Goal 2: Reduce Human Disease

What about the impact of regulation of genes in response to external stimulation on human health

We are focusing a lot on the genes that may be protective or harmful to our lives. But what about the regulation of genes in response to external stimulations, such as psychosocial and/or environmental, that are probably more accountable for whether we live healthier or not.

Submitted by (@jiang001)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

Rationale: Years of research in the mind-heart field have set examples that looking at changes during dynamic stimulations (chronic, acute, and acute superimposed on chronic) are more meaningful for us to better understand how the body truly works. Therefore, research design in mimicking real dynamic process is necessary to truly capture the healthy or harmful phenotypes driven by genotypes. I suggest the NHLBI to establish a platform gathering resources to promote more sophisticated research from basic to clinical to better understand the underlying mechanisms of psychosocial impact on cardiovascular diseases that has come to a sizable problem for the human being in US and world wide.

Feasibility and challenges of addressing this CQ or CC :

We have performed researches that allow us to identify phenotypes that are only appearing under emotional stress testing. Currently we are examining whether certain intervention may modify these kinds of changes. Even our studies fail to demonstrate changes with intervention, the findings support future studies focusing on testing dynamic changes under stress that reflects daily living. Resting data obtained in laboratory does not truly represent what human beings experiences.

Name of idea submitter and other team members who worked on this idea : Wei Jiang from Duke University

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Goal 2: Reduce Human Disease

Sleep Disorders and Brain Maturation

What is the effect of sleep disorders on child development? Specifically, how sleep apnea with intermittent hypoxia and or sleep deprivation alters the normal trajectory of maturation of brain regions controlling cognition, behavior and the cardiovascular system?

Submitted by (@raouf.amin)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

The significance of the behavioral and cardiovascular findings in children as they relate to health during adulthood is unknown. It remains to be defined whether the behavioral and cardiovascular abnormalities observed in children with sleep apnea are a reflection of structural and functional brain abnormalities, which might persist into adulthood and predispose to health problems at an older age.

A fundamental question that deserve investigation whether brain maturation in children with sleep apnea and sleep deprivation deviate from normal trajectory and whether brain plasticity can restore normal structure and function.

Such knowledge on brain maturation and plasticity in children with sleep disorders could lead to the identification of brain biomarkers that might signal risk for future mood and behavioral disorders and or cardiovascular diseases. The new knowledge will also identify sensitive period(s) during child development for interventions.

Feasibility and challenges of addressing this CQ or CC :

In the last decade, the application of new technologies of fMRI and diffusion MRI have permitted the study of the evolving brain connectome across all stages of development and created new potentials to inform our etiologic understanding of many pediatric and adult diseases.

We now can for the first time examine the brain developmental trajectories in children with chronic medical conditions including sleep disorders and compare the findings to normative data.

Name of idea submitter and other team members who worked on this idea : Raouf Amin, Mark DiFrancesco, Scott Holland

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Goal 2: Reduce Human Disease

Why does loss of endoglin in adult blood cells lead to cardiac hypertrophy in HHT patients

Liver arteriovenous venous malformations creates a high flow shunt that over time creates high output cardiac failure with no effective treatments.

Submitted by (@mariannes.clancy)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Name of idea submitter and other team members who worked on this idea : Marianne Clancy MPA, Chris Hughes PhD

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Goal 4: Develop Workforce and Resources

Bridge “translational gap”

Provide resources and training to improve the ability of scientists to bridge the “translational gap”. Continue and expand the VITA program.

Submitted by (@societyforvascularsurgery)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Name of idea submitter and other team members who worked on this idea : Society for Vascular Surgery

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5 net votes
7 up votes
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Goal 3: Advance Translational Research

Improve patient compliance through community health workers

What are effective strategies for community-based participatory dissemination and implementation research initiatives in rural settings? • Limited number of studies that adapt evidence- or practice-based interventions to rural settings • Needs innovative approaches to engaging the rural community • New intervention approaches needs testing in rural communities • Building a team would have to involve of local community ...more »

Submitted by (@nhlbiforumadministrator)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

• Nearly 60 million Americans living in rural communities face additional barriers to receiving effective prevention and treatment services.

• Rural residents often enter care later in the course of their illness than their urban peers, enter care with more serious symptoms, and require more intensive and expensive treatment.

• The rural communities in the US are closely connected and can be leveraged to disseminate heart, lung, blood, and sleep relevant preventive and/or treatment options within those communities.

• Enhance understanding of community resilience factors, cultural, and individual factors that may enhance the provision and utilization of prevention and treatment services in these communities.

• Generate knowledge to improve the organization, efficiency, effectiveness, quality, and services for rural and frontier populations.

• Support movement of evidence-based effective health care and prevention and the public health knowledge base in rural communities in the US.

• Stimulate implementation science in rural and frontier communities

• High return on investment.

Feasibility and challenges of addressing this CQ or CC :

• NHLBI investigators could initiate controlled trials that would maximize the opportunities available in rural communities.

• Documented sustainable interventions and scientific research could serve to reduce morbidity and mortality in high-risk rural populations.

Name of idea submitter and other team members who worked on this idea : NHLBI Staff

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Goal 4: Develop Workforce and Resources

Training and mentor support in global health

Why can’t all training grants (T, K, etc) be opened out to all people working in US institutions, regardless of citizenship or green-card?

Why can’t we establish mechanisms for US junior investigators and mentors interested in global NHLBI areas?

Submitted by (@nhlbiforumadministrator)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

Current policy does not allow non-citizens and green-card holders to apply for most K and T grants. However, given the changing nature of US workforce, this policy needs to change. Current mechanisms do not easily enable US investigators to get support for global work……training and/or research.

Feasibility and challenges of addressing this CQ or CC :

Why not?

Name of idea submitter and other team members who worked on this idea : K.M. Venkat Narayan

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Goal 3: Advance Translational Research

Direct thrombin inhibitors and anti-Xa (Ten A) inhibitors in trauma patients - physiologic effects and impact on outcomes

Direct thrombin inhibitors and anti-Xa (Ten A) inhibitors are new, undetectable and irreversible. We have no data on how well these drugs correlate with current measures of coagulopathy such as thromboelastography, or whether antifibrinolytics should be used in patients who are on these drugs. These drugs may increase incidence of traumatic brain injury after minor injury. They are also going to be used increasingly in ...more »

Submitted by (@nhlbiforumadministrator)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

Understanding pathophysiology of coagulopathy in trauma patients due to these drugs may lead to innovations in management of coagulopathy and help increase our ability to predict/prognostic poor clinical outcomes in patients on these new anticoagulants, detect these drugs in a timely manner and develop antidotes/reversal agents. 

Feasibility and challenges of addressing this CQ or CC :

These are eminently feasible with adequate support from the NHLBI. Challenges will be finding collaborations or institutions that have enough clinical volume and adequate basic science/translational research infrastructure to look at these questions seriously.

Name of idea submitter and other team members who worked on this idea : Sudha Jayaraman

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Goal 2: Reduce Human Disease

Can one integrate cardiac imaging studies with genetic,clinical, "omics", and historical data to predict disease and personalize

There are many novel imaging modalities, including radiographic, scintigraphic, sonographic, MR-based, and molecular for the heart and vessels. Patients have unique medical "signatures"- genetic risk factor profiles, epigenetic markings, "omics" profiles, and personal clinical and family history as well as symptom constellation and physical exam findings. Can these all be integrated into a single personalized profile ...more »

Submitted by (@dpinsky)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Feasibility and challenges of addressing this CQ or CC :

This will require a combination of informatics, state of the art imaging, and state of the art genetics and omics profiling with integration with the electronic health record.

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Goal 2: Reduce Human Disease

Translational and basic research on high triglycerides as an additional risk for cardiovascular disease.

Compelling Question (CQ)

Submitted by (@hwu000)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

Previous studies have focused on high cholesterol as a risk factor for cardiovascular disease (CVD). Recent epidemiologic and genetic studies with apoCIII mutation, for example, have identified significant contribution of high triglycerides (TGs) to the development of atherosclerotic CVD. In particular, the epidemics of obesity, even from young age, in the US and worldwide have caused significant increases in the prevalence of hypertriglyceridemia, which has become a serious health problem. However, how hypertriglyceridemia increases risk for atherosclerotic CVD remains largely unknown. Further translational and basic studies would be needed to examine how TG-rich lipoproteins and cholesterol-rich lipoproteins cooperate to increase the risk for CVD. Basic research would need to be conducted at integrative, cellular and molecular levels including examining how TGs are metabolized and how TG-rich lipoproteins, along with cholesterol-rich lipoproteins, cause atherosclerosis. These studies would guide clinical approach on TG- versus cholesterol-lowering therapy for prevention and treatment of atherosclerotic CVD.

Feasibility and challenges of addressing this CQ or CC :

The challenges include combining large clinical studies and basic research. Clinical studies includes confirming high TGs as an independent risk for atherosclerotic CVD, developing novel TG-lowering therapy and examining whether these novel TG-lowering therapy, with apoCIII as a target for example, would be beneficial in prevention and treatment of CVD. It is also important to examine effects of novel TG-lowering therapy on adiposity, adipose tissue function and risk of diabetes. Basic science needs to elucidate how TGs are metabolized in vivo, causing hypertriglyceridemia, and how hypertriglyceridemia increases risk for atherosclerotic CVD, and identify novel pathways for these pathophysiological processes, which would provide novel strategies for development of new therapy for CVD. Collaborative approach with great financial support will make all these feasible.

Name of idea submitter and other team members who worked on this idea : Huaizhu Wu, MD

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4 up votes
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Goal 2: Reduce Human Disease

Treatment Options for Diabetics and Impact on Cardiovascular Health

As a clinician, over the years I have noted major differences in adverse cardiovascular outcomes in diabetics who are treated with insulin +/- oral agents compared to those only treated with oral agents. Cardiovascular events occur much less often and at a much later timeframe in diabetics ("Type 2/adult onset") treated with insulin as the primary method. Even with newer agents, there may be slight improvement, but ...more »

Submitted by (@patty.gladowski)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Critical Challenge (CC)

Details on the impact of addressing this CQ or CC :

Delaying the onset of injury to vasculature in Type 2 diabetics would have a major impact on quality of life for the diabetic and costs to the healthcare system. Dialysis and related costs are around $200,000/yr and interfere with life and ability to work, leg ulcers are often chronic and in many cases result in amputation.

Feasibility and challenges of addressing this CQ or CC :

This study could be performed in the clinical setting or could be completed with chart review to determine diabetics on insulin on insulin and review outcomes. If access to charts for patients continuously treated for five years or longer were available, this study could be done in a shorter timeframe and at less cost. A long term and costly alternative would be to begin a clinical trial. Medical claims data may be an alternative, but it would be important to identify onset of diabetes and treatment for a minimum of five years.

Name of idea submitter and other team members who worked on this idea : Patricia Gladowski

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7 up votes
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Goal 2: Reduce Human Disease

Defining critical elements for irreversible myocardial injury

What are the critical mechanisms that account for progression from reversible to irreversible ischemia and reperfusion injury?

Submitted by (@nhlbiforumadministrator)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

Understanding the mechanism of how myocardium becomes irreversibly injured will provide clarity for therapeutic intervention.

Feasibility and challenges of addressing this CQ or CC :

Advances in proteomics and databases of post-translational modifications may support the feasibility of discoveries in this area.

This information is key for designing novel therapeutic strategies for acute myocardial ischemic injury. This understanding will define the critical timing, location, and distribution of modulators, and amplitude required for activation of components involved in protective pathways.

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Goal 1: Promote Human Health

Environmental Exposures and Atopic Disease

As the current chair of the Research and Training Division, I would like to convey that the AAAAI membership would like the NHLBI to consider the following in the development of its strategic plan:

 

What are the molecular and cellular responses in the lung that occur after environmental stimuli (including allergens) that predict homeostatic resilience or transition to atopic diseases?

Submitted by (@wheeze)

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Name of idea submitter and other team members who worked on this idea : Mitchell Grayson on behalf of the American Academy of Allergy, Asthma, and Immunology

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8 up votes
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