Macrophages are essential for HIV-1 pathogenesis and represent major viral reservoirs. Therefore, it is critical to understand macrophage infection, especially in tissue macrophages, which are widely infected in vivo, but poorly permissive to cell-free infection. Although cell-to-cell transmission of HIV-1 is a determinant mode of macrophage infection in vivo, how HIV-1 transfers toward macrophages remains elusive. Here, we demonstrate that fusion of infected CD4+ T lymphocytes with human macrophages leads to their efficient and productive infection. Importantly, several tissue macrophage populations undergo this heterotypic cell fusion, including synovial, placental, lung alveolar, and tonsil macrophages. We also find that this mode of infection is modulated by the macrophage polarization state. This fusion process engages a specific short-lived adhesion structure and is controlled by the CD81 tetraspanin, which activates RhoA/ROCK-dependent actomyosin contractility in macrophages. Our study provides important insights into the mechanisms underlying infection of tissue-resident macrophages, and establishment of persistent cellular reservoirs in patients.

In children, single-sided deafness (SSD) affects the development of linguistic and social skills and can impede educational progress. These difficulties may relate to cortical changes that occur following SSD, such as reduced inter-hemispheric functional asymmetry and maladaptive brain plasticity. To investigate these neuronal changes and their evolution in children, a non-invasive technique is required that is little affected by motion artifacts. Here, we present a research protocol that uses functional near-infrared spectroscopy (fNIRS) to evaluate the reorganization of cortical auditory asymmetry in children with SSD; it also examines how the cortical changes relate to auditory and language skills. The protocol is designed for children whose SSD has not been treated, because hearing restoration can alter both brain reorganization and behavioral performance. We propose a single-center, cross-sectional study that includes 30 children with SSD (congenital or acquired moderate-to-profound deafness) and 30 children with normal hearing (NH), all aged 5–16 years. The children undergo fNIRS during monaural and binaural stimulation, and the pattern of cortical activity is analyzed using measures of the peak amplitude and area under the curve for both oxy- and deoxyhemoglobin. These cortical measures can be compared between the two groups of children, and analyses can be run to determine whether they relate to binaural hearing (speech-in-noise and sound localization), speech perception and production, and quality of life (QoL). The results could be of relevance for developing individualized rehabilitation programs for SSD, which could reduce patients’ difficulties and prevent long-term neurofunctional and clinical consequences.

Swallowing is a complex function that relies on both brainstem and cerebral control. Cerebral neurofunctional evaluations are mostly based on functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), performed with the individual laying down; which is a non-ecological/non-natural position for swallowing. According to the PRISMA guidelines, a review of the non-invasive non-radiating neurofunctional tools, other than fMRI and PET, was conducted to explore the cerebral activity in swallowing during natural food intake, in accordance with the PRISMA guidelines. Using Embase and PubMed, we included human studies focusing on neurofunctional imaging during an ecologic swallowing task. From 5948 unique records, we retained 43 original articles, reporting on three different techniques: electroencephalography (EEG), magnetoencephalography (MEG) and functional near infra-red spectroscopy (fNIRS). During swallowing, all three techniques showed activity of the pericentral cortex. Variations were associated with the modality of the swallowing process (volitional or non-volitional) and the substance used (mostly water and saliva). All techniques have been used in both healthy and pathological conditions to explore the precise time course, localization or network structure of the swallowing cerebral activity, sometimes even more precisely than fMRI. EEG and MEG are the most advanced and mastered techniques but fNIRS is the most ready-to-use and the most therapeutically promising. Ongoing development of these techniques will support and improve our future understanding of the cerebral control of swallowing.

The Deglutition Handicap Index (DHI) is a self-report measure for patients at risk of oropharyngeal dysphagia on deglutition-related aspects of functional health status (FHS) and health-related quality of life (HR-QoL). The DHI consists of 30 items which are subsumed within the Symptom, Functional and Emotional subscales. The purpose of this study was to evaluate the psychometric properties of the DHI using Classic Test Theory according to the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) criteria. A total of 453 patients with dysphagia with different aetiologies were recruited concurrently at two academic hospitals. Dysphagia was confirmed by fiberoptic endoscopic and/or videofluoroscopic evaluation of swallowing. In addition, a healthy control group of 132 participants were recruited. Structural validity was determined using exploratory and confirmatory factor analyses and internal consistency by calculating Cronbach’s alpha coefficients. Hypothesis testing was evaluated using Mann–WhitneyU-tests, linear regression analysis and correlations analysis. Diagnostic performance and receiver operating characteristic curves analysis were calculated. Factor analyses indicated that the DHI is a unidimensional measure. The DHI has good internal consistency with some indication of item redundancy, weak to moderate structural validity and strong hypothesis testing for construct validity. The DHI shows high diagnostic performance as part of criterion validity. These findings support that the DHI is an appropriate choice as a patient self-report measure to evaluate FHS and HR-QoL in dysphagia. Ongoing validation to assess the measure for possible item redundancy and to examine the dimensionality of the DHI using item response theory is recommended.

Aminoglycosides (AGs), such as tobramycin, are essential antibiotics in the management of pulmonary infections in patients with cystic fibrosis (CF). They induce ototoxicity without the relationship being clearly described in the literature. Our aim is to propose a mathematical and statistical model describing the relationship between the estimated cumulative exposure (Area Under the Curve, AUC) to tobramycin and ototoxicity with audiogram interpretation in young patients with CF. Cumulative AUCs were estimated for each course of tobramycin, for the 106 individuals with CF (between 4 and 22 years of age) enrolled in this retrospective study (35 who had received IV tobramycin, 71 controls). Mean hearing loss was calculated for each audiogram and a statistical model was developed to predict hearing loss. The model confirms a significant relationship between cumulative tobramycin exposure and changes in hearing acuity: Meanhearingloss=2.7+(3×10^-5)×AUC_tobramycin+individual_susceptibility However, the ototoxic effect is not clinically perceptible (mean hearing loss: 3.8 dB). The impact of AUC on hearing loss is minor in these subjects who received a limited number of courses of tobramycin (median: 5 courses). A significant relationship between cumulative exposure to tobramycin and ototoxicity was demonstrated. Individual treatment susceptibility should not be overlooked. As ototoxicity is not clinically perceptible in the study subjects, hearing tests should be continued during adulthood to provide individualized medical guidance and to obtain a lifetime analysis of the relationship between exposure and hearing loss.