Annual high-dose oral vitamin D and falls and fractures in older women : a randomized controlled trial

Context Improving vitamin D status may be an important modifiable risk factor to reduce falls and fractures; however, adherence to daily supplementation is typically poor.

Objective To determine whether a single annual dose of 500 000 IU of cholecalciferol administered orally to older women in autumn or winter would improve adherence and reduce the risk of falls and fracture.

Design, Setting, and Participants A double-blind, placebo-controlled trial of 2256 community-dwelling women, aged 70 years or older, considered to be at high risk of fracture were recruited from June 2003 to June 2005 and were randomly assigned to receive cholecalciferol or placebo each autumn to winter for 3 to 5 years. The study concluded in 2008.

Intervention 500 000 IU of cholecalciferol or placebo.

Main Outcome Measures Falls and fractures were ascertained using monthly calendars; details were confirmed by telephone interview. Fractures were radiologically confirmed. In a substudy, 137 randomly selected participants underwent serial blood sampling for 25-hydroxycholecalciferol and parathyroid hormone levels.

Results Women in the cholecalciferol (vitamin D) group had 171 fractures vs 135 in the placebo group; 837 women in the vitamin D group fell 2892 times (rate, 83.4 per 100 person-years) while 769 women in the placebo group fell 2512 times (rate, 72.7 per 100 person-years; incidence rate ratio [RR], 1.15; 95% confidence interval [CI], 1.02-1.30; P = .03). The incidence RR for fracture in the vitamin D group was 1.26 (95% CI, 1.00-1.59; P = .047) vs the placebo group (rates per 100 person-years, 4.9 vitamin D vs 3.9 placebo). A temporal pattern was observed in a post hoc analysis of falls. The incidence RR of falling in the vitamin D group vs the placebo group was 1.31 in the first 3 months after dosing and 1.13 during the following 9 months (test for homogeneity; P = .02). In the substudy, the median baseline serum 25-hydroxycholecalciferol was 49 nmol/L. Less than 3% of the substudy participants had 25-hydroxycholecalciferol levels lower than 25 nmol/L. In the vitamin D group, 25-hydroxycholecalciferol levels increased at 1 month after dosing to approximately 120 nmol/L, were approximately 90 nmol/L at 3 months, and remained higher than the placebo group 12 months after dosing.

Conclusion Among older community-dwelling women, annual oral administration of high-dose cholecalciferol resulted in an increased risk of falls and fractures.

The influence of specific luminal factors on the colonic epithelium : high-dose butyrate and physical changes suppress early carcinogenic events in rats

INTRODUCTION Although luminal delivery of butyrate is one putative mechanism by which biology of the colonic epithelium might be influenced by changes in luminal contents, there is a paucity of supportive cause–effect evidence. This study aimed to directly establish whether distal colonic butyrate delivery is able to alter the response of the distal colonic epithelium to a carcinogen.
METHODS Groups of male Sprague-Dawley rats with chronically intubated colons received infusions of 80 mM butyrate or 0.9 percent saline into distal colon two or five times daily. Three weeks after exposure to azoxymethane (15 mg/kg subcutaneously), the density of aberrant crypts was quantified in distal colon.
RESULTS Infusions of 0.5 ml twice daily, whether containing saline or butyrate, decreased the number of aberrant crypt foci by 45 percent compared with rats receiving no infusions (P = 0.004, analysis of variance). Similar results were obtained when infusions were restricted to the postinitiation phase. When infusions were increased to 1 ml five times daily, saline infusions similarly suppressed aberrant crypt formation (38 percent), but butyrate infusions suppressed it to a greater degree (by 64 percent; P = 0.02 compared with saline infusion, t-test).
CONCLUSIONS High levels of butyrate delivery to the distal colonic lumen alter the epithelial response to a carcinogen in otherwise healthy rats. This finding directly supports the notion that the effects of butyrate on cells in vitro do occur in vivo provided a sufficient dose is delivered. The effect of infusion of liquid per se on the epithelial response highlights the potential impact physical changes alone can have on the colonic epithelium.

Annual high-dose vitamin D3 and mental well-being: randomised controlled trial

Background Epidemiological evidence supports a relationship between vitamin D and mental well-being, although evidence from large-scale placebo-controlled intervention trials is lacking.

Aims To examine if vitamin D supplementation has a beneficial effect on mood in community-dwelling older women; if a single annual large dose of vitamin D has a role in the prevention of depressive symptoms; and if there is an association between serum 25-hydroxyvitamin D levels and mental health.

Method A double-blind, randomised, placebo-controlled trial of women aged 70 or older (the Vital D Study: ISRCTN83409867 and ACTR12605000658617). Participants were randomly assigned to receive 500 000 IU vitamin D3 (cholecalciferol) orally or placebo every autumn/winter for 3–5 consecutive years. The tools utilised at various time points were the General Health Questionnaire, the 12-item Short Form Health Survey, the Patient Global Impression–Improvement scale and the WHO Well-Being Index. Serum 25-hydroxyvitamin D levels were measured in a subset of 102 participants.

Results In this non-clinical population, no significant differences between the vitamin D and placebo groups were detected in any of the measured outcomes of mental health. Serum 25-hydroxyvitamin D levels in the vitamin D group were 41% higher than the placebo group 12 months following their annual dose. Despite this difference, scores from the questionnaires did not differ. Furthermore, there was no interaction between those on antidepressant/anxiety medication at baseline and the treatment groups.

Conclusions The lack of improvement in indices of mental well-being in the vitamin D group does not support the hypothesis that an annual high dose of vitamin D3 is a practical intervention to prevent depressive symptoms in older community-dwelling women.

High strain rate tensile properties of rapidly cured woven carbon fibre composites

Tensile tests at high speeds corresponding to automotive crash events were conducted to understand the dynamic properties of rapidly cured woven carbon fiber composites. The High Strain Rate (HSR) experiments were conducted on a servo-hydraulic machine at constant velocities up to a maximum of 25 m/s (82 ft/s). Results from HSR tests were compared with the static results to determine the rate sensitivity of the composite. A high speed camera was used to capture the failure at HSR. The tensile properties of rapidly cured laminate were compared to oven cured laminate to justify its productivity while maintaining the desired properties. The methodology used to achieve constant velocity during HSR tests is discussed in detail. The specimen geometry was specially designed to suit the test rig and to achieve high speeds during tests. All the specimens failed with linear elasticity until sudden brittle fracture. The Scanning Electron Microscopy (SEM) images of the fracture zone were used to identify the failure modes observed at static and high strain rates.

Recrystallization of 304SS during and after high strain rate deformation

During the hot working of austenitic stainless steels the shape of the flow curve is strongly influenced by the strain rate. Low strain rate deformation results in flow curves typical of dynamic recrystallization (DRX) but as the strain rate increases the shape changes to a ‘flat-top’ curve. This has traditionally been thought to indicate no DRX is taking place and that dynamic recovery (DRV) is the only operating softening mechanism. Examining the work-hardening behaviour and corresponding deformation microstructures showed this is not the case for austenitic stainless steel, as clear evidence of dynamic recrystallization process can be seen. The post-deformation recrystallization kinetics can be modelled using a standard Avrami equation with an Avrami exponent, n, of 1.15. With an increasing value of the Zener-Hollomon parameter it was found that the kinetics of recrystallization become less strain rate sensitive until at the highest values (highest strain rates/lowest temperatures) the recrystallization kinetics become strain rate insensitive.

Effects of sublethal fenitrothion ingestion on cholinesterase inhibition, standard metabolism, thermal preference, and prey-capture ability in the Australian central bearded dragon (Pogona vitticeps, Agamidae)

The central bearded dragon (Pogona vitticeps) is a medium-sized lizard that is common in semiarid habitats in Australia and that potentially is at risk of fenitrothion exposure from use of the chemical in plague locust control. We examined the effects of single sublethal doses of this organophosphate (OP; low dose = 2.0 mg/kg; high dose = 20 mg/kg; control = vehicle alone) on lizard thermal preference, standard metabolic rate, and prey-capture ability. We also measured activities of plasma total cholinesterase (ChE) and acetylcholinesterase before and at 0, 2, 8, 24, 120, and 504 h after OP dosing. Predose plasma total ChE activity differed significantly between sexes and averaged 0.66 ± 0.06 and 0.45 ± 0.06 μmol/min/ml for males and females, respectively. Approximately 75% of total ChE activity was attributable to butyrylcholinesterase. Peak ChE inhibition reached 19% 2 h after OP ingestion in the low-dose group, and 68% 8 h after ingestion in high-dose animals. Neither OP doses significantly affected diurnal body temperature, standard metabolic rate, or feeding rate. Plasma total ChE levels remained substantially depressed up to 21 d after dosing in the high-dose group, making this species a useful long-term biomonitor of OP exposure in its habitat.

Anomalous evaporation behavior of ZnO powder milled mechanically under high-energy conditions

ZnO powder showed anomalous evaporation behavior after its mechanical milling treatment under high-energy conditions. The amount of generated vapor is about 10 times higher in the first 15 min of annealing at 1300 °C than that of unmilled ZnO powders. The strong ball impacts are responsible for the greatly enhanced evaporation ability. Low-energy ball milling involving shearing actions and rare weak impacts leads only to a small evaporation rate enhancement. The possible explanation of the high evaporation rate of the heavily milled material is the existence of large fraction of weakly bonded atoms in grain boundaries, surface defects and strained areas.

Characterization of high fluid strain micro contractions to study the stress on biological fluids

Microfluidics has the potential to enhance the understanding of the biological fluids under strain, due to the laminar nature of the fluid and the possibility to mimic the real conditions. We present advances on charaterization of a microfluidic platform to study high strain rate flows in the transport of biological fluids. These advances are improvements on the reproduction of a  constant extensional strain rate using micro contractions and development of 3D numerical models. The micro geometries have been fabricated in polydimethyl siloxame (PDMS) using standard soft-lithography techniques with a photolithographically patterned mold. A comparison of some microcontractions with different funnel characteristics is presented. The Micro Particle Image Velocimetry technique has been applied to validate the numerical simulations. We demonstrate the use of microfluidics in the reproduction of a large range of controllable extensional strains that can be used in the study of the effect of flow on biological fluids.