Goal 3: Advance Translational Research

Spinal Cord Injury: hype, unmet promises, and misery which does not need to be

Research to "fix" spinal cord injury in humans, has been insanely hyped, rare in reality, and very disappointing in its clinical applicability to human patients. After a parade of rat models, mouse models, cat models, dog models, African green monkey models, pig models, guinea pig models, hamster models, rabbit models, gerbil models, etc. one wonders whether most researchers or funders will ever have any interest in ...more »

Submitted by (@mgwmgw)

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

Details on the impact of addressing this CQ or CC :

So, how about we put a moratorium on FDA approval of all research related to a cure for spinal cord injury when done by any persons or organizations who have not published every single one of their past experiments in the time required, and for any research which involves other species than humans.

 

Also, how many different ways of creating stem-like cells do we need? Let's stop creating stem-like cells and start applying the ones we have to human patients.

 

How about spending the animal model money instead on improving the quality of life for people living with disabilities. Let us start with actually enforcing the ADA on all new enough buildings.

 

When we make technology for doctors to use, we consult doctors. When we make technology for teachers to use, we consult teachers. When we make technology for disabled people to use… we consult insurance companies, and medical professionals who are not and have never been disabled. We fail to apply the most basic usability testing to the tools which disabled people must use. For example, has any wheelchair designer tried to propel a manual wheelchair uphill on wet grass? How about across a cobblestone street? or down a normally bumpy sidewalk? Now imagine that your butt has atrophied and you are sitting on your hip bones. How painful would that be? Now remember that pressure sores resulting from this bad design can be fatal, and then tell me why we do not take this more seriously.

Feasibility and challenges of addressing this CQ or CC :

The misery which does not need to be is not a new idea: http://badcripple.blogspot.com/2015/01/obsession-with-walking.html

 

Let's get the price of tools for disabled people down to the point where most patients can really afford them, or where the insurance can actually cover them. Let's get exoskeletons price-competitive with wheelchairs, for example, instead of using them to make soldiers able to carry heavier packs in war.

Name of idea submitter and other team members who worked on this idea : Mary-Anne Wolf (inspired by the Bad Cripple blog of William Peace and by the Wheelchair Driver website forum)

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Goal 2: Reduce Human Disease

What are the mechanisms of lung injury after HCT

Despite major advances in supportive care and tissue typing non relapse mortality rates for adults undergoing hematopoietic cell transplantation are still between 15-20 % at 2 years. Lung injury and respiratory failure is a major causes of death after HCT. Although the BMT-CTN has a focused agenda on GVHD, reduction of lung toxicities will be important to improve outcomes. NHLBI should encourage researched from the ...more »

Submitted by (@giralts)

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

Details on the impact of addressing this CQ or CC :

Discovery of mechanisms of lung injury in the HCT setting are likely to be relevant for the non HCT setting.

The BMT CTN prospectively collects data on lung toxicity on all HCT recipients on trial, samples exist in the repository that could be used for biomarker discovery.

Feasibility and challenges of addressing this CQ or CC :

Main challenge is to get the two teams of investigators working together

Name of idea submitter and other team members who worked on this idea : Sergio Giralt

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88 up votes
29 down votes
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Goal 2: Reduce Human Disease

RFA on EC-cardiomyocyte interactions in the mechanisms and treatments of cardiovascular diseases

Often under recognized, the cardiac endothelial cells are highly abundant in the heart, and may have important roles in modulating cardiac function, besides simply serving as structural component of blood vessels. Evidences of ours and others have indicated an emerging role of cardiac endothelial cells signaling to cardiomyocytes to mediate important pathophysiological responses. Nonetheless, detailed mechanisms of ...more »

Submitted by (@hcai00)

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

Details on the impact of addressing this CQ or CC :

Successfully addressing this question would no double reveal novel mechanisms and ways of monitoring treatment responses of cardiovascular disease, ultimately leading to novel drug targets, valuable biomarkers and extended new directions of basic research as well.

Feasibility and challenges of addressing this CQ or CC :

Tools of studying these cells are mostly available. Both adult cardiomyocytes and endothelial cells from the heart can be isolated and cultured, although cardiomyotyes need to used within 24 hrs and cannot be passaged. However successful preparation of these cells from WT and transgenic animals would permit co-culture experiments and mechanistic studies. These cells can also be studied using in-situ techniques either detecting molecular changes/events or dynamic interactions. Potential challenges would side in selective targeting of these cells, for example, either ECs or cardiomyocytes, once a potential therapeutic is in the testing. Nonetheless, PECAM-ab conjugated techniques have been employed to specifically deliver proteins to endothelial cells, so I am confident most of the challenges can be worked out, particularly within a RFA awardees group with frequent exchanges of ideas.

Name of idea submitter and other team members who worked on this idea : Hua Linda Cai, University of California Los Angeles

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27 net votes
30 up votes
3 down votes
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Goal 1: Promote Human Health

Hand Held Device to treat PTSD and Traumatic Brain Injury

Undo Obesity, Now! Hand Held Electronic Device to Treat Obesity Undo PTSD/TBI Hand held vagus nerve stimulator for PTSD and traumatic brain injury PTSD may be similar to depression and epilepsy. Traumatic brain injury may relate to nerve injury and nerve inflammation Vagus nerve stimulation causes nerve function regeneration. Vagus nerve stimulation stops inflammation. Vagus nerve stimulation treats depression. Vagus ...more »

Submitted by (@chrislahr22)

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

Details on the impact of addressing this CQ or CC :

This could revolutionize the treatment of PTSD and traumatic brain injury. No drugs, no surgery.

Feasibility and challenges of addressing this CQ or CC :

App is in development.

Power source and electrical wave generator produced by Apple

Stimulator cord produced by Apple.

Ear Stimulator in production by General Motors Global Research and Development.

Name of idea submitter and other team members who worked on this idea : Chris Lahr, Nitin Gupta,Derek Lahr, Christian R. Gomez, Ingrid Espinoza, Ryan Marshall, Thomas Abell, Omer H. Yilmaz

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Goal 1: Promote Human Health

Hypothermia and hemostasis after severe trauma

There is a need to employ new molecular tools to delineate the difference between beneficial and uncontrolled shock-induced hypothermia, because data on hypothermia and hemostasis are incomplete or lacking, especially on the duration, depth and type of hypothermia.

 

availability of targeted resource grant funding

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 :

improvement of survival with life threatening traumatic injuries with new metabolically modulating strategies, including "simple hypothermia", improved understanding of the relationship between ischemia and reperfusion, the role of inflammatory and metabolic pathways, definition and identification of appropriate targets for therapy, the role for mechanical devices, and relationship between timely application of hypothermia and rewarming.

Feasibility and challenges of addressing this CQ or CC :

the tools and animal models are available to study hemostatic and metabolic modulation/hypothermia in traumatic injury

Trauma is the major cause of death in young individuals in the US, and globally, with uncontrolled hemorrhage representing the major cause of preventable deaths. Hypothermia, used in life threatening cardiovascular states, also holds enormous promise for application in traumatic injuries. Early deployment (pre-hospital) of novel protective metabolically modulating strategies to attenuate cellular injury from shock and reperfusion, such as hypothermia could be beneficial. However, the relationship between hypothermia in traumatic setting is complex, with data suggesting detrimental outcomes if it occurred spontaneously. In contrast, hypothermia induced in a controlled manner can protect tissues from ischemic injury.

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

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7 up votes
15 down votes
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Goal 1: Promote Human Health

Injury, regeneration and repair of the developing lung

Understanding injury, regeneration and repair of the developing lung.

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 :

While we are fully supportive of the recent emphasis on patient‐centered outcomes and implementation science, we are also reminded of the critical importance of investigating underlying mechanisms of pulmonary, critical care and sleep disorders. Recent discoveries have created exciting progress in the areas of cystic fibrosis, pulmonary hypertension, pulmonary fibrosis, and biological therapies in asthma. Only through further efforts to elucidate underlying mechanisms are new therapeutic approaches likely to emerge. Promoting further academic‐industry interactions are likely to yield benefits, which will ultimately lead to improvements in the health of our nation.

Name of idea submitter and other team members who worked on this idea : Research Advocacy Committee, American Thoracic Society

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Goal 2: Reduce Human Disease

Mechanical interaction of the cerebral vascular system with the brain parenchyma during mild traumatic brain injury

Dangerous mechanical interaction of the cerebral vascular system with the brain parenchyma during mild traumatic brain injury from either a blast wave or from impact may result from a combination of shear and compression deformation waves that causes non-diffusive extracellular fluid motion. Measure the mechanical response, to a combination of shear and compressive deformation, of animal model specimens containing the ...more »

Submitted by (@haslach)

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

Details on the impact of addressing this CQ or CC :

Such research would give insight into the immediate mechanical causes of cerebral artery dissection or of mild traumatic brain injury that occur prior to observed biochemical responses and would lay a foundation for counter-measures.

Feasibility and challenges of addressing this CQ or CC :

Develop a mathematical model for the mechanical interaction of the vascular system with the brain parenchyma and for flow in the glymphatic system during mild traumatic brain injury to predict forces generated in the extracellular fluid and in the walls of the cerebral arteries.

Name of idea submitter and other team members who worked on this idea : Henry W. Haslach, Jr.

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13 up votes
10 down votes
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Goal 2: Reduce Human Disease

What are the molecular mechanisms of lung injury, and how do they differ in children?

Both adults and children have significant morbidity and mortality due to lung injury, but have different etiologies and outcomes. It is possible that the underlying pathobiology in the two groups is different. There are no targeted therapies for lung injury, indicating that the cause is still not understood.

Submitted by (@rft2106)

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

Details on the impact of addressing this CQ or CC :

Mortality rates for acute lung injury in pediatrics vary from about 10-30%. Immunosuppressed patients and those with cancer have higher rates. Morbidity following long ICU stays have social impacts on family and education, and can put patients at risk of future lung complications.

 

Though ECMO shows promise of improving outcomes, large clinical studies are lacking. ECMO is also fraught with signifiant risks and high costs. A molecular understanding of the pathobiology of lung injury could lead to specific therapies to improve survival and decrease morbidity.

Feasibility and challenges of addressing this CQ or CC :

(1) The heterogeneity of both adults and children with lung injury hinders the applicability of clinical and translational studies. (2) Reliable animal models of pediatric lung injury are lacking.

Name of idea submitter and other team members who worked on this idea : Rebecca Turcotte

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4 up votes
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Goal 1: Promote Human Health

Control of the molecular and cellular characteristics of regional variations in the lung

What are the regional variations in cellular and molecular characteristics (from epigenetics to microbiome) in the lung, and what controls these variations?

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 :

Advance in this research will help to understand the heterogeneity of lung disease

Feasibility and challenges of addressing this CQ or CC :

Novel technologies, e.g. single cell analysis and imaging have been developed to get high resolution characterization of the cells in the lung.

Many lung diseases are heterogeneous with regional variations, which are not fully characterized at the molecular and cellular level. Mechanisms underlying the formation of the regional variations are also poorly understood.

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

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12 up votes
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Goal 2: Reduce Human Disease

Novel methods to diagnose and treat microvascular ischemia

Microvascular ischemia is common, particularly in the setting of critical illness. We need better ways to evaluate, diagnose and treat these conditions, whether they relate to microvascular myocardial ischemia, as a primary diagnosis of complication of other acute illness, or non-myocardial ischemia during the course of surgery, injury, infection or acute illness.

Submitted by (@greg.martin)

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

Details on the impact of addressing this CQ or CC :

Development of effective diagnostics would lead to improved treatments for myocardial and non-myocardial microvascular ischemia, and also advance understanding to extend the advance beyond this setting.

Name of idea submitter and other team members who worked on this idea : Society of Critical Care Medicine Executive Committee/Council

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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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6 up votes
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