skin infection is a frequent and recurrent problem in children with the common inflammatory skin disease atopic dermatitis (AD).
colonizes the skin of the majority of children with AD and exacerbates ...the disease. The first step during colonization and infection is bacterial adhesion to the cornified envelope of corneocytes in the outer layer, the stratum corneum. Corneocytes from AD skin are structurally different from corneocytes from normal healthy skin. The objective of this study was to identify bacterial proteins that promote the adherence of
to AD corneocytes.
strains from clonal complexes 1 and 8 were more frequently isolated from infected AD skin than from the nasal cavity of healthy children. AD strains had increased ClfB ligand binding activity compared to normal nasal carriage strains. Adherence of single
bacteria to corneocytes from AD patients
was studied using atomic force microscopy. Bacteria expressing ClfB recognized ligands distributed over the entire corneocyte surface. The ability of an isogenic ClfB-deficient mutant to adhere to AD corneocytes compared to that of its parent clonal complex 1 clinical strain was greatly reduced. ClfB from clonal complex 1 strains had a slightly higher binding affinity for its ligand than ClfB from strains from other clonal complexes. Our results provide new insights into the first step in the establishment of
colonization in AD patients. ClfB is a key adhesion molecule for the interaction of
with AD corneocytes and represents a target for intervention.
For genetic research to contribute more fully to furthering our knowledge of neuropathic pain, we require an agreed, valid, and feasible approach to phenotyping, to allow collaboration and ...replication in samples of sufficient size. Results from genetic studies on neuropathic pain have been inconsistent and have met with replication difficulties, in part because of differences in phenotypes used for case ascertainment. Because there is no consensus on the nature of these phenotypes, nor on the methods of collecting them, this study aimed to provide guidelines on collecting and reporting phenotypes in cases and controls for genetic studies. Consensus was achieved through a staged approach: (1) systematic literature review to identify all neuropathic pain phenotypes used in previous genetic studies; (2) Delphi survey to identify the most useful neuropathic pain phenotypes and their validity and feasibility; and (3) meeting of experts to reach consensus on the optimal phenotype(s) to be collected from patients with neuropathic pain for genetic studies. A basic "entry level" set of phenotypes was identified for any genetic study of neuropathic pain. This set identifies cases of "possible" neuropathic pain, and controls, and includes: (1) a validated symptom-based questionnaire to determine whether any pain is likely to be neuropathic; (2) body chart or checklist to identify whether the area of pain distribution is neuroanatomically logical; and (3) details of pain history (intensity, duration, any formal diagnosis). This NeuroPPIC "entry level" set of phenotypes can be expanded by more extensive and specific measures, as determined by scientific requirements and resource availability.
Mass spectrometric methods have long been suggested as ways of measuring $^{14}$C/$^{12}$C ratios for carbon dating. One problem has been to distinguish between $^{14}$N and $^{14}$C. With negative ...ions and a tandem electrostatic accelerator, the $^{14}$N background is virtually absent and fewer than three $^{14}$C atoms in 10$^{16}$ atoms of $^{12}$ C have been easily measured.
Neuroepithelial attachments at adherens junctions are essential for the self-renewal of neural stem and progenitor cells and the polarized organization of the developing central nervous system. The ...balance between stem cell maintenance and differentiation depends on the precise assembly and disassembly of these adhesive contacts, but the gene regulatory mechanisms orchestrating this process are not known. Here, we demonstrate that two Forkhead transcription factors, Foxp2 and Foxp4, are progressively expressed upon neural differentiation in the spinal cord. Elevated expression of either Foxp represses the expression of a key component of adherens junctions, N-cadherin, and promotes the detachment of differentiating neurons from the neuroepithelium. Conversely, inactivation of Foxp2 and Foxp4 function in both chick and mouse results in a spectrum of neural tube defects associated with neuroepithelial disorganization and enhanced progenitor maintenance. Together, these data reveal a Foxp-based transcriptional mechanism that regulates the integrity and cytoarchitecture of neuroepithelial progenitors.
► Foxp2 and Foxp4 are highly expressed during spinal cord and cortical neurogenesis ► Foxp4 acts downstream of proneural genes to promote neuroepithelial detachment ► Foxp4 opposes Sox2 in regulating N-cadherin expression and progenitor maintenance ► Foxp4 mutant mice display a range of defects in spinal cord and cortical development
Neural stem and progenitor cells are held in a proliferative, neuroepithelial state by cadherin-based adhesions. Rousso et al. identify a crucial role for the Forkhead transcription factors Foxp2 and Foxp4 in repressing N-cadherin expression and disassembling these adhesions during neurogenesis.
Options for mechanical circulatory support as a bridge to heart transplantation in children with severe heart failure are limited.
We conducted a prospective, single-group trial of a ventricular ...assist device designed specifically for children as a bridge to heart transplantation. Patients 16 years of age or younger were divided into two cohorts according to body-surface area (cohort 1, <0.7 m(2); cohort 2, 0.7 to <1.5 m(2)), with 24 patients in each group. Survival in the two cohorts receiving mechanical support (with data censored at the time of transplantation or weaning from the device owing to recovery) was compared with survival in two propensity-score-matched historical control groups (one for each cohort) undergoing extracorporeal membrane oxygenation (ECMO).
For participants in cohort 1, the median survival time had not been reached at 174 days, whereas in the matched ECMO group, the median survival was 13 days (P<0.001 by the log-rank test). For participants in cohort 2 and the matched ECMO group, the median survival was 144 days and 10 days, respectively (P<0.001 by the log-rank test). Serious adverse events in cohort 1 and cohort 2 included major bleeding (in 42% and 50% of patients, respectively), infection (in 63% and 50%), and stroke (in 29% and 29%).
Our trial showed that survival rates were significantly higher with the ventricular assist device than with ECMO. Serious adverse events, including infection, stroke, and bleeding, occurred in a majority of study participants. (Funded by Berlin Heart and the Food and Drug Administration Office of Orphan Product Development; ClinicalTrials.gov number, NCT00583661.).
Detailed whole brain segmentation is an essential quantitative technique in medical image analysis, which provides a non-invasive way of measuring brain regions from a clinical acquired structural ...magnetic resonance imaging (MRI). Recently, deep convolution neural network (CNN) has been applied to whole brain segmentation. However, restricted by current GPU memory, 2D based methods, downsampling based 3D CNN methods, and patch-based high-resolution 3D CNN methods have been the de facto standard solutions. 3D patch-based high resolution methods typically yield superior performance among CNN approaches on detailed whole brain segmentation (>100 labels), however, whose performance are still commonly inferior compared with state-of-the-art multi-atlas segmentation methods (MAS) due to the following challenges: (1) a single network is typically used to learn both spatial and contextual information for the patches, (2) limited manually traced whole brain volumes are available (typically less than 50) for training a network. In this work, we propose the spatially localized atlas network tiles (SLANT) method to distribute multiple independent 3D fully convolutional networks (FCN) for high-resolution whole brain segmentation. To address the first challenge, multiple spatially distributed networks were used in the SLANT method, in which each network learned contextual information for a fixed spatial location. To address the second challenge, auxiliary labels on 5111 initially unlabeled scans were created by multi-atlas segmentation for training. Since the method integrated multiple traditional medical image processing methods with deep learning, we developed a containerized pipeline to deploy the end-to-end solution. From the results, the proposed method achieved superior performance compared with multi-atlas segmentation methods, while reducing the computational time from >30 h to 15 min. The method has been made available in open source (https://github.com/MASILab/SLANTbrainSeg).
Display omitted
•SLANT method distributes multiple independent 3D deep networks.•SLANT was proposed for high-resolution whole brain segmentation.•Better than multi-atlas segmentation, while reducing time to 15 minutes.•Auxiliary labels on 5111 initially unlabeled scans were used for training.•The method has been made in Docker and available in open source.
Background
Definitions and diagnostic criteria for all medical conditions are regularly subjected to reviews and revisions as knowledge advances. In the field of Alzheimer's disease (AD) research, it ...has taken almost three decades for diagnostic nomenclature to undergo major re‐examination. The shift towards presymptomatic and pre‐dementia stages of AD has brought prevention and treatment trials much closer to each other than before.
Methods
Here we discuss: (i) the impact of diagnostic reliability on the possibilities for developing preventive strategies for AD; (ii) the scientific evidence to support moving from observation to action; (iii) ongoing intervention studies; and (iv) the methodological issues and prospects for balancing strategies for high‐risk individuals with those for broad population‐based prevention.
Results
The associations between neuropathology and cognition are still not entirely clear. In addition, the risk factors for AD dementia and the neuropathological hallmarks of AD may not necessarily be the same. Cognitive impairment has a clearer clinical significance and should therefore remain the main focus of prevention. Risk/protective factors for dementia/AD need to be studied from a life‐course perspective. New approaches in prevention trials include enrichment strategies based on genetic risk factors or beta‐amyloid biomarkers (at least four ongoing pharmacological trials), and multidomain interventions simultaneously targeting various vascular and lifestyle‐related risk factors (at least three ongoing trials). Experience from prevention programmes in other chronic diseases can provide additional methodological improvements.
Conclusions
Building infrastructures for international collaborations is necessary for managing the worldwide public health problem of AD and dementia. The International Database on Aging and Dementia (IDAD) and the European Dementia Prevention Initiative (EDPI) are examples of ongoing international efforts aiming to improve the methodology of preventive studies and provide the basis for larger intervention trials.
Direct selection for litter size was compared with selection for ovulation rate, ova success, or uterine capacity and for indexes of ovulation rate with ova success or uterine capacity. Selection was ...simulated for 10 generations in a mouse population based on a model integrating ovulation rate, potential embryonic viability, and uterine capacity. Two indexes including ovulation rate (OR) and ova success (OS) were I =.291 X OR +2.19 X OS and I =.165 X OR +.736 X OS. Heritabilities for ovulation rate and ova success, assumed in the simulation and to derive the indexes, were 0.25 and 0.06, respectively. Both indexes resulted in the same response in litter size, 12.9% greater than response to direct selection for litter size. Two indexes including OR and uterine capacity (TUC = true total uterine capacity; UC uterine capacity measured as number born for a female with right ovary excised) were I =.881 X OR +.223 X TUC and I =.876 X OR +.568 X UC. Heritabilities assumed for uterine capacity were 0.9 (TUC) and 0.065 (UC). The first index assumed true parameters for uterine capacity (TUC) and resulted in a response in litter size that was 23.9% greater than direct selection. The second index was calculated using parameters estimated under a unilateral ovariectomy model and resulted in response that was 14.7% greater than direct selection. Selection for OR, TUC, UC, or OS resulted in responses that were 4.5, 48.5, 38.7, or 74.8%, respectively, less than that from direct selection for litter size
PDF
