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Introduction: 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 d...

BACKGROUND Black cisgender gay, bisexual and other sexual minority men (SMM) and transgender women (TW) continue to be heavily impacted by HIV. Further research is needed to better understand HIV prevention and care outcomes among Black SMM and TW, including the impact of substance use and sleep health, as well as whether neighborhood and network factors mediate and moderate these relationships. OBJECTIVE The current paper outlines the study methods being utilized in the recently launched follow-up study to the Neighborhoods and Networks (N2) study, which we refer to as N2 Part 2 (N2P2). METHODS Building on the N2 Cohort Study in Chicago from 2018 to 2022, N2P2 employs a prospective longitudinal cohort design and observational-implementation hybrid approach. With sustained high levels of community engagement, we aim to recruit a new sample of 600 Black SMM and TW participants residing in the Chicago metropolitan statistical area (MSA). Participants are asked to partake in three study visits across an 18-month study-period (one visit every 9 months). Four different forms of data are collected per wave: (1) an in-person survey, (2) biological specimen collection, (3) a daily remote ecological momentary assessment (EMA) for 14 days after each study visit, and (4) data from electronic health records (EHR). These forms of data collection continue to assess neighborhood and network factors and specifically explore substance use, sleep, immune function, obesity, and implementation of potential interventions that address relevant constructs (e.g., alcohol use, PrEP adherence). RESULTS The N2P2 study was funded in August 2021 by the National Institute of Drug Abuse (R01DA054553 and R21DA053156) and National Heart, Lung, and Brain Institute (R01HL160325). The study was launched in November 2022. Recruitment and enrollment for the first wave of data collection is still ongoing. CONCLUSIONS The N2P2 study is applying innovative methods to comprehensively explore the impacts of substance use and sleep health on HIV-related outcomes among an HIV status neutral cohort of Black SMM and TW in Chicago. The study is applying an observational-implementation hybrid design in order to help us achieve findings that support rapid translation, a critical priority among populations such as Black SMM and TW that experience long-standing inequities with regards to HIV and other health-related outcomes. N2P2 will directly build off of the findings that have resulted from the original N2 study among Black SMM and TW in Chicago. These findings include a better understanding of multi-level (e.g., individual, network, neighborhood) factors that contribute to HIV-related outcomes and viral suppression among Black SMM and TW.

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 Results Among 1011 participants (median age, 51 years), 18% reported current, 6% intermittent, and 76% no cannabis use at baseline; 88% reported 100% ART adherence. Current cannabis users were more likely to be Conclusions Among a cohort of older PWH, current cannabis users had a higher risk of

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. Although supplementation was not associated with protection, the effects of probiotics on immunity after infection were not examined. To address this question, we measured antibody titers to HIV Env and commensal bacteria in plasma from the vaccination/supplementation time points as well as after SHIV acquisition. We found that a trend toward lower HIV Env-specific titers in the animals given probiotics plus vaccine became greater after SHIV infection. Significantly lower IgA titers were observed in animals vaccinated and supplemented compared to vaccine alone due to a delay in antibody kinetics at week 2 post infection. We observed no difference, however, in titers to commensal bacteria during probiotic supplementation or after SHIV infection. These results suggest that probiotic supplementation may be a strategy for reducing IgA-specific HIV antibodies in the plasma, a correlate associated with increased HIV infection in the RV144 clinical trial.

While functions of the gastrointestinal (GI) microbiome include maintenance of immune homeostasis and protection against infectious disease, its role in determining disease severity duringPlasmodiuminfection has been limited to mouse models and observational human cohorts. Here, we performed controlledPlasmodiuminfection in both humans and rhesus macaques (RMs) to experimentally determine the impact of GI microbiome composition on disease progression. Through analysis of serially collected microbiome samples, we identified a high-risk microbial signature that strongly associated with increased risk of developing severe parasitemia in human participants. Importantly, we identified a parallel phenomenon in RMs. The combined weight of this evidence demonstrates that pre-infection GI microbiome composition is highly indicative ofP. falciparumdisease risk. Moreover, our observation thatP. fragile-microbiome dynamics in RMs closely mirrorsP. falciparum-microbiome interactions in humans strongly supports the use of this model in pre-clinical investigations of novel microbiome-targeting approaches to reduce malaria burden.

Objective Syndemic conditions have been linked to engagement in receptive condomless anal sex (CAS) and HIV seroconversion. However, little is known about the biological pathways whereby syndemics could amplify vulnerability to HIV and other sexually transmitted infections (STIs). Design HIV-negative sexual minority men (i.e., gay, bisexual, and other men who have sex with men) were recruited from four STI clinics in South Florida for a cross-sectional study. Methods Participants completed assessments for four syndemic conditions: depression, post-traumatic stress disorder, hazardous alcohol use, and any stimulant use (i.e., any self-reported use or reactive urine toxicology results). Cytokine and chemokine levels were measured using LEGENDplex from the rectal swabs of 92 participants reporting receptive CAS and no antibiotic use in the past three months. Results After controlling for age, race/ethnicity, pre-exposure prophylaxis (PrEP) use, and number of receptive CAS partners, a greater number of syndemic conditions was associated with higher levels of rectal cytokines/chemokines relevant to immune activation, inflammation, and the expansion and maintenance of T-helper 17 target cells, including rectal interferon-gamma (β = 0.22; p = 0.047), CXCL-8 (β = 0.24; p = 0.025), and interleukin-23 (β = 0.22; p = 0.049). Elevations in rectal cytokine or chemokine levels were most pronounced among participants experiencing two or more syndemic conditions compared to those experiencing no syndemic conditions. PrEP use was independently associated with elevations in multiple rectal cytokines/chemokines. Conclusions Syndemic conditions could increase biological vulnerability to HIV and other STIs in sexual minority men by potentiating rectal immune dysregulation.

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. All antibiotics disrupted the microbiome, including reduced abundances of fermentative bacteria and increased abundances of potentially pathogenic bacteria, including Enterobacteriaceae in the stool, and decreased Helicobacteraceae in the colon. This was associated with decreased SCFAs, indicating altered bacterial metabolism. Importantly, antibiotic use also substantially altered local immune responses, including increased neutrophils and Th17 cells in the colon. Furthermore, we observed increased soluble CD14 in plasma, indicating microbial translocation. These data provide a longitudinal evaluation of antibiotic-induced changes to the composition and function of colonic bacterial communities associated with specific alterations in mucosal and systemic immunity.

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, California. METHODS. In total, 78 methamphetamine-using sexual minority men with an undetectable HIV viral load (< 40 copies/mL) completed self-report measures of cannabis use and substance use disorder severity. Plasma biomarkers of monocyte activation (i.e., sCD14 and sCD163) and intestinal barrier integrity (iFABP) were measured. The associations of hazardous cannabis use with these measurements were examined after adjusting for substance use disorder severity, age, antiretroviral therapy regimen, CD4+ T-cell count, and IL-6. RESULTS. Hazardous cannabis users had the highest mean sCD14 levels (2,181 ng/mL) compared to non-hazardous users (1,991 ng/mL) and non-users (1,859 ng/mL; p = 0.05). In adjusted analyses, greater cannabis use severity was associated with higher sCD14 compared to non-users (Unstandardized Beta = 133.6 ng/mL, p = 0.03). Cannabis use severity was not significantly associated with sCD163 or iFABP. CONCLUSIONS: Hazardous cannabis use is independently associated with elevations in a clinically relevant marker of immune activation in methamphetamine users with treated HIV.

An effective vaccine to prevent HIV transmission has not yet been achieved. Modulation of the microbiome via probiotic therapy has been suggested to result in enhanced mucosal immunity. Here, we evaluated whether probiotic therapy could improve the immunogenicity and protective efficacy of SIV/HIV vaccination. Rhesus macaques were co-immunized with an SIV/HIV DNA vaccine via particle-mediated epidermal delivery and an HIV protein vaccine administered intramuscularly with Adjuplex™ adjuvant, while receiving daily oral Visbiome® probiotics. Probiotic therapy alone led to reduced frequencies of colonic CCR5+ and CCR6+ CD4+ T cells. Probiotics with SIV/HIV vaccination led to similar reductions in colonic CCR5+ CD4+ T cell frequencies. SIV/HIV-specific T cell and antibody responses were readily detected in the periphery of vaccinated animals but were not enhanced with probiotic treatment. Combination probiotics and vaccination did not impact rectal SIV/HIV target populations or reduce the rate of heterologous SHIV acquisition during the intrarectal challenge. Finally, post-infection viral kinetics were similar between all groups. Thus, although probiotics were well-tolerated when administered with SIV/HIV vaccination, vaccine-specific responses were not significantly enhanced. Additional work will be necessary to develop more effective strategies of microbiome modulation in order to enhance mucosal vaccine immunogenicity and improve protective immune responses.

This study reported that on 2 July, 2020, the Department of Health in Hawaii notified the public that a fitness instructor had signs and symptoms of COVID-19, which is a coronavirus infection caused by SARS-CoV-2. The instructor was one of the individuals who became infected with COVID-19 before the onset of symptoms. The average attack rate in classes taught by the instructors was 95% or less of 21 students. Among the 21 primary cases, 20% had symptoms of SARS-CoV-2 illness. It was not required for fitness facilities to require masks. The Hawaii Department of Health placed individuals with exposure to instructors in different facilities under quarantine. Those with exposure to the most recent symptom were not quarantined. Facility Y placed barriers between stationary bikes and the room. It also instituted a single-direction foot traffic flow. During this investigation, participants were exposed to fitness instructors who had taught before their symptoms onset. Although they were most likely infected, the transmission rate was highest among the instructors on the day of their symptoms. Not wearing face masks and prolonged close contact were identified as factors that led to the transmission. During this SARS-CoV-2 community transmission, fitness facilities should implement effective ventilation and other administrative controls to reduce transmission. Physical distancing and wearing a mask are also important to prevent hand-washing. The CDC's guidance for fitness centers states that the use of exercise equipment or activities that are entirely outdoors could reduce the risk of respiratory illness transmission among users. An additional set of administrative controls includes modifying fitness areas to provide a distance between patrons and staff members. Also, implementing visual cues to make foot traffic flow through the facility easier.

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 (n = 9) and adult (n = 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. Vaginal biopsies were profiled by proteomic analysis. The vaginal microbiome was assessed by 16S rRNA sequencing. We were powered to detect a 2.2-fold increase in infection rates between age groups, however, we identified no significant differences in susceptibility. This model cannot capture epidemiological factors or may not best represent biological differences of HIV susceptibility. No immune cell subsets measured were significantly different between groups. Inflammatory marker MCP-1 was significantly higher (adj p = .02), and sCD40L trended higher (adj p = .06) in vaginal cytobrushes of adults. Proteomic analysis of vaginal biopsies showed no significant (adj p

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 ra...

HIV-2 infection is characterized by low viremia and slow disease progression as compared to HIV-1 infection. Circulating CD14++CD16+ 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. We analyzed by flow cytometry these PBMC subsets from Paris area residents: 29 asymptomatic, untreated PLWHIV-2 from the IMMUNOVIR-2 study, part of the ANRS-CO5 HIV-2 cohort: 19 long-term non-progressors (LTNP; infection ≥8 years, undetectable viral load, stable CD4 counts≥500/μL; 17 of West-African origin -WA), and 10 non-LTNP (P; progressive infection; 9 WA); and 30 age-and sex-matched controls: 16 blood bank HD with unknown geographical origin, and 10 HD of WA origin (GeoHD). We measured plasma bacterial translocation markers by ELISA. Non-classical monocyte counts were higher in GeoHD than in HD (54 vs. 32 cells/μL, p = 0.0002). Slan+ monocyte counts were twice as high in GeoHD than in HD (WA: 28 vs. 13 cells/μL, p = 0.0002). Thus cell counts were compared only between participants of WA origin. They were similar in LTNP, P and GeoHD, indicating that there were no HIV-2 related differences. cDC counts did not show major differences between the groups. Interestingly, inflammatory monocyte counts correlated with plasma sCD14 and LBP only in PLWHIV-2, especially LTNP, and not in GeoHD. In conclusion, in LTNP PLWHIV-2, inflammatory monocyte counts correlated with LBP or sCD14 plasma levels, indicating a potential innate immune response to subclinical bacterial translocation. As GeoHD had higher inflammatory monocyte counts than HD, our data also show that specific controls are important to refine innate immunity studies.

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 in vitro or in vivo. Recently, a newly developed SHIV, SHIV.C.CH505.375H.dCT (SHIV.CH505), which incorporates vpu-env (gp140) sequences from a transmitted/founder HIV-1 subtype C strain, was shown to retain attributes of primary HIV-1 strains. However, a comprehensive analysis of the immunopathology that results from infection with this virus, especially in critical tissue compartments like the intestinal mucosa, has not been completed. In this study, we evaluated the viral dynamics and immunopathology of SHIV.CH505 in rhesus macaques. In line with previous findings, we found that SHIV.CH505 is capable of infecting and replicating efficiently in rhesus macaques, resulting in peripheral viral kinetics similar to that seen in pathogenic SIV and HIV infection. Furthermore, we observed significant and persistent depletions of CCR5(+) and CCR6(+) CD4(+) T cells in mucosal tissues, decreases in CD4(+) T cells producing Th17 cell-associated cytokines, CD8(+) T cell dysfunction, and alterations of B cell and innate immune cell function, indicating that SHIV.CH505 elicits intestinal immunopathology typical of SIV/HIV infection. These findings suggest that SHIV.CH505 recapitulates the early viral replication dynamics and immunopathogenesis of HIV-1 infection of humans and thus can serve as a new model for HIV-1 pathogenesis, treatment, and prevention research. IMPORTANCE The development of chimeric SHIVs has been instrumental in advancing our understanding of HIV-host interactions and allowing for in vivo testing of novel treatments. However, many of the currently available SHIVs have distinct drawbacks and are unable to fully reflect the features characteristic of primary SIV and HIV strains. Here, we utilize rhesus macaques to define the immunopathogenesis of the recently developed SHIV.CH505, which was designed without many of the limitations of previous SHIVs. We observed that infection with SHIV.CH505 leads to peripheral viral kinetics and mucosal immunopathogenesis comparable with those caused by pathogenic SIV and HIV. Overall, these data provide evidence of the value of SHIV.CH505 as an effective model of SIV/HIV infection and an important tool that can be used in future studies, including preclinical testing of new therapies or prevention strategies.

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 (SCFA), 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. All antibiotics disrupted the microbiome, including reduced abundances of fermentative bacteria and increased abundances of potentially pathogenic bacteria, including Enterobacteriaceae in stool, and decreased Helicobacteraceae in the colon. This was associated with decreased SCFAs, indicating altered bacterial metabolism. Importantly, antibiotic use also substantially altered local immune responses, including increased neutrophils and Th17 cells in the colon. Furthermore, we observed increased soluble-CD14 in plasma, indicating microbial translocation. These data provide a longitudinal evaluation of antibiotic-induced changes to the composition and function of colonic bacterial communities, associated with specific alterations in mucosal and systemic immunity.

During the summer of 2016, the Hawaii Department of Health responded to the second-largest domestic foodborne hepatitis A virus (HAV) outbreak in the post-vaccine era. The epidemiological investigation included case finding and investigation, sequencing of RNA positive clinical specimens, product trace-back and virologic testing and sequencing of HAV RNA from the product. Additionally, an online survey open to all Hawaii residents was conducted to estimate baseline commercial food consumption. We identified 292 confirmed HAV cases, of whom 11 (4%) were possible secondary cases. Seventy-four (25%) were hospitalised and there were two deaths. Among all cases, 94% reported eating at Oahu or Kauai Island branches of Restaurant Chain A, with 86% of those cases reporting raw scallop consumption. In contrast, a food consumption survey conducted during the outbreak indicated 25% of Oahu residents patronised Restaurant Chain A in the 7 weeks before the survey. Product trace-back revealed a single distributor that supplied scallops imported from the Philippines to Restaurant Chain A. Recovery, amplification and sequence comparison of HAV recovered from scallops revealed viral sequences matching those from case-patients. Removal of product from implicated restaurants and vaccination of those potentially exposed led to the cessation of the outbreak. This outbreak further highlights the need for improved imported food safety.

BackgroundCannabis 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.MethodsThe impact of cannabis use on peripheral immune cell frequency, activation, and function was assessed in 198 HIV-infected, antiretroviral-treated individuals by flow cytometry. Individuals were categorized into heavy, medium, or occasional cannabis users or noncannabis users based on the amount of the cannabis metabolite 11-nor-carboxy-tetrahydrocannabinol (THC-COOH) detected in plasma by mass spectrometry.ResultsHeavy cannabis users had decreased frequencies of human leukocyte antigen (HLA)-DR+CD38+CD4+ and CD8+ T-cell frequencies, compared to frequencies of these cells in non-cannabis-using individuals. Heavy cannabis users had decreased frequencies of intermediate and nonclassical monocyte subsets, as well as decreased frequencies of interleukin 23- and tumor necrosis factor-α-producing antigen-presenting cells.ConclusionsWhile the clinical implications are unclear, our findings suggest that cannabis use is associated with a potentially beneficial reduction in systemic inflammation and immune activation in the context of antiretroviral-treated HIV infection.

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. PBio therapy resulted in significantly increased frequencies of B cells expressing IgA in the colon and lymph node (LN), likely because of significantly increased LN T follicular helper cell frequencies and LN follicles. Increased frequencies of IL-23+ APCs in the colon were found post-PBio treatment, which correlated with LN T follicular helper cells. Finally, VSL#3 significantly downmodulated the response of TLR2-, TLR3-, TLR4-, and TLR9-expressing HEK293 cells to stimulation with Pam3CSK4, polyinosinic-polycytidylic acid, LPS, and ODN2006, respectively. These data provide a mechanism for the beneficial impact of PBio on mucosal health and implicates the use of PBio therapy in the context of vaccination or preventative approaches to enhance protection from mucosal infection by improving immune defenses at the mucosal portal of entry.

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. We additionally assessed the colon proteome to elucidate molecular pathways altered early after infection. We demonstrate increased T-cell activation (HLA-DR+) beginning 3–14 days post-SIV challenge, reduced peripheral zonulin 3–14 days post-SIV, and evidence of microbial translocation 14 days post-SIV. The onset of mucosal dysfunction preceded peripheral and mucosal Th17 depletion, which occurred 14–28 days post-SIV, and gut neutrophil accumulation was not observed. Proteins involved in epithelial structure were downregulated 3 days post-SIV followed by an upregulation of immune proteins 14 days post-SIV. These data demonstrate that immune perturbations such as Th17 loss and neutrophil infiltration occur after alterations to epithelial structural protein pathways, suggesting that epithelial damage occurs prior to widespread immune dysfunction.

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. Individuals were categorized into heavy, medium, or occasional cannabis users or noncannabis users based on the amount of the cannabis metabolite 11-nor-carboxy-tetrahydrocannabinol (THC-COOH) detected in plasma by mass spectrometry. RESULTS: Heavy cannabis users had decreased frequencies of human leukocyte antigen (HLA)-DR(+)CD38(+)CD4(+) and CD8(+) T-cell frequencies, compared to frequencies of these cells in non-cannabis-using individuals. Heavy cannabis users had decreased frequencies of intermediate and nonclassical monocyte subsets, as well as decreased frequencies of interleukin 23– and tumor necrosis factor-α–producing antigen-presenting cells. CONCLUSIONS: While the clinical implications are unclear, our findings suggest that cannabis use is associated with a potentially beneficial reduction in systemic inflammation and immune activation in the context of antiretroviral-treated HIV infection.

Microbial translocation has been linked to systemic immune activation in HIV-1 disease, yet mechanisms by which microbes may contribute to HIV-associated intestinal pathogenesis are poorly understood. Importantly, our understanding of the impact of translocating commensal intestinal bacteria on mucosal-associated T cell responses in the context of ongoing viral replication that occurs early in HIV-1 infection is limited. We previously identified commensal Escherichia coli-reactive Th1 and Th17 cells in normal human intestinal lamina propria (LP). In this article, we established an ex vivo assay to investigate the interactions between Th cell subsets in primary human LP mononuclear cells (LPMCs), commensal E. coli, and CCR5-tropic HIV-1Bal. Addition of heat-killed E. coli to HIV-1–exposed LPMCs resulted in increases in HIV-1 replication, CD4 T cell activation and infection, and IL-17 and IFN-γ production. Conversely, purified LPS derived from commensal E. coli did not enhance CD4 T cell infection. E. coli exposure induced greater proliferation of LPMC Th17 than Th1 cells. Th17 cells were more permissive to infection than Th1 cells in HIV-1–exposed LPMC cultures, and Th17 cell infection frequencies significantly increased in the presence of E. coli. The E. coli-associated enhancement of infection was dependent on the presence of CD11c+ LP dendritic cells and, in part, on MHC class II-restricted Ag presentation. These results highlight a potential role for translocating microbes in impacting mucosal HIV-1 pathogenesis during early infection by increasing HIV-1 replication and infection of intestinal Th1 and Th17 cells.

In this novel, a woman becomes obsessed with the man who confessed to killing her younger brother in a hit-and-run accident eight years ago.

Angiostrongylus eosinophilic meningitis is caused by infection with larvae of the rat lungworm, Angiostrongylus cantonensis. We report the case of an adult who ingested a raw, giant African snail (Achatina fulica) on the island of O‘ahu in Hawai‘i and developed an eosinophilic meningoencephalitis with severe headache, confusion, sixth cranial nerve palsy, ataxia, limb weakness, and paresthesia. He was treated with lumbar punctures to relieve pressure, high dose corticosteroids, and 14 days of albendazole. He had a prolonged convalescence, requiring 3 months of prednisone, and still had evidence of motor nerve weakness 4 months after exposure. A field investigation at the site of exposure yielded 5 of 9 Achatina fulica snails with evidence of A. cantonensis DNA by PCR. Cerebrospinal fluid samples from the patient were negative acutely but positive on day 15 of symptoms, using an investigational, real-time PCR assay. We discuss clinical management of this case in light of the current medical literature.

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. In case of positive anti-DNA or anti-ENA, the patient was referred to the department of internal medicine. One hundred patients were enrolled, mean age 33.1 ± 8.4 years. Most patients presented underlying psychiatric disorders: depression (46%), schizophrenia (13%), anxiety disorder (6%), and personality disorder (10%). A quarter of the cohort did not display underlying psychiatric disorders before hospitalization. Positive ANA ≥1:160 were found in 32 of the 100 patients tested (32%). No patients presented anti-DNA antibodies. One patient had positive anti-sjogrën's syndrome related antigen A (SSA), but did not present any features of SLE or Sjögren syndrome. Thus, systematic screening of SLE is not relevant in young women hospitalized in psychiatric department. However, clinicians should keep in mind that SLE can present with pure psychiatric symptoms.

Human peripheral blood contains antigen-presenting cells (APC), including dendritic cells (DC) and monocytes, that may encounter microbes that have translocated from the intestine to the periphery in disease states like HIV-1 infection and inflammatory bowel disease. We investigated the response of DC and monocytes in peripheral blood mononuclear cells (PBMC) to a panel of representative commensal enteric bacteria, includingEscherichia coli,Enterococcussp., andBacteroides fragilis. All three bacteria induced significant upregulation of the maturation and activation markers CD40 and CD83 on myeloid dendritic cells (mDC) and plasmacytoid dendritic cells (pDC). However, only mDC produced cytokines, including interleukin-10 (IL-10), IL-12p40/70, and tumor necrosis factor alpha (TNF-α), in response to bacterial stimulation. Cytokine profiles in whole PBMC differed depending on the stimulating bacterial species:B. fragilisinduced production of IL-23, IL-12p70, and IL-10, whereasE. coliandEnterococcusinduced an IL-10-predominant response. mDC and monocyte depletion experiments indicated that these cell types differentially produced IL-10 and IL-23 in response toE. coliandB. fragilis. Bacteroides thetaiotaomicrondid not induce levels of IL-23 similar to those ofB. fragilis, suggesting thatB. fragilismay have unique proinflammatory properties amongBacteroidesspecies. The addition of recombinant human IL-10 to PBMC cultures stimulated with commensal bacteria abrogated the IL-23 response, whereas blocking IL-10 significantly enhanced IL-23 production, suggesting that IL-10 controls the levels of IL-23 produced. These results indicate that blood mDC and monocytes respond differentially to innate stimulation with whole commensal bacteria and that IL-10 may play a role in controlling the proinflammatory response to translocated microbes.

Modules that perform photorefractive two-beam coupling operations have been built, characterized, and tested. These portable modules, interconnected by fiber optics, dispense with the need for repeated alignment and greatly facilitate the prototyping of complex signal- or image-processing photorefractive circuits. To evaluate the performance of the modules in a photorefractive circuit, we interconnected them in the feature extractor configuration: a ring configuration composed of two modules that selects the strongest signal within the signals presented on its input. With two signals at the input, an output contrast ratio of 45.4 dB is obtained for an input contrast ratio of 5 dB.

International audience; Objective To investigate association between genetic polymorphisms of GST, CYP and renal outcome or occurrence of adverse drug reactions (ADRs) in lupus nephritis (LN) treated with cyclophosphamide (CYC). CYC, as a pro-drug, requires bioactivation through multiple hepatic cytochrome P450s and glutathione S transferases (GST). Methods We carried out a multicentric retrospective study including 70 patients with proliferative LN treated with CYC. Patients were genotyped for polymorphisms of the CYP2B6, CYP2C19, GSTP1, GSTM1 and GSTT1 genes. Complete remission (CR) was defined as proteinuria 105Val GSTP1 genotype were respectively 38%, 60% and 44%. In multivariate analysis, the Ile -> 105Val GSTP1 genotype was an independent factor of poor renal outcome (achievement of CR or PR) (OR = 5.01 95% CI [1.02-24.51]) and the sole factor that influenced occurrence of ADRs was the GSTM1 null genotype (OR = 3.34 95% CI [1.064-10.58]). No association between polymorphisms of cytochrome P450s gene and efficacy or ADRs was observed. Conclusion This study suggests that GST polymorphisms highly impact renal outcome and occurrence of ADRs related to CYC in LN patients.