A 250 μg/week dose of vitamin D was as effective as a 50 μg/d dose in healthy adults, but a regimen of four weekly followed by monthly doses of 1250 μg raised the risk of hypercalciuria

The risk of vitamin D insufficiency is increased in persons having limited sunlight exposure and dietary vitamin D. Supplementation compliance might be improved with larger doses taken less often, but this may increase the potential for side effects. The objective of the present study was to determine whether a weekly or weekly/monthly regimen of vitamin D supplementation is as effective as daily supplementation without increasing the risk of side effects. Participants were forty-eight healthy adults who were randomly assigned for 3 months to placebo or one of three supplementation regimens: 50 μg/d (2000 IU/d, analysed dose 70 μg/d), 250 μg/week (10 000 IU/week, analysed dose 331 μg/week) or 1250 μg/week (50 000 IU/week, analysed dose 1544 μg/week) for 4 weeks and then 1250 μg/month for 2 months. Daily and weekly doses were equally effective at increasing serum 25-hydroxyvitamin D, which was significantly greater than baseline in all the supplemented groups after 30 d of treatment. Subjects in the 1250 μg treatment group, who had a BMI >26 kg/m2, had a steady increase in urinary Ca in the first 3 weeks of supplementation, and, overall, the relative risk of hypercalciuria was higher in the 1250 μg group than in the placebo group (P= 0·01). Although vitamin D supplementation remains a controversial issue, these data document that supplementing with ≤ 250 μg/week ( ≤ 10 000 IU/week) can improve or maintain vitamin D status in healthy populations without the risk of hypercalciuria, but 24 h urinary Ca excretion should be evaluated in healthy persons receiving vitamin D3 supplementation in weekly single doses of 1250 μg (50 000 IU).

Impairment of simulated motorcycle riding performance under low dose alcohol

Crash statistics that include the blood alcohol concentration (BAC) of vehicle operators reveal that crash involved motorcyclists are over represented at low BACs (e.g., ≤0.05%). This riding simulator study compared riding performance and hazard response under three low dose alcohol conditions (sober, 0.02% BAC, 0.05% BAC). Forty participants (20 novice, 20 experienced) completed simulated rides in urban and rural scenarios while responding to a safety-critical peripheral detection task (PDT). Results showed a significant increase in the standard deviation of lateral position in the urban scenario and PDT reaction time in the rural scenario under 0.05% BAC compared with zero alcohol. Participants were most likely to collide with an unexpected pedestrian in the urban scenario at 0.02% BAC, with novice participants at a greater relative risk than experienced riders. Novices chose to ride faster than experienced participants in the rural scenario regardless of BAC. Not all results were significant, emphasising the complex situation of the effects of low dose BAC on riding performance, which needs further research. The results of this simulator study provide some support for a legal BAC for motorcyclists below 0.05%.

A single dose of azithromycin does not improve clinical outcomes of children hospitalised with bronchiolitis : a randomised, placebo-controlled trial

Objective Bronchiolitis, one of the most common reasons for hospitalisation in young children, is particularly problematic in Indigenous children. Macrolides may be beneficial in settings where children have high rates of nasopharyngeal bacterial carriage and frequent prolonged illness. The aim of our double-blind placebo-controlled randomised trial was to determine if a large single dose of azithromycin (compared to placebo) reduced length of stay (LOS), duration of oxygen (O2) and respiratory readmissions within 6 months of children hospitalised with bronchiolitis. We also determined the effect of azithromycin on nasopharyngeal microbiology. Methods Children aged ≤18 months were randomised to receive a single large dose (30 mg/kg) of either azithromycin or placebo within 24 hrs of hospitalisation. Nasopharyngeal swabs were collected at baseline and 48hrs later. Primary endpoints (LOS, O2) were monitored every 12 hrs. Hospitalised respiratory readmissions 6-months post discharge was collected. Results 97 children were randomised (n = 50 azithromycin, n = 47 placebo). Median LOS was similar in both groups; azithromycin = 54 hours, placebo = 58 hours (difference between groups of 4 hours 95%CI -8, 13, p = 0.6). O2 requirement was not significantly different between groups; Azithromycin = 35 hrs; placebo = 42 hrs (difference 7 hours, 95%CI -9, 13, p = 0.7). Number of children re-hospitalised was similar 10 per group (OR = 0.9, 95%CI 0.3, 2, p = 0.8). At least one virus was detected in 74% of children. The azithromycin group had reduced nasopharyngeal bacterial carriage (p = 0.01) but no difference in viral detection at 48 hours. Conclusion Although a single dose of azithromycin reduces carriage of bacteria, it is unlikely to be beneficial in reducing LOS, duration of O2 requirement or readmissions in children hospitalised with bronchiolitis. It remains uncertain if an earlier and/or longer duration of azithromycin improves clinical and microbiological outcomes for children.

The relationship between ambient ultraviolet radiation (UVR) and objectively measured personal UVR exposure dose is modified by season and latitude

Despite the widespread use of ambient ultraviolet radiation (UVR) as a proxy measure of personal exposure to UVR, the relationship between the two is not well-defined. This paper examines the effects of season and latitude on the relationship between ambient UVR and personal UVR exposure. We used data from the AusD Study, a multi-centre cross-sectional study among Australian adults (18-75 years), where personal UVR exposure was objectively measured using polysulphone dosimeters. Data were analysed for 991 participants from 4 Australian cities of different latitude: Townsville (19.3 °S), Brisbane (27.5 °S), Canberra (35.3 °S) and Hobart (42.8 °S). Daily personal UVR exposure varied from 0.01 to 21 Standard Erythemal Doses (median=1.1, IQR: 0.5–2.1), on average accounting for 5% of the total available ambient dose. There was an overall positive correlation between ambient UVR and personal UVR exposure (r=0.23, p<0.001). However, the correlations varied according to season and study location: from strong correlations in winter (r=0.50) and at high latitudes (Hobart, r=0.50; Canberra, r=0.39), to null or even slightly negative correlations, in summer (r=0.01) and at low latitudes (Townsville, r=-0.06; Brisbane, r=-0.16). Multiple regression models showed significant effect modification by season and location. Personal exposure fraction of total available ambient dose was highest in winter (7%) and amongst Hobart participants (7%) and lowest in summer (1%) and in Townsville (4%). These results suggest season and latitude modify the relationship between ambient UVR and personal UVR exposure. Ambient UVR may not be a good indicator for personal exposure dose under some circumstances.

Morphometric analysis of the thoracic intervertebral foramen osseous anatomy in adolescent idiopathic scoliosis using low dose computerized tomography

Introduction. The dimensions of the thoracic intervertebral foramen in adolescent idiopathic scoliosis (AIS) have not previously been quantified. During posterior approach scoliosis correction surgery pedicle screws may occasionally breach into the foramen. Better understanding of the dimensions of the foramen may be useful in surgical planning. This study describes a reproducible method for measurement of the thoracic foramen in AIS using computerized tomography (CT). Methods. In 23 pre-operative female patients with Lenke 1 type AIS with right side convexity major curves confined to the thoracic spine the foraminal height (FH), foraminal width (FW), pedicle to superior articular process distance (P-SAP) and cross sectional foraminal area (FA) were measured using multiplanar reconstructed CT. Measurements were made at entrance, midpoint and exit of the thoracic foramina from T1/T2 to T11/T12. Results were correlated with potential dependent variables of major curve Cobb Angle measured on X-ray and CT, Age, Weight, Lenke classification subtype, Risser Grade and number of spinal levels in the major curve. Results. The FH, FW, P-SAP and FA dimensions and ratios are all significantly larger on the convexity of the major curve and maximal at or close to the apex. Mean thoracic foraminal dimensions change in a predictable manner relative to position on the major thoracic curve. There was no significant correlation with the measured foraminal dimensions or ratios and the potential dependent variables. The average ratio of convexity to concavity dimensions at the apex foramina for entrance, midpoint and exit respectively are FH (1.50, 1.38, 1.25), FW (1.28, 1.30, 0.98), FA (2.06, 1.84, 1.32), P-SAP (1.61, 1.47, 1.30). Conclusion. Foraminal dimensions of the thoracic spine are significantly affected by AIS. Foraminal dimensions have a predictable convexity to concavity ratio relative to the proximity to the major curve apex. Surgeons should be aware of these anatomical differences during scoliosis correction surgery.

Using low dose computerized tomography to morphometrically analyse the thoracic intervertebral foramen osseous anatomy in adolescent idiopathic scoliosis

INTRODUCTION The dimensions of the thoracic intervertebral foramen in adolescent idiopathic scoliosis (AIS) have not previously been quantified. During posterior approach scoliosis correction surgery pedicle screws may occasionally breach into the foramen. Better understanding of the dimensions of the foramen may be useful in surgical planning. This study describes a reproducible method for measurement of the thoracic foramen in AIS using computerized tomography (CT). METHODS In 23 pre-operative female patients with Lenke 1 type AIS with right side convexity major curves confined to the thoracic spine the foraminal height (FH), foraminal width (FW), pedicle to superior articular process distance (P-SAP) and cross sectional foraminal area (FA) were measured using multiplanar reconstructed CT. Measurements were made at entrance, midpoint and exit of the thoracic foramina from T1/T2 to T11/T12. Results were correlated with potential dependent variables of major curve Cobb Angle measured on X-ray and CT, Age, Weight, Lenke classification subtype, Risser Grade and number of spinal levels in the major curve. RESULTS The FH, FW, P-SAP and FA dimensions and ratios are all significantly larger on the convexity of the major curve and maximal at or close to the apex. Mean thoracic foraminal dimensions change in a predictable manner relative to position on the major thoracic curve. There was no significant correlation with the measured foraminal dimensions or ratios and the potential dependent variables. The average ratio of convexity to concavity dimensions at the apex foramina for entrance, midpoint and exit respectively are FH (1.50, 1.38, 1.25), FW (1.28, 1.30, 0.98), FA (2.06, 1.84, 1.32), P-SAP (1.61, 1.47, 1.30). CONCLUSION Foraminal dimensions of the thoracic spine are significantly affected by AIS. Foraminal dimensions have a predictable convexity to concavity ratio relative to the proximity to the major curve apex. Surgeons should be aware of these anatomical differences during scoliosis correction surgery.

Low-dose curcumin stimulates proliferation, migration and phagocytic activity of olfactory ensheathing cells

One of the promising strategies for neural repair therapies is the transplantation of olfactory ensheathing cells (OECs) which are the glial cells of the olfactory system. We evaluated the effects of curcumin on the behaviour of mouse OECs to determine if it could be of use to further enhance the therapeutic potential of OECs. Curcumin, a natural polyphenol compound found in the spice turmeric, is known for its anti-cancer properties at doses over 10 µM, and often at 50 µM, and it exerts its effects on cancer cells in part by activation of MAP kinases. In contrast, we found that low-dose curcumin (0.5 µM) applied to OECs strikingly modulated the dynamic morphology, increased the rate of migration by up to 4-fold, and promoted significant proliferation of the OECs. Most dramatically, low-dose curcumin stimulated a 10-fold increase in the phagocytic activity of OECs. All of these potently stimulated behavioural characteristics of OECs are favourable for neural repair therapies. Importantly, low-dose curcumin gave a transient activation of p38 kinases, which is in contrast to the high dose curcumin effects on cancer cells in which these MAP kinases tend to undergo prolonged activation. Low-dose curcumin mediated effects on OECs demonstrate cell-type specific stimulation of p38 and ERK kinases. These results constitute the first evidence that low-dose curcumin can modulate the behaviour of olfactory glia into a phenotype potentially more favourable for neural repair and thereby improve the therapeutic use of OECs for neural repair therapies

Partial intervertebral fusion secures successful outcomes after thoracoscopic anterior scoliosis correction: A low-dose computed tomography study

Study Design Retrospective review of prospectively collected data. Objectives To analyze intervertebral (IV) fusion after thoracoscopic anterior spinal fusion (TASF) and explore the relationship between fusion scores and key clinical variables. Summary of Background Information TASF provides comparable correction with some advantages over posterior approaches but reported mechanical complications, and their relationship to non-union and graft material is unclear. Similarly, the optimal combination of graft type and implant stiffness for effecting successful radiologic union remains undetermined. Methods A subset of patients from a large single-center series who had TASF for progressive scoliosis underwent low-dose computed tomographic scans 2 years after surgery. The IV fusion mass in the disc space was assessed using the 4-point Sucato scale, where 1 indicates <50% and 4 indicates 100% bony fusion of the disc space. The effects of rod diameter, rod material, graft type, fusion level, and mechanical complications on fusion scores were assessed. Results Forty-three patients with right thoracic major curves (mean age 14.9 years) participated in the study. Mean fusion scores for patient subgroups ranged from 1.0 (IV levels with rod fractures) to 2.2 (4.5-mm rod with allograft), with scores tending to decrease with increasing rod size and stiffness. Graft type (autograft vs. allograft) did not affect fusion scores. Fusion scores were highest in the middle levels of the rod construct (mean 2.52), dropping off by 20% to 30% toward the upper and lower extremities of the rod. IV levels where a rod fractured had lower overall mean fusion scores compared to levels without a fracture. Mean total Scoliosis Research Society (SRS) questionnaire scores were 98.9 from a possible total of 120, indicating a good level of patient satisfaction. Conclusions Results suggest that 100% radiologic fusion of the entire disc space is not necessary for successful clinical outcomes following thoracoscopic anterior selective thoracic fusion.

Effects of inoculating dose on the kinetics of Chlamydia muridarum genital infection in female mice

Chlamydia trachomatis infections have been implicated in problems such as pelvic inflammatory disease and infertility in females. Although there are some studies examining the kinetics of ascending infection, there is limited information on the kinetics of pathology development and cellular infiltrate into the reproductive tissues in relation to the effects of inoculating dose, and a better understanding of these is needed. The murine model of female genital tract Chlamydia muridarum infection is frequently used as a model of human C. trachomatis reproductive tract infection. To investigate the kinetics of ascending genital infection and associated pathology development, female BALB/c mice were intravaginally infected with C. muridarum at doses ranging from 5102 to 2.6106 inclusion forming units. We found that the inoculating dose affects the course of infection and the ascension of bacteria, with the highest dose ascending rapidly to the oviducts. By comparison, the lowest dose resulted in the greatest bacterial load in the lower reproductive tract. Interestingly, we found that the dose did not significantly affect inflammatory cell infiltrate in the various regions. Overall, this data show the effects of infectious dose on the kinetics of ascending chlamydial infection and associated inflammatory infiltration in BALB/c mice.

Investigation of molecular mechanisms regulating biomineralization of pearl oyster Pinctada maxima

Biomineralization is a process encompassing all mineral containing tissues produced within an organism. The most dynamic example of this process is the formation of the mollusk shell, comprising a variety of crystal phases and microstructures. The organic component incorporated within the shell is said to dictate this remarkable architecture. Subsequently, for the past decade considerable research have been undertaken to identify and characterize the protein components involved in biomineralization. Despite these efforts the general understanding of the process remains ambiguous. This study employs a novel molecular approach to further the elucidation of the shell biomineralization. A microarray platform has been custom generated (PmaxArray 1.0) from the pearl oyster Pinctada maxima. PmaxArray 1.0 consists of 4992 expressed sequence tags (ESTs) originating from the mantle, an organ involved in shell formation. This microarray has been used as the primary tool for three separate investigations in an effort to associate transcriptional gene expression from P. maxima to the process of shell biomineralization. The first investigation analyzes the spatial expression of ESTs throughout the mantle organ. The mantle was dissected into five discrete regions and each analyzed for gene expression with PmaxArray 1.0. Over 2000 ESTs were differentially expressed among the tissue sections, identifying five major expression regions. Three of these regions have been proposed to have shell formation functions belonging to nacre, prismatic calcite and periostracum. The spatial gene expression map was confirmed by in situ hybridization, localizing a subset of ESTs from each expression region to the same mantle area. Comparative sequence analysis of ESTs expressed in the proposed shell formation regions with the BLAST tool, revealed a number of the transcripts were novel while others showed significant sequence similarities to previously characterized shell formation genes. The second investigation correlates temporal EST expression during P. maxima larval ontogeny with transitions in shell mineralization during the same period. A timeline documenting the morphologicat microstructural and mineralogical shell characteristics of P. maxima throughout larval ontogeny has been established. Three different shell types were noted based on the physical characters and termed, prodissoconch I, prodissoconch 11 and dissoconch. PmaxArray 1.0 analyzed ESTs expression of animals throughout the larval development of P. maxima, noting up-regulation of 359 ESTs in association with the shell transitions from prodissoconch 1 to prodissoconch 11 to dissoconch. Comparative sequence analysis of these ESTs indicates a number of the transcripts are novel as well as showing significant sequence similarities between ESTs and known shell matrix associated genes and proteins. These ESTs are discussed in relation to the shell characters associated with their temporal expression. The third investigation uses PmaxArray 1.0 to analyze gene expression in the mantle tissue of P. maxima specimens exposed to sub-lethal concentrations of a shell-deforming toxin, tributyltin (TBT). The shell specific effects of TBT are used in this investigation to interpret differential expression of ESTs with respect to shell formation functions. A lethal and sublethal TBT concentration range was established for P. maxima, noting a concentration of 50 ng L- 1 TBT as sub-lethal over a 21 day period. Mantle tissue from P. maxima animals treated with 50 ng L- 1 TBT was assessed for differential EST expression with untreated control animals. A total of 102 ESTs were identified as differentially expressed in association with TBT exposure, comparative sequence identities included an up-regulation of immunity and detoxification related genes and down-regulation of several shell matrix genes. A number of transcripts encoding novel peptides were additionally identified. The potential actions of these genes are discussed with reference to TBT toxicity and shell biomineralization. This thesis has used a microarray platform to analyze gene expression in spatial, temporal and toxicity investigations, revealing the involvement of numerous gene transcripts in specific shell formation functions. Investigation of thousands of transcripts simultaneously has provided a holistic interpretation of the organic components regulating shell biomineralization.