-fold increase in osteogenic gene induction of nanopatterned substrates, indicating that the sol-gel nanopatterning method offers a promising route for translation to future clinical orthopedic implants.

Indazole-6-phenylcyclopropylcarboxylic Acids as Selective GPR120 Agonists with in Vivo Efficacy.

GPR120 agonists have therapeutic potential for the treatment of diabetes, but few selective agonists have been reported. We identified an indazole-6-phenylcyclopropylcarboxylic acid series of GPR120 agonists and conducted SAR studies to optimize GPR120 potency. Furthermore, we identified a (S,S)-cyclopropylcarboxylic acid structural motif which gave selectivity against GPR40. Good oral exposure was obtained with some compounds displaying unexpected high CNS penetration. Increased MDCK efflux was utilized to identify compounds such as 33 with lower CNS penetration, and activity in oral glucose tolerance studies was demonstrated. Differential activity was observed in GPR120 null and wild-type mice indicating that this effect operates through a mechanism involving GPR120 agonism.

Long-term Evaluation of the "Get Fit for Active Living" Program.

This study examined six- and 12-month levels of adherence to physical activity, functional changes, and psychosocial determinants of physical activity in 176 older adults who participated in the "Get Fit for Active Living (GFAL)" pilot program. Functional and psychosocial measures were conducted in person at six months; psychosocial measures and physical activity participation were assessed by telephone interview at 12 months. Ninety-five per cent were retained in the study at the six-month follow-up, and 88 per cent at 12 months. The self-reported adherence rate to exercise at 12 months was 66 per cent. The main reason for continued exercise participation was to maintain health (45%). Reasons for nonadherence were illness (38%) and lack of motivation (32%). Results identify factors associated with positive behaviour change that health promoters can utilize when targeting the older adult population. The GFAL project results can serve as a model for sustainable, community-based older-adult exercise programs.

Analysis of Osteoclastogenesis/Osteoblastogenesis on Nanotopographical Titania Surfaces.

A focus of orthopedic research is to improve osteointegration and outcomes of joint replacement. Material surface topography has been shown to alter cell adhesion, proliferation, and growth. The use of nanotopographical features to promote cell adhesion and bone formation is hoped to improve osteointegration and clinical outcomes. Use of block-copolymer self-assembled nanopatterns allows nanopillars to form via templated anodization with control over height and order, which has been shown to be of cellular importance. This project assesses the outcome of a human bone marrow-derived co-culture of adherent osteoprogenitors and osteoclast progenitors on polished titania and titania patterned with 15 nm nanopillars, fabricated by a block-copolymer templated anodization technique. Substrate implantation in rabbit femurs is performed to confirm the in vivo bone/implant integration. Quantitative and qualitative results demonstrate increased osteogenesis on the nanopillar substrate with scanning electron microscopy, histochemical staining, and real-time quantitative reverse-transcription polymerase chain reaction analysis performed. Osteoblast/osteoclast co-culture analysis shows an increase in osteoblastogenesis-related gene expression and reduction in osteoclastogenesis. Supporting this in vitro finding, in vivo implantation of substrates in rabbit femora indicates increased implant/bone contact by ≈20%. These favorable osteogenic characteristics demonstrate the potential of 15 nm titania nanopillars fabricated by the block-copolymer templated anodization technique.

Osteoclastogenesis/osteoblastogenesis using human bone marrow-derived cocultures on nanotopographical polymer surfaces.

BACKGROUND: Optimised nanotopography with controlled disorder (NSQ50) has been shown to stimulate osteogenesis and new bone formation in vitro. Following osteointegration the implant interface must undergo constant remodeling without inducing immune response. AIM: We aimed to assess the effect of nanotopography on bone remodelling using osteoclast and osteoblast cocultures. MATERIALS & METHODS: We developed a novel osteoblast/osteoclast coculture using solely human bone marrow derived mesenchymal and hematopeotic progenitor cells without extraneous supplementation. The coculture was been applied to NSQ50 or flat control polycarbonate substrates and assessed using immunohistochemical and immunofluorescent microscopy, scanning electron microscopy and quantitative reverse-transcription PCR methods. RESULTS: These confirm the presence of mature osteoclasts, osteoblasts and bone formation in coculture. Osteoblast differentiation increased on NSQ50, with no significant difference in osteoclast differentiation. CONCLUSION: Controlled disorder nanotopography appears to be selectively bioactive. We recommend this coculture method to be a better in vitro approximation of the osseous environment encountered by implants.

Metal ion levels and revision rates in metal-on-metal hip resurfacing arthroplasty: a comparative study.

Metal-on-metal (MoM) bearings in hip surgery are related to increased blood levels of metal ions. The nature of the relationship between ion levels and failure is still not fully understood. This study compares three cohorts of patients, 120 patients in each cohort, treated with a hip resurfacing arthroplasty, grouped by brand and diameter of femoral component on average four years postoperatively: Birmingham Hip Resurfacing ≥50 mm, Durom resurfacing ≥50 mm and Durom resurfacing <50 mm. The median blood ion levels of cobalt and chromium were significantly lower in the cohort with the large Durom resurfacing than the other two cohorts (P<0.05). The large BHR and large Durom HRA had revision rates of 3.3%. The small Durom HRA had a revision rate of 8.3%. Elevated blood ion levels can indicate a failing MoM bearing. The large BHR and large Durom HRA have similar revision rates yet the large Durom HRA had significantly lower metal ion levels. When similar ion levels were reported for BHR and small Durom the latter had significantly higher revision rates. This suggests ion levels do not absolutely predict the rate of HRA failure. Since MoM generation of metal ions is not the sole reason of failure, regular clinical and radiographic follow-up should also be in place for patients with these joints.

Flexibility of older adults aged 55-86 years and the influence of physical activity.

Cross-sectional age-related differences in flexibility of older adults aged 55-86 years of varying activity levels were examined. Shoulder abduction and hip flexion flexibility measurements were obtained from 436 individuals (205 men, 71 ± 9 years; 231 women, 72 ± 8 years). Total physical activity was assessed using the Minnesota Leisure-Time Physical Activity Questionnaire. Shoulder abduction showed a significant decline averaging 5 degrees/decade in men and 6 degrees/decade in women. Piecewise linear regression showed an accelerated decline in men starting at the age of 71 years of 0.80 degrees/year, whereas in women the onset of decline (0.74 degrees/year) was 63 years. Men and women showed a significant decline in hip flexion (men: 6 degrees/decade; women: 7 degrees/decade). Piecewise linear regression revealed a rate of decline of 1.16 degrees/year beginning at 71 years in men and in women a single linear decline of 0.66 degrees/year. Multiple regression analysis showed that age and physical activity accounted for only 9% of the variance in hip flexion in women and 10% in men, with age but not physical activity remaining significant. Similarly for shoulder abduction, age was significant but not physical activity, in a model that described 8% of the variance for both sexes.

Physical activity-related injuries in older adults: a scoping review.

The purpose of this project is to conduct a comprehensive and systematic scoping review to identify and document the breadth of literature related to physical activity-related injuries in older adults. The population of interest was adults (both males and females) over the age of 65 years, participating in exercise, leisure-time, or sport-type physical activities. The initial search yielded 16,828 articles, with 43 articles ultimately included. The final 43 articles utilized the following study designs: three experimental (two randomized control and one non-randomized control), 14 prospective studies, and 26 retrospective. The results of this scoping review would suggest that it may be premature to provide definitive incidence rates, causes, and correlates of physical activity-related injuries in older adults. However, the current literature does not suggest that older adults are at an increased risk of injury from participation in physical activities. Future research should utilize a consistent definition of 'injury' and consistent and comprehensive descriptors of injuries--including intensity level of engagement of activity and burden/severity of injury. In addition, injury rates in specific populations are needed, particularly for the oldest-old, for those in assisted-living situations, and for subgroups with clinical conditions. Finally, greater surveillance and documentation of older adult initiatives and interventions are needed in order to identify programs successful in reducing the injury rates of their target populations.

A 12-month incidence of exercise-related injuries in previously sedentary community-dwelling older adults following an exercise intervention.

OBJECTIVES: Fear of injury is reported as a barrier to exercise by older adults. However, the literature is limited in describing exercise injuries in older adults. DESIGN: This study prospectively evaluated the 12-month incidence of exercise-related injuries to community-dwelling older adults (n=167 respondents; 63 men, 104 women; mean age 69±5 year). METHODS: A questionnaire developed for use in older adults was administered to document self-reported injuries. Linear regression analysis was conducted to identify covariates related to injury outcomes. RESULTS: 23 people (14%) reported injuries. 41% of injuries were to the lower extremities, where the most common type was overuse muscle strains (32%, n=7). Overexertion was the most common cause of injury (n=9) and walking accounted for half of the activities during which injury occurred. 70% of injuries required medical treatment. 44% were not able to continue exercising after injury and return-to-activity time varied from 1 to 182 days. Sex, age and exercise volume were not significantly associated with injury occurrence. CONCLUSIONS: These results showed similar, or lower, exercise-related injury rates as compared with previous reports on younger and middle-aged adults; however, the definition of, and criteria for, 'injury' reporting varies in the literature. This study indicates that older adults taking up exercise are not at increased risk of injury versus younger age groups.

Developments in stem cells: implications for future joint replacements.

Will stem cell research reverse the projected sevenfold increase in primary and revision knee replacements expected in the United States between 2005 and 2030? A focus on prevention and treatment of osteoarthritis may end the need for primary joint replacements. A more likely scenario can be described as slow and incremental changes in the prevention and treatment of osteoarthritis, accompanied by the continuing development of implant technology. Since the discovery of stem cells in the 1950s, research has increased exponentially. Expanded autologous chondrocytes, and more recently ex vivo expanded skeletal stem cells, are currently injected into osteochondral defects in the hope of regenerating cartilage and halting progression towards osteoarthritis. In addition, mesenchymal stem cells are being injected into human joints as a treatment for osteoarthritis despite a lack of quantitative research. Concurrently, stem cell research continues to contribute to chemical and topographical advancements in implant design. Advances in co-culture techniques mean it is possible that biologic articular replacements will develop prior to the cessation of the need for arthroplasty and radically change the nature of joint replacements. Whether it is through implant design or a potential cure for the pain attributable to osteoarthritis, as we hope to show in this 'forward look article', it is our opinion that stem cells will certainly impact future joint replacement.

A positive hip arthrogram may predict lower function in patients with primary hip arthroplasty.

BACKGROUND: A local anesthetic hip arthrogram is a simple test mainly used as an adjunct to define the origin of hip pain. Temporary pain relief (a positive response) following an injection may lead to a surgeon recommending hip surgery. However, it is unclear whether relief of pain corresponds to better postoperative pain relief or function. QUESTIONS/PURPOSES: We therefore compared the function in patients with a positive response to a local anesthetic hip arthrogram who underwent primary THA and patients with typical osteoarthritis presentation who underwent primary THA without a preoperative arthrogram. METHODS: We retrospectively reviewed 22 patients who had a positive response to a local anesthetic hip arthrogram who subsequently underwent primary hip arthroplasty and a control group of 74 patients who had typical osteoarthritis hip pain and subsequent primary hip arthroplasty without having a previous arthrogram. All patients completed the Oxford Hip Score, WOMAC™ function short form, and the SF-12 preoperatively and at regular clinical followups. The minimum followups were 28 months (mean, 42 months; range, 28-72 months) for the study group and 33 months (mean, 52 months; range, 33-73 months) for the control group. RESULTS: Patients in the arthrogram group had lower mean functional scores: 30 versus 39 for the Oxford Hip Score, 39 versus 46 for the WOMAC™, and 36 versus 42 for the physical component of the SF-12. CONCLUSIONS: Preoperative use of a local anesthetic hip arthrogram remains an important tool to differentiate spinal disorders or confirm the hip as the cause of pain. However, patients who have a preoperative hip arthrogram to clarify symptoms may report a lower function score and pain relief than patients who do not.

Flexibility training and functional ability in older adults: a systematic review.

Background. As indicated in a recent systematic review relating to Canada's Physical Activity Guidelines for Older Adults, exercise interventions in older adults can maintain or improve functional abilities. Less is known about the role of flexibility in the maintenance or improvement of functional abilities, and there currently does not exist a synthesis of the literature supporting a consensus on flexibility training prescription. Purpose. To systematically review the effects of flexibility-specific training interventions on measures of functional outcomes in healthy older adults over the age of 65 years. Methods. Five electronic databases were searched for intervention studies involving concepts related to aging, flexibility, functional outcomes, and training interventions. After evaluating the articles for relevance, 22 studies were considered. Results. The results suggested that while flexibility-specific interventions may have effects on range of motion (ROM) outcomes, there is conflicting information regarding both the relationship between flexibility interventions and functional outcomes or daily functioning. Conclusions. Due to the wide range of intervention protocols, body parts studied, and functional measurements, conclusive recommendations regarding flexibility training for older adults or the validity of flexibility training interventions as supplements to other forms of exercise, or as significant positive influences on functional ability, require further investigation.

A candidate for Lr19, an exotic gene conditioning leaf rust resistance in wheat.

Lr19, one of the few widely effective genes conferring resistance to leaf rust in wheat, was transferred from the wild relative Thinopyrum ponticum to durum wheat. Since Lr19 confers a hypersensitive response to the pathogen, it was considered likely that the gene would be a member of the major nucleotide-binding site (NBS)-leucine-rich repeat (LRR) plant R gene family. NBS profiling, based on PCR amplification of conserved NBS motifs, was applied to durum wheat-Th. ponticum recombinant lines involving different segments of the alien 7AgL chromosome arm, carrying or lacking Lr19. Differential PCR products were isolated and sequenced. From one such sequence (AG15), tightly linked to Lr19, a 4,121-bp full-length cDNA was obtained. Its deduced 1,258 amino acid sequence has the characteristic NBS-LRR domains of plant R gene products and includes a coiled-coil (CC) region typical of monocots. The genomic DNA sequence showed the presence of two exons and a short intron upstream of the predicted stop codon. Homology searches revealed considerable identity of AG15 with the cloned wheat resistance gene Pm3a and a lower similarity with wheat Lr1, Lr21, and Lr10. Quantitative PCR on leaf-rust-infected and non-infected Lr19 carriers proved AG15 to be constitutively expressed, as is common for R genes.

Homoeologous gene silencing in tissue cultured wheat callus.

BACKGROUND: In contrast to diploids, most polyploid plant species, which include the hexaploid bread wheat, possess an additional layer of epigenetic complexity. Several studies have demonstrated that polyploids are affected by homoeologous gene silencing, a process in which sub-genomic genomic copies are selectively transcriptionally inactivated. This form of silencing can be tissue specific and may be linked to developmental or stress responses. RESULTS: Evidence was sought as to whether the frequency of homoeologous silencing in in vitro cultured wheat callus differ from that in differentiated organs, given that disorganized cells are associated with a globally lower level of DNA methylation. Using a reverse transcription PCR (RT-PCR) single strand conformation polymorphism (SSCP) platform to detect the pattern of expression of 20 homoeologous sets of single-copy genes known to be affected by this form of silencing in the root and/or leaf, we observed no silencing in any of the wheat callus tissue tested. CONCLUSION: Our results suggest that much of the homoeologous silencing observed in differentiated tissues is probably under epigenetic control, rather than being linked to genomic instability arising from allopolyploidization. This study reinforces the notion of plasticity in the wheat epi-genome.

Variation for homoeologous gene silencing in hexaploid wheat.

The absence of expression of individual members of a homoeologous set of genes in a polyploid is a well-established phenomenon. However, the extent to which such 'homoeologous silencing' can vary between individual genotypes within a species is unexplored. We have used the single-strand conformation polymorphism assay to identify homoeologue non-expression at 15 single-copy genes across a panel of 16 wheat varieties, representative of the genetic diversity present in modern northern European winter wheat (Triticum aestivum). There was no evidence for any homoeologous silencing at seven of the fifteen genes, but in the remaining eight, at least one of the three homoeologues varied qualitatively for expression in either the root or the seedling leaf. The identity of the non-expressed homoeologue was generally consistent, but when the expression profiles of eight informative genes were compared, only two varieties shared the same pattern of silencing. A small-scale study suggested that silencing patterns were largely inherited across self-pollinated generations, and some evidence is presented for the epigenetic segregation of these patterns in a population bred from parents having contrasting silencing profiles. Epigenetic variation exerts a significant effect on phenotype, so given the ubiquity and variability in homoeologous silencing observed in wheat, we suggest that it is likely to play a considerable role in generating phenotypic variation. Thus epigenetic profiling may need to be incorporated as part of the analytical tool kit for predictive wheat breeding.

Powdery mildew resistance in 155 Nordic bread wheat cultivars and landraces.

The occurrence and distribution of seedling resistance genes and the presence of adult plant resistance to powdery mildew, was investigated in a collection of 155 Nordic bread wheat landraces and cultivars by inoculation with 11 powdery mildew isolates. Eighty-nine accessions were susceptible in the seedling stage, while 66 accessions showed some resistance. Comparisons of response patterns allowed postulation of combinations of genes Pm1a, Pm2, Pm4b, Pm5, Pm6, Pm8 and Pm9 in 21 lines. Seedling resistance was three times more frequent in spring wheat than in winter wheat. The most commonly postulated genes were Pm1a+Pm2+Pm9 in Sweden, Pm5 in Denmark and Norway, and Pm4b in Finland. Forty-five accessions were postulated to carry only unidentified genes or a combination of identified and unidentified genes that could not be resolved by the 11 isolates. Complete resistance to all 11 isolates was present in 18 cultivars. Adult plant resistance was assessed for 109 accessions after natural infection with a mixture of races. In all, 92% of the accessions developed less than 3-5% pathogen coverage while nine lines showed 10-15% infected leaf surface. The characterization of powdery mildew resistance in Nordic wheat germplasm could facilitate the combination of resistance genes in plant breeding programmes to promote durability of resistance and disease management.

Quantification of the tissue-culture induced variation in barley (Hordeum vulgare L.).

BACKGROUND: When plant tissue is passaged through in vitro culture, many regenerated plants appear to be no longer clonal copies of their donor genotype. Among the factors that affect this so-called tissue culture induced variation are explant genotype, explant tissue origin, medium composition, and the length of time in culture. Variation is understood to be generated via a combination of genetic and/or epigenetic changes. A lack of any phenotypic variation between regenerants does not necessarily imply a concomitant lack of genetic (or epigenetic) change, and it is therefore of interest to assay the outcomes of tissue culture at the genotypic level. RESULTS: A variant of methylation sensitive AFLP, based on the isoschizomeric combinations Acc65I/MseI and KpnI/MseI was applied to analyze, at both the sequence and methylation levels, the outcomes of regeneration from tissue culture in barley. Both sequence mutation and alteration in methylation pattern were detected. Two sets of regenerants from each of five DH donor lines were compared. One set was derived via androgenesis, and the other via somatic embryogenesis, developed from immature embryos. These comparisons delivered a quantitative assessment of the various types of somaclonal variation induced. The average level of variation was 6%, of which almost 1.7% could be accounted for by nucleotide mutation, and the remainder by changes in methylation state. The nucleotide mutation rates and the rate of epimutations were substantially similar between the andro- and embryo-derived sets of regenerants across all the donors. CONCLUSION: We have developed an AFLP based approach that is capable of describing the qualitative and quantitative characteristics of the tissue culture-induced variation. We believe that this approach will find particular value in the study of patterns of inheritance of somaclonal variation, since non-heritable variation is of little interest for the improvement of plant species which are sexually propagated. Of significant biological interest is the conclusion that the mode of regeneration has no significant effect on the balance between sequence and methylation state change induced by the tissue culture process.

21st century wheat breeding: plot selection or plate detection?

The publicly reported limited application of marker-assisted selection (MAS) in wheat breeding programmes to date is reviewed and contrasted with the current situation, in which it has increasingly become technically feasible to tag almost any gene with a microsatellite assay. Although this capability is starting to have an impact on the conduct of large breeding programmes, a much more profound change in breeding strategy will become possible when single nucleotide polymorphism (SNP) technology has matured sufficiently so that the throughput of molecular marker-based genotyping is able to keep pace with the numbers of plants that breeders routinely handle in the field. We explore the extent to which the genomics revolution might generate a change in the conventional breeding paradigm, which has operated with such success for the best part of the 20th century, and identify the need for a substantial reduction in assay price before MAS is likely to make more than a marginal impact on present practice.