Left ventricular function and mechanics following prolonged endurance exercise: an update and meta-analysis with insights from novel techniques.

BACKGROUND: The cardiac consequences of undertaking endurance exercise are the topic of recent debate. The purpose of this review is to provide an update on a growing body of literature, focusing on left ventricular (LV) function following prolonged endurance exercise over 2 h in duration which have employed novel techniques, including myocardial speckle tracking, to provide a more comprehensive global and regional assessment of LV mechanics. METHODS: Prospective studies were filtered independently following a pre-set criteria, resulting in the inclusion of 27 studies in the analyses. A random-effects meta-analysis was used to determine the weighted mean difference and 95% confidence intervals (CI) of LV functional and mechanical data from pre-to-post-exercise. Narrative commentary was also provided where volume of available evidence precluded meta-analysis. RESULTS: A significant overall reduction in LV longitudinal strain (Ɛ) n = 22 (- 18 ± 1 to - 17 ± 1%; effect size (d) - 9: - 1 to - 0.5%), strain rate n = 10 (SR; d - 0.9: - 0.1.3 to - 0.5 l/s) and twist n = 5 (11.9 ± 2.2 to 8.7 ± 2.2°, d - 1: - 1.6 to - 0.3°) was observed following strenuous endurance exercise (range 120-1740 min) (P  0.05). CONCLUSION: The meta-analysis and narrative commentary demonstrated that a reduction in LV function and mechanics is evident following prolonged endurance exercise. The mechanism(s) responsible for these changes are complex and likely multi-factorial in nature and may be linked to right and left ventricular interaction

Impaired Orthostatic Blood Pressure Recovery is associated with Unexplained and Injurious Falls

Background/Objectives: Cardiovascular disorders are recognised as important modifiable risk factors for falls. However the association between falls and orthostatic hypotension (OH) remains ambivalent, particularly because of poor measurement methods of previous studies. Our goal was to determine for the first time to what extent OH (and variants) are risk factors for incident falls, unexplained falls (UF), injurious falls (IF) and syncope using dynamic blood pressure (BP) measurements in a population study. Design: Nationally Representative Longitudinal Cohort Study - The Irish Longitudinal Study on Ageing (TILDA) – wave 1 (2009-2011) with 2 year follow-up at wave 2 (2012-2013). Setting: Community dwelling adults. Participants: 4127 participants were randomly sampled from the population of older adults aged ≥50 years resident in Ireland. Measurements: Continuous BP recordings measured during active stands were analysed. OH and variants (initial OH and impaired orthostatic BP stabilisation OH(40)) were defined using dynamic BP measurements. Associations with the number of falls, UF, IF and syncope reported two years later were assessed using negative binomial and modified Poisson regression. Results: Participants had a mean age 61.5(8.2) years (54.2% female). OH(40) was associated with increased relative risk of UF (RR:1.52 95%CI:1.03-2.26). OH was associated with all-cause falls (IRR:1.40 95%CI:1.01-1.96), UF(RR:1.81 95%CI:1.06-3.09), and IF(RR:1.58 95%CI:1.12-2.24). IOH was not associated with any outcome. Conclusion: With the exception of initial orthostatic hypotension, beat-to-beat measures of impaired orthostatic BP recovery (delayed or incomplete stabilisation) are independent risk factors for future falls, unexplained falls, and injurious falls

Assessment of Equine Autoimmune Thrombocytopenia (EAT) by flow cytometry

RATIONALE: Thrombocytopenia is a platelet associated process that occurs in human and animals as result of i) decreased production; ii) increased utilization; iii) increased destruction coupled to the presence of antibodies, within a process know as immune-mediated thrombocytopenia (IMT); or iv) platelet sequestration. Thus, the differentiation of the origin of IMT and the development of reliable diagnostic approaches and methodologies are important in the clarification of IMT pathogenesis. Therefore, there is a growing need in the field for easy to perform assays for assessing platelet morphological characteristics paired with detection of platelet-bound IgG. OBJECTIVES: This study is aimed to develop and characterize a single color flow cytometric assay for detection of platelet-bound IgG in horses, in combination with flow cytometric assessment of platelet morphological characteristics. FINDINGS: The FSC and SSC evaluation of the platelets obtained from the thrombocytopenic animals shows several distinctive features in comparison to the flow cytometric profile of platelets from healthy animals. The thrombocytopenic animals displayed i) increased number of platelets with high FSC and high SSC, ii) a significant number of those gigantic platelets had strong fluorescent signal (IgG bound), iii) very small platelets or platelet derived microparticles were found significantly enhanced in one of the thrombocytopenic horses, iv) significant numbers of these microplatelet/microparticles/platelet-fragments still carry very high fluorescence. CONCLUSIONS: This study describes the development and characterization of an easy to perform, inexpensive, and noninvasive single color flow cytometric assay for detection of platelet-bound IgG, in combination with flow cytometric assessment of platelet morphological characteristics in horses

Intraspecific Correlations of Basal and Maximal Metabolic Rates in Birds and the Aerobic Capacity Model for the Evolution of Endothermy

The underlying assumption of the aerobic capacity model for the evolution of endothermy is that basal (BMR) and maximal aerobic metabolic rates are phenotypically linked. However, because BMR is largely a function of central organs whereas maximal metabolic output is largely a function of skeletal muscles, the mechanistic underpinnings for their linkage are not obvious. Interspecific studies in birds generally support a phenotypic correlation between BMR and maximal metabolic output. If the aerobic capacity model is valid, these phenotypic correlations should also extend to intraspecific comparisons. We measured BMR, Msum (maximum thermoregulatory metabolic rate) and MMR (maximum exercise metabolic rate in a hop-flutter chamber) in winter for dark-eyed juncos (Junco hyemalis), American goldfinches (Carduelis tristis; Msum and MMR only), and black-capped chickadees (Poecile atricapillus; BMR and Msum only) and examined correlations among these variables. We also measured BMR and Msum in individual house sparrows (Passer domesticus) in both summer, winter and spring. For both raw metabolic rates and residuals from allometric regressions, BMR was not significantly correlated with either Msum or MMR in juncos. Moreover, no significant correlation between Msum and MMR or their mass-independent residuals occurred for juncos or goldfinches. Raw BMR and Msum were significantly positively correlated for black-capped chickadees and house sparrows, but mass-independent residuals of BMR and Msum were not. These data suggest that central organ and exercise organ metabolic levels are not inextricably linked and that muscular capacities for exercise and shivering do not necessarily vary in tandem in individual birds. Why intraspecific and interspecific avian studies show differing results and the significance of these differences to the aerobic capacity model are unknown, and resolution of these questions will require additional studies of potential mechanistic links between minimal and maximal metabolic output

Transformation of spin information into large electrical signals via carbon nanotubes

Spin electronics (spintronics) exploits the magnetic nature of the electron, and is commercially exploited in the spin valves of disc-drive read heads. There is currently widespread interest in using industrially relevant semiconductors in new types of spintronic devices based on the manipulation of spins injected into a semiconducting channel between a spin-polarized source and drain. However, the transformation of spin information into large electrical signals is limited by spin relaxation such that the magnetoresistive signals are below 1%. We overcome this long standing problem in spintronics by demonstrating large magnetoresistance effects of 61% at 5 K in devices where the non-magnetic channel is a multiwall carbon nanotube that spans a 1.5 micron gap between epitaxial electrodes of the highly spin polarized manganite La0.7Sr0.3MnO3. This improvement arises because the spin lifetime in nanotubes is long due the small spin-orbit coupling of carbon, because the high nanotube Fermi velocity permits the carrier dwell time to not significantly exceed this spin lifetime, because the manganite remains highly spin polarized up to the manganite-nanotube interface, and because the interfacial barrier is of an appropriate height. We support these latter statements regarding the interface using density functional theory calculations. The success of our experiments with such chemically and geometrically different materials should inspire adventure in materials selection for some future spintronicsComment: Content highly modified. New title, text, conclusions, figures and references. New author include

Adult case of partial trisomy 9q

Background: \ud Complete and partial trisomy 9 is the fourth most common chromosomal disorder. It is also associated with various congenital characteristics affecting the cranio-facial, skeletal, central nervous, gastrointestinal, cardiac and renal systems. Very few cases have been reported in adults. Partial trisomy 9q is also associated with short stature, poor growth and growth hormone deficiency. This is the first reported case of an extensive endocrinology investigation of short stature in trisomy 9q and the outcome of growth hormone treatment.\ud \ud Case Presentation: \ud The case involves a 23-year-old female of pure partial trisomy 9q. The case involves a 23-year old female with pure partial trisomy 9q involving a duplication of 9q22.1 to q32, de novo, confirmed by genetic studies using fluorescene in situ hybridization (FISH) method. The diagnosis was at 6 years of age. She did not demonstrate all the congenital morphologies identified with trisomy 9q disorders especially in relation to multi-organ morphologies. There is also a degree of associated intellectual impairment. At prepuberty, she was referred for poor growth and was diagnosed with partial growth hormone deficiency. She responded very well to treatment with growth hormone and is currently living an independent life with some support.\ud \ud Conclusions: \ud Trisomy 9q is associated with short stature and failure to thrive. Growth hormone deficiency should be identified in cases of trisomy 9q and treatment offered. This is the first reported case of response to growth hormone replacement in partial trisomy 9

Multiple reassortment events in the evolutionary history of H1N1 influenza A virus since 1918

The H1N1 subtype of influenza A virus has caused substantial morbidity and mortality in humans, first documented in the global pandemic of 1918 and continuing to the present day. Despite this disease burden, the evolutionary history of the A/H1N1 virus is not well understood, particularly whether there is a virological basis for several notable epidemics of unusual severity in the 1940s and 1950s. Using a data set of 71 representative complete genome sequences sampled between 1918 and 2006, we show that segmental reassortment has played an important role in the genomic evolution of A/H1N1 since 1918. Specifically, we demonstrate that an A/H1N1 isolate from the 1947 epidemic acquired novel PB2 and HA genes through intra-subtype reassortment, which may explain the abrupt antigenic evolution of this virus. Similarly, the 1951 influenza epidemic may also have been associated with reassortant A/H1N1 viruses. Intra-subtype reassortment therefore appears to be a more important process in the evolution and epidemiology of H1N1 influenza A virus than previously realized

Effects of preload manipulation on right ventricular contractility: invasive pressure-area loop versus non-invasive strain-area loop.

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WNT signaling regulates self-renewal and differentiation of prostate cancer cells with stem cell characteristics

Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear Β-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer cells express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector Β-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the self-renewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.Peer reviewe

Cis and Trans Effects of Human Genomic Variants on Gene Expression

This work was funded by the Louis-Jeantet Foundation (http://www.jeantet.ch/), the European Research Council (Grant ID: 260927 http://erc.europa.eu/), the Swiss National Foundation (Grant ID: 130342 http://www.snf.ch), NCCR Frontiers In Genetics (http://www.frontiers-in-genetics.org), the UK Medical Research Council (http://www.mrc.ac.uk) and the Wellcome Trust (Grant ID: 092731).