Publications by authors named "Jennifer Manuzak"

Article Synopsis
  • HIV and malaria often occur together in the same regions, leading to co-infection that worsens the symptoms of both diseases, but the mechanisms behind this increase in severity are not well understood.
  • A pilot study in rhesus macaques treated with antiretroviral therapy (ART) aimed to explore the effects of co-infection, revealing persistent viral loads and decreased CD4+ T-cells despite treatment, along with signs of anemia and parasitemia.
  • The study also found that co-infection increased inflammatory markers and altered neutrophil behavior, suggesting that inflammation and gastrointestinal dysfunction could play key roles in the aggravated disease pathology seen in HIV and malaria co-infection.
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In tropical areas, the simultaneous transmission of multiple vector-borne diseases is common due to ecological factors shared by arthropod vectors. Malaria and dengue virus, transmitted by and mosquitoes, respectively, are among the top vector-borne diseases that cause significant morbidity and mortality in endemic areas. Notably, tropical areas often have suitable conditions for the co-existence of these mosquito species, highlighting the importance of identifying markers that accurately indicate the risk of acquiring each specific disease entity.

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Article Synopsis
  • Black cisgender gay, bisexual, and other sexual minority men (SMM) and transgender women (TW) are disproportionately impacted by HIV, highlighting the need for more research focused on the effects of substance use and sleep health in this demographic.* -
  • The N2 Part 2 (N2P2) study builds on the original Neighborhoods and Networks (N2) study, aiming to identify socioenvironmental factors that influence HIV prevention and treatment in Black SMM and TW across Chicago.* -
  • Utilizing a longitudinal cohort design, N2P2 will engage 600 participants over 18 months, collecting various data types to assess neighborhood influences and factors like substance use and sleep on health outcomes.*
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Importance: Prenatal cannabis use is rising and is a major public health issue. Cannabis use in pregnancy and during lactation has been associated with increased maternal and offspring morbidity and mortality.

Objective: This review aims to summarize the existing literature and current recommendations for cannabis use during pregnancy or lactation.

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Compared to young heterosexual men, young sexual and gender minorities (YSGM) have elevated systemic inflammation and unique intestinal microbial profiles, influenced by HIV infection and substance use. However, links between cannabis use and microbial dysbiosis in this population have not been well described. In this pilot study, we aimed to characterize the complex interrelationships between cannabis use and microbial community structure in YSGM in relationship to HIV status.

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Background: Conflicting evidence exists on the impact of cannabis use on antiretroviral therapy (ART) adherence among people with human immunodeficiency virus (PWH). We leveraged data collected among older PWH to characterize longitudinal associations between cannabis use and ART adherence.

Methods: AIDS Clinical Trials Group (ACTG) A5322 study participants were categorized as <100% (≥1 missed dose in past 7 days) or 100% (no missed doses) ART adherent.

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The induction of robust circulating antibody titers is a key goal of HIV-1 vaccination. Probiotic supplementation is an established strategy to enhance microbiota and boost antibody responses to vaccines. A recent study tested whether oral probiotics could enhance vaccine-specific mucosal immunity by testing vaccination with and without supplementation in a Rhesus macaque Simian-Human Immunodeficiency Virus challenge model.

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Cannabis is widely used for recreational and medical purposes, but its therapeutic efficacy remains unresolved for many applications as data from retrospective studies show dramatic discrepancy. We hypothesized that false self-reporting of cannabis use and lack of differentiation of heavy users from light or occasional users contribute to the conflicting outcomes. The goal of this study was to develop an objective biomarker of cannabis use and test how application of such biomarker impacts clinical study outcomes and dose-response measures.

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Multisystem inflammatory syndrome in children (MIS-C) occurs during or recently following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and is characterized by persistent fever, inflammation, and severe illness requiring hospitalization. The majority of patients with MIS-C also present with gastrointestinal (GI) symptoms, including abdominal pain, vomiting, and diarrhea. In this issue of the JCI, Yonker, Gilboa, and colleagues identified zonulin as a biomarker of GI permeability in children with MIS-C and present the results of an intriguing proof-of-concept study indicating that zonulin may represent a potential therapeutic target for MIS-C treatment and prevention.

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Article Synopsis
  • An effective vaccine to prevent HIV transmission is still under development, and probiotic therapy has been proposed as a way to potentially boost immune responses during vaccination.
  • In a study with rhesus macaques, researchers tested whether daily oral probiotics could enhance the effectiveness of SIV/HIV vaccines, but found no significant improvements in immune responses or protection against infection.
  • The findings suggest that while probiotics are safe to use with SIV/HIV vaccinations, they did not enhance the vaccine’s effectiveness, indicating more research is needed to find better ways to leverage the microbiome for improving vaccine responses.
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In Sub-Saharan Africa, young women 15-24 years of age account for nearly 30% of all new HIV infections, however, biological and epidemiological factors underlying this disproportionate infection rate are unclear. In this study, we assessed biological contributors of SIV/HIV susceptibility in the female genital tract (FGT) using adolescent ( = 9) and adult ( = 10) pigtail macaques (PTMs) with weekly low-dose intravaginal challenges of SIV. Immunological variables were captured in vaginal tissue of PTMs by flow cytometry and cytokine assays.

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HIV-2 infection is characterized by low viremia and slow disease progression as compared to HIV-1 infection. Circulating CD14CD16 monocytes were found to accumulate and CD11c conventional dendritic cells (cDC) to be depleted in a Portuguese cohort of people living with HIV-2 (PLWHIV-2), compared to blood bank healthy donors (HD). We studied more precisely classical monocytes; CD16 inflammatory (intermediate, non-classical and slan monocytes, known to accumulate during viremic HIV-1 infection); cDC1, important for cross-presentation, and cDC2, both depleted during HIV-1 infection.

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The diverse bacterial communities that colonize the gastrointestinal tract play an essential role in maintaining immune homeostasis through the production of critical metabolites such as short-chain fatty acids (SCFAs) and this can be disrupted by antibiotic use. However, few studies have addressed the effects of specific antibiotics longitudinally on the microbiome and immunity. We evaluated the effects of four specific antibiotics: enrofloxacin, cephalexin, paromomycin, and clindamycin, in healthy female rhesus macaques.

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Simian-human immunodeficiency viruses (SHIVs) have been utilized to test vaccine efficacy and characterize mechanisms of viral transmission and pathogenesis. However, the majority of SHIVs currently available have significant limitations in that they were developed using sequences from chronically HIV-infected individuals or uncommon HIV subtypes or were optimized for the macaque model by serially passaging the engineered virus or Recently, a newly developed SHIV, SHIV.C.

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Article Synopsis
  • Gastrointestinal (GI) mucosal dysfunction in HIV infection contributes to health issues and persists despite treatment, partly due to factors that aren't fully understood.
  • Research reveals that increased neutrophil lifespan is linked to neutrophil buildup in the GI tract of HIV patients, suggesting this could be a new target for treatment.
  • The study also shows that the balance of gut bacteria, particularly a lower Lactobacillus to Prevotella ratio, affects neutrophil survival, indicating that restoring beneficial bacteria may help reduce inflammation in HIV and similar chronic conditions.
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Background: The use of stimulants, such as methamphetamine, has been associated with greater immune activation in treated HIV infection. However, relatively little is known about whether concomitant cannabis use is associated with lower immune activation among HIV-positive stimulant users.

Setting: HIV-positive, sexual minority men with biologically confirmed, recent methamphetamine use were enrolled in San Francisco, CA.

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HIV and pathogenic SIV infection are characterized by mucosal dysfunction including epithelial barrier damage, loss of Th17 cells, neutrophil infiltration, and microbial translocation with accompanying inflammation. However, it is unclear how and when these contributing factors occur relative to one another. In order to determine whether any of these features initiates the cycle of damage, we longitudinally evaluated the kinetics of mucosal and systemic T-cell activation, microbial translocation, and Th17 cell and neutrophil frequencies following intrarectal SIV infection of rhesus macaques.

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Background: Cannabis is a widely used drug in the United States, and the frequency of cannabis use in the human immunodeficiency virus (HIV)-infected population is disproportionately high. Previous human and macaque studies suggest that cannabis may have an impact on plasma viral load; however, the relationship between cannabis use and HIV-associated systemic inflammation and immune activation has not been well defined.

Methods: The impact of cannabis use on peripheral immune cell frequency, activation, and function was assessed in 198 HIV-infected, antiretroviral-treated individuals by flow cytometry.

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On the basis that diagnosis of neuropsychiatric systemic lupus erythematosus (NPSLE) is sometimes difficult and systemic lupus erythematosus (SLE) can present with isolated psychiatric symptoms, we initiated a survey in a psychiatric department to screen for NPSLE in young female inpatients.We prospectively studied consecutive young female patients referred to the department of psychiatry. Antinuclear antibodies (ANA), anti-deoxyribonucleic acid (DNA), and antiextractable soluble nuclear antigens (ENA) in the serum of patients were screened.

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Article Synopsis
  • - The study aimed to explore how genetic variations (polymorphisms) in specific enzymes (GST and CYP) affect kidney outcomes and adverse drug reactions in lupus nephritis patients treated with cyclophosphamide (CYC).
  • - Involving 70 patients, it found that certain genetic profiles, especially the GSTP1 variant, were linked to poorer kidney outcomes, while the GSTM1 null genotype was tied to a higher risk of adverse reactions.
  • - The results highlight that GST genetic polymorphisms significantly influence kidney health and medication side effects in lupus nephritis treatment, while cytochrome P450 variations showed no significant impact.
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Unlabelled: An altered intestinal microbiome during chronic human immunodeficiency virus (HIV) infection is associated with mucosal dysfunction, inflammation, and disease progression. We performed a preclinical evaluation of the safety and efficacy of fecal microbiota transplantation (FMT) as a potential therapeutic in HIV-infected individuals. Antiretroviral-treated, chronically simian immunodeficiency virus (SIV)-infected rhesus macaques received antibiotics followed by FMT.

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Given the critical role of mucosal surfaces in susceptibility to infection, it is imperative that effective mucosal responses are induced when developing efficacious vaccines and prevention strategies for infection. Modulating the microbiota in the gastrointestinal (GI) tract through the use of probiotics (PBio) is a safe and well-tolerated approach to enhance mucosal and overall health. We assessed the longitudinal impact of daily treatment with the VSL#3 probiotic on cellular and humoral immunity and inflammation in healthy macaques.

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