The pelvis rotates in the sagittal plane during daily activities. These rotations have a direct effect on the functional orientation of the acetabulum. The aim of this study was to quantify changes ...in pelvic tilt between different functional positions.
Pre-operatively, pelvic tilt was measured in 1517 patients undergoing total hip arthroplasty (THA) in three functional positions - supine, standing and flexed seated (the moment when patients initiate rising from a seated position). Supine pelvic tilt was measured from CT scans, standing and flexed seated pelvic tilts were measured from standardised lateral radiographs. Anterior pelvic tilt was assigned a positive value.
The mean pelvic tilt was 4.2° (-20.5° to 24.5°), -1.3° (-30.2° to 27.9°) and 0.6° (-42.0° to 41.3°) in the three positions, respectively. The mean sagittal pelvic rotation from supine to standing was -5.5° (-21.8° to 8.4°), from supine to flexed seated was -3.7° (-48.3° to 38.6°) and from standing to flexed seated was 1.8° (-51.8° to 39.5°). In 259 patients (17%), the extent of sagittal pelvic rotation could lead to functional malorientation of the acetabular component. Factoring in an intra-operative delivery error of ± 5° extends this risk to 51% of patients.
Planning and measurement of the intended position of the acetabular component in the supine position may fail to predict clinically significant changes in its orientation during functional activities, as a consequence of individual pelvic kinematics. Optimal orientation is patient-specific and requires an evaluation of functional pelvic tilt pre-operatively. Cite this article: Bone Joint J 2017;99-B:184-91.
The affinities of extinct organisms are often difficult to resolve using morphological data alone. Chemical analysis of carbonaceous specimens can complement traditional approaches, but the search ...for taxon-specific signals in ancient, thermally altered organic matter is challenging and controversial, partly because suitable positive controls are lacking. Here, we show that non-destructive Fourier Transform Infrared Spectroscopy (FTIR) resolves in-situ molecular fingerprints in the famous 407 Ma Rhynie chert fossil assemblage of Aberdeenshire, Scotland, an important early terrestrial Lagerstätte. Remarkably, unsupervised clustering methods (principal components analysis and K-mean) separate the fossil spectra naturally into eukaryotes and prokaryotes (cyanobacteria). Additional multivariate statistics and machine-learning approaches also differentiate prokaryotes from eukaryotes, and discriminate eukaryotic tissue types, despite the overwhelming influence of silica. We find that these methods can clarify the affinities of morphologically ambiguous taxa; in the Rhynie chert for example, we show that the problematic "nematophytes" have a plant-like composition. Overall, we demonstrate that the famously exquisite preservation of cells, tissues and organisms in the Rhynie chert accompanies similarly impressive preservation of molecular information. These results provide a compelling positive control that validates the use of infrared spectroscopy to investigate the affinity of organic fossils in chert.
With the current UK expansion of proton therapy there is a great opportunity for clinical oncologists to develop a translational interest in the associated scientific base and clinical results. In ...particular, the underpinning controversy regarding the conversion of photon dose to proton dose by the relative biological effectiveness (RBE) must be understood, including its important implications. At the present time, the proton prescribed dose includes an RBE of 1.1 regardless of tissue, tumour and dose fractionation. A body of data has emerged against this pragmatic approach, including a critique of the existing evidence base, due to choice of dose, use of only acute-reacting in vivo assays, analysis methods and the reference radiations used to determine the RBE. Modelling systems, based on the best available scientific evidence, and which include the clinically useful biological effective dose (BED) concept, have also been developed to estimate proton RBEs for different dose and linear energy transfer (LET) values. The latter reflect ionisation density, which progressively increases along each proton track. Late-reacting tissues, such as the brain, where α/β = 2 Gy, show a higher RBE than 1.1 at a low dose per fraction (1.2–1.8 Gy) at LET values used to cover conventional target volumes and can be much higher. RBE changes with tissue depth seem to vary depending on the method of beam delivery used. To reduce unexpected toxicity, which does occasionally follow proton therapy, a more rational approach to RBE allocation, using a variable RBE that depends on dose per fraction and the tissue and tumour radiobiological characteristics such as α/β, is proposed.
•Proton therapy prescriptions contain a constant relative biological effectiveness (RBE) weighting factor.•If the RBE is incorrect, over- or under-dosage may occur.•The RBE is actually variable, increasing at low dose in late-reacting normal tissues.•RBE can be modelled, providing safer dose prescriptions.
The Ediacaran period witnessed transformational change across the Earth-life system, but life on land during this interval is poorly understood. Non-marine/transitional Ediacaran sediments preserve a ...variety of probable microbially induced sedimentary structures and fossil matgrounds, and the ecology, biogeochemistry and sedimentological impacts of the organisms responsible are now ripe for investigation. Here, we report well-preserved fossils from emergent siliciclastic depositional environments in the Ediacaran of Newfoundland, Canada. These include exquisite, mouldically preserved microbial mats with desiccation cracks and flip-overs, abundant
-type fossils and, most notably, assemblages of centimetre-to-metre-scale, subparallel, branching, overlapping, gently curving ribbon-like features preserved by aluminosilicate and phosphate minerals, with associated filamentous microfossils. We present morphological, petrographic and taphonomic evidence that the ribbons are best interpreted as fossilized current-induced biofilm streamers, the earliest record of an important mode of life (macroscopic streamer formation) for terrestrial microbial ecosystems today. Their presence shows that late Ediacaran terrestrial environments could produce substantial biomass, and supports recent interpretations of
as a current-influenced microbial mat fossil, which we here suggest existed on a 'streamer-arumberiamorph spectrum'. Finally, the absence of classic Ediacaran macrobiota from these rocks despite evidently favourable conditions for soft tissue preservation upholds the consensus that those organisms were exclusively marine.
Background
We previously reported that probiotic and peanut oral immunotherapy (PPOIT) was effective at inducing sustained unresponsiveness compared with placebo in a double‐blind, placebo‐controlled ...randomized trial. This study evaluated the impact of PPOIT on health‐related quality of life (HRQL).
Method
Fifty‐one participants (PPOIT 24; placebo 27) from the PPOIT trial completed Food Allergy Quality of Life Questionnaire (FAQLQ‐PF) and Food Allergy Independent Measure (FAIM) at pre‐treatment, end‐of‐treatment and 3 months after end‐of‐treatment. A total of 42 participants (20 PPOIT; 22 placebo) completed measures at 12 months post‐treatment. Changes over time in PPOIT and placebo groups were examined by repeated‐measures analysis of variance and paired t tests.
Results
Probiotic and peanut oral immunotherapy was associated with significant improvement in FAQLQ‐PF (F = 3.63, P = .02), with mean difference 0.8 at 3 months post‐treatment (P = .05) and 1.3 at 12 months post‐treatment (P = .005), exceeding the 0.5 minimal clinically important difference for FAQLQ‐PF. For FAIM, mean difference was 0.5 (P = .03) at 3 months and 0.4 (P = .04) at 12 months post‐treatment. In placebo group, post‐treatment FAQLQ and FAIM remained unchanged from pretreatment. Improvement in FAQLQ‐PF and FAIM scores related specifically to acquisition of sustained unresponsiveness rather than to receiving PPOIT treatment or participation in the trial.
Conclusions
Probiotic and peanut oral immunotherapy has a sustained beneficial effect on psychosocial impact of food allergy at 3 and 12 months after end‐of‐treatment. Treatment was not associated with reduced HRQL relative to baseline in either PPOIT or placebo groups, indicating that PPOIT was well tolerated and psychological well‐being was not negatively impacted. Improved HRQL was specifically associated with acquisition of sustained unresponsiveness.
Chondroitin sulfate proteoglycans (CSPGs) are inhibitory extracellular matrix molecules that are upregulated after CNS injury. Degradation of CSPGs using the enzyme chondroitinase ABC (ChABC) can ...promote functional recovery after spinal cord injury. However, the mechanisms underlying this recovery are not clear. Here we investigated the effects of ChABC treatment on promoting plasticity within the spinal cord. We found robust sprouting of both injured (corticospinal) and intact (serotonergic) descending projections as well as uninjured primary afferents after a cervical dorsal column injury and ChABC treatment. Sprouting fibers were observed in aberrant locations in degenerating white matter proximal to the injury in regions where CSPGs had been degraded. Corticospinal and serotonergic sprouting fibers were also observed in spinal gray matter at and below the level of the lesion, indicating increased innervation in the terminal regions of descending projections important for locomotion. Spinal-injured animals treated with a vehicle solution showed no significant sprouting. Interestingly, ChABC treatment in uninjured animals did not induce sprouting in any system. Thus, both denervation and CSPG degradation were required to promote sprouting within the spinal cord. We also examined potential detrimental effects of ChABC-induced plasticity. However, although primary afferent sprouting was observed after lumbar dorsal column lesions and ChABC treatment, there was no increased connectivity of nociceptive neurons or development of mechanical allodynia or thermal hyperalgesia. Thus, CSPG digestion promotes robust sprouting of spinal projections in degenerating and denervated areas of the spinal cord; compensatory sprouting of descending systems could be a key mechanism underlying functional recovery.
This study investigated the possibility that sublethal food preservation stresses (high or low temperature and osmotic and pH stress) can lead to changes in the nature and scale of antibiotic ...resistance (ABR) expressed by three food-related pathogens (Escherichia coli, Salmonella enterica serovar Typhimurium, and Staphylococcus aureus). The study found that some sublethal stresses significantly altered antibiotic resistance. Incubation at sublethal high temperature (45°C) decreased ABR. Incubation under increased salt (>4.5%) or reduced pH (<5.0) conditions increased ABR. Some of the pathogens continued to express higher levels of ABR after removal of stress, suggesting that in some cases the applied sublethal stress had induced stable increases in ABR. These results indicate that increased use of bacteriostatic (sublethal), rather than bactericidal (lethal), food preservation systems may be contributing to the development and dissemination of ABR among important food-borne pathogens.
High atomic number (Z) materials such as gold preferentially absorb kilovoltage x-rays compared to soft tissue and may be used to achieve local dose enhancement in tumours during treatment with ...ionizing radiation. Gold nanoparticles have been demonstrated as radiation dose enhancing agents in vivo and in vitro. In the present study, we used multiple endpoints to characterize the cellular cytotoxic response of a range of cell lines to 1.9 nm gold particles and measured dose modifying effects following transient exposure at low concentrations. Gold nanoparticles caused significant levels of cell type specific cytotoxicity, apoptosis and increased oxidative stress. When used as dose modifying agents, dose enhancement factors varied between the cell lines investigated with the highest enhancement being 1.9 in AGO-1522B cells at a nanoparticle concentration of 100 microg ml(-1). This study shows exposure to 1.9 nm gold particles to induce a range of cell line specific responses including decreased clonogenic survival, increased apoptosis and induction of DNA damage which may be mediated through the production of reactive oxygen species. This is the first study involving 1.9 nm nanometre sized particles to report multiple cellular responses which impact on the radiation dose modifying effect. The findings highlight the need for extensive characterization of responses to gold nanoparticles when assessing dose enhancing potential in cancer therapy.
Chronic infection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) affects an estimated 35 million and 75 million individuals worldwide, respectively. These viruses induce ...persistent inflammation which often drives the development or progression of organ-specific diseases and even cancer including Hepatocellular Carcinoma (HCC). In this study, we sought to examine inflammatory responses following HIV or HCV stimulation of macrophages or Kupffer cells (KCs), that may contribute to virus mediated inflammation and subsequent liver disease. KCs are liver-resident macrophages and reports have provided evidence that HIV can stimulate and infect them. In order to characterize HIV-intrinsic innate immune responses that may occur in the liver, we performed microarray analyses on KCs following HIV stimulation. Our data demonstrate that KCs upregulate several innate immune signaling pathways involved in inflammation, myeloid cell maturation, stellate cell activation, and Triggering Receptor Expressed on Myeloid cells 1 (TREM1) signaling. TREM1 is a member of the immunoglobulin superfamily of receptors and it is reported to be involved in systemic inflammatory responses due to its ability to amplify activation of host defense signaling pathways. Our data demonstrate that stimulation of KCs with HIV or HCV induces the upregulation of TREM1. Additionally, HIV viral proteins can upregulate expression of TREM1 mRNA through NF-кB signaling. Furthermore, activation of the TREM1 signaling pathway, with a targeted agonist, increased HIV or HCV-mediated inflammatory responses in macrophages due to enhanced activation of the ERK1/2 signaling cascade. Silencing TREM1 dampened inflammatory immune responses elicited by HIV or HCV stimulation. Finally, HIV and HCV infected patients exhibit higher expression and frequency of TREM1 and CD68 positive cells. Taken together, TREM1 induction by HIV contributes to chronic inflammation in the liver and targeting TREM1 signaling may be a therapeutic option to minimize HIV induced chronic inflammation.
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