Osteochondroma : the local effects and the management.

Osteochondroma is a common benign bone tumour, presenting as a single or multiple lesions, pedunculated or sessile type, mainly in 1st-2nd decades and mostly in males. The presented case series, studied the local effect of (osteochondroma) at the end of long bones with best line of treatment (RQ). Eighteen patients with osteochondromas, with an age range of 9- 45 years, mean age 19.6 ± 11.147 years, were seen from October 2016 to November 2018. There were 8 cases with painful lesion due to (mechanical interaction) or (pressure on near by neurovascular bundle), or from (inflamed bursa). Four cases were asymptomatic, 3 cases had Growth disturbances of the fellow bone, 3 cases presented with neurological symptoms and one case had vascular complications. Osteochondromas may present with different types of local effects on its surrounding tissues. Surgical excision is the best line of treatment.

A Chemical Biology Approach to Model Pontocerebellar Hypoplasia Type 1B (PCH1B).

Mutations of EXOSC3 have been linked to the rare neurological disorder known as Pontocerebellar Hypoplasia type 1B (PCH1B). EXOSC3 is one of three putative RNA-binding structural cap proteins that guide RNA into the RNA exosome, the cellular machinery that degrades RNA. Using RNAcompete, we identified a G-rich RNA motif binding to EXOSC3. Surface plasmon resonance (SPR) and microscale thermophoresis (MST) indicated an affinity in the low micromolar range of EXOSC3 for long and short G-rich RNA sequences. Although several PCH1B-causing mutations in EXOSC3 did not engage a specific RNA motif as shown by RNAcompete, they exhibited lower binding affinity to G-rich RNA as demonstrated by MST. To test the hypothesis that modification of the RNA-protein interface in EXOSC3 mutants may be phenocopied by small molecules, we performed an in-silico screen of 50 000 small molecules and used enzyme-linked immunosorbant assays (ELISAs) and MST to assess the ability of the molecules to inhibit RNA-binding by EXOSC3. We identified a small molecule, EXOSC3-RNA disrupting (ERD) compound 3 (ERD03), which ( i) bound specifically to EXOSC3 in saturation transfer difference nuclear magnetic resonance (STD-NMR), ( ii) disrupted the EXOSC3-RNA interaction in a concentration-dependent manner, and ( iii) produced a PCH1B-like phenotype with a 50% reduction in the cerebellum and an abnormally curved spine in zebrafish embryos. This compound also induced modification of zebrafish RNA expression levels similar to that observed with a morpholino against EXOSC3. To our knowledge, this is the first example of a small molecule obtained by rational design that models the abnormal developmental effects of a neurodegenerative disease in a whole organism.