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The big blue octopus, Octopus cyanea, occurs on coral reefs throughout the Indo-Pacific region from East Africa to the Hawaiian Islands, wherein it is of great ecological and socio-economic importance. However, many components of its intraspecific biodiversity, such as population structure, are unresolved due to a lack of informative genetic markers. To address this issue, which may compromise conservation and sustainability efforts, the development and characterisation of the first species-specific microsatellite loci for O. cyanea are described here. The eight loci were characterised by the genotyping of 40 adults from Madagascar, which revealed an average of 13.5 alleles per locus (range 9-18). The observed and expected heterozygosity per locus ranged from 0.432 to 0.949 and from 0.481 to 0.989, respectively. No evidence of linkage disequilibrium was detected between pairs of loci. Genotype proportions at six loci conformed to Hardy-Weinberg equilibrium expectations, with two loci exhibiting significant heterozygote deficits. These loci are applicable to multiple areas of eco-evolutionary research and, thus, represent a valuable resource for future studies of O. cyanea.

In children, levels of play, physical activity, and fitness are key indicators of health and disease and closely tied to optimal growth and development. Cardiopulmonary exercise testing (CPET) provides clinicians with biomarkers of disease and effectiveness of therapy, and researchers with novel insights into fundamental biological mechanisms reflecting an integrated physiological response that is hidden when the child is at rest. Yet the growth of clinical trials utilizing CPET in pediatrics remains stunted despite the current emphasis on preventative medicine and the growing recognition that therapies used in children should be clinically tested in children. There exists a translational gap between basic discovery and clinical application in this essential component of child health. To address this gap, the NIH provided funding through the Clinical and Translational Science Award (CTSA) program to convene a panel of experts. This report summarizes our major findings and outlines next steps necessary to enhance child health exercise medicine translational research. We present specific plans to bolster data interoperability, improve child health CPET reference values, stimulate formal training in exercise medicine for child health care professionals, and outline innovative approaches through which exercise medicine can become more accessible and advance therapeutics across the broad spectrum of child health.

We present a semi-quantitative survey of ‘live’ (stained) and dead hormosinacean foraminifera at six sites (500–2,000 m water depth; bottom-water oxygen concentrations 0.007–2.43 ml L−1) across the Indian margin oxygen minimum zone (OMZ). Abundance of stained and dead specimens was highest at 800 m followed by 1,100 m, lowest at 2,000 m (stained) and 500 m (dead). The peak at 800 m possibly represents a release from oxygen stress combined with a rich food supply (‘edge effect’). We recognised 31 species (27 Reophax, 2 Hormosinella, 1 Hormosina and 1 Nodosinella) among the 605 stained and dead specimens; the majority (21) are apparently undescribed. Species richness was low at 2,000 m; within the OMZ, it was maximal at 1,100 m and minimal at 500 m for both stained and dead populations. Three species (R. agglutinatus, R. aff. bilocularis and R. dentaliniformis) occurred across the entire depth range. However, most species were either confined to the 2,000-m site or to one or more sites within the OMZ. Multivariate analysis of assemblage composition revealed that the 2,000-m site was distinct from shallower sites. Within the OMZ, the 900- and 1,100-m sites were the most similar, and the 500-m site the most distinct. Stained:dead test ratios were maximal at 500–835 m, perhaps reflecting enhanced preservation of cytoplasm at very low oxygen concentrations. At least two Reophax species are common to the Indian and Pakistan margin OMZ; one of these may be confined to the core of the Arabian Sea OMZ.

Background Existing six minute walk distance (6MWD) prediction equations were developed using healthy children and include relatively small sample sizes. Children with congenital heart disease and pulmonary hypertension (PH) are often small-for-age, so the existing pediatric prediction equations are likely a poor fit for children with PH. Currently, there are no equations for 6MWD among children with PH. Objectives Evaluate the validity of five existing pediatric prediction equations among the 6MWD of children with PH, including for each World Health Organization (WHO) class. Develop a validated predictive equation for use in children with PH. Methods/results The 6MWDs from 711 six minute walk tests (6MWTs) of children aged four through 18years with PH were analyzed retrospectively and were evaluated against existing pediatric prediction equations. Existing pediatric prediction equations overestimated the walk distance among our population. The predicted distances versus actual distances were significantly different for each WHO class, with higher class associated with greater difference. A new prediction equation for 6MWD among children with PH was developed and validated with 65 additional 6MWTs. Our prediction equation demonstrates higher goodness of fit for all WHO classes than the preexisting pediatric equations. Conclusions Existing prediction equations for 6MWD among healthy children are not accurate for children with PH, particularly for children with more advanced stages of the disease (WHO classes III and IV). We present a new prediction equation for children with PH (WHO classes I through IV) that provides reference for medical care and management.

The big blue octopus, Octopus cyanea, occurs on coral reefs throughout the Indo-Pacific region from East Africa to the Hawaiian Islands, wherein it is of great ecological and socio-economic importance. However, many components of its intraspecific biodiversity, such as population structure, are unresolved due to a lack of informative genetic markers. To address this issue, which may compromise conservation and sustainability efforts, the development and characterisation of the first species-specific microsatellite loci for O. cyanea are described here. The eight loci were characterised by the genotyping of 40 adults from Madagascar, which revealed an average of 13.5 alleles per locus (range 9–18). The observed and expected heterozygosity per locus ranged from 0.432 to 0.949 and from 0.481 to 0.989, respectively. No evidence of linkage disequilibrium was detected between pairs of loci. Genotype proportions at six loci conformed to Hardy–Weinberg equilibrium expectations, with two loci exhibiting significant heterozygote deficits. These loci are applicable to multiple areas of eco-evolutionary research and, thus, represent a valuable resource for future studies of O. cyanea.

BackgroundData assessing the effect of altitude on Fontan haemodynamics are limited to experimental models and case reports. Both suggest a detrimental impact. This study describes exercise performance in patients with Fontan circulation and matched controls at a low altitude versus at sea level. We sought to assess the impact of increasing altitude on functional capacity in patients with Fontan palliation.MethodsA retrospective review of 22 patients at low altitude (1602 metres) and 119 patients at sea level with Fontan circulation, as well as age-, gender-, and altitude-matched controls, underwent maximal cardiopulmonary exercise testing. Linear regression models were created to determine the influence of altitude on differences in exercise variables between Fontan patients and their matched controls.ResultsPeak oxygen consumption was 28.4 millilitres per kilogram per minute (72% predicted) for the sea-level cohort and 24.2 millilitres per kilogram per minute (63% predicted) for the moderate altitude cohort. The matched case–control differences for patients at moderate altitude were greater for peak oxygen consumption (−29% against −13%, p = 0.04), anaerobic threshold (−36% against −5%, p = 0.001), and oxygen pulse (−35% against −18%, p = 0.007) when compared with patients living at sea level. When compared to institution-matched controls, the same parameters fell by 3%, 8.9%, and 4.2%, respectively, for each increase of 1000 feet in residential altitude (p = 0.03, p = 0.001, and p = 0.05, respectively).ConclusionsPatients with Fontan circulation at a higher altitude have impairment in aerobic capacity when compared with patients at sea level. Reduction in exercise capacity is associated with a reduction in stroke volume, likely related to increased pulmonary vascular resistance.

Limited evidence suggests renin-angiotensin-aldosterone system (RAAS) polymorphisms alter the blood pressure (BP) response to aerobic exercise training. We examined if RAAS polymorphisms influenced postexercise hypotension in men with high normal to Stage 1 hypertension. Forty-seven men (44.2+/-1.4 years, 145.1+/-1.6/85.5+/-1.1 mmHg) randomly completed three experiments: seated rest (control) and two cycle exercise bouts at 40% (LITE) and 60% (MOD) of maximal oxygen consumption. Ambulating BP was measured for 14 h after each experiment. RAAS polymorphisms associated with hypertension (i.e. angiotensin converting I enzyme, ACE I/D; angiotensin II type 1 receptor, AT1R A/C; and intron 2 of aldosterone synthase, Int2 W/C) were analyzed using polymerase chain reaction and restriction enzyme digestion. Repeated measure ANOVA tested if BP differed between experimental conditions by RAAS genotypes. Compared to men with 0-2 variant alleles, men withor =3 combined RAAS variant alleles had lower average systolic BP (SBP) (P=0.030) and lower average diastolic BP (DBP) (P=0.009) for 14 h only after LITE. In contrast, average BP was not different for MOD and control between RAAS variant allele groups over this time period (Por =0.05). LITE reduced BP in men withor =3 variant RAAS alleles for 14 h, whereas MOD had no influence on BP in these men. In order to optimally prescribe exercise for its BP lowering benefits in those with hypertension, additional knowledge of how genetic variation affects the BP response to exercise is needed.

Octopus vulgaris, Octopus cyanea and Callistoctopus ornatus may co-occur in near-shore shallow reef habitats across the Southwestern Indian Ocean. All three species are harvested, both by small vessels and individual spearfishers and are of considerable socio-economic importance. Phenotypic-based discrimination of the three species is unreliable and at present species-specific catch data are not collected, preventing evaluation of species specific fisheries effects. In light of increasing exploitation rates the development of an unambiguous means of species discrimination is required for sustainable management and conservation of species and intraspecific stocks. In this study, a simple, cost effective, molecular technique to differentiate the three species is described.

Cystic fibrosis (CF) patients with advanced lung disease are at risk for developing pulmonary vascular disease and pulmonary hypertension, characterized by progressive exercise intolerance beyond the exercise-limiting effects of airways disease in CF. We report on a patient with severe CF lung disease who experienced clinically significant improvements in exercise tolerance and pulmonary hypertension without changing lung function during sildenafil therapy.

A trinomial distribution probability model was used to determine the rejection probabilities of various proposed tier-testing schemes for drug content uniformity testing of a unique drug product. The use of this probability model helped in defining a sampling plan and associated acceptance limits for uniformity of the constituted formulation that would assure an appropriate level of control for both releasing acceptable lots (those having desirable distributions of drug content) and rejecting unacceptable lots (those having undesirable distributions of drug content). The ATRIGEL® Delivery System with 10% doxycycline hyclate presents a challenge when testing for content uniformity because each product unit must be individually constituted just prior to application. This two-stage product is composed of doxycycline hyclate powder filled in one syringe and a liquid polymer formulation consisting of poly(dl-lactide) dissolved in N-methyl-2-pyrrolidone in another syringe. The drug substance and polymer formulation syringes are connected via Luer-Lok® fittings and the drug is blended with the delivery system by cycling the contents between the two syringes. The resulting constituted formulation is a viscous flowable mixture that is used to treat diseased tooth pockets in patients with periodontal disease.

This study sought to assess the safety of cardiopulmonary stress testing in 40 children with pulmonary arterial hypertension and to compare exercise responses in this patient cohort with those of a healthy control population. Patients with pulmonary hypertension had significant impairment in aerobic capacity, with a peak oxygen consumption of 20.7 +/- 6.9 versus 35.5 +/- 7.4 ml/kg/min in healthy controls (p0.0001). Peak oxygen consumption was strongly correlated with invasive measures of disease severity, including pulmonary vascular resistance index (r = -0.6, p = 0.006). Exercise testing can be performed safely in this group of patients and can yield valuable clinical information.

Cardiopulmonary exercise testing is widely used in a variety of cardiovascular conditions. Ventilatory efficiency slope can be derived from submaximal exercise testing. The present study sought to evaluate the relationship between ventilatory efficiency slope and functional capacity, outcomes, and disease severity in pediatric patients with pulmonary hypertension.Seventy six children and young adults with a diagnosis of pulmonary hypertension (PH) performed 258 cardiopulmonary exercise tests from 2001 to 2011. Each individual PH test was matched to a control test. Ventilatory efficiency slope was compared to traditional measures of functional capacity and disease severity including WHO functional classification, peak oxygen consumption, and invasive measures of pulmonary arterial pressures and pulmonary vascular resistance.Ventilatory efficiency slope was significantly higher in patients with pulmonary arterial hypertension, with an estimated increase of 7.2 for each increase in WHO class (p0.0001), compared with normal control subjects (38.9 vs. 30.9, p0.001). Ventilatory efficiency slope correlated strongly with invasive measures of disease severity including pulmonary vascular resistance index (r =0.61), pulmonary artery pressure (r =0.58), mean pulmonary artery pressure/mean aortic pressure ratio (r =0.52), and peak VO2 (r=-0.58). Ventilatory efficiency slope in 12 patients with poor outcomes (9 death, 3 lung transplant), was significantly elevated compared to patients who did not (51.1 vs. 37.9, p0.001).Ventilatory efficiency slope correlates well with invasive and noninvasive markers of disease severity including peak VO2, WHO functional class, and catheterization variables in pediatric patients with PH. Ventilatory efficiency slope may be a useful noninvasive marker for disease severity.

Blood pressure (BP) is immediately lowered after a session of dynamic exercise, e.g. postexercise hypotension (PEH). The optimal exercise intensity needed to evoke PEH has not been established. We examined the effect of light (LITE) and moderate (MOD) exercise intensity on PEH.Subjects were 49 men (mean +/- SEM, 43.8 +/- 1.4 years) with high normal to stage 1 hypertension (145.0 +/- 1.5/85.8 +/- 1.1 mmHg). Men randomly completed three blinded experiments: a control session and two cycle exercise bouts, one at 40% (LITE) and the other at 60% (MOD) of maximal oxygen consumption.Experiments began with a baseline period and were conducted at the same time of day and separated by/= 2 days. Subjects wore an ambulatory BP monitor after the experiments. Repeated measure analysis of variance (ANOVA) tested if BP and heart rate differed over time and between experimental conditions. Multivariate regression tested factors related to the BP response.For 9 h after all experiments, average awake systolic blood pressure (SBP) increased and diastolic blood pressure (DBP) decreased compared with baseline (P0.001). Average awake SBP increased up to 6.9 mmHg less (P0.001) and DBP decreased 2.6 mmHg more (P0.05) after exercise versus control. For 5 h, PEH was greater after MOD; but over the course of 9 h, LITE was as effective as MOD in eliciting PEH. Baseline BP was the primary factor explaining the BP response (beta = -0.434 to -0.718, r = 0.096-0.295).LITE and MOD evoked PEH throughout the daytime hours. Lower intensity dynamic exercise such as walking, contributes to BP control in men with hypertension.

The minimum duration of exercise needed to acutely lower blood pressure (BP) has not been established. The purpose of this study is to compare the effects of short and long duration on the BP response to a session of aerobic exercise.Subjects were 45 men (mean +/- SEM, 43.4 +/- 1.5 years) with elevated BP (144.6 +/- 1.6/85.2 +/- 1.1 mm Hg). Using a parallel design, men were randomly assigned to 40% (LITE, n = 23) or 60% (MOD, n = 22) of maximal oxygen consumption. Following assignment, they completed 3 experiments: a no-exercise control, and a 15-minute SHORT and 30-minute LONG cycle bout. Subjects left the laboratory wearing an ambulatory BP monitor. Repeated measure analysis of variance tested if BP differed among experimental conditions (no-exercise control, LONG, and SHORT) and over time within groups (LITE and MOD).For 9 hours, systolic BP increased from baseline after all conditions (P.001); however, systolic BP was reduced by 5.6 +/- 2.0 and 4.3 +/- 1.6 mm Hg after SHORT and LONG with LITE, and 4.1 +/- 1.6 and 4.9 +/- 1.9 mm Hg with MOD, respectively, compared with no-exercise control (P.05). For 9 hours, diastolic BP (DBP) decreased from baseline after all conditions (P.001). DBP was reduced by 2.1 +/- 1.0 and 3.6 +/- 1.4 mm Hg after SHORT and LONG with MOD for 3 hours (P.05), and average DBP was lower by 2.4 +/- 1.0 mm Hg after LONG with LITE for 9 hours versus no-exercise control (P.05).The immediate BP-lowering effects of short-duration, lower intensity exercise are comparable to those of higher amounts of exercise. Additional investigation is needed to better quantify the dose of exercise needed to lower BP.

ObjectivesWe sought to describe the prevalence of restrictive lung function in structural congenital heart disease and to determine the effect of cardiothoracic surgical intervention.MethodsThe data from a retrospective review of the spirometry findings from pediatric patients with structural congenital heart disease were compared with the data from 220 matched controls. Restrictive lung function was defined as a forced vital capacity of 80%.ResultsOf the children with congenital heart disease, 20% met the criteria for restrictive lung function compared with 13.2% of the controls (P = .03). The prevalence in those with congenital heart disease without a surgical history was similar to that of the controls (odds ratio, 0.62; 95% confidence interval, 0.34-1.13). Restrictive lung function was more likely if surgical intervention had occurred within the first year of life (odds ratio, 1.96; 95% confidence interval, 1.08-3.55; P