Dopamine neurotransmitter and its receptors play a critical role in the cell signaling process responsible for information transfer in neurons functioning in the nervous system. Development of improved therapeutics for such disorders as Parkinson's disease and schizophrenia would be significantly enhanced with the availability of the 3D structure for the dopamine receptors and of the binding site for dopamine and other agonists and antagonists. We report here the 3D structure of the long isoform of the human D2 dopamine receptor, predicted from primary sequence using firstprinciples theoretical and computational techniques (i.e., we did not use bioinformatic or experimental 3D structural information in predicting structures). The predicted 3D structure is validated by comparison of the predicted binding site and the relative binding affinities of dopamine, three known dopamine agonists (antiparkinsonian), and seven known antagonists (antipsychotic) in the D2 receptor to experimentally determined values. These structures correctly predict the critical residues for binding dopamine and several antagonists, identified by mutation studies, and give relative binding affinities that correlate well with experiments. The predicted binding site for dopamine and agonists is located between transmembrane (TM) helices 3, 4, 5, and 6, whereas the best antagonists bind to a site involving TM helices 2, 3, 4, 6, and 7 with minimal contacts to TM helix 5. We identify characteristic differences between the binding sites of agonists and antagonists.W ith the implication of G protein-coupled receptor (GPCR) in many diseases (1, 2), the need to solve the highresolution 3D structure of this class of integral membrane proteins to enable structure-based drug design is an important problem in structural biology. Despite the importance of solving the structure of the GPCRs, the only experimental 3D structure available for a GPCR is bovine rhodopsin. This lack of structures is because the GPCRs are bound to the membrane, making it difficult to express in sufficient quantities for crystallization.To provide structural and ligand binding information on GPCRs, we have been developing first-principles computational techniques for predicting the 3D structure of GPCRs using only the amino acid sequence (MembStruk) and for predicting binding site and binding energy of various ligands to GPCRs (HierDock). Using these techniques, we have reported the structure of olfactory receptors (3, 4), bovine rhodopsin (4, 5), and other GPCRs (4). Dopamine neurotransmitter plays a critical role in cellular signaling processes responsible for information transfer in neurons functioning in the nervous system (6, 7). Dopamine receptors (DR) belong to the superfamily of GPCRs, and to date there are five reported sequences for the human DR with multiple isoforms for each. The DRs may be subdivided based on their pharmacological behavior into the D1-like and the D2-like subfamilies, and these are ideal targets for treating schizophrenia and Parkinson's disease; th...

Objective We evaluated focused training in coronary artery anastomosis with a porcine heart model and portable task station. Methods At “Boot Camp,” 33 first-year cardiothoracic surgical residents participated in 4-hour coronary anastomosis sessions (6–7 attending surgeons per group of 8–9 residents). At beginning, midpoint, and session end, anastomosis components were assessed on a 3-point rating scale (1 good, 2 average, 3 below average). Performances were video recorded and reviewed by 3 surgeons in a blinded fashion. Participants completed questionnaires at session end, with follow-up surveys at 6 months. Results Ten to 18 end-to-side anastomoses with porcine model and task station were performed. Initial assessments ranged from 2.11 ± 0.58 (forceps use) to 2.44 ± 0.48 (needle angles). Midpoint scores ranged from 1.76 ± 0.63 (forceps use) to 1.91 ± 0.49 (needle angles). Session end scores ranged from 1.29 ± 0.45 (needle holder use) to 1.58 ± 0.50 (needle transfer and suture management and tension; P < .001). Video recordings confirmed improved performance (interrater reliability > 0.5). All respondents agreed that task station and porcine model were good methods of training. At 6 months, respondents noted that the anastomosis session provided a basis for training; however, only slightly more than half continued to practice outside the operating room. Conclusions Four-hour focused training with porcine model and task station resulted in improved ability to perform anastomoses. Boot Camp may be useful in preparing residents for coronary anastomosis in the clinical setting, but emphasis on simulation development and deliberate practice is necessary.

The human insular cortex, or the lobus insularis, is considered the developmentally most primitive lobe of the telencephalon. Covered by an overlying cortical lid, the insula has functions that are distinct from yet related to those of the adjacent temporal lobe and deep limbic structures. In the first part of this paper the authors outline the development of the human insula, including the cellular heterogeneity comprising the various parts of the insular lobe. Using the understanding gained from the development of the insula they then address implications of insular development for cortical development and connection as well as for tumorigenesis and tumor spread from the insula to other cortical structures, most notably the temporal lobe. An understanding of cortico-insular development and interconnection allows for both a better understanding of insular pathology and also facilitates planning of resection of cortico-insular gliomas to avoid damage to eloquent structures.

OBJECT Demonstrating the value of spine care requires adequate outcomes assessment. Long-term outcomes are best measured as overall improvement in quality of life (QOL) after surgical intervention. Present registries often require parallel data entry, introducing inefficiencies and limiting compliance. The authors detail the methodology of constructing an integrated electronic health record (EHR) system to collect QOL metrics and demonstrate the effect of data collection on routine clinical workflow. A streamlined approach to collecting QOL data can capture patient data without requiring dual data entry and without increasing clinic visit times. METHODS Through extensive literature review, a combination of QOL assessments was selected, consisting of the Patient Health Questionnaire-2 and -9, Oswestry Disability Index, Neck Disability Index, and visual analog scale for pain. These metrics were used to provide assessment of QOL following spine surgery and were incorporated into standard clinic workflow by a multidisciplinary team of surgeons, advanced practice providers, and health care information technology specialists. A clinical dashboard tracking more than 25 patient variables was developed. Clinic flow was assessed and opportunities for improvement reviewed. Duration of clinic visits before and after initiation of QOL measure capture was recorded, with assessment of mean clinic visit times for the 12 months before and the 12 months after implementation. RESULTS The integrated QOL capture was instituted for 3 spine surgeons in a tertiary care academic center. In the 12-month period prior to initiating collection of QOL data, 806 new patient visits were completed with an average visit time of 127.9 ± 51.5 minutes. In the 12 months after implementation, 1013 new patient visits were recorded, with 791 providing QOL measures with an average visit time of 117.0 ± 45.7 minutes. Initially the primary means of collecting patient outcome data was via paper form, with gradual transition to collection via entry into the electronic medical records system. To improve electronic data capture, paper forms were eliminated and an online portal used as part of the patient rooming process. This improved electronic capture to nearly 98% without decreasing the number of patients enrolled in the process. CONCLUSIONS A systematic approach to collecting spine-related QOL data within an EHR system is feasible and offers distinct advantages over registries that require dual data entry. The process of data collection does not impact patients’ clinical visit or providers’ clinical workflow. This approach is scalable, and may form the foundation for a decentralized outcomes registry network.