Phenotypes of CF rabbits generated by CRISPR/Cas9-mediated disruption of the CFTR gene.

Existing animal models of cystic fibrosis (CF) have provided key insights into CF pathogenesis but have been limited by short lifespans, absence of key phenotypes, and/or high maintenance costs. Here, we report the CRISPR/Cas9-mediated generation of CF rabbits, a model with a relatively long lifespan and affordable maintenance and care costs. CF rabbits supplemented solely with oral osmotic laxative had a median survival of approximately 40 days and died of gastrointestinal disease, but therapeutic regimens directed toward restoring gastrointestinal transit extended median survival to approximately 80 days.

Transcatheter Replacement of Failed Bioprosthetic Valves: Large Multicenter Assessment of the Effect of Implantation Depth on Hemodynamics After Aortic Valve-in-Valve.

Background: Transcatheter valve implantation inside failed bioprosthetic surgical valves (valve-in-valve [ViV]) may offer an advantage over reoperation. Supra-annular transcatheter valve position may be advantageous in achieving better hemodynamics after ViV. Our objective was to define targets for implantation that would improve hemodynamics after ViV.

Proceedings from Heart Rhythm Society's emerging technologies forum, Boston, MA, May 12, 2015.

Physicians are in an excellent position to significantly contribute to medical device innovation, but the process of bringing an idea to the bedside is complex. To begin to address these perceived barriers, the Heart Rhythm Society convened a forum of stakeholders in medical device innovation in conjunction with the 2015 Heart Rhythm Society Annual Scientific Sessions. The forum facilitated open discussion on medical device innovation, including obstacles to physician involvement and possible solutions.

Obstructive sleep apnea: role of intermittent hypoxia and inflammation.

Obstructive sleep apnea results in intermittent hypoxia via repetitive upper airway obstruction leading to partial or complete upper airway closure, apneas and hypopneas, respectively. Intermittent hypoxia leads to sympathetic nervous system activation and oxidative stress with a resultant systemic inflammatory cascade. The putative mechanism by which obstructive sleep apnea has been linked to numerous pathologic conditions including stoke, cardiovascular disease, hypertension, and metabolic derangements is through these systemic effects.

Targeting Sleep Disordered Breathing to Prevent Heart Failure: What is the Evidence?

The inter-relationships of sleep disordered breathing (SDB) and heart failure (HF) are becoming increasingly well-characterized. The pathways linking the two entities are likely bi-directional and key underlying pathophysiological mechanisms at play include autonomic nervous system fluctuations, intermittent hypoxia, intrathoracic cardiac mechanical influences, rostral fluid shifts and up-regulation of systemic inflammation and oxidative stress. Given the increased morbidity and mortality which accompanies heart failure, the recognition and treatment of factors such as sleep disordered breathing is paramount in order to mitigate these untoward downstream health consequences.

Statistical 3D Prostate Imaging Atlas Construction via Anatomically Constrained Registration.

Statistical imaging atlases allow for integration of information from multiple patient studies collected across different image scales and modalities, such as multi-parametric (MP) MRI and histology, providing population statistics regarding a specific pathology within a single canonical representation. Such atlases are particularly valuable in the identification and validation of meaningful imaging signatures for disease characterization within a population. Despite the high incidence of prostate cancer, an imaging atlas focused on different anatomic structures of the prostate, i.

Oxidative damage and Alzheimer's disease: are antioxidant therapies useful?

Oxidative stress is a key factor involved in the development and progression of Alzheimer's disease, and it is well documented that free radical oxidative damage, particularly of neuronal lipids, proteins, nucleic acids and sugars, is extensive in brains of Alzheimer's disease patients. However, oxidative stress may elicit compensatory responses and downstream adaptations such as amyloid-beta deposition and neurofibrillary tangle formation, which may function as "shields" to ensure that neuronal cells do not succumb to oxidative injuries. Although during the past several years our understanding of the mechanisms leading to neuronal damage and death in the course of Alzheimer's disease has improved significantly, we have not found an effective therapeutic to fight this devastating disorder.