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Centers for Disease Control and Prevention - ERA

PURPOSENIOSH intends to support the Centers of Excellence in Total Worker Health (TWH). These Centers will conduct rigorous research and translation activities to prevent harmful exposures, improve working conditions, and advance worker well-being. The Centers will develop practical, scalable solutions for employers and workers. All projects must use the NIOSH Worker Well-Being Questionnaire (WellBQ) and share data with the HERO Worker Well-Being Clearinghouse. Large Research Projects require economic evaluation. PRIORITY AREAS High-risk occupations: First responders, vehicle mechanics, and technicians, with emphasis on occupational exposures, related health risks, and prevention strategies Young workers, SMEs Chronic disease Mental health, stress Substance use disorder Artificial intelligence (AI), digital technologiesThis is a multi-component NOFO.COMPONENT STRUCTUREPercentages indicate maximum share of total budget.Overall Component (Required)Provides Center leadership and integration. Applicants should show strong coordination, scientific direction, and alignment across projects.Administration, Evaluation, and Emerging Issues Core (Required; up to 15%)Supports management and Center-wide evaluation. Applicants should describe oversight, data governance, and quality assurance.Optional activities include emerging issues and shared research resources.Outreach, Dissemination, and Impact Core (Required; up to 15%)Supports communication, worker/employer engagement, training, translation, implementation, and dissemination strategies.Research Projects (Required; about 60 to 70%)Includes all research activities. Applicants may propose a mix of projects. Research project distinctions are based on scope and complexity rather than cost. Projects should demonstrate scientific rigor and potential for sustained impact.Small Research Projects (Required; at least one project; up to 3 years)Exploratory, feasibility, early-stage intervention, surveillance, or measurement studies.Priority areas: high-risk occupations, young workers, SMEs.Should show innovation and potential to expand. Large Research Projects (Required; at least one project; up to 5 years)Multiyear etiologic, mechanistic, intervention, or translational studies.Priority areas: chronic disease, mental health, substance use disorder. Economic evaluation is required. Projects should include strong design and analytic plans. Pilot/Feasibility Program (Optional; 12 18 months) Short-term studies generating preliminary data or testing AI/digital technology approaches.

Centers for Disease Control and Prevention - ERA

<p><strong>PURPOSE</strong><br>NIOSH intends to support the Centers of Excellence in Total Worker Health® (TWH).&nbsp;These Centers will conduct rigorous research and translation activities to prevent harmful exposures, improve working conditions, and advance worker well-being. The Centers will develop practical, scalable solutions for employers and workers. All projects must use the NIOSH Worker Well-Being Questionnaire (WellBQ) and share data with the HERO Worker Well-Being Clearinghouse. Large Research Projects&nbsp;require&nbsp;economic evaluation.&nbsp;</p><p><strong>PRIORITY AREAS</strong><br>• High-risk occupations: First responders, vehicle mechanics, and technicians, with emphasis on occupational exposures, related health risks, and prevention strategies<br>• Young workers, SMEs&nbsp;<br>• Chronic disease<br>• Mental health, stress<br>• Substance use disorder<br>• Artificial intelligence (AI), digital technologies</p><p>This is a multi-component NOFO.</p><p><strong>COMPONENT STRUCTURE</strong><br>Percentages indicate maximum share of total budget.</p><p><strong>Overall Component (Required)</strong><br>Provides Center leadership and integration. Applicants should show strong coordination, scientific direction, and alignment across projects.</p><p><strong>Administration, Evaluation, and Emerging Issues Core (Required; up to 15%)</strong><br>Supports management and Center-wide evaluation. Applicants should describe oversight, data governance, and quality assurance.Optional activities include emerging issues and shared research resources.</p><p><strong>Outreach, Dissemination, and Impact Core (Required; up to 15%)</strong><br>Supports communication, worker/employer engagement, training, translation, implementation, and dissemination strategies.</p><p><strong>Research Projects (Required; about 60 to 70%)</strong><br>Includes all research activities. Applicants may propose&nbsp;a mix of&nbsp;projects.&nbsp;Research project distinctions are based on scope and complexity rather than cost. Projects should demonstrate scientific rigor and potential for sustained impact.</p><ul><li data-list-item-id="ea042ead4bda90f7afca9db4ed6265ccb"><i><strong>Small Research Projects (Required; at least one project; up to 3 years)</strong></i><br>Exploratory, feasibility, early-stage intervention, surveillance, or measurement studies.<br>Priority areas: high-risk occupations, young workers, SMEs.<br>Should show innovation and potential to expand.&nbsp;</li><li data-list-item-id="eab66fe3983b477c58a224d9b02cf204c"><i><strong>Large Research Projects (Required; at least one project; up to 5 years)</strong></i><br>Multiyear etiologic, mechanistic, intervention, or translational studies.<br>Priority areas: chronic disease, mental health, substance use disorder.&nbsp;<br>Economic evaluation&nbsp;is required. Projects should include strong design and analytic plans.&nbsp;</li><li data-list-item-id="ed259d50833d70d74aa5cc6f2b4cd83d6"><i><strong>Pilot/Feasibility Program (Optional; 12–18 months)</strong></i>&nbsp;<br>Short-term studies generating preliminary data or testing AI/digital technology approaches.</li></ul>

NHLBI - National Heart Lung and Blood Institute

PROJECT SUMMARY The lack of non-invasive, real-time assessments of circadian rhythm metrics hinders the translation of circadian rhythm knowledge into clinical practice. Circadian rhythms are internal physiological processes that cycle every ~24 hours. Light is the most potent stimulus for circadian rhythm entrainment to environmental time. Misalignment of the circadian system with environmental time increases the risk of both chronic diseases (e.g., cardiovascular disease, obesity) and acute mental and physical health impairments, underscoring the need for accessible clinical assessment tools. The mechanisms underlying individual variability in circadian (mis)alignment are unclear; one potential mechanism would involve variations in how light is processed in the eye. This project will test the hypothesis that differences in multiple metrics of pupillary response to light stimuli will correlate with differences in circadian metrics – and be a potential biomarker for individual differences. Wavelength, duration, and intensity of light differentially affect the response of retinal image-forming (e.g., rods, cones) cells and non-image-forming (NIF) intrinsically photosensitive retinal ganglion cells (ipRGCs) that contain melanopsin. The NIF pathway is crucial for circadian entrainment to environmental time and impacts the pupillary light reflex, melatonin concentrations, and other physiology. Variations in the post-illumination pupillary response (PIPR), an ipRGC- linked response, have been linked to neurological conditions, including circadian rhythm sleep-wake disorders (CRSWD), suggesting that pupillary response could be used as a potential non-invasive close-to-real-time diagnostic and monitoring tool. Relationships between pupil responses during and after light stimuli and circadian timing metrics should be established. Our specific aims are to quantify (i) different metrics of pupil response during and after light stimuli of various intensities, wavelengths, and durations (ii) and their relationships with dim-light melatonin onset (DLMO, the current gold standard measurement for circadian phase) (Aim 1) and in individuals with two intrinsic circadian sleep-wake phase disorders (CSWPD) with altered sleep timing (Aim 2). An outpatient week of monitoring of sleep timing will be immediately followed by the inpatient protocol for both participant groups (Aim 1, healthy controls, leveraging a funded R01 experiment; Aim 2: Individuals with CRSWD funded with the F32 funds). The inpatient protocol will consist of multiple pupillometry sessions and an evening saliva collection for DLMO. During pupillometry, participants will be exposed to wavelengths of light designed to target the ipRGC cells (blue light) or not (red light) with a matched number of photons of different intensities and durations. This F32 award will incorporate training in the measurement and analysis of physiological measures, circadian rhythms, and photobiology, phenotyping of people with CSWPD, advanced statistical training, grant and manuscript writing, scientific communication, and lab management. Establishing a strong foundation in these areas will facilitate Dr. McCullar’s transition to an independent scientist uniquely poised to establish outpatient testing that provides non-invasive close-to-real- time assessments of circadian metrics that can be used to evaluate and monitor individuals with circadian (or other NIF- linked) pathologies, as well as tools to help facilitate the integration of circadian system monitoring into clinical practice.

NIMH - National Institute of Mental Health

Project Summary Recent genetic studies of intellectual disability (ID), autism spectrum disorder (ASD), and epilepsy (EPI) have revealed a significant association of these disorders with genes encoding proteins involved in glutamatergic synapse structure and function. One key protein known to regulate glutamatergic synapses is SynGAP1, a RasGAP critical for synaptic plasticity, learning, memory, and cognition. Deleterious mutations in SYNGAP1 in humans result in intellectual disability, autistic-like behaviors, and epilepsy. Knock-in model mice with mutations found in humans and heterozygous Syngap1 knock-out mice exhibit deficits in synaptic plasticity, learning, and memory, as well as seizures. We have recently discovered that the catalytic activity of SynGAP1's GAP domain is not required for synaptic plasticity and normal behavior in mice. Instead, SynGAP1 plays a unique structural role at the synapse, forming complexes with synaptic scaffolding proteins and dynamically regulating synapse structure and function. In addition, we have recently discovered that the mRNA splicing of the α1 splice variant of SynGAP1, the most significant isoform of SynGAP1 for synaptic complex formation and synaptic plasticity, occurs through a unique non-canonical splicing mechanism. Here, using a combination of molecular biological, biochemical, cell biological, and in vivo studies, we propose to investigate the structure and function of SynGAP1 critical for synapse complex formation, synaptic plasticity, and cognition. Moreover, using molecular biological, cell biological, and in vivo studies, we will characterize the molecular mechanisms underlying the unique noncanonical splicing of SYNGAP1 required for synapse complex formation, synaptic plasticity, and cognition. These studies will not only reveal novel mechanisms underlying the regulation of SynGAP1 function but will also uncover new pathways and candidates for therapies to cure SYNGAP1-related Intellectual Disability (SRID) and other SynGAP1-related disorders.

NIMH - National Institute of Mental Health

PROJECT SUMMARY/ABSTRACT Sensory processing difficulties are one of the biggest challenges to daily life for individuals with autism spectrum disorder (ASD). Sensory reactivity can be considered a biological response to sensory stimuli, for which individuals can vary continuously from low to high responses, for example in terms of heart rate reactivity or neural responses. We hypothesize that sensory over-responsivity (SOR), an extreme negative behavioral or affective response to everyday stimuli, emerges from early alterations in sensory reactivity and may be detected in the first six months of life. Understanding and identifying SOR emergence early in life has important implications for early intervention and limiting the extent to which SOR impairs other key developmental processes, such as social and language development, participation in school and the community, and overall well-being. Yet very few standardized, behavioral measures of SOR exist across the lifespan, and to our knowledge, no such measure exists for infants in the first 6 months of life, when these essential functions are in a key period of development. We propose to fill this critical research gap by identifying physiological (heart rate) responses to sensory stimuli and testing our hypothesis that atypical biological sensory reactivity is present and measurable before clear behavioral responses to sensory stimuli emerge. First, we will examine two existing datasets to: 1) identify candidate physiological markers of SOR in 3-month-old infants at low (LL) and elevated (EL) familial likelihood for ASD and 2) examine longitudinal changes in behavioral responses to sensory stimuli during a standardized sensory task in LL and EL infants between 6-24 months. Then, we will develop and pilot a series of standardized, naturalistic prompts that can be used to study physiological responses to aversive sensory stimuli in the first 6 months of life. Identification of physiological markers of SOR in the first 6 months would promote earlier detection of atypical development, with implications for supporting infants with atypical sensory reactivity much earlier in life, before the core features of ASD emerge.

NIMH - National Institute of Mental Health

Abstract Despite the effectiveness of antiretroviral therapies (ART) in reducing systemic HIV viral loads, central nervous system (CNS) dysfunction remains prevalent in 30-50% of people living with HIV (PWH). ART does not eliminate viral reservoirs in the CNS, leading to chronic neuroimmune dysfunction and conditions like HIV-associated neurocognitive disorder (HAND). Current preclinical research has primarily focused on models that simulate acute HIV infection, but there is a pressing need for models that accurately reflect CNS dysfunction in the context of chronic ART-suppressed infections. Recent advancements in immunodeficient mouse models with humanized immune systems have shown promise, allowing for natural HIV infection and crossing of the blood-brain barrier. These models have provided insights into HIV infection in the CNS and the role of human microglia cells. However, significant gaps remain, particularly in developing models that incorporate multiple human CNS cell types and accurately represent chronic infection dynamics. This proposal aims to develop preclinical NeuroHIV models that better mimic CNS-immune interactions in general and in particular during ART suppression. Specifically, our goal is to develop the next generation NeuroHIV model composed of autologous peripheral human immune cells, relevant human glial cell types, and an intact blood-brain barrier all in the context of ART-mediated HIV suppression.

NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development

Maternal prenatal stress and nutrition influence fetal growth and long-term child outcomes. Maternal perceived stress and undernutrition frequently co-occur and affect overlapping biological stress pathways related to oxidative stress, Still, little is known about the interactive effects of maternal prenatal stress and nutrition on fetal and long-term child outcomes and neurological development. The proposed R00 research will leverage data from the “Enhancing Nutrition and Antenatal Infection Treatment for Maternal and Child Health” (ENAT) trial to examine interactive effects of maternal prenatal stress and nutrition intervention on long-term child outcomes. The ENAT study randomized n=2390 pregnant women to receive an “enhanced nutrition” package or “standard care” and collected data on maternal prenatal stress (Cohen’s Perceived Stress Scale) throughout the pre- and postnatal period. Using data from ENAT, we will determine independent and interactive effects of maternal prenatal perceived stress and nutrition intervention on children’s cognitive and neural developmental at 24 months of age. Child outcomes will include stress-sensitive outcomes previously shown to be sensitive to early life adversity, including attention, memory, and language. We will also use electroencephalography (EEG) to examine neural oscillation across different frequency bands as an index of neural maturation. To study underlying biological pathways, we will use maternal and infant blood samples examine whether maternal and newborn telomere lengths may serve as biomarkers of in-utero programming of birth and child outcomes in relation to maternal prenatal perceived stress and nutrition. We hypothesize that higher levels of maternal prenatal stress will be associated with poorer cognitive and neural oscillatory child outcomes. Telomeres are non-coding tandem repeats at the end of the chromosomes that maintain genome and cell integrity. Telomeres erode over time and stress and poor nutrition can lead to accelerated erosion and cellular aging. Children with low birthweight have been found to have shorter telomeres. We therefore hypothesize that effects of prenatal stress on birth and child outcomes will be mediated by maternal and newborn telomere length, but that such associations will be attenuated in offspring of women who received nutrition intervention This R00 will enable me to lead an innovative research program in child neurodevelopment and establish me as a leader and innovative scholar utilizing advanced methods to uncover mechanistic processes that shape childhood development in domestic and global settings. The proposed research aligns with NICHD’s goal to set a foundation for healthy pregnancies and lifelong living. We will generate epidemiologic and biologic evidence linking maternal prenatal nutrition and stress with newborn and childhood outcomes that are sensitive to prenatal stress and form long-term outcomes related to school achievement and mental health. We will use this knowledge to guide public health decisions regarding pre- and postnatal intervention both domestically and globally, and to develop future intervention to support optimal child development and health.

NIA - National Institute on Aging

PROJECT SUMMARY As the burden of Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD) grows, understanding how occupational factors impact brain and cognitive health is critical. However, research on the role of occupational stimulation, such as occupational complexity, remains inconclusive, and the impact of occupational stressors on cognitive and brain health has yet to be explored. Jobs with repetitive tasks, low autonomy, and high physical demands may contribute to cognitive decline, brain atrophy, and increased dementia risk. Furthermore, there is a lack of evidence on how these factors specifically impact US Latinos, who are often employed in low-wage occupations and face a higher risk of AD/ADRD. Understanding how occupational stressors and complexity affect cognitive and brain aging among US Latinos, is crucial. The overarching research objectives of this proposal are: (1) to investigate how physical and mental occupational stressors affect mid-life cognitive function in US immigrant Latinas in rural and semi-rural areas – an underrepresented group in research, and (2) to disentangle the effects of occupational complexity from physical occupational stressors on brain and cognitive health in US Latinos, considering effect heterogeneity by Latin American heritage, and US nativity. The central hypothesis is that higher occupational complexity promotes cognitive and brain health, but occupational stressors may outweigh benefits. To address these objectives, I will (1) estimate the longitudinal effect of physical and mental occupational stressors from early adulthood to midlife on cognitive function; (2) estimate the individual effects of physical occupational stressors and occupational complexity on AD/ADRD neuroimaging biomarkers and (3) estimate the individual and joint effects of hypothetical interventions on physical occupational stressors and occupational complexity on cognitive function, cognitive decline, and mild cognitive impairment, and evaluate effect heterogeneity by sex, Latin American heritage, and US nativity. I will use data from two NIA-funded studies: (1) Center for the Health Assessment of Mothers and Children of Salinas Maternal Cognition Study and the Hispanic Community Health Study/Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA), and ancillary study SOL-INCA-MRI. Under the guidance of a multidisciplinary mentorship team, the accompanying training plan builds on my background in medicine, epidemiology and statistical methods with additional training in (1) occupational epidemiology; (2) measuring and modeling cognitive function on Spanish-speaking/bilingual communities; (3) neuroimaging biomarkers for AD/ADRD research. The combined research and training plans will prepare me to become a successful researcher integrating clinical expertise, cutting-edge epidemiologic methods, and social science theories to understand social drivers of AD/ADRD. The findings will uncover the mechanisms linking occupational exposures and AD/ADRD and inform interventions and policies to reduce AD/ADRD by improving working conditions.

NIAID - National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY Chronic obstructive pulmonary disease (COPD) is characterized by decreased lung function and increased inflammation, punctuated by periods of increased coughing and shortness of breath known as exacerbations. Exacerbated COPD results in not only a hastening of lung decline but also a decline in the quality of life and mental health of patients. The obligate human pathogen nontypeable Haemophilus influenzae (NTHi) is the primary cause of exacerbated COPD, responsible for a minimum of ~30% of all exacerbations. The macrolides azithromycin and clarithromycin are predominantly prescribed to treat NTHi-complicated COPD due to its broad activity and immunomodulatory effects that decrease inflammation and the prevalence of future exacerbations. However, due to intrinsic factors and acquired mutations, macrolide treatment is becoming less effective against this bacterial pathogen. The primary objective of this proposal is to optimize the current treatment method for NTHi-exacerbated COPD by addressing established macrolide resistance and the ability to gain macrolide resistance while maintaining the benefits of macrolides. We performed a Tn-Seq screening to identify genes necessary for intrinsic resistance to clarithromycin and cross-referenced the results with those of another screening our lab performed for genes necessary for infection in the murine lung to explore the idea that drugs targeting proteins with dual requirements for both conditions would restore sensitivity to resistant strains and would constrain potential escape mutations. We characterized the gene encoding for the outer membrane protein Omp26, homolog of the E. coli periplasmic chaperone Skp, and found that deletion of omp26 resulted in susceptibility to clarithromycin in strains overexpressing the macrolide efflux pump AcrAB and that Omp26 plays a role in resistance to the human complement system. I hypothesize that targeting macrolide intrinsic resistance factor Omp26 in NTHi can be exploited to make NTHi more sensitive to macrolides and to host immune clearance mechanisms and potentially restore macrolide sensitivity to resistant strains. Experiments proposed in Aim 1 will investigate the function of Omp26 by defining its role in serum resistance, examining how it contributes to the composition of outer membrane proteins, and performing a survey of the necessity of Omp26 for infection in the murine lung across multiple strains of NTHi. Aim 2 will address the effect Omp26 has on major lung virulence associated phenotypes including heavy metal resistance, acquisition of host-sequestered nutrients, and resistance to oxidative stress. Finally, the experiments proposed in Aim 3 will determine the efficacy of targeting Omp26 in macrolide resistant clinical NTHi isolates with ribosomal mutations. Collectively, this data will contribute to further studies in the role periplasmic chaperones play in virulence and provide the framework necessary for the designing of in vitro assays based on the identified mechanisms of Omp26 to screen for future drugs for the treatment of nontypeable H. influenzae-exacerbated COPD.

NIMH - National Institute of Mental Health

Project Summary Suicide is currently the second leading cause of death amongst adolescents. Interpersonal dysfunction is a significant risk factor for suicidal thoughts and behaviors (STBs), but it is primarily assessed through self-report methods that are inherently problematic due to subjective retrospective recall bias. By depending on self-report of interpersonal functioning, we overlook crucial information about how at-risk youth are interacting with others. To address these gaps, this K23 proposes mentorship in online social networking (OSN) as an objective, ecologically valid assessment of interpersonal behavior (i.e., texting, engagement on social media) in adolescents with STBs. The research aims of the study are to (1) establish active online interpersonal behavior mechanisms in adolescents with STBs, (2) determine passive online interpersonal behavior mechanisms in adolescents with STBs, and (3) identify mediators (e.g., psychopathology, biological sex) relevant to the relationship between OSN and STBs. Multimodal data (OSN, self/parent/clinician report) will be collected from N=84 13–17-year-olds, with the full range of STBs. One month of active (i.e., texting/posting frequency) and passive (i.e., ratio of time spent on apps to texting, inter-day app/platform switching) OSN data will be collected from adolescents’ smartphones and analyzed using mentored statistical approaches to multimodal data including structural equation modeling (SEM). The candidate proposes training in (1) use of OSN as a real- world assessment of interpersonal functioning behaviors in adolescents, (2) gaining expertise in the relationship between STBs and OSN in adolescents, and (3) gaining skills with relevant multimodal data analysis (e.g., SEM) to understand what psychosocial factors may mediate OSN behavioral mechanisms and suicide risk. A team of multi-disciplinary mentors bring expertise in adolescent developmental psychopathology, computer science, interpersonal functioning, and translational research. Combined with the relevant and diverse resources available at McLean Hospital and Harvard Medical School will ensure this candidate receives the necessary training and support to successfully complete the project and launch the candidate’s career in adolescent suicide prevention. Data will directly inform future R01s leveraging this information to prevent suicide risk in adolescents, including (1) probing diagnostic/assessment specificity, (2) using experimental therapeutics to evaluate change in detected interpersonal behavior mechanisms following established evidence-based treatments for STBs, and (3) the development of mechanism-informed just-in-time adaptive social media/mobile health interventions. Completion of the proposed research and training goals will uniquely position the candidate to become a leader in the highly relevant field of adolescent social media and suicide prevention.

NIMH - National Institute of Mental Health

PROJECT SUMMARY The mammalian brain has up to 100 trillion synapses, representing an immense potential reservoir for information storage. Most theories of memory storage in the brain assume that memories are stored by changes in synaptic strength but, despite decades of work on synaptic plasticity and neuromodulation, and tantalizing progress the best understood mechanisms that change synaptic strength have yet been shown to underlie memory storage in the intact brain. A key reason is the challenge of measuring and manipulating synaptic strength at identified synapses at the population scale during learning. These challenges can now be addressed by new technologies for imaging and manipulating synaptic function at scale during behavior. We propose here to make a major advance in synaptic manipulation. Optogenetics has revolutionized neural circuit analysis by enabling stimulation or inhibition of action potential firing in select neurons. Chemical optogenetics has extended optical control to the synapse by enabling light- activation and ilght-block of the receptors that mediate synaptic transmission, plasticity and neuromodulation. Synthetic photoswitches have been developed to control ionotropic receptors for fast signaling and G protein coupled receptors for neuromodulation. The number of receptors has expanded greatly in the past 5 years, and there has been great success in using these in the brain of awake behaving animals from flies to fish to mouse. We propose to make a quantum leap in the precision of synapse control through new schemes for targeting optical control of receptors to specific synaptic compartments and specific classes of synaptic connections. Each neurotransmitter has multiple receptors, creating great complexity. The difficulty for analysis is increased by the fact the same receptor may be found on multiple cells in a circuit and, in fact, in more than one location in a particular cell, with distinct function at each location. Our method enables us to selectively control receptors in a genetically selected manner. We now add the ability to restrict control to one compartment in the cell: say the presynaptic site, where transmitter release is regulated, or the postsynaptic site, where the response to transmitter is regulated. We add to this, methods for enhancing penetration of control light through brain tissue— a key step to reduce invasiveness of implanted fiber optics and to ease the transition of the application to larger brains. The project is made possible by an inter-disciplinary collaboration between molecular and cell biologist Isacoff and synthetic chemist Trauner, who co-developed chemical optogenetics have collaborated extensively since, physical chemist Cohen, a pioneer in upconverting nanoparticles that turn IR light into visible light, and circuit neuroscientist Lammel, an expert in optogenetic and behavioral analysis.

National Institutes of Health

This Notice of Funding Opportunity (NOFO) invites applications from clinical centers to participate in a consortium to test anti-obesity medication (AOM) treatment strategies for youth with obesity that maximize benefits and minimize risks of AOM use. Such intervention strategies should support the promotion of healthy growth and development; adequate nutritional status/intake, healthy eating and physical activity behaviors; mental health and well-being (e.g., body image, self-esteem, mood, etc.), and quality of life and be feasible to implement in clinical care settings. Priority areas include testing strategies to determine optimal developmental stage for AOM initiation, rate and amount of weight loss, AOM class, dose, frequency, and duration, and content and intensity of adjunct lifestyle therapies that may be imperative to ensure normal psychological and physical development and to potentially avoid lifelong dependence on AOMs. Investigators should also evaluate potential predictors of response/ nonresponse to various treatment strategies under evaluation. The clinical centers may conduct independent or multicenter trials but will collaborate on the development of protocols, use of common measures and data elements, use of a central laboratory and standardized procedures to collect data and biospecimens, and data analyses and manuscripts. This NOFO uses a cooperative agreement mechanism (U01) and runs in parallel with a companion NOFO (RFA-DK-27-136).

National Institutes of Health

This Notice of Funding Opportunity (NOFO) invites applications from clinical centers to participate in a consortium to test anti-obesity medication (AOM) treatment strategies for youth with obesity that maximize benefits and minimize risks of AOM use. Such intervention strategies should support the promotion of healthy growth and development; adequate nutritional status/intake, healthy eating and physical activity behaviors; mental health and well-being (e.g., body image, self-esteem, mood, etc.), and quality of life and be feasible to implement in clinical care settings. Priority areas include testing strategies to determine optimal developmental stage for AOM initiation, rate and amount of weight loss, AOM class, dose, frequency, and duration, and content and intensity of adjunct lifestyle therapies that may be imperative to ensure normal psychological and physical development and to potentially avoid lifelong dependence on AOMs. Investigators should also evaluate potential predictors of response/ nonresponse to various treatment strategies under evaluation. The clinical centers may conduct independent or multicenter trials but will collaborate on the development of protocols, use of common measures and data elements, use of a central laboratory and standardized procedures to collect data and biospecimens, and data analyses and manuscripts. This NOFO uses a cooperative agreement mechanism (U01) and runs in parallel with a companion NOFO (RFA-DK-27-136).

National Institutes of Health

This Notice of Funding Opportunity (NOFO) invites applications for a Research Coordinating Center (RCC) to participate in a consortium of clinical centers that will test anti-obesity medication (AOM) treatment strategies for youth with obesity that maximize benefits and minimize risks of AOM use. Such intervention strategies should support the promotion of healthy growth and development; adequate nutritional status/intake, healthy eating and physical activity behaviors; mental health and well-being (e.g., body image, self-esteem, mood, etc.), and quality of life and be feasible to implement in clinical care settings. Priority areas include testing strategies to determine optimal developmental stage for AOM initiation, rate and amount of weight loss, AOM class, dose, frequency, and duration, and content and intensity of adjunct lifestyle therapies that may be imperative to ensure normal psychological and physical development and to potentially avoid lifelong dependence on AOMs. Investigators should also evaluate potential predictors of response/ nonresponse to various treatment strategies under evaluation. The clinical centers may conduct independent or multicenter trials but will collaborate on the development of protocols, use of common measures and data elements, use of a central laboratory and standardized procedures to collect data and biospecimens, and data analyses and manuscriptsThe RCC will lead, manage, and harmonize efforts for the Consortium including 1) providing management and administrative support; 2) providing leadership and expertise on statistical design and analysis, 3) providing research coordination with a central laboratory, 4) harmonizing data collection methods and use of common data elements, 5) developing the database; 6) conducting data management and data analyses for Consortium studies; and 7) fostering research collaborations. This NOFO uses a cooperative agreement mechanism (U24) and runs in parallel with a companion NOFO (RFA-DK-27-121).

National Institutes of Health

This Notice of Funding Opportunity (NOFO) invites applications for a Research Coordinating Center (RCC) to participate in a consortium of clinical centers that will test anti-obesity medication (AOM) treatment strategies for youth with obesity that maximize benefits and minimize risks of AOM use. Such intervention strategies should support the promotion of healthy growth and development; adequate nutritional status/intake, healthy eating and physical activity behaviors; mental health and well-being (e.g., body image, self-esteem, mood, etc.), and quality of life and be feasible to implement in clinical care settings. Priority areas include testing strategies to determine optimal developmental stage for AOM initiation, rate and amount of weight loss, AOM class, dose, frequency, and duration, and content and intensity of adjunct lifestyle therapies that may be imperative to ensure normal psychological and physical development and to potentially avoid lifelong dependence on AOMs. Investigators should also evaluate potential predictors of response/ nonresponse to various treatment strategies under evaluation. The clinical centers may conduct independent or multicenter trials but will collaborate on the development of protocols, use of common measures and data elements, use of a central laboratory and standardized procedures to collect data and biospecimens, and data analyses and manuscriptsThe RCC will lead, manage, and harmonize efforts for the Consortium including 1) providing management and administrative support; 2) providing leadership and expertise on statistical design and analysis, 3) providing research coordination with a central laboratory, 4) harmonizing data collection methods and use of common data elements, 5) developing the database; 6) conducting data management and data analyses for Consortium studies; and 7) fostering research collaborations. This NOFO uses a cooperative agreement mechanism (U24) and runs in parallel with a companion NOFO (RFA-DK-27-121).

NIMH - National Institute of Mental Health

PROJECT SUMMARY/ABSTRACT Incidence rates of eating disorders among adolescents are consistently rising, signaling an imperative to improve care options for these debilitating psychiatric conditions. Currently, many young people with eating disorders experience delayed or restricted access to evidence-based treatment, which increases risk for poor treatment outcomes and a chronic symptom course. Emerging work within other mental health conditions suggests that brief and single-session interventions represent promising, low-resource approaches to promoting positive clinical changes and/or promote later engagement in longer-term mental health treatment. However, no research to date has tested single-session interventions among youth with eating disorders and their families. In the current proposal, we outline a Type I Hybrid Effectiveness-Implementation Trial testing a single-session consultation (SSC) protocol for treatment-seeking youth with eating disorders and their caregivers who are waiting for specialty care. Following a Preparatory Phase during which we engage key-stakeholders, we will evaluate two aims: (1) Test the feasibility, acceptability of both the SSC and the methods for evaluating this intervention via an iterative case series (n = 10 families) and (2) Evaluate target engagement and preliminary efficacy of the SSC in engaging hypothesized mechanisms of change (hope; self-efficacy; motivation), symptom change, and promoting later treatment engagement through conducting a pilot randomized controlled trial (n = 44 families). The proposed study will yield a finalized version of the SSC and assessment procedures to test in a fully powered, randomized, controlled trial. Further, throughout study activities, we intend to collect data on a range of indicators relevant to implementation using the RE-AIM framework. Short-term, our results will provide critical information regarding the feasibility and acceptability of a single-session intervention for youth on a waitlist for eating disorder treatment and their families. Long-term, innovative approaches to promoting treatment access and treatment success in youth with eating disorders like the SSC are critical to reduce harms caused by long waits for treatment, bridge gaps in services, and increase motivation to participate in future care.

National Institutes of Health

NIMH seeks applications for pilot research to adapt, optimize, and test behavioral interventions that address common sleep problems in adolescents and young adults with or at risk for a mental health disorder. This notice of funding opportunity (NOFO) supports pilot clinical trials designed to evaluate the feasibility, tolerability, acceptability, safety, and potential effectiveness of the approach in real world settings. Applications should aim to conduct a preliminary test of the intervention's impact on sleep and mental health outcomes, as well as an examination of the mechanisms that underlie the intervention's effectiveness, and to obtain preliminary data needed as a prerequisite for larger-scale effectiveness trials. In addition, interdisciplinary, collaborative teams of investigators from the fields of mental health, sleep medicine, developmental science, clinical trials research methods, behavioral economics, implementation science, data science, and human computer interaction are encouraged.

National Institutes of Health

NIMH seeks applications for pilot research to adapt, optimize, and test behavioral interventions that address common sleep problems in adolescents and young adults with or at risk for a mental health disorder. This notice of funding opportunity (NOFO) supports pilot clinical trials designed to evaluate the feasibility, tolerability, acceptability, safety, and potential effectiveness of the approach in real world settings. Applications should aim to conduct a preliminary test of the intervention's impact on sleep and mental health outcomes, as well as an examination of the mechanisms that underlie the intervention's effectiveness, and to obtain preliminary data needed as a prerequisite for larger-scale effectiveness trials. In addition, interdisciplinary, collaborative teams of investigators from the fields of mental health, sleep medicine, developmental science, clinical trials research methods, behavioral economics, implementation science, data science, and human computer interaction are encouraged.

NIMH - National Institute of Mental Health

PROJECT SUMMARY Significance: Despite availability of modern antiretroviral therapy regimens in the United States, many people living with HIV (PWH) experience barriers to care, and targets to End the HIV Epidemic (EHE) have still not been achieved. Case management is an evidence-based intervention which can improve HIV outcomes; however, these programs require extensive human resources to deliver services to PWH who are hardest to reach, which can limit feasibility. To realize EHE targets, implementation innovations are needed to optimize delivery of these programs to facilitate viral suppression and retention in care. Setting: The HIV Enhanced Access to Treatment (HEAT) program at Massachusetts General Hospital is a Ryan-White supported intensive case management program for PWH who experience significant barriers to care, often due to mental health comorbidities, substance use, homelessness/unstable housing, and/or language/cultural barriers. Innovation: We propose to develop a novel multi-level case management implementation toolkit in conjunction with community partners, with components for both patients and care team members, that is designed specifically to optimize care for PWH with the greatest barriers to care who are often unreached. Investigators: Our multidisciplinary team of investigators with expertise in clinical epidemiology (Suzanne McCluskey), HIV program leadership (Jacqueline Chu), qualitative research (Christina Psaros), and implementation science (Ingrid Bassett) is well-suited to address these public health challenges through the following Specific Aims: Aim 1) We will conduct a mixed-methods study to assess the determinants of viral suppression achieved through participation in the HEAT program. We will analyze historical data from the HEAT program, followed by semi-structured in-depth interviews with HEAT program participants, HEAT program staff, and representatives of community-based organizations, guided by the Consolidated Framework for Implementation Research. Aim 2) We will employ a Delphi process to develop a toolkit to optimize the delivery of Ryan White-supported intensive case management programs. We will invite participation from multiple levels of stakeholders including HEAT program participants, HEAT program staff and leadership, representatives from partnering community- based organizations, Ryan White program administrators, and leaders of external Ryan White-supported programs. Aim 3) We will evaluate the pilot implementation of the toolkit within the HEAT program using the Proctor outcomes framework, assessing implementation outcomes of feasibility, acceptability, and appropriateness, as well as preliminary recipient-level outcomes of viral suppression and retention in care at six months. Impact: This study proposal responds directly to the NIH EHE priorities through development of an innovative strategy to expand engagement in HIV care with a focus on populations that are largely unreached. Results of this work will inform development of a future cluster randomized trial to evaluate deployment of the toolkit across Ryan White programs in priority areas where EHE targets have not been met.

NIMH - National Institute of Mental Health

PROJECT SUMMARY/ABSTRACT Across sub-Saharan Africa, approximately one-third of new HIV infections occur among men. Men in highly mobile occupations, such as fishing, are particularly vulnerable to poor HIV prevention engagement. Fisherfolk (men and women who work in the fishing industry) are the largest key/priority population in Kenya. Despite significant declines in HIV incidence in other populations in sub-Saharan Africa, fishermen have persistently high rates of HIV acquisition. Kenya has been a leader in scaling up biomedical HIV prevention, including oral tenofovir-based pre-exposure prophylaxis (PrEP), a daily pill that is highly effective with sufficient adherence. However, efforts to improve daily oral PrEP use have not been effectively deployed to address the unique barriers experienced by mobile fishermen, particularly as new HIV prevention technologies and regimens are introduced such as long-acting injectable PrEP (e.g., CAB-LA; injection every 2 months and lenacapavir; injection every 6 months), event- driven PrEP (oral PrEP taken before and after sexual contact), and post-exposure prophylaxis (oral PrEP taken after potential HIV exposure). Without tailored delivery strategies, these innovations risk reproducing the same access and adherence challenges that have limited the impact of existing prevention tools in this population. Evidence-based approaches tailored to the needs of mobile fishermen are urgently needed to optimize their engagement in biomedical HIV prevention. Evidence-based approaches such as differentiated and patient- centered service delivery for HIV prevention have been endorsed by the WHO, yet these service delivery models have not yet been effectively harnessed to improve mobile fishermen’s uptake and adherence to biomedical HIV prevention. Meaningful engagement of community members in tailoring evidence-based HIV interventions is recognized as an approach that may increase sustainability, ownership, and acceptance of interventions. However, established methods to effectively engage mobile populations, including fishermen, in research are limited. Community-led, participatory approaches in global HIV research have infrequently been utilized with priority populations such as mobile fishermen yet may be vital to addressing prevention gaps. The proposed research uses community-engaged and participatory approaches to identify factors influencing fishermen’s engagement in HIV prevention (Aim 1) and to co-design an evidence-based intervention in collaboration with fishermen (Aim 2). The co-designed intervention will then be piloted to evaluate its implementation and client outcomes (Aim 3). Completion of the proposed training and research plan will provide me with an expanded skillset in community-engaged research, intervention design, and implementation science approaches. I will be mentored by a team of experienced Kenyan and UCSF mentors. A future R01 will evaluate the co-designed intervention at scale.

NHLBI - National Heart Lung and Blood Institute

Abstract (30 lines) Cystic fibrosis (CF) is a life-limiting genetic disease affecting multiple organ systems. Over the past several decades, novel therapies have driven improvements in lung function and survival. However, the burden of taking multiple treatments for people with CF (pwCF) have been substantial. The recent introduction of elexacaftor/tezacaftor/ivacaftor (ETI), a highly effective CF transmembrane conductance regulator (CFTR) modulator now used by approximately 80% of pwCF, has led to marked improvements in lung function and reductions in pulmonary exacerbations. This has prompted many pwCF and their healthcare providers to reconsider the necessity of conventional CF therapies, such as inhaled dornase alfa (DA) and hypertonic saline (HTS). While some studies have suggested that discontinuing these treatments may not immediately affect lung function, the longer-term consequences of reducing the conventional therapies remain unclear, particularly for individuals with more advanced lung disease. Additionally, ETIs have been linked to potential adverse effects including liver dysfunction and mental health issues. Robust real-world data studies are essential to understand the safety profile and variability in individual responses to guide clinical decision- making. To address these critical knowledge gaps in this rare but high-cost and -burden disease, we propose a comprehensive epidemiologic study leveraging patient registries and healthcare databases to evaluate the impact of reducing conventional CF therapies and the safety profile of ETI. We will link information in the Cystic Fibrosis Foundation Patient Registry to the healthcare database for pwCF insured by Medicaid or commercial insurances from Carelon Research to identify detailed information on genotype and phenotype, lung function, medication use, clinical outcomes, and adverse effects. The specific aims are to: (1) assess the effectiveness of adhering to conventional CF therapies among pwCF who initiated ETI; (2) identify and assess the effectiveness of an adaptive strategy, based on clinical course and pulmonary function test measures, to discontinue traditional CF medications compared to fixed strategies; and (3) assess non-pulmonary adverse events potentially associated with ETI treatment, like depression and liver disease. We have assembled an interdisciplinary team of methodological and clinical experts with prior collaboration and deep clinical and methodological experience relevant to the research questions, data sources, data linkage, and analytic methods, supported by extensive preliminary analyses demonstrating feasibility. This approach will allow us to examine the real-world outcomes of treatment discontinuation and identify optimal usage patterns of traditional CF medications based on lung function values and exacerbation history in the ETI era. Findings from this study will provide evidence-based guidance to optimize CF therapy, balancing the benefits of simplifying treatment regimens with the potential risks of medication discontinuation and drug-related complications.

NIMH - National Institute of Mental Health

PROJECT ABSTRACT Long-acting injectable (LAI) pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART) represent a promising but underutilized class of HIV medications that can significantly benefit patients who struggle with oral medication adherence. Despite their potential, LAIs face substantial implementation barriers due to their logistical complexity compared to traditional oral medications. While high-volume LAI delivery is currently rare across U.S. HIV clinics, clinical decision support (CDS) systems offer a potential solution for efficiently scaling LAI programs. This project addresses the critical need for infrastructural support in LAI delivery by developing and evaluating a comprehensive Resource Package to accelerate the adoption of LAI-specific CDS in HIV clinics nationwide. We hypothesize that providing clinics with a standardized Resource Package will lead to more efficient workflows, improved care coordination, enhanced patient outcomes, and sustainable LAI program growth. The Resource Package will include: (1) a compendium of LAI-specific CDS tool options with implementation guidance, (2) decision-making worksheets for CDS design, (3) low-fidelity prototypes with adaptable wireframes, (4) build checklists for tool development, and (5) evaluation metrics for assessing CDS tools. Our project has three specific aims. First, we will identify promising CDS tools and processes through synthesis of practices at 10 Clinical Partner Sites currently delivering LAIs at high volume. Second, we will co-create the Resource Package through five multi-disciplinary working groups, each including clinicians, CDS end-users, builders, and implementation scientists. Third, we will assess the Resource Package's impact on clinics' readiness to build LAI CDS tools and their progress in the build process through pre-post surveys and in-depth qualitative analysis. The project will be carried out by an interdisciplinary team including implementation scientists, clinicians, and CDS specialists, working collaboratively with 10 Clinical Partner Sites, two national dissemination partners, and a Community Advisory Board. This research directly responds to NIMH priorities (PAR-22-060 and NOT-MH-23-275) by developing a systematic intervention to promote organizational readiness and capacity for implementing LAIs with fidelity and effectiveness. By establishing a standardized approach to CDS development for LAIs, this project aims to overcome a significant barrier to widespread LAI implementation, ultimately expanding access to these valuable HIV prevention and treatment options for vulnerable populations currently underserved by conventional oral medication approaches.

National Institutes of Health

Purpose. This Funding Opportunity Announcement (FOA) issued by the National Institute of Dental and Craniofacial Research and the National Institute on Aging, National Institutes of Health, solicits grant applications from institutions/organizations that propose investigator-initiated clinical research focused on the oral health of special needs populations, including those with developmental or acquired physical or mental disabilities, people with mental retardation (MR), people living with HIV/AIDS, and frail or functionally dependent elders. Mechanism of Support. This FOA will utilize the Research Project Grant (R01) award mechanism. Funds Available and Anticipated Number of Awards. Awards issued under this FOA are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications. Eligible Institutions/Organizations. Public/State Controlled Institution of Higher Education; Private Institution of Higher Education; Nonprofit with 501(c)(3) IRS Status (Other than Institution of Higher Education); Nonprofit without 501(c)(3) IRS Status (Other than Institution of Higher Education); Small Business; For-Profit Organization (Other than Small Business); State Government; U.S. Territory or Possession; Indian/Native American Tribal Government (Federally Recognized); Indian/Native American Tribal Government (Other than Federally Recognized); Indian/Native American Tribally Designated Organization; Non-domestic (non-U.S.) Entity (Foreign Organization); Hispanic-serving Institution; Historically Black Colleges and Universities (HBCUs); Tribally Controlled Colleges and Universities (TCCUs); Alaska Native and Native Hawaiian Serving Institutions; Regional Organization; Other(s): Eligible agencies of the Federal government; Faith-based or community based organizations.

NIMH - National Institute of Mental Health

Project Summary/Abstract Depressive symptoms represent a serious challenge to youth mental health. There is therefore an urgent need for the identification of possible mechanisms underlying risk for youth depressive symptoms. This is especially crucial for certain high-risk populations, such as youth with a history of adversity exposure. Dysregulation of the oral microbiome, the community of microorganisms inhabiting the human oral cavity, may function as a mechanism underlying risk for depressive symptoms in youth. The oral microbiome is a compelling putative mechanism for youth depressive symptoms because it is manipulable via non-invasive interventions, such as probiotic supplementation, while, at the same time, remarkably resilient to insults once it has stabilized in early adulthood. Indeed, oral microbiome dysregulation has been linked to depressive symptoms, experimentally in animal models and observationally in human youth. However, in order for potential mechanisms underlying this link to be elucidated, there is a need for research that examines the oral microbiome and depressive symptoms longitudinally, that examines the microbiome at a functional level, and that incorporates neuroimaging to better understand depressive symptom etiology. The current project will address these gaps by leveraging a 3-year longitudinal study of youth, ages 6-16 at the first timepoint (N=152), with the first 2 timepoints completed and the 3rd underway. This project oversamples for adversity-exposed youth (N=66), a population at increased risk of both depressive symptoms and oral microbiome dysregulation. Oral microbiome composition and depressive symptoms will have been assessed at all three timepoints, and functional Magnetic Resonance Imaging (fMRI) conducted at the final timepoint. We will analyze the relationship between the oral microbiome and depressive symptoms, and the relationship between the oral microbiome and functional brain connectivity. We hypothesize that elevated pathogenic taxa, increased pro-inflammatory functions of the oral microbiome, and decreased aromatic amino acid precursor biosynthesis will be associated with increased depressive symptoms. We further hypothesize these same indicators of oral microbiome dysregulation will also be associated with altered functional brain connectivity, especially within the affective limbic network, reward network, default mode network, and cognitive control network. This project’s findings will yield critical understanding about potential peripheral mechanisms underlying depressive symptoms in both typically developing and high-risk youth.