Olfactory Reference Syndrome: A Case Report and Screening Tool

Olfactory reference syndrome (ORS) is a lesser known disorder that is related to obsessive–compulsive disorder. ORS is the obsessional and inaccurate belief that one is emitting a foul odor leading to embarrassment or concern about offending others, excessive hygiene behaviors, and social avoidance that significantly interferes with daily functioning. Although ORS is rare, it is challenging to diagnose. ORS-sufferers first seek treatment from non- psychiatric providers (e.g., dermatologists, dentists.) to alleviate the perceived odor, which frequently leads to misdiagnosis and unnecessary treatments. Additionally, because ORS-sufferers can have limited insight and ideas of reference, they can be misdiagnosed as having a psychotic or delusional disorder. We present a case report of a 42-year-old woman with ORS, and how the correct diagnosis of ORS provided with psychiatric treatment led to significant improvement in her daily functioning. We provide a literature review on the disorder as well as a short screener to assess ORS

Antitumor Polycyclic Acridines. 20. Search for DNA Quadruplex Binding Selectivity in a Series of 8,13-Dimethylquino[4,3,2-kl]acridinium Salts: Telomere-Targeted Agents

The growth-inhibitory activities of an extensive series of quaternized quino[4,3,2-kl]acridinium salts against tumor cell lines in vitro have been measured and their biological properties interpreted in the light of differential binding to different DNA isoforms. Selectivity for quadruplex DNA binding and stabilization by compounds were explored through an array of methods: UV absorption and fluorescence emission spectroscopy, surface plasmon resonance, and competition dialysis. Quadruplex DNA interaction was further characterized through FRET and DNA polymerase arrest assays. Telomerase inhibition, inferred from the TRAP assay, is attributed to quadruplex stabilization, supported by the strong correlation (R2 = 0.81) across the series between quadruplex DNA binding affinity and TRAP inhibition potency. Growth inhibition potency in the NCI60 human tumor cell line panel is more marked in compounds with greater DNA duplex binding affinity (R2 = 0.82). Quantification of relative quadruplex and duplex binding affinity constants puts some of these ligands among the most selective quadruplex DNA interactive agents reported to date

Structure-based design of selective and potent G quadruplex-mediated telomerase inhibitors

The telomerase enzyme is a potential therapeutic target in many human cancers. A series of potent inhibitors has been designed by computer modeling, which exploit the unique structural features of quadruplex DNA. These 3,6,9-trisubstituted acridine inhibitors are predicted to interact selectively with the human DNA quadruplex structure, as a means of specifically inhibiting the action of human telomerase in extending the length of single-stranded telomeric DNA. The anilino substituent at the 9-position of the acridine chromophore is predicted to lie in a third groove of the quadruplex. Calculated relative binding energies predict enhanced selectivity compared with earlier 3,6-disubstituted compounds, as a result of this substituent. The ranking order of energies is in accord with equilibrium binding constants for quadruplex measured by surface plasmon resonance techniques, which also show reduced duplex binding compared with the disubstituted compounds. The 3,6,9-trisubstututed acridines have potent in vitro inhibitory activity against human telomerase, with EC(50) values of up to 60 nM