Hip geometric parameters are associated with radiographic and clinical hip osteoarthritis: Findings from a cross-sectional study in UK Biobank.

OBJECTIVE: To examine the extent to which geometric parameters derived from dual-energy x-ray absorptiometry (DXA) scans in the UK Biobank study are related to hip osteoarthritis (HOA) independently of sex, age and body size. DESIGN: Femoral neck width (FNW), diameter of the femoral head (DFH) and hip axis length (HAL) were derived automatically from left hip DXA scans in UK Biobank using outline points placed around the hip by a machine-learning program. Correlations were calculated between geometric parameters, age, height, and weight. Logistic regression was used to examine the relationship of geometric parameters with radiographic HOA, hospital diagnosed HOA (HESOA), and Cox proportional hazards model to evaluate the relationship with total hip replacement (THR). Analyses were adjusted for sex, age, height, weight, and geometric parameters. RESULTS: The study consisted of 40,312 participants. In age and sex-adjusted analyses, FNW, HAL and DFH were related to increased risk of radiographic HOA. In a model adjusted for age, sex, height, weight and other geometric parameters, both FNW and HAL retained independent relationships with radiographic HOA [FNW: odds ratios 2.38 (2.18-2.59), HAL: 1.25 (1.15-1.36)], while DFH was now protective [0.55 (0.50-0.61)]. Only FNW was independently related to HESOA [2.20 (1.80-2.68)] and THR [hazard ratios 2.51 (1.89-3.32)]. CONCLUSION: Greater FNW and HAL were independently related to an increased risk of radiographic HOA, whereas greater DFH appeared to be protective. Greater FNW was independently associated with HESOA and THR. These results suggest that DXA-derived geometric parameters, particularly FNW, could help determine HOA and THR risk.

Cam morphology but neither acetabular dysplasia nor pincer morphology is associated with osteophytosis throughout the hip: findings from a cross-sectional study in UK Biobank.

OBJECTIVES: To examine whether acetabular dysplasia (AD), cam and/or pincer morphology are associated with radiographic hip osteoarthritis (rHOA) and hip pain in UK Biobank (UKB) and, if so, what distribution of osteophytes is observed. DESIGN: Participants from UKB with a left hip dual-energy X-ray absorptiometry (DXA) scan had alpha angle (AA), lateral centre-edge angle (LCEA) and joint space narrowing (JSN) derived automatically. Cam and pincer morphology, and AD were defined using AA and LCEA. Osteophytes were measured manually and rHOA grades were calculated from JSN and osteophyte measures. Logistic regression was used to examine the relationships between these hip morphologies and rHOA, osteophytes, JSN, and hip pain. RESULTS: 6,807 individuals were selected (mean age: 62.7; 3382/3425 males/females). Cam morphology was more prevalent in males than females (15.4% and 1.8% respectively). In males, cam morphology was associated with rHOA [OR 3.20 (95% CI 2.41-4.25)], JSN [1.53 (1.24-1.88)], and acetabular [1.87 (1.48-2.36)], superior [1.94 (1.45-2.57)] and inferior [4.75 (3.44-6.57)] femoral osteophytes, and hip pain [1.48 (1.05-2.09)]. Broadly similar associations were seen in females, but with weaker statistical evidence. Neither pincer morphology nor AD showed any associations with rHOA or hip pain. CONCLUSIONS: Cam morphology was predominantly seen in males in whom it was associated with rHOA and hip pain. In males and females, cam morphology was associated with inferior femoral head osteophytes more strongly than those at the superior femoral head and acetabulum. Further studies are justified to characterise the biomechanical disturbances associated with cam morphology, underlying the observed osteophyte distribution.

Predictors of total hip replacement in community based older adults: a cohort study.

OBJECTIVE: The purpose of this study is to describe predictors of total hip replacement (THR) in community dwelling older adults. A better understanding of predictors of THR can aid in triaging patients and researching preventative strategies. DESIGN: At baseline, participants had assessment of radiographic OA and cam morphology (from pelvic radiographs), shape mode scores and hip bone mineral density (BMD; from dual energy X-ray absorptiometry (DXA)). After 2.6 and 5 years, participants reported hip pain using WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index), and had hip structural changes assessed using magnetic resonance imaging (MRI). Risk of THR was analysed using mixed-effect Poisson regression. RESULTS: Incidence of THR for OA over 14 years was 4.6% (37/801). As expected, WOMAC hip pain and hip radiographic OA both predicted risk of THR. Additionally, shape mode 2 score (decreasing acetabular coverage) (RR 1.83/SD; 95% CI 1.1-3.04), shape mode 4 score (non-spherical femoral head) (RR 0.59/SD; 95% CI 0.36-0.96), cam morphology (α > 60°) (RR 2.2/SD; 95% CI 1.33-3.36), neck of femur BMD (RR 2.09/SD, 95% CI 1.48-2.94) and bone marrow lesions (BMLs) increased risk of THR (RR 7.10/unit; 95% CI 1.09-46.29). CONCLUSION: In addition to hip pain and radiographic hip OA, measures of hip shape, cam morphology, BMD and BMLs independently predict risk of THR. This supports the role of hip bone geometry and structure in the pathogenesis of end stage hip OA and has identified factors that can be used to improve prediction models for THR.

Subregional statistical shape modelling identifies lesser trochanter size as a possible risk factor for radiographic hip osteoarthritis, a cross-sectional analysis from the Osteoporotic Fractures in Men Study.

OBJECTIVE: Statistical shape modelling (SSM) of hip dual-energy X-ray absorptiometry (DXA) scans has identified relationships between hip shape and radiographic hip OA (rHOA). We aimed to further elucidate shape characteristics related to rHOA by focusing on subregions identified from whole-hip shape models. METHOD: SSM was applied to hip DXAs obtained in the Osteoporotic Fractures in Men Study. Whole-hip shape modes (HSMs) associated with rHOA were combined to form a composite at-risk-shape. Subsequently, subregional HSMs (cam-type and lesser trochanter modes) were built, and associations with rHOA were examined by logistic regression. Subregional HSMs were further characterised, by examining associations with 3D-HSMs derived from concurrent hip CT scans. RESULTS: 4,098 participants were identified with hip DXAs and radiographs. Composite shapes from whole-hip HSMs revealed that lesser trochanter size and cam-type femoral head are related to rHOA. From sub-regional models, lesser trochanter mode (LTM)1 [OR 0.74; 95%CI 0.63.0.87] and cam-type mode (CTM)3 [OR 1.27; 1.13.1.42] were associated with rHOA, associations being similar to those for whole hip HSMs. 515 MrOS participants had hip DXAs and 3D-HSMs derived from hip CT scans. LTM1 was associated with 3D-HSMs that also represented a larger lesser trochanter [3D-HSM7 (beta (ß)-0.23;-0.33,-0.14) and 3D-HSM9 (ß0.36; 0.27.0.45)], and CTM3 with 3D-HSMs describing cam morphology [3D-HSM3 (ß-0.16;-0.25,-0.07) and 3D-HSM6 (ß 0.19; 0.10.0.28)]. CONCLUSION: Subregional SSM of hip DXA scans suggested larger lesser trochanter and cam morphology underlie associations between overall hip shape and rHOA. 3D hip modelling suggests our subregional SSMs represent true anatomical variations in hip shape, warranting further investigation.

Osteoarthritis as an organ disease: from the cradle to the grave.

Considered for decades as a cartilage disease, recent studies of osteoarthritis (OA) take us back to the concepts discussed at the naming of the disorder as "bone-joint-inflammation". By describing the joint as an organ, can OA be called an organ disease - similar to heart disease? Is there a systemic (which system?) involvement? Would this help with diagnosis or therapy? Hyperplasia of the joint tissues is one of the most notable early features of the disease: articular cartilage thickens, chondrocytes proliferate and increase matrix biosynthesis, but not its incorporation; the subchondral bone densifies but is hypomineralised and there is an increase in bone marrow fat content. Associations between OA and hypertension, hypercholesterolaemia and blood glucose suggest systemic and metabolic components are involved. The source of pain is still unknown but here is evidence for peripheral and central sensitisation. Joint deformity is difficult to quantify, but statistical shape modelling provides a tool to use as an imaging biomarker. A genome-wide association study meta-analysis has identified novel genes associated with hip shape with many genes related to tissue growth and development. There are associations between hip shapes and age of first walking as well as with obesity through adulthood. These life-course events and a recapitulation in old age of developmental processes suggest that the cradle may affect our path to the grave. These observations suggest that tissue regeneration approaches, treating only the cartilage in OA joints, may only be of limited benefit.

Diversity of bacterioplankton in contrasting Tibetan lakes revealed by high-density microarray and clone library analysis.

Tibetan lakes represent a unique microbial environment and are a good ecosystem to investigate the microbial diversity of high mountain lakes and their relationship with environmental factors. The diversity and community structure of bacterioplankton in Tibetan lakes was determined using DNA fingerprinting analysis, high-density 16S rRNA gene microarray (PhyloChip) analysis, and extensive clone library analysis of bacterial 16S rRNA genes. A previously unseen high microbial diversity (1732 operational taxonomic units based on PhyloChip data) and numerous novel bacterial 16S rRNA gene sequences were observed. Abundant SAR11-like sequences retrieved from saline Lake Qinghai demonstrated a unique SAR11 phylogenetic sister clade related to the freshwater LD12 clade. Water chemistry (e.g. salinity) and altitude played important roles in the selection of bacterial taxa (both presence and relative abundance) in Tibetan lakes. The ubiquity and uniqueness of bacterial taxa, as well as the correlation between environmental factors and bacterial taxa, was observed to vary gradually with different phylogenetic levels. Our study suggested high microbial cosmopolitanism and high endemicity observed at higher and lower phylogenetic levels, respectively.

Callus cultures for phytometabolism studies: phytometabolites of 3-trifluoromethylphenol in Lemnaceae plants and callus cultures.

Plant callus cultures have the potential to advance phytoremediation science by allowing study of cellular phytometabolism in absence of sorption, translocation, microbial degradation, and other phytoremediation processes; however, studies demonstrating the applicability of results from callus cultures to whole plants are limited. The aim of this study was to evaluate the feasability and applicability of using callus cultures to study phytometabolism. This aim was accomplished through evaluation of induction and growth of Lemnaceae callus cultures and comparison of phytometabolism in callus cultures and whole plants. Four out of eight published methods for callus culture of Lemnaceae successfully induced callus cultures that exhibited doubling times of 1.7 to 23 wks. Callus cultures and whole plants of Landoltia punctata and Lemna minor metabolized 3-trifluoromethylphenol (3-TFMP) through conjugation with glucopyranoside, malonyl-glucopyranoside, and glucopyranosyl-apiofuranoside. However, concentrations of metabolites were approximately 10 times less in callus cultures than in plants. While results demonstrated applicability of callus cultures results to whole plants, the low success rate of callus induction procedures, length of time required to produce substantial callus mass, and the low accumulation of metabolites in callus cultures may limit the feasibility of callus cultures for assessing phytometabolism.

Assessment of plant-driven removal of emerging organic pollutants by duckweed.

Constructed treatment wetlands have the potential to reclaim wastewaters through removal of trace concentrations of emerging organic pollutants, including pharmaceuticals, personal care products, and pesticides. Flask-scale assessments incorporating active and inactivated duckweed were used to screen for plant-associated removal of emerging organic pollutants in aquatic plant systems. Removals of four of eight pollutants, specifically atrazine, meta-N,N-diethyl toluamide (DEET), picloram, and clofibric acid, were negligible in all experimental systems, while duckweed actively increased aqueous depletion of fluoxetine, ibuprofen, 2,4-dichlorophenoxyacetic acid, and triclosan. Active plant processes affecting depletion of experimental pollutants included enhancement of microbial degradation of ibuprofen, uptake of fluoxetine, and uptake of degradation products of triclosan and 2,4-dichlorophenoxyacetic acid. Passive plant processes, particularly sorption, also contributed to aqueous depletion of fluoxetine and triclosan. Overall, studies demonstrated that aquatic plants contribute directly and indirectly to the aqueous depletion of emerging organic pollutants in wetland systems through both active and passive processes.

Polyamine metabolism and cancer prevention.

Colorectal cancer is one of a number of cancers that may be amenable to prevention. The NSAIDs (non-steroidal anti-inflammatory drugs) have been shown to be effective chemopreventative agents in humans, but their mechanism of action is not clear. The polyamines are cellular polycations that are essential for cell growth and are overproduced in cancer cells. It is our hypothesis that inhibition of polyamine metabolism is an integral part of the mechanism of cancer prevention mediated by NSAIDs.

Environmental distribution of the trichloroethene reductive dehalogenase gene (tceA) suggests lateral gene transfer among Dehalococcoides.

The trichloroethene reductive dehalogenase gene (tceA) of Dehalococcoides spp. was detected in 12 of 21 trichloroethene-to-ethene dechlorinating enrichment cultures established from aquifer and sediment samples collected from diverse geographic locations in the USA. Analysis of the tceA chromosomal regions indicated that the tceA genes shared greater than 95% sequence identity, and all shared identical tceAB spacer sequences and tceB genes downstream of tceA. A putative transposable element (PTE) was present 1077 bp downstream of the tceB stop codon in three of eight chromosomal regions analyzed. Sequence identity was interrupted downstream of tceB and upstream or downstream of the PTE, suggesting that intrachromosomal or interchromosomal transfer of tceAB had occurred.

Sequestration of a fluorinated analog of 2,4-dichlorophenol and metabolic products by L. minor as evidenced by 19F NMR.

Fate of halogenated phenols in plants was investigated using nuclear magnetic resonance (NMR) to identify and quantify contaminants and their metabolites. Metabolites of 4-chloro-2-fluorophenol (4-Cl-2-FP), as well as the parent compound, were detected in acetonitrile extracts using 19F NMR after various exposure periods. Several fluorinated metabolites with chemical shifts approximately 3.5 ppm from the parent compound were present in plant extracts. Metabolites isolated in extracts were tentatively identified as fluorinated-chlorophenol conjugates through examination of signal-splitting patterns and relative chemical shifts. Signal intensity was used to quantify contaminant and metabolite accumulation within plant tissues. The quantity of 4-Cl-2-F metabolites increased with time and mass balance closures of 90-110% were achieved. In addition, solid phase 19F NMR was used to identify 4-Cl-2-FP which was chemically bound to plant material. This work used 19F NMR for developing a time series description of contaminant accumulation and transformation in aquatic plant systems.

Role of plant activity and contaminant speciation in aquatic plant assimilation of 2,4,5-trichlorophenol.

Aquatic plants uptake, transform and sequester organic contaminants and are used as a bioremediation strategy for the removal of pollutants from wastewaters. A better understanding of factors affecting rate of uptake of contaminants by aquatic plants is needed to improve engineered systems for removal of pollutants from wastewaters. This work focused on delineating sorption to plant surfaces and understanding effects of plant metabolic activity, inhibition, and media pH on the uptake of the ionizable contaminant 2,4,5-trichlorophenol (TCP) by aquatic plant Lemna minor. During L. minor exposure to TCP (0.5-13.9 mg l(-1)), a range of plant metabolic activities was measured using oxygen production rate (0-18.4 micromol h(-1)). A positive correlation was shown between contaminant uptake rate and plant activity. Contaminant uptake was examined at a range of media pH values (6-9) and uptake rates were linearly correlated to fraction of contaminant in protonated form. These results demonstrated a link between plant activity and uptake of contaminant by plants and stress the importance of incorporating plant metabolic activity and contaminant speciation in development of natural and engineered phytoremediation systems. This research also indicates that aquatic plants can actively accumulate trace-organic contaminants and may ultimately serve as a sink for these materials in the natural environment.

Activity of Desulfitobacterium sp. strain Viet1 demonstrates bioavailability of 2,4-dichlorophenol previously sequestered by the aquatic plant Lemna minor.

Aquatic plants take up and sequester organic contaminants such as chlorophenols through incorporation in cell wall materials and storage in vacuoles. The ultimate fate of plant-sequestered chlorophenols, however, remains unclear. This research investigated 2,4-dichlorophenol (2,4-DCP) sequestration by the aquatic plant Lemna minor and evaluated contaminant release and bioavailability after plant death and cellular disruption. 14C-labeled 2,4-DCP was used to establish that contaminant removed from the aqueous phase was retained internal to L. minor. An assay with Desulfitobacterium sp. strain Viet1 was used to assess the readily bioavailable fraction of plant-sequestered 2,4-DCP and plant metabolites of 2,4-DCP. In plant-free systems, strain Viet1 dechlorinated 2,4-DCP to stoichiometric amounts of 4-chlorophenol (4-CP) as a stable and quantifiable end product. Anaerobic microcosms containing inactivated L. minor, which had accumulated 3.8 micromol of 2,4-DCP equivalents/g of plant material (fresh weight) during a preceding aerobic exposure, were inoculated with strain Viet1. After 118 d of incubation with strain Viet1, 43.5% (+/-1.4%) of the contaminant was recovered as 4-CP, indicating a large portion of plant-sequestered 2,4-DCP was bioavailable for dechlorination by strain Viet1. In contrast, 4-CP formation was not observed in autoclaved microcosms, and only 26.1% (+/-1.0%) of plant-sequestered 2,4-DCP was recovered in the aqueous phase. These findings demonstrate contaminant cycling between plants and microorganisms, and emphasize that understanding the mechanisms and pathways of contaminant sequestration by plants is critical for predicting long-term contaminant fate.

Rotational acceleration measurements--evaluating helmet protection.

PURPOSE: Current helmet testing standards do not address the rotational components of an impact to the head. We describe a new testing paradigm used to measure the rotational acceleration of a headform and a protective helmet following an impact to the head in the horizontal plane. This impact simulation allows for the testing of currently available head protection devices in conditions thought to be important for the generation of cerebral concussion. The degree to which a particular helmet dampens rotational acceleration, and thus protects against concussion, can be assessed. METHODS: Our testing device consists of a pneumatic piston that provides a measured impact to a standard headform. Four different helmets were tested using the described paradigm. RESULTS: Acceleration curves for each helmet and the corresponding headform are presented. CONCLUSIONS: Clear differences in rotational acceleration were demonstrated. Possible avenues of further investigation are discussed.

Genetic identification of a putative vinyl chloride reductase in Dehalococcoides sp. strain BAV1.

Dehalococcoides sp. strain BAV1 couples growth with the reductive dechlorination of vinyl chloride (VC) to ethene. Degenerate primers targeting conserved regions in reductive dehalogenase (RDase) genes were designed and used to PCR amplify putative RDase genes from strain BAV1. Seven unique RDase gene fragments were identified. Transcription analysis of VC-grown BAV1 cultures suggested that bvcA was involved in VC reductive dechlorination, and the complete sequence of bvcA was obtained. bvcA was absent in Dehalococcoides isolates that failed to respire VC, yet was detected in four of eight VC-respiring mixed cultures.

Low-intensity hematopoietic stem-cell transplantation across human leucocyte antigen barriers in dyskeratosis congenita.

Since the results of conventional hematopoietic stem-cell transplantation (HSCT) for patients with dyskeratosis congenita (DC) are poor owing to the high incidence of transplant-related complications, we explored the use of a low-intensity HSCT regimen. We report two children with DC with severe cytopenia, who underwent successful HSCT from a matched unrelated donor after conditioning with fludarabine, cyclophosphamide, and antithymocyte globulin. Graft-versus-host-disease (GVHD) prophylaxis consisted of corticosteroids and cyclosporin A. The regimen was well tolerated, no significant transplant-related complications were observed, and engraftment was rapid and complete. At 15 and 16 months after HSCT, the children were fully engrafted, in excellent clinical condition, full-donor chimerism, and no signs of GVHD. We conclude that a low-intensity regimen is sufficient to induce durable engraftment using matched unrelated donor HSCT in DC patients, with minimal 1-year transplant-related toxicity. Longer follow-up will determine whether this regimen also reduces long-term toxicity.

The utility of plasma polymerase chain reaction for human herpes virus-6 among pediatric bone marrow transplant recipients: results of a pilot study.

We evaluated the utility of plasma polymerase chain reaction (PCR) for surveillance of human herpes virus 6 (HHV-6) infection among pediatric bone marrow transplant (BMT) recipients. We used a prospective, non-interventional design involving a study group and controls. BMT recipients and healthy controls were evaluated. BMT subjects had HHV-6 PCR done biweekly for 12 weeks post transplantation, while a single PCR test was done on controls. For the PCR assay, EDTA blood was collected and DNA extracted from whole blood and cell-free plasma using standard procedures. The PCR was first performed on DNA from whole blood and if a positive result was obtained, the test was repeated on the DNA from the plasma. Thirty BMT recipients (13 autologous and 17 allogeneic) were enrolled, on whom a total of 156 PCR tests were performed, while six tests were done on six healthy controls. The median age of BMT subjects was 6.2 years (range 0.5-17.5 years). The median age of the control subjects was 6.6 years (range 2-10 years). Among asymptomatic BMT patients who had PCR surveillance, the positivity rate was 3.3% (1/30) on whole blood and 0% (0/30) on plasma. None of the six healthy subjects had a positive PCR test on whole blood. During the period of the surveillance study, 14 patients had diagnostic evaluations for HHV-6 disease because of clinical symptoms. Two of these patients were diagnosed with disease associated with HHV-6 (graft failure and encephalitis) and had positive PCR tests on whole blood and plasma and whole blood and cerebrospinal fluid, respectively. We conclude that despite the fact that HHV-6 seropositivity rates are high among children, the frequency of HHV-6 plasma PCR positivity is low in pediatric BMT subjects who are asymptomatic for HHV-6 disease. Given that a positive test on plasma is consistent with active infection, this increases the utility of the PCR test as a diagnostic aid in evaluating syndromes presumed to be due to HHV-6 in pediatric bone marrow transplant recipients.

A quantitative relationship that demonstrates mercury methylation rates in marine sediments are based on the community composition and activity of sulfate-reducing bacteria.

A quantitative framework was developed which estimates mercury methylation rates (MMR) in sediment cores based on measured sulfate reduction rates (SRR) and the community composition sulfate-reducing bacterial consortia. MMR and SRR as well as group-specific 16S rRNA concentrations (as quantified by probe signal) associated with sulfate-reducing bacteria (SRB) were measured in triplicate cores of saltmarsh sediments. Utilizing previously documented conversion factors in conjunction with field observations of sulfate reduction, MMR were calculated, and the results were compared to experimentally derived measurements of MMR. Using our novel field data collected in saltmarsh sediment where sulfate reduction activity is high, calculated and independently measured MMR results were consistently within an order of magnitude and displayed similar trends with sediment depth. In an estuarine sediment where sulfate reduction activity was low, calculated and observed MMR diverged by greater than an order of magnitude, but again trends with depth were similar. We have expanded the small database generated to date on mercury methylation in sulfur-rich marine sediments. The quantitative frameworkwe have developed further elucidates the coupling of mercury methylation to sulfate reduction by basing calculated rates of mercury methylation on the activity and community composition of sulfate-reducing bacteria. The quantitative framework may also provide a promising alternative to the difficult and hazardous determination of MMR using radiolabeled mercury.

A computer system for continuous long-term recording, processing, and analysis of physiological data of brain injured patients in ICU settings.

The objective of this project was to assemble and test a computer-based system for continuous long-term physiological data acquisition. The system would be used to study short-term (heart rate variability) and long-term (circadian rhythms) dynamics of physiological parameters in severely brain injured patients in ICU settings. A system has been built using open-source software and the Linux operating system as the platform. The system consists of three main parts: data acquisition, processing and analysis. The system was tested in ICU and experimental settings for long periods of time (up to 10 days of non-stop recording). The system appeared to function properly and accurately. Samples of the data according to the stages of acquisition-analysis process are presented in the paper. Avenues for the system use and development are discussed.