Assessment of the angiogenic potential of 2-deoxy-D-ribose using a novel in vitro 3D dynamic model in comparison with established in vitro assays

Angiogenesis is a highly ordered physiological process regulated by the interaction of endothelial cells with an extensive variety of growth factors, extracellular matrix components and mechanical stimuli. One of the most important challenges in tissue engineering is the rapid neovascularization of constructs to ensure their survival after transplantation. To achieve this, the use of pro-angiogenic agents is a widely accepted approach. The study of angiogenesis has gained momentum over the last two decades. Although there are various in vitro, ex vivo, and in vivo angiogenesis models that enable testing of newly discovered pro-angiogenic agents, the problem with researching angiogenesis is the choice of the most appropriate assay. In vivo assays are the most representative and reliable models, but they are expensive, time-consuming and can cause ethical concerns whereas in vitro assays are relatively inexpensive, practical, and reproducible, but they are usually lack of enabling the study of more than one aspect of angiogenesis, and they do not fully represent the complexity of physiological angiogenesis. Therefore, there is a need for the development of an angiogenesis model that allows the study of angiogenesis under physiologically more relevant, dynamic conditions without causing ethical concerns. Accordingly, in this study, we developed 3D in vitro dynamic angiogenesis model, and we tested the angiogenic potential of 2-deoxy-D-ribose (2dDR) in comparison with vascular endothelial growth factor (VEGF) using newly developed in vitro 3D dynamic model and well-established in vitro models. Our results obtained using conventional in vitro assays demonstrated that 2dDR promoted proliferation, migration and tube formation of human aortic endothelial cells (HAECs) in a dose-dependent manner. Then, the angiogenic activity of 2dDR was further assessed using the newly developed 3D in vitro model, which enabled the monitoring of cell proliferation and infiltration simultaneously under dynamic conditions. Our results showed that the administration of 2dDR and VEGF significantly enhanced the outgrowth of HAECs and the cellular density under either static or dynamic conditions

Marijuana Use Is Not Associated with Changes in Opioid Prescriptions or Pain Severity among People Living with HIV and Chronic Pain

Background:People living with HIV (PLWH) commonly report marijuana use for chronic pain, although there is limited empirical evidence to support its use. There is hope that marijuana may reduce prescription opioid use. Our objective was to investigate whether marijuana use among PLWH who have chronic pain is associated with changes in pain severity and prescribed opioid use (prescribed opioid initiation and discontinuation).Methods:Participants completed self-report measures of chronic pain and marijuana use at an index visit and were followed up for 1 year in the Center for AIDS Research Network of Integrated Clinical Systems (CNICS). Self-reported marijuana use was the exposure variable. Outcome variables were changes in pain and initiation or discontinuation of opioids during the study period. The relationship between exposure and outcomes was assessed using generalized linear models for pain and multivariable binary logistic regression models for opioid initiation/discontinuation.Results:Of 433 PLWH and chronic pain, 28% reported marijuana use in the past 3 months. Median pain severity at the index visit was 6.3/10 (interquartile range 4.7-8.0). Neither increases nor decreases in marijuana use were associated with changes in pain severity, and marijuana use was not associated with either lower odds of opioid initiation or higher odds of opioid discontinuation.Conclusions:We did not find evidence that marijuana use in PLWH is associated with improved pain outcomes or reduced opioid prescribing. This suggests that caution is warranted when counseling PLWH about potential benefits of recreational or medical marijuana

Brief report: The association of chronic pain and long-term opioid therapy with HIV treatment outcomes

Background: Chronic pain occurs in up to 85% of persons living with HIV and is commonly treated with long-term opioid therapy (LTOT). We investigated the impact of chronic pain and LTOT on HIV outcomes. Methods: This was prospective cohort study conducted between July 2015 and July 2016 in 5 HIV primary care clinics. Chronic pain was defined as ≥moderate pain for ≥3 months on the Brief Chronic Pain Questionnaire. Chronic pain and LTOT were assessed at an index visit. Suboptimal retention, defined as at least one "no-show" to primary care, and virologic failure were measured over the subsequent year. Multivariable logistic regression models were built for each outcome adjusting for site. Results: Among 2334 participants, 25% had chronic pain, 27% had suboptimal retention, 12% had virologic failure, and 19% were prescribed LTOT. Among individuals not on LTOT, chronic pain was associated with increased odds of suboptimal retention [adjusted odds ratio (aOR) 1.46, 95% confidence interval (CI): 1.10 to 1.93, P = 0.009] and virologic failure (aOR 1.97, 95% CI: 1.39 to 2.80, P < 0.001). Among individuals with chronic pain, there was no association between LTOT and retention, but LTOT was associated with lower rates of virologic failure (aOR 0.56, 95% CI: 0.33 to 0.96, P = 0.03). Conclusions: Chronic pain in participants not on LTOT was associated with virologic failure. This reinforces the need to identify effective chronic pain treatments for persons living with HIV and investigate their impact on HIV outcomes. The apparent protective association between LTOT and virologic failure in those with pain merits further exploration

Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study

A41 Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study In: Addiction Science & Clinical Practice 2017, 12(Suppl 1): A4

Search for gravitational-wave transients associated with magnetar bursts in advanced LIGO and advanced Virgo data from the third observing run

Gravitational waves are expected to be produced from neutron star oscillations associated with magnetar giant f lares and short bursts. We present the results of a search for short-duration (milliseconds to seconds) and longduration (∼100 s) transient gravitational waves from 13 magnetar short bursts observed during Advanced LIGO, Advanced Virgo, and KAGRA’s third observation run. These 13 bursts come from two magnetars, SGR1935 +2154 and SwiftJ1818.0−1607. We also include three other electromagnetic burst events detected by FermiGBM which were identified as likely coming from one or more magnetars, but they have no association with a known magnetar. No magnetar giant flares were detected during the analysis period. We find no evidence of gravitational waves associated with any of these 16 bursts. We place upper limits on the rms of the integrated incident gravitational-wave strain that reach 3.6 × 10−²³ Hz at 100 Hz for the short-duration search and 1.1 ×10−²² Hz at 450 Hz for the long-duration search. For a ringdown signal at 1590 Hz targeted by the short-duration search the limit is set to 2.3 × 10−²² Hz. Using the estimated distance to each magnetar, we derive upper limits upper limits on the emitted gravitational-wave energy of 1.5 × 1044 erg (1.0 × 1044 erg) for SGR 1935+2154 and 9.4 × 10^43 erg (1.3 × 1044 erg) for Swift J1818.0−1607, for the short-duration (long-duration) search. Assuming isotropic emission of electromagnetic radiation of the burst fluences, we constrain the ratio of gravitational-wave energy to electromagnetic energy for bursts from SGR 1935+2154 with the available fluence information. The lowest of these ratios is 4.5 × 103