Astaxanthin Reduces Heart Rate and Carbohydrate Oxidation Rates During Exercise in Overweight Individuals

International Journal of Exercise Science 16(2): 252-266, 2023. Astaxanthin (AX) is an antioxidant which may spare endogenous carbohydrates and improve fat oxidation rates, thus improving metabolic flexibility. To date, no studies have attempted to examine the impact of AX in an overweight cohort, whom often suffer from metabolic inflexibility. Nineteen subjects (mean ± SD: age: 27.5 ± 6.3 years; height: 169.7 ± 9.0 cm; body mass: 96.4 ± 17.9 kg; BF%: 37.9 ± 7.0%; BMI: 33.4 ± 5.6 kg/m2; VO2peak: 25.9 ± 6.7 ml·kg−1·min−1) were recruited and supplemented with either 12 mg of AX or placebo (PLA) for 4 weeks. Subjects completed a graded exercise test on a cycling ergometer to examine changes in substrate oxidation rates. A total of 5 stages, each lasting 5 min and resistance increased 15 W each stage, were completed to examine changes in levels of glucose and lactate, fat and carbohydrate (CHO) oxidation rates, heart rate, and rating of perceived exertion (RPE). Although there were no changes found in rates of fat oxidation, blood lactate or glucose, or RPE (all p \u3e 0.05), a significant decrease was observed in CHO oxidation from pre to post supplementation in the AX group only. Further, the AX group demonstrated a 7% decrease in heart rate across the graded exercise test. These findings suggest that 4 weeks of AX supplementation may offer some cardiometabolic benefits to overweight individuals, and be a favorable supplement for these individuals beginning an exercise program

Whole-genome sequencing for national surveillance of Shiga toxin–producing Escherichia coli O157

Background. National surveillance of gastrointestinal pathogens, such as Shiga toxin–producing Escherichia coli O157 (STEC O157), is key to rapidly identifying linked cases in the distributed food network to facilitate public health interventions. In this study, we used whole-genome sequencing (WGS) as a tool to inform national surveillance of STEC O157 in terms of identifying linked cases and clusters and guiding epidemiological investigation. Methods. We retrospectively analyzed 334 isolates randomly sampled from 1002 strains of STEC O157 received by the Gastrointestinal Bacteria Reference Unit at Public Health England, Colindale, in 2012. The genetic distance between each isolate, as estimated by WGS, was calculated and phylogenetic methods were used to place strains in an evolutionary context. Results. Estimates of linked clusters representing STEC O157 outbreaks in England and Wales increased by 2-fold when WGS was used instead of traditional typing techniques. The previously unidentified clusters were often widely geographically distributed and small in size. Phylogenetic analysis facilitated identification of temporally distinct cases sharing common exposures and delineating those that shared epidemiological and temporal links. Comparison with multi locus variable number tandem repeat analysis (MLVA) showed that although MLVA is as sensitive as WGS, WGS provides a more timely resolution to outbreak clustering. Conclusions. WGS has come of age as a molecular typing tool to inform national surveillance of STEC O157; it can be used in real time to provide the highest strain-level resolution for outbreak investigation. WGS allows linked cases to be identified with unprecedented specificity and sensitivity that will facilitate targeted and appropriate public health investigations

A case for revising the strength of the relationship between childhood asthma and atopy in the developing world

Introduction. Asthma is the commonest chronic condition of children. Diagnosis remains difficult and many surrogate markers are used, such as documenting evidence of atopy.Method. Two studies investigated the role of atopy in childhood asthma. The first documented the prevalence and nature of allergy sensitivities in a group of asthmatic children compared with non-asthmatic children in Pretoria, South Africa. The second enrolled a random sample of asthmatic children and their mothers attending the Children’s Chest and Allergy Clinic at Steve Biko Academic Hospital, Pretoria. Children were classified as having atopic or non-atopic asthma. Mothers completed a questionnaire to reveal atopic features.Results. In the first study, only 45.0% of asthmatic children had a positive skin-prick test (SPT), as opposed to 16.2% of control children. This is a lower proportion than in many reported international studies. In the second study, 64 children with atopic asthma and 36 with non-atopic asthma were studied, along with their mothers. The proportion of children with atopic asthma did not differ for mothers with and without a positive SPT (p=0.836), a history of asthma (p=0.045) or symptoms suggestive of an allergic disease (p=1.000), or who were considered to be allergic (p=0.806). The odds ratio (OR) of a child having atopic asthma when he or she had a mother with a doctor-diagnosed history of asthma was 4.76, but the sensitivity was low (21.9%).Conclusion. The data demonstrate that fewer asthmatic children in South Africa are atopic than was previously thought. Also, all maternal allergic or asthmatic associations are poor predictors of childhood atopic asthma. Despite the increased risk of atopic asthma in a child of a mother who has a doctor diagnosis of asthma (OR 4.76; p=0.045), this is a poor predictor of atopic asthma (sensitivity 21.9%

Acute impact of conventional and eccentric cycling on platelet and vascular function in patients with chronic heart failure.

Evidence-based guidelines recommend exercise therapy for patients with chronic heart failure (CHF). Such patients have increased atherothrombotic risk. Exercise can transiently increase platelet activation and reactivity and decrease vascular function in healthy participants, although data in CHF is scant. Eccentric (ECC) cycling is a novel exercise modality which may be particularly suited to patients with CHF, but the acute impacts of ECC on platelet and vascular function are currently unknown. Our null hypothesis was that ECC and concentric (CON) cycling, performed at matched external workloads, would not induce changes in platelet or vascular function in patients with CHF. Eleven patients with heart failure with reduced ejection fraction (HFrEF) took part in discrete bouts of ECC and CON cycling. Before and immediately after exercise, vascular function was assessed by measuring diameter and flow mediated dilation (FMD) of the brachial artery. Platelet function was measured by the flow cytometric determination of glycoprotein IIb/IIIa activation and granule exocytosis in the presence and absence of platelet agonists. ECC increased baseline artery diameter (pre: 4.0±0.8mm vs post: 4.2±0.7mm, P=0.04) and decreased FMD%. When changes in baseline artery diameter were accounted for the decrease in FMD post-ECC was no longer significant. No changes were apparent after CON. Neither ECC nor CON resulted in changes to any platelet function measures (all P>0.05). These results suggest both ECC and CON cycling at a moderate intensity and short duration can be performed by patients with HFrEF, without detrimental impacts on vascular or platelet function

The impact of contact tracing in clustered populations

The tracing of potentially infectious contacts has become an important part of the control strategy for many infectious diseases, from early cases of novel infections to endemic sexually transmitted infections. Here, we make use of mathematical models to consider the case of partner notification for sexually transmitted infection, however these models are sufficiently simple to allow more general conclusions to be drawn. We show that, when contact network structure is considered in addition to contact tracing, standard “mass action” models are generally inadequate. To consider the impact of mutual contacts (specifically clustering) we develop an improvement to existing pairwise network models, which we use to demonstrate that ceteris paribus, clustering improves the efficacy of contact tracing for a large region of parameter space. This result is sometimes reversed, however, for the case of highly effective contact tracing. We also develop stochastic simulations for comparison, using simple re-wiring methods that allow the generation of appropriate comparator networks. In this way we contribute to the general theory of network-based interventions against infectious disease

Depletion-Driven Morphological Control of Bundled Actin Networks

The actin cytoskeleton is a semiflexible biopolymer network whose morphology is controlled by a wide range of biochemical and physical factors. Actin is known to undergo a phase transition from a single-filament state to a bundled state by the addition of polyethylene glycol (PEG) molecules in sufficient concentration. While the depletion interaction experienced by these biopolymers is well-known, the effect of changing the molecular weight of the depletant is less well understood. Here, we experimentally identify a phase transition in solutions of actin from networks of filaments to networks of bundles by varying the molecular weight of PEG polymers, while holding the concentration of these PEG polymers constant. We examine the states straddling the phase transition in terms of micro and macroscale properties. We find that the mesh size, bundle diameter, persistence length, and intra-bundle spacing between filaments across the line of criticality do not show significant differences, while the relaxation time, storage modulus, and degree of bundling change between the two states do show significant differences. Our results demonstrate the ability to tune actin network morphology and mechanics by controlling depletant size, a property which could be exploited to develop actin-based materials with switchable rigidity.Comment: 22 pages, 10 figures. Authors James Clarke and Francis Cavanna contributed equally; Changes: Added modeling work, extended dynamic light scattering analysi

Immunomodulation by imiquimod in patients with high-risk primary melanoma.

Imiquimod is a synthetic Toll-like receptor 7 (TLR7) agonist approved for the topical treatment of actinic keratoses, superficial basal cell carcinoma, and genital warts. Imiquimod leads to an 80-100% cure rate of lentigo maligna; however, studies of invasive melanoma are lacking. We conducted a pilot study to characterize the local, regional, and systemic immune responses induced by imiquimod in patients with high-risk melanoma. After treatment of the primary melanoma biopsy site with placebo or imiquimod cream, we measured immune responses in the treated skin, sentinel lymph nodes (SLNs), and peripheral blood. Treatment of primary melanomas with 5% imiquimod cream was associated with an increase in both CD4+ and CD8+ T cells in the skin, and CD4+ T cells in the SLN. Most of the CD8+ T cells in the skin were CD25 negative. We could not detect any increases in CD8+ T cells specifically recognizing HLA-A(*)0201-restricted melanoma epitopes in the peripheral blood. The findings from this small pilot study demonstrate that topical imiquimod treatment results in enhanced local and regional T-cell numbers in both the skin and SLN. Further research into TLR7 immunomodulating pathways as a basis for effective immunotherapy against melanoma in conjunction with surgery is warranted