Hepcidin modifies the relationship between anemia, erythrocyte indices, and neurocognitive performance in virally suppressed people with HIV.

Objective: Neurocognitive (NC) impairment in people with HIV (PWH) is associated with erythrocyte indices, which may serve as indicators of iron metabolism, inflammation, and related factors. Erythropoiesis requires iron, regulated by a multifaceted system of peptide hormones, including hepcidin. This study postulated that hepcidin might modify the relationship between erythrocyte indices and NC performance in PWH.

Genetic Variations in EIF2AK3 are Associated with Neurocognitive Impairment in People Living with HIV.

Based on emerging evidence on the role for specific single-nucleotide variants (SNVs) in EIF2AK3 encoding the integrated stress response kinase PERK, in neurodegeneration, we assessed the association of EIF2AK3 SNVs with neurocognitive performance in people with HIV (PWH) using a candidate gene approach. This retrospective study included the CHARTER cohort participants, excluding those with severe neuropsychiatric comorbidities. Genome-wide data previously obtained for 1047 participants and targeted sequencing of 992 participants with available genomic DNA were utilized to interrogate the association of three noncoding and three coding EIF2AK3 SNVs with the continuous global deficit score (GDS) and global neurocognitive impairment (NCI; GDS ≥ 0.

Contemporary Antiretroviral Therapy Dysregulates Iron Transport and Augments Mitochondrial Dysfunction in HIV-Infected Human Microglia and Neural-Lineage Cells.

HIV-associated cognitive dysfunction during combination antiretroviral therapy (cART) involves mitochondrial dysfunction, but the impact of contemporary cART on chronic metabolic changes in the brain and in latent HIV infection is unclear. We interrogated mitochondrial function in a human microglia (hμglia) cell line harboring inducible HIV provirus and in SH-SY5Y cells after exposure to individual antiretroviral drugs or cART, using the MitoStress assay. cART-induced changes in protein expression, reactive oxygen species (ROS) production, mitochondrial DNA copy number, and cellular iron were also explored.

A haptoglobin (HP) structural variant alters the effect of APOE alleles on Alzheimer's disease.

Background: Haptoglobin (HP) is an antioxidant of apolipoprotein E (APOE), and previous reports have shown HP binds with APOE and amyloid beta (Aβ) to aid its clearance. A common structural variant of the HP gene distinguishes it into two alleles: HP1 and HP2.

Methods: HP genotypes were imputed in 29 cohorts from the Alzheimer's Disease Genetics Consortium (N = 20,512).

Anemia and Erythrocyte Indices Are Associated With Neurocognitive Performance Across Multiple Ability Domains in Adults With HIV.

Background: Anemia is linked to neurocognitive impairment (NCI) in people with HIV (PWH), but its impact within specific ability domains, and in diverse populations with HIV, is uncertain.

Methods: Participants included 1339 PWH enrolled in observational HIV cohort studies with a mean of 3 comprehensive neurocognitive assessments over 30 months. Global and domain-specific neurocognitive function were assessed by the global deficit score and domain deficit score (GDS and DDS, respectively) or as GDS-defined or DDS-defined NCI (GDS ≥ 0.

A Haptoglobin Exon Copy Number Variant Associates With HIV-Associated Neurocognitive Impairment in European and African-Descent Populations.

A common two-exon deletion distinguishes the gene encoding the free hemoglobin capturing protein-haptoglobin (HP)-into two alleles: and . To evaluate the impact of this copy number variant (CNV) on neurocognitive impairment (NCI) in people living with HIV, we imputed this variant in 432 European-descent (EUR) and 491 African-descent (AFR) participants from the CNS HIV Antiretroviral Therapy Effects Research Study using an optimized imputation pipeline and evaluated its associations with NCI. At baseline, in AFR, the allele decreased the odds of NCI (defined by a global deficit score, GDS, ; Odds Ratio, = 0.

Replication of European hypertension associations in a case-control study of 9,534 African Americans.

Objective: Hypertension is more prevalent in African Americans (AA) than other ethnic groups. Genome-wide association studies (GWAS) have identified loci associated with hypertension and other cardio-metabolic traits like type 2 diabetes, coronary artery disease, and body mass index (BMI), however the AA population is underrepresented in these studies. In this study, we examined a large AA cohort for the generalizability of 14 Metabochip array SNPs with previously reported European hypertension associations.

Multimodal single-cell omics analysis identifies epithelium-immune cell interactions and immune vulnerability associated with sex differences in COVID-19.

Sex differences in the susceptibility of SARS-CoV-2 infection and severity have been controversial, and the underlying mechanisms of COVID-19 in a sex-specific manner remain understudied. Here we inspected sex differences in SARS-CoV-2 infection, hospitalization, admission to the intensive care unit (ICU), sera inflammatory biomarker profiling, and single-cell RNA-sequencing (scRNA-seq) profiles across nasal, bronchoalveolar lavage fluid (BALF), and peripheral blood mononuclear cells (PBMCs) from COVID-19 patients with varying degrees of disease severities. Our propensity score-matching observations revealed that male individuals have a 29% elevated likelihood of SARS-CoV-2 positivity, with a hazard ratio (HR) 1.

Isofurans and Isoprostanes as Potential Markers of Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage: A Prospective Observational Study.

Background: F2-Isoprostanes (F2-IsoPs) and Isofurans (IsoF), specific markers of lipid peroxidation in vivo, have been reported to be elevated and have prognostic implications following subarachnoid hemorrhage (SAH). Platelet activation and vasoconstriction are attributed to these compounds. Elevated IsoF to F2-IsoPs ratios have been proposed as in vivo biomarkers of mitochondrial dysfunction.

Higher CSF Ferritin Heavy-Chain (Fth1) and Transferrin Predict Better Neurocognitive Performance in People with HIV.

HIV-associated neurocognitive disorder (HAND) remains prevalent despite antiretroviral therapy and involves white matter damage in the brain. Although iron is essential for myelination and myelin maintenance/repair, its role in HAND is largely unexplored. We tested the hypotheses that cerebrospinal fluid (CSF) heavy-chain ferritin (Fth1) and transferrin, proteins integral to iron delivery and myelination, are associated with neurocognitive performance in people with HIV (PWH).

Network medicine links SARS-CoV-2/COVID-19 infection to brain microvascular injury and neuroinflammation in dementia-like cognitive impairment.

Background: Dementia-like cognitive impairment is an increasingly reported complication of SARS-CoV-2 infection. However, the underlying mechanisms responsible for this complication remain unclear. A better understanding of causative processes by which COVID-19 may lead to cognitive impairment is essential for developing preventive and therapeutic interventions.

Mitochondrial DNA haplogroups and domain-specific neurocognitive performance in adults with HIV.

Neurocognitive (NC) impairment (NCI) is an important cause of morbidity in persons with HIV (PWH). In the high-energy environment of the central nervous system, mitochondria contribute to neuroinflammation and aging, which may ultimately drive the pathogenesis of neurodegenerative diseases. Mitochondrial DNA (mtDNA) haplogroups are associated with health outcomes in PWH.

Large Mitochondrial DNA Deletions in HIV Sensory Neuropathy.

Objective: The primary objective of this study was to evaluate the correlation of large mitochondrial DNA (mtDNA) deletions in skin samples of people with HIV (PWH) with measures of neuropathy and prior exposure to therapy. We hypothesized that deletions would be associated with neuropathy. As secondary objectives, we determined the correlation of deletion burden with demographic data and neuropathy measures.

Network medicine links SARS-CoV-2/COVID-19 infection to brain microvascular injury and neuroinflammation in dementia-like cognitive impairment.

Background: Dementia-like cognitive impairment is an increasingly reported complication of SARS-CoV-2 infection. However, the underlying mechanisms responsible for this complication remain unclear. A better understanding of causative processes by which COVID-19 may lead to cognitive impairment is essential for developing preventive interventions.

Plasma Citrate and Succinate Are Associated With Neurocognitive Impairment in Older People With HIV.

Background: Neurocognitive impairment (NCI) is associated with monocyte activation in people with HIV (PWH). Activated monocytes increase glycolysis, reduce oxidative phosphorylation, and accumulate citrate and succinate, tricarboxylic acid (TCA) cycle metabolites that promote inflammation-this metabolic shift may contribute to NCI and slowed gait speed in PWH.

Methods: Plasma citrate and succinate were assayed by liquid chromatography-mass spectrometry from 957 participants upon entry to a multicenter, prospective cohort of older PWH.

A network medicine approach to investigation and population-based validation of disease manifestations and drug repurposing for COVID-19.

The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to unprecedented social and economic consequences. The risk of morbidity and mortality due to COVID-19 increases dramatically in the presence of coexisting medical conditions, while the underlying mechanisms remain unclear. Furthermore, there are no approved therapies for COVID-19.

Higher iron stores and the HFE 187C>G variant delay onset of peripheral neuropathy during combination antiretroviral therapy.

Objective: People with HIV (PWH) continue to experience sensory neuropathy and neuropathic pain in the combination antiretroviral therapy (cART) era for unclear reasons. This study evaluated the role of iron in a previously reported association of iron-loading hemochromatosis (HFE) gene variants with reduced risk of neuropathy in PWH who received more neurotoxic cART, since an iron-related mechanism also might be relevant to neuropathic symptoms in PWH living in low-resource settings today.

Design: This time-to-event analysis addressed the impact of systemic iron levels on the rapidity of neuropathy onset in PWH who initiated cART.

Correction to: HIV Infection and Neurocognitive Disorders in the Context of Chronic Drug Abuse: Evidence for Divergent Findings Dependent upon Prior Drug History.

Corrected sentence in Interactions between the Effects of Drug Use and HIV-1 Infection Leads to Accelerated Disease Progression: "White matter damage (Tang et al. 2015; Alakkas et al. 2019), mitochondrial dysfunction (Buch et al.

A Network Medicine Approach to Investigation and Population-based Validation of Disease Manifestations and Drug Repurposing for COVID-19.

The global Coronavirus Disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to unprecedented social and economic consequences. The risk of morbidity and mortality due to COVID-19 increases dramatically in the presence of co-existing medical conditions while the underlying mechanisms remain unclear. Furthermore, there are no proven effective therapies for COVID-19.

New insights into genetic susceptibility of COVID-19: an ACE2 and TMPRSS2 polymorphism analysis.

Background: Coronavirus Disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has now been confirmed worldwide. Yet, COVID-19 is strangely and tragically selective. Morbidity and mortality due to COVID19 rise dramatically with age and co-existing health conditions, including cancer and cardiovascular diseases.

Correction to: A candidate gene study of intermediate histopathological phenotypes in HIV-associated neurocognitive disorders.

Due to a production error data in Table 1 were not presented correctly.

HIV Infection and Neurocognitive Disorders in the Context of Chronic Drug Abuse: Evidence for Divergent Findings Dependent upon Prior Drug History.

The fronto-striatal circuitry, involving the nucleus accumbens, ventral tegmental area, and prefrontal cortex, mediates goal-directed behavior and is targeted by both drugs of abuse and HIV-1 infection. Acutely, both drugs and HIV-1 provoke increased dopamine activity within the circuit. However, chronic exposure to drugs or HIV-1 leads to dysregulation of the dopamine system as a result of fronto-striatal adaptations to oppose the effects of repeated instances of transiently increased dopamine.

A candidate gene study of intermediate histopathological phenotypes in HIV-associated neurocognitive disorders.

HIV-associated neurocognitive disorders (HAND) describe a spectrum of neuropsychological impairment caused by HIV-1 infection. While the sequence of cellular and physiological events that lead to HAND remains obscure, it likely involves chronic neuroinflammation. Host genetic markers that increase the risk for HAND have been reported, but replication of such studies is lacking, possibly due to inconsistent application of a behavioral phenotype across studies.