Manipulating the exposome to enable better ageing

The sum total of life course exposures creates an exposome that has a significant impact on age-related health. Understanding the interplay between exposome factors and the (epi) genome, offers pertinent insights into the ageing process and its relationship with the accumulation of allostatic load. We propose to exploit this to develop a biomimetic approach that will provide insight into how evolution through natural selection in other species has solved many age related human health issues. In particular, we will emphasise the need to reconnect a more mechanistic approach to medical science with a broader natural sciences approach, using biomimetics to mitigate the global burden of age related ill health. In particular, we will discuss how such an approach indicates leverage of the activities of the Nrf 2 gene to enhance health span via reintroduction of the classical 'Food as Medicine' concept, including modulation of the microbiome and the creation of more salutogenic and biophilic environments. Additionally, we will discuss how this approach integrates with novel and developing senotherapies

981-46 Impact of a Comprehensive Management Program on the Hospitalization Rate for Patients with Advanced Heart Failure

Patients with advanced heart failure have a course that is often characterized by frequent hospitalizations and progressive deterioration. These patients are commonly referred to specialized centers for consideration of heart transplantation (Tx). To assess the impact of the changes in therapy made in conjunction with heart transplantation evaluation on patient outcomes, we assessed the hospitalization rate and patient's functional status in the 6 months prior to referral compared to the 6 months after referral. Since 1/91, 214 patients were evaluated, accepted for Tx, and discharged having undergone adjustments in medical therapy and a comprehensive patient education program. At time of referral patients had mean LVEF 0.21, NYHA class 3.3, VO2 max 11.0ml/kg, and had undergone a total of 429 hospitalizations in the previous 6 months. During evaluation patients had their ACE inhibitor dose increased by a mean 91.5mg/day of captopril or the equivalent, were diuresed a mean 4.2 liters, were placed on a flexible regimen of loop diuretics, and were counseled on dietary management and home based progressive aerobic exercise. After 6 months of follow-up there were only 63 hospitalizations required (mean hospitalization rate per patient over the 6 months pre-evaluation 2.00±1.45 vs post-evaluation 0.29±0.53 p<0.00001). Patient's NYHA class improved to 2.4 (p<0.0001) and VO2 max increased to 15.2 (p<0.001). Excluding the 12 elective status Tx, 14 urgent status Tx, and 9 deaths within 6 months yielded similar results (344 pre vs 34 post-evaluation hospitalizations). 64 patients (30%) improved their functional status to the point that transplantation was deferred in favor of sustained medical therapy.Referral to a heart failure specialty program is associated with a dramatic occurred between day 10±1 and 3 month. 4 patients died after hospital discharge (no death directly related to thromboembolic disease). Thus no higher risk of PE can be seen in patients with free floating prox-DVT and anticoagulant therapy should be efficient to prevent recurrent PE in such patient

Did giraffe cardiovascular evolution solve the problem of heart failure with preserved ejection fraction?

The evolved adaptations of other species can be a source of insight for novel biomedical innovation. Limitations of traditional animal models for the study of some pathologies are fueling efforts to find new approaches to biomedical investigation. One emerging approach recognizes the evolved adaptations in other species as possible solutions to human pathology. The giraffe heart, for example, appears resistant to pathology related to heart failure with preserved ejection fraction (HFpEF)-a leading form of hypertension-associated cardiovascular disease in humans. Here, we postulate that the physiological pressure-induced left ventricular thickening in giraffes does not result in the pathological cardiovascular changes observed in humans with hypertension. The mechanisms underlying this cardiovascular adaptation to high blood pressure in the giraffe may be a bioinspired roadmap for preventive and therapeutic strategies for human HFpEF

Incorporating one health into medical education

One Health is an emerging concept that stresses the linkages between human, animal, and environmental health, as well as the need for interdisciplinary communication and collaboration to address health issues including emerging zoonotic diseases, climate change impacts, and the human-animal bond. It promotes complex problem solving using a systems framework that considers interactions between humans, animals, and their shared environment. While many medical educators may not yet be familiar with the concept, the One Health approach has been endorsed by a number of major medical and public health organizations and is beginning to be implemented in a number of medical schools. In the research setting, One Health opens up new avenues to understand, detect, and prevent emerging infectious diseases, and also to conduct translational studies across species. In the clinical setting, One Health provides practical ways to incorporate environmental and animal contact considerations into patient care. This paper reviews clinical and research aspects of the One Health approach through an illustrative case updating the biopsychosocial model and proposes a basic set of One Health competencies for training and education of human health care providers

A Physician’s View of One Health: Challenges and Opportunities

One Health is one of the most important movements and emerging concepts in health today. The convergence of the fields of human and animal medicine has the potential to generate novel scientific hypotheses, create effective new therapies and potentially transform how physicians, veterinarians and their patients understand health and disease. Despite this potential, One Health has not yet gained significant awareness or traction in human medical communities. From its inception, One Health, sometimes also called One Medicine, has been piloted primarily by leaders from the world of veterinary medicine. Although the specific term was coined perhaps 10 years ago, comparative medicine has been quietly evident on university campuses with veterinary and medical schools for decades longer. Although a few physicians have played major leadership roles in One Health, in the United States, despite over ten years of the movement’s robust growth, many have still not heard of it. Furthermore, physicians with some awareness of One Health often believe it to be primarily and exclusively about zoonotic infections and global health. The much broader scope and potential of One Health as also including comparative physiology and medicine is not being communicated effectively. Consequently, the human medical community remains largely disengaged. This is problematic because without significant engagement from physicians, nurses and other human health care professionals, the potential of One Health cannot be realized. To advance One Health it is imperative that we first understand the roots of under-engagement of the human medical community. This, in turn, can guide the development of novel and engaging opportunities for physician which demonstrate the power relevance of One Health’s comparative, collaborative and cooperative approach.[...

Impacts of Psychopharmaceuticals on the Neurodevelopment of Aquatic Wildlife: A Call for Increased Knowledge Exchange across Disciplines to Highlight Implications for Human Health

The global use of psychopharmaceuticals such as antidepressants has been steadily increasing. However, the environmental consequences of increased use are rarely considered by medical professionals. Worldwide monitoring efforts have shown that pharmaceuticals are amongst the multitude of anthropogenic pollutants found in our waterways, where excretion via urine and feces is thought to be the primary mode of pharmaceutical contamination. Despite the lack of clarity surrounding the effects of the unintentional exposure to these chemicals, most notably in babies and in developing fetuses, the US Environmental Protection Agency does not currently regulate any psychopharmaceuticals in drinking water. As the underlying reasons for the increased incidence of mental illness—particularly in young children and adolescents—are poorly understood, the potential effects of unintentional exposure warrant more attention. Thus, although links between environmental contamination and physiological and behavioral changes in wildlife species—most notably in fish—have been used by ecologists and wildlife biologists to drive conservation policy and management practices, we hypothesize that this knowledge may be underutilized by medical professionals. In order to test this hypothesis, we created a hierarchically-organized citation network built around a highly-cited “parent” article to explore connections between aquatic toxicology and medical fields related to neurodevelopment. As suspected, we observed that studies in medical fields such as developmental neuroscience, obstetrics and gynecology, pediatrics, and psychiatry cite very few to no papers in the aquatic sciences. Our results underscore the need for increased transdisciplinary communication and information exchange between the aquatic sciences and medical fields

The evolution of capture myopathy in hooved mammals: a model for human stress cardiomyopathy?

Background and objectivesCapture myopathy (CM) syndromes in wildlife may be a model for human stress cardiomyopathy, including Takotsubo cardiomyopathy. Emotional stress or grief may trigger heart attack-like symptoms, and occasionally, sudden death in some humans. Similarly, wildlife exposed to predatory stresses, chase, or capture occasionally results in sudden death. To better understand the nature of vulnerability to stress-induced sudden death, we studied cases of CM in hooved mammals-ungulates-and hypothesized that CM would be associated with a syndrome of longevity-related traits.MethodologyWe reconstructed the evolution of CM in ungulates then determined how a set of life history traits explained variation in the likelihood that CM was reported.ResultsCM is broadly reported, but not in all genera, and phylogenetic analyses suggest that it is an evolutionarily labile trait. We found that the following traits were significantly associated with reports of CM: greater brain mass, faster maximum running speed, greater minimum group size and greater maximum longevity.Conclusions and implicationsCM may be an unavoidable consequence of adaptations to reduce predation risk that include increased running speed, sociality and having larger brains. Moreover, longer-lived species seem to be more likely to be susceptible to CM. Exploring variable susceptibility to CM highlights the evolutionary origins of the disorder, potential basic mechanisms that underlie vulnerability to the phenomenon, and the potential for reduction of risk through modification of life history trajectory

A planetary health perspective for kidney disease

No abstract available

Incidence of thrombus formation on the CardioSEAL and the Amplatzer interatrial closure devices.

Transcatheter closure for atrial septal defect (ASD) and patent foramen ovale (PFO) is a promising alternative to surgical closure or anticoagulant therapy. A potential complication is thrombus formation on the device after implantation. From February 2001 to June 2003, 66 patients with atrial communication were treated successfully with the Amplatzer device (16 septal and 20 PFO occluders) or the CardioSEAL device (30). Patients were discharged on antiplatelet medication (aspirin and clopidogrel) and/or anticoagulation. Fifty patients (76%) had transesophageal echocardiography (TEE) 1 month after device implantation (28 +/- 10 days). No patient experienced a thromboembolic episode during follow-up. TEE revealed that thrombus formation occurred more frequently on the CardioSEAL device (5 of 23 patients; 22%) than on the Amplatzer device (0 of 27 patients; 0%) (p = 0.02). Although thrombus disappeared or markedly diminished after additional anticoagulation therapy in 3 patients, 1 patient had surgical explantation of the device due to progressive increase in the size of thrombus with hypermobility despite intensive anticoagulation therapy. There was no variable associated with the presence of thrombus formation on the occluder other than the use of the CardioSEAL device. One month after insertion, the CardioSEAL device is more likely to have thrombus present than the Amplatzer device