Circulating total 25(OH)D and calculated free 25(OH)D in professional academy footballers at a northerly latitude in the UK.

There is limited data on the vitamin D status of UK-based professional academy footballers. Therefore, the objective of this study was to report total 25(OH)D, free 25(OH)D and free 1, 25(OH)2D at the end of the winter (March) and summer periods (October) in a cohort (n = 27) of professional academy footballers in northern England. Blood samples were collected to measure total 25(OH)D, parathyroid hormone, vitamin D binding protein, albumin and calcium. Free 25(OH)D and 1, 25(OH)2D were calculated. Dietary vitamin D intake and retrospective summer sunlight exposure were also collected. At the end of winter, 2/27 (7.4%) players were vitamin D deficient (25(OH)D < 30 nmol/l) and 11/27 (40.7%) were insufficient (25(OH)D > 30 nmol/l < 50 nmol/l). By the end of summer, none were deficient but 3/14 (21.4%) were still insufficient. Median total 25(OH)D (82.2 nmol/l [IQR: 50.3-90.2] vs. 54.2 nmol/l [IQR: 36.8-71.9]; P = .02), free 25(OH)D (25.8 pmol/l [IQR: 15.1-33.1] vs. 13.2 pmol/l [IQR: 9.0-14.9]; P = .005) and free 1, 25(OH)2D (389 fmol/l [IQR: 209-594] vs. 212 fmol/l [IQR: 108-278]; P = .034) were significantly higher at the end of summer than the end of winter. At the end of winter, free 25(OH)D was lower (P = .003) in those vitamin D insufficient (8.8 pmol/l [IQR: 5.5-11.8]) vs. sufficient (13.7 pmol/l [IQR: 12.0-17.0]). There was a high prevalence of vitamin D insufficiency at the end of the winter. Free 25(OH)D was also lower at the winter timepoint and in players that were insufficient vs. sufficient.

Fuligopyrones from the Fruiting Bodies of Myxomycete Fuligo septica Offer Short-Term Protection from Abiotic Stress Induced by UV Radiation.

The myxomycete Fuligo septica, colloquially referred to as "dog vomit fungus", forms vibrant yellow fruiting bodies (aethalia) on wood chips during warm and humid conditions in spring. In 2018, ideal climatic conditions in Sydney, Australia, provided a rare opportunity to access abundant quantities of F. septica aethalia, which enabled the isolation, purification, structure elucidation, and biological screening of two avenalumamide pyrones, fuligopyrone (1) and fuligopyrone B (2). While 1 and 2 did not exhibit any appreciable biological activity, their significant UV absorption at 325 nm suggested they may be acting as transient sunscreens to help protect the fruiting mass from exposure to sunlight. In support of this hypothesis, exposing a solution of 2 to direct sunlight for 5 min resulted in rapid equilibration with a mixture of 2E,4Z-fuligopyrone B (10) and 2Z,4E-fuligopyrone B (11) photoisomers.

Characterisation and heterologous biosynthesis of burnettiene A, a new polyene-decalin polyketide from Aspergillus burnettii.

Chemical exploration of the recently described Australian fungus, Aspergillus burnettii, uncovered a new metabolite, burnettiene A. Here, we characterise the structure of burnettiene A as a polyene-decalin polyketide. Bioinformatic analysis of the genome of A. burnettii identified a putative biosynthetic gene cluster for burnettiene A (bue), consisting of eight genes and sharing similarity to the fusarielin gene cluster. Introduction of the reassembled bue gene cluster into Aspergillus nidulans for heterologous expression resulted in the production of burnettiene A under native promoters. Omission of bueE encoding a cytochrome P450 led to the production of preburnettiene A, confirming that BueE is responsible for catalysing the regiospecific multi-oxidation of terminal methyl groups to carboxylic acids. Similarly, bueF was shown to encode an ester-forming methyltransferase, with its omission resulting in the production of the tricarboxylic acid, preburnettiene B. Introduction of an additional copy of the transcription factor bueR under the regulation of the gpdA promoter significantly improved the heterologous production of the burnettienes. Burnettiene A displayed strong in vitro cytotoxicity against mouse myeloma NS-1 cells (MIC 0.8 µg mL-1).

Assessment, treatment and prevention of vitamin D deficiency.

Vitamin D deficiency is prevalent among various groups in the UK, and can result from insufficient sunlight exposure and dietary intake. There is a population-wide recommendation of 10 micrograms (400 international units) of vitamin D per day, with a daily supplement advised. However, supplement use is often suboptimal, compounding the risk of deficiency. Long-term vitamin D deficiency can cause rickets in children and osteomalacia or osteoporosis in adults. Therefore, it is important that nurses recognise which groups are at increased risk of vitamin D deficiency and understand how to assess people's vitamin D status. Nurses also need to be able to support the prevention and treatment of low vitamin D levels, which typically involves supplementation and lifestyle changes.

Novel plant-based meat alternatives: future opportunities and health considerations.

Present food systems threaten population and environmental health. Evidence suggests reduced meat and increased plant-based food consumption would align with climate change and health promotion priorities. Accelerating this transition requires greater understanding of determinants of plant-based food choice. A thriving plant-based food industry has emerged to meet consumer demand and support dietary shift towards plant-based eating. 'Traditional' plant-based diets are low-energy density, nutrient dense, low in saturated fat and purportedly associated with health benefits. However, fast-paced contemporary lifestyles continue to fuel growing demand for meat-mimicking plant-based convenience foods which are typically ultra-processed. Processing can improve product safety and palatability and enable fortification and enrichment. However, deleterious health consequences have been associated with ultra-processing, though there is a paucity of equivocal evidence regarding the health value of novel plant-based meat alternatives (PBMAs) and their capacity to replicate the nutritional profile of meat-equivalents. Thus, despite the health halo often associated with plant-based eating, there is a strong rationale to improve consumer literacy of PBMAs. Understanding the impact of extensive processing on health effects may help to justify the use of innovative methods designed to maintain health benefits associated with particular foods and ingredients. Furthering knowledge regarding the nutritional value of novel PBMAs will increase consumer awareness and thus support informed choice. Finally, knowledge of factors influencing engagement of target consumer subgroups with such products may facilitate production of desirable, healthier PBMAs. Such evidence-based food manufacturing practice has the potential to positively influence future individual and planetary health.

Esterase-Mediated Sustained Release of Peptide-Based Therapeutics from a Self-Assembled Injectable Hydrogel.

A synthetic strategy for conjugating small molecules and peptide-based therapeutics, via a cleavable ester bond, to a lipidated ß3-tripeptide is presented. The drug-loaded ß3-peptide was successfully co-assembled with a functionally inert lipidated ß3-tripeptide to form a hydrogel. Quantitative release of lactose from the hydrogel, by the action of serum esterases, is demonstrated over 28 days. The esterase-mediated sustained release of the bioactive brain-derived neurotrophic factor (BDNF) peptide mimics from the hydrogel resulted in increased neuronal survival and normal neuronal function of peripheral neurons. These studies define a versatile strategy for the facile synthesis and co-assembly of self-assembling ß3-peptide-based hydrogels with the ability to control drug release using endogenous esterases with potential in vivo applications for sustained localized drug delivery.

Determination of Free 25(OH)D Concentrations and Their Relationships to Total 25(OH)D in Multiple Clinical Populations.

Context: The optimal measure of vitamin D status is unknown. Objective: To directly measure circulating free 25-hydroxyvitamin D [25(OH)D] concentrations and relationships to total 25(OH)D in a clinically diverse sample of humans. Design: Cross-sectional analysis. Setting: Seven academic sites. Patients: A total of 1661 adults: healthy (n = 279), prediabetic (n = 479), outpatients (n = 714), cirrhotic (n = 90), pregnant (n = 20), nursing home resident (n = 79). Interventions: Merge research data on circulating free 25(OH)D (directly-measured immunoassay), total 25(OH)D (liquid chromatography/tandem mass spectrometry), D-binding protein [DBP; by radial (polyclonal) immunodiffusion assay], albumin, creatinine, intact parathyroid hormone, and DBP haplotype. Main outcome measures: Distribution of free 25(OH)D (ANOVA with Bonferroni correction for post hoc comparisons) and relationships between free and total 25(OH)D (mixed-effects modeling incorporating clinical condition, DBP haplotype with sex, race, estimated glomerular filtration rate (eGFR), body mass index (BMI), and other covariates). Results: Free 25(OH)D was 4.7 ± 1.8 pg/mL (mean ± SD) in healthy persons and 4.3 ± 1.9 pg/mL in outpatients, with levels of 0.5 to 8.1 pg/mL and 0.9 to 8.1 pg/mL encompassing 95% of healthy persons and outpatients, respectively. Free 25(OH)D was higher in patients with cirrhosis (7.1 ± 3.0 pg/mL; P < 0.0033) and nursing home residents (7.9 ± 2.1 pg/mL; P < 0.0033) than in other groups and differed between whites and blacks (P < 0.0033) and between DBP haplotypes (P < 0.0001). Mixed-effects modeling of relationships between free and total 25(OH)D identified clinical conditions (patients with cirrhosis > nursing home residents > patients with prediabetes > outpatients > pregnant women) and BMI (lesser effect) as covariates affecting relationships but not eGFR, sex, race, or DBP haplotype. Conclusions: Total 25(OH)D, health condition, race, and DBP haplotype affected free 25(OH)D, but only health conditions and BMI affected relationships between total and free 25(OH)D. Clinical importance of free 25(OH)D needs to be established in studies assessing outcomes.

Vitamin D in obesity.

PURPOSE OF REVIEW: Vitamin D is essential for bone health, and may also have important functions in immunity and other systems. Vitamin D deficiency is common, and testing and supplementation is increasing. Serum vitamin D is lower in obese people; it is important to understand the mechanism of this effect and whether it indicates clinically significant deficiency. RECENT FINDINGS: Vitamin D is fat soluble, and distributed into fat, muscle, liver, and serum. All of these compartments are increased in volume in obesity, so the lower vitamin D likely reflects a volumetric dilution effect and whole body stores of vitamin D may be adequate. Despite lower serum vitamin D, obese adults do not have higher bone turnover or lower bone mineral density. Patients undergoing bariatric surgery do have bone loss, and ensuring vitamin D sufficiency in these patients may help to attenuate bone loss. SUMMARY: Lower vitamin D in obese people is a consistent finding across age, ethnicity, and geography. This may not always reflect a clinical problem. Obese people need higher loading doses of vitamin D to achieve the same serum 25-hydroxyvitamin D as normal weight.

Free 25-hydroxyvitamin D is low in obesity, but there are no adverse associations with bone health.

BACKGROUND: The mechanism and clinical significance of low circulating 25-hydroxyvitamin D [25(OH)D] in obese people are unknown. Low total 25(OH)D may be due to low vitamin D-binding proteins (DBPs) or faster metabolic clearance. However, obese people have a higher bone mineral density (BMD), which suggests that low 25(OH)D may not be associated with adverse consequences for bone. OBJECTIVE: We sought to determine whether 1) vitamin D metabolism and 2) its association with bone health differ by body weight. DESIGN: We conducted a cross-sectional observational study of 223 normal-weight, overweight, and obese men and women aged 25-75 y in South Yorkshire, United Kingdom, in the fall and spring. A subgroup of 106 subjects was also assessed in the winter. We used novel techniques, including an immunoassay for free 25(OH)D, a stable isotope for the 25(OH)D3 half-life, and high-resolution quantitative tomography, to make a detailed assessment of vitamin D physiology and bone health. RESULTS: Serum total 25(OH)D was lower in obese and overweight subjects than in normal-weight subjects in the fall and spring (geometric means: 45.0 and 40.8 compared with 58.6 nmol/L, respectively; P < 0.001) but not in the winter. Serum 25(OH)D was inversely correlated with body mass index (BMI) in the fall and spring and in the winter. Free 25(OH)D and 1,25-dihydroxyvitamin D [1,25(OH)2D] were lower in obese subjects. DBP, the DBP genotype, and the 25(OH)D3 half-life did not differ between BMI groups. Bone turnover was lower, and bone density was higher, in obese people. CONCLUSIONS: Total and free 25(OH)D and 1,25(OH)2D are lower at higher BMI, which cannot be explained by lower DBP or the shorter half-life of 25(OH)D3 We speculate that low 25(OH)D in obesity is due to a greater pool of distribution. Lower 25(OH)D may not reflect at-risk skeletal health in obese people, and BMI should be considered when interpreting serum 25(OH)D as a marker of vitamin D status.