Duodenal Expression of 25 Hydroxyvitamin D3-1α-hydroxylase Is Higher in Adolescents Than in Children and Adults.

CONTEXT: Puberty is associated with increased dietary calcium absorption. However, little is known about the metabolic adaptations that enhance calcium absorption during puberty. OBJECTIVES: To investigate duodenal 25-hydroxy vitamin D-1α-hydroxylase (CYP 27B1) mRNA expression and duodenal 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) production in children, adolescents, and adults. DESIGN AND METHODS: CYP27B1a nd IGF1 mRNA expression and 1,25(OH)2D3 production were determined in duodenal biopsies. CYP27B1 expression was also determined after IGF1R inhibitor treatment of human and mice duodenal explants. mRNA expression was determined by RT-PCR, and CYP27B1 activity was determined by incubating duodenal explants with 25(OH)D3 and measuring 1,25(OH)2D3 production by radioimmunoassay. RESULTS: CYP27B1 mRNA expression was 13.7 and 10.4 times higher in biopsies from adolescents compared to adults and children, respectively. IGF1 mRNA expression was 30% and 45% higher in explants from adolescents and children, respectively, compared to adults. Inhibition of IGF1 receptor activity decreased CYP27B1 expression in explants from both mice (85%) and humans (24%). 1,25(OH)2D3 production reached a maximum velocity of 768 ± 268 pmol/l/mg protein at 748.8 nmol/l of 25(OH)D3 in children and adolescents, whereas the maximum velocity was 86.4 ± 43.2 pmol/l/mg protein in adults. The substrate concentration at which the enzyme shows half of its maximum activity was similar in all groups, ranging between 624 and 837 nmol/L of 25(OH)D3. CONCLUSIONS: Increased CYP27B1 expression and local duodenal 1,25(OH)2D3 production during puberty may be a metabolic adaptation that promotes dietary calcium absorption. IGF1, a major factor in skeletal growth, is also involved in the modulation of CYP27B1 expression in the gut and may increase calcium supply for the growing bone.

A single-unit design structure and gender differences in the swimming world championships.

Four 50 meter male/female finals - the freestyle, butterfly, breaststroke, and backstroke - swum during individual events at the Swimming World Championships (SWCs) can be defined in four clusters. The aim of the present study was to use a single-unit design structure, in which the swimmer was defined at only one scale, to evaluate gender differences in start reaction times among elite swimmers in 50 m events. The top six male and female swimmers in the finals of four swimming stroke final events in six SWCs were analyzed. An unpaired t-test was used. The p-values were evaluated using Neo-Fisherian significance assessments (Hurlbert and Lombardi, 2012). For the freestyle, gender differences in the start reaction times were positively identified for five of the six SWCs. For the backstroke, gender differences in the start reaction times could be dismissed for five of the six SWCs. For both the butterfly and breaststroke, gender differences in the start reaction times yielded inconsistent statistical differences. Pooling all swimmers together (df = 286) showed that an overall gender difference in the start reaction times could be positively identified: p = 0.00004. The contrast between the gender differences in start reaction times between the freestyle and backstroke may be associated with different types of gender adaptations to swimming performances. When the natural groupings of swimming stroke final events were ignored, sacrificial pseudoreplication occurred, which may lead to erroneous statistical differences.

The role of vitamin D receptor in innate and adaptive immunity: a study in hereditary vitamin D-resistant rickets patients.

CONTEXT: Vitamin D has regulatory effects on innate and adaptive immunity. Curiously, hereditary vitamin D-resistant rickets (HVDRR) patients show no increased incidence of infectious or autoimmune diseases. OBJECTIVES: The aim of the study was to investigate the role of vitamin D and the vitamin D receptor (VDR) in innate and adaptive immune responses in monocytes and lymphocytes from HVDRR patients. DESIGN AND METHODS: Fifteen HVDRR patients and 17 controls participated in the investigation. Activated monocytes (lipopolysaccharides) and lymphocytes (anti-CD3, CD28, and α-GalCer) were incubated with and without 25(OH)D3 (100 nM). The mRNA expressions of CYP27B1 and VDR; vitamin D response (TLR2); vitamin D response elements binding protein (hnRNP); antimicrobial peptides cathelicidin and ß-defensin; the transcription factor enhancer binding proteins C/EBPα, C/EBPß, and C/EBPε and enzymes involved in NO generation, Nos2, and Arginase1 were analyzed by RT-PCR. TNF-α, interferon-γ, IL-4, IL-10, and IL-17 concentrations in lymphocyte cultures media were measured by ELISA. RESULTS: Cathelicidin expression was lower in HVDRR monocytes than in control monocytes. 25(OH)D3 increased significantly the expression of cathelicidin in control monocytes (2.3-fold) but only slightly in HVDRR monocytes. 25(OH)D3 increased the expression of VDR (2-fold), C/EBPε (2-fold), C/EBPß (1.7-fold), and hnRNP and suppressed TLR2 only in control monocytes. Unexpectedly, 25(OH)D3 increased the expression of CYP27b1, C/EBPα, Nos2, and Arginase1 in HVDRR monocytes. TNFα and IL-17 concentrations were significantly higher in HVDRR lymphocyte cultures than in controls. 25(OH)D3 suppressed IL-17 only in control lymphocyte. 25(OH)D3 increased IL-4, IL-10, and interferon-γ concentrations in control lymphocyte media but not in HVDRR. CONCLUSIONS: Our results demonstrate impairments in various components of innate immunity in HVDTRR patients' monocytes and a proinflammatory cytokine profile in their lymphocytes. The underlying VDR-independent compensatory mechanisms that protect HVDRR patients from infections and autoimmune diseases remain undetermined.

Experimental versus evaluation unit and multiplicity problem in cell biology study.

Yizraeli and Weihs, Cell Biochem Biophys, 61: 605-618, 2011 evaluated the effect of electrical treatment on proliferative metabolic-activity of three experimental cell conditions. They reported, that the "...three independent experiments were done in triplicate (three samples in parallel, O.V.) for each condition...", in three time-points. Therefore, I suggest, that any three samples in parallel (triplicate) in the same experiment shared more similar environmental conditions compared to any three samples (no triplicate) from three different independent experiments. Moreover, the absence of basic statistical information in the manuscript of Yizraeli and Weihs (2011) might be associated with hidden common statistical errors: (a) implicit pseudoreplication due to incorrect determination of the experimental and evaluation units and (b) simultaneous inference without correction of p-values due to ignoring the overall type I error rate.

Constant and variable stiffness and damping of the leg joints in human hopping.

The present study deals with the stiffness and damping profiles of the leg joints during the ground-contact phase of hopping. A two-dimensional (sagittal plane) jumping model, consisting of four linked rigid segments and including the paired feet, shanks, thighs, and the head-arms-trunk segment, was developed. The segments were interconnected by damped torsional springs, representing the action of the muscles, tendons and ligaments across the joint and of the other joint tissues. A regressive function was used to express stiffness and damping, and included second-order dependence on angle and first-order dependence on angular velocity. By eliminating redundancies in the numerical solution using multicollinearity diagnostic algorithms, the model results revealed that the correct and sufficient nonlinearity for the joint stiffness is of the first order. Damping was found negligible. The stiffness profiles obtained were bell-shaped with a maximum near midstance and nonzero edge values. In predicting the joint moments, the obtained variable joint stiffnesses provided a closer agreement compared to a constant stiffness model. The maximal stiffness was found to be in linear correlation with the initial stiffness in each joint, providing support to the of muscles' preactivation strategy during the flight phase of hopping. All stiffnesses increased with increasing hopping frequency. The model presented provides an effective tool for future designing of artificial legs and robots and for the development of more accurate control strategies.

Dynamic loading on the human musculoskeletal system -- effect of fatigue.

OBJECTIVE: A study was conducted to investigate the effects of fatigue on the ability of human musculoskeletal system to deal with the onslaught of the heel strike initiated shock waves. DESIGN: Running on a treadmill at the anaerobic threshold level for 30 min was used to acquire the experimental data on the foot strike initiated shock waves. BACKGROUND: Muscles act to lower the bending stress on bone and to attenuate the dynamic load on human musculoskeletal system. Fatigue may diminish their ability to dissipate and attenuate loading on the system. Knowledge of the effects of fatigue on the ability of the human musculoskeletal system to attenuate the shock waves may help in design of the training procedures and exercises. METHODS: Twenty-two young healthy males participated in this study. Each one was running on the treadmill at the speed corresponding to his anaerobic threshold for 30 min. The heel strike induced shock waves were recorded every 5 min on the tibial tuberosity and sacrum. The data obtained were analyzed in both temporal and frequency domains. RESULTS: The results reveal significant increase in the dynamic loading experienced by the human musculoskeletal system with fatigue. This may be attributed to the inability of the fatigued system to provide an efficient way to attenuate shock waves. CONCLUSIONS: The analysis of the recorded signals suggests that fatigue contributes to the reduction of the human musculoskeletal system's capacity to attenuate and dissipate those shock waves. This capacity appears to be a function not only of the fatigue level, but also of the vertical location along the skeleton. RELEVANCE: Fatigue during running may affect the ability of the human musculoskeletal system to attenuate and dissipate the heel strike induced shock waves. The study of the fatigue effect on shock wave attenuation provides information that may benefit the runner.

Shock Transmission and Fatigue in Human Running.

The goal of this research was to analyze the effects of fatigue on the shock waves generated by foot strike. Twenty-two subjects were instrumented with an externally attached, lightweight accelerometer placed over the tibial tuberosity. The subjects ran on a treadmill for 30 min at a speed near their anaerobic threshold. Fatigue was established when the end-tidal CO2 pressure decreased. The results indicated that approximately half of the subjects reached the fatigue state toward the end of the test. Whenever fatigue occurred, the peak acceleration was found to increase. It was thus concluded that there is a clear association between fatigue and increased heel strike-induced shock waves. These results have a significant implication for the etiology of running injuries, since shock wave attenuation has been previously reported to play an important role in preventing such injuries.