Vitamin D metabolites are associated with musculoskeletal injury in young adults: a prospective cohort study

The relationship between vitamin D metabolites and lower body (pelvis and lower limb) overuse injury is unclear. In a prospective cohort study, we investigated the association between vitamin D metabolites and incidence of lower body overuse musculoskeletal and bone stress injury in young adults undergoing initial military training during all seasons. In 1637 men and 530 women (age, 22.6 ± 7.5 years; BMI, 24.0 ± 2.6 kg∙m-2 ; 94.3% white ethnicity), we measured serum 25-hydroxyvitamin D (25(OH)D) and 24,25- dihydroxyvitamin D (24,25(OH)2D) by high-performance liquid chromatography tandem mass spectrometry, and 1,25-dihydroxyvitamin D (1,25(OH)2D) by immunoassay during week 1 of training. We examined whether the relationship between 25(OH)D and 1,25(OH)2D:24,25(OH)2D ratio was associated with overuse injury. During 12 weeks training, 21.0% sustained ≥1 overuse musculoskeletal injury, and 5.6% sustained ≥1 bone stress injury. After controlling for sex, BMI, 2.4 km run time, smoking, bone injury history, and Army training course (Officer, standard, or Infantry), lower body overuse musculoskeletal injury incidence was higher for participants within the second lowest versus highest quartile of 24,25(OH)2D (OR: 1.62 [95%CI 1.13–2.32; P = 0.009]) and lowest versus highest cluster of 25(OH)D and 1,25(OH)2D:24,25(OH)2D (OR: 6.30 [95%CI 1.89–21.2; P = 0.003]). Lower body bone stress injury incidence was higher for participants within the lowest versus highest quartile of 24,25(OH)2D (OR: 4.02 [95%CI 1.82–8.87; P < 0.001]) and lowest versus highest cluster of 25(OH)D and 1,25(OH)2D:24,25(OH)2D (OR: 22.08 [95%CI 3.26–149.4; P = 0.001]), after controlling for the same covariates. Greater conversion of 25(OH)D to 24,25(OH)2D, relative to 1,25(OH)2D (i.e., low 1,25(OH)2D:24,25(OH)2D), and higher serum 24,25(OH)2D were associated with a lower incidence of lower body overuse musculoskeletal and bone stress injury. Serum 24,25(OH)2D may have a role in preventing overuse injury in young adults undertaking arduous physical training

The Cosmological Baryon Density from the Deuterium Abundance at a redshift z = 3.57

We present a measurement of the deuterium to hydrogen ratio in a quasar absorption system at redshift z = 3.57 towards QSO 1937-1009. We use a two component fit, with redshifts determined from unsaturated metal lines, to fit the hydrogen and deuterium features simultaneously. We find a low value of D/H = 2.3 \pm 0.6 \times 10^{-5}, which does not agree with other measurements of high D/H (Songaila et al. 1994, Carswell et al. 1994). The absorption system is very metal poor, with metallicities less than 1/100 solar. Standard models of chemical evolution show the astration of deuterium is limited to a few percent from primordial for systems this metal-poor, so we believe our value represents the primordial one. Using predictions of standard big-bang nucleosynthesis and measurements of the cosmic microwave background, our measurement gives the density of baryons in units of the critical density, $\Omega_b h^2 = 0.024 \pm 0.006$, where H_0 = 100 h km s^{-1] Mpc^{-1}.Comment: 10 pages, 2 Figures, also available at http://nately.ucsd.edu/ ; submitted to Natur

Influence of Vitamin D Supplementation by Simulated Sunlight or Oral D3 on Respiratory Infection during Military Training.

PURPOSE: To determine the relationship between vitamin D status and upper respiratory tract infection (URTI) of physically active men and women across seasons (study 1). Then, to investigate the effects on URTI and mucosal immunity of achieving vitamin D sufficiency (25(OH)D ≥50 nmol·L-1) by a unique comparison of safe, simulated-sunlight or oral D3 supplementation in winter (study 2). METHODS: In study 1, 1,644 military recruits were observed across basic military training. In study 2, a randomized controlled trial, 250 men undertaking military training received either placebo, simulated-sunlight (1.3x standard erythemal dose, three-times-per-week for 4-weeks and then once-per-week for 8-weeks) or oral vitamin D3 (1,000 IU·day-1 for 4-weeks and then 400 IU·day-1 for 8-weeks). URTI was diagnosed by physician (study 1) and Jackson common cold questionnaire (study 2). Serum 25(OH)D, salivary secretory immunoglobulin A (SIgA) and cathelicidin were assessed by LC-MS/MS and ELISA. RESULTS: In study 1, only 21% of recruits were vitamin D sufficient during winter. Vitamin D sufficient recruits were 40% less likely to suffer URTI than recruits with 25(OH)D 0.05). Supplementation did not affect salivary SIgA or cathelicidin. CONCLUSION: Vitamin D sufficiency reduced the URTI burden during military training

Rodent models of focal cerebral ischemia: procedural pitfalls and translational problems

Rodent models of focal cerebral ischemia are essential tools in experimental stroke research. They have added tremendously to our understanding of injury mechanisms in stroke and have helped to identify potential therapeutic targets. A plethora of substances, however, in particular an overwhelming number of putative neuroprotective agents, have been shown to be effective in preclinical stroke research, but have failed in clinical trials. A lot of factors may have contributed to this failure of translation from bench to bedside. Often, deficits in the quality of experimental stroke research seem to be involved. In this article, we review the commonest rodent models of focal cerebral ischemia - middle cerebral artery occlusion, photothrombosis, and embolic stroke models - with their respective advantages and problems, and we address the issue of quality in preclinical stroke modeling as well as potential reasons for translational failure

Solid-state epimerisation and disproportionation of pilocarpine HCl: Why we need a 5-stage approach to validate melting point measurements for heat-sensitive drugs

Melting points for new drugs are reported in regulatory documents, e.g. investigational brochures, and frequently in published research; however, the authors do not typically consider that heat-induced degradation can affect the melting point measurement. Applying a single heating rate is not adequate, and thus many melting points in the literature and regulatory documentation are not valid. Our aim was to validate a five-stage approach for the melting point measurement of heat-sensitive drugs. These stages are; 1) observe melting; 2) record mass loss; 3) measure melting points at different heating rates; 4) characterise degradation and 5) test for potential isomerisation. Applying this approach to pilocarpine HCl illustrated the sensitivity of a melting point to thermal degradation. Due to salt disproportionation & loss of HCl gas, pilocarpine's melting point decreased by 14 °C when the heating rate was lowered from 20 to 1 °C/min. Epimerization occurred before melting was reached. Increasing the heating rate diminished disproportionation; however, this did not remove epimerization. Thus, the melting point of pilocarpine HCl of 205.5 ± 0.4 °C measured at 20 °C/min represents the melt of a racemic mixture containing inactive isopilocarpine. Heating above the melting point accelerated degradation, a rate of 5°C/min recovered just 38 ± 1% of pilocarpine. Such data predicted a shelf-life of 6.6years. Pilocarpine successfully validated the multistage approach by providing new knowledge concerning its thermal stability. Our 5-stage approach must be applied to all new drugs especially if their formulation requires heat. For example, thermal stability is an infrequently considered pre-requisite in the emerging field of 3D printing

Iron status is associated with tibial structure and vitamin D metabolites in healthy young men.

The influence of iron on collagen synthesis and vitamin D metabolism has implications for bone health. This cross-sectional observational study investigated associations between markers of iron status and tibial structure, vitamin D metabolites, and circulating biochemical markers of bone metabolism in young healthy men. A total of 343 male British Army recruits participated (age 22 ± 3 y, height 1.77 ± 0.06 m, body mass 75.5 ± 10.1 kg). Circulating biochemical markers of iron status, vitamin D metabolites, and bone metabolism, and tibial structure and density by high-resolution peripheral quantitative computed tomography scans (HRpQCT) were measured in participants during week 1 of basic military training. Associations between markers of iron status and HRpQCT outcomes, bone metabolism, and vitamin D metabolites were tested, controlling for age, height, lean body mass, and childhood exercise volume. Higher ferritin was associated with higher total, trabecular, and cortical volumetric bone mineral density, trabecular volume, cortical area and thickness, stiffness, and failure load (all p ≤ 0.037). Higher soluble transferrin receptor (sTfR) was associated with lower trabecular number, and higher trabecular thickness and separation, cortical thickness, and cortical pore diameter (all p ≤ 0.033). Higher haemoglobin was associated with higher cortical thickness (p = 0.043). Higher ferritin was associated with lower βCTX, PINP, total 25(OH)D, and total 24,25(OH)2D, and higher 1,25(OH)2D:24,25(OH)2D ratio (all p ≤ 0.029). Higher sTfR was associated with higher PINP, total 25(OH)D, and total 24,25(OH)2D (all p ≤ 0.025). The greater density, size, and strength of the tibia, and lower circulating concentrations of markers of bone resorption and formation with better iron stores (higher ferritin) are likely as a result of the direct role of iron in collagen synthesis

Sex differences in iron status during military training: a prospective cohort study of longitudinal changes and associations with endurance performance and musculoskeletal outcomes

This study investigated sex differences in iron status, and associations between iron status and endurance and musculoskeletal outcomes, in military training. 2,277 British Army trainees (581 women) participated. Iron markers and endurance performance (2.4 km run) were measured at the start (week 1) and end (week 13) of training. Whole-body areal body mineral density (aBMD) and markers of bone metabolism were measured at week 1. Injuries during training were recorded. Training decreased haemoglobin in men and women (mean change [95% CI], -0.1 [-0.2, -0.0] and -0.7 [-0.9, -0.6] g∙d-1, both p < 0.001), but more so in women (p < 0.001). Ferritin decreased in men and women (-27 [-28, -23] and -5 [-8, -1] ug∙L, both p ≤ 0.001), but more so in men (p < 0.001). sTfR increased in men and women (2.9 [2.3, 3.6] and 3.8 [2.7, 4.9] nmol∙L, both p < 0.001), with no difference between sexes (p = 0.872). RDW increased in men (0.3 [0.2, 0.4]%, p < 0.001), but not women (0.1 [-0.1, 0.2]%, p = 0.956). MCV decreased in men (-1.5 [-1.8, -1.1] fL, p < 0.001), but not women (0.4 [-0.4, 1.3] fL, p = 0.087). Lower ferritin was associated with slower 2.4 km run time (p = 0.018), sustaining a lower limb overuse injury (p = 0.048), lower aBMD (p = 0.021), and higher βCTX and P1NP (both p < 0.001) controlling for sex. Improving iron stores before training may protect haemoglobin in women and improve endurance and protect against injury

Vitamin D Metabolites are Associated with Physical Performance in Young Healthy Adults.

Purpose To determine vitamin D metabolites and vitamin D receptor (VDR) single-nucleotide polymorphisms (SNPs) relationships with physical performance. Methods In 1205 men and 322 women (94.8% white Caucasian, 22.0 ± 2.8 years) commencing military training, we measured: serum vitamin D metabolites (25-hydroxyvitamin D (25(OH)D) and 24,25-dihydroxyvitamin D (24,25(OH)2D) by high-performance liquid chromatography tandem mass spectrophotometry, and 1,25-dihydroxyvitamin D (1,25(OH)2D) by immunoassay); VDR SNPs (rs2228570, rs4516035, and rs7139166 by polymerase chain reaction genotyping); and endurance performance by 2.4 km run, muscle strength by maximal dynamic lift, and muscle power by maximal vertical jump. Results Serum 25(OH)D was negatively associated with 2.4 km run time and positively associated with muscle power (β = –12.0 and 90.1), 1,25(OH)2D was positively associated with run time and negatively associated with strength and muscle power (β = 5.6, –1.06, and –38.4), and 24,25(OH)2D was negatively associated with run time (β = –8.9; P < 0.01), after controlling for age, sex, smoking, alcohol, physical activity, time outdoors, season, and BMI. Vitamin D metabolites (25(OH)D, 1,25(OH)2D, and 24,25(OH)2D) together explained variances of 5.0% in run time, 0.7% in strength, and 0.9% in muscle power (ΔF P < 0.001). All performance measures were superior with low 1,25(OH)2D:24,25(OH)2D ratio (P < 0.05). VDR SNPs were not associated with physical performance (ΔF P ≥ 0.306). Conclusions Vitamin D metabolites accounted for a small portion of variance in physical performance. Associations between vitamin D metabolites and run time were the most consistent. VDR SNPs explained no variance in performance. Greater conversion of 25(OH)D to 24,25(OH)2D, relative to 1,25(OH)2D (i.e., low 1,25(OH)2D:24,25(OH)2D ratio), was favourable for performance, indicating 24,25(OH)2D may have a role in optimising physical performance