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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.

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 h/night 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/kg2 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 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.

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.

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

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.

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.

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.

Objective: To assess the effect of continuous positive airway pressure (CPAP) on blood pressure (BP), glucose and lipid profile, in women with moderate-to-severe obstructive sleep apnoea (OSA). Methods: We conducted a multicentre, open-label, randomized controlled trial in 307 consecutive women diagnosed with moderate-to-severe OSA (apnoea-hypopnoea index ≥15) in 19 Spanish Sleep Units. Women were randomized to receive effective CPAP (n=151) or conservative treatment (n=156) for 3 months. Systolic (SBP) and diastolic office BP (DBP), fasting glucose, glycated haemoglobin (HbA1c), insulin resistance measured by the homeostasis model assessment (HOMA) and total, LDL and HDL cholesterol were assessed at baseline and at the end of the follow-up. Data were analysed on an intention-to-treat basis, with adjustment for baseline values, body mass index, age, and specific medical treatment. The results are expressed as adjusted intergroup changes (95%CI). Results: Women had a mean (SD) age 57.1 (10.1) years, body mass index 34.3 (7.0) Kg/m2, ESS 9.8 (4.4) and apnoea-hypopnoea index 38.6 (20.8). Compared to the control group, the CPAP group achieved a significantly greater improvement in DBP (mean difference -2.04 mmHg; 95%CI -4.02 to -0.05; p=0.045), and a non-significant improvement in SBP (mean difference -1.54 mmHg, 95%CI -4.58 to 1.51; p=0.32). No differences were shown in fasting glucose, HbA1c, HOMA, and cholesterol measures between groups. Conclusion: In women with moderate-to-severe OSA, 3 months of CPAP therapy improves BP, but not the glucose and lipid profile, compared to conservative treatment.

Continuous positive airway pressure (CPAP) is the treatment of choice in patients with symptomatic obstructive sleep apnea (OSA). CPAP treatment improves quality of life (QoL) in men with OSA, but its role in women has not yet been assessed.To investigate the effect of CPAP on QoL in women with moderate to severe OSA.We conducted a multicenter, open-label randomized controlled trial in 307 consecutive women diagnosed with moderate to severe OSA (apnea-hypopnea index, ≥15) in 19 Spanish sleep units. Women were randomized to receive effective CPAP therapy (n = 151) or conservative treatment (n = 156) for 3 months. The primary endpoint was the change in QoL based on the Quebec Sleep Questionnaire. Secondary endpoints included changes in daytime sleepiness, mood state, anxiety, and depression. Data were analyzed on an intention-to-treat basis with adjustment for baseline values and other relevant clinical variables.The women in the study had a mean (SD) age of 57.1 (10.1) years and a mean (SD) Epworth Sleepiness Scale score of 9.8 (4.4), and 77.5% were postmenopausal. Compared with the control group, the CPAP group achieved a significantly greater improvement in all QoL domains of the Quebec Sleep Questionnaire (adjusted treatment effect between 0.53 and 1.33; P 0.001 for all domains), daytime sleepiness (-2.92; P 0.001), mood state (-4.24; P = 0.012), anxiety (-0.89; P = 0.014), depression (-0.85; P = 0.016), and the physical component summary of the 12-item Short Form Health Survey (2.78; P = 0.003).In women with moderate or severe OSA, 3 months of CPAP therapy improved QoL, mood state, anxiety and depressive symptoms, and daytime sleepiness compared with conservative treatment. Clinical trial registered with www.clinicaltrials.gov (NCT02047071).

Rationale: Continuous positive airway pressure (CPAP) is the treatment of choice in patients with symptomatic obstructive sleep apnea (OSA). CPAP treatment improves quality of life (QoL) in men with OSA, but its role in women has not yet been assessed. Objectives: To investigate the effect of CPAP on QoL in women with moderate to severe OSA. Methods: We conducted a multicenter, open-label randomized controlled trial in 307 consecutive women diagnosed with moderate to severe OSA (apnea-hypopnea index, >= 15) in 19 Spanish sleep units. Women were randomized to receive effective CPAP therapy (n = 151) or conservative treatment (n = 156) for 3 months. The primary endpoint was the change in QoL based on the Quebec Sleep Questionnaire. Secondary endpoints included changes in daytime sleepiness, mood state, anxiety, and depression. Data were analyzed on an intention-to-treat basis with adjustment for baseline values and other relevant clinical variables. Measurements and Main Results: The women in the study had a mean (SD) age of 57.1 (10.1) years and a mean (SD) Epworth Sleepiness Scale score of 9.8 (4.4), and 77.5% were postmenopausal. Compared with the control group, the CPAP group achieved a significantly greater improvement in all QoL domains of the Quebec Sleep Questionnaire (adjusted treatment effect between 0.53 and 1.33; P < 0.001 for all domains), daytime sleepiness (-2.92; P < 0.001), mood state (-4.24; P = 0.012), anxiety (-0.89; P = 0.014), depression ( 0.85; P = 0.016), and the physical component summary of the 12-item Short Form Health Survey (2.78; P = 0.003). Conclusions: In women with moderate or severe OSA, 3 months of CPAP therapy improved QoL, mood state, anxiety and depressive symptoms, and daytime sleepiness compared with conservative treatment.