Understanding the effect of mechanical forces on ovarian cancer progression.

OBJECTIVE: Mechanical forces including tension, compression, and shear stress are increasingly implicated in tumor progression and metastasis. Understanding the mechanisms behind epithelial ovarian cancer (EOC) progression and metastasis is critical, and this study aimed to elucidate the effect of oscillatory and constant tension on EOC. METHODS: SKOV-3 and OVCAR-8 EOC cell lines were placed under oscillatory tension for 3 days and compared to cells placed under no tension. Cell proliferation, migration, and invasion were analyzed while RNAseq and Western Blots helped investigate the biological mechanisms underlying the increasingly aggressive state of the experimental cells. Finally, in vivo experiments using SCID mice assisted in confirming the in vitro results. RESULTS: Oscillatory tension (OT) and constant tension (CT) significantly increased SKOV-3 proliferation, while OT caused a significant increase in proliferative genes, migration, and invasion in this cell line. CT did not cause significant increases in these areas. Neither OT nor CT increased proliferation or invasion in OVCAR-8 cells, while both tension types significantly increased cellular migration. Two proteins involved in metastasis, E-cadherin and Snail, were both significantly affected by OT in both cell lines, with E-cadherin levels decreasing and Snail levels increasing. In vivo, tumor growth and weight for both cell types were significantly increased, and ascites development was significantly higher in the experimental OVCAR-8 group than in the control group. CONCLUSIONS: This study found that mechanical forces are influential in EOC progression and metastasis. Further analysis of downstream mechanisms involved in EOC metastasis will be critical for improvements in EOC treatment.

First Documented Pathologies in Tenontosaurus tilletti with Comments on Infection in Non-Avian Dinosaurs.

In 2001, a nearly complete sub-adult Tenontosaurus tilletti was collected from the Antlers Formation (Aptian-Albian) of southeastern Oklahoma. Beyond its exceptional preservation, computed tomography (CT) and physical examination revealed this specimen has five pathological elements with four of the pathologies a result of trauma. Left pedal phalanx I-1 and left dorsal rib 10 are both fractured with extensive callus formation in the later stages of healing. Left dorsal rib 7 (L7) and right dorsal rib 10 (R10) exhibit impacted fractures compressed 26 mm and 24 mm, respectively. The fracture morphologies in L7 and R10 indicate this animal suffered a strong compressive force coincident with the long axis of the ribs. All three rib pathologies and the pathological left phalanx I-1 are consistent with injuries sustained in a fall. However, it is clear from the healing exhibited by these fractures that this individual survived the fall. In addition to traumatic fractures, left dorsal rib 10 and possibly left phalanx I-1 have a morphology consistent with post-traumatic infection in the form of osteomyelitis. The CT scans of left metacarpal IV revealed the presence of an abscess within the medullary cavity consistent with a subacute form of hematogenous osteomyelitis termed a Brodie abscess. This is only the second reported Brodie abscess in non-avian dinosaurs and the first documented occurrence in herbivorous dinosaurs. The presence of a Brodie abscess, known only in mammalian pathological literature, suggest mammalian descriptors for bone infection may be applicable to non-avian dinosaurs.

25-Hydroxyvitamin D status, light exposure and sleep quality in UK dwelling South Asian and Caucasian postmenopausal women.

There is a lack of research into 25-hydroxyvitamin D (25(OH)D) status, light exposure and sleep patterns in South Asian populations. In addition, results of research studies are conflicting as to whether there is an association between 25(OH)D status and sleep quality. We investigated 25(OH)D status, self-reported and actigraphic sleep quality in n = 35 UK dwelling postmenopausal women (n = 13 South Asians, n = 22 Caucasians), who kept daily sleep diaries and wore wrist-worn actiwatch (AWL-L) devices for 14 days. A subset of n = 27 women (n = 11 South Asian and n = 16 Caucasian) also wore a neck-worn AWL-L device to measure their light exposure. For 25(OH)D concentration, South Asians had a median ± IQR of 43.8 ± 28.2 nmol/L, which was significantly lower than Caucasians (68.7 ± 37.4 nmol/L)(P = 0.001). Similarly, there was a higher sleep fragmentation in the South Asians (mean ± SD 36.9 ± 8.9) compared with the Caucasians (24.7 ± 7.1)(P = 0.002). Non-parametric circadian rhythm analysis of rest/activity patterns showed a higher night-time activity (L5) (22.6 ± 14.0 vs. 10.5 ± 4.4; P = 0.0008) and lower relative amplitude (0.85 ± 0.07 vs. 0.94 ± 0.02; P < 0.0001) in the South Asian compared with the Caucasian women. More South Asians (50%) met the criteria for sleep disorders (PSQI score >5) than did Caucasians (27%) (P = 0.001, Fishers Exact Test). However, there was no association between 25(OH)D concentration and any sleep parameter measured (P > 0.05) in either ethnic group. South Asians spent significantly less time in illuminance levels over 200 lx (P = 0.009) than did Caucasians. Overall, our results show that postmenopausal South Asian women have lower 25(OH)D concentration than Caucasian women. They also have higher sleep fragmentation, as well as a lower light exposure across the day. This may have detrimental implications for their general health and further research into sleep quality and light exposure in the South Asian ethnic group is warranted.

Higher bone resorption excretion in South Asian women vs. White Caucasians and increased bone loss with higher seasonal cycling of vitamin D: Results from the D-FINES cohort study.

Few data exist on bone turnover in South Asian women and it is not well elucidated as to whether Western dwelling South Asian women have different bone resorption levels to that of women from European ethnic backgrounds. This study assessed bone resorption levels in UK dwelling South Asian and Caucasian women as well as evaluating whether seasonal variation in 25-hydroxyvitamin D [25(OH)D] is associated with bone resorption in either ethnic group. Data for seasonal measures of urinary N-telopeptide of collagen (uNTX) and serum 25(OH)D were analysed from n=373 women (four groups; South Asian postmenopausal n=44, South Asian premenopausal n=50, Caucasian postmenopausal n=144, Caucasian premenopausal n=135) (mean (±SD) age 48 (14) years; age range 18-79years) who participated in the longitudinal D-FINES (Diet, Food Intake, Nutrition and Exposure to the Sun in Southern England) cohort study (2006-2007). A mixed between-within subjects ANOVA (n=192) showed a between subjects effect of the four groups (P<0.001) on uNTX concentration, but no significant main effect of season (P=0.163). Bonferroni adjusted Post hoc tests (P≤0.008) suggested that there was no significant difference between the postmenopausal Asian and premenopausal Asian groups. Season specific age-matched-pairs analyses showed that in winter (P=0.04) and spring (P=0.007), premenopausal Asian women had a 16 to 20nmolBCE/mmol Cr higher uNTX than premenopausal Caucasian women. The (amplitude/mesor) ratio (i.e. seasonal change) for 25(OH)D was predictive of uNTX, with estimate (SD)=0.213 (0.015) and 95% CI (0.182, 0.245; P<0.001) in a non-linear mixed model (n=154). This showed that individuals with a higher seasonal change in 25(OH)D, adjusted for overall 25(OH)D concentration, showed increased levels of uNTX. Although the effect size was smaller than for the amplitude/mesor ratio, the mesor for 25(OH)D concentration was also predictive of uNTX, with estimate (SD)=-0.035 (0.004), and 95% CI (-0.043, -0.028; P<0.001). This study demonstrates higher levels of uNTX in premenopausal South Asian women than would be expected for their age, being greater than same-age Caucasian women, and similar to postmenopausal Asian women. This highlights potentially higher than expected bone resorption levels in premenopausal South Asian women which, if not offset by concurrent increased bone formation, may have future clinical and public health implications which warrant further investigation. Individuals with a larger seasonal change in 25(OH)D concentration showed an increased bone resorption, an association which was larger than that of the 25(OH)D yearly average, suggesting it may be as important clinically to ensure a stable and steady 25(OH)D concentration, as well as one that is high enough to be optimal for bone health.

Concurrent beneficial (vitamin D production) and hazardous (cutaneous DNA damage) impact of repeated low-level summer sunlight exposures.

BACKGROUND: The concurrent impact of repeated low-level summer sunlight exposures on vitamin D production and cutaneous DNA damage, potentially leading to mutagenesis and skin cancer, is unknown. OBJECTIVES: This is an experimental study (i) to determine the dual impact of repeated low-level sunlight exposures on vitamin D status and DNA damage/repair (via both skin and urinary biomarkers) in light-skinned adults; and (ii) to compare outcomes following the same exposures in brown-skinned adults. METHODS: Ten white (phototype II) and six South Asian volunteers (phototype V), aged 23-59 years, received 6 weeks' simulated summer sunlight exposures (95% ultraviolet A/5% ultraviolet B, 1·3 standard erythemal doses three times weekly) wearing summer clothing exposing ~35% body surface area. Assessments made were circulating 25-hydroxyvitamin D [25(OH)D], immunohistochemistry for cyclobutane pyrimidine dimer (CPD)-positive nuclei and urinary biomarkers of direct and oxidative (8-oxo-deoxyguanosine) DNA damage. RESULTS: Serum 25(OH)D rose from mean 36·5 ± 13·0 to 54·3 ± 10·5 nmol L-1 (14·6 ± 5·2 to 21·7 ± 4·2 ng mL-1 ) in phototype II vs. 17·2 ± 6·3 to 25·5 ± 9·5 nmol L-1 (6·9 ± 2·5 to 10·2 ± 3·8 ng mL-1 ) in phototype V (P < 0·05). Phototype II skin showed CPD-positive nuclei immediately postcourse, mean 44% (range 27-84) cleared after 24 h, contrasting with minimal DNA damage and full clearance in phototype V (P < 0·001). The findings did not differ from those following single ultraviolet radiation (UVR) exposure. Urinary CPDs remained below the detection threshold in both groups; 8-oxo-deoxyguanosine was higher in phototype II than V (P = 0·002), but was unaffected by UVR. CONCLUSIONS: Low-dose summer sunlight exposures confer vitamin D sufficiency in light-skinned people concurrently with low-level, nonaccumulating DNA damage. The same exposures produce minimal DNA damage but less vitamin D in brown-skinned people. This informs tailoring of sun-exposure policies.

Low serum 25-hydroxyvitamin D is associated with increased risk of stress fracture during Royal Marine recruit training.

UNLABELLED: The aim of this study was to investigate vitamin D status and stress fracture risk during Royal Marine military training. Poor vitamin D status was associated with an increased risk of stress fracture. Vitamin D supplementation may help to reduce stress fracture risk in male military recruits with low vitamin D status. INTRODUCTION: Stress fracture is a common overuse injury in military recruits, including Royal Marine (RM) training in the UK. RM training is recognised as one of the most arduous basic training programmes in the world. Associations have been reported between serum 25-hydroxyvitamin D (25(OH)D) and risk of stress fracture, but the threshold of 25(OH)D for this effect remains unclear. We aimed to determine if serum 25(OH)D concentrations were associated with stress fracture risk during RM training. METHODS: We prospectively followed 1082 RM recruits (males aged 16-32 years) through the 32-week RM training programme. Troops started training between September and July. Height, body weight and aerobic fitness were assessed at week 1. Venous blood samples were drawn at weeks 1, 15 and 32. Serum samples were analysed for 25(OH)D and parathyroid hormone (PTH). RESULTS: Seventy-eight recruits (7.2 %) suffered a total of 92 stress fractures. Recruits with a baseline serum 25(OH)D concentration below 50 nmol L(-1) had a higher incidence of stress fracture than recruits with 25(OH)D concentration above this threshold (χ(2) (1) = 3.564, p = 0.042; odds ratio 1.6 (95 % confidence interval (CI) 1.0-2.6)). Baseline serum 25(OH)D varied from 47.0 ± 23.7 nmol L(-1) in February, to 97.3 ± 24.6 nmol L(-1) in July (overall mean 69.2 ± 29.2 nmol L(-1), n = 1016). There were weak inverse correlations between serum 25(OH)D and PTH concentrations at week 15 (r = -0.209, p < 0.001) and week 32 (r = -0.214, p < 0.001), but not at baseline. CONCLUSION: Baseline serum 25(OH)D concentration below 50 nmol L(-1) was associated with an increased risk of stress fracture. Further studies into the effects of vitamin D supplementation on stress fracture risk are certainly warranted.

Ethnicity and social deprivation contribute to vitamin D deficiency in an urban UK population.

We receive a large number of 25 hydroxyvitamin D (25OHD) assay requests from General Medical Practitioners (GPs) in primary care. We have investigated whether this rate of requesting is related to the ethnicity of the local urban population based in Central Manchester or Trafford areas with very different ethnic populations. Data on assay requesting was collected from January-December 2013. Samples were assayed using an ABSciex 5500 tandem mass spectrophotometer and the Chromsystems 25OHD kit for LC-MS/MS. 11,291 requests for 25OHD measurement received from Central Manchester GPs and 5176 requests from Trafford GPs. Overall 29% of patients were profoundly deficient (<25nmol/L) and a further 32% were insufficient (25-50nmol/L). Using the 2011 Census data we have analysed our data by ethnicity (categorized here as white, Asian, black, Chinese, other) based on patient's home postcode and related this to the Index of Multiple Deprivation (IMD). In areas where >70% of the population were non-white (NW), 69% had 25OHD <50nmol/L. Areas where <5% of patients were NW, 42% of patients were still insufficient. There was a significant correlation between the Index of Social Deprivation (IMD) and the percentage of patients with 25OHD <50nmol/L (p<0.0001). Areas with the highest Index of Social Deprivation (IMD ranking <16,000) showed no association between ethnicity and IMD (p=0.69). We have shown that over 61% of all patients in these urban areas of Manchester and Trafford showed increased risk of bone, and potentially other diseases, based on their 25OHD assay results alone and that social deprivation, as well as ethnicity, contribute to the poor 25OHD levels seen in these patients.

Automated immunoassays for 25-hydroxyvitamin D (25-OHD): do plasticisers interfere?

The international quality assessment scheme for vitamin D metabolites (DEQAS) was established in 1989. The scheme involves the quarterly distribution of 5 serum samples prepared from blood collected in plain plastic bags. Following transfer of the donors to a clinic using different bags, sera were found to contain a contaminant that interfered in both the local LC-MS/MS assay and the NIST reference measurement procedure for 25-OHD. It seemed likely that the contaminant was a substance, possibly a plasticiser, leached from the plastic bag. It was subsequently suggested that the unidentified contaminant might also cause interference in certain automated non-extraction assays for 25-OHD. This was investigated in 3 automated immunoassays by comparing serum 25-OHD results from blood collected simultaneously into plain glass tubes and plastic bags. There was no significant difference in results, indicating that the leached substance had no effect on any of the 3 immunoassays examined.

Sunlight exposure and photoprotection behaviour of white Caucasian adolescents in the UK.

BACKGROUND: Sun exposure has positive and negative effects on health, yet little is known about the sun exposure behaviour of UK adolescents, including those more prone or less prone to sunburn. OBJECTIVE: To examine sun exposure behaviour of UK white Caucasian adolescents including time spent outdoors, holiday behaviour, use of sunscreen and clothing, with assessment for differences between sun-reactive skin type groups. METHODS: White Caucasian adolescents (12-15 years) attending schools in Greater Manchester completed a two-page questionnaire to assess sun exposure and photoprotective behaviour. RESULTS: A total of 133 adolescents (median age 13.4 years; 39% skin type I/II, 61% skin type III/IV) completed the questionnaire. In summer, adolescents spent significantly longer outdoors at weekends (median 4 h/day, range 0.25-10) than on weekdays (2, 0.25-6; P < 0.0001). When at home in the UK during summer, 44% reported never wearing sunscreen compared to just 1% when on a sunny holiday. Sunscreen use was also greater (frequency/coverage) when on a sunny holiday than at home in the UK summer (P < 0.0001). Adolescents of skin types I/II (easy burning) spent significantly less time outdoors than skin types III/IV (easy tanning) on summer weekends (P < 0.001), summer weekdays (P < 0.05) and on a sunny holiday (P = 0.001). Furthermore, skin types I/II reported greater sunscreen use during summer in the UK and on sunny holiday (both P < 0.01), and wore clothing covering a greater skin area on a sunny holiday (P < 0.01) than skin types III/IV. There was no difference in sun exposure behaviour/protection between males and females. CONCLUSION: The greater sun-protective measures reported by adolescents of sun-reactive skin type group I/II than III/IV suggest those who burn more easily are aware of the greater need to protect their skin. However, use of sunscreen during the UK summer is low and may need more effective promotion in adolescents.

Sunlight exposure behaviour and vitamin D status in photosensitive patients: longitudinal comparative study with healthy individuals at U.K. latitude.

BACKGROUND: Low vitamin D status is prevalent in wintertime in populations at northerly latitudes. Photosensitive patients are advised to practise sun avoidance, but their sunlight exposure levels, photoprotective measures and resulting vitamin D status are unknown. OBJECTIVES: To examine seasonal vitamin D status in photosensitive patients relative to healthy individuals and to assess quantitatively behavioural and demographic contributors. METHODS: This was a longitudinal prospective cohort study (53·5°N) examining year-round 25-hydroxyvitamin D [25(OH)D] levels, sun-exposure behaviour and oral vitamin D intake in photosensitive patients diagnosed at a photoinvestigation unit (n = 53), compared with concurrently assessed healthy adults (n = 109). RESULTS: Photosensitive patients achieved seasonal 25(OH)D variation, but insufficient (< 20 ng mL(-1); 50 nmol L(-1)) and even deficient (< 10 ng mL(-1); 25 nmol L(-1)) levels occurred at the summer peak in 47% and 9% of patients, respectively, rising to 73% and 32% at the winter trough. Adjusting for demographic factors, the mean values were lower than for healthy volunteers by 18% [95% confidence interval (CI) 4-29] in summer (P = 0·02) and 25% (95% CI 7-39) in winter (P = 0·01). Behavioural factors explained 25(OH)D differences between cohorts. Patients demonstrated lower weekend ultraviolet B doses (P < 0·001), smaller skin surface area exposure (P = 0·004) and greater sunscreen use (P < 0·001), while average oral vitamin D intake was low in both groups (photosensitive: 2·94 µg per day). Supplementation and summer surface area exposure predicted summer peak and winter trough 25(OH)D levels. A 1 µg per day increment in supplementary vitamin D raised summer and winter 25(OH)D by 5% (95% CI 3-7) and 9% (95% CI 5-12), respectively (both P < 0·001). CONCLUSIONS: Photosensitive patients are, through their photoprotective measures, at high risk of year-round low vitamin D status. Guidance on oral measures should target this patient group and their physicians.

Bone marrow levels of 25 hydroxy vitamin D are not depressed in cases of hip fracture compared with controls.

There is little information on tissue as distinct from plasma levels of vitamin D metabolites in cases of hip fracture compared with controls. Femoral neck fractures in the elderly are associated with increased cortical remodelling and endosteal resorption, leading to regional increases in porosity and reduced cortical thickness. Vitamin D metabolites play a central role in the maintenance of normal serum calcium levels and may, through interactions with parathyroid hormone, exert an important influence on bone structure. To investigate whether hip fracture might be associated with tissue vitamin D deficiency, we have measured by radioimmunoassay the levels of 25 hydroxy vitamin D (25 (OH)D) in bone marrow samples extracted from the proximal femurs of 16 female subjects who had suffered fracture (mean age = 82.1 years, standard error (se) 1.9) and nine sex matched post mortem controls (mean age = 83.8 years, se 2.5). Twenty five (OH)D concentrations were significantly greater in the fracture cases (median = 3.7, IQR = 2.5-3.9 ng/g) than in the control group (median = 1.5, IQR = 0.9-2.3 ng/g; P = 0.0007, non-parametric Wilcoxon/Kruskal-Wallis test). It was suggested in the 1970s that bone loss and hip fracture risk in the UK were driven by vitamin D deficiency. Our results suggest that the alterations in femoral neck bone microstructure and remodelling in hip fracture cannot be assigned to the single cause of relative deficiency of vitamin D. Vitamin D deficiency or insufficiency may nevertheless increase remodelling and loss of bone tissue and contribute causally to a minority of hip fractures.

Greater seasonal cycling of 25-hydroxyvitamin D is associated with increased parathyroid hormone and bone resorption.

SUMMARY: This analysis assessed whether seasonal change in 25-hydroxyvitamin D concentration was associated with bone resorption, as evidenced by serum parathyroid hormone and C-terminal telopeptide concentrations. The main finding was that increased seasonal fluctuation in 25-hydroxyvitamin D was associated with increased levels of parathyroid hormone and C-terminal telopeptide. INTRODUCTION: It is established that adequate 25-hydroxyvitamin D (25(OH)D, vitamin D) concentration is required for healthy bone mineralisation. It is unknown whether seasonal fluctuations in 25(OH)D also impact on bone health. If large seasonal fluctuations in 25(OH)D were associated with increased bone resorption, this would suggest a detriment to bone health. Therefore, this analysis assessed whether there is an association between seasonal variation in 25(OH)D and bone resorption. METHODS: The participants were (n = 279) Caucasian and (n = 88) South Asian women (mean (±SD); age 48.2 years (14.4)) who participated in the longitudinal Diet, Food Intake, Nutrition and Exposure to the Sun in Southern England study (2006-2007). The main outcomes were serum 25(OH)D, serum parathyroid hormone (sPTH) and serum C-terminal telopeptide of collagen (sCTX), sampled once per season for each participant. RESULTS: Non-linear mixed modelling showed the (amplitude/mesor) ratio for seasonal change in log 25(OH)D to be predictive of log sPTH (estimate = 0.057, 95 % CI (0.051, 0.063), p < 0.0001). Therefore, individuals with a higher seasonal change in log 25(OH)D, adjusted for overall log 25(OH)D concentration, showed increased levels of log sPTH. There was a corresponding significant ability to predict the range of seasonal change in log 25(OH)D through the level of sCTX. Here, the corresponding parameter statistics were estimate = 0.528, 95 % CI (0.418, 0.638) and p ≤ 0.0001. CONCLUSIONS: These findings suggest a possible detriment to bone health via increased levels of sPTH and sCTX in individuals with a larger seasonal change in 25(OH)D concentration. Further larger cohort studies are required to further investigate these preliminary findings.

Hypovitaminosis D in dogs with spirocercosis.

BACKGROUND: Spirocercosis in dogs is characterized by esophageal nodules that can undergo neoplastic transformation. Hypovitaminosis D has been associated with neoplasia formation. We hypothesized hypovitaminosis D in neoplastic spirocercosis and that it could be a risk factor for neoplastic transformation. OBJECTIVE: To measure and compare vitamin D status, assessed by serum 25-hydroxyvitamin D [25(OH)D] concentrations in non-neoplastic (n = 25) and neoplastic (n = 26) spirocercosis client-owned dogs and healthy dogs (n = 24). ANIMALS: Twenty-five non-neoplastic dogs, 26 neoplastic dogs, and 24 healthy dogs. METHODS: Fifty-one dogs were randomly selected from 119 dogs diagnosed with spirocercosis presenting to our hospital, and further divided into non-neoplastic or neoplastic groups. Exclusion criteria included dogs less than 1 year old, with concurrent diseases, received corticosteroids, or treated prophylactically for spirocercosis. Serum 25(OH)D concentration was measured by high-performance liquid chromatography. Spirocercosis dogs' appetites were graded and compared. RESULTS: Serum 25(OH)D concentrations were significantly different among all groups (P < .001). 25-Hydroxyvitamin D concentrations were significantly lower in neoplastic group (median 30.7 nmol/L [range 14.7-62.2]) compared to non-neoplastic (median 52.7 nmol/L [range 19.1-129.7, P < .05]) and healthy groups (median 74.6 nmol/L [range 37.4-130.5, P < .005]). 25-hydroxyvitamin D concentrations were significantly lower in non-neoplastic spirocercosis dogs compared to healthy ones (P < .05). Neoplastic and non-neoplastic spirocercosis dogs had similar appetite scores (P = 1.0). 25-Hydroxyvitamin D concentrations were not significantly different between dogs with normal (P = .087) and abnormal (P = .125) appetites within neoplastic and non-neoplastic spirocercosis groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Further studies are warranted to determine potential use of vitamin D treatment in spirocercosis and explore role of hypovitaminosis D in pathogenesis of malignant transformation.

Lifestyle factors including less cutaneous sun exposure contribute to starkly lower vitamin D levels in U.K. South Asians compared with the white population.

BACKGROUND: Long-standing concerns over the vitamin D status of South Asian adults in the U.K. require studies using statistically valid sample sizes to measure annual variation and contributory lifestyle factors. OBJECTIVES: To measure annual variation in the vitamin D status of U.K. South Asians, to determine the associated lifestyle influences, and to compare these with a similar study of white adults. METHODS: A single-centre, prospective cohort study measuring circulating 25-hydroxyvitamin D [25(OH)D], sunlight exposure levels and lifestyle factors for 1 year in 125 ambulant South Asian adults with sun-reactive skin type V, aged 20-60 years, in Greater Manchester, U.K. (53·5°N). RESULTS: The 25(OH)D levels of South Asians were alarmingly low. In summer, their median 25(OH)D level was 9·0 ng mL(-1) , [interquartile range (IQR) 6·7-13·1], falling to 5·8 ng mL(-1) (IQR 4·0-8·1) in winter. This compared with values in the white population of 26·2 ng mL(-1) (IQR 19·9-31·5) in summer and 18·9 ng mL(-1) IQR (11·6-23·7) in winter. Median daily dietary vitamin D was lower in South Asians (1·32 µg vs. 3·26 µg for white subjects) and was compounded by low supplement use. Despite similar times spent outdoors, ultraviolet (UV) dosimeters recorded lower personal UV exposure among South Asians, indicating sun avoidance when outside, while sun exposure diaries recorded lower amounts of skin surface exposure. CONCLUSIONS: The majority of South Asians never reached sufficiency in vitamin D status. Lifestyle differences, with lower oral intake, sun exposure and rates of cutaneous production due to darker skin, indicate that standard advice on obtaining sufficient vitamin D needs modification for the South Asian community in the U.K.

Vitamin D status and muscle function in children with neurofibromatosis type 1 (NF1).

OBJECTIVES: The aim of this cross-sectional study was to assess the vitamin D status and muscle function in children with NF1 compared with their unaffected siblings. METHODS: NF1 children between 5 and 18 years of age and who had at least one unaffected sibling were identified. Serum concentrations of 25-hydroxyvitamin D (25(OH)D), calcium, inorganic phosphate, alkaline phosphate, parathyroid hormone and 1,25-dihydroxyvitamin D were measured. The Leonardo Mechanography Ground Reaction Force Platform (GRFP) was used to measure EFI, jump power, force and height. RESULTS: There was no significant difference in 25(OH)D between NF1 subjects and unaffected siblings. Relative jump power and force were found to be significantly different. The adjusted means (95% confidence limits) of non-NF1 and NF1 children for relative jump power (W/kg), controlling for body mass and age, were 37.31 (34.14, 40.49) and 32.51 (29.34, 35.68), respectively (P=0.054); and force (N/kg), controlling for body mass, age and gender, were 25.79 (24.28, 27.30) and 21.12 (19.61, 22.63), respectively (P<0.0001). Jumping parameters were not related to serum 25(OH)D. CONCLUSIONS: There was no significant relationship between vitamin D status and NF1 status in children. NF1 children had significantly impaired jumping power and force, when compared to their unaffected siblings.

Vitamin D deficiency in UK South Asian Women of childbearing age: a comparative longitudinal investigation with UK Caucasian women.

SUMMARY: This is the first 1-year longitudinal study which assesses vitamin D deficiency in young UK-dwelling South Asian women. The findings are that vitamin D deficiency is extremely common in this group of women and that it persists all year around, representing a significant public health concern. INTRODUCTION: There is a lack of longitudinal data assessing seasonal variation in vitamin D status in young South Asian women living in northern latitudes. Studies of postmenopausal South Asian women suggest a lack of seasonal change in 25-hydroxy vitamin D [25(OH)D], although it is unclear whether this is prevalent among premenopausal South Asians. We aimed to evaluate, longitudinally, seasonal changes in 25(OH)D and prevalence of vitamin D deficiency in young UK-dwelling South Asian women as compared with Caucasians. We also aimed to establish the relative contributions of dietary vitamin D and sun exposure in explaining serum 25(OH)D. METHODS: This is a 1-year prospective cohort study assessing South Asian (n = 35) and Caucasian (n = 105) premenopausal women living in Surrey, UK (51° N), aged 20-55 years. The main outcome measured was serum 25(OH)D concentration. Secondary outcomes were serum parathyroid hormone, self-reported dietary vitamin D intake and UVB exposure by personal dosimetry. RESULTS: Serum 25(OH)D <25 nmol/L was highly prevalent in South Asians in the winter (81 %) and autumn (79.2 %). Deficient status (below 50 nmol/L) was common in Caucasian women. Multi-level modelling suggested that, in comparison to sun exposure (1.59, 95 %CI = 0.83-2.35), dietary intake of vitamin D had no impact on 25(OH)D levels (-0.08, 95 %CI = -1.39 to 1.23). CONCLUSIONS: Year-round vitamin D deficiency was extremely common in South Asian women. These findings pose great health threats regarding the adverse effects of vitamin D deficiency in pregnancy and warrant urgent vitamin D public health policy and action.

Hypovitaminosis D in dogs with inflammatory bowel disease and hypoalbuminaemia.

OBJECTIVES: To compare serum vitamin D metabolites and plasma parathyroid hormone concentrations in dogs with inflammatory bowel disease and normal albumin concentration, dogs with inflammatory bowel disease and hypoalbuminaemia, healthy dogs and hospitalised ill dogs with non-gastrointestinal illness. METHODS: Serum 25 hydroxyvitamin D and 1,25 dihydroxyvitamin D concentrations were measured in 36 healthy dogs, 49 hospitalised ill dogs with non-gastrointestinal illnesses, 21 dogs with inflammatory bowel disease and normoalbuminaemia and 12 dogs with inflammatory bowel disease and hypoalbuminaemia. Plasma parathyroid hormone and ionised calcium concentrations were measured in a subset of these dogs. RESULTS: Concentrations of serum 25 hydroxyvitamin D were lower in hypoalbuminaemic dogs with inflammatory bowel disease than in the healthy dogs (P<0·001), hospitalised ill dogs (P<0·001) and normoalbuminaemic dogs with inflammatory bowel disease (P<0·001). Dogs with inflammatory bowel disease and hypoalbuminaemia had a higher plasma concentration of parathyroid hormone (P<0·01) and lower plasma concentration of ionised calcium (P<0·001) than hospitalised ill dogs. Dogs with inflammatory bowel disease had a positive correlation between serum 25 hydroxyvitamin D concentrations and serum albumin (P<0·0001), serum calcium (P<0·0001) and plasma ionised calcium (P<0·0005) concentrations. CLINICAL SIGNIFICANCE: Dogs with inflammatory bowel disease and hypoalbuminaemia frequently have ionised hypocalcaemia, high parathyroid hormone and low serum 25 hydroxyvitamin D concentrations. Further studies are indicated to establish the pathogenesis of this disease complication as well as therapeutic strategies to reverse this state.

Proceedings of the Rank Forum on Vitamin D.

The Rank Forum on Vitamin D was held on 2nd and 3rd July 2009 at the University of Surrey, Guildford, UK. The workshop consisted of a series of scene-setting presentations to address the current issues and challenges concerning vitamin D and health, and included an open discussion focusing on the identification of the concentrations of serum 25-hydroxyvitamin D (25(OH)D) (a marker of vitamin D status) that may be regarded as optimal, and the implications this process may have in the setting of future dietary reference values for vitamin D in the UK. The Forum was in agreement with the fact that it is desirable for all of the population to have a serum 25(OH)D concentration above 25 nmol/l, but it discussed some uncertainty about the strength of evidence for the need to aim for substantially higher concentrations (25(OH)D concentrations>75 nmol/l). Any discussion of 'optimal' concentration of serum 25(OH)D needs to define 'optimal' with care since it is important to consider the normal distribution of requirements and the vitamin D needs for a wide range of outcomes. Current UK reference values concentrate on the requirements of particular subgroups of the population; this differs from the approaches used in other European countries where a wider range of age groups tend to be covered. With the re-emergence of rickets and the public health burden of low vitamin D status being already apparent, there is a need for urgent action from policy makers and risk managers. The Forum highlighted concerns regarding the failure of implementation of existing strategies in the UK for achieving current vitamin D recommendations.

Sunlight and dietary contributions to the seasonal vitamin D status of cohorts of healthy postmenopausal women living at northerly latitudes: a major cause for concern?

UNLABELLED: We assessed sunlight and dietary contributions to vitamin D status in British postmenopausal women. Our true longitudinal 25-hydroxyvitamin D (25(OH)D) measurements varied seasonally, being lower in the north compared to the south and lower in Asian women. Sunlight exposure in summer and spring provided 80% total annual intake of vitamin D. INTRODUCTION: Vitamin D deficiency is highlighted as a potential problem for countries at high latitude, but there are few true longitudinal, seasonal data to allow regional comparisons. We aimed to directly compare seasonal variation in vitamin D status (25(OH)D) in postmenopausal women at two northerly latitudes and to assess the relative contributions of sunlight exposure and diet. METHODS: Vitamin D status was assessed in 518 postmenopausal women (age 55-70 years) in a two-centre cohort study with serum collected at fixed three-monthly intervals from summer 2006 for immunoassay measurement of 25(OH)D and parathyroid hormone. At 57° N (Aberdeen, Scotland, UK), there were 338 Caucasian women; at 51° N (Surrey, South of England, UK), there were 144 Caucasian women and 35 Asian women. UVB exposure (polysulphone film badges) and dietary vitamin D intakes (food diaries) were also estimated. RESULTS: Caucasian women had lower 25(OH)D (p < 0.001) at 57° N compared to 51° N. Median (interquartile range) in nanomoles per litre for summer (June-August) at 57° N was 43.0 (20.9) and at 51° N was 62.5 (26.6) and for winter (December-February) at 57° N was 28.3 (18.9) and at 51° N was 39.9 (24.0). For Asian women at 51° N, median 25(OH)D was 24.0 (15.8) nmol/L in summer and 16.9 (15.9) nmol/L in winter. Median dietary vitamin D intakes were 80-100 IU for Caucasians and 50-65 IU for the Asian women. Sunlight was the main contributor to 25(OH)D with spring and summer providing >80% total annual intake. CONCLUSIONS: These longitudinal data show significant regional and ethnic differences in UVB exposure and vitamin D status for postmenopausal women at northerly latitudes. The numbers of women who are vitamin D deficient is a major concern and public health problem.