Exon Skipping Therapy.

Exondys 51 is the first therapy for Duchenne muscular dystrophy (DMD) to have been granted accelerated approval by the FDA. Approval was granted based on using dystrophin expression as a surrogate marker. Exondys 51 targets DMD exon 51 for skipping to restore the reading frame for 13% of Duchenne patients.

Group 1 innate lymphoid-cell-derived interferon-γ maintains anti-viral vigilance in the mucosal epithelium.

The oropharyngeal mucosa serves as a perpetual pathogen entry point and a critical site for viral replication and spread. Here, we demonstrate that type 1 innate lymphoid cells (ILC1s) were the major immune force providing early protection during acute oral mucosal viral infection. Using intravital microscopy, we show that ILC1s populated and patrolled the uninfected labial mucosa. ILC1s produced interferon-γ (IFN-γ) in the absence of infection, leading to the upregulation of key antiviral genes, which were downregulated in uninfected animals upon genetic ablation of ILC1s or antibody-based neutralization of IFN-γ. Thus, tonic IFN-γ production generates increased oral mucosal viral resistance even before infection. Our results demonstrate barrier-tissue protection through tissue surveillance in the absence of rearranged-antigen receptors and the induction of an antiviral state during homeostasis. This aspect of ILC1 biology raises the possibility that these cells do not share true functional redundancy with other tissue-resident lymphocytes.

Listening to the Data: Computational Approaches to Addiction and Learning.

Computational approaches hold great promise for identifying novel treatment targets and creating translational therapeutics for substance use disorders. From circuitries underlying decision-making to computationally derived neural markers of drug-cue reactivity, this review is a summary of the approaches to data presented at our 2023 Society for Neuroscience Mini-Symposium. Here, we highlight data- and hypothesis-driven computational approaches that recently afforded advancements in addiction and learning neuroscience. First, we discuss the value of hypothesis-driven algorithmic modeling approaches, which integrate behavioral, neural, and cognitive outputs to refine hypothesis testing. Then, we review the advantages of data-driven dimensionality reduction and machine learning methods for uncovering novel predictor variables and elucidating relationships in high-dimensional data. Overall, this review highlights recent breakthroughs in cognitive mapping, model-based analysis of behavior/risky decision-making, patterns of drug taking, relapse, and neuromarker discovery, and showcases the benefits of novel modeling techniques, across both preclinical and clinical data.

Expert Consensus on Pediatric Urodynamics Reporting Using Modified Delphi Technique.

PURPOSE: Urodynamic testing (UDS) is an important tool in the management of pediatric lower urinary tract conditions. There have been notable efforts to standardize pediatric UDS nomenclature and technique, but no formal guidelines exist on essential elements to include in a clinical report. We sought to identify ideal structure and elements of a pediatric UDS assessment based on expert consensus. MATERIALS AND METHODS: Pediatric urologists regularly performing UDS were queried using a Delphi process. Participants were invited representing varied geographic, experience, and societal involvement. Participants underwent 3 rounds of questionnaires between November 2022 and August 2023 focusing on report organization, elements, definitions, and automated electronic health record clinical decision support. Professional billing requirements were also considered. Consensus was defined as 80% agreeing either in favor of or against a topic. Elements without consensus were discussed in subsequent rounds. RESULTS: A diverse sample of 30 providers, representing 27 institutions across 21 US states; Washington, District of Columbia; and Canada completed the study. Participants reported interpreting an average number of 5 UDS reports per week (range 1-22). The finalized consensus report identifies 93 elements that should be included in a pediatric UDS report based on applicable study conditions and findings. CONCLUSIONS: This consensus report details the key elements and structure agreed upon by an expert panel of pediatric urologists. Further standardization of documentation should aid collaboration and research for patients undergoing UDS. Based on this information, development of a standardized UDS report template using electronic health record implementation principles is underway, which will be openly available for pediatric urologists.

The Medicago SymCEP7 hormone increases nodule number via shoots without compromising lateral root number.

Legumes acquire soil nutrients through nitrogen-fixing root nodules and lateral roots. To balance the costs and benefits of nodulation, legumes negatively control root nodule number by autoregulatory and hormonal pathways. How legumes simultaneously coordinate root nodule and lateral root development to procure nutrients remains poorly understood. In Medicago (Medicago truncatula), a subset of mature C-TERMINALLY ENCODED PEPTIDE (CEP) hormones can systemically promote nodule number, but all CEP hormones tested to date negatively regulate lateral root number. Here we showed that Medicago CEP7 produces a mature peptide, SymCEP7, that promotes nodulation from the shoot without compromising lateral root number. Rhizobial inoculation induced CEP7 in the susceptible root nodulation zone in a Nod factor-dependent manner, and, in contrast to other CEP genes, its transcription level was elevated in the ethylene signaling mutant sickle. Using mass spectrometry, fluorescence microscopy and expression analysis, we demonstrated that SymCEP7 activity requires the COMPACT ROOT ARCHITECTURE 2 receptor and activates the shoot-to-root systemic effector, miR2111. Shoot-applied SymCEP7 rapidly promoted nodule number in the pM to nM range at concentrations up to five orders of magnitude lower than effects mediated by root-applied SymCEP7. Shoot-applied SymCEP7 also promoted nodule number in White Clover (Trifolium repens) and Lotus (Lotus japonicus), which suggests that this biological function may be evolutionarily conserved. We propose that SymCEP7 acts in the Medicago shoot to counter balance the autoregulation pathways induced rapidly by rhizobia to enable nodulation without compromising lateral root growth, thus promoting the acquisition of nutrients other than nitrogen to support their growth.

Multi-Factor Coral Disease Risk: A new product for early warning and management.

Ecological forecasts are becoming increasingly valuable tools for conservation and management. However, there are few examples of near-real-time forecasting systems that account for the wide range of ecological complexities. We developed a new coral disease ecological forecasting system that explores a suite of ecological relationships and their uncertainty and investigates how forecast skill changes with shorter lead times. The Multi-Factor Coral Disease Risk product introduced here uses a combination of ecological and marine environmental conditions to predict the risk of white syndromes and growth anomalies across reefs in the central and western Pacific and along the east coast of Australia and is available through the US National Oceanic and Atmospheric Administration Coral Reef Watch program. This product produces weekly forecasts for a moving window of 6 months at a resolution of ~5 km based on quantile regression forests. The forecasts show superior skill at predicting disease risk on withheld survey data from 2012 to 2020 compared with predecessor forecast systems, with the biggest improvements shown for predicting disease risk at mid- to high-disease levels. Most of the prediction uncertainty arises from model uncertainty, so prediction accuracy and precision do not improve substantially with shorter lead times. This result arises because many predictor variables cannot be accurately forecasted, which is a common challenge across ecosystems. Weekly forecasts and scenarios can be explored through an online decision support tool and data explorer, co-developed with end-user groups to improve use and understanding of ecological forecasts. The models provide near-real-time disease risk assessments and allow users to refine predictions and assess intervention scenarios. This work advances the field of ecological forecasting with real-world complexities and, in doing so, better supports near-term decision making for coral reef ecosystem managers and stakeholders. Secondarily, we identify clear needs and provide recommendations to further enhance our ability to forecast coral disease risk.

Age-related changes of deep-brain neurophysiological activity.

Cognitive decline with age is associated with brain atrophy and reduced brain activations, but the underlying neurophysiological mechanisms are unclear, especially in deeper brain structures primarily affected by healthy aging or neurodegenerative processes. Here, we characterize time-resolved, resting-state magnetoencephalography activity of the hippocampus and subcortical brain regions in a large cohort of healthy young (20-30 years) and older (70-80 years) volunteers from the Cam-CAN (Cambridge Centre for Ageing and Neuroscience) open repository. The data show age-related changes in both rhythmic and arrhythmic signal strength in multiple deeper brain regions, including the hippocampus, striatum, and thalamus. We observe a slowing of neural activity across deeper brain regions, with increased delta and reduced gamma activity, which echoes previous reports of cortical slowing. We also report reduced occipito-parietal alpha peak associated with increased theta-band activity in the hippocampus, an effect that may reflect compensatory processes as theta activity, and slope of arrhythmic activity were more strongly expressed when short-term memory performances were preserved. Overall, this study advances the understanding of the biological nature of inter-individual variability in aging. The data provide new insight into how hippocampus and subcortical neurophysiological activity evolve with biological age, and highlight frequency-specific effects associated with cognitive decline versus cognitive maintenance.

Racism-related stress and mental health among black women living in Los Angeles County, California: A comparison of postpartum mood and anxiety disorder screening scales.

PURPOSE: To assess Black women's exposure to and appraisal of racism-related stress during the postpartum period and to distinguish its impact on three indicators of postpartum mood and anxiety disorders (PMADs) symptoms. METHODS: Data from the Black Mothers' Mental Wellness Study (N = 231) and linear regression models estimated the associations between racism-related stress and the PMAD indicators: 3-item Edinburgh Postnatal Depression Scale (EPDS-3), 8-item Patient Health Questionnaire (PHQ-8), and PHQ-15. RESULTS: The majority of participants (80.5%, N = 186) experienced racism a few times a year or more, of which 37.1% (N = 69) were bothered somewhat and 19.3% (N = 36) a lot. Racism-related stress, income, level of education, and history of mental health diagnosis explained greater variance in PMAD symptoms as measured by the PHQ-8 score (R2 = 0.58, p = < 0.001) compared to the EPDS-3 (R2 = 0.46, p = < 0.001) or the PHQ-15 (R2 = 0.14, p = 0.035). CONCLUSIONS: Racism is a stressor for Black women living in Los Angeles County, California. Racism-related stress and emotional expression of PMAD symptoms were salient to the postpartum mental health of the Black women in this study. Findings from this study suggest that the PHQ-8 should be used to assess how racism impacts Black women's postpartum mental health.

Unlocking the future of patient Education: ChatGPT vs. LexiComp® as sources of patient education materials.

BACKGROUND: ChatGPT is a conversational artificial intelligence technology that has shown application in various facets of healthcare. With the increased use of AI, it is imperative to assess the accuracy and comprehensibility of AI platforms. OBJECTIVE: This pilot project aimed to assess the understandability, readability, and accuracy of ChatGPT as a source of medication-related patient education as compared with an evidence-based medicine tertiary reference resource, LexiComp®. METHODS: Patient education materials (PEMs) were obtained from ChatGPT and LexiComp® for 8 common medications (albuterol, apixaban, atorvastatin, hydrocodone/acetaminophen, insulin glargine, levofloxacin, omeprazole, and sacubitril/valsartan). PEMs were extracted, blinded, and assessed by 2 investigators independently. The primary outcome was a comparison of the Patient Education Materials Assessment Tool-printable (PEMAT-P). Secondary outcomes included Flesch reading ease, Flesch Kincaid grade level, percent passive sentences, word count, and accuracy. A 7-item accuracy checklist for each medication was generated by expert consensus among pharmacist investigators, with LexiComp® PEMs serving as the control. PEMAT-P interrater reliability was determined via intraclass correlation coefficient (ICC). Flesch reading ease, Flesch Kincaid grade level, percent passive sentences, and word count were calculated by Microsoft® Word®. Continuous data were assessed using the Student's t-test via SPSS (version 20.0). RESULTS: No difference was found in the PEMAT-P understandability score of PEMs produced by ChatGPT versus LexiComp® [77.9% (11.0) vs. 72.5% (2.4), P=0.193]. Reading level was higher with ChatGPT [8.6 (1.2) vs. 5.6 (0.3), P < 0.001). ChatGPT PEMs had a lower percentage of passive sentences and lower word count. The average accuracy score of ChatGPT PEMs was 4.25/7 (61%), with scores ranging from 29% to 86%. CONCLUSION: Despite comparable PEMAT-P scores, ChatGPT PEMs did not meet grade level targets. Lower word count and passive text with ChatGPT PEMs could benefit patients, but the variable accuracy scores prevent routine use of ChatGPT to produce medication-related PEMs at this time.

The Influence of Kynurenine Metabolites on Neurodegenerative Pathologies.

As the kynurenine pathway's links to inflammation, the immune system, and neurological disorders became more apparent, it attracted more and more attention. It is the main pathway through which the liver breaks down Tryptophan and the initial step in the creation of nicotinamide adenine dinucleotide (NAD+) in mammals. Immune system activation and the buildup of potentially neurotoxic substances can result from the dysregulation or overactivation of this pathway. Therefore, it is not shocking that kynurenines have been linked to neurological conditions (Depression, Parkinson's, Alzheimer's, Huntington's Disease, Schizophrenia, and cognitive deficits) in relation to inflammation. Nevertheless, preclinical research has demonstrated that kynurenines are essential components of the behavioral analogs of depression and schizophrenia-like cognitive deficits in addition to mediators associated with neurological pathologies due to their neuromodulatory qualities. Neurodegenerative diseases have been extensively associated with neuroactive metabolites of the kynurenine pathway (KP) of tryptophan breakdown. In addition to being a necessary amino acid for protein synthesis, Tryptophan is also transformed into the important neurotransmitters tryptamine and serotonin in higher eukaryotes. In this article, a summary of the KP, its function in neurodegeneration, and the approaches being used currently to target the route therapeutically are discussed.

SARS-CoV-2 Serosurveys: How Antigen, Isotype and Threshold Choices Affect the Outcome.

BACKGROUND: Evaluating the performance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological assays and clearly articulating the utility of selected antigens, isotypes, and thresholds is crucial to understanding the prevalence of infection within selected communities. METHODS: This cross-sectional study, implemented in 2020, screened PCRconfirmed coronavirus disease 2019 patients (n 86), banked prepandemic and negative samples (n 96), healthcare workers and family members (n 552), and university employees (n 327) for antiSARS-CoV-2 receptor-binding domain, trimeric spike protein, and nucleocapsid protein immunoglobulin (Ig)G and IgA antibodies with a laboratory-developed enzyme-linked immunosorbent assay and tested how antigen, isotype and threshold choices affected the seroprevalence outcomes. The following threshold methods were evaluated: (i) mean 3 standard deviations of the negative controls; (ii) 100 specificity for each antigen-isotype combination; and (iii) the maximal Youden index. RESULTS: We found vastly different seroprevalence estimates depending on selected antigens and isotypes and the applied threshold method, ranging from 0.0 to 85.4. Subsequently, we maximized specificity and reported a seroprevalence, based on more than one antigen, ranging from 9.3 to 25.9. CONCLUSIONS: This study revealed the importance of evaluating serosurvey tools for antigen-, isotype-, and threshold-specific sensitivity and specificity, to interpret qualitative serosurvey outcomes reliably and consistently across studies.

Robust Carborane-Based Metal-Organic Frameworks for Hexane Separation.

Hexane isomers play a vital role as feedstocks and fuel additives in the petrochemical industry. However, their similar physical and chemical properties lead to significant challenges in the separation process. Traditional thermal separation techniques are energy-intensive and lead to significant carbon footprint penalties. As such, there is a growing demand for the development of less energy-intensive nonthermal separation methods. Adsorption-based separation methods, such as using solid sorbents or membranes, have emerged as promising alternatives to distillation. Here, we report the successful synthesis of two novel metal-organic frameworks (MOFs), NU-2004 and NU-2005, by incorporating a carborane-based three-dimensional (3D) linker and using aluminum and vanadium nodes, respectively. These MOFs exhibit exceptional thermal stability and structural rigidity compared to other MIL-53 analogues, which is further corroborated using synchrotron studies. Furthermore, the inclusion of the quasi-spherical 3D linker in NU-2004 demonstrates significant advancements in the separation of hexane isomers compared to other MIL MOFs containing two-dimensional (2D) and aliphatic 3D linkers.

Engineering Metal-Organic Frameworks for Selective Separation of Hexane Isomers Using 3-Dimensional Linkers.

Metal-organic frameworks (MOFs) are highly tunable materials with potential for use as porous media in non-thermal adsorption or membrane-based separations. However, many separations target molecules with sub-angstrom differences in size, requiring precise control over the pore size. Herein, we demonstrate that this precise control can be achieved by installing a three-dimensional linker in an MOF with one-dimensional channels. Specifically, we synthesized single crystals and bulk powder of NU-2002, an isostructural framework to MIL-53 with bicyclo[1.1.1]pentane-1,3-dicarboxylic acid as the organic linker component. Using variable-temperature X-ray diffraction studies, we show that increasing linker dimensionality limits structural breathing relative to MIL-53. Furthermore, single-component adsorption isotherms demonstrate the efficacy of this material for separating hexane isomers based on the different sizes and shapes of these isomers.

Direct Oral Anticoagulants: Probability of Recurrent Venous Thromboembolism and Bleeding Risk in an Obese Population.

BACKGROUND: Direct-acting oral anticoagulants (DOACs) have become the preferred drugs for managing venous thromboembolism (VTE). Despite their advantages over vitamin K antagonists such as warfarin, their use in obese patients remains controversial with many providers reluctant to switch patients managed on warfarin. Outcome research that opts to increase provider confidence when prescribing DOACs for patients with obesity will be invaluable. OBJECTIVE: This investigation evaluated whether patients with a body mass index (BMI) 35 kg/m2 or greater who were prescribed a DOAC had a higher risk for a recurrent VTE or bleed event relative to warfarin. METHODS: The study was conducted in West Virginia which has the highest rate of obesity in the United States. RESULTS: Of the total study population (1633), 2.3% (37) had a recurrent thrombotic event, 5.5% (89) had a major bleed event, and 10.7% (174) had some type of bleeding event. No individual patient characteristic was associated with recurrent thrombosis-including BMI. Older age, antiplatelet use, and taking a medication with a theoretical risk of increasing the effect of DOACs were associated with any and major bleeding events. The use of warfarin was associated with major bleeding events more frequently versus a DOAC. Body mass index was not a predictor for recurrent VTE or any bleed or major bleed events. CONCLUSIONS: These findings support the conclusion that DOACs are an appropriate and effective drug class for the management of VTE in patients with obesity.

Nanoparticles systemically biodistribute to regenerating skeletal muscle in DMD.

Skeletal muscle disease severity can often progress asymmetrically across muscle groups and heterogeneously within tissues. An example is Duchenne Muscular Dystrophy (DMD) in which lack of dystrophin results in devastating skeletal muscle wasting in some muscles whereas others are spared or undergo hypertrophy. An efficient, non-invasive approach to identify sites of asymmetry and degenerative lesions could enable better patient monitoring and therapeutic targeting of disease. In this study, we utilized a versatile intravenously injectable mesoporous silica nanoparticle (MSNP) based nanocarrier system to explore mechanisms of biodistribution in skeletal muscle of mdx mouse models of DMD including wildtype, dystrophic, and severely dystrophic mice. Moreover, MSNPs could be imaged in live mice and whole muscle tissues enabling investigation of how biodistribution is altered by different types of muscle pathology such as inflammation or fibrosis. We found MSNPs were tenfold more likely to aggregate within select mdx muscles relative to wild type, such as gastrocnemius and quadriceps. This was accompanied by decreased biodistribution in off-target organs. We found the greatest factor affecting preferential delivery was the regenerative state of the dystrophic skeletal muscle with the highest MSNP abundance coinciding with the regions showing the highest level of embryonic myosin staining and intramuscular macrophage uptake. To demonstrate, muscle regeneration regulated MSNP distribution, we experimentally induced regeneration using barium chloride which resulted in a threefold increase of intravenously injected MSNPs to sites of regeneration 7 days after injury. These discoveries provide the first evidence that nanoparticles have selective biodistribution to skeletal muscle in DMD to areas of active regeneration and that nanoparticles could enable diagnostic and selective drug delivery in DMD skeletal muscle.

Discrimination during childbirth and postpartum care utilization among Black birthing people in California, United States.

BACKGROUND: The purpose of this study was to investigate the relationship between discrimination during childbirth hospitalization and postpartum care utilization among Black birthing people in California, United States. METHODS: This was a secondary analysis of data from the Listening to Mothers in California survey, a population-based survey of individuals with a singleton hospital-based birth in California in 2016. The primary outcome was number of postpartum care visits. The primary exposures were racial, language, and insurance discrimination. A multiple linear regression model was used to estimate associations between discrimination and postpartum care use, adjusting for sociodemographic covariates. RESULTS: Black birthing people in the sample had an average of two postpartum visits. Almost 15% of the sample reported one or more forms of discrimination during hospital-based childbirth. In adjusted models, racial discrimination (ß = 0.09, 95% CI = 0.04-0.14, p < 0.01) and language discrimination (ß = 1.03, 95% CI = 0.98-1.07, p < 0.01) were associated with increased postpartum visits, while insurance discrimination was linked to decreased postpartum visits (ß = -0.96, 95% CI = -1.04 to -0.89, p < 0.01). CONCLUSION: Among Black birthing people in California, the drivers of postpartum care utilization after childbirth are complex. There are multiple negative drivers (e.g., experiencing racial and language discrimination and unmet needs), barriers (e.g., insurance discrimination), and positive drivers (e.g., clinician type and education) that affect postpartum care utilization among Black birthing people.

Unique Considerations in Episodic Migraine: Underserved Populations.

PURPOSE OF REVIEW: Episodic migraine is a common and disabling neurological disorder that is underdiagnosed and undertreated. Additional barriers are put in place for those who belong to an underserved population. This could be based on race, ethnicity, gender, sexual orientation, or socioeconomic status. RECENT FINDINGS: There has been a lot of interest in understanding the extent of these disparities, but studies for many of these groups are lacking. More work is needed to understand the disparities and needs of underserved populations. Most of the literature has been done for Black populations but there are many other underserved communities that need assessment and intervention. The healthcare community needs to take action to improve support for populations with a higher incidence of migraine and disability, yet a lower rate of diagnosis and treatment. Some recommendations include awareness of biases, systemic changes, education, and including diverse populations in research and training.

Single position robot-assisted pedicle screw placement with S2-alar-iliac fixation in lateral decubitus: cadaveric feasibility study and early clinical experience.

OBJECTIVES: Single position lateral fusion with robotic assistance eliminates the need for surgical staging while harnessing the precision of robotic adjuncts. We expand on this technique by demonstrating the technical feasibility of placing bilateral pedicle screws with S2-alar-iliac (S2AI) fixation while in the lateral position. METHODS: A cadaveric study was performed using 12 human specimens. A retrospective clinical series was also performed for patients who had undergone robot-assisted placement of S2AI screws in lateral decubitus between June 2020 and June 2022. Case demographics, implant placement time, implant size, screw accuracy, and complications were recorded. Early postoperative radiographic outcomes were reported. RESULTS: In the cadaveric series, a total of 126 screws were placed with robotic assistance in 12 cadavers of which 24 screws were S2AI. There were four breaches from pedicle screws and none with S2AI screws for an overall accuracy rate of 96.8%. In the clinical series, four patients (all male, mean age 65.8 years) underwent single position lateral surgery with S2AI distal fixation. Mean BMI was 33.6 and mean follow-up was 20.5 months. Mean radiographic improvements were lumbar lordosis 12.3 ± 4.7°, sagittal vertical axis 1.5 ± 2.1 cm, pelvic tilt 8.5 ± 10.0°, and pelvic incidence-lumbar lordosis mismatch 12.3 ± 4.7°. A total of 42 screws were placed of which eight screws were S2AI. There were two breaches from pedicle screws and none from S2AI screws for an overall accuracy rate of 95.2%. No repositioning or salvage techniques were required for the S2AI screws. CONCLUSIONS: We demonstrate here the technical feasibility of single position robot-assisted placement of S2-alar-iliac screws in the lateral decubitus position for single position surgery.

Racial/ethnic differences in social support and health among Asian American and non-Hispanic White midlife women: Results from the Study of Women's Health Across the Nation (SWAN).

OBJECTIVE: Although prior research suggests Asian Americans experience physical health advantages relative to other racial/ethnic groups, increasing evidence points to health inequalities within Asian American subgroups. Disparities are especially pronounced among middle-aged Asian American women, who remain an understudied population, despite studies showing that midlife corresponds with distinct social stressors and changes in the availability of protective resources, such as social support. Thus, the purpose of the study was to examine racial/ethnic differences in social support and self-rated health (SRH) among middle-aged women. DESIGN: With data from the Study of Women's Health Across the Nation (SWAN; N = 1258), we used modified Poisson regression models to estimate incidence rate ratios (IRR), examining how social support shaped the risk of fair-to-poor SRH by race/ethnicity. We tested interactions between perceived stress, social support and race/ethnicity to determine whether the stress-buffering role of social support varies by group. RESULTS: Results demonstrate racial/ethnic differences in SRH. Higher levels of social support were linked to higher fair-to-poor SRH among Chinese American women (IRR = 1.24; 95% CI [1.02, 1.52]); while greater social support conferred lower risk among White women. Interaction analyses revealed additional nuances in the stress-buffering effects of social support among Chinese American women, such that the health benefits of social support depended on levels of perceived stress (IRR = 0.75; 95% CI [0.57, 1.00]). CONCLUSIONS: These findings highlight important distinctions in the ways that psychosocial factors shape health across racial/ethnic groups. In particular, this study helps advance our understanding of important subgroup differences in the stress-buffering role of social support for Asian American midlife women. Interventions should focus on identifying sources of social strain among Asian American women that can increase the risk for poor health and identify alternative sources of support that mitigate stressors to improve health.

Current published evidence on barriers and proposed strategies for genetic testing implementation in health care settings: A scoping review.

BACKGROUND: The slow uptake of genetic testing in routine clinical practice warrants the attention of researchers and practitioners to find effective strategies to facilitate implementation. OBJECTIVES: This study aimed to identify the barriers to and strategies for pharmacogenetic testing implementation in a health care setting from published literature. METHODS: A scoping review was conducted in August 2021 with an expanded literature search using Ovid MEDLINE, Web of Science, International Pharmaceutical Abstract, and Google Scholar to identify studies reporting implementation of pharmacogenetic testing in a health care setting, from a health care system's perspective. Articles were screened using DistillerSR and findings were organized using the 5 major domains of Consolidated Framework for Implementation Research (CFIR). RESULTS: A total of 3536 unique articles were retrieved from the above sources, with only 253 articles retained after title and abstract screening. Upon screening the full texts, 57 articles (representing 46 unique practice sites) were found matching the inclusion criteria. We found that most reported barriers and their associated strategies to the implementation of pharmacogenetic testing surrounded 2 CFIR domains: intervention characteristics and inner settings. Factors relating to cost and reimbursement were described as major barriers in the intervention characteristics. In the same domain, another major barrier was the lack of utility studies to provide evidence for genetic testing uptake. Technical hurdles, such as integrating genetic information to medical records, were identified as an inner settings barrier. Collaborations and lessons from early implementers could be useful strategies to overcome majority of the barriers across different health care settings. Strategies proposed by the included implementation studies to overcome these barriers are summarized and can be used as guidance in future. CONCLUSION: Barriers and strategies identified in this scoping review can provide implementation guidance for practice sites that are interested in implementing genetic testing.