Effects of highly active antiretroviral therapy initiation on epigenomic DNA methylation in persons living with HIV.

Highly active antiretroviral therapy (HAART) helps improve some measures of accelerated epigenetic aging in persons living with HIV (PLWH), but its overall impact on the epigenome is not fully understood. In this study, we analyzed the DNA methylation profiles of PLWH ( = 187) shortly before and approximately 2-3 years after they started HAART, as well as matched seronegative (SN) controls ( = 187), taken at two time intervals. Our aim was to identify specific CpGs and biologic pathways associated with HIV infection and initiation of HAART.

Decreased but persistent epigenetic age acceleration is associated with changes in T-cell subsets after initiation of highly active antiretroviral therapy in persons living with HIV.

Introduction: Persons living with HIV (PLWH) experience the early onset of age-related illnesses, even in the setting of successful human immunodeficiency virus (HIV) suppression with highly active antiretroviral therapy (HAART). HIV infection is associated with accelerated epigenetic aging as measured using DNA methylation (DNAm)-based estimates of biological age and of telomere length (TL).

Methods: DNAm levels (Infinium MethylationEPIC BeadChip) from peripheral blood mononuclear cells from 200 PLWH and 199 HIV-seronegative (SN) participants matched on chronologic age, hepatitis C virus, and time intervals were used to calculate epigenetic age acceleration, expressed as age-adjusted acceleration residuals from 4 epigenetic clocks [Horvath's pan-tissue age acceleration residual (AAR), extrinsic epigenetic age acceleration (EEAA), phenotypic epigenetic age acceleration (PEAA), and grim epigenetic age acceleration (GEAA)] plus age-adjusted DNAm-based TL (aaDNAmTL).

Comparing Transcriptomic Points of Departure to Apical Effect Concentrations For Larval Fathead Minnow Exposed to Chemicals with Four Different Modes Of Action.

It is postulated that below a transcriptomic-based point of departure, adverse effects are unlikely to occur, thereby providing a chemical concentration to use in screening level hazard assessment. The present study extends previous work describing a high-throughput fathead minnow assay that can provide full transcriptomic data after exposure to a test chemical. One-day post-hatch fathead minnows were exposed to ten concentrations of three representatives of four chemical modes of action: organophosphates, ecdysone receptor agonists, plant photosystem II inhibitors, and estrogen receptor agonists for 24 h.

Intersectional stigma and the non-communicable disease syndemic in the context of HIV: protocol for a multisite, observational study in the USA.

Introduction: The increasing burden of non-communicable diseases, such as hypertension, diabetes and dyslipidaemia, presents key challenges to achieving optimal HIV care outcomes among ageing people living with HIV. These diseases are often comorbid and are exacerbated by psychosocial and structural inequities. This interaction among multiple health conditions and social factors is referred to as a syndemic.

Microfluidic Isolation of Neuronal-Enriched Extracellular Vesicles Shows Distinct and Common Neurological Proteins in Long COVID, HIV Infection and Alzheimer's Disease.

Long COVID (LongC) is associated with a myriad of symptoms including cognitive impairment. We reported at the beginning of the COVID-19 pandemic that neuronal-enriched or L1CAM+ extracellular vesicles (nEVs) from people with LongC contained proteins associated with Alzheimer's disease (AD). Since that time, a subset of people with prior COVID infection continue to report neurological problems more than three months after infection.

Automated traffic monitoring of neurosurgical operating room.

Background: Operating room (OR) traffic disrupts airflow and increases particle count, which predisposes patients to surgical site infections, particularly in longer surgeries with hardware placement. The aim of this study is to evaluate the rate of traffic during neurosurgical procedures, as well as reasons for and perceptions of OR traffic.

Methods: This is a single-center, multimethod study monitoring neurosurgical OR traffic through direct observation, automated monitoring, and interviews.

Mutualism reduces the severity of gene disruptions in predictable ways across microbial communities.

Predicting evolution in microbial communities is critical for problems from human health to global nutrient cycling. Understanding how species interactions impact the distribution of fitness effects for a focal population would enhance our ability to predict evolution. Specifically, does the type of ecological interaction, such as mutualism or competition, change the average effect of a mutation (i.

Erratum: Accelerated aging with HIV begins at the time of initial HIV infection.

[This corrects the article DOI: 10.1016/j.isci.

Mutualism reduces the severity of gene disruptions in predictable ways across microbial communities.

Predicting evolution in microbial communities is critical for problems from human health to global nutrient cycling. Understanding how species interactions impact the distribution of fitness effects for a focal population would enhance our ability to predict evolution. Specifically, it would be useful to know if the type of ecological interaction, such as mutualism or competition, changes the average effect of a mutation (i.

Mosaic chromosomal alterations detected in men living with HIV and the relationship to non-Hodgkin lymphoma.

Objectives: People with HIV (PWH) have an elevated risk of non-Hodgkin lymphoma (NHL) and other diseases. Studying clonal hematopoiesis (CH), the clonal expansion of mutated hematopoietic stem cells, could provide insights regarding elevated NHL risk.

Design: Cohort analysis of participants in the Multicenter AIDS Cohort Study ( N  = 5979).

Siglec-9 Restrains Antibody-Dependent Natural Killer Cell Cytotoxicity against SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection alters the immunological profiles of natural killer (NK) cells. However, whether NK antiviral functions are impaired during severe coronavirus disease 2019 (COVID-19) and what host factors modulate these functions remain unclear. We found that NK cells from hospitalized COVID-19 patients degranulate less against SARS-CoV-2 antigen-expressing cells (in direct cytolytic and antibody-dependent cell cytotoxicity [ADCC] assays) than NK cells from mild COVID-19 patients or negative controls.

Pilot testing and optimization of a larval fathead minnow high throughput transcriptomics assay.

Concentrations at which global gene expression profiles in cells or animals exposed to a test substance start to differ significantly from those of controls have been proposed as an alternative point of departure for use in screening level hazard assessment. The present study describes pilot testing of a high throughput compatible transcriptomics assay with larval fathead minnows. One day post hatch fathead minnows were exposed to eleven different concentrations of three metals, three selective serotonin reuptake inhibitors, and four neonicotinoid-like compounds for 24 h and concentration response modeling was applied to whole body gene expression data.

No Association of IFNL4 Genotype With Opportunistic Infections and Cancers Among Men With Human Immunodeficiency Virus 1 Infection.

Background: IFNL4 genetic variants that are strongly associated with clearance of hepatitis C virus have been linked to risk of certain opportunistic infections (OIs) and cancers, including Kaposi sarcoma, cytomegalovirus infection, and herpes simplex virus infection. As the interferon (IFN) λ family plays a role in response to viral, bacterial, and fungal infections, IFNL4 genotype might affect risk for a wide range of OIs/cancers.

Methods: We examined associations between genotype for the functional IFNL4 rs368234815 polymorphism and incidence of 16 OIs/cancers among 2310 men with human immunodeficiency virus (2038 white; 272 black) enrolled in the Multicenter AIDS Cohort Study during 1984-1990.

Comparison of anal pre-cancer screening strategies among men who have sex with men.

Purpose: Comparison of anal pre-cancer screening strategies in men who have sex with men (MSM).

Methods: MSM in the Multicenter AIDS Cohort Study underwent repeated anal cytology (aCyt), oncogenic human papillomavirus (oncHPV) testing. A subset received High-Resolution Anoscopy (HRA).

Developing Indicators of Nutrient Pollution in Streams Using 16S rRNA Gene Metabarcoding of Periphyton-Associated Bacteria.

Indicators based on nutrient-biota relationships in streams can inform water quality restoration and protection programs. Bacterial assemblages could be particularly useful indicators of nutrient effects because they are species-rich, important contributors to ecosystem processes in streams, and responsive to rapidly changing conditions. Here, we sampled 25 streams weekly (12-14 times each) and used 16S rRNA gene metabarcoding of periphyton-associated bacteria to quantify the effects of total phosphorus (TP) and total nitrogen (TN).

Accelerated aging with HIV begins at the time of initial HIV infection.

Living with HIV infection is associated with early onset of aging-related chronic conditions, sometimes described as accelerated aging. Epigenetic DNA methylation patterns can evaluate acceleration of biological age relative to chronological age. The impact of initial HIV infection on five epigenetic measures of aging was examined before and approximately 3 years after HIV infection in the same individuals (n=102).

Association of Matrix Metalloproteinase 7 Expression With Pathologic Response After Neoadjuvant Treatment in Patients With Resected Pancreatic Ductal Adenocarcinoma.

Importance: The use of neoadjuvant therapy (NAT) in resectable pancreatic ductal adenocarcinoma (PDAC) remains controversial. A favorable pathologic response (complete or marked tumor regression) to NAT is associated with better outcomes in patients with resected PDAC. The role of NAT for early systemic control compared with immediate surgical resection for PDAC is under investigation.

KIR2DL5B and HLA DRB1*12 alleles seems to be associated with protection against HIV-1 in serodiscordant couples in Burkina Faso.

The human immunodeficiency virus (HIV) belongs to the Retroviridae family and remains a public health problem in sub-Saharan Africa. Recent reports from WHO have shown that 33 million people died from HIV infections. HIV is one of the most serious fatal human diseases of the 20th and 21st centuries.

Increased Rate of Epigenetic Aging in Men Living With HIV Prior to Treatment.

Epigenetic aging is accelerated in tissues of persons living with HIV (PLWH) and may underlie the early onset of age-related illnesses. This study examines the rate-of-change in epigenetic age in PLWH following HIV infection but before HAART, using archived longitudinal samples from the Multicenter AIDS Cohort Study. DNA was isolated from cryopreserved peripheral blood mononuclear cells from 101 men living with HIV, with baseline visit <2.

HIV-infection and cocaine use regulate semen extracellular vesicles proteome and miRNAome in a manner that mediates strategic monocyte haptotaxis governed by miR-128 network.

Background: Extracellular vesicles (EVs) are regulators of cell-cell interactions and mediators of horizontal transfer of bioactive molecules between cells. EV-mediated cell-cell interactions play roles in physiological and pathophysiological processes, which maybe modulated by exposure to pathogens and cocaine use. However, the effect of pathogens and cocaine use on EV composition and function are not fully understood.

Single center, open label dose escalating trial evaluating once weekly oral ixazomib in ART-suppressed, HIV positive adults and effects on HIV reservoir size in vivo.

Background: Achieving a functional or sterilizing cure for HIV will require identification of therapeutic interventions that reduce HIV reservoir size in infected individuals. Proteasome inhibitors, such as ixazomib, impact multiple aspects of HIV biology including latency, transcription initiation, viral replication, and infected cell killing through the HIV protease - Casp8p41 pathway, resulting in latency reversal and reduced measures of HIV reservoir size ex vivo.

Methods: We conducted a phase 1b/2a dose escalating, open label trial of weekly oral ixazomib for 24 weeks in antiretroviral (ART)-suppressed, HIV positive adults (NCT02946047).

De Novo Assembly of the Nearly Complete Fathead Minnow Reference Genome Reveals a Repetitive but Compact Genome.

The fathead minnow is a widely used model organism in environmental toxicology. The lack of a high-quality fathead minnow reference genome, however, has severely hampered its uses in toxicogenomics. We present the de novo assembly and annotation of the fathead minnow genome using long PacBio reads, Bionano and Hi-C scaffolding data, and large RNA-sequencing data sets from different tissues and life stages.

Signature changes in gut microbiome are associated with increased susceptibility to HIV-1 infection in MSM.

Background: Men who have sex with men (MSM) have been disproportionately affected by HIV-1 since the beginning of the AIDS pandemic, particularly in the USA and Europe. Compared to men who have sex with women (MSW), MSM have a distinct fecal microbiome regardless of HIV-1 infection. However, it is unclear whether the MSM-associated gut microbiome affects the susceptibility and progression of HIV-1 infection.

Superior Mesenteric Artery Stenosis Due to Disseminated Tuberculosis in a Pediatric Patient.

Disseminated tuberculosis (TB) associated with mesenteric arteritis has not been established in children. We present the case of an 8-year-old woman who presented with TB and superior mesenteric artery stenosis. Although rare, large vessel involvement from Takayasu arteritis can occur in TB.