A proverb comprehension task was administered to typically-achieving children and adolescents who were aged 9, 11 and 14 years (n = 31 per group). Two types of unfamiliar concrete proverbs were presented in a multiple-choice format - expressions whose literal meanings could be true in the real world (e.g. The baby has no teeth) and expressions whose literal meanings could not be true (e.g. Every dog is a lion at home). No differences were found in ease of understanding between the two types of proverbs for any age groups. The results are explained in terms of children’s early-emerging ability to think metaphorically and are consistent with the view that figurative language ‘is a direct, automatic and natural reflection of the way people think, reason and imagine’. Implications of the study for designing instructional programmes in proverb comprehension for children and adolescents are discussed.
Significance Statement CKD is accompanied by abnormal inflammation, which contributes to progressive loss of functional renal tissue and accelerated cardiovascular disease. Although studies have documented that dysregulation of monocyte maturation and function is associated with CKD and its complications, it is not well characterized. This study reveals that a distinctive human monocyte subtype with high propensity for releasing proinflammatory mediators and activating endothelial cells is increased in adults with CKD compared with adults with high cardiovascular risk and normal kidney function. It also demonstrates that human monocyte adhesion to endothelial layers and responses to specific inflammatory migration signals are enhanced in CKD. These findings offer insights into the mechanisms of CKD-associated intravascular and localized inflammation and may suggest potential targets for therapeutic interventions. Background Cardiovascular disease (CVD) in patients with CKD is associated with increased circulating intermediate monocytes (IMs). Dysregulation of monocyte maturation and function is associated with CKD and its complications, but it is incompletely characterized. Methods To explore monocyte repertoire abnormalities in CKD, we studied properties of monocyte subpopulations, including IM subpopulations distinguished by HLA-DR expression level, in individuals with or without CKD. Using flow cytometry, we profiled monocyte populations in blood samples from adults with CKD, healthy volunteers (HVs), and patient controls (PCs) with high CVD risk. Monocyte subpopulations were also derived from single-cell RNA-sequencing profiles of paired blood and biopsy samples from kidney transplant recipients. We quantified intracellular cytokine production, migration, and endothelial adhesion in ex vivo assays of PBMCs. Results Of four predefined blood monocyte subpopulations, only HLA-DRhi IMs were increased in individuals with CKD compared with HVs and PCs. In HVs and patients with CKD, LPS-stimulated HLA-DRhi IMs isolated from blood produced higher amounts of TNF and IL-1β than other monocyte populations. Single-cell analysis revealed four monocyte clusters common to blood and kidneys, including an HLA-DRhi IM–like cluster that was enriched in kidneys versus blood. Migration toward CCL5 and CX3CL1 and adhesion to primary endothelial cell layers were increased in monocyte subpopulations in individuals with CKD compared with HVs. Monocyte adhesion to endothelial cells was partly dependent on CX3CR1/CX3CL1 interaction. Conclusions CKD is associated with an increased number of a distinctive proinflammatory IM subpopulation and abnormalities of monocyte migration and endothelial adhesion. Dysregulated monocyte maturation and function may represent targetable factors contributing to accelerated CVD in CKD.
Bortezomib is a proteasome inhibitor, used in the treatment of multiple myeloma. Bortezimib induced peripheral neuropathy (BIPN) is classically a painful, sensory predominant, length dependent axonal neuropathy [1]. Atypical presentations including demyelinating neuropathies can occur, though rarely (2].We identified 4 patients from the Manchester Centre for Clinical Neuroscience with atypical BIPN. All 4 had multiple myeloma and developed symptoms within 2 cycles of intravenous treatment.Case 1 and 2 developed proximal and distal motor weakness and neuropathic pain. Neurophysiology confirmed mixed demyelinating/axonal neuropathy in both. Cerebral Spinal Fluid analysis confirmed albuminocytological dissociation. Immunomodulatory treatment with IVIg and steroids had minimal effect.Case 3 developed left hand weakness, predominantly affecting the radial musculature with motor conduction block on neurophysiology.Case 4 developed whole body paraesthesias, ataxia and thoracic radicular pain after 2 cycles, neurophysiology confirmed a sensory neuronopathy.Case 2 died due to disease progression, the other 3 cases improved on withdrawal of Bortezimib.ConclusionBIPN can cause neuropathy phenotypes including sensory neuronopathy, motor neuropathy with conduction block and severe demyelinating polyradiculoneuritis. Immunogenic, as well as toxic mechanisms may have a role in the pathogenesis of BIPN.1. Chaudhry V, Cornblath D, Polydefkis M, Ferguson A, Borrello I. Characteristics of bortezomib- and thalidomide-induced peripheral neuropathy. Journal of the Peripheral Nervous System. 2008;13(4):275–2822. Thawani S, Tanji K, De Sousa E, Weimer L, Brannagan T. Bortezomib-Associated Demyelinating Neuropathy—Clinical and Pathologic Features. Journal of Clinical Neuromuscular Disease. 2015;16(4):202–209tim.lavin@srft.nhs.uk
A systematic but individual approach was employed in one District with all diabetic patients who requested the change from human insulin to animal insulin. Psychometric assessments and clinical interviews were recorded throughout the process. There are strong suggestions that problems with control were erroneously attributed by the patients to the human insulin, and this view was given validity by the media. Nevertheless, accepting patients' preferences and giving them control led to a good outcome in terms of emotional adjustment. This approach demonstrates a patientcentred approach wherein objective medical evidence is but one source of information upon which to base clinical practice.
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