Frequency of educational computer use as a longitudinal predictor of educational outcomes in young people with specific language impairment

Computer use draws on linguistic abilities. Using this medium thus presents challenges for young people with Specific Language Impairment (SLI) and raises questions of whether computer-based tasks are appropriate for them. We consider theoretical arguments predicting impaired performance and negative outcomes relative to peers without SLI versus the possibility of positive gains. We examine the relationship between frequency of computer use (for leisure and educational purposes) and educational achievement; in particular examination performance at the end of compulsory education and level of educational progress two years later. Participants were 49 young people with SLI and 56 typically developing (TD) young people. At around age 17, the two groups did not differ in frequency of educational computer use or leisure computer use. There were no associations between computer use and educational outcomes in the TD group. In the SLI group, after PIQ was controlled for, educational computer use at around 17 years of age contributed substantially to the prediction of educational progress at 19 years. The findings suggest that educational uses of computers are conducive to educational progress in young people with SLI

Non-Equilibrium Edge Channel Spectroscopy in the Integer Quantum Hall Regime

Heat transport has large potentialities to unveil new physics in mesoscopic systems. A striking illustration is the integer quantum Hall regime, where the robustness of Hall currents limits information accessible from charge transport. Consequently, the gapless edge excitations are incompletely understood. The effective edge states theory describes them as prototypal one-dimensional chiral fermions - a simple picture that explains a large body of observations and calls for quantum information experiments with quantum point contacts in the role of beam splitters. However, it is in ostensible disagreement with the prevailing theoretical framework that predicts, in most situations, additional gapless edge modes. Here, we present a setup which gives access to the energy distribution, and consequently to the energy current, in an edge channel brought out-of-equilibrium. This provides a stringent test of whether the additional states capture part of the injected energy. Our results show it is not the case and thereby demonstrate regarding energy transport, the quantum optics analogy of quantum point contacts and beam splitters. Beyond the quantum Hall regime, this novel spectroscopy technique opens a new window for heat transport and out-of-equilibrium experiments.Comment: 13 pages including supplementary information, Nature Physics in prin

Homozygous microdeletion of exon 5 in ZNF277 in a girl with specific language impairment

Peer reviewedPublisher PD

Multi-level evidence of an allelic hierarchy of USH2A variants in hearing, auditory processing and speech/language outcomes.

Language development builds upon a complex network of interacting subservient systems. It therefore follows that variations in, and subclinical disruptions of, these systems may have secondary effects on emergent language. In this paper, we consider the relationship between genetic variants, hearing, auditory processing and language development. We employ whole genome sequencing in a discovery family to target association and gene x environment interaction analyses in two large population cohorts; the Avon Longitudinal Study of Parents and Children (ALSPAC) and UK10K. These investigations indicate that USH2A variants are associated with altered low-frequency sound perception which, in turn, increases the risk of developmental language disorder. We further show that Ush2a heterozygote mice have low-level hearing impairments, persistent higher-order acoustic processing deficits and altered vocalizations. These findings provide new insights into the complexity of genetic mechanisms serving language development and disorders and the relationships between developmental auditory and neural systems

Th1-Th17 Cells Mediate Protective Adaptive Immunity against Staphylococcus aureus and Candida albicans Infection in Mice

We sought to define protective mechanisms of immunity to Staphylococcus aureus and Candida albicans bloodstream infections in mice immunized with the recombinant N-terminus of Als3p (rAls3p-N) vaccine plus aluminum hydroxide (Al(OH3) adjuvant, or adjuvant controls. Deficiency of IFN-γ but not IL-17A enhanced susceptibility of control mice to both infections. However, vaccine-induced protective immunity against both infections required CD4+ T-cell-derived IFN-γ and IL-17A, and functional phagocytic effectors. Vaccination primed Th1, Th17, and Th1/17 lymphocytes, which produced pro-inflammatory cytokines that enhanced phagocytic killing of both organisms. Vaccinated, infected mice had increased IFN-γ, IL-17, and KC, increased neutrophil influx, and decreased organism burden in tissues. In summary, rAls3p-N vaccination induced a Th1/Th17 response, resulting in recruitment and activation of phagocytes at sites of infection, and more effective clearance of S. aureus and C. albicans from tissues. Thus, vaccine-mediated adaptive immunity can protect against both infections by targeting microbes for destruction by innate effectors

Missing upper incisors: a retrospective study of orthodontic space closure versus implant

Background: The aim of this retrospective study was to compare the esthetic, periodontal, and functional outcomes of orthodontic space closure versus implant substitution in patients with missing maxillary incisors 5 years after completion of treatment. Methods: The study group consisted of ten patients treated with orthodontic space closure (six males, four females, mean age 19 ± 2.1 years at the completion of treatment) and ten patients treated with implant insertion (five males, five females, mean age 20 ± 1.4 years at the time of implant insertion). Tooth mobility, plaque index, probing depth, infraocclusion, open gingival embrasure (black triangle), and temporomandibular joint function were recorded at the 5.6 years follow-up. Self-perceived dental esthetic appearance was also evaluated through a visual analog scale (VAS) questionnaire. T-test was used to evaluate the data. Results: All patients were equally satisfied with the appearance of their teeth 5.6 ± 0.4 years after the completion of treatment. No statistically significant differences were found in relation to the VAS scores of the subjects (P < 0.857). No significant differences were found in tooth mobility, plaque index (P < 0.632), and the prevalence of signs and symptoms of temporomandibular disorders. However, significant infraocclusion was noticed in all implant patients (P < 0.001). Probing depth was also significantly higher in implant patients (P < 0.001). Conclusions: Orthodontic space closure and implant of missing maxillary incisors produced similar, well-accepted esthetic results. None of the treatments impaired temporomandibular joint function. Nevertheless, infraocclusion was evident in implant patients. Space closure patients also showed better periodontal health in comparison with implant patients

Future therapeutic targets in rheumatoid arthritis?

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. Without adequate treatment, patients with RA will develop joint deformity and progressive functional impairment. With the implementation of treat-to-target strategies and availability of biologic therapies, the outcomes for patients with RA have significantly improved. However, the unmet need in the treatment of RA remains high as some patients do not respond sufficiently to the currently available agents, remission is not always achieved and refractory disease is not uncommon. With better understanding of the pathophysiology of RA, new therapeutic approaches are emerging. Apart from more selective Janus kinase inhibition, there is a great interest in the granulocyte macrophage-colony stimulating factor pathway, Bruton's tyrosine kinase pathway, phosphoinositide-3-kinase pathway, neural stimulation and dendritic cell-based therapeutics. In this review, we will discuss the therapeutic potential of these novel approaches

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

Effects of Ferumoxides – Protamine Sulfate Labeling on Immunomodulatory Characteristics of Macrophage-like THP-1 Cells

Superparamagnetic Iron Oxide (SPIO) complexed with cationic transfection agent is used to label various mammalian cells. Labeled cells can then be utilized as an in vivo magnetic resonance imaging (MRI) probes. However, certain number of in vivo administered labeled cells may be cleared from tissues by the host's macrophages. For successful translation to routine clinical application of SPIO labeling method it is important that this mode of in vivo clearance of iron does not elicit any diverse immunological effects. The purpose of this study was to demonstrate that SPIO agent ferumoxides-protamine sulfate (FePro) incorporation into macrophages does not alter immunological properties of these cells with regard to differentiation, chemotaxis, and ability to respond to the activation stimuli and to modulate T cell response. We used THP-1 cell line as a model for studying macrophage cell type. THP-1 cells were magnetically labeled with FePro, differentiated with 100 nM of phorbol ester, 12-Myristate-13-acetate (TPA) and stimulated with 100 ng/ml of LPS. The results showed 1) FePro labeling had no effect on the changes in morphology and expression of cell surface proteins associated with TPA induced differentiation; 2) FePro labeled cells responded to LPS with slightly higher levels of NFκB pathway activation, as shown by immunobloting; TNF-α secretion and cell surface expression levels of CD54 and CD83 activation markers, under these conditions, were still comparable to the levels observed in non-labeled cells; 3) FePro labeling exhibited differential, chemokine dependent, effect on THP-1 chemotaxis with a decrease in cell directional migration to MCP-1; 4) FePro labeling did not affect the ability of THP-1 cells to down-regulate T cell expression of CD4 and CD8 and to induce T cell proliferation. Our study demonstrated that intracellular incorporation of FePro complexes does not alter overall immunological properties of THP-1 cells. The described experiments provide the model for studying the effects of in vivo clearance of iron particles via incorporation into the host's macrophages that may follow after in vivo application of any type of magnetically labeled mammalian cells. To better mimic the complex in vivo scenario, this model may be further exploited by introducing additional cellular and biological, immunologically relevant, components

Characterization of NLRP12 during the Development of Allergic Airway Disease in Mice

Among the 22 members of the nucleotide binding-domain, leucine rich repeat-containing (NLR) family, less than half have been functionally characterized. Of those that have been well studied, most form caspase-1 activating inflammasomes. NLRP12 is a unique NLR that has been shown to attenuate inflammatory pathways in biochemical assays and mediate the lymph node homing of activated skin dendritic cells in contact hypersensitivity responses. Since the mechanism between these two important observations remains elusive, we further evaluated the contribution of NLRP12 to organ specific adaptive immune responses by focusing on the lung, which, like skin, is exposed to both exogenous and endogenous inflammatory agents. In models of allergic airway inflammation induced by either acute ovalbumin (OVA) exposure or chronic house dust mite (HDM) antigen exposure, Nlrp12−/− mice displayed subtle differences in eosinophil and monocyte infiltration into the airways. However, the overall development of allergic airway disease and airway function was not significantly altered by NLRP12 deficiency. Together, the combined data suggest that NLRP12 does not play a vital role in regulating Th2 driven airway inflammation using common model systems that are physiologically relevant to human disease. Thus, the allergic airway inflammation models described here should be appropriate for subsequent studies that seek to decipher the contribution of NLRP12 in mediating the host response to agents associated with asthma exacerbation