New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Stress-strain curve transition region demonstrates heart valve collagen fiber alignment

Heart valves demonstrate a characteristic stress-strain curve with a low slope portion, in which collagen fibers uncrimp, and a high slope region, in which the uncrimped collagen fibers bear load. The acuteness of the transition between these two regions depends upon collagen fiber alignment. We assessed the radius of transition curvature (RoTC) as an indicator of differences in collagen fiber alignment of porcine aortic and mitral valves (AV, MV, n=46 hearts) with age (6 weeks, 6 months, 6 years) in both the radial and circumferential directions. The RoTC of radial strips was 3-5 times greater than that of circumferential strips. Radially, RoTC was greater in the AV than in MV. Circumferentially, RoTC was lowest in the center of the MV anterior leaflet (MVAC), followed by AV, and then the free edge of the MV anterior leaflet. RoTC decreased with age, particularly in AV radial strips, likely due to age-related increases in collagen alignment and crosslinking. These findings are consistent with circumferentially oriented collagen fibers within valves, especially the high collagen fiber alignment in the MVAC. In conclusion, RoTC is an easily calculated parameter that may be useful in characterizing the orientation of fibers and the matrix composition of biological materials

Myocardial Disease and Long-Distance Space Travel: Solving the Radiation Problem

Radiation-induced cardiovascular disease is a well-known complication of radiation exposure. Over the last few years, planning for deep space missions has increased interest in the effects of space radiation on the cardiovascular system, as an increasing number of astronauts will be exposed to space radiation for longer periods of time. Research has shown that exposure to different types of particles found in space radiation can lead to the development of diverse cardiovascular disease via fibrotic myocardial remodeling, accelerated atherosclerosis and microvascular damage. Several underlying mechanisms for radiation-induced cardiovascular disease have been identified, but many aspects of the pathophysiology remain unclear. Existing pharmacological compounds have been evaluated to protect the cardiovascular system from space radiation-induced damage, but currently no radioprotective compounds have been approved. This review critically analyzes the effects of space radiation on the cardiovascular system, the underlying mechanisms and potential countermeasures to space radiation-induced cardiovascular disease.Thoracic Surger

Emerging trends in heart valve engineering: Part I. solutions for future

As the first section of a multi-part review series, this section provides an overview of the ongoing research and development aimed at fabricating novel heart valve replacements beyond what is currently available for patients. Here we discuss heart valve replacement options that involve a biological component or process for creation, either in vitro or in vivo (tissue-engineered heart valves), and heart valves that are fabricated from polymeric material that are considered permanent inert materials that may suffice for adults where growth is not required. Polymeric materials provide opportunities for cost-effective heart valves that can be more easily manufactured and can be easily integrated with artificial heart and ventricular assist device technologies. Tissue engineered heart valves show promise as a regenerative patient specific model that could be the future of all valve replacement. Because tissue-engineered heart valves depend on cells for their creation, understanding how cells sense and respond to chemical and physical stimuli in their microenvironment is critical and therefore, is also reviewed

Emerging trends in heart valve engineering: Part III. Novel technologies for mitral valve repair and replacement

In this portion of an extensive review of heart valve engineering, we focus on the current and emerging technologies and techniques to repair or replace the mitral valve. We begin with a discussion of the currently available mechanical and bioprosthetic mitral valves followed by the rationale and limitations of current surgical mitral annuloplasty methods; a discussion of the technique of neo-chordae fabrication and implantation; a review the procedures and clinical results for catheter-based mitral leaflet repair; a highlight of the motivation for and limitations of catheter-based annular reduction therapies; and introduce the early generation devices for catheter-based mitral valve replacement

Emerging trends in heart valve engineering: Part II. Novel and standard technologies for aortic valve replacement

The engineering of technologies for heart valve replacement (i.e., heart valve engineering) is an exciting and evolving field. Since the first valve replacement, technology has progressed by leaps and bounds. Innovations emerge frequently and supply patients and physicians with new, increasingly efficacious and less invasive treatment options. As much as any other field in medicine the treatment of heart valve disease has experienced a renaissance in the last 10 years. Here we review the currently available technologies and future options in the surgical and transcatheter treatment of aortic valve disease. Different valves from major manufacturers are described in details with their applications