Lower extremities magnetic resonance angiography with blood pressure cuff compression: Quantitative dynamic analysis

Purpose

To quantitatively evaluate changes induced by the application of a femoral blood‐pressure cuff (BPC) on run‐off magnetic resonance angiography (MRA), which is a method generally previously proposed to reduce venous contamination in the leg.

Materials and Methods

This study was Health Insurance Portability and Accountability Act (HIPAA)‐ and Institutional Review Board (IRB)‐compliant. We used time‐resolved gradient‐echo gadolinium (Gd)‐enhanced MRA to measure BPC effects on arterial, venous, and soft‐tissue enhancement. Seven healthy volunteers (six men) were studied with the BPC applied at the mid‐femoral level unilaterally using a 1.5T MR system after intravenous injection of Gd‐BOPTA. Different statistical tools were used such as the Wilcoxon signed rank test and a cubic smoothing spline fit.

Results

We found that BPC application induces delayed venous filling (as previously described), but also induces significant decreases in arterial inflow, arterial enhancement, vascular‐soft tissue contrast, and delayed peak enhancement (which have not been previously measured).

Conclusion

The potential benefits from using a BPC for run‐off MRA must be balanced against the potential pitfalls, elucidated by our findings. J. Magn. Reson. Imaging 2009;29:1450–1456. © 2009 Wiley‐Liss, Inc.     

Development and initial validation of a cost-effective,re-usable,ultrasound-compatible suprapubic catheter insertion training simulator

IntroductionSuprapubic catheterization (SPC) is a fundamental skill required of urology trainees. A lack of affordable simulation models and unpredictability of bedside SPCs limit experiential learning opportunities. Our objective was to develop and initially validate a re-usable, low-cost, ultrasound (US)-compatible SPC simulator for acquiring skills that transfer to the bedside.MethodsThe model was constructed using six components. Staff urologists and interventional radiologists (IRs) conducted a SPC and rated the model on three domains with multiple subcategories on a five-point Likert scale: anatomic realism; usefulness as a training tool; and global/overall reaction. Participants in our first-year urology “boot camp” received SPC training, practiced, and were evaluated via an objective structured clinical examination (OSCE). Staff ratings and OSCE scores determined the model’s initial face and content validity.ResultsTwelve staff physicians participated in the study. The mean scores for urologists and IRs, respectively, were: anatomical realism: 4.10 and 3.70; usefulness as a training tool: 4.23 and 4.24; and overall reaction: 4.40 and 4.44. Staff strongly agreed that the model should be incorporated into the residency curriculum. Over the past four years, 25 boot camp participants scored a mean of 99.7% (±1.8) on the OSCE, with high technical performance and entrustment scores (4.8 and 4.7, respectively). The model cost $55 CAD.ConclusionsThis novel, multiple-use, low-cost, easily reproducible US-compatible SPC simulator demonstrated initial face and content validity via high staff urologist and IR ratings and OSCE scores of first-year urology residents. Additional research is required for construct validation.     

Comparative Evaluation of Rapid Isothermal Amplification and Antigen Assays for Screening Testing of SARS-CoV-2

Human transmission of SARS-CoV-2 and emergent variants of concern continue to occur globally, despite mass vaccination campaigns. Public health strategies to reduce virus spread should therefore rely, in part, on frequent screening with rapid, inexpensive, and sensitive tests. We evaluated two digitally integrated rapid tests and assessed their performance using stored nasal swab specimens collected from individuals with or without COVID-19. An isothermal amplification assay combined with a lateral flow test had a limit of detection of 10 RNA copies per reaction, and a positive percent agreement (PPA)/negative percent agreement (NPA) during the asymptomatic and symptomatic phases of 100%/100% and 95.83/100%, respectively. Comparatively, an antigen-based lateral flow test had a limit of detection of 30,000 copies and a PPA/NPA during the asymptomatic and symptomatic phases of 82.86%/98.68% and 91.67/100%, respectively. Both the isothermal amplification and antigen-based lateral flow tests had optimized detection of SARS-CoV-2 during the peak period of transmission; however, the antigen-based test had reduced sensitivity in clinical samples with qPCR Ct values greater than 29.8. Low-cost, high-throughput screening enabled by isothermal amplification or antigen-based techniques have value for outbreak control.     

Functional analysis of novel KCNQ2 mutations found in patients with Benign Familial Neonatal Convulsions

Benign Familial Neonatal Convulsions (BFNC) are a rare epilepsy disorder with an autosomal-dominant inheritance. It is linked to mutations in the potassium channel genes KCNQ2 and KCNQ3. These encode for Kv7.2 and Kv7.3 potassium ion channels, which produce an M-current that regulates the potential firing action in neurons through modulation of the membrane potential. We report on the biophysical and biochemical properties of V589X, T359K and P410fs12X mutant-KCNQ2 ion channels that were detected in three BFNC families. Mutant KCNQ2 cDNAs were co-expressed with WT-KCNQ2 and KCNQ3 cDNAs in HEK293 cells to mimic heterozygous expression of the KCNQ2 mutations in BFNC patients. The resulting potassium currents were measured using patch-clamp techniques and showed an approximately 75% reduction in current and a depolarized shift in the voltage dependence of activation. Furthermore, the time-constant of activation of M-currents in cells expressing T359K and P410fs12X was slower compared to cells expressing only wild-type proteins. Immunofluorescent labeling of HEK293 cells stably expressing GFP-tagged KCNQ2-WT or mutant α-subunits indicated cell surface expression of WT, V589X and T359K mutants, suggesting a loss-of-function, while P410fs12X was predominantly retained in the ER and sub-cellular compartments outside the ER suggesting an effectively haplo-insufficient effect.     

The impact of telomere erosion on memory CD8+ T cells in patients with X-linked lymphoproliferative syndrome

Patients with X-linked lymphoproliferative syndrome (XLP) experience excessive T cell proliferation after primary Epstein-Barr virus (EBV) infection, due to mutations in the signalling lymphocyte activation molecule (SLAM) associated protein (SAP) molecule. We examined the impact of dysfunctional proliferative control on the extent of CD8+ T cell differentiation in XLP patients who recovered from primary EBV infection. Although these young patients have normal numbers of lytic and latent EBV-epitope-specific CD8+ T cells, they were extremely differentiated as defined by loss of CCR7 and CD27, low telomerase activity and very short telomeres. This was not a direct effect arising from the loss of SAP, but was due to excessive T cell stimulation due to this defect. Thus, transduction of XLP CD8+ T cells with the catalytic component of telomerase (hTERT), but not SAP, prevented telomere loss and considerably extended proliferative lifespan in vitro. These results indicate that excessive proliferation in CD8+ T cells in XLP patients may lead to end-stage differentiation and loss of functional EBV-specific CD8+ T cells through replicative senescence. This may contribute to the defective immunity found in XLP patients who survive acute EBV infection who develop EBV-related B cell lymphomas before the fourth decade of life.