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Squamous cell carcinomas (SCC) are sun-induced skin cancers that are particularly numerous and aggressive in patients taking T cell immunosuppressant medications. Imiquimod is a topical immune response modifier and TLR7 agonist that induces the immunologic destruction of SCC and other skin cancers. TLR7 activation by imiquimod has pleiotropic effects on innate immune cells but its effects on T cells remain largely uncharacterized. Because tumor destruction and formation of immunologic memory are ultimately T cell mediated effects, we studied the effects of imiquimod therapy on effector T cells infiltrating human SCC. SCC treated with imiquimod prior to excision contained dense T cell infiltrates associated with tumor cell apoptosis and histologic evidence of tumor regression. Effector T cells from treated SCC produced more IFN-γ, granzyme and perforin and less IL-10 and TGF-β than T cells from untreated tumors. Treatment of normal human skin with imiquimod induced activation of resident T cells and reduced IL-10 production but had no effect on IFN-γ, perforin or granzyme, suggesting that these latter effects arise from recruitment of distinct populations of T cells into tumors. Thus, imiquimod stimulates tumor destruction by recruiting cutaneous effector T cells from blood and by inhibiting tonic anti-inflammatory signals within the tumor.

Electronic monitoring can improve compliance with orthoses in patients with spinal deformity during a short observation period.

SLC44A2 (solute carrier 44a2), also known as CTL2 (choline transporter-like protein 2), is expressed in many supporting cell types in the cochlea and is implicated in hair cell survival and antibody-induced hearing loss. In mice with the mixed C57BL/6-129 background, homozygous deletion of Slc44a2 exons 3–10 (Slc44a2Δ/Δ) resulted in high-frequency hearing loss and hair cell death. To reduce effects associated with age-related hearing loss (ARHL) in these strains, mice carrying the Slc44a2Δ allele were backcrossed to the ARHL-resistant FVB/NJ strain and evaluated after backcross seven (N7) (99 % FVB). Slc44a2Δ/Δ mice produced abnormally spliced Slc44a2 transcripts that contain a frameshift and premature stop codons. Neither full-length SLC44A2 nor a putative truncated protein could be detected in Slc44a2Δ/Δ mice, suggesting a likely null allele. Auditory brain stem responses (ABRs) of mice carrying the Slc44a2Δ allele on an FVB/NJ genetic background were tested longitudinally between the ages of 2 and 10 months. By 6 months of age, Slc44a2Δ/Δ mice exhibited hearing loss at 32 kHz, but at 12 and 24 kHz had sound thresholds similar to those of wild-type Slc44a2+/+ and heterozygous +/Slc44a2Δ mice. After 6 months of age, Slc44a2Δ/Δ mutants exhibited progressive hearing loss at all frequencies and +/Slc44a2Δ mice exhibited moderate threshold elevations at high frequency. Histologic evaluation of Slc44a2Δ/Δ mice revealed extensive hair cell and spiral ganglion cell loss, especially in the basal turn of the cochlea. We conclude that Slc44a2 function is required for long-term hair cell survival and maintenance of hearing.