The Association Between the Long-Term Change in Directly Measured Cardiorespiratory Fitness and Mortality Risk

Introduction: There is a strong inverse association between cardiorespiratory fitness (CRF) and mortality outcomes. This relationship has predominantly been assessed cross-sectionally, however low CRF is a modifiable risk factor, thus assessing this association using a single baseline measure may be sub-optimal. Purpose: To examine the association of the long-term change in CRF, measured using cardiopulmonary exercise testing (CPX) with all-cause and disease-specific mortality. Methods: Participants included 833 apparently healthy men and women (42.9±10.8 years) who underwent two maximal CPXs, the second CPX being ≥ 1 year following the baseline assessment. Participants were followed for 17.7 ± 11.8 years for allcause, cardiovascular disease (CVD), and cancer mortality. Cox-proportional hazard models were performed to determine the association between the change in CRF, computed as visit 1 (V1) peak oxygen consumption (VO2peak (ml·kg-1·min-1)) – visit 2 (V2) VO2peak, and mortality outcomes. Results: During follow-up, 172 participants died. Overall, the change in CPX-derived CRF was inversely related to all-cause, CVD, and cancer mortality (p\u3c0.05). Each 1 ml·kg-1·min-1 increase was associated with a 10.8, 14.7, and 15.9% reductions in allcause, CVD, and cancer mortality, respectively. The inverse relationship between CRF and all-cause mortality remained significant (p\u3c0.05) when men and women were examined independently, after adjusting for years since first CPX, baseline VO2peak, and age. Conclusion: Long-term changes in CRF were inversely related to mortality outcomes, and mortality was better predicted by CRF measured at subsequent examination than baseline CRF. These findings support the recent American Heart Association scientific statement advocating CRF as a clinical vital sign that should be assessed routinely in clinical practice, as well as support regular participation in physical activity to maintain adequate CRF levels across the lifespan

AN EVALUATION OF THREE AREAS FOR POTENTIAL POPULATONS OF WHOOPING CRANES

Sandhill crane (Grus canadensis) populations were evaluated on the Seney NWR, Michigan, the Okefenokee Swamp, Georgia, and in southcentral Florida to evaluate their suitability to support introduced whooping cranes (G. americana). This paper compares data collected at these sites and additional data collected in northcentral Florida. The length of the egg-laying period varied from 4.5 months in central Florida to 1 month at Seney, but egg-laying ceased at all sites from mid-May to early June. Mean clutch sizes were similar 0.7-1.9). Renesting ranged from 79% in northcentral Florida to \u3c=5% at Seney. These dates and values are consistent with nesting successes that ranged from 48% in northcentral Florida to 80% at Seney. Average annual recruitment, 12.3 juveniles/lOa adults, was highest on the Kissimmee Prairie in southcentral Florida. Average annual horne range size for the non-migratory populations were 1 km2 on the Okefenokee and 6.6 km2 on the Kissimmee. Nesting season horne range sizes ranged from 0.5 km2 on the Okefenokee to 1.8 km2 at Seney. All candidate populations successfully satisfied most of the guidelines for potential whooping crane populations as established by the Whooping Crane Recovery Team. Once reintroduction techniques have been refined, any or all of the study sites have the capacity to accommodate a flock of whooping cranes commensurate with Whooping Crane Recovery Team recommendations

Cardiorespiratory Fitness and Mortality in Healthy Men and Women

Background There is a well-established inverse relationship between cardiorespiratory fitness (CRF) and mortality. However, this relationship has almost exclusively been studied using estimated CRF. Objectives This study aimed to assess the association of directly measured CRF, obtained using cardiopulmonary exercise (CPX) testing with all-cause, cardiovascular disease (CVD), and cancer mortality in apparently healthy men and women. Methods Participants included 4,137 self-referred apparently healthy adults (2,326 men, 1,811 women; mean age: 42.8 ± 12.2 years) who underwent CPX testing to determine baseline CRF. Participants were followed for 24.2 ± 11.7 years (1.1 to 49.3 years) for mortality. Cox-proportional hazard models were performed to determine the relationship of CRF (ml·kg-1·min-1) and CRF level (low, moderate, and high) with mortality outcomes. Results During follow-up, 727 participants died (524 men, 203 women). CPX-derived CRF was inversely related to all-cause, CVD, and cancer mortality. Low CRF was associated with higher risk for all-cause (hazard ratio [HR]: 1.73; 95% confidence interval [CI]: 1.20 to 3.50), CVD (HR: 2.27; 95% CI: 1.20 to 3.49), and cancer (HR: 2.07; 95% CI: 1.18 to 3.36) mortality compared with high CRF. Further, each metabolic equivalent increment increase in CRF was associated with a 11.6%, 16.1%, and 14.0% reductions in all-cause, CVD, and cancer mortality, respectively. Conclusions Given the prognostic ability of CPX-derived CRF for all-cause and disease-specific mortality outcomes, its use should be highly considered for apparently healthy populations as it may help to improve the efficacy of the individualized patient risk assessment and guide clinical decisions

The Influence of Change in Cardiorespiratory Fitness With Short-Term Exercise Training on Mortality Risk From The Ball State Adult Fitness Longitudinal Lifestyle Study

Objective To assess the influence of changes in cardiorespiratory fitness (CRF) after exercise training on mortality risk in a cohort of self-referred, apparently healthy adults. Patients and Methods A total of 683 participants (404 men, 279 women; mean age: 42.7±11.0 y) underwent two maximal cardiopulmonary exercise tests (CPX) between March 20, 1970, and December 11, 2012, to assess CRF at baseline (CPX1) and post-exercise training (CPX2). Participants were followed for an average of 29.8±10.7 years after their CPX2. Cox proportional hazards models were performed to determine the relationship of CRF change with mortality, with change in CRF as a continuous variable, as well as a categorical variable. A Wald chi-square test was used to compare the coefficients estimating the relationship of peak oxygen consumption (VO2peak) at CPX1 with VO2peak measured at CPX2 with time until death for all-cause mortality. Results During the follow-up period there were 180 deaths. When assessed independently, there were 20% (95% CI, 10–49%) and 38% (95% CI, 7–66%) lower mortality risks per 1 metabolic equivalent improvement in CRF (P\u3c.01) in men and women, respectively, after multivariable adjustment. Those that remained unfit had ∼2-fold higher risk for all-cause mortality compared with those that remained fit and CRF at CPX2 was a stronger predictor of all-cause mortality than at CPX1 (P=.02). Conclusion Improving CRF through exercise training lowers mortality risk. Clinicians should encourage individuals to participate in exercise training to improve CRF to lower risk of mortality

The Association between the Change in Directly Measured Cardiorespiratory Fitness across Time and Mortality Risk

Background The relationship between cardiorespiratory fitness (CRF) and mortality risk has typically been assessed using a single measurement, though some evidence suggests the change in CRF over time influences risk. This evidence is predominantly based on studies using estimated CRF (CRFe). The strength of this relationship using change in directly measured CRF over time in apparently healthy men and women is not well understood. Purpose To examine the association of change in CRF over time, measured using cardiopulmonary exercise testing (CPX), with all-cause and disease-specific mortality and to compare baseline and subsequent CRF measurements as predictors of all-cause mortality. Methods Participants included 833 apparently healthy men and women (42.9 ± 10.8 years) who underwent two maximal CPXs, the second CPX being ≥1 year following the baseline assessment (mean 8.6 years, range 1.0 to 40.3 years). Participants were followed for up to 17.7 (SD 11.8) years for all-cause-, cardiovascular disease- (CVD), and cancer mortality. Cox-proportional hazard models were performed to determine the association between the change in CRF, computed as visit 1 (CPX1) peak oxygen consumption (VO2peak [mL·kg−1·min−1]) – visit 2 (CPX2) VO2peak, and mortality outcomes. A Wald-Chi square test of equality was used to compare the strength of CPX1 to CPX2 VO2peak in predicting mortality. Results During follow-up, 172 participants died. Overall, the change in CPX-CRF was inversely related to all-cause, CVD, and cancer mortality (p < 0.05). Each 1 mL·kg−1·min−1 increase was associated with a ~11, 15, and 16% (all p < 0.001) reduction in all-cause, CVD, and cancer mortality, respectively. The inverse relationship between CRF and all-cause mortality was significant (p < 0.05) when men and women were examined independently, after adjusting for years since first CPX, baseline VO2peak, and age. Further, the Wald Chi-square test of equality found CPX2 VO2peak to be a significantly stronger predictor of all-cause mortality than CPX1 VO2peak (p < 0.05). Conclusion The change in CRF over time was inversely related to mortality outcomes, and mortality was better predicted by CRF measured at subsequent test than CPX1 CRF. These findings emphasize the importance of adopting lifestyle behaviors that promote CRF, as well as support the need for routine assessment of CRF in clinical practice to better assess risk

Growth characteristics in individuals with osteogenesis imperfecta in North America: results from a multicenter study.

PurposeOsteogenesis imperfecta (OI) predisposes people to recurrent fractures, bone deformities, and short stature. There is a lack of large-scale systematic studies that have investigated growth parameters in OI.MethodsUsing data from the Linked Clinical Research Centers, we compared height, growth velocity, weight, and body mass index (BMI) in 552 individuals with OI. Height, weight, and BMI were plotted on Centers for Disease Control and Prevention normative curves.ResultsIn children, the median z-scores for height in OI types I, III, and IV were -0.66, -6.91, and -2.79, respectively. Growth velocity was diminished in OI types III and IV. The median z-score for weight in children with OI type III was -4.55. The median z-scores for BMI in children with OI types I, III, and IV were 0.10, 0.91, and 0.67, respectively. Generalized linear model analyses demonstrated that the height z-score was positively correlated with the severity of the OI subtype (P &lt; 0.001), age, bisphosphonate use, and rodding (P &lt; 0.05).ConclusionFrom the largest cohort of individuals with OI, we provide median values for height, weight, and BMI z-scores that can aid the evaluation of overall growth in the clinic setting. This study is an important first step in the generation of OI-specific growth curves

Effects of geolocators on hatching success, return rates, breeding movements, and change in body mass in 16 species of Arctic-breeding shorebirds

Additional Authors: Bruce Casler; Maureen Christie; Jonathan T. Coleman; Jesse R. Conklin; Willow B. English; H. River Gates; Olivier Gilg; Marie-Andrée Giroux; Ken Gosbell; Chris Hassell; Jim Helmericks; Andrew Johnson; Borgný Katrínardóttir; Kari Koivula; Jean-Francois Lamarre; Johannes Lang; David B. Lank; Nicolas Lecomte; Joe Liebezeit; Vanessa Loverti; Laura McKinnon; Clive Minton; David Mizrahi; Erica Nol; Veli-Matti Pakanen; Johanna Perz; Ron Porter; Jennie Rausch; Jeroen Reneerkens; Nelli Rönkä; Sarah Saalfeld; Nathan Senner; Benoît Sittler; Paul A. Smith; Kristine Sowl; Audrey Taylor; David H. Ward; Stephen YezerinacCitation: Weiser, E.L., R.B. Lanctot, S.C. Brown, J.A. Alves, P.F. Battley, R. Bentzen, J. Bêty, M.A. Bishop, M. Boldenow, L. Bollache, B. Casler, M. Christie, J.T. Coleman, J.R. Conklin, W.B. English, H.R. Gates, O. Gilg, M.-A. Giroux, K. Gosbell, C. Hassell, J. Helmericks, A. Johnson, B. Katrínardóttir, K. Koivula, E. Kwon, J.-F. Lamarre, J. Lang, D.B. Lank, N. Lecomte, J. Liebezeit, V. Loverti, L. McKinnon, C. Minton, D. Mizrahi, E. Nol, V.-M. Pakanen, J. Perz, R. Porter, J. Rausch, J. Reneerkens, N. Rönkä, S. Saalfeld, N. Senner, B. Sittler, P.A. Smith, K. Sowl, A. Taylor, D.H. Ward, S. Yezerinac, and B.K. Sandercock. 2016. Effects of geolocators on hatching success, return rates, breeding movements and change in body mass in 16 species of Arctic-breeding shorebirds. Movement Ecology 4: art12. URL: http://movementecologyjournal.biomedcentral.com/articles/10.1186/s40462-016-0077-6Background: Geolocators are useful for tracking movements of long-distance migrants, but potential negative effects on birds have not been well studied. We tested for effects of geolocators (0.8–2.0 g total, representing 0.1–3.9 % of mean body mass) on 16 species of migratory shorebirds, including five species with 2–4 subspecies each for a total of 23 study taxa. Study species spanned a range of body sizes (26–1091 g) and eight genera, and were tagged at 23 breeding and eight nonbreeding sites. We compared breeding performance and return rates of birds with geolocators to control groups while controlling for potential confounding variables. Result: We detected negative effects of tags for three small-bodied species. Geolocators reduced annual return rates for two of 23 taxa: by 63 % for semipalmated sandpipers and by 43 % for the arcticola subspecies of dunlin. High resighting effort for geolocator birds could have masked additional negative effects. Geolocators were more likely to negatively affect return rates if the total mass of geolocators and color markers was 2.5–5.8 % of body mass than if tags were 0.3–2.3 % of body mass. Carrying a geolocator reduced nest success by 42 % for semipalmated sandpipers and tripled the probability of partial clutch failure in semipalmated and western sandpipers. Geolocators mounted perpendicular to the leg on a flag had stronger negative effects on nest success than geolocators mounted parallel to the leg on a band. However, parallel-band geolocators were more likely to reduce return rates and cause injuries to the leg. No effects of geolocators were found on breeding movements or changes in body mass. Among-site variation in geolocator effect size was high, suggesting that local factors were important. Conclusions: Negative effects of geolocators occurred only for three of the smallest species in our dataset, but were substantial when present. Future studies could mitigate impacts of tags by reducing protruding parts and minimizing use of additional markers. Investigators could maximize recovery of tags by strategically deploying geolocators on males, previously marked individuals, and successful breeders, though targeting subsets of a population could bias the resulting migratory movement data in some species

The Epoxygenases CYP2J2 Activates the Nuclear Receptor PPARα In Vitro and In Vivo

Peroxisome proliferator-activated receptors (PPARs) are a family of three (PPARalpha, -beta/delta, and -gamma) nuclear receptors. In particular, PPARalpha is involved in regulation of fatty acid metabolism, cell growth and inflammation. PPARalpha mediates the cardiac fasting response, increasing fatty acid metabolism, decreasing glucose utilisation, and is the target for the fibrate lipid-lowering class of drugs. However, little is known regarding the endogenous generation of PPAR ligands. CYP2J2 is a lipid metabolising cytochrome P450, which produces anti-inflammatory mediators, and is considered the major epoxygenase in the human heart.Expression of CYP2J2 in vitro results in an activation of PPAR responses with a particular preference for PPARalpha. The CYP2J2 products 8,9- and 11-12-EET also activate PPARalpha. In vitro, PPARalpha activation by its selective ligand induces the PPARalpha target gene pyruvate dehydrogenase kinase (PDK)4 in cardiac tissue. In vivo, in cardiac-specific CYP2J2 transgenic mice, fasting selectively augments the expression of PDK4.Our results establish that CYP2J2 produces PPARalpha ligands in vitro and in vivo, and suggests that lipid metabolising CYPs are prime candidates for the integration of global lipid changes to transcriptional signalling events

Secondary metabolites of the sponge-derived fungus Acremonium persicinum

This study reports the isolation and characterization of six new acremine metabolites, 5-chloroacremine A (4), 5-chloroacremine H (5), and acremines 0 (6), P (7), Q(8), and R (9), together with the known acremines A (1), F (2), and N (3) from the fungus Acremonium persicinum cultured from the marine sponge Anomoianthella rubra. The relative configuration of acremine F (2) was determined by analyses of proton coupling constant values and NOESY data, and the absolute configuration confirmed as (IS, 4S, 6R) by X-ray crystallographic analysis of the borate ester derivative 15. Acremines O, P, and R were each shown to be of 8R configuration by H-1 NMR analyses of MPA esters. The relative configurations suggested for acremines P and Q were each deduced by molecular modeling together with NOESY and coupling constant data. The (3)J(H-C) values in acremine P were measured using the pulse sequence EXSIDE, and the observed (3)J(H8-C4) of 5.4 Hz and small (3)J(H-C) values

Canagliflozin impairs T cell effector function via metabolic suppression in autoimmunity

Augmented T cell function leading to host damage in autoimmunity is supported by metabolic dysregulation, making targeting immunometabolism an attractive therapeutic avenue. Canagliflozin, a type 2 diabetes drug, is a sodium glucose co-transporter 2 (SGLT2) inhibitor with known off-target effects on glutamate dehydrogenase and complex I. However, the effects of SGLT2 inhibitors on human T cell function have not been extensively explored. Here, we show that canagliflozin-treated T cells are compromised in their ability to activate, proliferate, and initiate effector functions. Canagliflozin inhibits T cell receptor signaling, impacting on ERK and mTORC1 activity, concomitantly associated with reduced c-Myc. Compromised c-Myc levels were encapsulated by a failure to engage translational machinery resulting in impaired metabolic protein and solute carrier production among others. Importantly, canagliflozin-treated T cells derived from patients with autoimmune disorders impaired their effector function. Taken together, our work highlights a potential therapeutic avenue for repurposing canagliflozin as an intervention for T cell-mediated autoimmunity