Effect of vitamin D supplementation on bone status, glucose homeostasis and immune function in children with vitamin D deficiency

Background: Between 1961-1971 vitamin D deficiency was recognized as a public health issue in the UK, because of the lack of effective sunlight and the population mix [1, 2]. In recent years, health care professionals have cited evidence suggesting a re-emergence of the vitamin D deficiency linked to a number of health consequences as a concern [3-6]. Evidence from observational studies has linked low vitamin D status with impairment in glucose homeostasis and immune dysfunction [7-9]. However, interventional studies, particularly those focused on paediatric populations, have been limited and inconsistent. There is a need for detailed studies, to clarify the therapeutic benefits of vitamin D in these important clinical areas. Objective: The aims of this PhD thesis were two-fold. Firstly, to perform preliminary work assessing the association between vitamin D deficiency and bone status, glucose homeostasis and immune function, and to explore any changes in these parameters following short term vitamin D3 replacement therapy. Secondly, to assess the effectiveness of an electronic surveillance system (ScotPSU) as a tool to determine the current incidence of hospital-based presentation of childhood vitamin D deficiency in Scotland. Methods: Active surveillance was performed for a period of two years as a part of an electronic web-based surveillance programme performed by the Scottish Paediatric Surveillance Unit (ScotPSU). The validity of the system was assessed by identifying cases with profound vitamin D deficiency (in Glasgow and Edinburgh) from the regional laboratory. All clinical details were checked against those identified using the surveillance system. Thirty-seven children aged 3 months to 10 years, who had been diagnosed with vitamin D deficiency, were recruited for the bone, glucose and immunity studies over a period of 24 months. Twenty-five samples were analysed for the glucose and bone studies; of these, 18 samples were further analysed for immune study. Treatment consisted of six weeks taking 5000 IU units cholecalciferol orally once a day. At baseline and after completion of treatment, 25 hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH), alkaline phosphatase (ALP), collagen type 1 cross-linked C-telopeptide (CTX), osteocalcin (OCN), calcium, phosphate, insulin, glucose, homeostasis model assessment index, estimated insulin resistance (HOMA IR), glycated hemoglobin (HbA1c), sex hormone binding globulin (SHBG), lipids profiles, T helper 1 (Th1) cytokines (interleukin-2 ( IL-2), tumor necrosis factors-alpha (TNF-α), interferon-gamma (INF-γ)), T helper 2 (Th2) cytokines (interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-6 (IL-6)), T helper 17 (Th17) cytokine (interleukin-17 (IL-17)), Regulatory T (Treg) cytokine (interleukin-10 (IL-10)) and chemokines/cytokines, linked with Th1/Th2 subset balance and/or differentiation (interleukin-8 (IL-8), interleukin-12 (IL-12), eosinophil chemotactic protein ( EOTAXIN), macrophage inflammatory proteins-1beta (MIP-1β), interferon-gamma-induced protein-10 (IP-10), regulated on activation, normal T cell expressed and secreted (RANTES), monocyte chemoattractant protein-1(MCP-1)) were measured. Leukoocyte subset analysis was performed for T cells, B cells and T regulatory cells and a luminex assay was used to measure the cytokiens. Results: Between September 2009 and August 2011, 163 cases of vitamin D deficiency were brought to the attention of the ScotPSU, and the majority of cases (n = 82) were reported in Glasgow. The cross-validation checking in Glasgow and Edinburgh over a one-year period revealed only 3 (11%) cases of clearly symptomatic vitamin D deficiency, which had been missed by the ScotPSU survey in Glasgow. While 16 (67%) symptomatic cases had failed to be reported through the ScotPSU survey in Edinburgh. For the 23 children who are included in bone and glucose studies, 22 (96%) children had basal serum 25(OH)D in the deficiency range (< 50 nmol/l) and one (4%) child had serum 25(OH)D in the insufficiency range (51-75 nmol/l). Following vitamin D3 treatment, 2 (9%) children had final serum 25(OH)D lower than 50 nmol/l, 6 (26%) children had final serum 25(OH)D between >50-75 nmol/l, 12 (52%) children reached a final serum 25(OH)D >75-150 nmol/l and finally 3 (13%) exceeded the normal reference range with a final 25(OH)D >150 nmol/l. Markers for remodelling ALP and PTH had significantly decreased (p = 0.001 and <0.0001 for ALP and PTH respectively). In 17 patients for whom insulin and HOMA IR data were available and enrolled in glucose study, significant improvements in insulin resistance (p = 0.04) with a trend toward a reduction in serum insulin (p = 0.05) was observed. Of those 14 children who had their cytokines profile data analysed and enrolled in the immunity study, insulin and HOMA IR data were missed in one child. A significant increase in the main Th2 secreted cytokine IL-4 (p = 0.001) and a tendency for significant increases in other Th2 secreted cytokines IL-5 (p = 0.05) and IL-6 (p = 0.05) was observed following vitamin D3 supplementation. Conclusion: An electronic surveillance system can provide data for studying the epidemiology of vitamin D deficiency. However, it may underestimate the number of positive cases. Improving vitamin D status in vitamin D deficient otherwise healthy children significantly improved their vitamin D deficient status, and was associated with an improvement in bone profile, improvements in insulin resistance and an alteration in main Th2 secreting cytokines.

Vitamin D status in the first-trimester: effects of Vitamin D deficiency on pregnancy outcomes.

Objective: To assess serum levels of 25-hydroxyvitamin D [25(OH)D] in the first trimester and to determine the factors affecting deficiency levels and its association with pregnancy outcomes. Methods: Serum 25(OH)D concentrations were measured at 11-14 weeks’ gestation in 229 singleton pregnancies using liquid chromatography-tandem mass spectrometry. Results: The median serum 25(OH)D concentration was 10.8 ng/mL and 45.9% of women had severe vitamin D deficiency with concentrations of <10 ng/mL. Logistic regression analysis revealed that covered dressing style, lack of multivitamin intake, season of blood sampling (November-April) were factors associated with 25(OH)D deficiency. There was a negative correlation between 25(OH)D levels and gestational age at sampling. Low 25(OH)D levels were not associated with adverse pregnancy outcomes. Higher rate of cesarean section (CS) was noted in women with 25(OH)D ≥10 ng/mL compared to those with 25(OH)D < 10mg/ml ( p= 0.01). Conclusion: A high prevalence of vitamin D deficiency was observed in early pregnancy which was related to dress code, use of multi-vitamins and season at sampling. Low 25(OH)D levels were not related with adverse pregnancy outcomes. Women with severe vitamin D deficiency were more likely to deliver vaginally.

Levels of vitamin D receptor and CYP24A1 in patients with end-stage renal disease.

Objective: This study was performed to detect the expression of vitamin D receptor (VDR) and cytochrome P450, family 24, subfamily A, polypeptide 1 (CYP24A1) in 24 end stage renal disease (ESRD) patients and 24 healthy controls. Method: In this study, 24 ESRD patients and 24 healthy controls were included. Results: In our study, the levels of VDR in patients with ESRD were reduced when compared with those from healthy controls (5.20±0.32 vs 8.59±1.03; P﹤0.01). However, the levels of CYP24A1 in ESRD patients were increased than those from healthy controls (50.18±21 vs 7.78±1.31; P﹤0.01). Correlation analysis showed that VDR levels were negatively correlated with CYP24A1 (r=-0.723; P﹤0.01). Conclusion: VDR levels were reduced and CYP24A1 levels were increased in patients with ESRD, and VDR levels were negatively correlated with CYP24A1.

Part of "Widows Mite" lying in the co. of Washington D.C. ; The above 2 plats represent two separate parts of that portion of a tract of land called Josephs Park, lying in Montg. Co. Md. /

Both tracts border on Rock Creek.

Plan of the town of Alexandria, D.C. with the environs : exhibiting the outlet of the Alexandria Canal, the shipping channel, wharves, Hunting Cr. &c. /

Relief shown by hachures. Depths shown by contours.

Plan of York Town in Virginia and adjacent country, exhibiting the operations of the American, French & English armies during the siege of that place in Oct. 1781. Surveyed from the 22nd. to the 28th. Octr.

Scale ca. 1:14,400.

Oscar Wilde como artesano: la mediación de la identidad a través de los objetos en "The picture of Dorian Gray" y "The importance of being Earnest"

Uno de los aspectos más documentados a la hora de estudiar las obras de Óscar Wilde en profundidad ha sido el concepto de máscara u ocultación. Este concepto fue tratado a su vez por el propio escritor en su ensayo titulado The Truth of Masks (1891), donde analiza, entre otras cosas, la puesta en escena y los objetos que aparecen a la hora de llevar a cabo la representación de las obras de teatro de Shakespeare. Por otra parte, no es necesario señalar que Wilde es harto reconocido por su gusto por la filosofía del arte y la estética, o mejor dicho, por su afinidad y apología al arte por el arte, así como también se le asocia con la figura del dandy decandente y esteta. Precisamente ambos aspectos, tanto el de la ocultación como el de la filosofía del arte y la estética, nos servirán como ineludible punto de partida para este estudio, que, mediante el análisis cultural de sus obras más representativas, completarán la recepción actual existente de Wilde. Se verá en este estudio que una faceta indispensable del escritor recae principalmente en la aportación que realiza el artesano, en estrecha comunión con el artista, tal y como él mismo defendió en numerosos de sus ensayos-conferencias, en los que propugnaba el individualismo mediante la realización del ser, en el plano artístico. Se ha llevado a cabo por tanto, un exhaustivo análisis para profundizar aún más en la conexión que existe entre estos conceptos, y ahondando por ende en la visión del artista artesano, que justificará ese nuevo perfil consumado del escritor, a través del análisis de los objetos en sus obras, escritos e, incluso, en su propia persona, entendida ésta como creación artística. No en vano, Wilde es el escritor que nos permite retomar el sentido etimológico de la palabra ‘persona’, para descubrir que, en su origen, ésta significaba ‘máscara’, y que consiguientemente, entronca directamente con la persona del escritor, y nos hace volver a plantearnos d��nde empieza o acaba la máscara y d��nde su propia persona artística...

The effects of vitamin D supplementation on maternal and neonatal outcome: A randomized clinical trial

Background: Vitamin D supplementation during pregnancy has been supposed to defend against adverse gestational outcomes. Objective: This randomized clinical trial study was conducted to assess the effects of 50,000 IU of vitamin D every two weeks supplementation on the incidence of gestational diabetes (GDM), gestational hypertension, preeclampsia and preterm labor, vitamin D status at term and neonatal outcomes contrasted with pregnant women that received 400 IU vitamin D daily. Materials and Methods: 500 women with gestational age 12-16 weeks and serum 25 hydroxy vitamin D (25 (OH) D ) less than 30 ng/ml randomly categorized in two groups. Group A received 400 IU vitamin D daily and group B 50,000 IU vitamin D every 2 weeks orally until delivery. Maternal and Neonatal outcomes were assessed in two groups. Results: The incidence of GDM in group B was significantly lower than group A (6.7% versus 13.4%) and odds ratio (95% Confidence interval) was 0.46 (0.24-0.87) (P=0.01). The mean ± SD level of 25 (OH) D at the time of delivery in mothers in group B was significantly higher than A (37.9 ± 19.8 versus 27.2 ± 18.8 ng/ml, respectively) (P=0.001). There were no differences in the incidence of preeclampsia, gestational hypertension, preterm labor, and low birth weight between two groups. The mean level of 25 (OH) D in cord blood of group B was significantly higher than group A (37.9 ± 18 versus 29.7 ± 19ng/ml, respectively). Anthropometric measures between neonates were not significantly different. Conclusion: Our study showed 50,000 IU vitamin D every 2 weeks decreased the incidence of GDM.

Association of vitamin D receptor gene variants with polycystic ovary syndrome: A case control study

Background: Vitamin D and insulin play an important role in susceptibility to polycystic ovary syndrome (PCOS), and therefore vitamin D receptor (VDR), parathyroid hormone (PTH), and insulin receptor (INSR) gene variants might be involved in the pathogenesis of PCOS. Objective: The present study was designed to investigate the possible associations between polymorphisms in VDR, PTH, and INSR genes and the risk of PCOS. Materials and Methods: VDR, PTH, and INSR gene variants were genotyped in 35 women with PCOS and 35 controls using Polymerase chain reaction – Restriction fragment length polymorphism method. Furthermore, serum levels of glucose and insulin were measured in all participants. Results: No significant differences were observed for the VDR FokI, VDR Tru9I, VDR TaqI,, PTH DraII, INSR NsiI, and INSR PmlI gene polymorphisms between the women with PCOS and controls. However, after adjustment for confounding factors, the VDR BsmI “Bb” genotype and the VDR ApaI "Aa" genotype were significantly under transmitted to the patients (p= 0.016; OR= 0.250; 95% CI= 0.081-0.769, and p= 0.017; OR= 0.260; 95% CI= 0.086-0.788, respectively). Furthermore, in the women with PCOS, insulin levels were lower in the participants with the INSR NsiI "NN" genotype compared with those with the "Nn + nn" genotypes (P= 0.045). Conclusion: The results showed an association between the VDR gene BsmI and ApaI polymorphisms and PCOS risk. These data also indicated that the INSR "NN" genotype was a marker of decreased insulin in women with PCOS. Our findings, however, do not lend support to the hypothesis that PTH gene DraII variant plays a role in susceptibility to PCOS.

Correlates of Vitamin D Status in Healthy Older Adults Living in Miami-Dade and its Association with Non-Skeletal Outcomes: A Cross-Sectional Study

Examining factors that affect vitamin D status in the fast-growing elderly population of Miami-Dade, Florida, is needed. Vitamin D deficiency in older adults has been linked to correlates of disability, including falls and fractures, and cardiovascular disease. The purpose of this study was to determine the proportion of vitamin D insufficient individuals and their relationship with vitamin D insufficiency in older adults (n=97) living in Miami-Dade. We evaluated the association between vitamin D status and 1) dual task physical performance to understand the link between vitamin D and cognition in the context of mobility; and 2) cardiometabolic risk, measured by galvanic skin response, pulse oximetry, and blood pressure to create a composite score based on autonomic nervous system and endothelial function. Participants completed baseline assessments that included serum levels of vitamin D, anthropometrics, body composition, dual task physical performance and cardiometabolic risk. Surveys to evaluate vitamin D intake, sun exposure, physical activity, and depressive symptoms were completed. Spearman’s correlations, independent t-tests, paired t-tests, repeated measures ANOVAs, and multiple logistic and linear regressions were used to examine the relationship of vitamin D insufficiency (25(OH)D /ml) and sufficiency (25(OH)D ≥30 ng/ml) with determinants of vitamin D status, dual task physical performance variables and cardiometabolic risk scores. Although the proportion of vitamin D insufficient individuals was lower when compared to the prevalance of the general United States elderly population, it was still common in healthy community-dwelling older adults living in Miami-Dade County, especially among Hispanics. Factors that affected skin synthesis (ethnicity, and sun exposure), and bioavailability/metabolism (obesity) were significant predictors of vitamin D status. Vitamin D insufficiency was not significantly correlated with worse dual task physical performance; however, cognitive performance was worse in the vitamin D insufficient group. Our results suggest a relationship of vitamin D insufficiency with executive dysfunction, and support an association with cardiometabolic risk using an innovative electro-sensor complex, possibly by modulating autonomic nervous system activity and vascular function, thus affecting cardiac performance.

Lines of Descent d'Anthony K. Appiah : un regard oblique sur le panafricanisme

Sur les traces de l’auteur afro-américain W.E.B. Du Bois, le philosophe Anthony Kwame Appiah se préoccupe dans son Lines of Descent (2014) de l’articulation entre identité personnelle, nationalisme culturel et universel cosmopolitique, à la lumière du signifiant social de la race. Appiah se penche spécifiquement sur l’influence qu’a exercée la pensée allemande de la fin du 19e siècle sur le d��veloppement de la pensée de Du Bois. Dans la foulée de travaux antérieurs 1, il s’y intéresse à la question de l’identité raciale et à la place qu’elle occupe dans sa théorisation du panafricanisme. Après un survol biographique des auteurs abord��s, cette note de lecture s’intéressera à ces trois thèses fortes en les soumettant à quelques réflexions critiques.

"Lines of Descent" d'Anthony K. Appiah : un regard oblique sur le panafricanisme.

Sur les traces de l’auteur afro-américain W.E.B. Du Bois, le philosophe Anthony Kwame Appiah se préoccupe dans son Lines of Descent (2014) de l’articulation entre identité personnelle, nationalisme culturel et universel cosmopolitique, à la lumière du signifiant social de la race. Appiah se penche spécifiquement sur l’influence qu’a exercée la pensée allemande de la fin du 19e siècle sur le d��veloppement de la pensée de Du Bois. Dans la foulée de travaux antérieurs 1, il s’y intéresse à la question de l’identité raciale et à la place qu’elle occupe dans sa théorisation du panafricanisme. Après un survol biographique des auteurs abord��s, cette note de lecture s’intéressera à ces trois thèses fortes en les soumettant à quelques réflexions critiques.

Lithic economy and territory of Epipaleolithic hunter–gatherers in the Middle Tagus: The case of Pena d'Água (Portugal)

In Central Portugal (westernmost Eurasia) the transition from the traditional Pleistocene hunter–gatherer societies to the complex Mesolithic societies of the Holocene has been debated for decades. While some argue that these differences were a progressive phenomenon that started with the shift from the Pleistocene to the Holocene, others defend that the Late Pleistocene patterns were fairly similar to those of the Epipaleolithic and that the major shift was rapid, dramatic and triggered by the necessary adaptation to the 8.2 ka cal BP (8.09–8.25 ka cal BP) climatic event. The study of lithic raw material provenance might be useful for this discussion, since it has been suggested that the Magdalenian and Epipaleolithic populations from this region were collecting this resources within a close range territory, whereas the Mesolithic populations were acquiring them at longer distances. In this paper, we present the results from p-XRF, VP-SEM-EDS and μ-XRD analysis done on the Epipaleolithic lithic assemblage from Pena d'Água Rockshelter, and in some geological samples from secondary sources located ∼14 km from this site. This layer is of major relevance for this debate since it is dated from 8.19 ka cal BP. If the transition was gradual, it would be expected that this assemblage would show some traits of higher-complexity seen in the Mesolithic, namely of longer distance acquisition. However, our results indicate correspondence between the archaeological chert types and some of the geological sources. The differences seen between the archaeological specimens and geological samples are mostly present in traits that can be related with manufacture, handling and post-depositional phenomena. The results suggest that, in what concerns to the economy of abiotic resources, the Epipaleolithic populations living at the time of the dramatic 8.2 ka cal BP cold event, were performing a short range acquisition of lithic raw materials which reinforces the idea of continuity from the Late Pleistocene to the 8.2 ka cal BP event and an abrupt and dramatic shift soon after this phenomena.

Child sex scandal in two countries rocks Anglican church

A CHILD sex scandal involving victims in Australia and Britain has hit the top echelon of the Anglican Church, with allegations that some of its most senior clergymen failed to respond properly to complaints of horrific abuse. The former archbishop of York, now Lord (David) Hope of Thornes, yesterday expressed regret over failing to report to police allegations in 1999 and 2003 about a former Queensland Anglican school principal, who rose to become the head of education for the church in Britain. The late reverend Robert Waddington has been accused of beating and sexually abusing students during the 1960s at St Barnabas boarding school in Ravenshoe, north Queensland, and later, when he was in charge of the choir as dean of Manchester. A joint investigation by The Australian and The Times newspaper in London has revealed that church officials, including Lord Hope, failed to report the 1999 allegations of abuse made by a former Queensland student and similar claims made in 2003 by the family of a choirboy in Manchester. The alleged victims were never told of the existence of the other allegations.

Accused headmaster turned me into pedophile, says convicted cleric Peter Gilbert

A CLERGYMAN who allegedly raped boys at a north Queensland boarding school in the 1960s has claimed he was ordered to take female hormones by his headmaster, who encouraged the "romantic love" of children among staff. Former Anglican brother Peter Gilbert - sentenced to seven years' jail in 2006 for the rape and indecent assault of children in the 1980s in South Australia - has blamed St Barnabas headmaster the late Robert Waddington for turning him into a pedophile. In a statement to one of his alleged victims, Gilbert said Waddington was molesting children himself and the Anglican priest would absolve the young teacher of his abuse of children in the confessional. The account has emerged as the top ranks of the Anglican church in Australia and Britain have been rocked by allegations of the covering-up of complaints made in 1999 and 2003 about Waddington's abuse while headmaster at the boarding school in Ravenshoe, north Queensland, and later, when he was dean of Manchester. A full investigation is being demanded into the handling of the complaints by the former Archbishop of York, now Lord (David) Hope of Thornes, and Australian church officials, including the former bishop of north Queensland, Clyde Wood.