Iron plays a significant role in the body, and is specifically important to athletes, since it is a dominant feature in processes such as oxygen transport and energy metabolism. Despite its ...importance, athlete populations, especially females and endurance athletes, are commonly diagnosed with iron deficiency, suggesting an association between sport performance and iron regulation. Although iron deficiency is most common in female athletes (~ 15–35% athlete cohorts deficient), approximately 5–11% of male athlete cohorts also present with this issue. Furthermore, interest has grown in the mechanisms that influence iron absorption in athletes over the last decade, with the link between iron regulation and exercise becoming a research focus. Specifically, exercise-induced increases in the master iron regulatory hormone, hepcidin, has been highlighted as a contributing factor towards altered iron metabolism in athletes. To date, a plethora of research has been conducted, including investigation into the impact that sex hormones, diet (e.g. macronutrient manipulation), training and environmental stress (e.g. hypoxia due to altitude training) have on an athlete’s iron status, with numerous recommendations proposed for consideration. This review summarises the current state of research with respect to the aforementioned factors, drawing conclusions and recommendations for future work.
Effective intervention strategies are urgently needed to control the COVID-19 pandemic. Human angiotensin-converting enzyme 2 (ACE2) is a membrane-bound carboxypeptidase that forms a dimer and serves ...as the cellular receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ACE2 is also a key negative regulator of the renin-angiotensin system that modulates vascular functions. We report here the properties of a trimeric ACE2 ectodomain variant, engineered using a structure-based approach. The trimeric ACE2 variant has a binding affinity of ~60 pM for the spike protein of SARS‑CoV‑2 (compared with 77 nM for monomeric ACE2 and 12-22 nM for dimeric ACE2 constructs), and its peptidase activity and the ability to block activation of angiotensin II receptor type 1 in the renin-angiotensin system are preserved. Moreover, the engineered ACE2 potently inhibits SARS‑CoV‑2 infection in cell culture. These results suggest that engineered, trimeric ACE2 may be a promising anti-SARS-CoV-2 agent for treating COVID-19.
Introduction We repeated our study of intensified training on a ketogenic low-carbohydrate (CHO), high-fat diet (LCHF) in world-class endurance athletes, with further investigation of a "carryover" ...effect on performance after restoring CHO availability in comparison to high or periodised CHO diets. Methods After Baseline testing (10,000 m IAAF-sanctioned race, aerobic capacity and submaximal walking economy) elite male and female race walkers undertook 25 d supervised training and repeat testing (Adapt) on energy-matched diets: High CHO availability (8.6 gâkg.sup.-1 âd.sup.-1 CHO, 2.1 gâkg.sup.-1 âd.sup.-1 protein; 1.2 gâkg.sup.-1 âd.sup.-1 fat) including CHO before/during/after workouts (HCHO, n = 8): similar macronutrient intake periodised within/between days to manipulate low and high CHO availability at various workouts (PCHO, n = 8); and LCHF (<50 gâd.sup.-1 CHO; 78% energy as fat; 2.1 gâkg.sup.-1 âd.sup.-1 protein; n = 10). After Adapt, all athletes resumed HCHO for 2.5 wk before a cohort (n = 19) completed a 20 km race. Results All groups increased VO.sub.2 peak (mlâkg.sup.-1 âmin.sup.-1) at Adapt (p = 0.02, 95%CI: 0.35-2.74). LCHF markedly increased whole-body fat oxidation (from 0.6 gâmin.sup.-1 to 1.3 gâmin.sup.-1 ), but also the oxygen cost of walking at race-relevant velocities. Differences in 10,000 m performance were clear and meaningful: HCHO improved by 4.8% or 134 s (95% CI: 207 to 62 s; p < 0.001), with a trend for a faster time (2.2%, 61 s -18 to +144 s; p = 0.09) in PCHO. LCHF were slower by 2.3%, -86 s (-18 to -144 s; p < 0.001), with no evidence of superior "rebound" performance over 20 km after 2.5 wk of HCHO restoration and taper. Conclusion Our previous findings of impaired exercise economy and performance of sustained high-intensity race walking following keto-adaptation in elite competitors were repeated. Furthermore, there was no detectable benefit from undertaking an LCHF intervention as a periodised strategy before a 2.5-wk race preparation/taper with high CHO availability. Trial registration Australia New Zealand Clinical Trial Registry: ACTRN12619000794101.
Neighbourhood environments significantly influence health and well-being, especially as people age. Our study uniquely highlights how one microscale feature (benches) influence older adults ...experiences of mobility and well-being, from their perspective. We also explore how these experiences affect and are affected by the social environment of the neighbourhoods where older adults live. We conducted one-on-one seated and walk-along interviews with individuals aged 60+ that live in three adjacent neighbourhoods in Vancouver, Canada. We collected data at two time points (n = 28, 2012; n = 22, 2014). We found that benches positively contributed to older adults’ mobility experiences by: (i) enhancing their use and enjoyment of green and blue spaces, (ii) serving as a mobility aid, and (iii) contributing to social cohesion and social capital. To address the increased needs of an aging demographic, urban planners might consider the quality and presence of microfeatures as part of an immediate and inexpensive strategy to create supportive neighbourhoods for people of all ages and abilities.
•Neighbourhood environments influence health and well-being as people age.•There are strong interconnections between built and social environments.•Microscale features can enable older adults' to accommodate to their abilities.•Benches can promote mobility and social connectedness for older adults.•Microscale features, like benches, are a prudent investment for communities.
Dietary exposures can have consequences for health years or decades later and this raises questions about the mechanisms through which such exposures are ‘remembered’ and how they result in altered ...disease risk. There is growing evidence that epigenetic mechanisms may mediate the effects of nutrition and may be causal for the development of common complex (or chronic) diseases. Epigenetics encompasses changes to marks on the genome (and associated cellular machinery) that are copied from one cell generation to the next, which may alter gene expression, but which do not involve changes in the primary DNA sequence. These include three distinct, but closely inter‐acting, mechanisms including DNA methylation, histone modifications and non‐coding microRNAs (miRNA) which, together, are responsible for regulating gene expression not only during cellular differentiation in embryonic and foetal development but also throughout the life‐course. This review summarizes the growing evidence that numerous dietary factors, including micronutrients and non‐nutrient dietary components such as genistein and polyphenols, can modify epigenetic marks. In some cases, for example, effects of altered dietary supply of methyl donors on DNA methylation, there are plausible explanations for the observed epigenetic changes, but to a large extent, the mechanisms responsible for diet–epigenome–health relationships remain to be discovered. In addition, relatively little is known about which epigenomic marks are most labile in response to dietary exposures. Given the plasticity of epigenetic marks and their responsiveness to dietary factors, there is potential for the development of epigenetic marks as biomarkers of health for use in intervention studies.
To evaluate long-term disability progression in pediatric-onset multiple sclerosis (POMS) and compare to adult-onset multiple sclerosis (AOMS).
This was a retrospective cohort study using ...prospectively collected clinical information from the Swedish MS Registry. Clinical features were compared and Kaplan-Meier and Cox proportional hazards regression were used to assess the risk of reaching sustained Expanded Disability Status Scale (EDSS) 3, 4, and 6 in POMS (multiple sclerosis MS onset <18 years) and AOMS (MS onset ≥18 years).
A total of 12,482 persons were included; 549 (4.4%) were classified as POMS. The POMS cohort took longer to reach all 3 disability milestones from their MS onset, but did so at a younger age than the AOMS cohort. Primary progressive course (hazard ratio HR 4.63; 95% confidence interval CI 1.46-14.7), higher relapse rate in the first 5 years of disease (HR 5.35; 95% CI 3.37-8.49), and complete remission from the initial relapse (HR 0.41; 95% CI 0.18-0.94) were associated with an altered risk of progression to EDSS 4 among POMS cases. The same pattern emerged for the risk of reaching EDSS 3 and 6.
Patients with pediatric-onset MS follow a distinctive clinical course, which should be considered in the treatment and management of the disease.
Background & Aims MicroRNAs (miRNAs) can promote or inhibit tumor growth and are therefore being developed as targets for cancer therapies. They are diverse not only in the messenger RNAs (mRNA) they ...target, but in their production; the same hairpin RNA structure can generate mature products from each strand, termed 5p and 3p , that can bind different mRNAs. We analyzed the expression, functions, and mechanisms of miR-28-5p and miR-28-3p in colorectal cancer (CRC) cells. Methods We measured levels of miR-28-5p and miR-28-3p expression in 108 CRC and 49 normal colorectal samples (47 paired) by reverse transcription, quantitative real-time polymerase chain reaction. The roles of miR-28 in CRC development were studied using cultured HCT116, RKO, and SW480 cells and tumor xenograft analyses in immunodeficient mice; their mRNA targets were also investigated. Results miR-28-5p and miR-28-3p were down-regulated in CRC samples compared with normal colon samples. Overexpression of miRNAs in CRC cells had different effects and the miRNAs interacted with different mRNAs: miR-28-5p altered expression of CCND1 and HOXB3 , whereas miR-28-3p bound NM23-H1 . Overexpression of miR-28-5p reduced CRC cell proliferation, migration, and invasion in vitro, whereas miR-28-3p increased CRC cell migration and invasion in vitro. CRC cells overexpressing miR-28 developed tumors more slowly in mice compared with control cells, but miR-28 promoted tumor metastasis in mice. Conclusion miR-28-5p and miR-28-3p are transcribed from the same RNA hairpin and are down-regulated in CRC cells. Overexpression of each has different effects on CRC cell proliferation and migration. Such information has a direct application for the design of miRNA gene therapy trials.
Choose to Move (CTM), an effective health-promoting intervention for older adults, was scaled-up across British Columbia, Canada. Adaptations that enable implementation at scale may lead to 'voltage ...drop'-diminished positive effects of the intervention. For CTM Phase 3 we assessed: i. implementation; ii. impact on physical activity, mobility, social isolation, loneliness and health-related quality of life (impact outcomes); iii. whether intervention effects were maintained; iv) voltage drop, compared with previous CTM phases.
We conducted a type 2 hybrid effectiveness-implementation pre-post study of CTM; older adult participants (n = 1012; mean age 72.9, SD = 6.3 years; 80.6% female) were recruited by community delivery partners. We assessed CTM implementation indicators and impact outcomes via survey at 0 (baseline), 3 (mid-intervention), 6 (end-intervention) and 18 (12-month follow-up) months. We fitted mixed-effects models to describe change in impact outcomes in younger (60-74 years) and older (≥ 75 years) participants. We quantified voltage drop as percent of effect size (change from baseline to 3- and 6-months) retained in Phase 3 compared with Phases 1-2.
Adaptation did not compromise fidelity of CTM Phase 3 as program components were delivered as intended. PA increased during the first 3 months in younger (+1 days/week) and older (+0.9 days/week) participants (p<0.001), and was maintained at 6- and 18-months. In all participants, social isolation and loneliness decreased during the intervention, but increased during follow-up. Mobility improved during the intervention in younger participants only. Health-related quality of life according to EQ-5D-5L score did not change significantly in younger or older participants. However, EQ-5D-5L visual analog scale score increased during the intervention in younger participants (p<0.001), and this increase was maintained during follow-up. Across all outcomes, the median difference in effect size, or voltage drop, between Phase 3 and Phases 1-2 was 52.6%. However, declines in social isolation were almost two times greater in Phase 3, compared with Phases 1-2.
Benefits of health-promoting interventions-like CTM-can be retained when implemented at broad scale. Diminished social isolation in Phase 3 reflects how CTM was adapted to enhance opportunities for older adults to socially connect. Thus, although intervention effects may be reduced at scale-up, voltage drop is not inevitable.
Abstract Bone mass is a key determinant of fracture risk. Maximizing bone mineral mass during childhood and adolescence may contribute to fracture risk reduction during adolescence and possibly in ...the elderly. Although more than 60% of the variance of peak bone mass (PBM), the amount of bone present in the skeleton at the end of its maturation process, is genetically determined, the remainder is likely influenced by factors amenable to positive intervention, such as adequate dietary intake of dairy products as a natural source of calcium and proteins, vitamin D, and regular weight-bearing physical activity. Low calcium and vitamin D intakes are associated with negative effects on bone, including suboptimal PBM acquisition. As suggested by intervention studies, regular intake of dairy products may have positive and possibly sustained effects on bone mineral mass gain, contributing thereby to fracture risk reduction. Further evidence from intervention studies suggests that weight-bearing physical activities, such as jumping, may contribute to bone mineral mass gain in children. Optimizing PBM acquisition through dietary and physical exercise measures may represent a valuable primary method for the prevention of fractures.
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