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During imaginative play, children may learn foundational skills important for academic success. Indeed, imaginative children, high in fantasy orientation (FO), may have advantages in skills that support positive classroom and social behavior. Yet findings are mixed regarding the classroom behavior of children high in fantasy orientation. The purpose of the current study was to examine the cognitive and social skills of children who typically engage in imaginative play in comparison to their peers in classroom contexts across multiple informants: child, teacher, and classroom observers. Ninety preschoolers and their teachers completed measures of fantasy orientation (FO), self-regulation, emotion knowledge, vocabulary, and social competence. Further, observers reported on children's classroom behaviors. Research Findings: Cluster analyses revealed children with higher scores on direct assessments of executive functioning, emotion knowledge, and vocabulary had higher FO. Additionally, children whose teachers reported them as socially competent had higher FO. Finally, children who were rated by classroom observers as high in emotive social play, peer conversation, and physical activity had higher FO. Thus, across multiple informants, children high in FO and imaginative play exhibited higher cognitive and social skills in the classroom. Practice or Policy: These findings suggest that children high in FO may have benefits in skills that are related to positive academic skills in comparison to peers. Curricula should continue to examine the utility of imaginative play as a context to support cognitive and socioemotional development.

Background: Similar immune responses in the nasal and bronchial mucosa implies that nasal allergen challenge (NAC) is a suitable early phase experimental model for drug development targeting allergic rhinitis (AR) and asthma. We assessed NAC reproducibility and the effects of intranasal corticosteroids (INCS) on symptoms, physiology, and inflammatory mediators. Methods: 20 participants with mild atopic asthma and AR underwent three single blinded nasal challenges each separated by three weeks (NCT03431961). Cohort A (n = 10) underwent a control saline challenge, followed by two allergen challenges. Cohort B (n = 10) underwent a NAC with no treatment intervention, followed by NAC with 14 days pre‐treatment with saline nasal spray (placebo), then NAC with 14 days pre‐treatment with INCS (220 μg triamcinolone acetonide twice daily). Nasosorption, nasal lavage, blood samples, forced expiratory volume 1 (FEV1), total nasal symptom score (TNSS), peak nasal inspiratory flow (PNIF) were collected up to 24 h after NAC. Total and active tryptase were measured as early‐phase allergy biomarkers (≤30 min) and IL‐13 and eosinophil cell counts as late‐phase allergy biomarkers (3–7 h) in serum and nasal samples. Period‐period reproducibility was assessed by intraclass correlation coefficients (ICC), and sample size estimates were performed using effect sizes measured after INCS. Results: NAC significantly induced acute increases in nasosorption tryptase and TNSS and reduced PNIF, and induced late increases in nasosorption IL‐13 with sustained reductions in PNIF. Reproducibility across NACs varied for symptoms and biomarkers, with total tryptase 5 min post NAC having the highest reproducibility (ICC = 0.91). Treatment with INCS inhibited NAC‐induced IL‐13 while blunting changes in TNSS and PNIF. For a similar crossover study, 7 participants per treatment arm are needed to detect treatment effects comparable to INCS for TNSS. Conclusion: NAC‐induced biomarkers and symptoms are reproducible and responsive to INCS. NAC is suitable for assessing pharmacodynamic activity and proof of mechanism for drugs targeting allergic inflammation. [ABSTRACT FROM AUTHOR]

Observational studies have identified the potential prognostic value for severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) viral load and anti‐SARS‐CoV‐2 antibodies in coronavirus disease 2019 (COVID‐19). However, viral load in nasopharyngeal (NP) swabs produced inconsistent results in prognostic analyses, and the prognostic value of viral load or antibodies has not been confirmed in large clinical trials. COVACTA and REMDACTA were double‐blind, randomized, controlled trials with a combined enrollment of 1078 patients hospitalized with COVID‐19 treated with tocilizumab or placebo in COVACTA or tocilizumab plus remdesivir or placebo plus remdesivir in REMDACTA. We assessed the potential prognostic value of NP and serum SARS‐CoV‐2 viral load and serum anti‐SARS‐CoV‐2 antibodies at baseline as biomarkers for clinical outcomes in patients enrolled in these trials. In adjusted Cox proportional hazard models, serum viral load was a more reliable predictor of clinical outcomes than NP viral load; high serum viral load was associated with higher risk for death and mechanical ventilation/death and lower likelihood of hospital discharge (high vs. negative viral load hazard ratios [95% confidence interval {CI}] were 2.87 [1.57–5.25], 3.86 [2.23–6.68], and 0.23 [0.14–0.36], respectively, in COVACTA and 8.11 [2.95–22.26], 10.29 [4.5–23.55], and 0.21 [0.15–0.29], respectively, in REMDACTA) and high serum viral load correlated with levels of inflammatory cytokines and lung damage biomarkers. High anti‐SARS‐CoV‐2 spike protein antibody (ACOV2S) levels were associated with higher likelihood of hospital discharge (high vs. below the limit of quantification hazard ratios [95% CI] were 2.55 [1.59–4.08] for COVACTA and 1.54 [1.13–2.09] for REMDACTA). These results support the role of baseline SARS‐CoV‐2 serum viral load and ACOV2S antibody titers in predicting clinical outcomes for patients hospitalized with COVID‐19. [ABSTRACT FROM AUTHOR]

During imaginative play, children may learn foundational skills important for academic success. Indeed, imaginative children, high in fantasy orientation (FO), may have advantages in skills that support positive classroom and social behavior. Yet findings are mixed regarding the classroom behavior of children high in fantasy orientation. The purpose of the current study was to examine the cognitive and social skills of children who typically engage in imaginative play in comparison to their peers in classroom contexts across multiple informants: child, teacher, and classroom observers. Ninety preschoolers and their teachers completed measures of fantasy orientation (FO), self-regulation, emotion knowledge, vocabulary, and social competence. Further, observers reported on children's classroom behaviors. Research Findings: Cluster analyses revealed children with higher scores on direct assessments of executive functioning, emotion knowledge, and vocabulary had higher FO. Additionally, children whose teachers reported them as socially competent had higher FO. Finally, children who were rated by classroom observers as high in emotive social play, peer conversation, and physical activity had higher FO. Thus, across multiple informants, children high in FO and imaginative play exhibited higher cognitive and social skills in the classroom. Practice or Policy: These findings suggest that children high in FO may have benefits in skills that are related to positive academic skills in comparison to peers. Curricula should continue to examine the utility of imaginative play as a context to support cognitive and socioemotional development. [ABSTRACT FROM AUTHOR]

Purpose Our aim was to investigate the prevalence, risk factors, and impact on outcome of nonconvulsive seizures (NCSz), nonconvulsive status epilepticus (NCSE), and periodic epileptiform discharges (PEDs) in surgical intensive care unit (SICU) patients with continuous electroencephalography (cEEG) monitoring. Methods This was a retrospective study of SICU patients who underwent cEEG monitoring for altered mental status over a 6-year period. We report the frequency of NCSz (including NCSE) and PEDs on cEEG. The primary outcome was death or severe disability at hospital discharge. Multivariable logistic regression was used to identify whether NCSz (including NCSE) and PEDs were independently associated with poor outcome (death, vegetative state or severe disability). Results Of 154 patients, the mean age was 64 ± 14 years old, and 40 % were women. The majority of patients were admitted following abdominal surgery (36 %) and liver transplantation (24 %). Sepsis developed in 100 (65 %) patients. Sixteen percent (n = 24) had NCSz [including 5 % (N = 8) with NCSE], and 29 % (N = 45) had PEDs. All eight patients with NCSE were septic. Clinical seizures prior to cEEG and coma were more common among patients who developed NCSz or NCSE compared to patients without NCSz or NCSE (70 vs. 27 %; p < 0.01; 75 vs. 52 %; p = 0.046 and 63 vs. 34 %; p = 0.09, respectively). NCSzs (including NCSE) were independently associated with poor outcome (20 vs. 3 %, OR 10.4, 95 % CI 1.0-53.7; p = 0.039). Conclusion In this retrospective study of SICU patients with cEEG monitoring for altered mental status, NCSz and periodic discharges were frequent and NCSz were independently associated with poor outcome. NCSz were more common when clinical seizures occurred before cEEG., Author(s): Pedro Kurtz [sup.1] [sup.2], Nicolas Gaspard [sup.3], Anna Sophia Wahl [sup.1], Rebecca Marie Bauer [sup.4], Lawrence J. Hirsch [sup.3], Hannah Wunsch [sup.5] [sup.6], Jan Claassen [sup.1] Author Affiliations: (1) [...]

Background: Whether integrase strand transfer inhibitors (INSTIs) can decrease HIV-1 DNA levels more rapidly than boosted PIs during primary HIV-1 infection (PHI) is unknown. We hypothesized that once-daily dolutegravir/tenofovir/emtricitabine could reduce the viral reservoir through rapid viral replication control further than once-daily darunavir/cobicistat/tenofovir/emtricitabine.Methods: The OPTIPRIM2-ANRS 169 study was a randomized (1:1), open-label, multicentre trial in adults with ≤5 or ≤3 HIV antibodies detected, respectively, by western blot or immunoblot in the last 10 days. The primary endpoint was total HIV-1 DNA levels in PBMCs at Week 48 (W48) adjusted for baseline levels. The main secondary endpoint was HIV-1 RNA level decrease.Results: Between April 2017 and August 2018, 101 patients were included from 31 hospitals. Most patients were men (93%), the median age was 36 years and 17% were Fiebig stage ≤3. The median (IQR) plasma HIV-1 RNA and DNA levels were, respectively, 5.8 (5.0-6.6) and 3.87 (3.52-4.15) log10 copies/million PBMCs. The median (IQR) decreases in HIV-1 DNA levels at W48 were -1.48 (-1.74 to -1.06) and -1.39 (-1.55 to -0.98) log10 copies/million PBMCs in the dolutegravir and darunavir/cobicistat groups, respectively (P = 0.52). Plasma HIV-1 RNA levels were <50 copies/mL in 24% versus 0% of patients in the dolutegravir and darunavir/cobicistat groups at W4, 55% versus 2% at W8, 67% versus 17% at W12, and 94% versus 90% at W48, respectively.Conclusions: Dolutegravir-based and darunavir-based regimens initiated during PHI strongly and similarly decreased the blood reservoir size. Considering the rapid viral suppression during a period of high HIV-1 transmission risk, dolutegravir-based regimens are a major first-line option. [ABSTRACT FROM AUTHOR]

Asthma is a complex, heterogeneous disease with a high unmet medical need, despite therapies targeting a multitude of pathways. The ability to quantitatively integrate preclinical and clinical data on these pathways could aid in the development and testing of novel targets and therapeutics. In this work, we develop a computational model of asthma biology, including key cell types and mediators, and create a virtual population capturing clinical heterogeneity. The simulated responses to therapies targeting IL‐13, IL‐4Rα, IL‐5, IgE, and TSLP demonstrate agreement with clinical endpoints and biomarkers of type 2 (T2) inflammation, including blood eosinophils, FEV1, IgE, and FeNO. We use the model to explore the potential benefit of targeting the IL‐33 pathway with anti‐IL‐33 and anti‐ST2. Model predictions are compared with data on blood eosinophils, FeNO, and FEV1 from recent anti‐IL‐33 and anti‐ST2 trials and used to interpret trial results based on pathway biology and pharmacology. Results of sensitivity analyses on the contributions of IL‐33 to the predicted biomarker changes suggest that anti‐ST2 therapy reduces circulating blood eosinophil levels primarily through its impact on eosinophil progenitor maturation and IL‐5‐dependent survival, and induces changes in FeNO and FEV1 through its effect on immune cells involved in T2 cytokine production. Finally, we also investigate the impact of ST2 genetics on the conferred benefit of anti‐ST2. The model includes representation of a wide array of biologic mechanisms and interventions that will provide mechanistic insight and support clinical program design for a wide range of novel therapies during drug development. [ABSTRACT FROM AUTHOR]

Questionnaires on food attitudes and behavior were completed by 2,200 American undergraduates from 6 regionally dispersed college campuses. Results indicate that a substantial minority of women and a much smaller minority of men have major concerns about eating and food with respect to both weight and health. Overall, 14% of women reported being embarrassed to buy a chocolate bar in the store. A 6-factor structure emerged: weight concern, diet and health orientation, beliefs about the diet-health link, food negativity/importance of food as a source of pleasure in life, eating disordered behaviors, and natural/ vegetarian food preferences. There were surprisingly few regional differences, virtually none if race and social class were taken into account. Gender was the strongest predictor of responses.

Background: Dolutegravir is a widespread integrase strand-transfer inhibitor (INSTI) recommended for treatment of primary HIV infection (PHI). PHI is a high-risk stage for sexual transmission because of the high viral load in semen. Yet dolutegravir concentrations in semen are lower than in blood during chronic treatment.Objectives: To compare the kinetics of HIV-RNA and total HIV-DNA in the genital compartment in subjects receiving either tenofovir/emtricitabine/dolutegravir or tenofovir/emtricitabine/darunavir/cobicistat as a first-line combined ART (cART) at the time of PHI.Patients and Methods: Eighteen subjects receiving tenofovir/emtricitabine/dolutegravir and 19 receiving tenofovir/emtricitabine/darunavir/cobicistat enrolled in the ANRS169 OPTIPRIM-2 trial participated in the genital substudy.Results: Between week (W) 0 and W2 HIV-RNA in seminal plasma (SP) decreased by 1 log10 copies/mL. Undetectable SP HIV-RNA was achieved in similar proportions between the two regimens at each timepoint. Overall, eight patients still presented detectable HIV-RNA or HIV-DNA in semen at W48; 15.4% and 28.6% presented detectable HIV-RNA and 9.1% and 14.3% presented detectable HIV-DNA in dolutegravir- and darunavir-based cART groups, respectively, with no significant difference.Conclusions: For the first time, to the best of our knowledge, we showed that a dolutegravir-based regimen initiated as soon as PHI reduces HIV-RNA and HIV-DNA with no difference compared with a control group receiving a darunavir-based regimen. Although the viral purge in semen seems longer after treatment in PHI than CHI, due to high viral loads, early dolutegravir-based treatment initiation permits a major decay of both viral particles and infected cells in semen, efficiently reducing the high risk of transmission during PHI. [ABSTRACT FROM AUTHOR]

Background: Tenofovir diphosphate (TFV-DP) concentration in dried blood spots (DBSs) is a reliable pharmacokinetics biomarker of adherence to tenofovir disoproxil fumarate (TDF). We aimed to use DBSs to estimate pill intake among participants using on-demand pre-exposure prophylaxis (PrEP) and to identify predictive factors associated with higher TFV-DP concentrations.Methods: DBSs were collected at the last study visit of the open-label phase of the ANRS IPERGAY study, assessing on-demand oral TDF/emtricitabine for PrEP among MSM and transgender female participants. We quantified TFV-DP in DBSs centrally. We assessed correlation between pill count and TFV-DP concentration by Spearman correlation and explored associations between participant demographics, sexual behaviour and PrEP use during sexual intercourse (SI) with TFV-DP concentrations by univariate and multivariate logistic regression models.Results: The median age of the 245 participants included in this study was 40 years, with a median body weight of 73 kg. Median (IQR) TFV-DP concentration reached 517 (128-868) fmol/punch, corresponding to an estimated intake of 8-12 tablets per month (2-3 doses per week). Only 39% of participants had a TFV-DP concentration above 700 fmol/punch. TFV-DP concentrations were moderately correlated with pill count (r: 0.59; P < 0.001). In multivariate analysis, only systematic use of PrEP during SI and more frequent episodes of SI in the past 4 weeks were significantly associated with higher TFV-DP levels [OR (95% CI): 11.30 (3.62-35.33) and 1.46 (1.19-1.79), respectively; P < 0.001].Conclusions: Among participants using on-demand PrEP, estimated pill intake reached 8-12 tablets per month and was correlated with frequency and systematic use of PrEP for SI. [ABSTRACT FROM AUTHOR]

GDC‐0334 is a novel small molecule inhibitor of transient receptor potential cation channel member A1 (TRPA1), a promising therapeutic target for many nervous system and respiratory diseases. The pharmacokinetic (PK) profile and pharmacodynamic (PD) effects of GDC‐0334 were evaluated in this first‐in‐human (FIH) study. A starting single dose of 25 mg was selected based on integrated preclinical PK, PD, and toxicology data following oral administration of GDC‐0334 in guinea pigs, rats, dogs, and monkeys. Human PK and PK‐PD of GDC‐0334 were characterized after single and multiple oral dosing using a population modeling approach. The ability of GDC‐0334 to inhibit dermal blood flow (DBF) induced by topical administration of allyl isothiocyanate (AITC) was evaluated as a target‐engagement biomarker. Quantitative models were developed iteratively to refine the parameter estimates of the dose‐concentration‐effect relationships through stepwise estimation and extrapolation. Human PK analyses revealed that bioavailability, absorption rate constant, and lag time increase when GDC‐0334 was administered with food. The inhibitory effect of GDC‐0334 on the AITC‐induced DBF biomarker exhibited a clear sigmoid‐Emax relationship with GDC‐0334 plasma concentrations in humans. This study leveraged emerging preclinical and clinical data to enable iterative refinement of GDC‐0334 mathematical models throughout the FIH study for dose selection in subsequent cohorts throughout the study. Study HighlightsWHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?GDC‐0334 is a novel, small molecule TRPA1 inhibitor and a pharmacokinetic‐pharmacodynamic (PK‐PD) modeling strategy could be implemented in a systematic and step‐wise manner to build and learn from emerging data for early clinical development. WHAT QUESTION DID THIS STUDY ADDRESS?Can noncompartmental and population‐based analyses be used to describe the PK and PD characteristics of GDC‐0334 in preclinical and clinical studies? WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?GDC‐0334 exposure generally increased with dose in rats, dogs, and monkeys. The starting dose (25 mg) in the clinical study was determined based on the preclinical data. GDC‐0334 exhibited linear PK in humans and the bioavailability was increased with food. The inhibitory effect of GDC‐0334 on dermal blood flow induced by the TRPA1 agonist allyl isothiocyanate in humans indicates a clear PK‐PD relationship. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?The models developed based on TRPA1 agonist‐induced dermal blood flow inhibition data can be used to predict PK‐PD relationships in future preclinical and clinical studies evaluating new drug entities that target TRPA1. [ABSTRACT FROM AUTHOR]

Background: Allergic rhinitis is characterized by rhinorrhea, nasal congestion, sneezing and nasal pruritus. Group 2 innate lymphoid cells (ILC2s), CD4+ T cells and eosinophils in nasal mucosa are increased significantly after nasal allergen challenge (NAC). Effects of intranasal corticosteroids (INCS) on ILC2s remain to be investigated. Methods: Subjects (n = 10) with allergic rhinitis and mild asthma were enrolled in a single‐blind, placebo‐controlled, sequential treatment study and treated twice daily with intranasal triamcinolone acetonide (220 µg) or placebo for 14 days, separated by a 7‐day washout period. Following treatment, subjects underwent NAC and upper airway function was assessed. Cells from the nasal mucosa and blood, sampled 24 h post‐NAC, underwent flow cytometric enumeration for ILC2s, CD4+ T and eosinophil progenitor (EoPs) levels. Cell differentials and cytokine levels were assessed in nasal lavage. Results: Treatment with INCS significantly attenuated ILC2s, IL‐5+/IL‐13+ILC2s, HLA‐DR+ILC2s and CD4+ T cells in the nasal mucosa, 24 h post‐NAC. EoP in nasal mucosa was significantly increased, while mature eosinophils were significantly decreased, 24 h post‐NAC in INCS versus placebo treatment arm. Following INCS treatment, IL‐2, IL‐4, IL‐5 and IL‐13 were significantly attenuated 24 h post‐NAC accompanied by significant improvement in upper airway function. Conclusion: Pre‐treatment with INCS attenuates allergen‐induced increases in ILC2s, CD4+ T cells and terminal differentiation of EoPs in the nasal mucosa of allergic rhinitis patients with mild asthma, with little systemic effect. Attenuation of HLA‐DR expression by ILC2s may be an additional mechanism by which steroids modulate adaptive immune responses in the upper airways. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Tryptase, a mast cell protease, has been identified as a potential therapeutic target in managing patients with refractory asthma. We assessed the efficacy, safety, pharmacokinetics, and pharmacodynamics of MTPS9579A, an anti‐tryptase antibody, in a phase 2a randomized trial for patients with uncontrolled asthma and a phase 1c trial to understand activity within the lower respiratory tract.Phase 2a patients (n = 134) received 1800 mg MTPS9579A or placebo intravenously every 4 weeks for 48 weeks. The primary endpoint was time to the first composite exacerbation event. Phase 1c patients (n = 27) received one intravenous dose of 300 or 1800 mg MTPS9579A or placebo. Both trials measured MTPS9579A concentrations and effects on tryptase in serum and nasal lining fluid; phase 1c also analyzed bronchial lining fluid.MTPS9579A did not meet the primary endpoint (hazard ratio = 0.90; 95% CI: 0.55–1.47; p = 0.6835); exacerbation rates in the placebo group were low. Serum and nasal MTPS9579A pharmacokinetics and tryptase levels were consistent with data from healthy volunteers. However, in phase 1c patients, compared to nasal levels, MTPS9579A bronchial concentrations were 6.8‐fold lower, and bronchial active and total tryptase levels were higher (119‐fold and 30‐fold, respectively). Pharmacokinetic/pharmacodynamic modeling predicted intravenous doses of 3800 mg every 4 weeks would be necessary to achieve 95% active tryptase inhibition from baseline.The MTPS9579A dose tested in the phase 2a study was insufficient to inhibit tryptase in bronchial lining fluid, likely contributing to the observed lack of efficacy. [ABSTRACT FROM AUTHOR]

Background: We used the Agence nationale de Recherches sur le sida et les hépatites virales (ANRS)-IPERGAY trial to qualitatively and quantitatively measure drug use among men who have sex with men under preexposure prophylaxis using 2 different methods, to better understand and collectively respond to risky practices. Method: We included 69 volunteers of the ANRS-IPERGAY trial. We measured drug use by 2 methods: (1) drug detection by hair analysis and (2) reported drug use by self-reported drug consumption. Results: New psychoactive substances (NPS) and conventional drugs were detected in 53 of the 69 (77%) volunteers by hair analysis and in 39 of the 69 (57%) volunteers by questionnaires. On the 219 hair segments analyzed, the most commonly used drugs were cocaine in 47 of the 69 (68%), 3,4-methylenedioxymethamphetamine/ecstasy in 31 of the 69 (45%), and NPS in 27 of the 69 (39%). On the 1061 collected questionnaires, the most commonly used drugs were cocaine in 31 of the 69 (45%), 3,4-methylenedioxymethamphetamine/ecstasy in 29 of the 69 (42%), and NPS in 16 of the 69 (23%). Hair analysis detects more conventional drugs and/or NPS use (P < 0.05). Drug use identified by hair was significantly associated with a higher number of sexual partners in the past 2 months (P ≤ 0.001), more often casual partners (P ≤ 0.001), condomless anal sex (P ≤ 0.005), hardcore sexual practices (P ≤ 0.001), a higher number of sexually transmitted infections, and chemsex (P ≤ 0.05). Conclusions: Self-report drug use by questionnaires remains the reference tool for harm reduction at the individual level because of its feasibility and low cost. However, hair analysis is more sensitive, objectively assessing consumption, and interesting to understand uses and to be able to collectively respond to risky practices with adapted messages. [ABSTRACT FROM AUTHOR]

Background and Purpose: Develop a translational assay of Transient Receptor Potential Ankyrin 1 (TRPA1) activity for use as a preclinical and clinical biomarker. Experimental Approach Allyl isothiocyanate (AITC), capsaicin or citric acid were applied to ears of wildtype and Trpa1‐knock out (Trpa1 KO) rats, and changes in dermal blood flow (DBF) were measured by laser speckle contrast imaging. In humans, the DBF, pain and itch responses to 5‐20% AITC applied to the forearm were measured and safety was evaluated. Reproducibility of the DBF, pain and itch responses to topically applied 10% and 15% AITC were assessed at two visits separated by 13‐15 days. DBF changes were summarized at 5‐minute intervals as areas under the curve (AUC) and maxima. Intraclass correlation coefficient (ICC) was calculated to assess arm‐arm and period‐period reproducibility. Key Results: AITC‐ and citric acid‐induced DBF were significantly reduced in Trpa1 KO rats compared to wildtype (90 ± 2% and 65 ± 11% reduction, respectively), whereas capsaicin response did not differ. In humans, each AITC concentration significantly increased DBF compared to vehicle with the maximal increase occurring 5 minutes post application. Ten percent and 15% AITC were selected as safe and effective stimuli. AUC from 0 to 5 minutes was the most reproducible metric of AITC‐induced DBF across arms (ICC = 0.92) and periods (ICC = 0.85). Subject‐reported pain was more reproducible than itch across visits (ICC = 0.76 vs 0.17, respectively). Conclusion and Implications: AITC‐induced DBF is a suitable target engagement biomarker of TRPA1 activity for preclinical and clinical studies of TRPA1 antagonists. [ABSTRACT FROM AUTHOR]

We assessed the coverage of sex acts by event-driven pre-exposure prophylaxis (ED-PrEP) over a 2-month period in 54 participants in the open label phase of the ANRS Ipergay trial. Participants received an electronic monitoring system device to record bottle openings. Self-questionnaires collected daily information on PrEP intake and sexual behavior. Intake was also estimated through returned pill counts. Full coverage of sex acts was defined as at least one pill taken both within 24 h before and within 48 h following sex. There was a strong correlation (r = − 0.92) between the number of bottle openings and returned pill counts. During the study, 42 participants (78%) practiced ED-PrEP and 12 (22%) daily PrEP with bottle openings at least 5 days/week whatever their sexual activity. Out of the 154 reported receptive anal sex acts, 81% were condomless: among them, PrEP coverage was hight: 97% among those practicing daily PrEP and 82% among those using ED-PrEP. [ABSTRACT FROM AUTHOR]

To the editor, Asthma is the most prevalent chronic lung inflammatory disorder characterized by reversible airflow obstruction, affecting 358 million people worldwide,[1] with aggravating factors like obesity, attention-deficit/hyperactivity disorder, socioeconomic status like poor healthcare affordability and facility, smoking and alcohol intake.[2] RNA sequencing (RNA-seq) in atopic asthma,[3] childhood asthma[4] and adult-onset severe asthma[5] has improved our understanding of cellular and molecular pathways involved. The transcriptomic RNA-seq was done on all 16 twin pairs, and the methylomic whole-genome bisulfite sequencing was done on 8 twin pairs (3 concordant asthmatic pairs; 5 concordant nonasthmatic pairs) wherein 6 individuals were asthmatics (GINA score 1 n = 1; 2 n = 1; 3 n = 4). Twin pairs discordant for asthma would be ideal for exploration of genetic vs environmental influence on asthma. [Extracted from the article]