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We developed a highly reproducible 32-marker mass cytometry panel able to measure all canonical immune lineages and perform detailed characterization of both CD4 and CD8 T cells in human peripheral blood mononuclear cells. In this panel, we identify six different T cell memory subsets, as well as markers of activation, cell cycling, and survival. In addition, this panel classifies all major CD4 T cell helper subsets. This panel enables detailed monitoring of CD4 and CD8 T cells in the context of infectious disease, cancer or autoimmunity with limited patient sample use. Detailed methods for standardization and optimization of the panel can be found in Supporting Information.

HIV infection induces a robust Tcell response that is sustained by high viremia, but falls following the onset of antiretroviral therapy (ART). Relatively little has been reported on the subsequent stability of the HIV-specific Tcell response in individuals on durable therapy. Such data are critical for powering clinical trials testing Tcell-based immunotherapies. In a cross-sectional study, HIV-specific Tcell responses were detectable by exvivo interferon (IFN)-γ ELISpot (average ∼1,100 spot-forming units [SFUs]/106 peripheral blood mononuclear cells) in persons living with HIV (PLWH; n= 34), despite median durableART suppression of 5.0 years. No substantial association was detected between the summed HIV-specific Tcell response and the size of the replication-competent HIV reservoir. Tcell responses were next measured in participants sampled weekly, monthly, or yearly. HIV-specific Tcell responses were highly stable over the time periods examined; within-individual variation ranged from 16% coefficient of variation (CV) for weekly to 27% CV for yearly sampling. These data were used to generate power calculations for future immunotherapy studies. The stability of the HIV-specific Tcell response in suppressed PLWH will enable powered studies of small sizes (e.g., n= 6-12), facilitating rapid and iterative testing for Tcell-based immunotherapies against HIV.

CD8+ T cell immunity is essential to the control of HIV viremia. We examined the safety and immunogenicity of MVA-vectored vaccines expressing highly conserved HIV regions in a first-in-man Phase I study in people living with HIV on ART. Participants received a single intramuscular dose of MVA.tHIVconsv3 (M3), MVA.tHIVconsv4 (M4), combined M3+M4 or saline in a 7:7:7:3 ratio. M3 and M4 span the same 6 HIV regions but differ by approximately 10% of amino acids; a design to increase vaccine coverage of circulating HIV variants. We employed ex vivo IFN-g ELISpot assays to measure changes in HIV-specific T cell magnitude and breadth to M3 and/or M4 immunogens following vaccination. We also examined whether M3, M4 or M3+M4 vaccination increased the ability of CD8+ T cells inhibit HIV in vitro replication. The M&M study is fully enrolled but presently is blinded. Analysis of blinded data show that vaccination was safe and well tolerated. Vaccination induced strong increases in the T cell response to M3, M4 vaccine immunogens producing a 2- to 18-fold increase in magnitude in 16/20 participants tested to date. M3/M4-specific T cell breadth also increased across participants. Vaccine-associated T cell responses mostly remained elevated (>2-fold increase) for at least 70 days post-vaccination visit. Vaccination was also associated with clear and sustained increases in in vitro virus inhibition. The percentage of the total HIV T cell response targeting conserved HIV regions in participants increased on average from 40 to 60% post-vaccination, suggesting M3/M4/M3+4 vaccination successfully produced a sustained shift in T cell immunodominance. Unblinded data will be presented at this meeting. Supported by U01AI131310

Objectives: Although an association between uric acid (UA) levels and obstructive sleep apnea (OSA) has been reported, the effect of continuous positive airway pressure (CPAP) on this measure is yet unclear. We aimed to investigate the effect of CPAP therapy on serum UA levels in patients with OSA. Methods: We conducted a multicenter, open-label, randomized controlled trial in 307 women diagnosed with moderate-to-severe OSA (apnea-hypopnea index [AHI] >= 15) in 19 Spanish Sleep Units. Women were randomized to CPAP (n =151) or conservative treatment (n =156) for 12 weeks. Changes in serum UA measures were assessed on an intention-to-treat basis. Additional analyses were conducted in the subgroup of women with CPAP adherence >= 4 hinight and those with UA levels >= 6 mg/dl. Results: Women had a mean (SD) age of 57.1 (10.1) years, median (first-third quartile) body mass index of 33.7 (29.0-38.5) mg/kg(2) and AHI of 32.0 (22.6-48.5). The average serum UA measure was 5.11 (1.26) mg/dl, and 80 (26.1%) participants had UA >= 6 mg/dl. Compared with the control group, the CPAP group did Keywords: not achieve any reduction in UA levels (non-adjusted intergroup difference -0.03 mg/dl, 95%CI-0.20 to 0.13; p = 0.702) after 12 weeks of follow-up. These results did not change when the analysis was restricted to women with CPAP adherence >= 4 h/night, or the subgroup of women with hyperuricemia. Conclusions: Twelve weeks of CPAP therapy does not reduce UA levels compared to conservative treatment in women with moderate-to-severe OSA. (C) 2018 SEPAR. Published by Elsevier Espana, S.L.U. All rights reserved.

A major limitation of current humanized mouse models is that they primarily enable the analysis of human-specific pathogens that infect hematopoietic cells. However, most human pathogens target other cell types, including epithelial, endothelial and mesenchymal cells. Here, we show that implantation of human lung tissue, which contains up to 40 cell types, including nonhematopoietic cells, into immunodeficient mice (lung-only mice) resulted in the development of a highly vascularized lung implant. We demonstrate that emerging and clinically relevant human pathogens such as Middle East respiratory syndrome coronavirus, Zika virus, respiratory syncytial virus and cytomegalovirus replicate in vivo in these lung implants. When incorporated into bone marrow/liver/thymus humanized mice, lung implants are repopulated with autologous human hematopoietic cells. We show robust antigen-specific humoral and T-cell responses following cytomegalovirus infection that control virus replication. Lung-only mice and bone marrow/liver/thymus-lung humanized mice substantially increase the number of human pathogens that can be studied in vivo, facilitating the in vivo testing of therapeutics.

Perfluoroalkyl surfactants include chemicals characterized by a fully fluorinated carbon chain (hydrophobic and oleophobic tail) bound to a hydrophilic head (a carboxyl or sulfonic group). These compounds are toxic and highly resistant to chemical/biological attack, and some are known to be bio-accumulative. This study investigates the sonochemical degradation at 500 kHz of different carboxylic and sulfonic perfluoroalkyl and polyfluoroalkyl substances (PFASs, 1.7 mM total organic fluorine) to assess the effect of chain length, functional head group, and substituents (–CH2–CH2– moiety and ether group) on the degradation rate. Under these conditions, the rates of defluorination determined for two widely used perfluoroalkyl substances, perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA), were 3.5 to 3.7 μM F− min−1, respectively. The degradation rate of perfluoroalkyl sulfonates decreased with the perfluorocarbon chain length as indicated by the 1.3 and 1.9-fold lower defluorination rates for perfluorohexane- and perfluorobutane sulfonate than that of PFOS. A similar trend was observed during the sonolysis of perfluoroalkyl carboxylate analogs with 6, 5 or 3 carbon atoms which had 1.1-, 1.8-, and 2.3-fold lower defluorination rates, respectively, than that of PFOA. Furthermore, perfluoroalkyl compounds appeared more amenable to sonolysis than the polyfluoroalkyl analogues with the same number of C atoms (defluorination rate of PFOS/6:2 fluorotelomer sulfonate ≈ 2.3). The results demonstrate that sonolysis is a promising approach to treat PFASs in aqueous streams. Furthermore, they underscore that the chemical structure of PFASs has a marked effect on the rate at which they undergo sonochemical degradation.

Continuous positive airway pressure (CPAP) reduces blood pressure levels in hypertensive patients with obstructive sleep apnoea (OSA). However, the role of CPAP in blood pressure and the metabolic profile in women has not yet been assessed. In this study we investigated the effect of CPAP on blood pressure levels and the glucose and lipid profile in women with moderate-to-severe OSA. A multicentre, open-label, randomised controlled trial was conducted in 307 women diagnosed with moderate-to-severe OSA (apnoea–hypopnoea index ≥15 events·h–1) in 19 Spanish Sleep Units. Women were randomised to CPAP (n=151) or conservative treatment (n=156) for 12 weeks. Changes in office blood pressure measures as well as in the glucose and lipid profile were assessed in both groups. Compared with the control group, the CPAP group achieved a significantly greater decrease in diastolic blood pressure (−2.04 mmHg, 95% CI −4.02– −0.05; p=0.045), and a nonsignificantly greater decrease in systolic blood pressure (−1.54 mmHg, 95% CI −4.58–1.51; p=0.32) and mean blood pressure (−1.90 mmHg, 95% CI −4.0–0.31; p=0.084). CPAP therapy did not change any of the metabolic variables assessed. In women with moderate-to-severe OSA, 12 weeks of CPAP therapy improved blood pressure, especially diastolic blood pressure, but did not change the metabolic profile, compared with conservative treatment., CPAP reduces blood pressure levels, but does not change the metabolic profile in women with sleep apnoea http://ow.ly/sW9h30bgbAy

Background: Continuous positive airway pressure (CPAP) is the treatment of choice for obstructive sleep apnoea (OSA), but compliance and variables involved in CPAP adherence in women are unknown. Objectives: To analyse CPAP adherence and variables associated with CPAP compliance in women with OSA. Methods: We analysed 151 women with moderate-to-severe OSA (AHI≥15) who participated in a randomized controlled trial (NCT02047071) and received CPAP for 3 months. Good adherence was defined as an objective average use ≥ 4 hours/night. To identify independents predictors of adherence, multivariate logistic regression analyses were performed. Results: Nine women were excluded from the analyses because they did not begin CPAP, two women dropped out, and 140 were still on CPAP therapy at the end of the follow-up. The mean CPAP use was 5.09±2.05 hours/night at the end of the first month and 5.24±1.99 hours/night at the end of the follow-up. 73.9% (105/142) of the women had good CPAP adherence at the end of the first month, and 79.6% (113/142) at the end of follow-up. Independent baseline predictors of good adherence were the number of hour of sleep (OR 1.34, 95%CI: 1.01 to 1.76, p=0.038) and the use of antidepressant drugs (OR 0.27, 95%CI: 0.11 to 0.67, p=0.005). In addition, a fewer number of side-effects during the follow-up period was also a predictor of good CPAP adherence (1.8±1.4vs 2.6±1.7, p=0.010). Conclusions: In women with moderate-severe OSA, CPAP adherence at 3 months was adequate. Longer sleep duration predicted better adherence , whereas antidepressant therapy and greater number of side -effects were associated with poorer CPAP adherence.