Approximating the Strength of the Intramolecular Hydrogen Bond in 2-Fluorophenol and Related Compounds: A New Application of a Classic Technique.

Fluorinated organic compounds are ubiquitous in the pharmaceutical and agricultural industries. To better discern the mode of action of these compounds, it is critical to understand the strengths of hydrogen bonds involving fluorine. While established techniques can determine these strengths for intermolecular complexes, there is no analogous scheme for intramolecular hydrogen bonds. This work uses 1H nuclear magnetic resonance spectroscopy to measure the strength of intramolecular hydrogen bonds in ortho-substituted phenols. Titration of each phenol with DMSO in CCl4 yields a free energy of binding (ΔG). Subtraction of this value from the ΔG of binding of the standard, 4-fluorophenol, is shown to give the difference in ΔG for the cis and trans isomers of the ortho-substituted phenols. This difference is conventionally taken to be approximately equal to the ΔG of the intramolecular hydrogen bond. These data complement theoretical methods, which yield slightly larger ΔGs. Both theory and experiment point to a weak intramolecular hydrogen bond in 2-fluorophenol. The other 2-X-phenols have stronger hydrogen bonds, following the order F < Cl ≈ Br < OCH3. The methodology developed here can be readily applied to other systems with intramolecular hydrogen bonds.

Satisfaction Academy: A Novel Residency Curriculum to Improve the Patient Experience in the Emergency Department.

Introduction: Patient satisfaction is a key indicator of health care value and an increasingly important metric used to assess emergency physician performance and often reimbursement. To our knowledge, there is no standardized curriculum within emergency medicine (EM) residency programs that focuses on the patient experience in EM. Methods: Our novel resident curriculum is an organized approach to enhancing patient-centered care by optimizing the patient experience. It spans the academic year, with key topics organized into a quarterly time line. Topics include physician courtesy and respect, pain management, discussion of diagnostic and therapeutic interventions, timely communication, and delivery of quality care. Each quarter has three components: introduction/didactics, an interactive workshop, and stories and reflection. The instructional methods used include didactic lectures, role-playing, and group reflection and storytelling. Results: Of 44 participants, 54.5% completed a preintervention survey, and 45.5% completed a postintervention survey. The surveys consisted of 5-point Likert scales measuring degree of agreement with statements that reflected desired behaviors and/or attitudes. On the postintervention survey, participants gave scores indicating general agreement with desired behaviors including sitting at the bedside, acknowledging all persons in the room, and giving an anticipated disposition, as well as with feeling more knowledgeable about patient satisfaction. Discussion: Our Satisfaction Academy has filled a significant gap related to enhancing the patient experience. This curriculum is generalizable to other EM residency programs, and the interactive peer-to-peer format is both engaging and customizable.

A potential regulatory loop between Lin28B:miR­212 in androgen-independent prostate cancer.

Lin28 is a family of RNA binding proteins and microRNA regulators. Two members of this family have been identified: Lin28A and Lin28B, which are encoded by genes localized in different chromosomes but share a high degree of sequence identity. The role of Lin28B in androgen-independent prostate cancer (AIPC) is not well understood. Lin28B is expressed in all grades of prostatic carcinomas and prostate cancer cell lines, but not in normal prostate tissue. In this study we found that Lin28B co-localized in the nucleus and cytoplasm of the DU145 AIPC. The expression of Lin28B protein positively correlated with the expression of the c-Myc protein in the prostate cancer cell lines and silencing of Lin28B also correlated with a lower expression of the c-Myc protein, but not with the downregulation of c-Myc messenger RNA (mRNA) in the DU145 AIPC cells. We hypothesized that Lin28B regul-ates the expression of c-Myc protein by altering intermediate c-Myc suppressors. Therefore, a microRNA profile of DU145 cells was performed after Lin28B siRNA silencing. Nineteen microRNAs were upregulated and eleven microRNAs were downregulated. The most upregulated microRNAs were miR-212 and miR-2278. Prior reports have found that miR-212 is suppressed in prostate cancer. We then ran TargetScan software to find potential target mRNAs of miR-212 and miR-2278, and it predicted Lin28B mRNA as a potential target of miR-212, but not miR-2278. TargetScan also predicted that c-Myc mRNA is not a potential target of miR-212 or miR-2278. These observations suggest that Lin28B:miR-212 may work as a regulatory loop in androgen-independent prostate cancer. Furthermore, we report a predictive 2-fold symmetric model generated by the superposition of the Lin28A structure onto the I-TASSER model of Lin28B. This structural model of Lin28B suggests that it shows unique microRNA binding characteristics. Thus, if Lin28B were to bind miRNAs in a manner similar to Lin28A, conformational changes would be necessary to prevent steric clashes in the C-terminal and linker regions between the CSD and ZNF domains.