An assessment of the dose and image quality difference between AP and PA positioned adult radiographic knee examinations.

INTRODUCTION: Knee X-rays are a standard examination to diagnose multiple conditions ranging from traumatic injuries, degeneration, and cancer. This study explores the differences between adult Anterior-Posterior (AP) and Posterior-Anterior (PA) weight-bearing knee examinations using absorbed radiation dose data and image quality. METHODS: The study modelled and compared AP and PA knee X-ray radiation dose data using Monte-Carlo software, an Ion Chamber, and thermoluminescence dosemeters (TLDs) on a Rando phantom. Imaging parameters used were 66kVp, 4mAs, 100cm distance and 13 × 24cm collimation. The interval data analysis used a two-tailed t-test. The image quality of a sample of the AP and PA knee X-rays was assessed using Likert 5-point ordinal Image Quality Scoring (IQS) and the Wilcoxon matched pairs test. RESULTS: Monte-Carlo modelling provided limited results; the Ion Chamber data for absorbed dose provided no variation between AP and PA positions but was similar to the AP TLD dose. The absorbed doses recorded with batches of TLDs demonstrated a 27.4% reduction (46.1µGy; p=0.01) in Skin Entrance Dose (ESD) and 9 - 58% dose reduction (1.6 - 16.4µGy; p=0.00-0.2) to the tissues and organs while maintaining diagnostic image quality (p=0.67). CONCLUSION: The study has highlighted the various challenges of using different dosimetry approaches to measure absorbed radiation dose in extremity (knee) X-ray imaging. The Monte-Carlo simulated absorbed knee dose was overestimated, but the simulated body organ/tissue doses were lower than the actual TLD absorbed doses. The Ion Chamber absorbed doses did not differentiate between the positions. The TLD organ/tissue absorbed doses demonstrated a reduction in dose in the PA position compared to the AP position, without a detrimental effect on image quality. The study findings in laboratory conditions raise awareness of opportunities and potential to lower radiation dose, with further study replicated in a clinical site recommended.

Cryo-EM structures of SARS-CoV-2 Omicron BA.2 spike

The BA.2 sub-lineage of the SARS-CoV-2 Omicron variant has gained in proportion relative to BA.1. As differences in spike (S) proteins may underlie differences in their pathobiology, here we determine cryo-EM structures of a BA.2 S ectodomain and compare these to previously determined BA.1 S structures. BA.2 Receptor Binding Domain (RBD) mutations induced remodeling of the internal RBD structure resulting in its improved thermostability and tighter packing within the 3-RBD-down spike. In the S2 subunit, the fusion peptide in BA.2 was less accessible to antibodies than in BA.1. Pseudovirus neutralization and spike binding assays revealed extensive immune evasion while defining epitopes of two RBD-directed antibodies, DH1044 and DH1193, that bound the outer RBD face to neutralize both BA.1 and BA.2. Taken together, our results indicate that stabilization of the 3-RBD-down state through interprotomer RBD-RBD packing is a hallmark of the Omicron variant, and reveal differences in key functional regions in the BA.1 and BA.2 S proteins.

Structural diversity of the SARS-CoV-2 Omicron spike

Aided by extensive spike protein mutation, the SARS-CoV-2 Omicron variant overtook the previously dominant Delta variant. Spike conformation plays an essential role in SARS-CoV-2 evolution via changes in receptor binding domain (RBD) and neutralizing antibody epitope presentation affecting virus transmissibility and immune evasion. Here, we determine cryo-EM structures of the Omicron and Delta spikes to understand the conformational impacts of mutations in each. The Omicron spike structure revealed an unusually tightly packed RBD organization with long range impacts that were not observed in the Delta spike. Binding and crystallography revealed increased flexibility at the functionally critical fusion peptide site in the Omicron spike. These results reveal a highly evolved Omicron spike architecture with possible impacts on its high levels of immune evasion and transmissibility.

Can Total Hip Arthroplasty for Hip Fracture Be Safely Performed by Trainees? A Retrospective Cohort Study.

BACKGROUND: No research is available comparing trainee and consultant outcomes for total hip arthroplasty (THA) for hip fracture. The aim of our study is to determine whether trainee-performed and consultant-performed THA produced equivalent radiological outcomes and complication rates for this patient cohort. METHODS: We performed a retrospective cohort study at our institution, with inclusion of patients who underwent a primary THA for hip fracture between March 30, 2017 and February 07, 2019. Relevant perioperative and outcome data were collected through electronic records. Radiological outcomes were assessed by 2 independent reviewers. Follow-up was performed until August 07, 2019. RESULTS: Eighty-seven patients were included in the study. The mean length of follow-up was 13 months (range, 6-29). Forty-three patients underwent consultant-led operations and 44 underwent trainee-performed (ST3-ST8) operations under consultant supervision. There were no significant differences between the 2 groups regarding complication risk (no recorded dislocation, infection requiring reoperation, revision or 30-day mortality in either group). There were also no significant differences between trainees and consultants regarding the radiological outcomes of mean acetabular component inclination (37.2° vs 36.7°, respectively, P = .74); offset difference (+7.1 mm vs +7.2 mm, respectively, P = .91); leg length difference (+6.4 mm vs +5.7 mm, respectively, P = .56); and barrack grade for femoral cement mantle. CONCLUSION: This study suggests that radiological and safety outcomes for trainees performing THA for hip fracture with appropriate supervision are equivalent to consultant surgeons. However, given the low event rate of complications, a larger study is required to determine whether there is any statistically significant difference.

Magnetic resonance spectroscopy assessment of brain injury after moderate hypothermia in neonatal encephalopathy: a prospective multicentre cohort study.

BACKGROUND: In neonatal encephalopathy, the clinical manifestations of injury can only be reliably assessed several years after an intervention, complicating early prognostication and rendering trials of promising neuroprotectants slow and expensive. We aimed to determine the accuracy of thalamic proton magnetic resonance (MR) spectroscopy (MRS) biomarkers as early predictors of the neurodevelopmental abnormalities observed years after neonatal encephalopathy. METHODS: We did a prospective multicentre cohort study across eight neonatal intensive care units in the UK and USA, recruiting term and near-term neonates who received therapeutic hypothermia for neonatal encephalopathy. We excluded infants with life-threatening congenital malformations, syndromic disorders, neurometabolic diseases, or any alternative diagnoses for encephalopathy that were apparent within 6 h of birth. We obtained T1-weighted, T2-weighted, and diffusion-weighted MRI and thalamic proton MRS 4-14 days after birth. Clinical neurodevelopmental tests were done 18-24 months later. The primary outcome was the association between MR biomarkers and an adverse neurodevelopmental outcome, defined as death or moderate or severe disability, measured using a multivariable prognostic model. We used receiver operating characteristic (ROC) curves to examine the prognostic accuracy of the individual biomarkers. This trial is registered with ClinicalTrials.gov, number NCT01309711. FINDINGS: Between Jan 29, 2013, and June 25, 2016, we recruited 223 infants who all underwent MRI and MRS at a median age of 7 days (IQR 5-10), with 190 (85%) followed up for neurological examination at a median age of 23 months (20-25). Of those followed up, 31 (16%) had moderate or severe disability, including one death. Multiple logistic regression analysis could not be done because thalamic N-acetylaspartate (NAA) concentration alone accurately predicted an adverse neurodevelopmental outcome (area under the curve [AUC] of 0·99 [95% CI 0·94-1·00]; sensitivity 100% [74-100]; specificity 97% [90-100]; n=82); the models would not converge when any additional variable was examined. The AUC (95% CI) of clinical examination at 6 h (n=190) and at discharge (n=167) were 0·72 (0·65-0·78) and 0·60 (0·53-0·68), respectively, and the AUC of abnormal amplitude integrated EEG at 6 h (n=169) was 0·73 (0·65-0·79). On conventional MRI (n=190), cortical injury had an AUC of 0·67 (0·60-0·73), basal ganglia or thalamic injury had an AUC of 0·81 (0·75-0·87), and abnormal signal in the posterior limb of internal capsule (PLIC) had an AUC of 0·82 (0·76-0·87). Fractional anisotropy of PLIC (n=65) had an AUC of 0·82 (0·76-0·87). MRS metabolite peak-area ratios (n=160) of NAA-creatine (<1·29) had an AUC of 0·79 (0·72-0·85), of NAA-choline had an AUC of 0·74 (0·66-0·80), and of lactate-NAA (>0·22) had an AUC of 0·94 (0·89-0·97). INTERPRETATION: Thalamic proton MRS measures acquired soon after birth in neonatal encephalopathy had the highest accuracy to predict neurdevelopment 2 years later. These methods could be applied to increase the power of neuroprotection trials while reducing their duration. FUNDING: National Institute for Health Research UK.

A novel technique for estimating component sizes in total knee arthroplasty.

INTRODUCTION: Intra-operative assessment of total knee arthroplasty (TKA) components is performed with manufacturer specific jigs. Pre-operative templating, patient specific knee cutting blocks and computer-assisted surgeries have also been used to improve alignment and sizing; although the literature shows marginal improvement in functional scores. We propose pre-operative shoe size as a simple measurement tool for estimating the component sizes required for TKA. We investigate the relationship between TKA implant sizes, height, body weight and shoe size. METHODS: Retrospective single centre cohort study of all patients undergoing primary knee arthroplasty over a four-month period (August-November 2015) was conducted. Standard data items recorded during routine admission. The spearman's rank correlation was used to assess the relationship between variables. RESULTS: One hundred and six patients were included in the final analysis. The mean age of the study group was 67.3 ±â€¯10.1 years (Range 44-90.) There were 42 male patients and 64 female patients. Statistically significant correlations were observed between: Shoe size and femoral component (rho = 0.589, p < 0.05); shoe size and tibial component (rho = 0.718, p < 0.05); shoe size and height (rho = 0.692, p < 0.05); height and femoral component (rho = 0.626, p < 0.05); height and tibial component (rho = 0.674, p < 0.05). CONCLUSION: We have demonstrated positive correlation between shoe and TKR component sizes. This relationship allows surgeons to estimate prosthesis size in the pre-operative setting.

Lesser Trochanter Avulsion Fracture in an Adolescent after Seizure.

BACKGROUND: Injury secondary to epileptic seizure is widely documented in the literature. In particular, uncontrolled muscular contractions generated during a seizure can lead to a variety of musculoskeletal injuries. CASE REPORT: We present the case of a 16-year-old male who presented on two separate occasions after a tonic-clonic seizure with hip pain, an antalgic gait, and marked discomfort on hip flexion. Radiologic investigation revealed an acute isolated fracture of the lesser trochanters. Such fractures in adolescents are normally secondary to athletic injury and in adults are mainly associated with the presence of metastatic bone disease. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: We present this case with its previously undocumented mechanism to highlight the injury to frontline emergency medical teams, create awareness of its presentation, and to discuss its potential mechanism and treatment.

New insights into phase distribution, phase composition and disorder in Y2(Zr,Sn)2O7 ceramics from NMR spectroscopy.

A combination of (89)Y and (119)Sn NMR spectroscopy and DFT calculations are used to investigate phase evolution, local structure and disorder in Y2Zr2-xSnxO7 ceramics, where a phase change is predicted, from pyrochlore to defect fluorite, with increasing Zr content. The ability of NMR to effectively probe materials that exhibit positional and compositional disorder provides insight into the atomic-scale structure in both ordered and disordered phases and, by exploiting the quantitative nature of the technique, we are able to determine detailed information on the composition of the phase(s) present and the average coordination number (and next-nearest neighbour environment) of the cations. In contrast to previous studies, a more complex picture of the phase variation with composition emerges, with single-phase pyrochlore found only for the Sn end member, and a single defect fluorite phase only for x = 0 to 0.6. A broad two-phase region is observed, from x = 1.8 to 0.8, but the two phases present have very different composition, with a maximum of 13% Zr incorporated into the pyrochlore phase, whereas the composition of the defect fluorite phase varies throughout. Preferential ordering of the anion vacancies in the defect fluorite phase is observed, with Sn only ever found in a six-coordinate environment, while remaining vacancies are shown to be more likely to be associated with Zr than Y. Our findings are then discussed in the light of those from previous studies, many of which utilize diffraction-based approaches, where, in most cases, a single phase of fixed composition has been assumed for the refinement procedure. The significant and surprising differences encountered demonstrate the need for complementary approaches to be considered for a detailed and accurate picture of both the long- and short-range structure of a solid to be achieved.

Accelerated polyethylene wear and early failure of the uncemented Reflection acetabular component: a ten to fifteen-year follow-up study.

PURPOSE: The Reflection® second-generation uncemented acetabular component was designed to address increased rates of failure observed with the early acetabular designs. However, the reported survivorship of this acetabular component has been conflicting. The aim of this study was to describe the ten to 15-year survivorship and polyethylene wear rate for the uncemented Reflection® acetabular component performed as part of a primary total hip replacement. METHODS: One hundred and four consecutive Reflection® uncemented acetabular components in 97 patients were identified from a prospective arthroplasty database with a minimum of ten years of follow-up. No patient was lost to follow-up. Mean cohort age was 59.1 years. RESULTS: There were 24 revisions of the acetabular component. The all-cause survival rate at ten years was 77.2% [95% confidence interval (CI) 73.9-80.5]. Mean linear wear was 0.20 mm [standard deviation (SD) 0.08] per year and the volumetric wear was 106.2 mm(3) per year. At final follow-up, more than half the patients had osteolysis identified around the femoral component. The mean Oxford Hip Score was 35.6 (SD 9.8) at a mean follow-up of 11.9 years, with six (11.1%) excellent, 26 (48.1%) good, 17 (31.5%) fair and five (9.3%) poor outcomes. Despite the fact that more than a third had a fair or poor outcome, only four (7.4%) were not satisfied with their hip. CONCLUSIONS: Due to the high rate of relatively asymptomatic polyethylene wear and osteolysis associated with this acetabular component, in our department, we now review all surviving patients both clinically and radiographically on an annual basis.

Variation in physical development in schoolboy rugby players: can maturity testing reduce mismatch?

OBJECTIVES: This study set out to pursue means of reducing mismatch in schoolboy rugby players. The primary objective was to determine whether application of previously reported thresholds of height and grip strength could be used to distinguish those 15-year-old boys appropriate to play under-18 school rugby from their peers. A secondary objective was to obtain normative data for height, weight and grip strength and to assess the variation within that data of current schoolboy rugby players. DESIGN: Cross-sectional cohort study. SETTING: 3 Scottish schools and 'Regional Assessment Centres' organised by the Scottish Rugby Union. PARTICIPANTS: 472 rugby playing youths aged 15 years (Regional Assessment Centres) and 382 schoolboys aged between 12 and 18 years (three schools). OUTCOME MEASURES: Height, weight and grip strength. RESULTS: 97% of 15-year-olds achieved the height and grip strength thresholds based on previous reported values. Larger mean values and wide variation of height, weight and grip strength were recorded in the schoolboy cohort. However, using the mean values of the cohort of 17-year-olds as a new threshold, only 7.7% of 15-year-olds would pass these thresholds. CONCLUSIONS: Large morphological variation was observed in schoolboy rugby players of the same age. Physical maturity tests described in earlier literature as pre-participation screening for contact sports were not applicable to current day 15-year-old rugby players. New criteria were measured and found to be better at identifying those 15-year-old players who had sufficient physical development to play senior school rugby.

Effects of plant flavonoids on Manduca sexta (tobacco hornworm) fifth larval instar midgut and fat body mitochondrial transhydrogenase.

The reversible, membrane-associated transhydrogenase that catalyzes hydride-ion transfer between NADP(H) and NAD(H) was evaluated and compared to the corresponding NADH oxidase and succinate dehydrogenase activities in midgut and fat body mitochondria from fifth larval instar Manduca sexta. The developmentally significant NADPH-forming transhydrogenation occurs as a nonenergy- or energy-linked activity with energy for the latter derived from either electron transport-dependent NADH or succinate utilization, or ATP hydrolysis by Mg++-dependent ATPase. In general, the plant flavonoids examined (chyrsin, juglone, morine, quercetin, and myricetin) affected all reactions in a dose-dependent fashion. Differences in the responses to the flavonoids were apparent, with the most notable being inhibition of midgut, but stimulation of fat body transhydrogenase by morin, and myricetin as also noted for NADH oxidase and succinate dehydrogenase. Although quercetin inhibited or stimulated transhydrogenase activity depending on the origin of mitochondria, it was without effect on either midgut or fat body NADH oxidase or succinate dehydrogenase. Observed sonication-dependent increases in flavonoid inhibition may well reflect an alteration in membrane configuration, resulting in increased exposure of the enzyme systems to the flavonoids. The effects of flavonoids on the transhydrogenation, NADH oxidase, and succinate dehydrogenase reactions suggest that compounds of this nature may prove valuable in the control of insect populations by affecting these mitochondrial enzyme components.

(119)Sn MAS NMR and first-principles calculations for the investigation of disorder in stannate pyrochlores.

The local structure and cation disorder in Y(2)Ti(2-x)Sn(x)O(7) pyrochlores, materials proposed for the encapsulation of lanthanide- and actinide-bearing radioactive waste, is studied using (119)Sn (I = 1/2) NMR spectroscopy. NMR provides an excellent probe of disorder, as it is sensitive to the atomic scale environment without the need for any long-range periodicity. However, the complex and overlapping spectral resonances that often result can be difficult to interpret. Here, we demonstrate how (119)Sn DFT calculations can be used to aid the spectral interpretation and assignment, confirming that Sn occupies only the six-coordinate pyrochlore B site, and that the Sn chemical shift is sensitive to the number of Sn/Ti on the neighbouring B sites. Although distinct resonances are resolved experimentally when the Ti content is low, there is significant spectral overlap for Ti-rich compositions. We establish that this is a result of two competing contributions to the Sn chemical shift; an upfield shift resulting from the incorporation of the more polarizing Ti(4+) cation onto the neighbouring B sites, and a concomitant downfield shift arising from the decrease in unit cell size. Despite the considerably easier spectral acquisition, the lower resolution in the (119)Sn spectra hinders the extraction of the detailed structural information previously obtained using (89)Y NMR. However, the spectra we obtain are consistent with a random distribution of Sn/Ti on the pyrochlore B sites. Finally, we consider whether an equilibrium structure has been achieved by investigating materials that have been annealed for different durations.

The effect of acetylcholine administration to sh-sy5y cells in the presence of levodopa (L-dopa) using conventional and sustained drug delivery - biomed 2010.

The purpose of the study was to evaluate the effects of conventional and sustained delivery of levodopa (L-dopa) alone or in combination with acetylcholine in SH-SY5Y neuroblastoma cells. The loss of dopaminergic neurons resulting in an imbalance between dopamine and acetylcholine is a hallmark feature of Parkinson disease. L-dopa has been shown to potentiate D2 receptor-mediated effects and inhibits acetylcholine release in Parkinson disease. According to the literature, conventionally administered L-dopa is short-lived and oxidized to metabolites which are neurotoxic and lead to a further decline in dopaminergic neurons. In addition, most in vitro studies do not taken into account that acetylcholine is elevated in vivo. SH-SY5Y cells were conventionally administered or in a sustained manner L-dopa, acetylcholine, or a combination of acetycholine and L-dopa for periods of 24, 48 and 72 hours, and evaluated for cell proliferation, cell viability, cellular damage, nitric oxide production, cellular glutathione levels, and hydrogen peroxide production. Overall, sustained delivery of L-dopa alone or in combination with acetylcholine showed decreases in cell number which were 50% less than those seen by conventional administration of the compounds within the first 48 hours of culture. However, regardless of administration of L-dopa alone or in combination with acetylcholine there were increases in cellular levels of MDA, nitric oxide, and hydrogen peroxide. Interestingly, the increases seen in the sustained delivery of L-dopa were less than those seen with conventional administration. In addition, the increased levels of the aforementioned parameters were delayed by 24 hours compared with conventional administration of these compounds. Appearances of the culture media following sustained delivery show increased in oxidized L-dopa. It is more than likely that the decreases in cell number and increased levels of nitric oxide, hydrogen peroxide, and MDA are a direct result of the oxidized metabolites of L-dopa.

Disordered lithium niobate rock-salt materials prepared by hydrothermal synthesis.

An investigation of the one-step hydrothermal crystallisation of lithium niobates reveals that reaction between Nb(2)O(5) and aqueous LiOH at 240 degrees C yields materials with a disordered rock-salt structure where the metals are statistically distributed over the cation sites. This contrasts with the well-studied reaction between Nb(2)O(5) and NaOH or KOH that produces ANbO(3) (A = Na, K) perovskites. Powder neutron diffraction shows that materials prepared at short reaction times and lower LiOH concentration (2.5 M) are lithium deficient and have a slight excess of niobium, but that at longer periods of reaction in 5 M LiOH, close to the ideal, stoichiometric Li(0.75)Nb(0.25)O composition is produced. Upon annealing this phase cleanly transforms into the known ordered rock-salt material Li(3)NbO(4), a process we have followed using thermodiffractometry, which indicates that transformation begins at approximately 700 degrees C. Solid-state (93)Nb and (7)Li NMR of the disordered and ordered rock-salt phases shows that both contain single metal sites but there is clear evidence for local disorder in the disordered samples. For the ordered material, NMR parameters derived from experiment are also compared to those calculated using density functional theory and are shown to be in good agreement.

Effects of the compounds 2-methoxynaphthoquinone, 2-propoxynaphthoquinone, and 2-isopropoxynaphthoquinone on ecdysone 20-monooxygenase activity.

The effects of the natural compound 2-methoxy-1,4-naphthoquinone, isolated from the leaves of Impatiens glandulifera and the synthetic compounds 2-propoxy-1,4-naphthoquinone and 2-isopropoxy-1,4-naphthoquinone on ecdysone 20-monooxygenase (E-20-M) activity were examined in three insect species. Homogenates of wandering stage third instar larvae of Drosophila melanogaster, or abdomens from adult female Aedes aegypti, or fat body or midgut from fifth instar larvae of Manduca sexta were incubated with radiolabelled ecdysone and increasing concentrations (from 1 x 10(-8) to 1 x 10(-3) M) of the three compounds. All three compounds were found to inhibit in a dose-dependent fashion the E-20-M activity in the three insect species. The concentration of these compounds required to elicit a 50% inhibition of this steroid hydroxylase activity in the three insect species examined ranged from approximately 3 x 10(-5) to 7 x 10(-4) M.

Complex posterior fracture-dislocation of the shoulder. Epidemiology, injury patterns, and results of operative treatment.

BACKGROUND: Complex posterior fracture-dislocations of the shoulder are rare and often associated with poor long-term function regardless of the choice of treatment. The purposes of this study were to evaluate the epidemiology and pathological anatomy of posterior fracture-dislocations of the shoulder and to assess the clinical and radiographic outcomes of a specific treatment protocol of open reduction and internal fixation. METHODS: We studied the demographic details of a consecutive series of twenty-six patients (twenty-eight shoulders in nineteen men and seven women with a mean age of fifty-three years) who sustained acute posterior dislocation of the humeral head with an associated Neer two, three, or four-part fracture. We used age and gender-specific local census data to assess the incidence of injury in our local population. All patients were treated by open relocation of the humeral head, bone-grafting of humeral head defects if they were causing residual shoulder instability, and internal fixation of the fracture. We recorded the prevalence of fracture complications that were clinically and radiographically apparent and assessed the functional outcome using three validated scoring systems (the Short Form-36 general health measure, the Disabilities of the Arm, Shoulder and Hand score, and the Constant score). RESULTS: The overall incidence of posterior fracture-dislocations was 0.6 per 100,000 population per year. The peak incidence was in middle-aged men, and most injuries were sustained during a seizure or a fall from a height. In all patients, there was a displaced primary fracture of the anatomic neck of the humerus, propagating from the area of an osteochondral fracture of the anterior aspect of the humeral head (a reverse Hill-Sachs lesion). We recognized three subtypes determined by the extent of the secondary fracture lines. At two years after surgery, the median Constant score was 83.5 points and the median Disabilities of the Arm, Shoulder and Hand score was 17.5 points. The eight components of the Short Form-36 score were not significantly different from those of age and sex-matched controls at two years. CONCLUSIONS: Acute complex posterior fracture-dislocations of the shoulder are rare, but they occur in patients who are younger than the majority of other patients who sustain a proximal humeral fracture. The use of open reduction and internal fixation to treat these fractures is associated with a relatively low risk of postoperative complications, and the functional outcome is generally favorable.