To observe and describe the development and underlying structure of the spinal manifestations of individuals osteologically diagnosed with DISH (Diffuse Idiopathic Skeletal Hyperostosis), using ...micro-XCT imaging.
A total of 72 individuals with DISH were identified in two modern skeletal collections in South Africa.
Vertebral columns affected by DISH were scanned at the micro-focus x-ray computed tomography facility at the Nuclear Energy Corporation of South Africa. Four features were macroscopically examined: (1) the origin of the new bone growth; (2) retention of the original vertebral cortex at the site of the new bone formation associated with DISH; (3) evidence of trabecular bone with or without sclerosis on the anterolateral surface of affected vertebrae; and (4) abnormal areas of osteosclerosis beyond features associated with DISH.
Considerable variation across and between the four recorded features was found. Of note, 81% (n = 58) of individuals had both developed trabecular bone within the flowing new bone formation (feature 3), without retention of the original vertebral cortex (feature 2).
Possible localised erosive/inflammatory processes destroyed the original cortex of the vertebral body and resulted in the expansion of trabeculae with new bone formation.
Micro-XCT imaging shed new light on the development of DISH, adding to literature suggesting that it could be an inflammatory disease.
Clinical histories of the individuals were not known.
The role of chronic inflammatory disease in the development of DISH should be further explored including both the extra-spinal and spinal manifestations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The neonatal crystallizable fragment receptor (FcRn) functions as an intracellular protection receptor for immunoglobulin G (IgG). Recently, several clinical studies have reported the lowering of ...circulating monomeric IgG levels through FcRn blockade for the potential treatment of autoimmune diseases. Many autoimmune diseases, however, are derived from the effects of IgG immune complexes (ICs). We generated, characterized, and assessed the effects of SYNT001, a FcRn-blocking monoclonal antibody, in mice, nonhuman primates (NHPs), and humans. SYNT001 decreased all IgG subtypes and IgG ICs in the circulation of humans, as we show in a first-in-human phase 1, single ascending dose study. In addition, IgG IC induction of inflammatory pathways was dependent on FcRn and inhibited by SYNT001. These studies expand the role of FcRn in humans by showing that it controls not only IgG protection from catabolism but also inflammatory pathways associated with IgG ICs involved in a variety of autoimmune diseases.
Ethanol exposure during pregnancy is an established cause of birth defects, including neurodevelopmental defects. Most adult neurons are produced during the second trimester-equivalent period. The ...fetal neural stem cells (NSCs) that generate these neurons are an important but poorly understood target for teratogenesis. A cohort of miRNAs, including miR-153, may serve as mediators of teratogenesis. We previously showed that ethanol decreased, while nicotine increased miR-153 expression in NSCs. To understand the role of miR-153 in the etiology of teratology, we first screened fetal cortical NSCs cultured ex vivo, by microarray and quantitative RT-PCR analyses, to identify cell-signaling mRNAs and gene networks as important miR-153 targets. Moreover, miR-153 over-expression prevented neuronal differentiation without altering neuroepithelial cell survival or proliferation. Analysis of 3'UTRs and in utero over-expression of pre-miR-153 in fetal mouse brain identified Nfia (nuclear factor-1A) and its paralog, Nfib, as direct targets of miR-153. In utero ethanol exposure resulted in a predicted expansion of Nfia and Nfib expression in the fetal telencephalon. In turn, miR-153 over-expression prevented, and partly reversed, the effects of ethanol exposure on miR-153 target transcripts. Varenicline, a partial nicotinic acetylcholine receptor agonist that, like nicotine, induces miR-153 expression, also prevented and reversed the effects of ethanol exposure. These data collectively provide evidence for a role for miR-153 in preventing premature NSC differentiation. Moreover, they provide the first evidence in a preclinical model that direct or pharmacological manipulation of miRNAs have the potential to prevent or even reverse effects of a teratogen like ethanol on fetal development.
A new synthetic route to nanoparticulate tungsten carbide–cobalt is demonstrated, using a sol–gel approach in an aqueous solution containing a biopolymer. On calcination, the biopolymer was found to ...act both as a source of carbon and also as an anti-sintering, structure-directing template. By keeping the tungsten carbide phase nanoparticulate, the hardness was found to be commensurate with that seen in more traditional ‘heat and beat’ syntheses.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The object of this study was to determine the sensitivity and specificity of the Cozart RapiScan onsite saliva test for methadone and opiates versus laboratory-based enzyme immunoassay (EIA) and gas ...chromatography-mass spectrometry (GC-MS) confirmation. Fifty saliva specimens were obtained from 28 volunteers among persons entering a substance abuse clinic. Specimens were tested onsite using the Cozart RapiScan Saliva test and Cozart RapiScan Reader. Specimens were retested by Cozart Microplate EIA assays on receipt at the laboratory and then frozen for later confirmation by GC-MS. For GC-MS, deuterated internal standards were added to specimen aliquots which were extracted using solid-phase columns at pH 6 and eluted with dichloromethane/isopropanol/ammonia (80:19:2). The dry residues were derivatized with PFOH and PFPA and dried, and the reconstituted extract was injected and quantitated by GC-MS. The Cozart RapiScan Methadone Saliva Assay was found to have a sensitivity and specificity of 100% ± 12% versus GC-MS (2-ng/mL cutoff) and a sensitivity of 100% ± 11% and a specificity of 95% ± 2.4% versus the Microplate EIA for methadone (30-ng/mL cutoff). The Cozart RapiScan Saliva Opiate test had a sensitivity of 100% ± 12% and a specificity of 92% ± 3.2% versus GC-MS (2-ng/mL cutoff) and a sensitivity of 96% ± 2.2% and specificity of 95% ± 2.4% versus the Microplate EIA for opiates (30-ng/mL cutoff).
The case history of a patient with a periorbital penetrating wooden foreign body is presented. The computerized tomography (CT) densities of several different sources of wood were compared using an ...experimental model. The clinical usefulness and practical limitations of CT in the evaluation of intracranial foreign bodies is discussed, and the management of this type of injury is reviewed.
Angioplasty of the proximal portions of major cerebral arteries at the base of the brain has shown promise as a therapy for symptomatic vasospasm after subarachnoid hemorrhage. The blind-ended, ...single-lumen balloon-dilatation catheter most widely used to date lacks steerability, limiting its application to unbranched stems and single branches at bi- or trifurcation points. To extend the capabilities of cerebral angioplasty, we describe two modifications of the basic technique that have allowed increased selectivity and successful angioplasty of multiple branches, both proximal and distal, involved by vasospasm. Of four patients treated, three showed early improvement in their clinical condition, likely attributable to the angioplasty procedure. Our modifications to the basic angioplasty technique enhanced its success. Further refinement of this technique in the treatment of vasospasm will make it safer in treating this serious and widespread disorder.
A model of the evaporation of water and saline solutions from a metal surface is developed. The evaporation of a droplet of moisture from a flat metal plate over which a uniform laminar flow of air ...occurs is modelled by assuming an analogy between heat and mass transfer. The model is adjusted to predict the evaporation of a saline solution under the assumption that the presence of the salt affects only the vapour pressure. The predictions of the model are compared with observed experimental evaporation rates and are found to be of reasonable accuracy. Predicted drying times for moisture films under conditions typical of those associated with building microclimates are determined. The implications of these drying times to the traditional estimation of time of wetness are assessed.
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IJS, IMTLJ, KILJ, KISLJ, NUK, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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