Background Repetitive transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex (DLPFC) is an established treatment for depression, but its underlying mechanism of action remains ...unknown. Abnormalities in two large-scale neuronal networks—the frontoparietal central executive network (CEN) and the medial prefrontal-medial parietal default mode network (DMN)—are consistent findings in depression and potential therapeutic targets for TMS. Here, we assessed the impact of TMS on activity in these networks and their relation to treatment response. Methods We used resting state functional magnetic resonance imaging to measure functional connectivity within and between the DMN and CEN in 17 depressed patients, before and after a 5-week course of TMS. Motivated by prior reports, we focused on connectivity seeded from the DLPFC and the subgenual cingulate, a key region closely aligned with the DMN in depression. Connectivity was also compared with a cohort of 35 healthy control subjects. Results Before treatment, functional connectivity in depressed patients was abnormally elevated within the DMN and diminished within the CEN, and connectivity between these two networks was altered. Transcranial magnetic stimulation normalized depression-related subgenual hyperconnectivity in the DMN but did not alter connectivity in the CEN. Transcranial magnetic stimulation also induced anticorrelated connectivity between the DLPFC and medial prefrontal DMN nodes. Baseline subgenual connectivity predicted subsequent clinical improvement. Conclusions Transcranial magnetic stimulation selectively modulates functional connectivity both within and between the CEN and DMN, and modulation of subgenual cingulate connectivity may play an important mechanistic role in alleviating depression. The results also highlight potential neuroimaging biomarkers for predicting treatment response.
•Trigonal pseudooctahedral 5d6 complexes with mixed MLCT–LC excitations phosphoresce strongly.•The pseudo-angular momentum model provides a framework for understanding the phosphorescence.•Both ...scalar relativistic effects and spin–orbit coupling play key roles.•TDDFT accurately predicts the ZFS and radiative decay rates of the substates of T1.•Accurate predictions of the non-radiative rates are the outstanding challenge in materials design.
We review theories of phosphorescence in cyclometalated complexes. We focus primarily on pseudooctahedrally coordinated t2g6 metals (e.g., Os(II)(bpy)32+, Ir(III)(ppy)3 and Ir(III)(ptz)3) as, for reasons that are explored in detail, these show particularly strong phosphorescence. We discuss both first principles approaches and semi-empirical models, e.g., ligand field theory. We show that together these provide a clear understanding of the photophysics and in particular the lowest energy triplet excitation, T1. In order to build a good model relativistic effects need to be included. The role of spin–orbit coupling is well-known, but scalar relativistic effects are also large – and are therefore also introduced and discussed. No expertise in special relativity or relativistic quantum mechanics is assumed and a pedagogical introduction to these subjects is given. Once both scalar relativistic effects and spin–orbit coupling are included, time dependent density functional theory (TDDFT) provides quantitatively accurate predictions of the radiative decay rates of the substates of T1 in phosphorescent organotransition-metal complexes. We describe the pseudo-angular momentum model, and show that it reproduces the key experimental findings. For example, this model provides a simple explanation of the relative radiative rates of the substates of T1, which differ by orders of magnitude. Special emphasis is placed on materials with potential applications as active materials in organic light-emitting diodes (OLEDs) and principles for the design of new complexes are identified on the basis of the insights provided by the theories reviewed. We discuss the remaining theoretical challenges, which include deepening our understanding of solvent effects and, vitally, understanding and predicting non-radiative decay rates.
The polymer polydimethylsiloxane (PDMS) is widely used to build microfluidic devices compatible with cell culture. Whilst convenient in manufacture, PDMS has the disadvantage that it can absorb small ...molecules such as drugs. In microfluidic devices like “Organs-on-Chip”, designed to examine cell behavior and test the effects of drugs, this might impact drug bioavailability. Here we developed an assay to compare the absorption of a test set of four cardiac drugs by PDMS based on measuring the residual non-absorbed compound by High Pressure Liquid Chromatography (HPLC). We showed that absorption was variable and time dependent and not determined exclusively by hydrophobicity as claimed previously. We demonstrated that two commercially available lipophilic coatings and the presence of cells affected absorption. The use of lipophilic coatings may be useful in preventing small molecule absorption by PDMS.
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•Binding of different compounds to PDMS varies greatly.•Previous reported correlations of absorption and LogP values could not be repeated.•Topological polar surface area possibly related to compound absorption.•A lipid based coating partially obviates compound absorption.•Presence of cultured cells affects free drug concentration, but less than substrate.
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