Abnormal Central Pulsatile Hemodynamics in Adolescents With Obesity: Higher Aortic Forward Pressure Wave Amplitude Is Independently Associated With Greater Left Ventricular Mass.

We hypothesized that increased aortic forward pressure wave amplitude (Pf), which is determined by characteristic impedance (Zc) in the proximal aorta, is the primary hemodynamic determinant of obesity-associated higher left ventricular (LV) mass in adolescents. Aortic pulsatile hemodynamics were measured noninvasively in 60 healthy adolescents (age 14-19 years; 42% male; 50% black) by sequential recordings of pulse waveforms via tonometry, brachial blood pressure, and pulsed Doppler and diameter of the LV outflow tract using 2-dimensional echocardiography. Adolescents who were overweight/obese (n=23; age 16.

High trans but not saturated fat beverage causes an acute reduction in postprandial vascular endothelial function but not arterial stiffness in humans.

A diet high in trans-fatty acids (TFAs) is associated with a higher risk of cardiovascular disease (CVD) than a diet high in saturated fatty acids (SFAs), but the mechanisms remain unclear. We hypothesized that a beverage high in TFAs would cause a larger reduction in postprandial endothelial function and an increase in arterial stiffness, in part from greater reductions in insulin sensitivity, compared with a beverage high in SFAs. Eleven healthy adults (aged 47±5 years) ingested a warm test beverage (520 kcal, 56 g total fat, 5 g carbohydrate, 1 g protein) high in either TFAs or SFAs in a randomized cross-over study.

Dietary Flaxseed Reduces Central Aortic Blood Pressure Without Cardiac Involvement but Through Changes in Plasma Oxylipins.

Unlabelled: In the year-long FlaxPAD clinical trial (Flaxseed for Peripheral Artery Disease), dietary flaxseed generated a powerful reduction in brachial systolic and diastolic blood pressure in patients with peripheral artery disease. Oxylipins were implicated as potential mechanistic mediators. However, the ability of flaxseed to impact central aortic hypertension, arterial stiffness, or cardiac performance was not investigated.

A review of the relative efficacy of dietary, nutritional supplements, lifestyle, and drug therapies in the management of hypertension.

Despite advancements in hypertensive therapies, the prevalence of hypertension and associated morbidities are still immense. Physicians are in great need for updated information on novel and effective antihypertensive therapies. Therefore, the study objective was to provide comprehensive information on the efficacy of available antihypertensive therapies.

Changes in health-related quality of life with treatment of longer-acting clotting factors: results in the A-LONG and B-LONG clinical studies.

Introduction: In haemophilia, prophylactic infusion of replacement factor can result in improvements in health-related quality of life (HRQoL) when compared with episodic treatment. The Haemophilia-specific Quality of Life (Haem-A-QoL) questionnaire assessed HRQoL in adults with severe haemophilia A or B who received prophylactic or episodic treatment with recombinant factor VIII or IX Fc fusion protein (rFVIIIFc or rFIXFc) in the A-LONG or B-LONG clinical studies.

Aims: Understand changes in HRQoL during the A-LONG and B-LONG trials.

Global proliferation of cephalopods.

Human activities have substantially changed the world's oceans in recent decades, altering marine food webs, habitats and biogeochemical processes [1]. Cephalopods (squid, cuttlefish and octopuses) have a unique set of biological traits, including rapid growth, short lifespans and strong life-history plasticity, allowing them to adapt quickly to changing environmental conditions [2-4]. There has been growing speculation that cephalopod populations are proliferating in response to a changing environment, a perception fuelled by increasing trends in cephalopod fisheries catch [4,5].

Ruminant and industrial trans-fatty acid uptake in the heart.

Dietary trans-fats are strongly associated with heart disease. However, the capacity for the tissues of the body, and specifically the heart, to take up trans-fats is unknown. It is also unknown if different trans-fats have different uptake capacities in the heart and other tissues of the body.

Long-acting recombinant factor VIII Fc fusion protein (rFVIIIFc) for perioperative haemostatic management in severe haemophilia A.

The Phase 3 A-LONG and Kids A-LONG studies demonstrated the prolonged half-life of rFVIIIFc compared with rFVIII, and the safety and efficacy of rFVIIIFc in subjects with severe haemophilia A. Eligible subjects from A-LONG and Kids A-LONG continued rFVIIIFc treatment by enrolling in ASPIRE, an ongoing extension study. Based on combined data from the primary studies and ASPIRE interim data, the safety and efficacy of rFVIIIFc in subjects requiring surgery were evaluated.

Estimated aortic stiffness is independently associated with cardiac baroreflex sensitivity in humans: role of ageing and habitual endurance exercise.

We hypothesised that differences in cardiac baroreflex sensitivity (BRS) would be independently associated with aortic stiffness and augmentation index (AI), clinical biomarkers of cardiovascular disease risk, among young sedentary and middle-aged/older sedentary and endurance-trained adults. A total of 36 healthy middle-aged/older (age 55-76 years, n=22 sedentary and n=14 endurance-trained) and 5 young sedentary (age 18-31 years) adults were included in a cross-sectional study. A subset of the middle-aged/older sedentary adults (n=12) completed an 8-week-aerobic exercise intervention.

Direct Ventral Hippocampal-Prefrontal Input Is Required for Anxiety-Related Neural Activity and Behavior.

The ventral hippocampus (vHPC), medial prefrontal cortex (mPFC), and basolateral amygdala (BLA) are each required for the expression of anxiety-like behavior. Yet the role of each individual element of the circuit is unclear. The projection from the vHPC to the mPFC has been implicated in anxiety-related neural synchrony and spatial representations of aversion.

Higher augmentation index is associated with tension-type headache and migraine in middle-aged/older humans with obesity.

Objective: Obesity is a major risk factor for chronic daily headaches, including migraine and tension-type headache (TTH). Although migraine is associated with increased risk of cardiovascular diseases (CVD), a relation between TTH and CVD risk has not been established. It was hypothesized that higher carotid-femoral pulse wave velocity (CFPWV) and augmentation index (AI), measures of aortic stiffness and pressure wave reflection, respectively, and biomarkers of CVD risk, would be higher among adults with obesity and migraine or TTH compared with those with no headache.

Recombinant Factor IX Fc Fusion Protein Maintains Full Procoagulant Properties and Exhibits Prolonged Efficacy in Hemophilia B Mice.

Introduction: Hemophilia B is an inherited X chromosome-linked disorder characterized by impaired blood clotting owing to the absence of functional coagulation factor IX. Due to the relatively short half-life of factor IX, patients with hemophilia B require frequent factor IX infusions to maintain prophylaxis. We have developed a recombinant factor IX (rFIX) fused to the Fc region of IgG (rFIXFc) with an extended half-life in animals and humans.

Recombinant factor VIII Fc (rFVIIIFc) fusion protein reduces immunogenicity and induces tolerance in hemophilia A mice.

Anti-factor VIII (FVIII) antibodies is a major complication of FVIII replacement therapy for hemophilia A. We investigated the immune response to recombinant human factor VIII Fc (rFVIIIFc) in comparison to BDD-rFVIII and full-length rFVIII (FL-rFVIII) in hemophilia A mice. Repeated administration of therapeutically relevant doses of rFVIIIFc in these mice resulted in significantly lower antibody responses to rFVIII compared to BDD-rFVIII and FL-rFVIII and reduced antibody production upon subsequent challenge with high doses of rFVIIIFc.

Evaluation of the toxicology and pharmacokinetics of recombinant factor VIII Fc fusion protein in animals.

Introduction: Recombinant factor VIII Fc fusion protein (rFVIIIFc) is a novel recombinant factor VIII with a prolonged half-life, developed for the treatment of hemophilia A. Studies that evaluated the toxicological effects of rFVIIIFc in 2 pharmacologically relevant species, cynomolgus monkeys and Sprague Dawley rats, are reported here.

Materials And Methods: In repeat-dose toxicology studies, rats and monkeys received 0, 50, 250, or 1000 IU/kg rFVIIIFc every other day for 4 weeks.

A randomized trial of the effects of ezetimibe on the absorption of omega-3 fatty acids in cardiac disease patients: A pilot study.

Background And Aims: Elevated levels of circulating omega-3 polyunsaturated fatty acids like alpha linolenic acid (ALA) may be beneficial for cardiovascular health. Circulating ALA concentrations are elevated dramatically by a cholesterol supplemented diet which increases ALA bioavailability through enhanced micelle formation in the intestines. Conversely, it is possible that drugs which inhibit cholesterol metabolism in the intestine may also inhibit fatty acid absorption.

Features in geometric receiver shapes modelling bat-like directivity patterns.

The directional properties of bat ears as receivers is a current area of interest in ultrasound research. This paper presents a new approach to analyse the relationship between morphological features and acoustical properties of the external ear of bat species. The beam pattern of Rousettus leschenaultii's right ear is measured and compared to that of receiver structures whose design is inspired by the bat ear itself and made of appropriate geometric shapes.

Long-term safety and efficacy of recombinant factor VIII Fc fusion protein (rFVIIIFc) in subjects with haemophilia A.

Introduction: The safety, efficacy and prolonged half-life of recombinant factor VIII Fc fusion protein (rFVIIIFc) in previously treated patients with severe haemophilia A was demonstrated in the phase 3 A-LONG and Kids A-LONG studies. Here, we report interim safety and efficacy data from the rFVIIIFc extension study, ASPIRE (ClinicalTrials.gov #NCT01454739).

Reproductive Failure in UK Harbour Porpoises Phocoena phocoena: Legacy of Pollutant Exposure?

Reproductive failure in mammals due to exposure to polychlorinated biphenyls (PCBs) can occur either through endocrine disrupting effects or via immunosuppression and increased disease risk. To investigate further, full necropsies and determination of summed 25 polychlorinated biphenyls congeners (∑PCBs lipid weight) in blubber were undertaken on 329 UK-stranded female harbour porpoises (1990-2012). In sexually mature females, 25/127 (19.

Manufacturing process used to produce long-acting recombinant factor VIII Fc fusion protein.

Recombinant factor VIII Fc fusion protein (rFVIIIFc) is a long-acting coagulation factor approved for the treatment of hemophilia A. Here, the rFVIIIFc manufacturing process and results of studies evaluating product quality and the capacity of the process to remove potential impurities and viruses are described. This manufacturing process utilized readily transferable and scalable unit operations and employed multi-step purification and viral clearance processing, including a novel affinity chromatography adsorbent and a 15 nm pore size virus removal nanofilter.

Myeloperoxidase is increased in human cerebral aneurysms and increases formation and rupture of cerebral aneurysms in mice.

Background And Purpose: Cerebral aneurysm (CA) affects 3% of the population and is associated with hemodynamic stress and inflammation. Myeloperoxidase, a major oxidative enzyme associated with inflammation, is increased in patients with CA, but whether myeloperoxidase contributes to CA is not known. We tested the hypotheses that myeloperoxidase is increased within human CA and is critical for formation and rupture of CA in mice.

Recombinant factor VIII Fc fusion protein for the prevention and treatment of bleeding in children with severe hemophilia A.

Background: Prophylactic factor replacement, which prevents hemarthroses and thereby reduces the musculoskeletal disease burden in children with hemophilia A, requires frequent intravenous infusions (three to four times weekly).

Objective: Kids A-LONG was a phase 3 open-label study evaluating the safety, efficacy and pharmacokinetics of a longer-acting factor, recombinant factor VIII Fc fusion protein (rFVIIIFc), in previously treated children with severe hemophilia A (endogenous FVIII level of < 1 IU dL(-1) [< 1%]).

Methods: The study enrolled 71 subjects.