Antimicrobial Peptides (AMP) in the Cell-Free Culture Media of and Exert Anti-Protist Activity against Eukaryotic Vertebrate Pathogens including and Species.

Anti-microbial peptides provide a powerful toolkit for combating multidrug resistance. Combating eukaryotic pathogens is complicated because the intracellular drug targets in the eukaryotic pathogen are frequently homologs of cellular structures of vital importance in the host organism. The entomopathogenic bacteria (EPB), symbionts of entomopathogenic-nematode species, release a series of non-ribosomal templated anti-microbial peptides.

Expression of membrane Hsp90 is a molecular signature of T cell activation.

Heat shock protein 90 (Hsp90) maintains cellular proteostasis during stress and has been under investigation as a therapeutic target in cancer for over two decades. We and others have identified a membrane expressed form of Hsp90 (mHsp90) that previously appeared to be restricted to rapidly proliferating cells exhibiting a metastatic phenotype. Here, we used HS-131, a fluor-tethered mHsp90 inhibitor, to quantify the effect of T cell activation on the expression of mHsp90 in human and mouse T cells.

Estrogen May Enhance Toll-Like Receptor 4-Induced Inflammatory Pathways in People With HIV: Implications for Transgender Women on Hormone Therapy.

Background: Transgender women (TW) are at increased risk for both human immunodeficiency virus (HIV) and cardiovascular disease (CVD). Antiretroviral therapy-treated HIV has been associated with a two-fold increased risk of CVD, potentially due to dysregulated Toll-like receptor (TLR)-induced immune activation. Use of estrogens in feminizing hormone therapy (FHT) may enhance inflammatory responses and the risk of cardiovascular mortality in TW.

Exposure of Leukocytes to HIV Preexposure Prophylaxis Decreases Mitochondrial Function and Alters Gene Expression Profiles.

The use of antiretroviral therapy (ART) as preexposure prophylaxis (PrEP) is an effective strategy for preventing HIV acquisition. The cellular consequences of PrEP exposure, however, have not been sufficiently explored to determine potential effects on health in individuals without HIV. In this study, peripheral blood mononuclear cells (PBMCs) from people without HIV were exposed to tenofovir disoproxil fumarate (TDF) or emtricitabine (FTC) overnight.

Macrophage maturation from blood monocytes is altered in people with HIV, and is linked to serum lipid profiles and activation indices: A model for studying atherogenic mechanisms.

People with HIV (PWH) are at increased risk for atherosclerotic cardiovascular disease (ASCVD). Proportions of vascular homing monocytes are enriched in PWH; however, little is known regarding monocyte-derived macrophages (MDMs) that may drive atherosclerosis in this population. We isolated PBMCs from people with and without HIV, and cultured these cells for 5 days in medium containing autologous serum to generate MDMs.

Prevalence of type 2 diabetes mellitus (T2DM) in India: A systematic review (1994-2018).

Aim: To conduct a systematic and critical review of published studies on prevalence of Type 2 diabetes mellitus (T2DM) in urban and rural areas of India.

Methods: We conducted a literature search in PubMed, EMBASE and Web of Science using the terms 'prevalence', 'Type 2 diabetes, 'India', 'urban' and 'rural' for English language articles published during January 1994-December 2018. We selected articles that reported the results of original studies that randomly sampled adults aged 15-80 years, and which reported T2DM prevalence based on the actual examination of blood samples.

Relationship between economic insecurity, inflammation, monocyte activation and intestinal integrity in children living with HIV in Uganda.

We aimed to evaluate differences in socio-economic variables in a Ugandan cohort of children with perinatally acquired HIV (PHIVs), HIV exposed uninfected (HEU) and HIV unexposed uninfected (HIV-) children and their associations with markers of inflammation and intestinal integrity. This is a cross-sectional study in 57 PHIV, 59 HEU and 56 HIV - children aged 2-10 years old enrolled in Uganda. Mean age of all participants was 7 years and 55% were girls.

Micronutrients, Metabolic Complications, and Inflammation in Ugandan Children With HIV.

Background: Selenium, zinc, and chromium are essential micronutrients. Their alterations have been associated with HIV disease progression, metabolic complications, and mortality.

Methods: This is a cross-sectional study in children with perinatally acquired HIV (PHIV, n = 57), HIV-exposed uninfected (HEU, n = 59), and HIV-unexposed uninfected (HIV-, n = 56) children aged 2 to 10 years old, age- and sex-matched, enrolled in Uganda.

Brief Report: Zinc Supplementation and Inflammation in Treated HIV.

Objective: In this study, we explored the effect of zinc supplementation on markers of inflammation and monocyte activation in antiretroviral therapy-treated HIV infection.

Methods: This is a phase I open-labeled randomized double-arm study, exploring the efficacy and safety of zinc supplementation on inflammation in ≥18-year-old people living with HIV in the US, on stable antiretroviral therapy and with zinc levels ≤75 µg/dL in the last 60 days. Patients were randomized 1:1 to zinc gluconate capsules at a dose of 45 mg (low-dose), or 90 mg (high-dose) elemental zinc daily for 16 weeks.

Altered Intestinal Permeability and Fungal Translocation in Ugandan Children With Human Immunodeficiency Virus.

Background: Children with perinatally acquired human immunodeficiency virus (HIV; PHIVs) face a lifelong cumulative exposure to HIV and antiretroviral therapy (ART). The relationship between gut integrity, microbial translocation, and inflammation in PHIV is poorly understood.

Methods: This is a cross-sectional study in 57 PHIVs, 59 HIV-exposed but uninfected children, and 56 HIV-unexposed and -uninfected children aged 2-10 years old in Uganda.

Oncologists' Perceptions of a Digital Tool to Improve Cancer Survivors' Cardiovascular Health.

Background: Cardiovascular (CV) disease continues to be a leading cause of morbidity and mortality with higher rates among cancer survivors than in the general population.

Objective: This study was aimed to understand oncology providers' attitudes toward a digital CV health tool, delivered via a tablet, to promote CV health in cancer survivors.

Methods: Using qualitative methods, 14 oncologists, from community and academic practice sites, were interviewed while they used the tool.

Altered Lipidome Composition Is Related to Markers of Monocyte and Immune Activation in Antiretroviral Therapy Treated Human Immunodeficiency Virus (HIV) Infection and in Uninfected Persons.

HIV infection and antiretroviral therapy (ART) have both been linked to dyslipidemia and increased cardiovascular disease (CVD) risk. Alterations in the composition of saturated (SaFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids are related to inflammation and CVD progression in HIV-uninfected (HIV-) populations. The relationships among the lipidome and markers of monocyte and immune activation in HIV-infected (HIV+) individuals are not well understood.

Fungal Translocation Is Associated with Immune Activation and Systemic Inflammation in Treated HIV.

The mechanisms causing HIV-associated immune activation remain incompletely understood. Alteration of intestinal integrity with subsequent translocation of bacterial products appears to play an important role; however, little is known about the impact of fungal translocation. We assessed the effect of fungal translocation and its association with immune activation in people living with HIV (PLWH) compared with uninfected controls.

HIV-exposed-uninfected infants have increased inflammation and monocyte activation.

Background: HIV-exposed-uninfected (HEU) infants have increased infectious morbidity and mortality; little is known about their levels of inflammation and monocyte activation.

Methods: Plasma samples obtained at birth and 6 months from 86 HEU mother-infant pairs enrolled in the National Institute of Child Health and Human Development cohorts in Brazil were compared with 88 HIV-unexposed mother-infant pairs. HIV-infected mothers received antiretroviral therapy during pregnancy, their infants received zidovudine prophylaxis and were not breastfed.

Serum Albumin Is Associated With Higher Inflammation and Carotid Atherosclerosis in Treated Human Immunodeficiency Virus Infection.

Background: This study was conducted to explore the associations between serum albumin and markers of inflammation and cardiovascular disease in treated human immunodeficiency virus (HIV)-infected adults.

Methods: We conducted a nested study within in the SATURN-HIV trial in which 147 HIV adults on stable antiretroviral therapy were (1) virally suppressed, (2) had a low-density lipoprotein (LDL)-cholesterol level <130 mg/dL, and (3) were randomized to 10 mg daily rosuvastatin or placebo. Measures of serum albumin, carotid intima media thickness ([cIMT] surrogate marker of atherosclerosis), inflammation, T cells, monocyte activation, and gut integrity were assessed at baseline, 48 and 96 weeks later.

Statin Therapy Does Not Reduce Liver Fat Scores in Patients Receiving Antiretroviral Therapy for HIV Infection.

Background & Aims: Therapies are needed to limit progression of fatty liver diseases in patients with human immunodeficiency virus (HIV) infection. We analyzed data from a prospective study of the effects of rosuvastatin (a statin) on hepatic steatosis in HIV-positive adults.

Methods: We performed a secondary analysis of data from a double-blind trial of adult patients with HIV infection (78% male; 68% African American; mean age, 46 y; body mass index, 29 kg/m; HIV1 RNA < 1000 copies/mL; low-density lipoprotein cholesterol, <130 mg/dL) receiving antiretroviral therapy.

Prospective Analysis of Lipid Composition Changes with Antiretroviral Therapy and Immune Activation in Persons Living with HIV.

Background: Lipid profiles are altered by HIV infection and antiretroviral therapy (ART). Among HIV-uninfected (HIV-) populations the concentrations of various lipid classes (ie, lyso-phosphatidylcholine, LPC) and their saturated (SaFA), mono-unsaturated (MUFA), and polyunsaturated fatty acid (PUFA) composition are related to cardiometabolic disease risk. Associations between changes in the lipidome and immune activation in HIV-infected (HIV+) individuals beginning ART have not been described.

Cellular fatty acid synthase is required for late stages of HIV-1 replication.

Background: Like all viruses, HIV-1 relies on host systems to replicate. The human purinome consists of approximately two thousand proteins that bind and use purines such as ATP, NADH, and NADPH. By virtue of their purine binding pockets, purinome proteins are highly druggable, and many existing drugs target purine-using enzymes.

Soluble TWEAK may predict carotid atherosclerosis in treated HIV infection.

Background: Soluble Tumor Necrosis Factor Weak Inducer of Apoptosis (sTWEAK) has been proposed as a novel biomarker of cardiovascular disease risk. This study compares levels of sTWEAK, sCD163 and the sCD163/sTWEAK ratio in HIV-infected and uninfected patients and their associations with cardiovascular and inflammatory factors.

Methods: The data for our analysis come from 274 HIV-infected adults and 59 controls.

HIV-positive youth who are perinatally infected have impaired endothelial function.

Objective: Evaluating cardiovascular disease risk in children and youth 13 to 24 years old who are facing a life time exposure to both HIV and antiretroviral therapy is a research priority. This study compares endothelial function measured by peripheral arterial tonometry in HIV-positive youth infected perinatally and behaviorally as well as HIV-negative controls.

Methods: Three groups of participants aged 8-30 year were enrolled; HIV-positive perinatally infected, HIV-positive behaviorally infected on antiretroviral therapy with HIV-1 RNA less than 1000 copies/ml, and HIV-negative controls.

Evaluation of the modified FINDRISC to identify individuals at high risk for diabetes among middle-aged white and black ARIC study participants.

Objective: To evaluate a modified Finnish Diabetes Risk Score (FINDRISC) for predicting the risk of incident diabetes among white and black middle-aged participants from the Atherosclerosis Risk in Communities (ARIC) study.

Research Design And Methods: We assessed 9754 ARIC cohort participants who were free of diabetes at baseline. Logistic regression and receiver operator characteristic (ROC) curves were used to evaluate a modified FINDRISC for predicting incident diabetes after 9 years of follow-up, overall and by race/gender group.

Altered Monocyte and Endothelial Cell Adhesion Molecule Expression Is Linked to Vascular Inflammation in Human Immunodeficiency Virus Infection.

Background: Human immunodeficiency virus (HIV)-infected individuals have increased risk for vascular thrombosis, potentially driven by interactions between activated leukocytes and the endothelium.

Methods: Monocyte subsets (CD14CD16, CD14CD16, CD14CD16) from HIV negative (HIV) and antiretroviral therapy-treated HIV positive (HIV) participants (N = 19 and 49) were analyzed by flow cytometry for adhesion molecule expression (lymphocyte function-associated antigen 1 [LFA-1], macrophage-1 antigen [Mac-1], CD11c/CD18, very late antigen [VLA]-4) and the fractalkine receptor (CX3CR1); these receptors recognize ligands (intercellular adhesion molecules [ICAMs], vascular cell adhesion molecule [VCAM]-1, fractalkine) on activated endothelial cells (ECs) and promote vascular migration. Plasma markers of monocyte (soluble [s]CD14, sCD163) and EC (VCAM-1, ICAM-1,2, fractalkine) activation and systemic (tumor necrosis factor receptor [TNFR-I], TNFR-II) and vascular (lipoprotein-associated phospholipase A [Lp-PLA]) inflammation were measured by enzyme-linked immunosorbent assay.

Comprehensive assessment of the arginine pathway and its relationship to inflammation in HIV.

Background: Nitric oxide helps maintain vascular function and is generated through the oxidation of arginine. Whether altered arginine metabolism may lead to elevated levels of inflammation in HIV is unclear.

Methods: We performed a cross-sectional analysis of HIV-infected adults on stable antiretroviral therapy with HIV-1 RNA less than 50 copies/ml and HIV-uninfected controls.

Equivalent Decline in Inflammation Markers with Tenofovir Disoproxil Fumarate vs. Tenofovir Alafenamide.

Background: Initiation of antiretroviral therapy (ART) and subsequent virologic suppression reduces immune activation and systemic inflammation.

Methods: We examined longitudinal changes in biomarkers of monocyte activation (sCD14, sCD163), and systemic (IL-6, hsCRP, sTNFR-I and D-dimer) and vascular (Lp-PLA) inflammation in a subgroup (N=100 per arm) of participants enrolled in a randomized, placebo-controlled trial comparing elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF; TAF) to E/C/F/tenofovir disoproxil fumarate (E/C/F/TDF; TDF) in treatment-naïve adults.

Results: For 194 participants (TAF, 98; TDF, 96), baseline levels of biomarkers did not differ by treatment arm; there were no differences in biomarker values between groups at weeks 12, 24, or 48 (p>0.

Rosuvastatin Decreases Intestinal Fatty Acid Binding Protein (I-FABP), but Does Not Alter Zonulin or Lipopolysaccharide Binding Protein (LBP) Levels, in HIV-Infected Subjects on Antiretroviral Therapy.

Introduction: Altered gastrointestinal (GI) barrier integrity and subsequent microbial translocation may contribute to immune activation in HIV infection. We have reported that rosuvastatin improved several markers of immune activation in HIV+ participants, but the effect of statin treatment on markers of GI barrier dysfunction is unknown.

Methods: SATURN-HIV is a randomized, double-blind, placebo-controlled trial assessing the effect of rosuvastatin (10mg/daily) on markers of cardiovascular disease, inflammation, and immune activation in ART-treated patients.