Cardiovirology Clinic for Primary Prevention in HIV Patients: a Quality Improvement Assessment

INTRODUCTION With effective highly active antiretroviral therapy (HAART), individuals with human immunodeficiency virus (HIV) infection now enjoy life expectancies approaching those of uninfected individuals. Prolonged longevity has increased the prevalence of non-communicable comorbidities within the HIV patient population. HIV is a known independent risk factor for atherosclerotic cardiovascular disease (ASCVD), imparting a 1.5-2 -fold higher incidence of major adverse cardiovascular events (MACE) on infected patients. Deaths from ASCVD have increased as a result, despite a decline in total mortality. The Center of Excellence for HIV/AIDS care established a Cardiovirology Clinic (CvC) focused on providing primary and secondary preventative cardiovascular care to its patients. To date, there are no known data on the efficacy of such an intervention. We sought to define the performance of this care model for primary prevention. METHODS Unique CvC patients (n=68) with a treatment delivery window between September 1, 2017 to August 31, 2018 were identified through billing records. All patients were receiving HAART as prescribed by their infectious disease provider. Those with established ASCVD (n=10) were excluded from analysis to limit the study to primary prevention patients. We collected data on ASCVD risk factors (family history of premature ASCVD and personal histories of smoking, diabetes, hypertension [with degree of control], dyslipidemia, drug and alcohol use, and exercise) from the electronic health record. Body-mass index and systolic (SBP) and diastolic (DBP) blood pressures were also collected. Laboratory values including CD4 cell count, HIV-1 viral load, proteinuria, glomerular filtration rate, total cholesterol (TC), triglycerides (TG), and high (HDL) and low density (LDL) lipoprotein were included in the data collection. Estimates of 5-year risk of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or need for major revascularization was calculated using the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) equations. Patient data were de-identified. Two-tailed, paired T-testing was performed for each factor comparing the initial and most recent follow-up values. Significance was defined as p value \u3c0.05. RESULTS Using univariate analysis, reductions in D:A:D risk (relative 32.01%, absolute 1.49%, p CONCLUSION In this initial assessment, treated HIV patients appeared to enjoy meaningful reductions in MACE risk through the preventive care they received in this clinic, suggesting that CvCs could be a partial solution to the growing ASCVD morbidity and mortality among HIV-infected individuals. Limitations of this study include a small patient population (n=58) (limiting us to univariate analyses) and short duration of follow up (≤ 1 year). Data collection will continue annually for 4 additional years. With increasing subject numbers, multivariate analyses to determine if components of ASCVD risk reduction show interactions, and which factors, interactions and interventions impart the greatest risk reduction, will be performed in improve the quality of care

Differential Impact of LPG-and PG-Deficient \u3cem\u3eLeishmania major\u3c/em\u3e Mutants on the Immune Response of Human Dendritic Cells

BACKGROUND: Leishmania major infection induces robust interleukin-12 (IL12) production in human dendritic cells (hDC), ultimately resulting in Th1-mediated immunity and clinical resolution. The surface of Leishmania parasites is covered in a dense glycocalyx consisting of primarily lipophosphoglycan (LPG) and other phosphoglycan-containing molecules (PGs), making these glycoconjugates the likely pathogen-associated molecular patterns (PAMPS) responsible for IL12 induction. METHODOLOGY/PRINCIPAL FINDINGS: Here we explored the role of parasite glycoconjugates on the hDC IL12 response by generating L. major Friedlin V1 mutants defective in LPG alone, (FV1 lpg1-), or generally deficient for all PGs, (FV1 lpg2-). Infection with metacyclic, infective stage, L. major or purified LPG induced high levels of IL12B subunit gene transcripts in hDCs, which was abrogated with FV1 lpg1- infections. In contrast, hDC infections with FV1 lpg2- displayed increased IL12B expression, suggesting other PG-related/LPG2 dependent molecules may act to dampen the immune response. Global transcriptional profiling comparing WT, FV1 lpg1-, FV1 lpg2- infections revealed that FV1 lpg1- mutants entered hDCs in a silent fashion as indicated by repression of gene expression. Transcription factor binding site analysis suggests that LPG recognition by hDCs induces IL-12 in a signaling cascade resulting in Nuclear Factor κ B (NFκB) and Interferon Regulatory Factor (IRF) mediated transcription. CONCLUSIONS/SIGNIFICANCE: These data suggest that L. major LPG is a major PAMP recognized by hDC to induce IL12-mediated protective immunity and that there is a complex interplay between PG-baring Leishmania surface glycoconjugates that result in modulation of host cellular IL12

US Cosmic Visions: New Ideas in Dark Matter 2017: Community Report

This white paper summarizes the workshop "U.S. Cosmic Visions: New Ideas in Dark Matter" held at University of Maryland on March 23-25, 2017.Comment: 102 pages + reference

Differential impact of LPG-and PG-deficient Leishmania major mutants on the immune response of human dendritic cells

<div><p>Background</p><p><i>Leishmania major</i> infection induces robust interleukin-12 (IL12) production in human dendritic cells (hDC), ultimately resulting in Th1-mediated immunity and clinical resolution. The surface of <i>Leishmania</i> parasites is covered in a dense glycocalyx consisting of primarily lipophosphoglycan (LPG) and other phosphoglycan-containing molecules (PGs), making these glycoconjugates the likely pathogen-associated molecular patterns (PAMPS) responsible for IL12 induction.</p><p>Methodology/Principal Findings</p><p>Here we explored the role of parasite glycoconjugates on the hDC IL12 response by generating <i>L</i>. <i>major</i> Friedlin V1 mutants defective in LPG alone, (FV1 <i>lpg1-</i>), or generally deficient for all PGs, (FV1 <i>lpg2-</i>). Infection with metacyclic, infective stage, <i>L</i>. <i>major</i> or purified LPG induced high levels of <i>IL12B</i> subunit gene transcripts in hDCs, which was abrogated with FV1 <i>lpg1-</i> infections. In contrast, hDC infections with FV1 <i>lpg2-</i> displayed increased <i>IL12B</i> expression, suggesting other PG-related/<i>LPG2</i> dependent molecules may act to dampen the immune response. Global transcriptional profiling comparing WT, FV1 <i>lpg1-</i>, FV1 <i>lpg2-</i> infections revealed that FV1 <i>lpg1-</i> mutants entered hDCs in a silent fashion as indicated by repression of gene expression. Transcription factor binding site analysis suggests that LPG recognition by hDCs induces IL-12 in a signaling cascade resulting in Nuclear Factor κ B (NFκB) and Interferon Regulatory Factor (IRF) mediated transcription.</p><p>Conclusions/Significance</p><p>These data suggest that <i>L</i>. <i>major</i> LPG is a major PAMP recognized by hDC to induce IL12-mediated protective immunity and that there is a complex interplay between PG-baring <i>Leishmania</i> surface glycoconjugates that result in modulation of host cellular IL12.</p></div

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Considerations in Women With Hypertension

Cardiovascular disease is the most common cause of death in women in the United States, and hypertension is a major contributor to cardiovascular mortality. The incidence of hypertension in women is steadily increasing, paralleling the epidemics of obesity and diabetes. Blood pressure control rates among women are suboptimal, even when secondary causes are identified and treated. There are few high-quality data describing specific hypertension-related outcomes in women. Some data comparing hypertensive women to age-matched men suggest advantages to sex-specific strategies, but further study is needed to determine optimal regimens for women throughout their lives. Pregnancy and menopause present unique, complex challenges in hypertension management