Combined effects of fire and drought are not sufficient to slow shrub encroachment in tallgrass prairie.

Woody encroachment-the spread of woody vegetation in open ecosystems-is a common threat to grasslands worldwide. Reversing encroachment can be exceedingly difficult once shrubs become established, particularly clonal species that resprout following disturbance. Single stressors are unlikely to reverse woody encroachment, but using multiple stressors in tandem could be successful in slowing or reversing encroachment. We explored whether increasing fire frequency in conjunction with multi-year drought could reduce growth and survival of encroaching shrubs in a tallgrass prairie in northeastern Kansas, USA. Passive rainout shelters (~ 50% rainfall reduction) were constructed over mature clonal shrubs (Cornus drummondii) and co-existing C4 grasses in two fire treatments (1-year and 4-year burn frequency). Leaf- and whole-plant level physiological responses to drought and fire frequency were monitored in shrubs and grasses from 2019 to 2022. Shrub biomass and stem density following fire were unaffected by five years of consecutive drought treatment, regardless of fire frequency. The drought treatment had more negative effects on grass leaf water potential and photosynthetic rates compared to shrubs. Shrub photosynthetic rates were remarkably stable across each growing season. Overall, we found that five consecutive years of moderate drought in combination with fire was not sufficient to reduce biomass production or stem density in an encroaching clonal shrub (C. drummondii). These results suggest that moderate but chronic press-drought events do not sufficiently stress encroaching clonal shrubs to negatively impact their resilience following fire events, even when fire frequency is high.

Physical function and physical activity in adults with X-linked hypophosphatemia.

We described physical function and activity in UK adults with X-linked hypophosphatemia (XLH). Our data indicate that low physical activity and impaired mobility are common in adults with XLH. Deficits in lower limbs muscle power and functional capacity contribute to the loss of physical function in adults with XLH. INTRODUCTION: There is a dearth of literature on physical function and physical activity in adults with X-linked hypophosphatemia (XLH). We described muscle strength and power, functional capacity, mobility and physical activity level and explored the relationships among these variables in adults with XLH. METHODS: Participants were recruited as part of a UK-based prospective cohort study, the RUDY Study. They underwent a clinical visit and physical examination, including assessment of handgrip strength, jump power (mechanography), six-minute walk test (6MWT) and short physical performance battery (SPPB), and completed the International Physical Activity Questionnaire (IPAQ). Performance data were analysed using parametric and non-parametric tests, whereas correlations were assessed by univariate analysis. RESULTS: Twenty-six adults with XLH (50% males) with a mean age of 44 ± 16.1 years were recruited. Jump power and 6MWT distances (p < 0.0001) were 54.4% and 38.6% lower respectively in individuals with XLH compared with normative values. These deficits were not associated with age or sex. Handgrip strength values were similar to expected values. Deficits in muscle power were more pronounced than those reported at 6MWT (p < 0.0001). Univariate analysis revealed only a correlation between total physical activity and muscle power (r = 0.545, p = 0.019). CONCLUSIONS: Adults with XLH have a marked deficit in lower limb muscle power and a reduced functional capacity, with a high incidence of impaired mobility and inactivity. In addition to metabolic effects of XLH, low physical activity may contribute to deficits in lower limb power. Further studies are required to develop novel treatment approaches to improve physical function and mobility.

Adult North Star Network (ANSN): Consensus Guideline For The Standard Of Care Of Adults With Duchenne Muscular Dystrophy.

There are growing numbers of adults with Duchenne Muscular Dystrophy living well into their fourth decade. These patients have complex medical needs that to date have not been addressed in the International standards of care. We sought to create a consensus based standard of care through a series of multi-disciplinary workshops with specialists from a wide range of clinical areas: Neurology, Cardiology, Respiratory Medicine, Gastroenterology, Endocrinology, Palliative Care Medicine, Rehabilitation, Renal, Anaesthetics and Clinical Psychology. Detailed reports of evidence reviewed and the consensus building process were produced following each workshop and condensed into this final document which was approved by all members of the Adult North Star Network including service users. The aim of this document is to provide a framework to improve clinical services and multi-disciplinary care for adults living with Duchenne Muscular Dystrophy.

Burden of disease associated with X-linked hypophosphataemia in adults: a systematic literature review.

This systematic review collated evidence on the burden of XLH in adults. Data captured highlight the substantial ongoing burden of XLH in adulthood and identified unmet needs. Greater awareness and understanding of the impact of XLH in adulthood are needed to improve care and outcomes in adults with XLH. INTRODUCTION: X-linked hypophosphataemia (XLH) is a rare metabolic bone disease characterized by renal phosphate wasting and musculoskeletal manifestations. Whilst the disease's impact in children is well documented, information on the effects of this progressive, debilitating condition on adults is lacking. This systematic review aimed to collate existing evidence on the burden of XLH in adulthood to identify unmet needs. METHODS: MEDLINE, Embase and Cochrane Library databases and recent congress reports were searched on 19 February 2019 for English-language publications describing the medical, humanistic and socio-economic impact of XLH in adults (≥ 18 years old). In addition, a structured Internet search was conducted. RESULTS: Of the 2351 articles identified, 91 met the selection criteria along with 44 congress abstracts. Data show that adults with XLH experience a range of clinical manifestations, particularly skeletal deformities and (pseudo)fractures, along with pain, dental abnormalities and impaired physical function and mobility. XLH in adulthood impacts on quality of life and places limitations on daily activities. The level of healthcare resource utilization among adults with XLH is indicative of substantial socio-economic burden; further research is needed to quantitate the economic impact on the healthcare system, society and patients. Adults with XLH may not receive appropriate care and treatment; a possible explanation for this is a lack of awareness among healthcare professionals. CONCLUSION: XLH in adults is associated with considerable disease burden and unmet needs. Forthcoming studies and increased awareness of the impact of XLH in adulthood should help to improve management of XLH in adulthood and patient outcomes.

The effect of vitamin D supplementation on knee osteoarthritis, the VIDEO study: a randomised controlled trial.

OBJECTIVE: Epidemiological data suggest low serum 25-hydroxyvitamin D3 (25-OH-D3) levels are associated with radiological progression of knee osteoarthritis (OA). This study aimed to assess whether vitamin D supplementation can slow the rate of progression. METHOD: A 3-year, double-blind, randomised, placebo-controlled trial of 474 patients aged over 50 with radiographically evident knee OA comparing 800 IU cholecalciferol daily with placebo. Primary outcome was difference in rate of medial joint space narrowing (JSN). Secondary outcomes included lateral JSN, Kellgren & Lawrence grade, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, function, stiffness and the Get up and Go test. RESULTS: Vitamin D supplementation increased 25-OH-D3 from an average of 20.7 (standard deviation (SD) 8.9) µg/L to 30.4 (SD 7.7) µg/L, compared to 20.7 (SD 8.1) µg/L and 20.3 (SD 8.1) µg/L in the placebo group. There was no significant difference in the rate of JSN over 3 years in the medial compartment of the index knee between the treatment group (average -0.01 mm/year) and placebo group (-0.08 mm/year), average difference 0.08 mm/year (95% confidence interval (CI) [-0.14-0.29], P = 0.49). No significant interaction was found between baseline vitamin D levels and treatment effect. There were no significant differences for any of the secondary outcome measures. CONCLUSION: Vitamin D supplementation did not slow the rate of JSN or lead to reduced pain, stiffness or functional loss over a 3-year period. On the basis of these findings we consider that vitamin D supplementation has no role in the management of knee OA.

Changes in the structural and material properties of the tibia in patients with spinal cord injury.

STUDY DESIGN: A cross-sectional study. OBJECTIVES: To measure the change of structural and material properties at different sites of the tibia in spinal cord-injured patients using peripheral quantitative computerised tomography (pQCT). SETTING: Orthopaedic research centre (UK). METHODS: Thirty-one subjects were measured--eight with acute spinal cord injury (SCI), nine with chronic SCI and fourteen able-bodied controls. pQCT scans were performed at 2% (proximal), 34% (diaphyseal) and 96% (distal) along the tibia from the tibial plateau. Structural measures of bone were calculated, and volumetric bone mineral density (vBMD) was also measured at all three levels. Muscle cross-sectional area was measured at the diaphyseal level. RESULTS: Structurally, there were changes in the cortical bone; in the diaphysis, the shape of the cross-section changed to offer less resistance to AP bending, and the cross-sectional area of the cortical shell decreased both proximally and distally. There were corresponding changes in vBMD in the anterior aspect of the cortical diaphysis, as well as proximal and distal trabecular bone. Changes in muscle occurred more rapidly than changes in bone. CONCLUSION: There were clear changes of both structure and material at all three levels of the tibia in chronic SCI patients. These changes were consistent with specific adaptations to reduced local mechanical loading conditions. To assess fracture risk in SCI and also to monitor the effect of therapeutic interventions, the structure of the bone should be considered in addition to trabecular bone mineral density.

Early treatment with zoledronic acid prevents bone loss at the hip following acute spinal cord injury.

UNLABELLED: Osteoporosis after spinal cord injury is common. Reductions in bone density are rapid and fracture rates are higher after injury. Early treatment with 4 mg zoledronic acid significantly reduced bone loss at the hip compared to untreated individuals in the first year. Treatment appeared safe and well tolerated. INTRODUCTION: Bone mineral density (BMD) is lost rapidly following spinal cord injury (SCI), predominantly in the lower limbs. Bone turnover markers suggest an early increase in resorption. METHODS: A randomised, open-label study of 14 patients with acute SCI randomised to receive 4 mg IV zoledronic acid or standard treatment. BMD was measured by dual-X-ray absorptiometry at the lumbar spine and hip (femoral neck, total and trochanter) at baseline, 3, 6 and 12 months. Bone turnover markers (serum C-terminal telopeptide and Procollagen I N-terminal peptide and urinary N-terminal telopeptide/Cr ratio) were also measured. RESULTS: After 12 months, there was a significant difference in BMD between the groups at the total hip (12.4%, p = 0.005), trochanter (13.4%, p = 0.028) and lumbar spine (2.7%, p = 0.033). However, the difference between groups at the femoral neck was not significant (4.8%, p = 0.741). In the treated group, bone resorption was reduced and remained reduced up to 12 months. Other than flu-like symptoms immediately after the infusion, no adverse events were observed. CONCLUSION: IV zoledronic acid is an effective and well-tolerated treatment to prevent bone mineral density loss at the total hip and trochanter for up to 12 months following SCI.

Insights into the genetic architecture of osteoarthritis from stage 1 of the arcOGEN study.

OBJECTIVES: The genetic aetiology of osteoarthritis has not yet been elucidated. To enable a well-powered genome-wide association study (GWAS) for osteoarthritis, the authors have formed the arcOGEN Consortium, a UK-wide collaborative effort aiming to scan genome-wide over 7500 osteoarthritis cases in a two-stage genome-wide association scan. Here the authors report the findings of the stage 1 interim analysis. METHODS: The authors have performed a genome-wide association scan for knee and hip osteoarthritis in 3177 cases and 4894 population-based controls from the UK. Replication of promising signals was carried out in silico in five further scans (44,449 individuals), and de novo in 14 534 independent samples, all of European descent. RESULTS: None of the association signals the authors identified reach genome-wide levels of statistical significance, therefore stressing the need for corroboration in sample sets of a larger size. Application of analytical approaches to examine the allelic architecture of disease to the stage 1 genome-wide association scan data suggests that osteoarthritis is a highly polygenic disease with multiple risk variants conferring small effects. CONCLUSIONS: Identifying loci conferring susceptibility to osteoarthritis will require large-scale sample sizes and well-defined phenotypes to minimise heterogeneity.

Anatomical distribution of synovitis in knee osteoarthritis and its association with joint effusion assessed on non-enhanced and contrast-enhanced MRI.

PURPOSE: To describe the anatomical distribution of synovitis and its association with joint effusion on non-enhanced and contrast-enhanced (CE) MRI in patients with knee osteoarthritis (OA). METHODS: Baseline MRI was performed at 1.5T using axial proton density (PD)-weighted (w) fat suppressed (fs) and axial and sagittal T1-w fs CE sequences. Synovial enhancement was scored in nine articular subregions. Maximum synovial enhancement was grouped as absent (0), equivocal (1) and definite (2 and 3). Effusion was scored from 0 to 3 on the axial sequences. We described the anatomical distribution of synovitis, its association with effusion and compared assessment of effusion on T1-w fs CE and PD fs sequences. RESULTS: 111 subjects were included and examined by MRI. 89.2% of knees exhibited at least one subregion with a minimum grade 2 and 39.6% at the maximum of a grade 3. The commonest sites for definite synovitis were posterior to the posterior cruciate ligament (PCL) in 71.2% and in the suprapatellar region in 59.5% of all knees. On T1-w fs CE, 73.0% of knees showed any effusion. Definite synovitis in at least one location was present in 96.3% knees with an effusion and in 70.0% without an effusion. Higher grades of effusion were scored on the PD fs sequence. CONCLUSION: Definite synovitis was present in the majority of knees with or without effusion with the commonest sites being posterior to the PCL and in the suprapatellar recess. Joint effusion as measured on PD fs images does not only represent effusion but also synovial thickening.

Vitamin D deficiency in patients with osteoarthritis undergoing total hip replacement: a cause for concern?

We measured the plasma 25-hydroxyvitamin D(3) (25(OH)D(3)) levels in 62 consecutive Caucasian patients undergoing total hip replacement for osteoarthritis. The patients were divided into two groups based on whether they were vitamin D sufficient or deficient. The groups were matched for age, gender and the American Society of Anaesthesiologists (ASA) grade. The prevalence of vitamin D deficiency in our patients was comparable with recent population-based studies performed in the United Kingdom. Patients with vitamin D deficiency had lower pre-operative Harris hip scores (Mann-Whitney test, p = 0.018) and were significantly less likely to attain an excellent outcome from total hip replacement (chi-squared test, p = 0.038). Vitamin D levels were found to positively correlate with both pre- and post-operative Harris hip scores. These results warrant further study of vitamin D deficiency in patients undergoing joint replacement as it is a risk factor for a suboptimal outcome which is relatively simple and cheap to correct.

Cross-calibration of dual-energy X-ray densitometers for a large, multi-center genetic study of osteoporosis.

Osteoporosis is a common disease with a strong genetic component characterized by reduced bone mass and an increased risk of fragility fractures. Bone mineral density (BMD) is the most important determinant of osteoporotic fracture risk, but the genes responsible for BMD regulation and fracture are incompletely defined. To enable multi-center studies to examine the genetic influences on BMD there is a requirement to standardize measurements across different manufacturers of bone densitometers, different versions of machines and different normative ranges. This paper describes a method developed to allow near-identical subjects with low age-adjusted BMD (based on Z-scores) to be recruited in 17 centers using 27 different densitometers. Cross-calibration was based on measurements using a European spine phantom circulated to all centers and measured ten times on each individual machine. From theses values an individual exponential curve, based on nominal versus observed BMD, was derived for each machine. As expected, there were large and significant variations in nominal BMD values, not only between scanners from different manufacturers but also between different versions of scanners from the same manufacturer. Hologic scanners tended to underestimate the nominal BMD, while Lunar scanners overestimated the value. Norland scanners gave mixed values over estimating BMD at the lower nominal value (0.5 g/cm2) while underestimating the value at the higher value (1.5 g/cm2). The validity of the exponential equations was tested using hip and spine measurements on 991 non-proband women from a familial osteoporosis study (FAMOS). After cross-calibration there was a considerable reduction in variation between machines. This observation, coupled with the absence of a similar reduction in variation attributable to a linear regression on age, demonstrated the validity of the cross-calibration approach. Use of the cross-calibration curves along with a standard normative range (in the case of this study, the Hologic normative range) allowed age-specific Z-scores to be used as an inclusion criterion in this genetic study, a method that will be useful for other trials where age-specific BMD inclusion criteria are required.

The genetic causes of basal ganglia calcification, dementia, and bone cysts: DAP12 and TREM2.

BACKGROUND: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), or Nasu-Hakola disease, is a presenile dementia associated with loss of myelin, basal ganglia calcification, and bone cysts. It is caused by recessively inherited mutations in two genes encoding subunits of a cell membrane-associated receptor complex: TREM2 and DAP12. The clinical course of PLOSL has not been characterized in a series of patients with TREM2 mutations. METHODS: The authors compare neurologic and neuroradiologic follow-up data of six patients carrying TREM2 mutations with PLOSL due to defective DAP12 genes. The authors review the known mutations in these two genes. RESULTS: Mutations in DAP12 and TREM2 result in a uniform disease phenotype. In Finnish and Japanese patients with PLOSL, DAP12 mutations predominate, whereas TREM2 is mutated more frequently elsewhere. CONCLUSIONS: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy should be considered in adult patients under age 50 years with dementia and basal ganglia calcification. Radiographs of ankles and wrists, and DNA test in uncertain cases, confirm the diagnosis.

Size at birth, adult intestinal calcium absorption and 1,25(OH)(2) vitamin D.

BACKGROUND: Adult bone mineral status is modified by early environmental influences, but the mechanism of this phenomenon is unknown. Intestinal calcium absorption and vitamin D metabolism are integrally involved in bone metabolism and may be programmed during early life. AIM: To examine the early-life influences on calcium absorption and its control in 322 post-menopausal female twins. METHODS: Intestinal calcium absorption was assessed by the stable strontium (Sr) method. Serum PTH, 25(OH) and 1,25(OH)(2) vitamin D were measured and recalled birth weight recorded. RESULTS: Fractional intestinal Sr absorption (alpha Sr) was correlated with serum 1,25(OH)(2) vitamin D (p<0.001), but not with 25(OH) vitamin D. Birth weight was inversely associated with serum 1,25(OH)(2) vitamin D (p=0.04), the association being independent of serum calcium, phosphate, creatinine and PTH. Birth weight was inversely correlated with alpha Sr (p=0.03), this association being independent of age, season, customary calcium intake and serum 25(OH) vitamin D; however, when serum 1,25(OH)(2) vitamin D was added into the model, the association became non-significant, suggesting that the association was partially mediated via serum 1,25(OH)(2) vitamin D. DISCUSSION: We found a significant inverse association between birth weight and intestinal calcium absorption that is partially explained by an association between serum 1,25(OH)(2) vitamin D and birth weight. This suggests a mechanism whereby the intra-uterine environment might affect adult skeletal status.

The cost-effectiveness of exclusion arteriography in extremity trauma.

The purpose of this study was to apply decision analysis to an established practice in vascular trauma diagnosis. While exclusion arteriography has resulted in an increase in positive surgical explorations, no formal analysis that determined either the cost-effectiveness of exclusion arteriography or the cost-effectiveness ratio has been reported in the literature. We created a decision model that compared exclusion arteriography and surgical exploration, the standard used prior to the development of extremity arteriography. The decision model used predominantly literature derived estimates for the prevalence of arterial injuries and the accuracy, complications, outcomes and costs of both arteriography and exploration. Exclusion arteriography is cost-effective. This finding is robust to changes in the major model variables. Compared to surgical exploration, exclusion arteriography is a superior strategy by dominance (more effective and costs less). Therefore, a cost-effectiveness ratio cannot be calculated. Under the base case assumption of 28% prevalence of arterial injury requiring operation, exclusion arteriography saves about $2000 and adds 0.3 quality adjusted life years (QALY) for each patient. Decision analysis can be successfully applied to problems in vascular trauma diagnosis.