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Restriction factors are a collection of antiviral proteins that form an important aspect of the innate immune system. Their constitutive expression allows immediate response to viral infection, ahead of other innate or adaptive immune responses. We review the molecular mechanism of restriction for four categories of restriction factors; TRIM5, tetherin, APOBEC3G and SAMHD1 and go on to consider how the TRIM5 and TRIMCyp proteins in particular, show promise for exploitation using gene therapy strategies. Such approaches could form an important alternative to current anti-HIV-1 drug regimens, especially if combined with strategies to eradicate HIV reservoirs. Autologous CD4+ T cells or their haematopoietic stem cell precursors engineered to express TRIMCyp restriction factors, and provided in a single therapeutic intervention could then be used to restore functional immunity with a pool of cells protected against HIV. We consider the challenges ahead and consider how early clinical phase testing may best be achieved. 相似文献
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Andrew Holden Andrew A. Hill Brendan Buckley Brigid Connor David Semple Stephen Merrilees Emma Marsh Aws Alfahad Ram Iyer 《Journal of vascular and interventional radiology : JVIR》2019,30(1):61-68
Purpose
A prospective, single-center, single-arm feasibility study evaluated procedural and short-term performance of the Advance Enforcer 35 focal-force percutaneous transluminal angioplasty (PTA) balloon catheter in treating stenoses of mature native arteriovenous (AV) hemodialysis access circuits.Materials and Methods
Twenty-eight patients undergoing treatment for stenosis of a mature native AV hemodialysis access circuit were enrolled at a single institution. Angiographic assessments of the study lesion were required at baseline and after the procedure. Adjunctive procedures for significant residual stenosis were permitted, and patients had clinical and imaging follow-up for as long as 6 months.Results
Treatment with the study balloon was effective in reducing the average percent diameter stenosis of the treated lesion from 66.3% (range, 43.8%–93.3%) before the procedure to 23.7% (range, ?6.7% to 51.4%) after the procedure. The average inflation pressure required was 12.3 atm. Only 1 patient required an adjunctive procedure, and all patients could resume normal dialysis following the study procedure. At 3 months, 62.0% of study lesions remained patent, and the 6-month patency rate was 25.1%. Two adverse events associated with the study procedure were reported: access-site hematoma and forearm pain (3.6% each).Conclusions
The results demonstrate safety of the study balloon in treating AV access stenosis. Nominal-diameter angioplasty was achieved at relatively low pressure in most study patients without the use of adjunctive procedures, and resumption of normal dialysis was achieved for all patients. 相似文献115.
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Aim: The aim of the paper was to identify changes in the extent and patterns of anabolic steroid use in the United Kingdom to better understand the public health implications within the context of the current health-related evidence base. Methods: Using the two time points between 1995 (prior to legislation changes in the United Kingdom) and 2015, a review of the evidence related to health harms was conducted, in conjunction with needle and syringe programme (NSP) data in Cheshire & Merseyside (UK) relating to anabolic steroid users. Findings: Dramatic increase in the number of anabolic steroid users accessing NSPs, 553 in 1995 to 2446 in 2015, now accounting for 54.9% of clients. With the inclusion of pharmacy NSPs, this rose to 5336 individual anabolic steroid users. Conclusions: Key changes in our knowledge during the 20 years, in particular, in relation to HIV prevalence, changes in the market and patterns of use make anabolic steroid use a public health concern. In the context of increasing numbers of injectors, there is a need for comprehensive interventions. 相似文献
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Wearable monitors for patients following discharge from an intensive care unit: practical lessons learnt from an observational study
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