Clinical examination and imaging resources in children and adolescent back pain.

Back pain is a relatively common complaint in children and adolescents. The pediatric patient presenting with back pain can often be challenging, and there are many well-known organic diagnoses that should not be missed. In younger children, an organic cause of back pain can often be found. However, back pain in older children and adolescents is often "non-specific." The differential diagnosis of back pain in children includes neoplasms, developmental, and inflammatory conditions. Basic steps should include an in-depth anamnesis, a systematic physical examination, and standard spine radiographs (anteroposterior and lateral). Nevertheless, advanced diagnostic imaging and laboratory studies should be included when indicated to avoid missing or delaying a serious diagnosis. If other types of imaging tests are necessary (magnetic resonance imaging, computed tomography, bone scan, or single photon emission computed tomography), they should be guided by diagnostic suspicion.

Altered regulation of the Spry2/Dyrk1A/PP2A triad by homocysteine impairs neural progenitor cell proliferation.

Hyperhomocysteinemia reduces neurogenesis in the adult mouse brain. Homocysteine (Hcy) inhibits postnatal neural progenitor cell (NPC) proliferation by specifically impairing the fibroblast growth factor receptor (FGFR)-Erk1/2-cyclin E signaling pathway. We demonstrate herein that the inhibition of FGFR-dependent NPC proliferation induced by Hcy is mediated by its capacity to alter the cellular methylation potential. Our results show that this alteration modified the expression pattern and activity of Sprouty2 (Spry2), a negative regulator of the above mentioned pathway. Both elevated concentrations of Hcy and methyltransferase activity inhibition induced Spry2 promoter demethylation in NPC cultures leading to a sustained upregulation of the expression of Spry2 mRNA and protein. In addition, protein levels of two kinases responsible for Spry2 activation/deactivation were altered by Hcy: Spry2 kinase Dyrk1A levels diminished while Spry2 phosphatase PP2A increased, leading to changes in the phosphorylation pattern, activity and stability of Spry2. In conclusion, Hcy inhibits NPC proliferation by indirect mechanisms involving alterations in DNA methylation, gene expression, and Spry2 function, causing FGFR signaling impairment.