Life-long tailoring of management for patients with hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease, characterised by complex pathophysiology and extensive genetic and clinical heterogeneity. In most patients, HCM is caused by mutations in cardiac sarcomere protein genes and inherited as an autosomal dominant trait. The clinical phenotype ranges from severe presentations at a young age to lack of left ventricular hypertrophy in genotype-positive individuals. No preventative treatment is available as the sequence and causality of the pathomechanisms that initiate and exacerbate HCM are unknown. Sudden cardiac death and end-stage heart failure are devastating expressions of this disease. Contemporary management including surgical myectomy and implantable cardiac defibrillators has shown significant impact on long-term prognosis. However, timely recognition of specific scenarios – including transition to the end-stage phase – may be challenging due to limited awareness of the progression patterns of HCM. This in turn may lead to missed therapeutic opportunities. To illustrate these difficulties, we describe two HCM patients who progressed from the typical hyperdynamic stage of asymmetric septal thickening to end-stage heart failure with severely reduced ejection fraction. We highlight the different stages of this complex inherited cardiomyopathy based on the clinical staging pro-posed by Olivotto and colleagues. In this way, we aim to provide a practical guide for clinicians and hope to increase awareness for this common form of cardiac disease

Basal and IL-1β enhanced chondrocyte chemotactic activity on monocytes are co-dependent on both IKKα and IKKβ NF-κB activating kinases

IKKα and IKKβ are essential kinases for activating NF-κB transcription factors that regulate cellular differentiation and inflammation. By virtue of their small size, chemokines support the crosstalk between cartilage and other joint compartments and contribute to immune cell chemotaxis in osteoarthritis (OA). Here we employed shRNA retroviruses to stably and efficiently ablate the expression of each IKK in primary OA chondrocytes to determine their individual contributions for monocyte chemotaxis in response to chondrocyte conditioned media. Both IKKα and IKKβ KDs blunted both the monocyte chemotactic potential and the protein levels of CCL2/MCP-1, the chemokine with the highest concentration and the strongest association with monocyte chemotaxis. These findings were mirrored by gene expression analysis indicating that the lowest levels of CCL2/MCP-1 and other monocyte-active chemokines were in IKKαKD cells under both basal and IL-1β stimulated conditions. We find that in their response to IL-1β stimulation IKKαKD primary OA chondrocytes have reduced levels of phosphorylated NFkappaB p65pSer536 and H3pSer10. Confocal microscopy analysis revealed co-localized p65 and H3pSer10 nuclear signals in agreement with our findings that IKKαKD effectively blunts their basal level and IL-1β dependent increases. Our results suggest that IKKα could be a novel OA disease target

Impact of Demographic Features, Lifestyle, and Comorbidities on the Clinical Expression of Hypertrophic Cardiomyopathy.

No abstract

Mission X: Train Like an Astronaut Pilot Study

Mission X: Train Like an Astronaut is an international educational challenge focusing on fitness and nutrition as we encourage students to "train like an astronaut." Teams of students (aged 8-12) learn principles of healthy eating and exercise, compete for points by finishing training modules, and get excited about their future as "fit explorers." The 18 core exercises (targeting strength, endurance, coordination, balance, spatial awareness, and more) involve the same types of skills that astronauts learn in their training and use in spaceflight. This first-of-its-kind cooperative outreach program has allowed 14 space agencies and various partner institutions to work together to address quality health/fitness education, challenge students to be more physically active, increase awareness of the importance of lifelong health and fitness, teach students how fitness plays a vital role in human performance for exploration, and inspire and motivate students to pursue careers in STEM fields. The project was initiated in 2009 in response to a request by the International Space Life Sciences Working Group. USA, Netherlands, Italy, France, Germany, Austria, Colombia, Spain, and United Kingdom hosted teams for the pilot this past spring, and Japan held a modified version of the challenge. Several more agencies provided input into the preparations. Competing on 131 teams, more than 3700 students from 40 cities worldwide participated in the first round of Mission X. OUTCOMES AND BEST PRACTICES Members of the Mission X core team will highlight the outcomes of this international educational outreach pilot project, show video highlights of the challenge, provide the working group s initial assessment of the project and discuss the future potential of the effort. The team will also discuss ideas and best practices for international partnership in education outreach efforts from various agency perspectives and experience

Insect-based aquafeeds modulate the fatty acid profile of zebrafish: a comparison on the different life stages

Insects are considered as an alternative and sustainable ingredient for feed production. In this study, Hermetia illucens (Hi) prepupae (fed on coffee roasted by-product added with 10% Schyzochytrium sp., a marine protist rich in polyunsaturated fatty acids) was processed into meal and included at graded levels in five experimental diets to replace dietary fish meal (0, 25, 50, 75, 100%) offered to zebrafish (Danio rerio) as experimental model. The fatty acids (FAs) profile of fish larvae (20 days), juveniles (2 months, deprived of the viscera) and adults (6 months, male and female, deprived of the viscera) specimens was investigated to evaluate the impact of dietary FM replacement with full-fat Hi prepupae meal. For the first time, the quantification of FAs in Danio rerio, performed by gas chromatography-mass spectrometry, was computed in absolute terms (mg 100g-1 dw), identifying the real variation in the content of any single FA. In fish, quantified total FAs in larvae, juvenile, adult male and adult female were 134±2, 235±8, 266±3 and 266±8 mg g-1 dw, respectively. With respect to zebrafish fed the control diet, specimens fed diet with increasing level of Hi prepupae meal showed significantly higher content of saturated and omega6 FAs, and significantly lower content of poly-unsaturated and omega3 FAs, reflecting partially the FAs composition of the administered diets. At the same time, the docosahexaenoic/eicosapentaenoic acid ratio increased significantly. Moreover, adult female showed a higher content of PUFA with respect to adult male, which could be justified by the needs of physiological reproductive processes. The principal component analysis demonstrated that the FAs composition in Danio rerio depends on both the life stage and the diet