Collision-induced dissociation of fatty acid [M - 2H + Na]- ions: charge-directed fragmentation and assignment of double bond position.

The collision-induced dissociation (CID) of cationic fatty acid-metal ion complexes has been extensively studied and, in general, provides rich structural information. In particular, charge-remote fragmentation processes are commonly observed allowing the assignment of double bond position. In a previous manuscript, we presented two methods to doubly deprotonate polyunsaturated fatty acids to form anionic fatty acid-sodium ion complexes, referred to as [M - 2H + Na] (-) ions. In the current manuscript, the CID behavior of these [M - 2H + Na] (-) ions is investigated for the first time. Significantly, we also present a deuterium-labeling experiment, which excludes the possibility that deprotonation occurs predominately at the α-carbon in the formation of fatty acid [M - H + NaF](-) ions. This supports our original proposal where deprotonation occurs at the bis-allylic positions of polyunsaturated fatty acids. CID spectra of polyunsaturated fatty acid [M - 2H + Na](-) ions display abundant product ions arising from acyl chain cleavages. Through the examination of fatty acid isomers, it is demonstrated that double bond position may be unequivocally determined for methylene-interrupted polyunsaturated fatty acids with three or more carbon-carbon double bonds. In addition, CID of [M - 2H + Na](-) ions was applied to 18:3 isomers of Nannochloropsis oculata and three isomers were tentatively identified: ∆(9,12,15)18:3, ∆(6,9,12)18:3, and ∆(5,8,11)18:3. We propose that structurally-informative product ions are formed via charge-driven fragmentation processes at the site of the resonance-stabilized carbanion as opposed to charge-remote fragmentation processes, which could be inferred if deprotonation occurred predominately at the α-carbon.

Implementation in a large health system of a program to identify women at high risk for breast cancer.

PURPOSE: PATIENTS AT HIGH RISK FOR DEVELOPING BREAST CANCER CAN BE IDENTIFIED USING A VALIDATED PREDICTIVE TOOL: the Gail model. Patients thus identified can undergo careful breast cancer screening and be considered for preventive measures, such as chemoprevention with tamoxifen or raloxifene. An organized health system can create a screening and high-risk intervention program for breast cancer and potentially save lives and resources. Multiple components of the health system must work together in a multidisciplinary manner to successfully implement such a program. METHODS: Aurora Health Care is a large health system in Wisconsin. In 2007, a medical center within Aurora initiated a program to identify patients at high risk for developing breast cancer and intervene with screening and prevention. The program used the Gail model, which was administered to patients presenting for comprehensive physical examination at the women's center. RESULTS: During the first year, 5,718 Gail model scores were calculated, and 15.2% of patients were deemed high risk. Most were counseled by their primary care providers, and few underwent screening with magnetic resonance imaging, genetics consultation, or chemoprevention. Primary care providers expressed concerns regarding the accuracy of the Gail model, the additional time necessary for patient counseling, how few patients underwent chemoprevention, and perceived medicolegal risk. The program was altered to address these concerns. CONCLUSION: Success of a breast cancer risk and intervention program in a large health system is more likely if concerns of participating disciplines are acknowledged and addressed.