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Purpose: To evaluate the spatial distribution and signal intensity changes following spinal cord activation in patients with spinal cord injury.Methods: This study used spinal functional magnetic resonance imaging (fMRI) based on signal enhancement by extra-vascular water protons (SEEP) to assess elicited responses during subcutaneous electrical stimulation at the right elbow and right thumb in the cervical spinal cord.Results: Seven healthy volunteers and seven patients with cervical spinal cord injury (SCI) were included in this study. Significant functional activation was observed mainly in the right side of the spinal cord at the level of the C5-C6 cervical vertebra in both the axial and sagittal planes. A higher percentage of signal changes (4.66 ± 2.08 % in injured subjects vs. 2.78 ± 1.66 % in normal) and more average activation voxels (4.69 ± 2.59 in injured subjects vs. 2.56 ± 1.13 in normal subject) in axial plane at the C5-C6 cervical vertebra with a statistically significant difference. The same trends were observed in the sagittal plane with higher percentage of signal changes and more average activation voxels, though no statistically significant difference compared with the control group.Conclusions: Spinal SEEP fMRI is a powerful noninvasive method for the study of local neuronal activation in the human spinal cord, which may be of clinical value for evaluating the effectiveness of interventions aimed at promoting recovery of function using electrical stimulation. [ABSTRACT FROM AUTHOR]

The purpose of this research was to use next generation sequencing to identify mutations in patients with primary immunodeficiency diseases whose pathogenic gene mutations had not been identified. Remarkably, four unrelated patients were found by next generation sequencing to have the same heterozygous mutation in an essential donor splice site of PIK3R1 (NM_181523.2:c.1425 + 1G > A) found in three prior reports. All four had the Hyper IgM syndrome, lymphadenopathy and short stature, and one also had SHORT syndrome. They were investigated with in vitro immune studies, RT-PCR, and immunoblotting studies of the mutation's effect on mTOR pathway signaling. All patients had very low percentages of memory B cells and class-switched memory B cells and reduced numbers of naïve CD4+ and CD8+ T cells. RT-PCR confirmed the presence of both an abnormal 273 base-pair (bp) size and a normal 399 bp size band in the patient and only the normal band was present in the parents. Following anti-CD40 stimulation, patient's EBV-B cells displayed higher levels of S6 phosphorylation (mTOR complex 1 dependent event), Akt phosphorylation at serine 473 (mTOR complex 2 dependent event), and Akt phosphorylation at threonine 308 (PI3K/PDK1 dependent event) than controls, suggesting elevated mTOR signaling downstream of CD40. These observations suggest that amino acids 435-474 in PIK3R1 are important for its stability and also its ability to restrain PI3K activity. Deletion of Exon 11 leads to constitutive activation of PI3K signaling. This is the first report of this mutation and immunologic abnormalities in SHORT syndrome. [ABSTRACT FROM AUTHOR]