Dynamics of the nasal microbiota in infancy: A prospective cohort study.

BACKGROUND Understanding the composition and dynamics of the upper respiratory tract microbiota in healthy infants is a prerequisite to investigate the role of the microbiota in patients with respiratory diseases. This is especially true in early life, when the immune system is in development. OBJECTIVE We sought to describe the dynamics of the upper respiratory tract microbiota in healthy infants within the first year of life. METHODS After exclusion of low-quality samples, microbiota characterization was performed by using 16S rDNA pyrosequencing of 872 nasal swabs collected biweekly from 47 unselected infants. RESULTS Bacterial density increased and diversity decreased within the first year of life (R(2) = 0.95 and 0.73, respectively). A distinct profile for the first 3 months of life was found with increased relative abundances of Staphlyococcaceae and Corynebacteriaceae (exponential decay: R(2) = 0.94 and 0.96, respectively). In addition, relative bacterial abundance and composition differed significantly from summer to winter months. The individual composition of the microbiota changed with increasing time intervals between samples and was best modeled by an exponential function (R(2) = 0.97). Within-subject dissimilarity in a 2-week time interval was consistently lower than that between subjects, indicating a personalized microbiota. CONCLUSION This study reveals age and seasonality as major factors driving the composition of the nasal microbiota within the first year of life. A subject's microbiota is personalized but dynamic throughout the first year. These data are indispensable to interpretation of cross-sectional studies and investigation of the role of the microbiota in both healthy subjects and patients with respiratory diseases. They might also serve as a baseline for future intervention studies.

Delay of cortical thinning in very preterm born children

Objective: Cortical gray matter thinning takes place during childhood due to pruning of inefficient synaptic connections and an increase in myelination. Alterations in brain structure occur in very preterm born children with prolonged maturation of the frontal lobes and smaller cortical and white matter volume. These findings give rise to the question if age affects cortical thinning differently in very preterm born children compared to controls. The aim of the present study was to investigate the relationship between age and cortical thickness in very preterm born children when compared to controls. Participants and Methods: Forty-one very preterm born children (<32 weeks gestational age and/or < 1500 gram birth weight) and 30term born controls were included in the study (7-12 years). The automated surface reconstruction software FreeSurfer was applied to obtain measurements of cortical thickness based on T1-weighted MRI images. Results: Cortical thickness was lower in bilateral frontal and left parietal regions and higher in left temporal gyri in very preterm born children compared to controls. However, these differences depended on age. In very preterm born children, age correlated negatively with cortical thickness in right frontal, parietal and inferior temporal regions. Accordingly, cortical thickness was higher in young compared to old very preterm born children in bilateral frontal, parietal and temporal regions. In controls, age was not associated with cortical thickness. Conclusions: In very preterm born children, cortical thinning still occurs between the age of 7 and 12 years, mainly in frontal and parietal areas. In controls, however, a substantial part of cortical thinning appears to be completed in these regions before they reach the age of 7 years. These data indicate a delay in cortical thinning in very preterm born children.

Cortical thickness decreases with age in very preterm born school-children but not in term born controls

Background: Cortical gray matter thinning occurs during childhood due to pruning of inefficient synaptic connections and an increase in myelination. Preterms show alterations in brain structure, with prolonged maturation of the frontal lobes, smaller cortical volumes and reduced white matter volume. These findings give rise to the question if there is a differential influence of age on cortical thinning in preterms compared to controls. Aims: To investigate the relationship between age and cortical thickness in preterms when compared to controls. Study design and outcome measures: The automated surface reconstruction software FreeSurfer was applied to obtain measurements of cortical thickness based on T1-weighted MRI images. Subjects: Forty-one preterms (< 32 weeks gestational age and/or < 1500 gram birth weight) and 30 controls were included in the study (7-12 years). Results: Cortical thickness was lower in bilateral frontal and left parietal regions and higher in left temporal gyri in preterms compared to controls. However, these differences depended on age. In preterms, age correlated negatively with cortical thickness in right frontal, parietal and inferior temporal regions. Accordingly, cortical thickness was higher in young compared to old preterms in bilateral frontal, parietal and temporal regions. In controls, age was not associated with cortical thickness. Conclusion: In preterms, cortical thinning still seems to occur between the age of 7 and 12 years, mainly in frontal and parietal areas whereas in controls, a substantial part of cortical thinning appears to be completed before they reach the age of 7 years. These data indicate slower cortical thinning in preterms than in controls.

Neural change following different memory training approaches in very preterm born children - A pilot study.

OBJECTIVE There is mixed evidence regarding neural change following cognitive training. Brain activation increase, decrease, or a combination of both may occur. We investigated training-induced neural change using two different memory training approaches. METHODS Very preterm born children (aged 7-12 years) were randomly allocated to a memory strategy training, an intensive working memory practice or a waiting control group. Before and immediately after the trainings and the waiting period, brain activation during a visual working memory task was measured using fMRI and cognitive performance was assessed. RESULTS Following both memory trainings, there was a significant decrease of fronto-parietal brain activation and a significant increase of memory performance. In the control group, no neural or performance change occurred after the waiting period. CONCLUSION These pilot data point towards a training-related decrease of brain activation, independent of the training approach. Our data highlight the high training-induced plasticity of the child's brain during development.

Toxicity of eosinophil MBP is repressed by intracellular crystallization and promoted by extracellular aggregation.

Eosinophils are white blood cells that function in innate immunity and participate in the pathogenesis of various inflammatory and neoplastic disorders. Their secretory granules contain four cytotoxic proteins, including the eosinophil major basic protein (MBP-1). How MBP-1 toxicity is controlled within the eosinophil itself and activated upon extracellular release is unknown. Here we show how intragranular MBP-1 nanocrystals restrain toxicity, enabling its safe storage, and characterize them with an X-ray-free electron laser. Following eosinophil activation, MBP-1 toxicity is triggered by granule acidification, followed by extracellular aggregation, which mediates the damage to pathogens and host cells. Larger non-toxic amyloid plaques are also present in tissues of eosinophilic patients in a feedback mechanism that likely limits tissue damage under pathological conditions of MBP-1 oversecretion. Our results suggest that MBP-1 aggregation is important for innate immunity and immunopathology mediated by eosinophils and clarify how its polymorphic self-association pathways regulate toxicity intra- and extracellularly.

Using MDEFT MRI Sequences to Target the GPi in DBS Surgery.

OBJECTIVE Recent advances in different MRI sequences have enabled direct visualization and targeting of the Globus pallidus internus (GPi) for DBS surgery. Modified Driven Equilibrium Fourier Transform (MDEFT) MRI sequences provide high spatial resolution and an excellent contrast of the basal ganglia with low distortion. In this study, we investigate if MDEFT sequences yield accurate and reliable targeting of the GPi and compare direct targeting based on MDEFT sequences with atlas-based targeting. METHODS 13 consecutive patients considered for bilateral GPi-DBS for dystonia or PD were included in this study. Preoperative targeting of the GPi was performed visually based on MDEFT sequences as well as by using standard atlas coordinates. Postoperative CT imaging was performed to calculate the location of the implanted leads as well as the active electrode(s). The coordinates of both visual and atlas based targets were compared. The stereotactic coordinates of the lead and active electrode(s) were calculated and projected on the segmented GPi. RESULTS On MDEFT sequences the GPi was well demarcated in most patients. Compared to atlas-based planning the mean target coordinates were located significantly more posterior. Subgroup analysis showed a significant difference in the lateral coordinate between dystonia (LAT = 19.33 ± 0.90) and PD patients (LAT = 20.67 ± 1.69). Projected on the segmented preoperative GPi the active contacts of the DBS electrode in both dystonia and PD patients were located in the inferior and posterior part of the structure corresponding to the motor part of the GPi. CONCLUSIONS MDEFT MRI sequences provide high spatial resolution and an excellent contrast enabling precise identification and direct visual targeting of the GPi. Compared to atlas-based targeting, it resulted in a significantly different mean location of our target. Furthermore, we observed a significant variability of the target among the PD and dystonia subpopulation suggesting accurate targeting for each individual patient.

Telomerase Is Essential for Zebrafish Heart Regeneration.

After myocardial infarction in humans, lost cardiomyocytes are replaced by an irreversible fibrotic scar. In contrast, zebrafish hearts efficiently regenerate after injury. Complete regeneration of the zebrafish heart is driven by the strong proliferation response of its cardiomyocytes to injury. Here we show that, after cardiac injury in zebrafish, telomerase becomes hyperactivated, and telomeres elongate transiently, preceding a peak of cardiomyocyte proliferation and full organ recovery. Using a telomerase-mutant zebrafish model, we found that telomerase loss drastically decreases cardiomyocyte proliferation and fibrotic tissue regression after cryoinjury and that cardiac function does not recover. The impaired cardiomyocyte proliferation response is accompanied by the absence of cardiomyocytes with long telomeres and an increased proportion of cardiomyocytes showing DNA damage and senescence characteristics. These findings demonstrate the importance of telomerase function in heart regeneration and highlight the potential of telomerase therapy as a means of stimulating cell proliferation upon myocardial infarction.