We Provided Psychological First Aid After the Las Vegas Shooting – Here’s What We Learned.

What is “psychological first aid”? How do mental health experts like you work side by side with traditional first responders? The goal of psychological first aid is to sooth, assist and help people function and cope in a healthy way in the wake of a traumatic event. It’s employed in the hours and days following the event, when people’s immediate needs, including medical care, as well as basic needs like food, shelter and water, must be met, along with their psychological and physical safety needs

Disagreeing About Disagreement: How Conflict in Social Networks Affects Political Behavior

At the center of debates on deliberative democracy is the issue of how much real deliberation citizens experience on a regular basis in their core social networks. These “disagreements about disagreement” come in a variety of forms, with scholars advocating significantly different empirical approaches (e.g., Huckfeldt, Johnson, and Sprague 2004; Mutz 2006), and coming to significantly different substantive conclusions. In this paper, we tackle these discrepancies through methodological advances and an investigation into the effects that conceptual differences have on key findings relating interpersonal political disagreement to political attitudes and behaviors Drawing on the 2008 ANES panel study, we explore the consequences of making different assumptions about the definition and measurement of disagreement, ultimately speaking to the on-going debate over whether a deliberative society can also be a participatory one (Mutz 2006)

HIV-Nef Protein Persists in the Lungs of Aviremic Patients with HIV and Induces Endothelial Cell Death

It remains a mystery why HIV-associated end-organ pathologies persist in the era of combined antiretroviral therapy (ART). One possible mechanism is the continued production of HIV-encoded proteins in latently HIV-infected T cells and macrophages. The proapoptotic protein HIV-Nef persists in the blood of ART-treated patients within extracellular vesicles (EVs) and peripheral blood mononuclear cells. Here we demonstrate that HIV-Nef is present in cells and EVs isolated from BAL of patients on ART. We hypothesize that HIV-Nef persistence in the lung induces endothelial apoptosis leading to endothelial dysfunction and further pulmonary vascular pathologies. The presence of HIV-Nef in patients with HIV correlates with the surface expression of the proapoptotic endothelial-monocyte–activating polypeptide II (EMAPII), which was implicated in progression of pulmonary emphysema via mechanisms involving endothelial cell death. HIV-Nef protein induces EMAPII surface expression in human embryonic kidney 293T cells, T cells, and human and mouse lung endothelial cells. HIV-Nef packages itself into EVs and increases the amount of EVs secreted from Nef-expressing T cells and Nef-transfected human embryonic kidney 293T cells. EVs from BAL of HIV+ patients and Nef-transfected cells induce apoptosis in lung microvascular endothelial cells by upregulating EMAPII surface expression in a PAK2-dependent fashion. Transgenic expression of HIV-Nef in vascular endothelial–cadherin+ endothelial cells leads to lung rarefaction, characterized by reduced alveoli and overall increase in lung inspiratory capacity. These changes occur concomitantly with lung endothelial cell apoptosis. Together, these data suggest that HIV-Nef induces endothelial cell apoptosis via an EMAPII-dependent mechanism that is sufficient to cause pulmonary vascular pathologies even in the absence of inflammation

Precise Quantitation of the Latent HIV-1 Reservoir: Implications for Eradication Strategies

The quantitative viral outgrowth assay (QVOA) provides a precise minimal estimate of the reservoir of resting CD4+ T-cell infection (resting cell infection [RCI]). However, the variability of RCI over time during antiretroviral therapy (ART), relevant to assess potential effects of latency-reversing agents or other interventions, has not been fully described. We performed QVOA on resting CD4+ T cells obtained via leukapheresis from 37 human immunodeficiency virus (HIV)–infected patients receiving stable suppressive ART for a period of 6 years. Patients who started ART during acute (n = 17) or chronic (n = 20) HIV infection were studied once HIV RNA levels were 6-fold were rare. We suggest that a 6-fold decline is a relevant threshold to reliably identify effects of antilatency interventions on RCI

Gold nanoparticles to improve HIV drug delivery

Antiretroviral therapy (ART) has improved lifespan and quality of life of patients infected with the HIV-1. However, ART has several potential limitations, including the development of drug resistance and suboptimal penetration to selected anatomic compartments. Improving the delivery of antiretroviral molecules could overcome several of the limitations of current ART

Risk of Arterial and Venous Thrombotic Events Among Patients with COVID-19:A Multi-National Collaboration of Regulatory Agencies from Canada, Europe, and United States

Purpose: Few studies have examined how the absolute risk of thromboembolism with COVID-19 has evolved over time across different countries. Researchers from the European Medicines Agency, Health Canada, and the United States (US) Food and Drug Administration established a collaboration to evaluate the absolute risk of arterial (ATE) and venous thromboembolism (VTE) in the 90 days after diagnosis of COVID-19 in the ambulatory (eg, outpatient, emergency department, nursing facility) setting from seven countries across North America (Canada, US) and Europe (England, Germany, Italy, Netherlands, and Spain) within periods before and during COVID-19 vaccine availability. Patients and Methods: We conducted cohort studies of patients initially diagnosed with COVID-19 in the ambulatory setting from the seven specified countries. Patients were followed for 90 days after COVID-19 diagnosis. The primary outcomes were ATE and VTE over 90 days from diagnosis date. We measured country -level estimates of 90 -day absolute risk (with 95% confidence intervals) of ATE and VTE. Results: The seven cohorts included 1,061,565 patients initially diagnosed with COVID-19 in the ambulatory setting before COVID19 vaccines were available (through November 2020). The 90 -day absolute risk of ATE during this period ranged from 0.11% (0.09- 0.13%) in Canada to 1.01% (0.97-1.05%) in the US, and the 90 -day absolute risk of VTE ranged from 0.23% (0.21-0.26%) in Canada to 0.84% (0.80-0.89%) in England. The seven cohorts included 3,544,062 patients with COVID-19 during vaccine availability (beginning December 2020). The 90 -day absolute risk of ATE during this period ranged from 0.06% (0.06-0.07%) in England to 1.04% (1.01-1.06%) in the US, and the 90 -day absolute risk of VTE ranged from 0.25% (0.24-0.26%) in England to 1.02% (0.99- 1.04%) in the US. Conclusion: There was heterogeneity by country in 90 -day absolute risk of ATE and VTE after ambulatory COVID-19 diagnosis both before and during COVID-19 vaccine availability. Plain Language Summary: Cohort studies of patients diagnosed with COVID-19 in both the ambulatory and hospital settings have suggested that SARS-CoV-2 infection promotes hypercoagulability that could lead to arterial or venous thromboembolism. However, few studies have examined how the risk of thromboembolism with COVID-19 has evolved over time across different countries. A new collaboration was established among the regulatory authorities of Canada, Europe, and the US within the International Coalition of Medicines Regulatory Authorities to evaluate the 90 -day risk of both arterial and venous thromboembolism after initial diagnosis of COVID-19 in the ambulatory or hospital setting from seven countries across North America (Canada, US) and Europe (England, Germany, Italy, Netherlands, and Spain) within periods before and during COVID-19 vaccine availability. The study found that there was variability in the risk of both arterial and venous thromboembolism by month across the countries among patients initially diagnosed with COVID-19 in the ambulatory or hospital setting. Differences in the healthcare systems, prevalence of comorbidities in the study cohorts, and approaches to the case definitions of thromboembolism likely contributed to the variability in estimates of thromboembolism risk across the countries

Peripheral Vγ9Vδ2 T Cells Are a Novel Reservoir of Latent HIV Infection

<div><p>Eradication of HIV infection will require the identification of all cellular reservoirs that harbor latent infection. Despite low or lack of CD4 receptor expression on Vδ2 T cells, infection of these cells has previously been reported. We found that upregulation of the CD4 receptor may render primary Vδ2 cells target for HIV infection <i>in vitro</i> and we propose that HIV-induced immune activation may allow infection of γδ T cells <i>in vivo</i>. We assessed the presence of latent HIV infection by measurements of DNA and outgrowth assays within Vδ2 cells in 18 aviremic patients on long-standing antiretroviral therapy. In 14 patients we recovered latent but replication-competent HIV from highly purified Vδ2 cells demonstrating that peripheral Vδ2 T cells are a previously unrecognized reservoir in which latent HIV infection is unexpectedly frequent.</p></div

Recovery of replication-competent virus from isolated Vδ2 cells.

<p>Representation of the culture conditions in isolated peripheral resting Vδ2 T cells in patients treated in acute HIV infection (AHI) and in chronic HIV infection (CHI). Each square represents one culture replicate that is gray when replication-competent HIV was recovered, and is open when culture replicates were negative. Vδ2 T cells were recovered at a higher frequency in patients treated in AHI than in patients treated in CHI, allowing more replicates for the outgrowth assays. However, HIV was more frequently recovered from CHI patients than from AHI patients.</p

Detection of replication-competent HIV and HIV DNA from isolated Vδ2 cells and resting CD4⁺ T cells (r-CD4).

<p>*Percentage of peripheral CD3⁺ Vδ2 cells or **CD3⁺CD4⁺HLA-DR^-CD69^- cells within total PBMC. Antibody cocktail used to isolate r-CD4 cells did not completely deplete γδ T cells.</p><p>n/a, not available.</p><p>LOQ, limit of quantitation.</p><p>Detection of replication-competent HIV and HIV DNA from isolated Vδ2 cells and resting CD4⁺ T cells (r-CD4).</p

Frequency of replication-competent HIV expressed as infectious units per million (IUPM) cells.

<p><b>A)</b> Comparison between the frequency of infection within isolated Vδ2 cells between patients treated in the acute HIV infection (AHI) and patients treated in the chronic HIV infection (CHI). <b>B)</b> Point estimate (95% CI) of the frequency of infection in isolated Vδ2 cells (circles) and resting CD4⁺ T (r-CD4) cells (triangles) in individual patients treated in AHI (left panel) or treated in CHI (right panel). Open symbols means HIVp24 was below the limit of detection, that was <10.67 for Vδ2 cells in patient A6, <0.1 for r-CD4 cells in patient A7, and <31.9 for Vδ2 cells in patient C3. <b>C)</b> Comparison of the point estimate of the frequency of infection between Vδ2 cells and r-CD4 cells in patients treated in AHI (left panel) and patients treated in CHI (right panel). p> 0.05, Wilcoxon signed-ranked test.</p