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Abstract: Objectives: In congenitally deaf children fit with a cochlear implant, little is known about the maturation of the auditory cortex. Cortical auditory evoked potentials are a useful methodology to study the auditory cortical system of children with cochlear implants. Nevertheless, these recordings are contaminated by a cochlear implant artifact. The objective of this study was to use independent component analysis to minimize the artifact of the cochlear implant to study cortical auditory evoked potentials. Study design: Prospective study. Method: A total of 5 children ranging in age from 21 to 49 months who were fitted with a cochlear implant for at least 6 months were included in this study. The stimuli were pure tones (750Hz, 200ms duration, 70dB SPL) presented with an irregular interstimulus interval (1000–2000ms) via loud speakers. The cortical auditory evoked potentials were recorded from 17 Ag–AgCl electrodes referenced to the nose. The peak latency and amplitude of each deflection culminating at the fronto-central and temporal sites were analyzed. Main outcome measures: The P100–N250 peak latencies and amplitudes of the cortical auditory evoked potentials recorded from children fitted with cochlear implants. Scalp map potentials distributions were done for each child for the N250 wave. Results: The use of independent component analysis permitted to minimize the cochlear implant artifact for the five children. Cortical auditory evoked potentials were recorded at fronto-central and temporal sites. Scalp map potentials distributions for the N2 wave showed activation of temporal generators contralateral at the CI for the five children. Conclusion: This preliminary electrophysiological study confirms the value and the limits of independent component analysis. It could allow longitudinal studies in cochlear implant users to examine the maturation of auditory cortex. It could also be used to identify objective cortical electrophysiological measures to help the fitting of CIs in children. [Copyright &y& Elsevier]

Abstract: The ability to combine evidence streams to establish disease freedom or prioritize surveillance is important for the evaluation of emerging diseases, such as viral hemorrhagic septicemia virus (VHSV) IVb in freshwater systems of the United States and Canada. Waterways provide a relatively unconstrained pathway for the spread of VHSV; and structured surveillance for emerging disease in open systems has many challenges. We introduce a decision framework for estimating VHSV infection probability that draws from multiple evidence streams and addresses challenges associated with the assessment of emerging disease. Using this approach, historical and risk-based evidence, whether empirical or expert-derived, supplement surveillance data to estimate disease probability. Surveillance-based estimates of VHSV prevalence were described using beta distributions. Subjective likelihood ratios (LRs), representing contextual risk, were elicited by asking experts to estimate the predicted occurrence of risk factors among VHSV-affected vs. VHSV-unaffected watersheds. We used the odds form of Bayes’ theorem to aggregate expert and surveillance evidence to predict the risk-adjusted posterior probability of VHSV-infection for given watersheds. We also used LRs representing contextual risk to quantify the time value of past surveillance data. This evidence aggregation model predicts disease probability from the combined assessment of multiple sources of information. The method also provides a flexible framework for iterative revision of disease freedom status as knowledge and data evolve. [Copyright &y& Elsevier]

Abstract: Objective: The aim of this study was to investigate in healthy adults the electrophysiological correlates of auditory–visual interactions involved in perception of bimodal events in a no-task paradigm. Methods: Event-related potentials were recorded in response to unimodal auditory (A), unimodal visual (V) and bimodal (AV) stimuli. Cross-modal interactions were estimated using the additive [AV−(A+V)] model. Results: The spatio-temporal analysis of ERPs and scalp current densities revealed several interaction patterns occurring at both early and late stages of sensory cortical processing: (1) amplitude decrease of the unimodal auditory N1 wave as early as 55ms, (2) amplitude increase of the unimodal auditory P2 wave from 150 to 195ms concomitant with new neural activity over the right fronto-temporal region, and (3) amplitude increase of the late unimodal visual response within 245–350ms post-stimulus. Conclusions: Our study provides evidence that several patterns of cross-modal interactions can be generated even if no task is required from subjects. Significance: The paradigm used here can thus be utilized for studying the maturation of the cross-modal processes in young children and in children with pathological development. [Copyright &y& Elsevier]

This study investigated the diet-additive interactions of a Lactobacilli-based probiotic (Pro) and postbiotic (Post) on immune parameters and cecal microbiota composition, with subsequent effects on the metabolome in broilers. A completely randomized block design was employed with 2 diets [standard (SD), and challenge (CD)] and 3 additive conditions (Control, Pro, Post) involving 1,368 one-day-old male Ross 308 broilers equally distributed among 36 pens in a 42 d study. Diets were formulated to contain identical nutrient levels, with CD higher than SD in non-starch polysaccharide content by including rye and barley. Total non-specific serum Ig A, M and G concentrations were determined weekly from d14 to 35. Following vaccination, titres of specific antibodies binding Newcastle disease virus (NDV) and infectious bursal disease virus (IBDV) were measured. Microbiota composition was analyzed by 16S rRNA gene sequencing at d14 and 35, and α- and β-diversity indexes (Observed, Chao1, Bray, Jaccard) were calculated. Cecal short-chain fatty acids and the semi-polar metabolome were determined in the Control SD and all CD groups at d35. At d35, a diet-additive interaction was observed on cecal microbiota composition. Within SD, Pro and Post did not affect operational taxonomic units (OTU) abundance (adjusted-P > 0.05) and diversity indexes (P > 0.05). Within CD, Pro and Post affected the relative abundances of 37 and 44 OTUs, respectively (adjusted-P < 0.05), with Post but not Pro affecting β-diversity indexes (P = 0.041 and 0.064 for Bray and Jaccard, respectively). Within CD, Post increased cecal acetate (21%; P = 0.007) and butyrate (41%; P = 0.002) concentration and affected the concentration of 2 metabolites (adjusted-P < 0.05), while Pro affected 240 metabolites (adjusted-P < 0.05). No diet-additive interactions were observed on serum Ig (P > 0.05), except for IgM at d14 (P = 0.004). Diet composition, but not the additives, affected immune status parameters. The Pro and Post affected cecal microbiota composition only under dietary challenging conditions as previously reported for growth., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

SARS-CoV-2 is the causative virus of COVID-19, which has been responsible for millions of deaths worldwide since its discovery. After its emergence, several variants have been identified that challenge the efficacy of the available vaccines. Previously, we generated and evaluated a vaccine based on a recombinant Bacillus Calmette-Guérin (rBCG) expressing the nucleoprotein (N) of SARS-CoV-2 (rBCG-N-SARS-CoV-2). This protein is a highly immunogenic antigen and well conserved among variants. Here, we tested the administration of this vaccine with recombinant N and viral Spike proteins (S), or Receptor Binding Domain (RBD-Omicron variant), plus a booster with the recombinant proteins only, as a novel and effective strategy to protect against SARS-CoV-2 variants., Methods: BALB/c mice were immunized with rBCG-N-SARS-CoV-2 and recombinant SARS-CoV-2 proteins in Alum adjuvant, followed by a booster with recombinant proteins to assess the safety and virus-specific cellular and humoral immune responses against SARS-CoV-2 antigens., Results: Immunization with rBCG-N-SARS-CoV-2 + recombinant proteins as a vaccine was safe and promoted the activation of CD4 + and CD8 + T cells that recognize SARS-CoV-2 N, S, and RBD antigens. These cells were able to secrete cytokines with an antiviral profile. This immunization strategy also induced robust titers of specific antibodies against N, S, and RBD and neutralizing antibodies of SARS-CoV-2., Conclusions: Co-administration of the rBCG-N-SARS-CoV-2 vaccine with recombinant SARS-CoV-2 proteins could be an effective alternative to control particular SARS-CoV-2 variants. Due to its safety and capacity to induce virus-specific immune responses, we believe the rBCG-N-SARS-CoV-2 + Proteins vaccine could be an attractive candidate to protect against this virus, especially in newborns., Competing Interests: Declaration of competing interest Patents for BCG-SARS-CoV-2. The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alexis Kalergis Parra has patent pending to PCT / CL2021 / 050123. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Vaccination is one of the most effective strategies for preventing infectious diseases but individual vaccine responses are highly heterogeneous. Host genetics and gut microbiota composition are 2 likely drivers of this heterogeneity. We studied 94 animals belonging to 4 lines of laying hens: a White Leghorn experimental line genetically selected for a high antibody response against the Newcastle Disease Virus (NDV) vaccine (ND3) and its unselected control line (CTR), and 2 commercial lines (White Leghorn [LEG] and Rhode Island Red [RIR]). Animals were reared in the same conditions from hatching to 42 d of age, and animals from different genetic lines were mixed. Animals were vaccinated at 22 d of age and their humoral vaccine response against NDV was assessed by hemagglutination inhibition assay and ELISA from blood samples collected at 15, 19, and 21 d after vaccination. The immune parameters studied were the 3 immunoglobulins subtypes A, M, and Y and the blood cell composition was assessed by flow cytometry. The composition of the cecal microbiota was assessed at the end of the experiment by analyzing amplified 16S rRNA gene sequences to obtain amplicon sequence variants (ASV). The 4 lines showed significantly different levels of NDV vaccine response at the 3 measured points, with, logically, a higher response of the genetically selected ND3 line, and intermediate and low responses for the unselected CTR control line and for the 2 commercial lines, respectively. The ND3 line displayed also a higher proportion of immunoglobulins (IgA, IgM, and IgY). The RIR line showed the most different blood cell composition. The 4 lines showed significantly different microbiota characteristics: composition, abundances at all taxonomic levels, and correlations between genera and vaccine response. The tested genetic lines differ for immune parameters and gut microbiota composition and functions. These phenotypic differences can be attributed to genetic differences between lines. Causal relationships between both types of parameters are discussed and will be investigated in further studies., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The gut microbiota is known to play an important role in energy harvest and is likely to affect feed efficiency. In this study, we used 16S metabarcoding sequencing to analyse the caecal microbiota of laying hens from feed-efficient and non-efficient lines obtained by divergent selection for residual feed intake. The two lines were fed either a commercial wheat-soybean based diet (CTR) or a low-energy, high-fibre corn-sunflower diet (LE). The analysis revealed a significant line x diet interaction, highlighting distinct differences in microbial community composition between the two lines when hens were fed the CTR diet, and more muted differences when hens were fed the LE diet. Our results are consistent with the hypothesis that a richer and more diverse microbiota may play a role in enhancing feed efficiency, albeit in a diet-dependent manner. The taxonomic differences observed in the microbial composition seem to correlate with alterations in starch and fibre digestion as well as in the production of short-chain fatty acids. As a result, we hypothesise that efficient hens are able to optimise nutrient absorption through the activity of fibrolytic bacteria such as Alistipes or Anaerosporobacter, which, via their production of propionate, influence various aspects of host metabolism., (© 2024. The Author(s).)

The understanding of the host immune response to SARS-CoV-2 variants of concern is critical for improving diagnostics, therapy development, and vaccines. Here, we analyzed the level of neutralizing antibodies against SARS-CoV-2 D614G, Delta, Gamma, Mu, and Omicron variants in D614G infected healthcare workers during a follow-up up to 6 months after recovery. We followed up 76 patients: 60.5% were women and 39.5% men. The 96.1% and 3.9% were symptomatic and asymptomatic, respectively. The most frequent symptoms were headache, myalgia, and cough. The 65.8%, 65.8%, and 92.1% of the infected individuals were positive for neutralizing antibodies against D614G variant at 2, 4, and 6 months of follow-up, respectively. The 26.3%, 48.7% and 65.8% of patients neutralized Delta variant, 19.7%, 32.9% and 52.6% of patients neutralized Gamma, 7.9%, 19.7% and 44.7% of patients neutralized Mu, and 4.0%, 9.2% and 15.8% of patients neutralized Omicron. Low neutralization against Gamma and Mu variants was observed during the follow-up, and very low against the Omicron variant was detected during the same period. The median of neutralizing antibody titers against D614G and Delta variants increased significantly during the follow-up. An association was observed between the levels of neutralizing antibodies against D614G and Delta variants and the severity of the disease. Our results suggest an immune escape from neutralizing antibodies with the Omicron variant because of the many mutations localized in the S protein., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Importance: It is uncertain whether a rapid-onset opioid is noninferior to a rapid-onset neuromuscular blocker during rapid sequence intubation when used in conjunction with a hypnotic agent., Objective: To determine whether remifentanil is noninferior to rapid-onset neuromuscular blockers for rapid sequence intubation., Design, Setting, and Participants: Multicenter, randomized, open-label, noninferiority trial among 1150 adults at risk of aspiration (fasting for <6 hours, bowel occlusion, recent trauma, or severe gastroesophageal reflux) who underwent tracheal intubation in the operating room at 15 hospitals in France from October 2019 to April 2021. Follow-up was completed on May 15, 2021., Interventions: Patients were randomized to receive neuromuscular blockers (1 mg/kg of succinylcholine or rocuronium; n = 575) or remifentanil (3 to 4 μg/kg; n = 575) immediately after injection of a hypnotic., Main Outcomes and Measures: The primary outcome was assessed in all randomized patients (as-randomized population) and in all eligible patients who received assigned treatment (per-protocol population). The primary outcome was successful tracheal intubation on the first attempt without major complications, defined as lung aspiration of digestive content, oxygen desaturation, major hemodynamic instability, sustained arrhythmia, cardiac arrest, and severe anaphylactic reaction. The prespecified noninferiority margin was 7.0%., Results: Among 1150 randomized patients (mean age, 50.7 [SD, 17.4] years; 573 [50%] women), 1130 (98.3%) completed the trial. In the as-randomized population, tracheal intubation on the first attempt without major complications occurred in 374 of 575 patients (66.1%) in the remifentanil group and 408 of 575 (71.6%) in the neuromuscular blocker group (between-group difference adjusted for randomization strata and center, -6.1%; 95% CI, -11.6% to -0.5%; P = .37 for noninferiority), demonstrating inferiority. In the per-protocol population, 374 of 565 patients (66.2%) in the remifentanil group and 403 of 565 (71.3%) in the neuromuscular blocker group had successful intubation without major complications (adjusted difference, -5.7%; 2-sided 95% CI, -11.3% to -0.1%; P = .32 for noninferiority). An adverse event of hemodynamic instability was recorded in 19 of 575 patients (3.3%) with remifentanil and 3 of 575 (0.5%) with neuromuscular blockers (adjusted difference, 2.8%; 95% CI, 1.2%-4.4%)., Conclusions and Relevance: Among adults at risk of aspiration during rapid sequence intubation in the operating room, remifentanil, compared with neuromuscular blockers, did not meet the criterion for noninferiority with regard to successful intubation on first attempt without major complications. Although remifentanil was statistically inferior to neuromuscular blockers, the wide confidence interval around the effect estimate remains compatible with noninferiority and limits conclusions about the clinical relevance of the difference., Trial Registration: ClinicalTrials.gov Identifier: NCT03960801.