In vertebrates ecto-5'-nucleotidase (e5NT) catalyzes the hydrolysis of extracellular AMP to adenosine and represents the major control point for extracellular adenosine levels. Due to its pivotal role for activation of P1 adenosine receptors, e5NT has emerged as an appealing drug target for treatment of inflammation, chronic pain, hypoxia, and cancer. Crystal structures of the dimeric human e5NT reveal an extensive 114° conformational switch between the open and closed forms of the enzyme. The dimerization interface is formed by the C-terminal domains and exhibits interchain motions of up to 13°. Complex structures with adenosine and AMPCP indicate that structural control of the domain movement determines the selectivity for monophosphate nucleotides. Binding modes of nucleotide-derived and flavonoid-based compounds complexed to the C-terminal domain in the open form reveal an additional binding pocket of ∼210 Å(3) that might be explored to design more potent inhibitors.

The CYP 17 and CYP 19 genes encode 17alpha-hydroxylase/17,20-lyase and aromatase, respectively, both involved in sex hormone synthesis. We investigated the association between 2 common polymorphisms in 1) the promoter region (T-->C substitution) of CYP 17, and 2) exon 3 (G-->A) of CYP 19, bone mineral density (BMD) and serum androgen/estradiol, in a case-control study of 252 postmenopausal women aged 64.5 +/- 9.2 yr (mean +/- SD). There was no significant difference in serum estradiol concentrations between cases (n = 136) and controls (n = 116). The CYP 19 genotype was significantly associated with serum estradiol (P = 0.002). Women with the AA genotype had higher serum estradiol concentrations compared with those with the GG genotype (P = 0.03). In older women, those with the CYP 19 GA and GG genotypes had an increased prevalence of osteoporosis (P = 0.04) and fractures (P = 0.003). We found no significant association between CYP 17 genotype and serum androgens and estradiol concentrations. However, a significant association was seen between BMD values at the femoral neck with CYP 17 genotype in cases (P = 0.04) and in the whole study population (P = 0.012). Subjects with the CC genotype had significantly lower BMD (mean +/- SD: TT, 0.7 +/- 0.16; CC, 0.6 +/- 0.08 g/cm(2); P = 0.006). In conclusion, both CYP 17 and CYP 19 are candidate genes for osteoporosis in postmenopausal women.

A previous modelling study predicted that the forces applied by the extensor muscles to stabilise the lumbar spine would be greater in spines that have a larger sagittal curvature (lordosis). Because the force-generating capacity of a muscle is related to its size, it was hypothesised that the size of the extensor muscles in a subject would be related to the size of their lumbar lordosis. Magnetic resonance imaging (MRI) data were obtained, together with age, height, body mass and back pain status, from 42 female subjects. The volume of the extensor muscles (multifidus and erector spinae) caudal to the mid-lumbar level was estimated from cross-sectional area measurements in axial T1-weighted MRIs spanning the lumbar spine. Lower lumbar curvature was determined from sagittal T1-weighted images. A stepwise linear regression model was used to determine the best predictors of muscle volume. The mean lower lumbar extensor muscle volume was 281 cm 3 (SD = 49 cm 3 ). The mean lower lumbar curvature was 30°(SD = 7°). Five subjects reported current back pain and were excluded from the regression analysis. Nearly half the variation in muscle volume was accounted for by the variables age (standardised coefficient, B = À3.2, P = 0.03) and lower lumbar curvature (B = 0.47, P = 0.002). The results support the hypothesis that extensor muscle volume in the lower lumbar spine is related to the magnitude of the sagittal curvature; this has implications for assessing muscle size as an indicator of muscle strength.

Brief bursts of high-intensity PA relevant to bone health can be captured by applying bone-specific thresholds of intensity to raw tri-axial accelerations averaged over 1-second epochs. Accumulating 1-2 minutes/day of high-intensity PA, equivalent to running in pre-menopausal women and slow jogging in post-menopausal women, is associated with better bone health.

This study evaluated the clinical utility of a new multisite ultrasound device capable of measuring speed of sound (SOS) at the phalanx, radius, tibia and metatarsal. The in vitro and in vivo short- and long-term precision were evaluated, reference data were collected for 409 healthy white women (236 premenopausal and 173 postmenopausal), and age and menopause related changes were calculated using linear regression. Fracture discrimination was evaluated using 109 women with vertebral fractures and the age-adjusted odds ratios calculated for each standard deviation decrease in SOS measurement. Correlations between SOS measurements and spine and femur bone mineral density (BMD) were calculated. T-score equivalence with BMD was also investigated together with the prevalence of osteoporosis as defined by the WHO criteria. The in vivo short-term precision standardized in T-score units ranged from 0.14 to 0.33 and long-term standardized precision was 0.35-0.65. Postmenopausal age-related bone loss expressed as the annual change in T-score ranged from 0.040 to 0.089 for SOS and 0.053 to 0.066 for BMD, whilst menopause-related annual loss ranged from 0.036 to 0.094 for SOS and 0.050 to 0.074 for BMD. Correlations between the different SOS sites ranged from r = 0.24 to 0.55, and between SOS and BMD from r = 0.12 to 0.47. The odds ratio (and 95% confidence intervals) for fracture per 1 SD decrease in SOS were 2.0 (1.22 to 3.23) for the phalanx; 1.5 (1.01 to 2.24) for the metatarsal; 1.4 (1.03 to 1.99) for the radius and 1.2 (0.87 to 1.66) for the tibia. Odds ratios for BMD in the same population ranged from 2.6 to 4.8 (1.70 to 8.29). The prevalence of osteoporosis as defined by T = <-2.5 in the age range 60-69 ranged from 7.1% to 20.6% for SOS and 6.4% to 12.1% for BMD. In conclusion, this study demonstrated that multisite ultrasound has adequate precision for investigating skeletal status, is capable of differentiating between pre- and postmenopausal women and women with vertebral fractures, has a T-score equivalence similar to that of dual-energy X-ray absorptiometry (DXA), and appears to be a promising new technique for evaluating skeletal status at clinically relevant sites.

Introduction To investigate student clinical placement concerns and opinions, during the initial COVID-19 pandemic outbreak and to inform educational institution support planning. Methods Between mid-June to mid-July 2020, educational institutions from 12 countries were invited to participate in an online survey designed to gain student radiographer opinion from a wide geographical spread and countries with varying levels of COVID-19 cases. Results 1277 respondents participated, of these 592 had completed clinical placements during January to June 2020. Accommodation and cohabiting risks were identified as challenging, as was isolation from family, travel to clinical placements, and to a lesser extent childcare. Students stated they had been affected by the feeling of isolation and concerns about the virus whilst on placement. Overall 35.4% of all respondents were ‘Not at all worried’ about being a radiographer, however, 64.6% expressed varying levels of concern and individual domestic or health situations significantly impacted responses (p ≤ 0.05). Year 4 students and recent graduates were significantly more likely to be ‘Not worried at all’ compared to Year 2 and 3 students (p ≤ 0.05). The need for improved communication regarding clinical placements scheduling was identified as almost 50% of students on clinical placements between January to June 2020 identified the completion of assessments as challenging. Furthermore, only 66% of respondents with COVID-19 imaging experience stated being confident with personal protective equipment (PPE) use. Conclusion Student radiographers identified key challenges which require consideration to ensure appropriate measures are in place to support their ongoing needs. Importantly PPE training is required before placement regardless of prior COVID-19 imaging experience. Implications for practice As the next academic year commences, the study findings identify important matters to be considered by education institutions with responsibility for Radiography training and as students commence clinical placements during the on-going global COVID-19 pandemic.

Regional variations in collagen arrangement show that the highly ordered layers of the articular cartilage are the most important elements in supporting high variable loads. In lesions changes occur in the deep tissue whilst the overlying cartilage appeared normal. We therefore suggest that the interface region is a key element in the early stages of the disease.

The results suggest that the performance advantage of expert radiologists is underpinned by superior pattern recognition skills, as evidenced by a quicker time to first fixate the pathology, and less time spent searching the image.