Direct coordination of pterin to FeII enables neurotransmitter biosynthesis in the pterin-dependent hydroxylases.

The pterin-dependent nonheme iron enzymes hydroxylate aromatic amino acids to perform the biosynthesis of neurotransmitters to maintain proper brain function. These enzymes activate oxygen using a pterin cofactor and an aromatic amino acid substrate bound to the FeII active site to form a highly reactive FeIV = O species that initiates substrate oxidation. In this study, using tryptophan hydroxylase, we have kinetically generated a pre-FeIV = O intermediate and characterized its structure as a FeII-peroxy-pterin species using absorption, Mössbauer, resonance Raman, and nuclear resonance vibrational spectroscopies. From parallel characterization of the pterin cofactor and tryptophan substrate-bound ternary FeII active site before the O2 reaction (including magnetic circular dichroism spectroscopy), these studies both experimentally define the mechanism of FeIV = O formation and demonstrate that the carbonyl functional group on the pterin is directly coordinated to the FeII site in both the ternary complex and the peroxo intermediate. Reaction coordinate calculations predict a 14 kcal/mol reduction in the oxygen activation barrier due to the direct binding of the pterin carbonyl to the FeII site, as this interaction provides an orbital pathway for efficient electron transfer from the pterin cofactor to the iron center. This direct coordination of the pterin cofactor enables the biological function of the pterin-dependent hydroxylases and demonstrates a unified mechanism for oxygen activation by the cofactor-dependent nonheme iron enzymes.

Effectiveness of a virtual patient simulation training on improving provider engagement in suicide safer care.

BACKGROUND: Health care providers have a critical opportunity to mitigate the public health problem of suicide. Virtual patient simulations (VPS) allow providers to learn and practice evidence-based suicide prevention practices in a realistic and risk-free environment. The purpose of this study was to test whether receiving VPS training increases the likelihood that providers will engage in effective suicide safer care practices. METHODS: Behavioral health and non-behavioral health providers (N = 19) at a Federally Qualified Health Center who work with patients at risk for suicide received the VPS training on risk assessment, safety planning, and motivation to engage in treatment. Providers' electronic health records were compared 6 months pre- and post-VPS training on their engagement in suicide safer care practices of screening, assessment, safety planning, and adding suicide ideation to the problem list. RESULTS: Most behavioral health providers were already engaging in evidence-based suicide prevention care prior to the VPS training. Findings demonstrated the VPS training may impact the likelihood that non-behavioral health providers engage in suicide safer care practices. CONCLUSION: VPS training in evidence-based suicide prevention practices can optimize and elevate all health care providers' skills in suicide care regardless of role and responsibility, demonstrating the potential to directly impact patient outcomes.

Nuclear Resonance Vibrational Spectroscopic Definition of the Fe(IV)2 Intermediate Q in Methane Monooxygenase and Its Reactivity.

Methanotrophic bacteria utilize the nonheme diiron enzyme soluble methane monooxygenase (sMMO) to convert methane to methanol in the first step of their metabolic cycle under copper-limiting conditions. The structure of the sMMO Fe(IV)2 intermediate Q responsible for activating the inert C-H bond of methane (BDE = 104 kcal/mol) remains controversial, with recent studies suggesting both "open" and "closed" core geometries for its active site. In this study, we employ nuclear resonance vibrational spectroscopy (NRVS) to probe the geometric and electronic structure of intermediate Q at cryogenic temperatures. These data demonstrate that Q decays rapidly during the NRVS experiment. Combining data from several years of measurements, we derive the NRVS vibrational features of intermediate Q as well as its cryoreduced decay product. A library of 90 open and closed core models of intermediate Q is generated using density functional theory to analyze the NRVS data of Q and its cryoreduced product as well as prior spectroscopic data on Q. Our analysis reveals that a subset of closed core models reproduce these newly acquired NRVS data as well as prior data. The reaction coordinate with methane is also evaluated using both closed and open core models of Q. These studies show that the potent reactivity of Q toward methane resides in the "spectator oxo" of its Fe(IV)2O2 core, in contrast to nonheme mononuclear Fe(IV)═O enzyme intermediates that H atoms abstract from weaker C-H bonds.

Structural characterization of a non-heme iron active site in zeolites that hydroxylates methane.

Iron-containing zeolites exhibit unprecedented reactivity in the low-temperature hydroxylation of methane to form methanol. Reactivity occurs at a mononuclear ferrous active site, α-Fe(II), that is activated by N2O to form the reactive intermediate α-O. This has been defined as an Fe(IV)=O species. Using nuclear resonance vibrational spectroscopy coupled to X-ray absorption spectroscopy, we probe the bonding interaction between the iron center, its zeolite lattice-derived ligands, and the reactive oxygen. α-O is found to contain an unusually strong Fe(IV)=O bond resulting from a constrained coordination geometry enforced by the zeolite lattice. Density functional theory calculations clarify how the experimentally determined geometric structure of the active site leads to an electronic structure that is highly activated to perform H-atom abstraction.

Virtual Music Therapy for Substance Use Disorders in a Federally Qualified Health Center.

BACKGROUND: Music therapy (MT) is an effective adjunctive treatment for substance use disorders (SUD), which is primarily available in inpatient treatment centers and rarely provided in outpatient primary care. METHODS: We evaluated the feasibility and acceptability of a virtual group MT program for SUD in a Federally Qualified Health Center (FQHC), and secondarily assessed patient perceptions of its effect. Feasibility was measured by implementation-related process measures, attendance and use of technology. Qualitative interviews eliciting participant perceptions were conducted to evaluate acceptability and effect. Mood scores, substance use and craving were measured before and after the intervention. RESULTS: Onboarding of the music therapist took 3.5 months. All MT sessions were attended by 1 to 5 individuals out of 6. Participants reported that group MT was "soothing" and "calming," gave them tools to treat cravings and stress, and created a sense of community. They reported that during sessions their cravings decreased. Anxiety and depression scores trended down, as did the number of days of substance use. They all stated they would seek out MT again. DISCUSSION: Our results suggest that remote group MT is feasible and acceptable to our FQHC patients with SUD. Patients reported an improvement in mood and their ability to manage stress, and a decrease in substance use. CONCLUSION: We wish to build on the results of this study to enhance our understanding of the effects of MT in the outpatient setting, and broaden our patients' access to MT in primary care.

A qualitative study of provider feedback on the feasibility and acceptability of virtual patient simulations for suicide prevention training.

Background: Healthcare organizations are often committed to preventing suicide among their patients, but they can struggle to adequately train providers and implement strategies grounded in evidence-based suicide prevention practices. Virtual patient simulations (VPS) offer the opportunity for providers at healthcare organizations and educational institutions to learn suicide prevention strategies using a realistic and risk-free environment. The purpose of this study was to gather feedback from leaders in the healthcare field regarding the feasibility and acceptability of VPS for their organizations. Methods: Participants (N=9) included administrators, managers, and educators from a variety of health care settings. They were invited to independently test the VPS and participate in a subsequent focus group to provide feedback. Participants were asked about VPS acceptability, satisfaction, potential fit within the intended context, feasibility of delivery, motivation to use, and likelihood of adoption. Responses were audio recorded and transcribed for coding and thematic analysis. Results: Themes emerged regarding perceived benefits of the VPS, considerations related to cost, barriers to implementation, and suggestions for improvement. Participants reported VPS trainings were acceptable and feasible, filling an important gap in the field especially around suicide safety planning, particularly for newer clinicians and students in training. Participants felt that this type of virtual training was particularly feasible given the recent increase in need for online trainings. Suggested improvements included the need to normalize the trial-and-error nature of the VPS for trainees prior to the start of the training, and to consider shortening the duration of the simulation due to learners not being able to bill for time while training. Conclusions: VPS may help to fill an important training need in the field of suicide prevention. The training suite may be best suited for certain settings, such as educational institutions, and most useful for populations including students and new clinicians. VPS may be particularly feasible for organizations that already utilize remote options for work and training.