A TDDFT investigation of the Photosystem II reaction center: Insights into the precursors to charge separation.

Photosystem II (PS II) captures solar energy and directs charge separation (CS) across the thylakoid membrane during photosynthesis. The highly oxidizing, charge-separated state generated within its reaction center (RC) drives water oxidation. Spectroscopic studies on PS II RCs are difficult to interpret due to large spectral congestion, necessitating modeling to elucidate key spectral features. Herein, we present results from time-dependent density functional theory (TDDFT) calculations on the largest PS II RC model reported to date. This model explicitly includes six RC chromophores and both the chlorin phytol chains and the amino acid residues <6 Å from the pigments' porphyrin ring centers. Comparing our wild-type model results with calculations on mutant D1-His-198-Ala and D2-His-197-Ala RCs, our simulated absorption-difference spectra reproduce experimentally observed shifts in known chlorophyll absorption bands, demonstrating the predictive capabilities of this model. We find that inclusion of both nearby residues and phytol chains is necessary to reproduce this behavior. Our calculations provide a unique opportunity to observe the molecular orbitals that contribute to the excited states that are precursors to CS. Strikingly, we observe two high oscillator strength, low-lying states, in which molecular orbitals are delocalized over ChlD1 and PheD1 as well as one weaker oscillator strength state with molecular orbitals delocalized over the P chlorophylls. Both these configurations are a match for previously identified exciton-charge transfer states (ChlD1+PheD1-)* and (PD2+PD1-)*. Our results demonstrate the power of TDDFT as a tool, for studies of natural photosynthesis, or indeed future studies of artificial photosynthetic complexes.

Do stroke clinical practice guideline recommendations for the intervention of thickened liquids for aspiration support evidence based decision making? A systematic review and narrative synthesis.

RATIONALE: Aspiration is a common sequela post stroke as a result of oropharyngeal dysphagia. It is primarily managed using the poorly empirically supported intervention of thickened liquids. Where evidence is limited, clinicians may rely on clinical practice guidelines to support decision making. The purpose of this systematic review and narrative synthesis was to evaluate the evidentiary bases of recommendations made by stroke clinical practice guidelines regarding the thickened liquids intervention. METHODS: A systematic review was conducted on stroke clinical guidelines retrieved via searches conducted across a range of databases including Academic Search Complete, CINAHL, MEDLINE, and the Cochrane Library as well as through association websites. Guidelines were eligible for inclusion if they focused on adult stroke populations, made recommendations relating to the thickened liquid intervention and were published between January 2010 and December 2018. Four independent reviewers rated methodological quality using the AGREE-II instrument. Intervention recommendations were extracted and analysed using the Criteria for Levels of Evidence Reported from the Canadian Stroke Best Practice Recommendations and a novel framework examining the appropriateness of the supporting evidence. RESULTS: Thirteen clinical guidelines were included in the review. Methodological quality was variable with seven rating as good-excellent overall. Thirty recommendations regarding the intervention were extracted. Of these, 16 recommendations were classed as a recommendation to use the treatment and all guidelines made this recommendation. Much of the evidence used to scaffold recommendations did not directly support the intervention. CONCLUSIONS: Despite the limited evidence base for the thickened liquid intervention, there was consensus among stroke guidelines in recommending it. This is despite limited empirical support. Furthermore, much of the evidence used to support recommendations was not appropriate, suggesting less than satisfactory evidence-based practices in formulating recommendations. In this case, clinical guidelines may not be reliable decision-support tools for facilitating clinical decision making.