Towards precision medicine for hypertension: a review of genomic, epigenomic, and microbiomic effects on blood pressure in experimental rat models and humans

Compelling evidence for the inherited nature of essential hypertension has led to extensive research in rats and humans. Rats have served as the primary model for research on the genetics of hypertension resulting in identification of genomic regions that are causally associated with hypertension. In more recent times, genome-wide studies in humans have also begun to improve our understanding of the inheritance of polygenic forms of hypertension. Based on the chronological progression of research into the genetics of hypertension as the "structural backbone," this review catalogs and discusses the rat and human genetic elements mapped and implicated in blood pressure regulation. Furthermore, the knowledge gained from these genetic studies that provide evidence to suggest that much of the genetic influence on hypertension residing within noncoding elements of our DNA and operating through pervasive epistasis or gene-gene interactions is highlighted. Lastly, perspectives on current thinking that the more complex "triad" of the genome, epigenome, and the microbiome operating to influence the inheritance of hypertension, is documented. Overall, the collective knowledge gained from rats and humans is disappointing in the sense that major hypertension-causing genes as targets for clinical management of essential hypertension may not be a clinical reality. On the other hand, the realization that the polygenic nature of hypertension prevents any single locus from being a relevant clinical target for all humans directs future studies on the genetics of hypertension towards an individualized genomic approach

Subtle Cardiovascular Dysfunction in the Unilateral 6-Hydroxydopamine-Lesioned Rat

The present study evaluated whether the unilateral 6-hydroxydopamine (6-OHDA) model of Parkinson's disease produces autonomic deficits. Autonomic parameters were assessed by implanting a small radiofrequency telemetry device which measured heart rate variability (HRV), diurnal rhythms of heart rate (HR), core body temperature (cBT) and locomotor activity (LA). Rats then received 6-OHDA lesion or sham surgery. 6-OHDA lesioned rats exhibited head and body axis biases, defective sensorimotor function (“disengage” test), and prominent apomorphine rotation (all P < .05 versus controls). Diurnal rhythm of HR was lower for 6-OHDA lesioned rats (n = 8) versus controls (n = 6; P < .05). Whilst HR decreased similarly in both groups during the day, there was a greater decrease in HR for the 6-OHDA lesioned rats at night (by 38 b.p.m. relative to 17 b.p.m. for controls). LA and cBT did not differ between surgery groups. This study indicates the unilateral 6-OHDA model of PD shows subtle signs of cardiovascular autonomic dysfunction

A collaborative approach to exploring the future of Cancer treatment and care in relation to Precision Medicine: A design perspective.

The Precision Medicine and the Future of Cancer project was jointly conceived by the Innovation School at Glasgow School of Art and the Institute of Cancer Sciences at the University of Glasgow. Graduating year Product Design students from the Innovation School were presented with a challenge-based project to produce a vision of the future based on current trends that relate to Precision Medicine(PM) and Cancer treatment. This project involved working closely with scientists, clinicians, patients, industry and academic professionals from Glasgow University, staff at Queen Elizabeth University Hospital and Clinical Innovation Zone, staff at Beatson West of Scotland Cancer Centre, Patient Representatives and external design experts from Studio AndThen and GOODD design consultancy. The objective of this project was to investigate, in both analytical and speculative ways, future forms and functions of cancer treatment and care in relation to Precision Medicine, to develop future scenarios and design artefacts, services, and the experiences associated with them. One of the most significant societal shifts currently taking place within the field of PM is the transformation around what it means to be a patient and a professional working within this context. The public’s role is developing beyond once-passive patients into stakeholders valued within the medical industry and healthcare sector for their participation in clinical trials, and contribution towards policy-making and decision-making committees. This new dynamic is changing the traditional patient-doctor relationship and challenging the hegemony of medical practice at an institutional level. The impetus for this shift is relentless technological acceleration and increased scientific research, in particular driven by advances in PM. This project asked students to consider what will happen in a cancer landscape ten years from now, where PM has evolved to the extent that new forms of medical practice, cancer treatment and care transform how we interact with each other, with professionals and the world around us. The brief gave students the opportunity to reflect on the underlying complexities regarding the future of health, technological acceleration, post-capitalism and human agency, to envision a future world context, develop it as an experiential exhibit, and produce the designed products, services and experiences for the people who might live and work within it. The project was divided into two sections: The first was a collaborative stage where groups of students were assigned a specific area of focus from Social, Technological, Economic, Ethical, Educational, Political, Legal, Ecological [STEEEPLE]. These groups focused on researching and exploring their specific lenses and gathering as much information and understanding while working with external experts to further their knowledge. This group stage culminated in an exhibition of the collaborative understanding of what the future could look like in 10 years from now, after exploring the possible consequences of current actions. The second stage saw students explore their individual response to the world that had been defined in the first stage. Each student had their own response to the research by iteratively creating a design outcome that was appropriate to the subject matter. This culminated in each student having created a design product/service/experience relating to the future scenario. A full report (Project Process Journal [PPJ]) is included within the repository of each student which breaks down their process of designing and the outcome they have designed. The project aims to tackle the emerging possibilities where medical professionals and design can collaborate, to create a future where forms of medical practice are more preventative and are more appropriate for an aging population now and into the future. The deposited materials are arranged as follows: Readme files - two readme files relate to stage one and stage two of the project as outlined above. Overview poster - gives a visual overview of the structure and timeline of the project. Data folders - the data folders for stage one of the project are named for the lens through which each group viewed possible futures. The data folders for stage two of the project are named for the individual students who conducted the work