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Object The purpose of this study was to validate a new prognostic index for patients with brain metastases. This index, the Graded Prognostic Assessment (GPA), is based on an analysis of 1960 patients whose data were extracted from the Radiation Therapy Oncology Group (RTOG) database. The GPA is based on 4 criteria: age, Karnofsky Performance Scale score, number of brain metastases, and the presence/absence of extracranial metastases. Each of the 4 criteria is given a score of 0, 0.5, or 1.0, so the patient with best prognosis would have a GPA score of 4.0. Methods Between April 2005 and December 2006, 140 eligible patients with brain metastases were treated at the Gamma Knife Center at the University of Minnesota. The GPA score was calculated for each patient, and the score was then correlated with survival. Survival duration was calculated from the date treatment began for the brain metastases. Eligibility criteria included patients treated with whole-brain radiation therapy, stereotactic radiosurgery, or both. Results The median survival time in months observed in the RTOG and Minnesota data by GPA score was as follows: GPA 3.5–4.0, 11.0 and 21.7; GPA 3.0, 8.9 and 17.5; GPA 1.5–2.5, 3.8 and 5.9; and GPA 0–1.0, 2.6 and 3.0, respectively. Conclusions The University of Minnesota data correlate well with the RTOG data and validate the use of the GPA as an effective prognostic index for patients with brain metastases. Clearly, not all patients with brain metastases have the same prognosis, and treatment decisions should be individualized accordingly. The GPA score does appear to be as prognostic as the RPA and is less subjective (because the RPA requires assessment of whether the primary disease is controlled), more quantitative, and easier to use and remember. A multiinstitutional validation study of the GPA is ongoing.

Weakly polar interactions between aromatic rings of amino acids and hydrogens of backbone amides (Ar-HN) have been shown to support local structures in proteins. Their role in secondary structures, however, has not been elucidated. To investigate the relationship between Ar-HN interaction and the stability of local and secondary structures of polypeptides and to improve the prediction of this interaction based on amino acid sequence, the structures of 560 nonhomologous proteins, from the Protein Data Bank, were searched for Ar-HN interactions between the aromatic ring of each Phe, Tyr, and Trp residue at position i and the backbone amide group of any residue, except Pro, at the positions i, i - 1, i - 2, i - 3, i + 1, i + 2, and i + 3. Ar-HN interactions were identified by calculating the chemical shift of the amide hydrogen caused by the proximal aromatic ring. Ar(i)-HN(i + 1, i + 2 and i + 3) interactions were more common (7.10%, 2.08%, and 0.54%, respectively) than were Ar(i)-HN(i - 1, i - 2, and i - 3) interactions (0.66%, <0.1%, and 0.18%, respectively). The value of the chi(1) torsion angle of the aromatic residue in position i depended on the direction of the Ar-HN interaction. The position of the aromatic ring in Ar(i)-HN(i + 1, i + 2, and i + 3) interactions was mostly trans, in Ar(i)-HN(i - 1, i - 2, and i - 3) interactions mainly gauche(-), and in Ar(i)-HN(i) interactions mostly gauche(+). The analyses of the secondary structures of the protein fragments containing Ar-HN interactions showed that Ar-HN interactions were in all types of secondary structures. Search results suggest that Ar-HN interactions have a stabilizing effect on all types of secondary structures.

Our results suggest that a restrictive transfusion practice is safe for severely head-injured patients.

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Replica exchange molecular dynamics simulations (300 ns) were used to study the dimerization of amyloid β(1-40) (Aβ(1-40)) polypeptide. Configurational entropy calculations revealed that at physiological temperature (310 K, 37°C) dynamic dimers are formed by randomly docked monomers. Free energy of binding of the two chains to each other was -93.56 ± 6.341 kJ mol . Prevalence of random coil conformations was found for both chains with the exceptions of increased β-sheet content from residues 16-21 and 29-32 of chain A and residues 15-21 and 30-33 of chain B with β-turn/β-bend conformations in both chains from residues 1-16, 21-29 of chain A, 1-16, and 21-29 of chain B. There is a mixed β-turn/β-sheet region from residues 33-38 of both chains. Analysis of intra- and interchain residue distances shows that, although the individual chains are highly flexible, the dimer system stays in a loosely packed antiparallel β-sheet configuration with contacts between residues 17-21 of chain A with residues 17-21 and 31-36 of chain B as well as residues 31-36 of chain A with residues 17-21 and 31-36 of chain B. Based on dihedral principal component analysis, the antiparallel β-sheet-loop-β-sheet conformational motif is favored for many low energy sampled conformations. Our results show that Aβ(1-40) can form dynamic dimers in aqueous solution that have significant conformational flexibility and are stabilized by collapse of the central and C-terminal hydrophobic cores with the expected β-sheet-loop-β-sheet conformational motif. Proteins 2017; 85:1024-1045. © 2017 Wiley Periodicals, Inc.

The conformational space available to GnRH and lGnRH-III was compared using 5.2 ns constant temperature and pressure molecular dynamics simulations with explicit TIP3P solvation and the AMBER v. 5.0 force field. Cluster analysis of both trajectories resulted in two groups of conformations. Results of free energy calculations, in agreement with previous experimental data, indicate that a conformation with a turn from residues 5 through 8 is preferred for GnRH in an aqueous environment. By contrast, a conformation with a helix from residues 2 through 7 with a bend from residues 6 through 10 is preferred for lGnRH-III in an aqueous environment. The side chains of His2 and Trp3 in lGnRH-III occupy different regions of phase space and participate in weakly polar interactions different from those in GnRH. The unique conformational properties of lGnRH-III may account for its specific anti cancer activity.