Evaluation of 5-(Trifluoromethyl)-1,2,4-oxadiazole-Based Class IIa HDAC Inhibitors for Huntington’s Disease

Using an iterative structure–activity relationship driven approach, we identified a CNS-penetrant 5-(trifluoromethyl)-1,2,4-oxadiazole (TFMO, 12) with a pharmacokinetic profile suitable for probing class IIa histone deacetylase (HDAC) inhibition in vivo. Given the lack of understanding of endogenous class IIa HDAC substrates, we developed a surrogate readout to measure compound effects in vivo, by exploiting the >100-fold selectivity compound 12 exhibits over class I/IIb HDACs. We achieved adequate brain exposure with compound 12 in mice to estimate a class I/IIb deacetylation EC₅₀, using class I substrate H4K12 acetylation and global acetylation levels as a pharmacodynamic readout. We observed excellent correlation between the compound 12 in vivo pharmacodynamic response and in vitro class I/IIb cellular activity. Applying the same relationship to class IIa HDAC inhibition, we estimated the compound 12 dose required to inhibit class IIa HDAC activity, for use in preclinical models of Huntington’s disease.     

Lymphangioma of the Ileocecal Valve Clinically Masquerading as a Submucosal Small Intestinal Gist: Report of a Case and Literature Review

Lymphangiomas are rare tumors affecting the gastrointestinal tract, and may be seen in the bowel, gall bladder, and pancreas. They resemble hemangiomas, but consist of spaces of variable sizes containing lymph. In this report, we describe the case of a 53-year-old male who presented with abdominal pain and constipation. Computerized tomography (CT) scan showed a polypoidal lesion at the ileocecal valve which was thought to be a gastrointestinal stromal tumor. Resected specimen did, however, show a lymphangioma. We also describe the clinicopathologic features of gastrointestinal lymphangiomas with a literature review.     

Knowledge and Attitudes of Saudi Dental Undergraduates on Oral Cancer

Oral cancer awareness among future dental practitioners may have an impact on the early detection and prevention of oral cancer. A cross-sectional survey was undertaken to assess the current knowledge of future Saudi dentists on oral cancer and their opinions on oral cancer prevention. A pretested questionnaire was sent to 550 undergraduate dental students in the fourth, fifth, and sixth year of the Al-Farabi College for Dentistry and Nursing, Riyadh, Saudi Arabia. Questions relating to knowledge of oral cancer, risk factors, and opinions on oral cancer prevention and practices were posed. Four hundred seventy-nine students returned the questionnaire (87.1 %). Eighty-one percent of respondents correctly answered questions relating to oral cancer awareness. Eighty-seven percent of respondents felt confident in performing a systematic oral examination to detect changes consistent with oral malignancy. Interestingly, 57 % of respondents had seen the use of oral cancer diagnostics aids. Thirty-seven percent of respondents felt inadequately trained to provide tobacco and alcohol cessation advice. There is a need to reinforce the undergraduate dental curriculum with regards to oral cancer education; particularly in its prevention and early detection. Incorporating the use of oral cancer diagnostic aids should be made mandatory.     

Migrating foreign body into the common carotid artery and internal jugular vein – A rare case

Ingested foreign bodies are a fairly common otorhinolaryngological emergencies encountered in Malaysia. The vast majority of these foreign bodies are fish bones which most commonly are impacted at the level of the cricopharynx. Rarely, however, a foreign body may migrate extraluminally and may even extrude subcutaneously. We report a rare occurrence where a fish bone not only migrated extraluminally, it was found to have migrated into the common carotid artery and the internal jugular vein and required surgical removal.