A Tool for Differential Diagnosis of Childhood Apraxia of Speech and Dysarthria in Children: A Tutorial

Purpose: While there has been mounting research centered on the diagnosis of childhood apraxia of speech (CAS), little has focused on differentiating CAS from pediatric dysarthria. Because CAS and dysarthria share overlapping speech symptoms and some children have both motor speech disorders, differential diagnosis can be challenging. There is a need for clinical tools that facilitate assessment of both CAS and dysarthria symptoms in children. The goals of this tutorial are to (a) determine confidence levels of clinicians in differentially diagnosing dysarthria and CAS and (b) provide a systematic procedure for differentiating CAS and pediatric dysarthria in children. Method: Evidence related to differential diagnosis of CAS and dysarthria is reviewed. Next, a web-based survey of 359 pediatric speech-language pathologists is used to determine clinical confidence levels in diagnosing CAS and dysarthria. Finally, a checklist of pediatric auditory–perceptual motor speech features is presented along with a procedure to identify CAS and dysarthria in children with suspected motor speech impairments. Case studies illustrate application of this protocol, and treatment implications for complex cases are discussed. Results: The majority (60%) of clinician respondents reported low or no confidence in diagnosing dysarthria in children, and 40% reported they tend not to make this diagnosis as a result. Going forward, clinicians can use the feature checklist and protocol in this tutorial to support the differential diagnosis of CAS and dysarthria in clinical practice. Conclusions: Incorporating this diagnostic protocol into clinical practice should help increase confidence and accuracy in diagnosing motor speech disorders in children. Future research should test the sensitivity and specificity of this protocol in a large sample of children with varying speech sound disorders. Graduate programs and continuing education trainings should provide opportunities to practice rating speech features for children with dysarthria and CAS

Dynamic changes in synaptic plasticity genes in ipsilateral and contralateral inferior colliculus following unilateral noise-induced hearing loss

Unilateral noise-induced hearing loss reduces the input to the central auditory pathway disrupting the excitatory and inhibitory inputs to the inferior colliculus (IC), an important binaural processing center. Little is known about the compensatory synaptic changes that occur in the IC as a consequence of unilateral noise-induced hearing loss. To address this issue, Sprague–Dawley rats underwent unilateral noise exposure resulting in severe unilateral hearing loss. IC tissues from the contralateral and ipsilateral IC were evaluated for acute (2-d) and chronic (28-d) changes in the expression of 84 synaptic plasticity genes on a PCR array. Arc and Egr1 genes were further visualized by in situ hybridization to validate the PCR results. None of the genes were upregulated, but many were downregulated post-exposure. At 2-d post-exposure, more than 75% of the genes were significantly downregulated in the contralateral IC, while only two were downregulated in the ipsilateral IC. Many of the downregulated genes were related to long-term depression, long-term potentiation, cell adhesion, immediate early genes, neural receptors and postsynaptic density. At 28-d post-exposure, the gene expression pattern was reversed with more than 85% of genes in the ipsilateral IC now downregulated. Most genes previously downregulated in the contralateral IC 2-d post-exposure had recovered; less than 15% remained downregulated. These time-dependent, asymmetric changes in synaptic plasticity gene expression could shed new light on the perceptual deficits associated with unilateral hearing loss and the dynamic structural and functional changes that occur in the IC days and months following unilateral noise-induced hearing loss

Immunoreactivity of Pluripotent Markers SSEA-5 and L1CAM in Human Tumors, Teratomas, and Induced Pluripotent Stem Cells

Pluripotent stem cell markers can be useful for diagnostic evaluation of human tumors. The novel pluripotent marker stage-specific embryonic antigen-5 (SSEA-5) is expressed in undifferentiated human induced pluripotent cells (iPSCs), but little is known about SSEA-5 expression in other primitive tissues (e.g., human tumors). We evaluated SSEA-5 immunoreactivity patterns in human tumors, cell lines, teratomas, and iPS cells together with another pluripotent cell surface marker L1 cell adhesion molecule (L1CAM). We tested two hypotheses: (1) SSEA-5 and L1CAM would be immunoreactive and colocalized in human tumors; (2) SSEA-5 and L1CAM immunoreactivity would persist in iPSCs following retinal differentiating treatment. SSEA-5 immunofluorescence was most pronounced in primitive tumors, such as embryonal carcinoma. In tumor cell lines, SSEA-5 was highly immunoreactive in Capan-1 cells, while L1CAM was highly immunoreactive in U87MG cells. SSEA-5 and L1CAM showed colocalization in undifferentiated iPSCs, with immunopositive iPSCs remaining after 20 days of retinal differentiating treatment. This is the first demonstration of SSEA-5 immunoreactivity in human tumors and the first indication of SSEA-5 and L1CAM colocalization. SSEA-5 and L1CAM warrant further investigation as potentially useful tumor markers for histological evaluation or as markers to monitor the presence of undifferentiated cells in iPSC populations prior to therapeutic use

Des(1–3)IGF-1 Treatment Normalizes Type 1 IGF Receptor and Phospho-Akt (Thr 308) Immunoreactivity in Predegenerative Retina of Diabetic Rats

Little is known about interventions that may prevent predegenerative changes in the diabetic retina. This study tested the hypothesis that immediate, systemic treatment with an insulin-like growth factor (IGF)-1 analog can prevent abnormal accumulations of type 1 IGF receptor, and phospho-Akt (Thr 308) immunoreactivity in predegenerative retinas of streptozotocin (STZ) diabetic rats. Type 1 IGF receptor immunoreactivity increased approximately 3-fold in both inner nuclear layer (INL) and ganglion cell layer (GCL) in retinas from STZ rats versus nondiabetic controls. Phospho-Akt (Thr 308) immunoreactivity increased 5-fold in GCL and 8-fold in INL of STZ rat retinas. In all cases, immunoreactive cells were significantly reduced in STZ des(1–3)IGF-1–treated versus STZ rats. Preliminary results suggested that vascular endothelial growth factor (VEGF) levels may also be reduced. Hyperglycemia/ failure of weight gain in diabetic rats continued despite systemic des(1–3)IGF-1. These data show that an IGF-1 analog can prevent early retinal biochemical abnormalities implicated in the progression of diabetic retinopathy, despite ongoing hyperglycemia

Human embryonic and neuronal stem cell markers in retinoblastoma

Retinoblastoma (RB) is the most common intraocular tumor of early childhood. The early onset of RB, coupled with our previous findings of cancer stem cell characteristics in RB, led us to hypothesize that subpopulations of RB tumors harbor markers and behaviors characteristic of embryonic and neuronal origin. Our RB sources included: human pathological tissues, and the human RB cell lines Y79 and WERI-RB27. Microarray screening, single and dual-label immunocytochemistry and RT-PCR were performed to detect embryonic and neuronal stem cell markers, such as Oct3/4, Nanog, CD133, and Musashi-1. To test for functional evidence of stem cell behavior, we examined RB cells for their ability to form neurospheres and retain BrdU label as indicators of self-renewal and slow cell cycling, respectively. Microarray comparisons of human RB tumors with normal retinal tissue detected upregulation of a number of genes involved in embryonic development that were also present in Y79 cells, including Oct3/4, Nanog, Musashi-1 and Musashi-2, prominin-1 (CD133), Jagged-2, Reelin, Thy-1, nestin, Meis-1,NCAM, Patched, and Notch4. Expression of Musashi-1, Oct3/4 and Nanog was confirmed by immunostaining and RT-PCR analyses of RB tumors and RB cell lines. CD133 expression was confirmed by PCR analysis. Y79 and WERI-RB27 contained populations of Hoechst-dim/ABCG2-positive cells that co-localized with embryonic stem cell markers Oct3/4-ABCG2 and Nanog-ABCG2. Subpopulations of Y79 and WERI-RB27 cells were label-retaining (as seen by BrdU incorporation) and were able to generate neurospheres, both hallmarks of a stem cell phenotype. Small subpopulation(s) of RB cells express human embryonic and neuronal stem cell markers. There are also subpopulations that demonstrate functional behavior (label retention and self-renewal) consistent with cancer stem cells. These findings support the hypothesis that RB is a heterogeneous tumor comprised of subpopulation(s) with stem cell-like properties

Evidence for the multiple hits genetic theory for inherited language impairment: a case study

Communication disorders have complex genetic origins, with constellations of relevant gene markers that vary across individuals. Some genetic variants are present in healthy individuals as well as those affected by developmental disorders. Growing evidence suggests that some variants may increase susceptibility to these disorders in the presence of other pathogenic gene mutations. In the current study, we describe eight children with specific language impairment and four of these children had a copy number variant in one of these potential susceptibility regions on chromosome 15. Three of these four children also had variants in other genes previously associated with language impairment. Our data support the theory that 15q11.2 is a susceptibility region for developmental disorders, specifically language impairment.University of Nebraska. Health Research ConsortiumBarkley Memorial Trus

Zeta function regularization for a scalar field in a compact domain

We express the zeta function associated to the Laplacian operator on $S^1_r\times M$ in terms of the zeta function associated to the Laplacian on $M$, where $M$ is a compact connected Riemannian manifold. This gives formulas for the partition function of the associated physical model at low and high temperature for any compact domain $M$. Furthermore, we provide an exact formula for the zeta function at any value of $r$ when $M$ is a $D$-dimensional box or a $D$-dimensional torus; this allows a rigorous calculation of the zeta invariants and the analysis of the main thermodynamic functions associated to the physical models at finite temperature.Comment: 19 pages, no figures, to appear in J. Phys.

Self dual models and mass generation in planar field theory

We analyse in three space-time dimensions, the connection between abelian self dual vector doublets and their counterparts containing both an explicit mass and a topological mass. Their correspondence is established in the lagrangian formalism using an operator approach as well as a path integral approach. A canonical hamiltonian analysis is presented, which also shows the equivalence with the lagrangian formalism. The implications of our results for bosonisation in three dimensions are discussed.Comment: 15 pages,Revtex, No figures; several changes; revised version to appear in Physical Review