2,282 research outputs found

    Abdominopelvic Splenosis—An Unusual Cause of Tenesmus

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    Splenosis is a rare condition defined as seeding and autotransplantation of splenic tissue, typically after blunt abdominal trauma (e.g. from road traffic collision). Sites of splenosis ranging from intrathoracic to intrapelvic have been reported, and symptoms vary greatly depending on the site and size of lesions. We present the use of Tc-99m sulphur colloid SPECT/CT in diagnosing a case of multiple abdominopelvic splenosis as the cause of new-onset tenesmus and constipation, which was initially thought to be due to colorectal malignancy, 47 years following the initial abdominal trauma

    Coherent states for compact Lie groups and their large-N limits

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    The first two parts of this article surveys results related to the heat-kernel coherent states for a compact Lie group K. I begin by reviewing the definition of the coherent states, their resolution of the identity, and the associated Segal-Bargmann transform. I then describe related results including connections to geometric quantization and (1+1)-dimensional Yang--Mills theory, the associated coherent states on spheres, and applications to quantum gravity. The third part of this article summarizes recent work of mine with Driver and Kemp on the large-N limit of the Segal--Bargmann transform for the unitary group U(N). A key result is the identification of the leading-order large-N behavior of the Laplacian on "trace polynomials."Comment: Submitted to the proceeding of the CIRM conference, "Coherent states and their applications: A contemporary panorama.

    Update on imaging in rheumatology – recent advances

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    Imaging plays a vital role in the diagnosis and management of rheumatological disorders. Traditionally, plain film radiography was widely used in arthropathies to assess periarticular bony changes; these often reflect established changes in the late stage of disease and thus have limited value in early diagnosis and disease monitoring. Magnetic resonance imaging (MRI) has become an important imaging modality in rheumatological disorders because it can assess both morphological and functional changes. It plays a substantial role in early diagnosis, monitoring of disease evolution, assessment of treatment responses and prognostication. More recently, advances in hardware and novel imaging sequences have aided the development of new MRI techniques: whole-body MRI, for example, is gaining in popularity and allows an assessment of overall inflammatory status in arthritis. Quantitative MRI shows promise in allowing more objective evaluation and standardization of imaging-based assessment of inflammatory arthritis. This article also discusses other emerging imaging techniques. These include high-resolution peripheral quantitative computed tomography in early detection and monitoring of periarticular bone damage, fluorescence optical imaging in visualizing active inflammation, and molecular imaging in investigating pathogenesis and disease evaluation on a cellular level

    Complex -Glycans Influence the Spatial Arrangement of Voltage Gated Potassium Channels in Membranes of Neuronal-Derived Cells

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    The intrinsic electrical properties of a neuron depend on expression of voltage gated potassium (Kv) channel isoforms, as well as their distribution and density in the plasma membrane. Recently, we showed that N-glycosylation site occupancy of Kv3.1b modulated its placement in the cell body and neurites of a neuronal-derived cell line, B35 neuroblastoma cells. To extrapolate this mechanism to other N-glycosylated Kv channels, we evaluated the impact of N-glycosylation occupancy of Kv3.1a and Kv1.1 channels. Western blots revealed that wild type Kv3.1a and Kv1.1 α-subunits had complex and oligomannose N-glycans, respectively, and that abolishment of the N-glycosylation site(s) generated Kv proteins without N-glycans. Total internal reflection fluorescence microscopy images revealed that N-glycans of Kv3.1a contributed to its placement in the cell membrane while N-glycans had no effect on the distribution of Kv1.1. Based on particle analysis of EGFP-Kv proteins in the adhered membrane, glycosylated forms of Kv3.1a, Kv1.1, and Kv3.1b had differences in the number, size or density of Kv protein clusters in the cell membrane of neurites and cell body of B35 cells. Differences were also observed between the unglycosylated forms of the Kv proteins. Cell dissociation assays revealed that cell-cell adhesion was increased by the presence of complex N-glycans of Kv3.1a, like Kv3.1b, whereas cell adhesion was similar in the oligomannose and unglycosylated Kv1.1 subunit containing B35 cells. Our findings provide direct evidence that N-glycans of Kv3.1 splice variants contribute to the placement of these glycoproteins in the plasma membrane of neuronal-derived cells while those of Kv1.1 were absent. Further when the cell membrane distribution of the Kv channel was modified by N-glycans then the cell-cell adhesion properties were altered. Our study demonstrates that N-glycosylation of Kv3.1a, like Kv3.1b, provides a mechanism for the distribution of these proteins to the cell body and outgrowths and thereby can generate different voltage-dependent conductances in these membranes

    Multiple courses of stereotactic re-irradiation in recurrent oligodendroglioma: a case report

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    INTRODUCTION: High grade gliomas are an insidious disease associated with an extremely poor prognosis. The role of re-irradiation for recurrent gliomas is unclear but several retrospective studies have indicated mild toxicity and modest outcomes with this regimen. With subsequent progression, it is unclear what options remain and more radiotherapy is rarely offered for fear of surpassing normal central nervous system tissue tolerance and causing significant side effects without significant benefit. CASE PRESENTATION: In this report, we describe a 37-year-old Caucasian male initially diagnosed with a grade IV oligodendroglioma, who received multiple courses of re-irradiation and experienced a survival of 10 years with minimal cognitive or neurologic deficits. CONCLUSION: Significant toxicity with multiple courses of radiation does not always occur. Re-irradiation should be considered in a salvage setting

    Ethnic inequalities and pathways to care in psychosis in England: a systematic review and meta-analysis

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    © The Author(s). 2018Background: As part of a national programme to tackle ethnic inequalities, we conducted a systematic review and meta-analysis of research on ethnic inequalities in pathways to care for adults with psychosis living in England and/or Wales. Methods: Nine databases were searched from inception to 03.07.17 for previous systematic reviews, including forward and backward citation tracking and a PROSPERO search to identify ongoing reviews. We then carried forward relevant primary studies from included reviews (with the latest meta-analyses reporting on research up to 2012), supplemented by a search on 18.10.17 in MEDLINE, Embase, PsycINFO and CINAHL for primary studies between 2012 and 2017 that had not been covered by previous meta-analyses. Results: Forty studies, all conducted in England, were included for our updated meta-analyses on pathways to care. Relative to the White reference group, elevated rates of civil detentions were found for Black Caribbean (OR = 3.43, 95% CI = 2.68 to 4.40, n = 18), Black African (OR = 3.11, 95% CI = 2.40 to 4.02, n = 6), and South Asian patients (OR = 1.50, 95% CI 1.07 to 2.12, n = 10). Analyses of each Mental Health Act section revealed significantly higher rates for Black people under (civil) Section 2 (OR = 1.53, 95% CI = 1.11 to 2.11, n = 3). Rates in repeat admissions were significantly higher than in first admission for South Asian patients (between-group difference p < 0.01). Some ethnic groups had more police contact (Black African OR = 3.60, 95% CI = 2.15 to 6.05, n = 2; Black Caribbean OR = 2.64, 95% CI = 1.88 to 3.72, n = 8) and criminal justice system involvement (Black Caribbean OR = 2.76, 95% CI = 2.02 to 3.78, n = 5; Black African OR = 1.92, 95% CI = 1.32 to 2.78, n = 3). The White Other patients also showed greater police and criminal justice system involvement than White British patients (OR = 1.49, 95% CI = 1.03 to 2.15, n = 4). General practitioner involvement was less likely for Black than the White reference group. No significant variations over time were found across all the main outcomes. Conclusions: Our updated meta-analyses reveal persisting but not significantly worsening patterns of ethnic inequalities in pathways to psychiatric care, particularly affecting Black groups. This provides a comprehensive evidence base from which to inform policy and practice amidst a prospective Mental Health Act reform. Trial registration: CRD42017071663Peer reviewedFinal Published versio

    Transmembrane helix dynamics of bacterial chemoreceptors supports a piston model of signalling.

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    Transmembrane α-helices play a key role in many receptors, transmitting a signal from one side to the other of the lipid bilayer membrane. Bacterial chemoreceptors are one of the best studied such systems, with a wealth of biophysical and mutational data indicating a key role for the TM2 helix in signalling. In particular, aromatic (Trp and Tyr) and basic (Arg) residues help to lock α-helices into a membrane. Mutants in TM2 of E. coli Tar and related chemoreceptors involving these residues implicate changes in helix location and/or orientation in signalling. We have investigated the detailed structural basis of this via high throughput coarse-grained molecular dynamics (CG-MD) of Tar TM2 and its mutants in lipid bilayers. We focus on the position (shift) and orientation (tilt, rotation) of TM2 relative to the bilayer and how these are perturbed in mutants relative to the wildtype. The simulations reveal a clear correlation between small (ca. 1.5 Å) shift in position of TM2 along the bilayer normal and downstream changes in signalling activity. Weaker correlations are seen with helix tilt, and little/none between signalling and helix twist. This analysis of relatively subtle changes was only possible because the high throughput simulation method allowed us to run large (n = 100) ensembles for substantial numbers of different helix sequences, amounting to ca. 2000 simulations in total. Overall, this analysis supports a swinging-piston model of transmembrane signalling by Tar and related chemoreceptors

    Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

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    The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition
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