A highly conserved region of 21 amino acids flanked by cysteine residues, contained within a larger repeated domain, has been proposed to be the antibodybinding site in the ovarian cancer biomarker CA125 (MUC16). In this study solid-phase peptide synthesis with Fmoc protection chemistry was used to assemble a 21-mer peptide corresponding to the most frequently occurring antibody binding sequence in CA125. Potentially significant sequence variants were also synthesized. Peptide secondary structure was investigated using Fourier transform infrared spectroscopy, revealing the consensus sequence peptide to be largely unstructured at physiological pH whether the cysteine residues were reduced or were oxidized to form an intramolecular disulfide bond. Substitution of serine for proline at position 8 (P8S) results in β-sheet formation in peptides involved in intramolecular disulfide bonds. This β-sheet structure does not persist in peptides incapable of intramolecular disulfide bonding because of sequence nor in peptides treated with the reducing agent dithiothreitol. In CA125, P8S is predicted to occur in ∼25% of repeat domains, suggesting that this structural motif is a non-negligible contributor to overall structure and function. These findings suggest that future structural characterization efforts of CA125 should be especially mindful of the amino acid sequence and oxidation state of the protein.

In our small series of patients presented we demonstrate that PCI and TAVR performed concurrently in the hybrid operating room is a feasible option in patients undergoing TAVR with coexisting CAD. Furthermore, we propose this single-stage approach in such high-risk patients as it decreases the number of procedures performed and may theoretically lower cost and hospital stay.

Therapy for human immunodeficiency virus (HIV)-infected patients requires chronic multidrug administration. The eventual failure of therapy in some patients has brought into question the tissue concentration of the drugs. With an appropriately radiolabeled compound, we could utilize positron emission tomography to provide quantitative time-activity curves for various tissues. We have developed a fluorine-18 labeled analog of Tenofovir, the active metabolite of Tenofovir DF, a commonly prescribed component of multidrug therapy. Because (1-(6-amino-9H-purin-9-yl)-3-fluoropropan-2-yloxy)methylphosphonic acid (FPMPA) has a chiral center, we prepared both enantiomers and confirmed that the S-isomer exhibited significantly higher antiviral activity than the R-isomer. In viral replication inhibition assays in human MT4 cells infected with SHIV DH12R , S-FPMPA had an IC 50 of 1.85 μM (95% CI; 0.8-5.53), while the R-isomer was inactive. An appropriate chiral precursor was prepared to allow the incorporation of fluorine-18. The [ 18 F]FPMPA in racemic, R, or S form was prepared in a 50 min synthesis in 38±5% yield (n = 23, corrected for decay). The product was of high radiochemical and enantiomeric purity. The specific activity of the final product was 4.0±1.8 Ci/μmol at EOB (end of bombardment). This product may provide information about drug tissue distribution in animal models under chronic drug treatment.

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The authors present the first report of spinal congenital dermal sinus with paramedian dual ostia leading to 2 intradural epidermoid cysts. This 7-year-old girl had a history of recurrent left paramedian lumbosacral subcutaneous abscesses, with no chemical or pyogenic meningitis. Admission MRI studies demonstrated bilateral lumbar dermal sinus tracts and a tethered spinal cord. At surgery to release the tethered spinal cord the authors encountered paramedian dermal sinus tracts with dual ostia, as well as 2 intradural epidermoid cysts that were not readily apparent on MRI studies. Congenital dermal sinus should be considered in the differential diagnosis of lumbar subcutaneous abscesses, even if the neurocutaneous signatures are located off the midline.