Elucidating interprotein energy transfer dynamics within the antenna network from purple bacteria.

In photosynthesis, absorbed light energy transfers through a network of antenna proteins with near-unity quantum efficiency to reach the reaction center, which initiates the downstream biochemical reactions. While the energy transfer dynamics within individual antenna proteins have been extensively studied over the past decades, the dynamics between the proteins are poorly understood due to the heterogeneous organization of the network. Previously reported timescales averaged over such heterogeneity, obscuring individual interprotein energy transfer steps. Here, we isolated and interrogated interprotein energy transfer by embedding two variants of the primary antenna protein from purple bacteria, light-harvesting complex 2 (LH2), together into a near-native membrane disc, known as a nanodisc. We integrated ultrafast transient absorption spectroscopy, quantum dynamics simulations, and cryogenic electron microscopy to determine interprotein energy transfer timescales. By varying the diameter of the nanodiscs, we replicated a range of distances between the proteins. The closest distance possible between neighboring LH2, which is the most common in native membranes, is 25 Šand resulted in a timescale of 5.7 ps. Larger distances of 28 to 31 Šresulted in timescales of 10 to 14 ps. Corresponding simulations showed that the fast energy transfer steps between closely spaced LH2 increase transport distances by ∼15%. Overall, our results introduce a framework for well-controlled studies of interprotein energy transfer dynamics and suggest that protein pairs serve as the primary pathway for the efficient transport of solar energy.

Engineering Exciton Dynamics with Synthetic DNA Scaffolds.

Excitons are the molecular-scale currency of electronic energy. Control over excitons enables energy to be directed and harnessed for light harvesting, electronics, and sensing. Excitonic circuits achieve such control by arranging electronically active molecules to prescribe desired spatiotemporal dynamics. Photosynthetic solar energy conversion is a canonical example of the power of excitonic circuits, where chromophores are positioned in a protein scaffold to perform efficient light capture, energy transport, and charge separation. Synthetic systems that aim to emulate this functionality include self-assembled aggregates, molecular crystals, and chromophore-modified proteins. While the potential of this approach is clear, these systems lack the structural precision to control excitons or even test the limits of their power. In recent years, DNA origami has emerged as a designer material that exploits biological building blocks to construct nanoscale architectures. The structural precision afforded by DNA origami has enabled the pursuit of naturally inspired organizational principles in a highly precise and scalable manner. In this Account, we describe recent developments in DNA-based platforms that spatially organize chromophores to construct tunable excitonic systems. The high fidelity of DNA base pairing enables the formation of programmable nanoscale architectures, and sequence-specific placement allows for the precise positioning of chromophores within the DNA structure. The integration of a wide range of chromophores across the visible spectrum introduces spectral tunability. These excitonic DNA-chromophore assemblies not only serve as model systems for light harvesting, solar conversion, and sensing but also lay the groundwork for the integration of coupled chromophores into larger-scale nucleic acid architectures.We have used this approach to generate DNA-chromophore assemblies of strongly coupled delocalized excited states through both sequence-specific self-assembly and the covalent attachment of chromophores. These strategies have been leveraged to independently control excitonic coupling and system-bath interaction, which together control energy transfer. We then extended this framework to identify how scaffold configurations can steer the formation of symmetry-breaking charge transfer states, paving the way toward the design of dual light-harvesting and charge separation DNA machinery. In an orthogonal application, we used the programmability of DNA chromophore assemblies to change the optical emission properties of strongly coupled dimers, generating a series of fluorophore-modified constructs with separable emission properties for fluorescence assays. Upcoming advances in the chemical modification of nucleotides, design of large-scale DNA origami, and predictive computational methods will aid in constructing excitonic assemblies for optical and computing applications. Collectively, the development of DNA-chromophore assemblies as a platform for excitonic circuitry offers a pathway to identifying and applying design principles for light harvesting and molecular electronics.

Peer support during in vivo exposure homework increases likelihood of prolonged exposure therapy completion.

Exposure-based treatments such as prolonged exposure therapy (PE) are effective for veterans with PTSD. However, dropout rates as high as 50% are common. The Department of Veterans Affairs employs peers to increase mental health treatment engagement, however peers are not routinely used to help patients complete PE homework assignments. The present study included 109 veterans who decided to drop out from exposure-based treatment after completing seven or fewer sessions and used a randomized controlled design to compare PE treatment completion rates in response to 2 forms of peer support: (1) standard weekly telephone-based peer support vs. (2) peer-assisted in vivo exposure, wherein peers accompanied veterans (virtually or in person) during a limited number of in vivo exposure assignments. There were no differences between instrumental vs general peer support conditions as randomized. However, post hoc analyses indicated that 87% of those who completed at least one peer-assisted in vivo exposure completed treatment, compared to 56% of those not completing any peer-assisted in vivo exposure. The dose effect of peer-assisted in vivo exposure increased to 93% with 2 or more peer-assisted exposures, and 97% with 3 or more peer-assisted exposures. The present study suggests that augmenting PE with instrumental peer support during in vivo exposure homework may reduce dropout if completed. Future research should test whether the impact of peer-assisted in vivo exposure is enhanced when offered at the beginning of treatment as opposed to waiting until the point of dropout.

Low-calorie sweeteners cause only limited metabolic effects in mice.

There are widespread concerns that low-calorie sweeteners (LCSs) cause metabolic derangement. These concerns stem in part from prior studies linking LCS consumption to impaired glucose tolerance in humans and rodents. Here, we examined this linkage in mice. In experiment 1, we provided mice with chow, water, and an LCS-sweetened solution (saccharin, sucralose, or acesulfame K) for 28 days and measured glucose tolerance and body weight across the exposure period. Exposure to the LCS solutions did not impair glucose tolerance or alter weight gain. In experiment 2, we provided mice with chow, water, and a solution containing saccharin, glucose, or a mixture of both for 28 days, and tested for metabolic changes. Exposure to the saccharin solution increased the insulinemic response of mice to the glucose challenge, and exposure to the saccharin + glucose solution increased the rate of glucose uptake during the glucose challenge. However, neither of these test solutions altered glucose tolerance, insulin sensitivity, plasma triglycerides, or percent body fat. In contrast, exposure to the glucose solution increased glucose tolerance, early insulin response, insulin sensitivity, and percent body fat. We conclude that whereas the LCS-containing solutions induced a few metabolic changes, they were modest compared with those induced by the glucose solution.

Multi-scale heterogeneity in vegetation and soil carbon in exurban residential land of southeastern Michigan, USA.

Exurban residential land (one housing unit per 0.2-16.2 ha) is growing in importance as a human-dominated land use. Carbon storage in the soils and vegetation of exurban land is poorly known, as are the effects on C storage of choices made by developers and residents. We studied C storage in exurban yards in southeastern Michigan, USA, across a range of parcel sizes and different types of neighborhoods. We divided each residential parcel into ecological zones (EZ) characterized by vegetation, soil, and human behavior such as mowing, irrigation, and raking. We found a heterogeneous mixture of trees and shrubs, turfgrasses, mulched gardens, old-field vegetation, and impervious surfaces. The most extensive zone type was turfgrass with sparse woody vegetation (mean 26% of parcel area), followed by dense woody vegetation (mean 21% of parcel area). Areas of turfgrass with sparse woody vegetation had trees in larger size classes (> 50 cm dbh) than did areas of dense woody vegetation. Using aerial photointerpretation, we scaled up C storage to neighborhoods. Varying C storage by neighborhood type resulted from differences in impervious area (8-26% of parcel area) and area of dense woody vegetation (11-28%). Averaged and multiplied across areas in differing neighborhood types, exurban residential land contained 5240 ± 865 g C/m2 in vegetation, highly sensitive to large trees, and 13 800 ± 1290 g C/m2 in soils (based on a combined sampling and modeling approach). These contents are greater than for agricultural land in the region, but lower than for mature forest stands. Compared with mature forests, exurban land contained more shrubs and less downed woody debris and it had similar tree size-class distributions up to 40 cm dbh but far fewer trees in larger size classes. If the trees continue to grow, exurban residential land could sequester additional C for decades. Patterns and processes of C storage in exurban residential land were driven by land management practices that affect soil and vegetation, reflecting the choices of designers, developers, and residents. This study provides an example of human-mediated C storage in a coupled human-natural system.

Meta-analysis of single-case design research: Application of multilevel modeling.

This study describes the benefits and challenges of meta-analyses of single-case design research using multilevel modeling. The researchers illustrate procedures for conducting meta-analyses using four-level multilevel modeling through open-source R code. The demonstration uses data from multiple-baseline or multiple-probe across-participant single-case design studies (n = 21) on word problem instruction for students with learning disabilities published between 1975 and 2023. Researchers explore changes in levels and trends between adjacent phases (baseline vs. intervention and intervention vs. maintenance) using the sample data. The researchers conclude that word problem solving of students with learning disabilities varies based on the complexity of the word problem measures involving single-word problem, mixed-word problem, and generalization questions. These moderating effects differed across adjacent phases. These findings extend previous literature on meta-analyses methodology by describing how multilevel modeling can be used to compare the impacts of time-varying predictors within and across cases when analyzing single-case design studies. Future researchers may want to use this methodology to explore the roles of time-varying predictors as well as case or study-level moderators. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Tennessee hospital noncompliance with price transparency legislation for 8 common laboratory tests.

OBJECTIVES: The goal of this study was to assess hospital compliance with federal price transparency mandates and barriers to pricing information in Tennessee. METHODS: All hospitals websites were queried for gross, cash, and BlueCross BlueShield of Tennessee prices for 8 high-frequency laboratory tests in 2 Centers for Medicare & Medicaid Services-mandated pricing sources: (1) a machine-readable file of all available services and (2) a consumer-friendly display of 300 shoppable services. Barriers, including click counts, data availability, and intrahospital price discrepancies, were noted. RESULTS: Of the 145 Tennessee hospitals assessed, 97.2% were noncompliant with the Centers for Medicare & Medicaid Services final rule. Subanalysis of available machine-readable files, price estimators, and shoppable services files demonstrated 49.6%, 95.1%, and 78.6% noncompliance, respectively. Barriers to pricing information included requiring protected health information (55.9%), missing at least 1 pricing source (7.6%), having no pricing sources available (6.2%), and involving more than 3 clicks to access the cash price in machine-readable files (54.1%) and price estimators (68.6%.) Average intrahospital discrepancy for basic metabolic panel cash prices across pricing sources was $101.30 (range, $0-1012.40). CONCLUSIONS: Our study showed high levels of noncompliance with price transparency laws, inconsistent and inaccessible pricing, and continued challenges facing patients in Tennessee.

Differences in Receipt of Neurologist Evaluation During Hospitalization for Ischemic Stroke by Race, Sex, Age, and Region: The REGARDS Study.

BACKGROUND AND OBJECTIVES: Improving access to health care providers with clinical expertise in stroke care may influence the use of recommended strategies for reducing disparities in quality of care. Few studies have examined differences in the receipt of evaluation by neurologists during the hospital stay. We examined the proportion of individuals hospitalized for acute ischemic stroke who received evaluation by a neurologist during the hospital stay and characterized differences in receipt of neurologist evaluation by race (Black vs White), sex, age, and study region (Stroke Belt residence vs other) among those experiencing a stroke who were participating in a national cohort study. METHODS: This cross-sectional study was conducted using medical record data abstracted from 1,042 participants enrolled in the national Reasons for Geographic and Racial Differences in Stroke cohort study (2003-2007) who experienced an adjudicated ischemic stroke between 2003 and 2016. Participants with a history of stroke before baseline, in-hospital death, hospice discharge following their stroke, or incomplete records were excluded resulting in 839 cases. Differences were assessed using modified Poisson regression adjusting for participant-level and hospital-level factors. RESULTS: Of the 839 incident strokes, 722 (86%) received evaluation by a neurologist during the hospital stay. There were no significant differences by age, race, or sex, yet Stroke Belt residents and those receiving care in rural hospitals were significantly less likely to receive neurologist evaluation compared with non-Stroke Belt residents (relative risk [RR] 0.95; 95% CI 0.90-1.01) and participants receiving care in urban hospitals (RR 0.74; 95% CI 0.63-0.86). Participants with a greater level of poststroke functional impairment (modified Rankin scale) and those with a greater number of risk factors were more likely to receive neurologist evaluation compared with those with lower levels of poststroke functional impairment (RR 1.04; 95% CI 1.01-1.06) and fewer risk factors (RR 1.02; 95% CI 1.00-1.04). DISCUSSION: While differences in access to neurologists during the hospital stay were partially explained by patient need in our study, there were also significant differences in access by region and urban-rural hospital status. Ensuring access to neurologists during the hospital stay in such settings may require policy-level and/or system-level changes.

Sculpting photoproducts with DNA origami.

Natural light-harvesting systems spatially organize densely packed dyes in different configurations to either transport excitons or convert them into charge photoproducts, with high efficiency. In contrast, artificial photosystems like organic solar cells and light-emitting diodes lack this fine structural control, limiting their efficiency. Thus, biomimetic multi-dye systems are needed to organize dyes with the sub-nanometer spatial control required to sculpt resulting photoproducts. Here, we synthesize 11 distinct perylene diimide (PDI) dimers integrated into DNA origami nanostructures and identify dimer architectures that offer discrete control over exciton transport versus charge separation. The large structural-space and site-tunability of origami uniquely provides controlled PDI dimer packing to form distinct excimer photoproducts, which are sensitive to interdye configurations. In the future, this platform enables large-scale programmed assembly of dyes mimicking natural systems to sculpt distinct photophysical products needed for a broad range of optoelectronic devices, including solar energy converters and quantum information processors.

Improving function through primary care treatment of posttraumatic stress disorder study outcomes: A randomized controlled trial of prolonged exposure for primary care in veterans.

INTRODUCTION: Despite high cost and wide prevalence of posttraumatic stress disorder (PTSD) in veteran populations, and Veterans Health Administration (VA)-wide mental health provider training in evidence-based treatments for PTSD, most veterans with PTSD do not receive best practices interventions. This may be because virtually all evidence-based PTSD treatment is offered through specialty clinics, which require multiple steps and referrals to access. One solution is to offer PTSD treatment in VA primary care settings, which are often the first and only contact point for veterans. METHOD: The present study, Improving Function Through Primary Care Treatment of PTSD (IMPACT), used a randomized controlled design to compare an adaptation of prolonged exposure for PTSD to primary care (PE-PC) versus best practices Primary Care Mental Health Integration (PCMHI) clinic treatment as usual (TAU) in terms of both functioning and psychological symptoms in 120 veterans recruited between April 2019 and September 2021. RESULTS: Participants were mostly males (81.7%) with a mean age of 43.6 years (SD = 12.8), and more than half were non-White veterans (50.8%). Both conditions evinced significant improvement over baseline across functioning, PTSD, and depression measures, with no differences observed between groups. As observed in prior studies, PTSD symptoms continued to improve over time in both conditions, as measured by structured clinical interview. DISCUSSION: Both PE-PC and best-practices TAU are effective in improving function and reducing PTSD severity and depression severity. Although we did not observe differences between the two treatments, note that this study site and two PCMHI clinics employ primarily cognitive behavioral therapies (e.g., exposure and behavioral activation). (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Disparate statin prescribing following hospital discharge for stroke or transient ischemic attack: Findings from COMPASS.

BACKGROUND: Published guidelines recommend high-intensity statins following an ischemic stroke or transient ischemic attack (TIA). The authors examined the potential for disparate patterns of statin prescribing in a cluster randomized trial of transitional care following acute stroke or TIA. METHODS: Medications taken before hospitalization and statins prescribed at discharge among stroke and TIA patients at 27 participating hospitals were examined. Any statin and intensive statin prescribed at discharge were compared by age (<65, 65-75, >75 years), racial category (White vs. Black), sex (male vs. female), and rurality (urban vs. non-urban) using logistic mixed models. RESULTS: Among 3211 patients (mean age 67 years; 47% female; 29% Black), 90% and 55%, respectively, were prescribed any statin or intensive statin therapy at discharge. White (vs. Black) patients (0.71, 0.51-0.98) less commonly received any statin prescription, while stroke (vs. TIA) patients (1.90, 1.38-2.62) and those residing in urban areas (1.66, 1.07-2.55) more commonly received any statin prescription. Among those prescribed a statin, only 42% of White and 51% of Black patients >75 years. were prescribed an intensive statin; the OR for intensive statin prescribing was 0.44 for patients >75 years and was similar in a subgroup not on a statin previously. CONCLUSION/RELEVANCE: Following stroke or TIA, statin prescribing remains lower in White patients, in those with TIA, and in those in non-urban areas. Intensive statin prescribing remains limited, particularly in patients >75 years. These data may inform efforts to improve guideline concordant prescribing for post-stroke patients.

Observation of parallel intersystem crossing and charge transfer-state dynamics in [Fe(bpy)3]2+ from ultrafast 2D electronic spectroscopy.

Transition metal-based charge-transfer complexes represent a broad class of inorganic compounds with diverse photochemical applications. Charge-transfer complexes based on earth-abundant elements have been of increasing interest, particularly the canonical [Fe(bpy)3]2+. Photoexcitation into the singlet metal-ligand charge transfer (1MLCT) state is followed by relaxation first to the ligand-field manifold and then to the ground state. While these dynamics have been well-studied, processes within the MLCT manifold that facilitate and/or compete with relaxation have been more elusive. We applied ultrafast two-dimensional electronic spectroscopy (2DES) to disentangle the dynamics immediately following MLCT excitation of this compound. First, dynamics ascribed to relaxation out of the initially formed 1MLCT state was found to correlate with the inertial response time of the solvent. Second, the additional dimension of the 2D spectra revealed a peak consistent with a ∼20 fs 1MLCT → 3MLCT intersystem crossing process. These two observations indicate that the complex simultaneously undergoes intersystem crossing and direct conversion to ligand-field state(s). Resolution of these parallel pathways in this prototypical earth-abundant complex highlights the ability of 2DES to deconvolve the otherwise obscured excited-state dynamics of charge-transfer complexes.

Temperature Optimization Within 2 Uniquely Designed Courier Lockboxes During Extreme Summer Temperatures.

OBJECTIVES: To determine optimal temperature profiles for 2 uniquely designed courier lockboxes (steel vs polymer) by standardizing daily ice (-20ºC) and cold (4-8ºC) pack placement. METHODS: Paired courier lockboxes were placed outside in direct sunlight. Ambient outdoor and lockbox temperatures were monitored during 2 4-day cycles, and temperature mean and range were determined daily (time frame, 4:00-10:00 pm). Control lockboxes without packs were compared with experimental paired lockboxes with either 2 cold packs placed at 4:00 pm or 4 ice packs placed at 8:00 am and replaced with 4 cold packs at 4:00 pm daily. RESULTS: Cycle 1 mean temperatures within control steel and polymer lockboxes were 31.8ºC (range, 18.4-44.1ºC) and 37.2ºC (range, 27.1-46.7ºC), respectively. The addition of 2 cold packs at 4:00 pm reduced mean temperatures to 29.1ºC (range, 19.1-37.2ºC) and 25.3ºC (range, 20.0-31.6ºC) in steel and polymer boxes, respectively. Cycle 2 mean temperatures within control steel and polymer lockboxes were 28.3ºC (range, 22.4-40.8ºC) and 31.6ºC (range, 23.8-41.0ºC), respectively. The addition of 4 ice packs at 8:00 am and replacement with 4 cold packs at 4:00 pm reduced mean temperatures to 24.3ºC (range, 17.4-27.9ºC) and 13.4ºC (range, 6.6-18.1ºC) in steel and polymer boxes, respectively. CONCLUSIONS: Standardizing instructions for ice and cold packs can decrease internal courier lockbox temperatures.

Nontuberculous Mycobacteria Lung Disease (NTM-LD): Current Recommendations on Diagnosis, Treatment, and Patient Management.

Nontuberculous mycobacteria (NTM) are a group of ubiquitous environmental bacteria that can be found in soil, dust, and water. Mycobacterium avium complex (MAC) is the most common pathogen and the one most associated with chronic pulmonary disease. In recent years, the prevalence of Mycobacterium avium complex-related pulmonary disease (MAC-PD) has increased and is an emerging public health concern. This is due to a combination of environmental and geographic factors, dynamic changes in organism virulence and antimicrobial susceptibility, and evolving host susceptibility. Given the dynamic nature of the disease, management of NTM pulmonary disease (NTM-PD) often includes a multimodal approach including antimicrobial therapy, airway clearance techniques, limiting environmental exposures, and reducing susceptibility to NTM through prevention of reflux and maintenance of body weight. This review will explore the most recent concepts in the diagnosis, treatment, and management of individuals with NTM pulmonary infection.

Tuning Optical Absorption and Emission Using Strongly Coupled Dimers in Programmable DNA Scaffolds.

Molecular materials for light harvesting, computing, and fluorescence imaging require nanoscale integration of electronically active subunits. Variation in the optical absorption and emission properties of the subunits has primarily been achieved through modifications to the chemical structure, which is often synthetically challenging. Here, we introduce a facile method for varying optical absorption and emission properties by changing the geometry of a strongly coupled Cy3 dimer on a double-crossover (DX) DNA tile. Leveraging the versatility and programmability of DNA, we tune the length of the complementary strand so that it "pushes" or "pulls" the dimer, inducing dramatic changes in the photophysics including lifetime differences observable at the ensemble and single-molecule level. The separable lifetimes, along with environmental sensitivity also observed in the photophysics, suggest that the Cy3-DX tile constructs could serve as fluorescence probes for multiplexed imaging. More generally, these constructs establish a framework for easily controllable photophysics via geometric changes to coupled chromophores, which could be applied in light-harvesting devices and molecular electronics.

Improving function through primary care treatment of PTSD: The IMPACT study protocol.

Despite the availability of effective psychological interventions for PTSD, access to and retention in these interventions remains problematic. Of note, the Veterans Health Administration (VHA) developed and implemented post-deployment health surveys that screen for PTSD in primary care (PC), but effective PC-based, psychological intervention treatment options have yet to be established. To address the literal physical gap between where the patients first present for care (i.e., primary care) and where they must go to receive first-line treatment for PTSD (i.e., specialty mental health), study investigators developed a 4-6 visit Prolonged Exposure for Primary Care (PE-PC) treatment that has shown efficacy in reduction of PTSD. To extend previous work to recovery-based mental health care, the Improving Function Through Primary Care Treatment of PTSD (IMPACT) study examined function as assessed by the World Health Organization Disability Assessment Schedule [WHODAS 2.0; (Axelsson, Lindsäter, Ljótsson, Andersson, & Hedman-Lagerlöf, 2017)]. Veterans presenting in VHA primary care mental health integration (PCMHI) clinics with PTSD or significant subsyndromal PTSD who met minimal inclusion and exclusion criteria were randomly assigned to PE-PC or treatment as usual (TAU). If proven effective in improving function, PE-PC would provide a new access point for high quality PTSD care and allow greater numbers of veterans to access effective PTSD treatment. Trial Registration: http://ClinicalTrials.gov: NCT03581981.