Effect of P to A Mutation of the N-Terminal Residue Adjacent to the Rgd Motif on Rhodostomin: Importance of Dynamics in Integrin Recognition

Rhodostomin (Rho) is an RGD protein that specifically inhibits integrins. We found that Rho mutants with the P48A mutation 4.4–11.5 times more actively inhibited integrin α5β1. Structural analysis showed that they have a similar 3D conformation for the RGD loop. Docking analysis also showed no difference between their interactions with integrin α5β1. However, the backbone dynamics of RGD residues were different. The values of the R2 relaxation parameter for Rho residues R49 and D51 were 39% and 54% higher than those of the P48A mutant, which caused differences in S2, Rex, and τe. The S2 values of the P48A mutant residues R49, G50, and D51 were 29%, 14%, and 28% lower than those of Rho. The Rex values of Rho residues R49 and D51 were 0.91 s−1 and 1.42 s−1; however, no Rex was found for those of the P48A mutant. The τe values of Rho residues R49 and D51 were 9.5 and 5.1 times lower than those of P48A mutant. Mutational study showed that integrin α5β1 prefers its ligands to contain (G/A)RGD but not PRGD sequences for binding. These results demonstrate that the N-terminal proline residue adjacent to the RGD motif affect its function and dynamics, which suggests that the dynamic properties of the RGD motif may be important in Rho's interaction with integrin α5β1

EEG Biofeedback as a Treatment for Substance Use Disorders: Review, Rating of Efficacy, and Recommendations for Further Research

Electroencephalographic (EEG) biofeedback has been employed in substance use disorder (SUD) over the last three decades. The SUD is a complex series of disorders with frequent comorbidities and EEG abnormalities of several types. EEG biofeedback has been employed in conjunction with other therapies and may be useful in enhancing certain outcomes of therapy. Based on published clinical studies and employing efficacy criteria adapted by the Association for Applied Psychophysiology and Biofeedback and the International Society for Neurofeedback and Research, alpha theta training—either alone for alcoholism or in combination with beta training for stimulant and mixed substance abuse and combined with residential treatment programs, is probably efficacious. Considerations of further research design taking these factors into account are discussed and descriptions of contemporary research are given

Reducing the time-lag between onset of chest pain and seeking professional medical help: a theory-based review

Background: Research suggests that there are a number of factors which can be associated with delay in a patient seeking professional help following chest pain, including demographic and social factors. These factors may have an adverse impact on the efficacy of interventions which to date have had limited success in improving patient action times. Theory-based methods of review are becoming increasingly recognised as important additions to conventional systematic review methods. They can be useful to gain additional insights into the characteristics of effective interventions by uncovering complex underlying mechanisms. Methods: This paper describes the further analysis of research papers identified in a conventional systematic review of published evidence. The aim of this work was to investigate the theoretical frameworks underpinning studies exploring the issue of why people having a heart attack delay seeking professional medical help. The study used standard review methods to identify papers meeting the inclusion criterion, and carried out a synthesis of data relating to theoretical underpinnings. Results: Thirty six papers from the 53 in the original systematic review referred to a particular theoretical perspective, or contained data which related to theoretical assumptions. The most frequently mentioned theory was the self-regulatory model of illness behaviour. Papers reported the potential significance of aspects of this model including different coping mechanisms, strategies of denial and varying models of treatment seeking. Studies also drew attention to the potential role of belief systems, applied elements of attachment theory, and referred to models of maintaining integrity, ways of knowing, and the influence of gender. Conclusions: The review highlights the need to examine an individual’s subjective experience of and response to health threats, and confirms the gap between knowledge and changed behaviour. Interventions face key challenges if they are to influence patient perceptions regarding seriousness of symptoms; varying processes of coping; and obstacles created by patient perceptions of their role and responsibilities. A theoretical approach to review of these papers provides additional insight into the assumptions underpinning interventions, and illuminates factors which may impact on their efficacy. The method thus offers a useful supplement to conventional systematic review methods