Calcitriol modulates the CD46 pathway in T cells

The complement regulator CD46 is a costimulatory molecule for human T cells that induces a regulatory Tr1 phenotype, characterized by large amounts of IL-10 secretion. Secretion of IL-10 upon CD46 costimulation is largely impaired in T cells from patients with multiple sclerosis (MS). Vitamin D can exert a direct effect on T cells, and may be beneficial in several pathologies, including MS. In this pilot study, we examined whether active vitamin D (1,25(OH)2D3 or calcitriol) could modulate the CD46 pathway and restore IL-10 production by CD46-costimulated CD4+ T cells from patients with MS. In healthy T cells, calcitriol profoundly affects the phenotype of CD46-costimulated CD4+ T cells, by increasing the expression of CD28, CD25, CTLA-4 and Foxp3 while it concomitantly decreased CD46 expression. Similar trends were observed in MS CD4+ T cells except for CD25 for which a striking opposite effect was observed: while CD25 was normally induced on MS T cells by CD46 costimulation, addition of calcitriol consistently inhibited its induction. Despite the aberrant effect on CD25 expression, calcitriol increased the IL-10:IFNc ratio, characteristic of the CD46-induced Tr1 phenotype, in both T cells from healthy donors and patients with MS. Hence, we show that calcitriol affects the CD46 pathway, and that it promotes anti-inflammatory responses mediated by CD46. Moreover, it might be beneficial for T cell responses in MS

Heavy metals in aquatic macrophytes from two small rivers polluted by urban, agricultural and textile industry sewages SW Poland

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Challenges in the surgical management of spine trauma in the morbidly obese patient: A case series

Object: The treatment of morbidly obese individuals with spine trauma presents unique challenges to spine surgeons and trauma staff. This study aims to increase awareness of current limitations in the surgical management of spine trauma in morbidly obese individuals, and to illustrate practical solutions. Methods: Six morbidly obese patients were treated surgically for spine trauma over a 2-year period at a single trauma center in Australia. All patients were involved in high-speed motor vehicle accidents and had multisystem injuries. All weighed in excess of 265 pounds (120 kg) with a body mass index ≥ 40 (range 47.8–67.1). Cases were selected according to the considerable challenges they presented in all aspects of their management. Results: Best medical and surgical care may be compromised and outcome adversely affected in morbidly obese patients with spine trauma. The time taken to perform all aspects of care is usually extended, often by many hours. Customized orthotics may be required. Imaging quality is often compromised and patients may not fit into scanners. Surgical challenges include patient positioning, surgical access, confirmation of the anatomical level, and obtaining adequate instrument length. Postoperative nursing care, wound healing, and venous thromboembolism prophylaxis are also significant issues. Conclusions: Management pathways and hospital guidelines should be developed to optimize the treatment of morbidly obese patients, but innovative solutions may be required for individual cases.Hannah E. Rosenfeld, Rebecca Limb, Patrick Chan, Mark Fitzgerald, William Pierre Litherland Bradley, and Jeffrey V. Rosenfel

Is routine ophthalmoscopy really necessary in candidemic patients?

The purpose of this study was to determine among patients with candidemia the real rate of ophthalmoscopy and the impact of performing ocular assessment on the outcome of the disease. We performed a post hoc analysis of a prospective, multicenter, population-based candidemia surveillance program implemented in Spain during 2010-2011 (CANDIPOP). Ophthalmoscopy was performed in only 168 of the 365 patients with candidemia (46%). Ocular lesions related to candidemia were found in only 13/168 patients (7.7%), of whom 1 reported ocular symptoms (incidence of symptomatic disease in the whole population, 0.27% [1/365]). Ophthalmological findings led to a change in antifungal therapy in only 5.9% of cases (10/168), and performance of the test was not related to a better outcome. Ocular candidiasis was not associated with a worse outcome and progressed favorably in all but 1 evaluable patient, who did not experience vision loss. The low frequency of ophthalmoscopy and ocular involvement and the asymptomatic nature of ocular candidiasis, with a favorable outcome in almost all cases, lead us to reconsider the need for systematic ophthalmoscopy in all candidemic patients