Etravirine with 2 NRTIs: an effective switch option for ARV simplification and side effect management

Etravirine (ETV) has been approved for use in treatment-experienced patients based on results of the Duet clinical trials [1]. Less experience exists with ETV in earlier stages of treatment. ETV has a favorable genetic barrier, lipid profile, and little associated CNS toxicity. These characteristics make ETV attractive as a switch strategy for simplification and/or management of side effects. A retrospective chart review was conducted at a large urban HIV clinic in Toronto. All patients who were switched to ETV plus 2 nucleosides and whose viral load (VL) was <200 copies/ml at the time of switch were included. Maintenance of viral suppression, CD4 and lipid changes at 24 weeks and reason for switch to ETV are reported. Seventy-three patients (67 male) were identified. Mean age was 46±10 and mean duration of HIV infection was 11.7±7.4 years. Switches were from efavirenz=29, atazanavir=23, lopinavir=16, other=5. Duration of prior regimen was long; median 195 weeks. CNS and GI intolerance were the most common reasons for switches. At the time of analysis, 63 patients had reached week 24. Three patients had discontinued ETV prior to week 24, 3 LTF/U, 4 had <24 weeks follow-up. 92% (67/73) maintained VL suppression (ITT); failures were 6 patients who stopped/lost-to-follow-up prior to week 24. On treatment, CD4 increased and lipid decreased changes as seen below. All patients who switched due to CNS side effects had subjective improvement.Switch to ETV plus 2 nucleosides maintained viral suppression, improved lipid profiles and improved side effect profile in this selected group of patients. 48 week f/u will be presented

The ephemeral effects of fact-checks on COVID-19 misperceptions in the United States, Great Britain and Canada

Widespread misperceptions about COVID-19 and the novel coronavirus threaten to exacerbate the severity of the pandemic. We conducted preregistered survey experiments in the United States, Great Britain, and Canada examining the effectiveness of fact-checks that seek to correct these false or unsupported misperceptions. Across three countries with differing levels of political conflict over the COVID-19 response, we demonstrate that fact-checks reduce targeted misperceptions, especially among the groups who are most vulnerable to these claims, and have minimal spillover effects on the accuracy of other beliefs about COVID-19. However, the positive effects of fact-checks on the accuracy of respondents’ beliefs fail to persist over time in panel data even after repeated exposure. These results suggest that fact-checks can successfully change the beliefs of the people who would benefit from them most but that their effects are disappointingly ephemeral

Minimal effects from injunctive norm and contentiousness treatments on COVID-19 vaccine intentions: evidence from 3 countries

Does information about how other people feel about COVID-19 vaccination affect immunization intentions? We conducted preregistered survey experiments in Great Britain (5,456 respondents across 3 survey waves from September 2020 to February 2021), Canada (1,315 respondents in February 2021), and the state of New Hampshire in the United States (1,315 respondents in January 2021). The experiments examine the effects of providing accurate public opinion information to people about either public support for COVID-19 vaccination (an injunctive norm) or public beliefs that the issue is contentious. Across all 3 countries, exposure to this information had minimal effects on vaccination intentions even among people who previously held inaccurate beliefs about support for COVID-19 vaccination or its perceived contentiousness. These results suggest that providing information on public opinion about COVID vaccination has limited additional effect on people’s behavioral intentions when public discussion of vaccine uptake and intentions is highly salient

Deficits in Analogical Reasoning in Adolescents with Traumatic Brain Injury

Individuals with traumatic brain injury (TBI) exhibit deficits in executive control, which may impact their reasoning abilities. Analogical reasoning requires working memory and inhibitory abilities. In this study, we tested adolescents with moderate to severe TBI and typically developing (TD) controls on a set of picture analogy problems. Three factors were varied: complexity (number of relations in the problems), distraction (distractor item present or absent), and animacy (living or non-living items in the problems). We found that TD adolescents performed significantly better overall than TBI adolescents. There was also an age effect present in the TBI group where older participants performed better than younger ones. This age effect was not observed in the TD group. Performance was affected by complexity and distraction. Further, TBI participants exhibited lower performance with distractors present than TD participants. The reasoning deficits exhibited by the TBI participants were correlated with measures of executive function that required working memory updating, attention, and attentional screening. Using MRI-derived measures of cortical thickness, correlations were carried out between task accuracy and cortical thickness. The TD adolescents showed negative correlations between thickness and task accuracy in frontal and temporal regions consistent with cortical maturation in these regions. This study demonstrates that adolescent TBI results in impairments in analogical reasoning ability. Further, TBI youth have difficulty effectively screening out distraction, which may lead to failures in comprehension of the relations among items in visual scenes. Lastly, TBI youth fail to show robust cortical–behavior correlations as observed in TD individuals

A global collaboration to study intimate partner violence-related head trauma: The ENIGMA consortium IPV working group

Intimate partner violence includes psychological aggression, physical violence, sexual violence, and stalking from a current or former intimate partner. Past research suggests that exposure to intimate partner violence can impact cognitive and psychological functioning, as well as neurological outcomes. These seem to be compounded in those who suffer a brain injury as a result of trauma to the head, neck or body due to physical and/or sexual violence. However, our understanding of the neurobehavioral and neurobiological effects of head trauma in this population is limited due to factors including difficulty in accessing/recruiting participants, heterogeneity of samples, and premorbid and comorbid factors that impact outcomes. Thus, the goal of the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium Intimate Partner Violence Working Group is to develop a global collaboration that includes researchers, clinicians, and other key community stakeholders. Participation in the working group can include collecting harmonized data, providing data for meta- and mega-analysis across sites, or stakeholder insight on key clinical research questions, promoting safety, participant recruitment and referral to support services. Further, to facilitate the mega-analysis of data across sites within the working group, we provide suggestions for behavioral surveys, cognitive tests, neuroimaging parameters, and genetics that could be used by investigators in the early stages of study design. We anticipate that the harmonization of measures across sites within the working group prior to data collection could increase the statistical power in characterizing how intimate partner violence-related head trauma impacts long-term physical, cognitive, and psychological health

The ENIGMA sports injury working group - an international collaboration to further our understanding of sport-related brain injury

Sport-related brain injury is very common, and the potential long-term effects include a wide range of neurological and psychiatric symptoms, and potentially neurodegeneration. Around the globe, researchers are conducting neuroimaging studies on primarily homogenous samples of athletes. However, neuroimaging studies are expensive and time consuming, and thus current findings from studies of sport-related brain injury are often limited by small sample sizes. Further, current studies apply a variety of neuroimaging techniques and analysis tools which limit comparability among studies. The ENIGMA Sports Injury working group aims to provide a platform for data sharing and collaborative data analysis thereby leveraging existing data and expertise. By harmonizing data from a large number of studies from around the globe, we will work towards reproducibility of previously published findings and towards addressing important research questions with regard to diagnosis, prognosis, and efficacy of treatment for sport-related brain injury. Moreover, the ENIGMA Sports Injury working group is committed to providing recommendations for future prospective data acquisition to enhance data quality and scientific rigor

Multimodal surface-based morphometry reveals diffuse cortical atrophy in traumatic brain injury.

<p>Abstract</p> <p>Background</p> <p>Patients with traumatic brain injury (TBI) often present with significant cognitive deficits without corresponding evidence of cortical damage on neuroradiological examinations. One explanation for this puzzling observation is that the diffuse cortical abnormalities that characterize TBI are difficult to detect with standard imaging procedures. Here we investigated a patient with severe TBI-related cognitive impairments whose scan was interpreted as normal by a board-certified radiologist in order to determine if quantitative neuroimaging could detect cortical abnormalities not evident with standard neuroimaging procedures.</p> <p>Methods</p> <p>Cortical abnormalities were quantified using multimodal surfaced-based morphometry (MSBM) that statistically combined information from high-resolution structural MRI and diffusion tensor imaging (DTI). Normal values of cortical anatomy and cortical and pericortical DTI properties were quantified in a population of 43 healthy control subjects. Corresponding measures from the patient were obtained in two independent imaging sessions. These data were quantified using both the average values for each lobe and the measurements from each point on the cortical surface. The results were statistically analyzed as z-scores from the mean with a p < 0.05 criterion, corrected for multiple comparisons. False positive rates were verified by comparing the data from each control subject with the data from the remaining control population using identical statistical procedures.</p> <p>Results</p> <p>The TBI patient showed significant regional abnormalities in cortical thickness, gray matter diffusivity and pericortical white matter integrity that replicated across imaging sessions. Consistent with the patient's impaired performance on neuropsychological tests of executive function, cortical abnormalities were most pronounced in the frontal lobes.</p> <p>Conclusions</p> <p>MSBM is a promising tool for detecting subtle cortical abnormalities with high sensitivity and selectivity. MSBM may be particularly useful in evaluating cortical structure in TBI and other neurological conditions that produce diffuse abnormalities in both cortical structure and tissue properties.</p

Modeling Conformational Ensembles of Slow Functional Motions in Pin1-WW

Protein-protein interactions are often mediated by flexible loops that experience conformational dynamics on the microsecond to millisecond time scales. NMR relaxation studies can map these dynamics. However, defining the network of inter-converting conformers that underlie the relaxation data remains generally challenging. Here, we combine NMR relaxation experiments with simulation to visualize networks of inter-converting conformers. We demonstrate our approach with the apo Pin1-WW domain, for which NMR has revealed conformational dynamics of a flexible loop in the millisecond range. We sample and cluster the free energy landscape using Markov State Models (MSM) with major and minor exchange states with high correlation with the NMR relaxation data and low NOE violations. These MSM are hierarchical ensembles of slowly interconverting, metastable macrostates and rapidly interconverting microstates. We found a low population state that consists primarily of holo-like conformations and is a “hub” visited by most pathways between macrostates. These results suggest that conformational equilibria between holo-like and alternative conformers pre-exist in the intrinsic dynamics of apo Pin1-WW. Analysis using MutInf, a mutual information method for quantifying correlated motions, reveals that WW dynamics not only play a role in substrate recognition, but also may help couple the substrate binding site on the WW domain to the one on the catalytic domain. Our work represents an important step towards building networks of inter-converting conformational states and is generally applicable