801 research outputs found

    Quantifying Muscle Size Asymmetry in Adolescent Idiopathic Scoliosis Using Three-dimensional Magnetic Resonance Imaging

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    STUDY DESIGN: This is a case-control study of prospectively collected data.OBJECTIVE: To quantify paraspinal muscle size asymmetry in adolescent idiopathic scoliosis (AIS) and determine if this asymmetry is i) greater than observed in adolescent controls with symmetrical spines; and ii) positively associated with skeletal maturity using Risser grade, scoliosis severity using the Cobb angle, and chronological age in years.SUMMARY OF BACKGROUND DATA: AIS is a three-dimensional deformity of the spine which occurs in 2.5-3.7% of the Australian population. There is some evidence of asymmetry in paraspinal-muscle activation and morphology in AIS. Asymmetrical paraspinal muscle forces may facilitate asymmetrical vertebral growth during adolescence.METHODS: An asymmetry index [Ln(concave/convex volume)] of i) deep and ii) superficial paraspinal-muscle volumes, at the level of the i) major curve apex (Thoracic 8-9 th vertebral level) and ii) lower-end vertebrae ( LEV , Thoracic 10-12 th vertebral level), was determined from 3D Magnetic Resonance Imaging (MRI) of 25 adolescents with AIS (all right thoracic curves), and 22 healthy controls (convex=left); all female, 10-16 years.RESULTS: Asymmetry index of deep paraspinal-muscle volumes was greater in AIS (0.16±0.20) than healthy spine controls (-0.06±0.13) at the level of the apex ( P 0.05). Asymmetry index was positively correlated with Risser grade (r=0.50, P 0.05). There was no difference in the asymmetry index of superficial paraspinal muscle volumes between AIS and controls ( P >0.05).CONCLUSIONS: The asymmetry of deep apical paraspinal-muscle volume in AIS at the scoliosis apex is greater than that observed at equivalent vertebral levels in controls and may play a role in the pathogenesis of AIS.</p

    Diagnosis and investigation of suspected haemophagocytic lymphohistiocytosis in adults: 2023 Hyperinflammation and HLH Across Speciality Collaboration (HiHASC) consensus guideline

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    Haemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome characterised by persistently activated cytotoxic lymphocytes and macrophages, which, if untreated, leads to multiorgan dysfunction and death. HLH should be considered in any acutely unwell patient not responding to treatment as expected, with prompt assessment to look for what we term the three Fs—fever, falling blood counts, and raised ferritin. Worldwide, awareness of HLH and access to expert management remain inequitable. Terminology is not standardised, classification criteria are validated in specific patient groups only, and some guidelines rely on specialised and somewhat inaccessible tests. The consensus guideline described in this Health Policy was produced by a self-nominated working group from the UK network Hyperinflammation and HLH Across Speciality Collaboration (HiHASC), a multidisciplinary group of clinicians experienced in managing people with HLH. Combining literature review and experience gained from looking after patients with HLH, it provides a practical, structured approach for all health-care teams managing adult (>16 years) patients with possible HLH. The focus is on early recognition and diagnosis of HLH and parallel identification of the underlying cause. To ensure wide applicability, the use of inexpensive, readily available tests is prioritised, but the role of specialist investigations and their interpretation is also addressed

    Multiple early factors anticipate post-acute COVID-19 sequelae.

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    Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific auto-antibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes, exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time, leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies

    Sex-Specific Differences in Cytokine Induction by the Glycolipid Adjuvant 7DW8-5 in Mice

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    7DW8-5 is a potent glycolipid adjuvant that improves malaria vaccine efficacy in mice by inducing IFN-γ and increasing protective CD8+ T cell responses. The addition of 7DW8-5 was previously shown to improve the efficacy of a CD8+ T cell-mediated heterologous ‘prime-and-trap’ malaria vaccine against Plasmodium yoelii sporozoite challenge in inbred female mice. Here, we report significant differential sex-specific responses to 7DW8-5 in inbred and outbred mice. Male mice express significantly less IFN-γ and IL-4 compared to females following intravenous 7DW8-5 administration. Additionally, unlike in female mice, 7DW8-5 did not improve the vaccine efficacy against sporozoite challenge in prime-and-trap vaccinated male mice. Our findings highlight the importance of including both female and male sexes in experimental adjuvant studies

    Impaired Glymphatic Function and Pulsation Alterations in a Mouse Model of Vascular Cognitive Impairment

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    ACKNOWLEDGMENTS Schematic diagrams in Figures 2, 8 are created withBiorender.com. FUNDING We gratefully acknowledge the grant support from the Alzheimer’s Society (152 (PG-157); 290 (AS-PG-15b-018); 228 (AS-DTC-2014-017), 314 (AS –PhD-16-006), and Alzheimer’s Research United Kingdom (ART-PG2010-3; ARUK-PG2013- 22; ARUK-PG2016B-6), and The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (G0700704/84698). ML and JB are funded by an Alzheimer’s Society Scotland Doctoral Training Programme and RS Macdonald Trust. ML was also funded by a China Scholarship Council (CSC)/University of Edinburgh scholarship.Peer reviewedPublisher PD

    Multiple early factors anticipate post-acute COVID-19 sequelae.

    No full text
    Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific auto-antibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8 &lt;sup&gt;+&lt;/sup&gt; T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes, exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time, leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies
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