Effects of reduced energy availability on bone metabolism in women and men

Background: The short-term effects of low energy availability (EA) on bone metabolism in physically active women and men are currently unknown. Purpose: We evaluated the effects of low EA on bone turnover markers (BTMs) in a cohort of women and a cohort of men, and compared effects between sexes. Methods: These studies were performed using a randomised, counterbalanced, crossover design. Eleven eumenorrheic women and eleven men completed two 5-day protocols of controlled (CON; 45 kcal·kgLBM-1.d-1) and restricted (RES; 15 kcal.kgLBM-1·d-1) EAs. Participants ran daily on a treadmill at 70% of their peak aerobic capacity (VO2 peak) resulting in an exercise energy expenditure of 15 kcal·kgLBM-1·d-1 and consumed diets providing 60 and 30 kcal·kgLBM-1·d-1. Blood was analysed for BTMs [β-carboxyl-terminal cross-linked telopeptide of type I collagen (β-CTX) and amino-terminal propeptide of type 1 procollagen (P1NP)], markers of calcium metabolism [( parathyroid hormone (PTH), albumin-adjusted calcium (ACa), magnesium (Mg) and phosphate (PO4)] and regulatory hormones [sclerostin, insulin-like growth factor 1 (IGF-1), triiodothyronine (T3), insulin, leptin, glucagon-like- peptide-2 (GLP-2)]. Results: In women,β-CTX AUC was significantly higher P=0.03) and P1NP AUC was significantly lower (P=0.01) in RES compared to CON. In men, neither β-CTX (P=0.46) n or P1NP (P=0.12) AUCs were significantly different between CON and RES. There were no significant differences between sexes for any BTM AUCs (all P values>0.05). Insulin and leptin AUCs were significantly lower following RES in women only (for both P=0.01). There were no differences in any AUCs of regulatory hormones or markers of calcium metabolism between men and women following RES (all P values>0.05). Conclusions: When comparing within groups, five days of low EA (15 kcal·kgLBM-1·d-1) decreased bone formation and increased bone resorption in women, but not in men, and no sex specific differences were detected

Parathyroid hormone secretion is controlled by both ionised calcium and phosphate during exercise and recovery in men

The mechanism by which PTH is controlled during and after exercise is poorly understood due to insufficient temporal frequency of measurements. Objective: To examine the temporal pattern of PTH, PO4, ACa and Ca2+ during and after exercise. Design and setting: A laboratory-based study with a cross-over design, comparing 30 min of running at 55%, 65% and 75%VO2max, followed by 2.5-h of recovery. Blood was obtained at baseline, after 2.5, 5, 7.5, 10, 15, 20, 25 and 30 min of exercise and after 2.5, 5, 7.5, 10, 15, 20, 25, 30, 60, 90 and 150 min of recovery. Participants: Ten men (age 23±1 y, height 1.82±0.07 m, body mass 77.0±7.5 kg) participated. Main Outcome Measures: PTH, PO4, ACa and Ca2+ Results: Independent of intensity, PTH concentrations decreased with the onset of exercise (-21 to -33%; P≤0.001), increased thereafter and were higher than baseline by the end of exercise at 75%VO2max (+52%; P≤0.001). PTH peaked transiently after 5–7.5 min of recovery (+73 to +110%; P≤0.001). PO4 followed a similar temporal pattern to PTH and Ca2+ followed a similar but inverse pattern to PTH. PTH was negatively correlated with Ca2+ across all intensities (r=-0.739 to -0.790; P≤0.001). When PTH was increasing, the strongest cross-correlation was with Ca2+ at 0 lags (3.5 min) (r=-0.902 to -0.950); during recovery, the strongest cross-correlation was with PO4 at 0 lags (8 min) (r=0.987 to 0.995). Conclusions: PTH secretion during exercise and recovery is controlled by a combination of changes in Ca2+ and PO4 in men

Bone metabolic responses to low energy availability achieved by diet or exercise in active eumenorrheic women

Purpose: We aimed to explore the effects of low energy availability (EA)[15 kcal·kg lean body mass (LBM)−1·d−1] achieved by diet or exercise on bone turnover markers in active, eumenorrheic women. Methods: By using a crossover design, ten eumenorrheic women (VO2 peak: 48.1 ± 3.3 ml·kg−1·min−1) completed all three, 3-day conditions in a randomised order: controlled EA (CON; 45 kcal·kgLBM−1·d−1), low EA through dietary energy restriction (D-RES; 15 kcal·kgLBM−1·d−1) and low EA through increasing exercise energy expenditure (E-RES; 15 kcal·kgLBM−1·d−1), during the follicular phase of three menstrual cycles. In CON, D-RES and E-RES, participants consumed diets providing 45, 15 and 45 kcal·kgLBM−1·d−1. In E-RES only, participants completed supervised running sessions (129 ± 10 min·d−1) at 70% of their VO2 peak that resulted in an exercise energy expenditure of 30 kcal·kg LBM−1·d−1. Blood samples were collected at baseline (BASE) and at the end of the 3-day period (D6) and analysed for bone turnover markers (β-CTX and P1NP), markers of calcium metabolism (PTH, albumin-adjusted Ca, Mg and PO4) and hormones (IGF-1, T3, insulin, leptin and 17β-oestradiol). Results: In D-RES, P1NP concentrations at D6 decreased by 17% (BASE: 54.8 ± 12.7 μg·L−1, D6: 45.2 ± 9.3 μg·L−1, P < 0.001, d = 0.91) and were lower than D6 concentrations in CON (D6: 52.5 ± 11.9 μg·L−1, P = 0.001). P1NP did not change significantly in E-RES (BASE: 55.3 ± 14.4 μg·L−1, D6: 50.9 ± 15.8 μg·L−1, P = 0.14). β-CTX concentrations did not change following D-RES (BASE: 0.48 ± 0.18 μg·L−1, D6: 0.55 ± 0.17 μg·L−1) or E-RES (BASE: 0.47 ± 0.24 μg·L−1, D6: 0.49 ± 0.18 μg·L−1) (condition × time interaction effect, P = 0.17). There were no significant differences in P1NP (P = 0.25) or β-CTX (P = 0.13) responses between D-RES and E-RES. Both conditions resulted in reductions in IGF-1 (−13% and − 23% from BASE in D-RES and E-RES, both P < 0.01) and leptin (−59% and − 61% from BASE in D-RES and E-RES, both P < 0.001); T3 decreased in D-RES only (−15% from BASE, P = 0.002) and PO4 concentrations decreased in E-RES only (−9%, P = 0.03). Conclusions: Low EA achieved through dietary energy restriction resulted in a significant decrease in bone formation but no change in bone resorption, whereas low EA achieved through exercise energy expenditure did not significantly influence bone metabolism. Both low EA conditions elicited significant and similar changes in hormone concentrations

Computer simulation of syringomyelia in dogs

Syringomyelia is a pathological condition in which fluid-filled cavities (syringes) form and expand in the spinal cord. Syringomyelia is often linked with obstruction of the craniocervical junction and a Chiari malformation, which is similar in both humans and animals. Some brachycephalic toy breed dogs such as Cavalier King Charles Spaniels (CKCS) are particularly predisposed. The exact mechanism of the formation of syringomyelia is undetermined and consequently with the lack of clinical explanation, engineers and mathematicians have resorted to computer models to identify possible physical mechanisms that can lead to syringes. We developed a computer model of the spinal cavity of a CKCS suffering from a large syrinx. The model was excited at the cranial end to simulate the movement of the cerebrospinal fluid (CSF) and the spinal cord due to the shift of blood volume in the cranium related to the cardiac cycle. To simulate the normal condition, the movement was prescribed to the CSF. To simulate the pathological condition, the movement of CSF was blocked

Bone metabolic marker concentrations across the menstrual cycle and phases of combined oral contraceptive use

There is a need to further understand the impact of the menstrual cycle and phase of combined oral contraceptive (COC) use on the pre-analytical variability of markers of bone metabolism in order to improve standardisation procedures for clinical practice and research. The aim of this study was to assess bone metabolism marker concentrations across the menstrual cycle and phases of COC use. Carboxy-terminal cross-linking telopeptide of type I collagen (β-CTX), procollagen type 1 N propeptide (P1NP) and Bone alkaline phosphatase (Bone ALP) concentrations were assessed in eumenorrheic women (n = 14) during the early follicular, ovulatory and mid-luteal phases of the menstrual cycle and in COC (Microgynon®) (n = 14) users on day 2-3 of pill consumption (PC1), day 15-16 pill consumption (PC2) and day 3-4 of the pill free interval (PFI). β-CTX was significantly (-16%) lower at PC2 compared to PC1 (P = 0.015) in COC users and was not affected by menstrual cycle phase (P > 0.05). P1NP and Bone ALP were not significantly different across either menstrual cycle phase or phase of COC use (all P > 0.05). There was no difference in pooled bone marker concentrations between eumenorrheic women and COC users (P > 0.05). In contrast to some previous studies, this study showed that bone marker concentrations do not significantly fluctuate across the menstrual cycle. Furthermore, bone resorption markers are significantly affected by phase of COC use, although bone formation markers do not significantly vary by COC phase. Therefore, the phase of COC use should be considered in clinical practice and research when assessing markers of bone metabolism as this can impact circulating concentrations of bone metabolic markers yet is not currently considered in existing guidelines for best practice

The legacy of 1300 years of land use in Jamaica

Despite decades of archaeological research on Jamaica, little is known about how settlers influenced landscape change on the island over time. Here, we examine the impact of human occupation through a multi-proxy approach using phytolith, charcoal, and stratigraphic analyses. White Marl was a continuously inhabited village settlement (ca. 1050–450 cal yrs BP) with large mounded midden areas, precolonial house structures, and human landscape management practices. We have shown that the local vegetation at White Marl was directly affected by human settlement through the use of agroforestry and burning, and suggest that fire was used to modify vegetation. Manioc phytoliths were found throughout human occupation and are broadly associated with increases in evidence for burning, suggesting fire was used to modify the landscape and clear vegetation for crop cultivation. The phytolith assemblages relate to three distinct temporal vegetation phases: (1) the earliest occupation dominated by arboreal vegetation (pre-ca. 870 cal yrs BP); (2) a transition to palm-dominated vegetation (ca. 870–670 cal yrs BP); and (3) the latest occupation representing European colonization associated with a more open, grass-dominated landscape (after ca. 670 cal yrs BP). These transitions occur independent of changes in paleoclimate records, suggesting humans were the dominant driver of vegetation change

A randomised controlled trial of the effects of albendazole in pregnancy on maternal responses to mycobacterial antigens and infant responses to bacille Calmette-Guérin (BCG) immunisation [ISRCTN32849447]

BACKGROUND: Maternal schistosomiasis and filariasis have been shown to influence infant responses to neonatal bacille Calmette-Guérin (BCG) immunisation but the effects of maternal hookworm, and of de-worming in pregnancy, are unknown. METHODS: In Entebbe, Uganda, we conducted a randomised, double-blind, placebo-controlled trial of a single dose of 400 mg of albendazole in the second trimester of pregnancy. Neonates received BCG. Interferon-gamma (IFN-γ) and interleukin (IL)-5 responses to a mycobacterial antigen (crude culture filtrate proteins (CFP) of Mycobacterium tuberculosis) were measured in a whole blood assay. We analysed results for binary variables using χ(2 )tests and logistic regression. We analysed continuous variables using Wilcoxon's tests. RESULTS: Maternal hookworm was associated with reduced maternal IFN-γ responses to CFP (adjusted odds ratio for IFN-γ > median response: 0.14 (95% confidence interval 0.02–0.83, p = 0.021). Conversely, maternal hookworm was associated with subsequent increased IFN-γ responses in their one-year-old infants (adjusted OR 17.65 (1.20–258.66; p = 0.013)). Maternal albendazole tended to reduce these effects. CONCLUSION: Untreated hookworm infection in pregnancy was associated with reduced maternal IFN-γ responses to mycobacterial antigens, but increased responses in their infants one year after BCG immunisation. The mechanisms of these effects, and their implications for protective immunity remain, to be determined

Middleborns disadvantaged? testing birth-order effects on fitness in pre-industrial finns

Parental investment is a limited resource for which offspring compete in order to increase their own survival and reproductive success. However, parents might be selected to influence the outcome of sibling competition through differential investment. While evidence for this is widespread in egg-laying species, whether or not this may also be the case in viviparous species is more difficult to determine. We use pre-industrial Finns as our model system and an equal investment model as our null hypothesis, which predicts that (all else being equal) middleborns should be disadvantaged through competition. We found no overall evidence to suggest that middleborns in a family are disadvantaged in terms of their survival, age at first reproduction or lifetime reproductive success. However, when considering birth-order only among same-sexed siblings, first-, middle-and lastborn sons significantly differed in the number of offspring they were able to rear to adulthood, although there was no similar effect among females. Middleborn sons appeared to produce significantly less offspring than first-or lastborn sons, but they did not significantly differ from lastborn sons in the number of offspring reared to adulthood. Our results thus show that taking sex differences into account is important when modelling birth-order effects. We found clear evidence of firstborn sons being advantaged over other sons in the family, and over firstborn daughters. Therefore, our results suggest that parents invest differentially in their offspring in order to both preferentially favour particular offspring or reduce offspring inequalities arising from sibling competition

A pilot study of a phenomenological model of adipogenesis in maturing adipocytes using Cahn–Hilliard theory

We consider the accumulation and formation of lipid droplets in an adipocyte cell. The process incorporates adipose nucleation (adipogenesis) and growth. At later stages, there will be merging of droplets and growth of larger droplets at the expense of the smaller droplets, which will essentially undergo lipolysis. The process is modeled by the use of the Cahn–Hilliard equation, which is mass-conserving and allows the formation of secondary phases in the context of spinodal decomposition. The volume of fluid (VOF) method is used to determine the total area that is occupied by the lipids in a given cross section. Further, we present an algorithm, applicable to all kinds of grids (structured or unstructured) in two spatial dimensions, to count the number of lipid droplets and the portion of the domain of computation that is occupied by the lipid droplets as a function of time during the process. The results are preliminary and are validated from a qualitative point using experiments carried out on cell cultures. It turns out that the Cahn–Hilliard theory can model many of the features during adipogenesis qualitatively

Mucociliary and long-term particle clearance in airways of patients with immotile cilia

Spherical monodisperse ferromagnetic iron oxide particles of 1.9 μm geometric and 4.2 μm aerodynamic diameter were inhaled by seven patients with primary ciliary dyskinesia (PCD) using the shallow bolus technique, and compared to 13 healthy non-smokers (NS) from a previous study. The bolus penetration front depth was limiting to the phase1 dead space volume. In PCD patients deposition was 58+/-8 % after 8 s breath holding time. Particle retention was measured by the magnetopneumographic method over a period of nine months. Particle clearance from the airways showed a fast and a slow phase. In PCD patients airway clearance was retarded and prolonged, 42+/-12 % followed the fast phase with a mean half time of 16.8+/-8.6 hours. The remaining fraction was cleared slowly with a half time of 121+/-25 days. In healthy NS 49+/-9 % of particles were cleared in the fast phase with a mean half time of 3.0+/-1.6 hours, characteristic of an intact mucociliary clearance. There was no difference in the slow clearance phase between PCD patients and healthy NS. Despite non-functioning cilia the effectiveness of airway clearance in PCD patients is comparable to healthy NS, with a prolonged kinetics of one week, which may primarily reflect the effectiveness of cough clearance. This prolonged airway clearance allows longer residence times of bacteria and viruses in the airways and may be one reason for increased frequency of infections in PCD patients