Methamphetamine Increases the Proportion of SIV-Infected Microglia/Macrophages,Alters Metabolic Pathways,and Elevates Cell Death Pathways: A Single-Cell Analysis

Both substance use disorder and HIV infection continue to affect many individuals. Both have untoward effects on the brain, and the two conditions often co-exist. In the brain, macrophages and microglia are infectable by HIV, and these cells are also targets for the effects of drugs of abuse, such as the psychostimulant methamphetamine. To determine the interaction of HIV and methamphetamine, we isolated microglia and brain macrophages from SIV-infected rhesus monkeys that were treated with or without methamphetamine. Cells were subjected to single-cell RNA sequencing and results were analyzed by statistical and bioinformatic analysis. In the animals treated with methamphetamine, a significantly increased proportion of the microglia and/or macrophages were infected by SIV. In addition, gene encoding functions in cell death pathways were increased, and the brain-derived neurotropic factor pathway was inhibited. The gene expression patterns in infected cells did not cluster separately from uninfected cells, but clusters comprised of microglia and/or macrophages from methamphetamine-treated animals differed in neuroinflammatory and metabolic pathways from those comprised of cells from untreated animals. Methamphetamine increases CNS infection by SIV and has adverse effects on both infected and uninfected microglia and brain macrophages, highlighting the dual and interacting harms of HIV infection and drug abuse on the brain.     

Chitinase-3-like Protein 1 Is Associated with Poor Virologic Control and Immune Activation in Children Living with HIV

Perinatally infected children living with HIV (CLWH) face lifelong infection and associated inflammatory injury. Chitinase-like 3 protein-1 (CHI3L1) is expressed by activated neutrophils and may be a clinically informative marker of systemic inflammation in CLWH. We conducted a multi-centre, cross-sectional study of CLWH, enrolled in the Early Pediatric Initiation Canadian Child Cure Cohort Study (EPIC⁴). Plasma levels of CHI3L1, pro-inflammatory cytokines, and markers of microbial translocation were measured by enzyme-linked immunosorbent assays. Longitudinal clinical characteristics (viral load, neutrophil count, CD4+ and CD8+ T-lymphocyte counts, and antiretroviral (ARV) regimen) were abstracted from patient medical records. One-hundred-and-five (105) CLWH (median age 13 years, 62% female) were included in the study. Seventy-seven (81%) had viral suppression on combination antiviral therapy (cART). The median CHI3L1 level was 25 μg/L (IQR 19–39). CHI3L1 was directly correlated with neutrophil count (ρ = 0.22, p = 0.023) and inversely correlated with CD4/CD8 lymphocyte ratio (ρ = −0.35, p = 0.00040). Children with detectable viral load had higher levels of CHI3L1 (40 μg/L (interquartile range, IQR 33–44) versus 24 μg/L (IQR 19–35), p = 0.0047). CHI3L1 levels were also correlated with markers of microbial translocation soluble CD14 (ρ = 0.26, p = 0.010) and lipopolysaccharide-binding protein (ρ = 0.23, p = 0.023). We did not detect differences in CHI3L1 between different cART regimens. High levels of neutrophil activation marker CHI3L1 are associated with poor virologic control, immune dysregulation, and microbial translocation in CLWH on cART.     

Patterns of Cerebrospinal Fluid Alzheimer’s Dementia Biomarkers in People Living with HIV: Cross-Sectional Study on Associated Factors According to Viral Control,Neurological Confounders and Neurocognition

People living with HIV (PLWH) age with an excess burden of comorbidities that may increase the incidence of age-related complications. There is controversy surrounding the hypothesis that HIV can accelerate neurodegeneration and Alzheimer’s dementia (AD). We performed a retrospective study to analyze the distribution of cerebrospinal fluid (CSF) AD biomarkers (beta amyloid 1–42 fragment, tau, and phosphorylated tau) in adult PLWH (on cART with undetectable viremia, n = 136, with detectable viremia, n = 121, and with central nervous system CNS disorders regardless of viremia, n = 72) who underwent a lumbar puncture between 2008 to 2018; HIV-negative controls with AD were included (n = 84). Five subjects (1.5%) presented CSF biomarkers that were compatible with AD: one was diagnosed with AD, whereas the others showed HIV encephalitis, multiple sclerosis, cryptococcal meningitis, and neurotoxoplasmosis. Regardless of confounders, 79.6% of study participants presented normal CSF AD biomarkers. Isolated abnormalities in CSF beta amyloid 1–42 (7.9%) and tau (10.9%) were associated with age, biomarkers of intrathecal injury, and inflammation, although no HIV-specific feature was associated with abnormal CSF patterns. CSF levels of AD biomarkers very poorly overlapped between HIV-positive clinical categories and AD controls. Despite the correlations with neurocognitive performance, the inter-relationship between amyloid and tau proteins in PLWH seem to differ from that observed in AD subjects; the main driver of the isolated increase in tau seems represented by non-specific CNS inflammation, whereas the mechanisms underlying isolated amyloid consumption remain unclear.     

Potential Role of Epstein–Barr Virus in Oral Potentially Malignant Disorders and Oral Squamous Cell Carcinoma: A Scoping Review

Though the oral cavity is anatomically proximate to the nasal cavity and acts as a key reservoir of EBV habitation and transmission, it is still unclear whether EBV plays a significant role in oral carcinogenesis. Many studies have detected EBV DNA in tissues and exfoliated cells from OSCC patients. However, very few studies have investigated the expression of functional EBV proteins implicated in its oncogenicity. The most studied are latent membrane protein 1 (LMP-1), a protein associated with the activation of signalling pathways; EBV determined nuclear antigen (EBNA)-1, a protein involved in the regulation of gene expression; and EBV-encoded small non-polyadenylated RNA (EBER)-2. LMP-1 is considered the major oncoprotein, and overexpression of LMP-1 observed in OSCC indicates that this molecule might play a significant role in oral carcinogenesis. Although numerous studies have detected EBV DNA and proteins from OSCC and oral potentially malignant disorders, heterogeneity in methodologies has led to discrepant results, hindering interpretation. Elucidating the exact functions of EBV and its proteins when expressed is vital in establishing the role of viruses in oral oncogenesis. This review summarises the current evidence on the potential role of EBV in oral oncogenesis and discusses the implications as well as recommendations for future research.     

Prevalence and Risk Factors Associated with HIV Infection Among Men Having Sex with Men in Ho Chi Minh City, Vietnam

To learn more about risk behaviors among men who have sex with men (MSM) in Vietnam and their prevalence of HIV, we conducted a study among MSM in Ho Chi Minh City (HCMC) to determine HIV-1 prevalence and behaviors associated with infection. This consisted of formative (35 MSM) and cross-sectional (600 MSM) studies at 72 sites, including 75 transvestites, 55 bisexuals, 10 sex workers, and 460 other MSM. Only 5.3% cohabited with a wife/girlfriend, but 30% reported ever having sex with a female. Prevalence of HIV was 8%, ranging from 33% in sex workers to 7% among transvestites and other MSM. Injecting drugs, selling sex, being 20–40 years old, having less than 6 years of education, and having more than five male anal sex partners in the past month were associated with being HIV-infected. MSM are an HIV bridge group, and should be included in sentinel surveillance. Targeted interventions should be implemented.     

Influence of Crystalline Admixtures and Their Synergetic Combinations with Other Constituents on Autonomous Healing in Cracked Concrete—A Review

Crystalline admixtures (CAs) are new materials for promoting self-healing in concrete materials to repair concrete cracks. They have been applied to tunnel, reservoir dam, road, and bridge projects. The fundamental research and development of CAs are needed concerning their practical engineering applications. This paper reviews the current research progress of commercial CAs, including self-made CA healing cracks; the composition of CA; healing reaction mechanism; the composition of healing products; distribution characteristics of healing products; the influence of service environment and crack characteristics on the healing performance of CA; and coupling healing performance of CA with fiber, expansive agent, and superabsorbent polymers. The current research findings are summarized, and future research recommendations are provided to promote the development of high-performance cement matrix composites.     

Markedly Enhanced Cytochrome P450 2E1 Induction and Lipid Peroxidation Is Associated with Severe Liver Injury in Fish Oil—Ethanol-Fed Rats

We evaluated the role of changes in cytochrome P-450 2E1 (CYP 2E1) and lipid peroxidation in relation to development of severe liver injury in fish oil–ethanol-fed rats. The experimental animals (male Wistar rats) were divided into 5 rats/group and were fed the following diets for 1 month: corn oil and ethanol (CO+E) or corn oil and dextrose (CO+D), and fish oil and ethanol (FO+E) or fish oil and dextrose (FO+D). For each animal, microsomal analysis of CYP 2E1 protein, aniline hydroxylase activity, fatty acid composition, and conjugated dienes was conducted. Also, evaluation of severity of pathology was done for each rat. The mean ± SD of the pathology score was significantly higher ( p < 0.01) in the FO+E (6.0 ± 1.3) group than in the CO+E group (3.0 ± 0.5). No pathological changes were evident in the dextrose-fed controls. The CYP 2E1 protein levels (mean ± SD) were significantly higher ( p < 0.01) in the FO+E group (13.1 ± 2.0) compared with the CO+E (4.7 ± 1.2) and FO+D (1.8 ± 0.5) groups. Higher levels of eicosapentaenoic and docosa-hexaenoic acids and lower levels of arachidonic acid were detected in liver microsomes from rats fed fish oil compared with corn oil. A significant correlation was obtained between CYP 2E1 protein and conjugated diene levels ( r = 0.78, p < 0.01). Our results showing markedly increased CYP 2E1 induction and lipid peroxidation in the FO+E group provides one possible explanation for the greater severity of liver injury in this group.     

Clinical characteristics and treatment outcome of patients with visceral leishmaniasis and HIV co‐infection in northwest Ethiopia

Objectives To describe the clinical presentation of patients with visceral leishmaniasis (VL) with and without human immunodeficiency virus (HIV) co‐infection and factors associated with poor outcome in northwest Ethiopia. Method Retrospective review of 241 patients with VL (92 with and 149 without HIV co‐infection). Results HIV co‐infection was present in 92 (38%) of the patients. Clinical presentation of VL was indistinguishable between patients with and without HIV co‐infection. Co‐infected patients had a poorer outcome i.e. either death or treatment failure (31.5%vs. 5.6%, P < 0.001). The presence of tuberculosis or sepsis syndrome among patients with VL and HIV co‐infected independently predicted death or treatment failure [odds ratio 4.5 (95% CI 1.47–13.92, P = 0.009) and 9.1 (95% CI 2.16–37.97, P = 0.003), respectively]. Despite having similar clinical presentation at the time of diagnosis, VL and HIV co‐infected patients had a higher mortality and treatment failure than immunocompetent patients. Conclusion The frequency of HIV co‐infection among patients with VL is high in the study area, and this co‐infection was associated with death or treatment failure. The clinical management of VL in HIV co‐infected patients is a major challenge that requires new treatment approaches to improve its outcome.     

Obesity is associated with higher risk of intensive care unit admission and death in influenza A (H1N1) patients: a systematic review and meta‐analysis

The aim of this study was to assess the association between obesity and the risk of intensive care unit (ICU) admission and death among patients hospitalized for influenza A (H1N1) viral infection. A systematic review of the Medline and Cochrane databases using ‘obesity’, ‘hospitalization’, ‘influenza A viral infection’, various synonyms, and reference lists of retrieved articles from January 2009 to January 2010. Studies comparing the prevalence of obesity among patients with confirmed infection for influenza A virus and who were either hospitalized or admitted to ICU/died were included. A total of 3059 subjects from six cross‐sectional studies, who were hospitalized for influenza A (H1N1) viral infection, were included in this meta‐analysis. Severely obese H1N1 patients (body mass index ≥ 40 kg m^?2, n = 804) were as twice as likely to be admitted to ICU or die (odds ration: 2.01, 95% confidence interval: 1.29–3.14, P < 0.002) compared with H1N1 patients who were not severely obese. Having a body mass index ≥ 30 kg m^?2 was similarly associated with a more than twofold increased risk of ICU admission or death although this did not reach statistical significance (2.14, 0.92–4.99, P < 0.07). This meta‐analysis supports the view that obesity is associated with higher risks of ICU admission or death in patients with influenza A (H1N1) infection. Therefore, morbid obese patients should be monitored more intensively when hospitalized.     

Clinical diagnosis of pandemic A(H1N1) 2009 influenza in children with negative rapid influenza diagnostic test by lymphopenia and lower C‐reactive protein levels

Background

The sensitivity of rapid influenza diagnostic test (RIDT) of children with influenza-like illness (ILI) remains low.

Objective

We compare the parameters between pandemic A(H1N1) 2009 influenza with negative RIDT and ILI not H1N1 for improving the low sensitivity of RIDT for children with ILI.

Methods

In a cohort of consecutive laboratory-confirmed H1N1 influenza, we identified 150 H1N1 children with positive RIDT, 152 H1N1 children with negative RIDT, and 75 children with ILI not H1N1. Viral load in throat, complete blood count (CBC), and C-reactive protein (CRP) levels between H1N1 children with negative RIDT and children with ILI not H1N1 were assessed.

Results

The diagnostic sensitivity of the RIDT was 45·5%. An analysis of CBC and CRP levels indicated that H1N1 children with negative RIDT had lower total leukocyte, neutrophil, lymphocyte, and basophil counts, and serum CRP levels (P < 0·01). Lymphocyte counts less than 1500 cells/mm³ and CRP levels <15 mg/l, determined by a receiver operating characteristic curve, showed a diagnostic sensitivity of 52·5% and 80·7%, respectively. Combining the lymphocyte counts and CRP levels provided a diagnostic sensitivity of 91·5%. Moreover, H1N1 children with negative RIDT had a lower viral load than those with positive RIDT (3·33 versus 4·48 log₁₀ copies/ml, P < 0·001); the viral load was negatively correlated to the lymphocyte count (P < 0·001).

Conclusions

A combination of a low lymphocyte count and a low CRP level could, in the early disease phase, provide a useful screening for H1N1 children with false-negative RIDT, potentially facilitating differential diagnoses.