HIV silencing and cell survival signatures in infected T cell reservoirs.

Rare CD4 T cells that contain HIV under antiretroviral therapy represent an important barrier to HIV cure1-3, but the infeasibility of isolating and characterizing these cells in their natural state has led to uncertainty about whether they possess distinctive attributes that HIV cure-directed therapies might exploit. Here we address this challenge using a microfluidic technology that isolates the transcriptomes of HIV-infected cells based solely on the detection of HIV DNA. HIV-DNA+ memory CD4 T cells in the blood from people receiving antiretroviral therapy showed inhibition of six transcriptomic pathways, including death receptor signalling, necroptosis signalling and antiproliferative Gα12/13 signalling. Moreover, two groups of genes identified by network co-expression analysis were significantly associated with HIV-DNA+ cells. These genes (n = 145) accounted for just 0.81% of the measured transcriptome and included negative regulators of HIV transcription that were higher in HIV-DNA+ cells, positive regulators of HIV transcription that were lower in HIV-DNA+ cells, and other genes involved in RNA processing, negative regulation of mRNA translation, and regulation of cell state and fate. These findings reveal that HIV-infected memory CD4 T cells under antiretroviral therapy are a distinctive population with host gene expression patterns that favour HIV silencing, cell survival and cell proliferation, with important implications for the development of HIV cure strategies.

A Pilot Feasibility Trial of an Upper Extremity Assistive System.

Objective: To develop and clinically evaluate a customizable active upper extremity (UE) assistive system with integrated functional electrical stimulation (FES) that improves function and independence of individuals during activities of daily living (ADLs). Design: Single-arm, prospective, open-label cohort feasibility trial. Setting: An academic research institution. Participants: Subjects were 5 adults with a medical history of stroke resulting in distal UE impairment (N=5). The subjects volunteered from recruitment materials that detailed information about the study. Interventions: A novel, wearable, lightweight, low-profile, and patient-tailored UE assistive system. It comprises a splint component and FES unit that may each be controlled by electromyography (EMG) signals, inertial measurement units (IMUs), manual control source (joystick), and/or voice control. Main Outcome Measures: Several occupational therapy outcome measures were used, including the Canadian Occupational Performance Measure (COPM), Action Research Arm Test (ARAT), The Box and Blocks Test (BBT), the ABILHAND-Manual Ability Measure, and Patient Reported Outcomes Measurement Information System (PROMIS) UE Short Form. Results: All participants learned to use our UE assistive system to perform ADLs and were able to use it independently at home. Most participants experienced a clinically meaningful improvement in both performance and satisfaction for the majority of their COPM goals while using the system. All participants experienced improvement in hand grip and release as shown by their baseline and post assessment scores for hand function (BBT, ARAT) and patient-reported outcomes (ABILHAND, PROMIS). Conclusions: The clinical outcomes suggest that our UE assistive system improves functional performance in patients with UE impairment, allowing them to engage more actively in ADLs. Further innovation including elbow and shoulder components will allow users to have more degrees of freedom during tasks.

Use of the color Doppler twinkle artifact for teaching ultrasound guided peripheral vascular access.

BACKGROUND: The optimal method for teaching ultrasound guided peripheral IV (USGPIV) insertion is unknown. Poor needle tip visualization has been cited for USGPIV failure. Twinkle artifact (TA), visualized with color Doppler, is used in other clinical settings. Our objective was to investigate whether teaching students USGPIV placement utilizing TA would enhance needle tip visualization and improve first pass success. METHODS: This was a prospective, randomized study of premedical and preclinical medical students without prior USGPIV experience. Students were given a standardized didactic session on USGPIV placement before being randomized and separated to learn and practice USGPIV with or without TA (control). The students were given 5 min to perform USGPIV on phantom models. The primary outcome was the rate of first pass success. Secondary outcomes included total time to cannulation, rate of posterior venous wall puncture, and total number of attempts. RESULTS: Rates of first pass success were similar in both the TA (82%) and control groups (57%), p = 0.095. There was a difference in the mean time to cannulation. The TA group achieved success at 50.76 s (SD 26.93) while the control group achieved success at 85.30 s (SD 65.47), p = 0.048. CONCLUSION: In this study of utilizing TA to aid in USGPIV placement, students were able to achieve successful cannulation in a shorter amount of time. There was no significant difference in first pass success. Future studies should utilize a larger sample size and evaluate the utility of TA when placing USGPIV on patients.

A comparison of homemade vascular access ultrasound phantom models for peripheral intravenous catheter insertion.

BACKGROUND: Ultrasound (U/S) guided peripheral IV catheter (PIV) placement is often needed after unsuccessful traditional IV attempts. Commercial U/S PIV training phantoms are expensive and difficult to alter. Non-commercial phantoms have been described; however, there has been no comparison of these models. The primary objectives of this study were to compare the echogenic and haptic properties of various non-commercial phantoms. Secondary objectives were to characterize the cost and ease of making the phantoms. METHODS: This prospective observational study trialed six unique phantom models: Amini Ballistics; Morrow Ballistics; University of California San Diego (UCSD) gelatin; Rippey Chicken; Nolting Spam; and Johnson Tofu. Total cost and creation time were noted. Emergency Ultrasound Fellowship trained physicians performed U/S guided PIV placement on each model to evaluate their resemblance to human tissue haptic and echogenicity properties, utility for training, and comparability to commercial phantoms (Likert scale 1-5; higher performance = 5). RESULTS: The Rippey model scored highest for each primary objective with an aggregate score of 4.8/5. UCSD ranked second and Nolting last for all primary objectives, with aggregate scores 3.7/5 and 1.3/5 respectively. Cost of production ranged from $4.39 (Johnson) to $29.76 (UCSD). Creation times ranged from 10 min (Johnson) to 120 min (UCSD). CONCLUSION: In our study the Rippey model performed best and offered a mid-level cost and creation time. Non-commercial U/S phantoms may represent cost-effective and useful PIV practice tools. Future studies should investigate the utility of these phantoms in teaching U/S guided PIV to novices and compare non-commercial to commercial phantoms.