TLR9 activation induces normal neutrophil responses in a child with IRAK-4 deficiency: involvement of the direct PI3K pathway.

International audiencePolymorphonuclear neutrophils (PMN) play a key role in innate immunity. Their activation and survival are tightly regulated by microbial products via pattern recognition receptors such as TLRs, which mediate recruitment of the IL-1R-associated kinase (IRAK) complex. We describe a new inherited IRAK-4 deficiency in a child with recurrent pyogenic bacterial infections. Analysis of the IRAK4 gene showed compound heterozygosity with two mutations: a missense mutation in the death domain of the protein (pArg12Cys) associated in cis-with a predicted benign variant (pArg391His); and a splice site mutation in intron 7 that led to the skipping of exon 7. A nontruncated IRAK-4 protein was detected by Western blotting. The patient's functional deficiency of IRAK-4 protein was confirmed by the absence of IRAK-1 phosphorylation after stimulation with all TLR agonists tested. The patient's PMNs showed strongly impaired responses (L-selectin and CD11b expression, oxidative burst, cytokine production, cell survival) to TLR agonists which engage TLR1/2, TLR2/6, TLR4, and TLR7/8; in contrast, the patient's PMN responses to CpG-DNA (TLR9) were normal, except for cytokine production. The surprisingly normal effect of CpG-DNA on PMN functions and apoptosis disappeared after pretreatment with PI3K inhibitors. Together, these results suggest the existence of an IRAK-4-independent TLR9-induced transduction pathway leading to PI3K activation. This alternative pathway may play a key role in PMN control of infections by microorganisms other than pyogenic bacteria in inherited IRAK-4 deficiency

Le retour à domicile après amygdalectomie ambulatoire chez l'enfant (évaluation d'une prescription systématique de paracétamol-codéine)

TOURS-BU Médecine (372612103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Petites brèches & méningo-encéphalocèles de l'étage antérieur de la base du crâne (nouvelles stratégies diagnostiques et thérapeutiques)

TOURS-BU Médecine (372612103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Les suppurations périamygdaliennes et péripharyngées chez l'enfant et l'adulte

TOURS-BU Médecine (372612103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Audio 4 : un test vocal simple et rapide pour le dépistage des surdités moyennes des enfants à l’âge de quatre ans

International audienc

Cortical electrophysiological markers of language abilities in children with hearing aids: a pilot study

Objective. To investigate cortical auditory evoked potentials (CAEPs) in pediatric hearing aid (HA) users, with and without language impairment. Design. CAEPs were measured in 11 pediatric HA users (age: 8–12 years) with moderate bilateral sensorineural hearing loss (HL); participants were classified according to language ability. CAEPs were also measured for a control group of 11 age-matched, normal-hearing (NH) children. Results. HL children without language impairment exhibited normal CAEPs. HL children with language impairment exhibited atypical temporal CAEPs, characterized by the absence of N1c; frontocentral responses displayed normal age-related patterns. Conclusion. Results suggest that abnormal temporal brain function may underlie language impairment in pediatric HA users with moderate sensorineural HL

Irreversible Qubit-Photon Coupling for the Detection of Itinerant Microwave Photons

International audienceSingle photon detection is a key resource for sensing at the quantum limit and the enabling technologyfor measurement-based quantum computing. Photon detection at optical frequencies relies on irreversiblephotoassisted ionization of various natural materials. However, microwave photons have energies 5 ordersof magnitude lower than optical photons, and are therefore ineffective at triggering measurable phenomenaat macroscopic scales. Here, we report the observation of a new type of interaction between a single two-level system (qubit) and a microwave resonator. These two quantum systems do not interact coherently;instead, they share a common dissipative mechanism to a cold bath: the qubit irreversibly switches to itsexcited state if and only if a photon enters the resonator. We have used this highly correlated dissipationmechanism to detect itinerant photons impinging on the resonator. This scheme does not require any priorknowledge of the photon waveform nor its arrival time, and dominant decoherence mechanisms do nottrigger spurious detection events (dark counts). We demonstrate a detection efficiency of 58% and a recordlow dark count rate of 1.4 per millisecond. This work establishes engineered nonlinear dissipation as a keyenabling resource for a new class of low-noise nonlinear microwave detectors

Long-Term Cognitive Prognosis of Profoundly Deaf Older Adults After Hearing Rehabilitation Using Cochlear Implants

International audienceObjectives - To analyze long-term cognitive status and function after cochlear implantation in profoundly deaf individuals. Design - Prospective observational longitudinal study. Setting - Ten academic medical centers referent for cochlear implantation. Participants - Individuals aged 65 and older who qualified for cochlear implantation (N=70). Measurements - Cognitive tests were administered before cochlear implantation and 1 and 5 or more years after cochlear implantation. Evaluation consisted of 6 tests assessing attention, memory, orientation, executive function, mental flexibility, and fluency. Cognitive status was determined as normal, mild cognitive impairment (MCI), or dementia. Speech perception in quiet and noisy conditions was assessed using disyllabic words, and quality of life was assessed using the Nijmegen Cochlear Implant Questionnaire. Results - Mean follow-up was 6.8 years (range 5.5-8.5 years). Speech perception scores and quality of life remained stable from 1 to 7 years after cochlear implantation. Of 31 participants (45%) with MCI before cochlear implantation, 2 (6%) developed dementia during follow-up, 19 (61%) remained stable, and 10 (32%) returned to normal cognition. None of the 38 with normal cognition developed dementia during follow-up, although 12 (32%) developed MCI. Conclusion - MCI is highly prevalent in older adults with profound hearing loss. Nevertheless, we observed a low rate of progression to dementia, and cognitive function improved in some individuals with MCI at baseline. These results highlight that cochlear implantation should be strongly considered in profoundly deaf individuals, even those with MCI, who may have a specific subtype of MCI, with a possible positive effect of hearing rehabilitation on neurocognitive functioning