ABSTRACT
HTLV-1 is an oncogenic human retrovirus and the etiologic agent of the highly aggressive ATL malignancy. Two viral genes, Tax and Hbz, are individually linked to oncogenic transformation and play an important role in the pathogenic process. Consequently, regulation of HTLV-1 gene expression is a central feature in the viral lifecycle and directly contributes to its pathogenic potential. Herein, we identified the cellular transcription factor YBX1 as a binding partner for HBZ. We found YBX1 activated transcription and enhanced Tax-mediated transcription from the viral 5' LTR promoter. Interestingly, YBX1 also interacted with Tax. shRNA-mediated loss of YBX1 decreased transcript and protein abundance of both Tax and HBZ in HTLV-1-transformed T-cell lines, as well as Tax association with the 5' LTR. Conversely, YBX1 transcriptional activation of the 5' LTR promoter was increased in the absence of HBZ. YBX1 was found to be associated with both the 5' and 3' LTRs in HTLV-1-transformed and ATL-derived T-cell lines. Together, these data suggest that YBX1 positively influences transcription from both the 5' and 3' promoter elements. YBX1 is able to interact with Tax and help recruit Tax to the 5' LTR. However, through interactions with HBZ, YBX1 transcriptional activation of the 5' LTR is repressed.
Subject(s)
Human T-lymphotropic virus 1 , Y-Box-Binding Protein 1 , Humans , Genes, Viral , Human T-lymphotropic virus 1/genetics , Promoter Regions, Genetic , RNA, Small Interfering , Terminal Repeat Sequences/genetics , Y-Box-Binding Protein 1/geneticsABSTRACT
IN BRIEF Diabetes applications for electronic devices (apps) leverage the computing power and wireless connectivity of smartphones to offer unique advantages over more traditional tools such as paper logbooks and glucose meters. As these apps and the devices they connect with continue to evolve, health care providers play an important role in guiding patients by recommending specific apps, demonstrating best practices on their usage, and cautioning against their limitations.
ABSTRACT
BACKGROUND: Less-invasive techniques for left ventricular assist device (LVAD) implantation have shown promising outcomes but are associated with significant postoperative pain. We aim to investigate the use of ultrasound-guided regional nerve blocks to improve pain management during these procedures. METHODS: We retrospectively reviewed patients implanted with a HeartMate 3 LVAD via complete sternal-sparing (CSS) approach at our institution from February 2018 to July 2018. Patients were grouped based on their postoperative pain management plan-those who received a regional nerve block plus multimodal analgesia and a control group who received standard multimodal analgesia alone. Pain scores and analgesic use were recorded for all patients during the initial 72 hours postoperatively. RESULTS: Preoperative characteristics were similar between cohorts. Of the 28 patients included in the study, 15 (54%) received a postoperative regional nerve block. Patients who received a nerve block had significantly lower pain scores and required a lower dose of opioid analgesics (70.7 ± 13.9 vs 124.6 ± 19.3 morphine equivalents, P = 0.029) during the first 72 hours postoperatively. There was no difference in time to extubation, intensive care unit length of stay, or hospital length of stay. CONCLUSIONS: Optimizing postoperative analgesia using a regional nerve block is associated with decreased opioid use and decreased postoperative pain after CSS LVAD implantation. Regional nerve blocks should be included as part of a protocol-based postoperative pain management program.