bluuebunny/crossref_metadata_2025 huggingface dataset:
Testing Targeted Approaches to Enhance Cancer Genetics Network Minority Recruitment within Asian Populations
Authors: Wenzel Lari , Bowen Deborah , Habbal Rana , Leighton Nancy , Vu Thuy , Anton-Culver Hoda
Published: April 2008

Background/Aims: Asian Americans have been underrepresented in cancer research. The purpose of this study was to evaluate the efficacy of a multiple arm recruitment approach in improving Asian recruitment into the Cancer Genetics Network (CGN). Methods: 1,096 potential participants, identified through cancer registries located at University of California, Irvine (UCI) and Fred Hutchinson Cancer Research Center (FHCRC), were randomly assigned to receive one of four recruitment approaches. Results: A 6.2% gain in Asian participation into the CGN was achieved over a 2-year period at FHCRC and UCI, which contributed a 2% CGN-wide increase in overall Asian enrollment. Site-specific differences in recruitment success by study arm were observed. Conclusion: Novel recruitment approaches can assist in improving recruitment of Asian populations into cancer genetic research studies.
Liver Position Is a Prenatal Predictive Factor of Prosthetic Repair in Congenital Diaphragmatic Hernia
Authors: Kunisaki Shaun M. , Barnewolt Carol E. , Estroff Judy A. , Nemes Luanne P. , Jennings Russell W. , Wilson Jay M. , Fauza Dario O.
Published: April 2008

Objective: To determine whether any common maternal-fetal variable has prenatal predictive value of prosthetic repair in congenital diaphragmatic hernia. Methods: This was a 5-year single-center retrospective review of fetal congenital diaphragmatic hernia referrals. Multiple prenatal variables were correlated with the need for a prosthetic repair. Statistical analyses were by Fisher’s exact and Mann-Whitney U-tests, as appropriate (p < 0.05). Results: Fetal liver position was a predictor of prosthetic repair. The presence or absence of liver herniation was correlated with prosthetic repair rates of 83.3 and 23.1%, respectively (p < 0.001). All patients with moderate/severe liver herniation required a prosthetic patch. Conclusion: Liver herniation has prenatal predictive value for the need for prosthetic repair in congenital diaphragmatic hernia. This finding should be valuable during prenatal counseling for clinical trials of engineered diaphragmatic repair.
Fetal Urogenital Sinus with Consecutive Hydrometrocolpos because of Labial Fusion: Prenatal Diagnostic Difficulties and Postpartal Therapeutic Management
Authors: Puhl A.G. , Steiner E. , Krämer W.W. , Weltzien A. , Skala C. , Passuello V. , Koelbl H.
Published: April 2008

Objective: To elucidate the differential diagnoses of tumorous dilations in the fetal pelvic region detected by prenatal ultrasound and the postnatal management demonstrated on a fetus with 29 weeks of gestation with a retrovesical located bottle-like cystic structure measuring 54 × 31 × 27 mm within the pelvis. Postnatal findings were a labial fusion and a consecutive hydrometrocolpos due to a urethrovaginal fistula. Method: Case report of a fetus affected by an intricate cloacal anomaly. Results: The long-term prognosis for this nonsyndromic form of hydrometrocolpos without any other structural defects or organic failures after operative sanitation is excellent. Final reconstruction is planned at about 12 months of age. Conclusion: Prenatal diagnosis of tumorous dilations in the fetal pelvic region often involves difficulties because of numerous differential diagnoses and possible presentation in late pregnancy. Magnetic resonance imaging could be a useful complementary tool for assessing these anomalies when ultrasonography is inconclusive. In some cases, the final diagnosis cannot be confirmed until after delivery.
Evaluation of Normal Fetal Branch Pulmonary Artery Diameters Measured by Ultrasonography: A Comparison with Congenital Diaphragmatic Hernia
Authors: Katayama Shuichi , Tada Katsuhiko , Nakanishi Yoshie , Takata Masayo , Kumazawa Kazumasa , Tsukahara Saya , Takamaru Eiko
Published: April 2008

Objective: The aim of this study was to examine the size of fetal branch pulmonary artery (PA) diameters in normal growth fetuses. Method: Fetal PA diameters were measured in 175 normal fetuses between 18 and 40 weeks of gestation from 2005 to 2006. In addition, 4 fetuses with left-sided congenital diaphragmatic hernia (CDH) from 2001 to 2006 were retrospectively reviewed. Branch PA diameters were measured from a cross-sectional image at the level of the three-vessel view (main PA, ascending aorta and superior vena cava) to demonstrate the long axis of both branch PAs whenever possible. Results: Both the left and right PA diameters were found to correlate strongly with the advancing gestational age (r = 0.78, p < 0.01, respectively). Left pulmonary artery to main pulmonary artery (LPA/MPA) ratio and right pulmonary artery to main pulmonary artery (RPA/MPA) ratio were calculated. These two parameters were almost constant throughout gestation. LPA in fetal left CDH was smaller than control. Both LPA/MPA and RPA/MPA were within the normal range in most cases. Conclusions: It is important to establish the normal range of branch PA diameters and it appears to be useful to compare the branch PA diameters in normal fetuses with that in cases of pulmonary hypoplasia.
Strategies for Conditional Two-Locus Nonparametric Linkage Analysis
Authors: Ängquist Lars , Hössjer Ola , Groop Leif
Published: April 2008

In this article we deal with two-locus nonparametric linkage (NPL) analysis, mainly in the context of conditional analysis. This means that one incorporates single-locus analysis information through conditioning when performing a two-locus analysis. Here we describe different strategies for using this approach. Cox et al. [Nat Genet 1999;21:213–215] implemented this as follows: (i) Calculate the one-locus NPL process over the included genome region(s). (ii) Weight the individual pedigree NPL scores using a weighting function depending on the NPL scores for the corresponding pedigrees at speciﬁc conditioning loci. We generalize this by conditioning with respect to the inheritance vector rather than the NPL score and by separating between the case of known (predeﬁned) and unknown (estimated) conditioning loci. In the latter case we choose conditioning locus, or loci, according to predeﬁned criteria. The most general approach results in a random number of selected loci, depending on the results from the previous one-locus analysis. Major topics in this article include discussions on optimal score functions with respect to the noncentrality parameter (NCP), and how to calculate adequate p values and perform power calculations. We also discuss issues related to multiple tests which arise from the two-step procedure with several conditioning loci as well as from the genome-wide tests.
Role of VGF-Derived Peptides in the Control of Food Intake, Body Weight and Reproduction
Authors: Jethwa Preeti H. , Ebling Francis J.P.
Published: April 2008

VGF is a 68-kDa polypeptide synthesized in neuronal and neuroendocrine cells. It is cleaved into a number of smaller peptides which are stored in dense core vesicles and are likely to be secreted products. The VGF gene is expressed abundantly in the brain, and in peripheral endocrine tissues including the pituitary gland, the adrenal glands and the pancreas but also in the gastrointestinal tract in both the myenteric plexus and in endocrine cells. Several lines of evidence including observation of changes in hypothalamic VGF expression in catabolic states, a hypermetabolic phenotype in transgenic mice lacking VGF signalling, and demonstration of bioactivity of various peptide fragments have led to the view that VGF and/or its derived peptides are involved in the regulation ofboth energy balance and reproduction.
Stained Glass
Authors: Terry Karen J.
Published: April 2008

This article presents the results of the Nature and Scope of Child Sexual Abuse by Catholic Priests from 1950 to 2002. Ninety-seven percent of dioceses (representing 99% of diocesan priests) and 64% of religious communities (representing 83% of religious priests) responded to the request for data. Findings showed that 4,392 priests (4%) had allegations of abuse, 10,667 victims made allegations, and the Church paid (at the time surveys were completed) $572.5 million for legal and treatment fees and as compensation to the victims (more than $1.3 billion to date). The study also provided information on the circumstances of the abuse (e.g., types of sexual acts, location, duration), the offenders (e.g., year of ordination, age, ministry duties, other behavioral problems), the victims (e.g., age and gender, family situation), and the dioceses (e.g., differences in abuse rates by region and population size). Importance of these results for policy and practice is discussed.
Trajectories of Abuse and Disclosure
Authors: Smith Margaret Leland , Rengifo Andres F. , Vollman Brenda K.
Published: April 2008

The distribution of the incidents of sexual abuse by Catholic priests in the United States ( event structure) and the reports of these abuse events ( reporting structure ) present two distinct trajectories, confounding existing individual-level research results. Data from an institutional census of records of abuse between 1950 and 2002 show a steady increase in cases through the late 1970s and early 1980s, followed by a surge in reporting in the mid-1990s and again in 2002. These patterns are stable throughout all regions of the Catholic Church in the United States. Rather than analyze the abuse or reporting from a conventionally individual, psychological framework, this research reframes the analyses for the event structure and the reporting of abuse by priests.
1,3-Digermabicyclo[1.1.0]butane with an Inverted Bridge Ge–Ge σ Bond
Authors: Iwamoto Takeaki , Yin Dongzhu , Boomgaarden Sven , Kabuto Chizuko , Kira Mitsuo
Published: April 2008

1,3-Digermabicyclo[1.1.0]butane 2 was synthesized as yellow crystals. The molecular structure, 13C NMR and UV–vis spectra, and theoretical calculations have revealed that 2 is a typical long bond isomer, similarly to the silicon congener 1. Structural comparison between 1 and 2 is achieved.
Fabrication of Layered Polydiacetylene Supramolecules on Electrospun Fibers
Authors: Chae Sang Kyun , Kim Seong Hun , Kim Jong-Man
Published: April 2008

A simple and straightforward strategy for the fabrication of layered conjugated polydiacetylene supramolecules on electrospun polymer fibers, based on the layer-by-layer deposition technique, was developed.
Parent Polythiophene Nanofibers
Authors: Zhang Xinyu , Surwade Sumedh P , Dua Vineet , Bouldin Ryan , Manohar Neha , Manohar Sanjeev K
Published: April 2008

Bulk quantities of parent polythiophene nanofibers can be synthesized rapidly and in one step by chemical oxidative polymerization of thiophene by FeCl3 using freeze-dried vanadium pentoxide nanofibers as seeds.
Tetrabenzylpyrophosphate: An Efficient Catalyst for the Synthesis of Carboxamides from Carboxylic Acids and Amines
Authors: Reddy Y Thirupathi , Reddy P Narsimha , Reddy P Raghotham , Crooks Peter A
Published: April 2008

An efficient method for the synthesis of simple and sterically hindered carboxamides from various carboxylic acids and amines using tetrabenzylpyrophosphate (TBPP) as a coupling agent in the presence of 4-(dimethylamino)pyridine (DMAP) is described. The reaction is operationally straightforward, proceeds under mild conditions at room temperature, and affords the desired product in high yield.
A Novel Method to Synthesize Monodispersed Magnetite Nanoparticles
Authors: Dang Feng , Enomoto Naoya , Hojo Junichi , Enpuku Keiji
Published: April 2008

Monodispersed ca. 30 nm magnetite nanoparticles were synthesized in a 20/80 ethanol–water solution under ultrasonic irradiation. Both the ethanol–water solution and ultrasonic irradiation were important for the synthesis of the monodispersed magnetite nanoparticles. The ethanol–water solvent improved the monodispersibility of the magnetite particles, on the other hand, limited the formation of magnetite under mechanical stirring. The 100% cubic magnetite particles were successfully synthesized in ethanol–water solution under ultrasonic irradiation.
Self-aggregation of Synthetic Zinc Chlorophyll Derivatives Possessing Fluoroalkyl Chains in Liquid Carbon Dioxide as Models of Green Photosynthetic Bacterial Antennae
Authors: Shibata Reiko , Koike Kazuhide , Hori Hisao , Tamiaki Hitoshi
Published: April 2008

Zinc chlorophyll derivatives possessing (multi)-perfluoroalkyl chain(s) in the 17-propionate residue were dissolved in liquid carbon dioxide to form their oligomers (=J-aggregates), while the alkyl-type analog was insoluble in the medium. These results indicated solubilization and stabilization of their supramolecules by an interaction between the perfluoroalkyl substituents and liquid carbon dioxide.
Separation of Cyclopropane Derivatives with Multichiral Centers by Gas Chromatography on Modified β-Cyclodextrin Stationary Phase
Authors: Shen Gangyi , Yang Xinling , Cui Jian , Zhou Meiyang , Ling Yun
Published: April 2008

A new pyridine heterocyclic β-cyclodextrin derivative, heptakis[2,6-di-O-pentyl-3-O-(2-chloro-5-pyridyl)methyl]-β-CD, was synthesized and explored as chiral stationary phase in capillary gas chromatographic separation. Cyclopropane derivatives with two chiral centers including four configurational isomers or three chiral centers including eight configurational isomers were well separated, which indicated the new pyridyl β-CD derivative possessing excellent chiral selectivity for separation of complex compounds including multichiral centers.
Rapid ELISA in Droplet on PDMS Dimple with Nanoliter Reagents Dispensed by Ink-jet Microchip
Authors: Kudo Yuki , Nishiwaki Moeka , Inoue Yoriko , Seino Nobuko , Nakagama Tatsuro , Uchiyama Katsumi
Published: April 2008

IgA ELISA was performed in a droplet using an ink-jet microchip for shortening the reaction time, saving the reaction reagents. Forty-five dimples (500-μm i.d., 100-μm depth) were prepared on a PDMS (polydimethylsiloxane) microchip plate (30×30 mm) for the reaction vessels. After the dimple was pored with nanoliter water containing glycerin, an antibody solution was firstly added for immobilization on the dimple, and then nanoliter reaction regents for ELISA (enzyme-linked immunosorbent assay) were added sequentially using an ink-jet chip. A good linear relationship between the fluorescence intensity of Ample®Red and concentration of IgA was obtained with each reaction time of 150 s.
Ionic Liquid Crystals: Self-assembly of Imidazolium Salts Containing an l-Glutamic Acid Moiety
Authors: Yazaki Sanami , Kamikawa Yuko , Yoshio Masafumi , Hamasaki Atsushi , Mukai Tomohiro , Ohno Hiroyuki , Kato Takashi
Published: April 2008

Liquid-crystalline (LC) behavior and ionic conductivities of imidazolium salts containing an l-glutamic acid moiety have been studied. The ionic conductivities of the (CF3SO2)2N− salt forming the columnar LC phase are higher than those of the Br− salt in the columnar LC state. The ionic conductivity shows a sudden decrease at the columnar–micellar cubic LC transition of the Br− salt.
Electrophilic Substitution of Platinum(II) Complexes with Thiophene Derivatives
Authors: Mori Atsunori , Sugie Atsushi , Furukawa Hirotoshi , Suzaki Yuji , Osakada Kohtaro , Akita Munetaka
Published: April 2008

The reaction of aryl(halo)platinum(II)(bpy) complexes with thiophene derivatives causes novel electrophilic substitution in the presence of AgNO3/KF as an activator to form thienyl complexes in 65–91% yields. The related reaction with (dihalo)platinum(II) also takes place to afford dithienylplatinum(II) complexes.
Breast cancer screening programme as setting for an adjunct research project: effect on programme attendance
Authors: Gram Inger T , Lund Eiliv
Published: April 2008

The purpose of this randomized controlled trial was to examine if an adjunct research project to a breast cancer screening programme would affect the high programme attendance. Women residing in the municipality of Tromsø aged 55 years or older, scheduled to receive an invitation letter to their first screening round in the Norwegian Breast Cancer Screening Programme during our 15-week recruitment period, were eligible. We randomly selected up to 25 invitees per screening day to receive a mailed request to participate in the research project named the Tromsø Mammography and Breast Cancer study. These women constituted the study arm, while the remaining eligible invitees served as the control arm. The attendance rate to the screening programme was 80.1% among the 253 women in the study arm and 74.8% among the 397 women in the control arm (P = 0.09). Our trial finds no effect on the high attendance to the breast cancer screening programme indicating that cancer screening programmes might be suitable settings for adjunct research projects.
Implementation of the newborn screening programme for sickle cell disease in England: results for 2003-2005
Authors: Streetly Allison , Clarke Mary , Downing Melanie , Farrar Lisa , Foo Ying , Hall Kate , Kemp Helena , Newbold Jane , Walsh Paul , Yates Jenny , Henthorn Joan
Published: April 2008

Objectives

This paper reports early screening results from the newborn sickle cell disease screening programme recently implemented in England.

Setting England.

Screening is offered at 5-8 days of age as part of the existing bloodspot test and offered to all babies irrespective of ethnicity.

Methods

The laboratory methods recommended are high performance liquid chromatography (HPLC) and iso-electric focusing (IEF). 15 Two methods of analysis must be applied to all screen positive results. The conditions screened for are:- Sickle cell anaemia (Hb SS), Hb SC disease, Hb S/β-thalassaemia, Hb S/DPunjab, Hb S/OArab, Hb S/HPFH. Carriers identified for the common haemoglobin variants are reported to parents and follow-up counselling is offered. A bespoke laboratory quality assurance programme has been established which has defined standards of satifactory performance.

Results

Provisional figures from the first seven months of screening (up to March 2004) 108,255 infants were screened gave a screen positive rate of 1:900 for these high prevalence areas and a carrier rate of 2.7%. Figures for 2004-2005 show about 250 significant screen positive results for sickle cell disorders and about 6,500 carriers were identified. The birth prevalence for screen positive results from 2004-05 is 1:1500. We estimate that when there is countrywide data, the national birth prevalence will be about 1:2000-1:2,500.

Conclusion

The results from the national newborn sickle cell screening programme in England - show that the sickle cell disorders are as common as cystic fibrosis (CF) in England, although the distribution of cases is concentrated in London and other urban areas. The findings and approach to implementation adopted in England may be of interest to other Western European countries with increasing rates of sickle cell disease who are considering such programmes and also to other developed countries.
The effect of an organized, nationwide breast cancer screening programme on non-organized mammography activities
Authors: Boncz Imre , Sebestyén Andor , Pintér Istvén , Battyéany Istvéan , Ember Istvéan
Published: April 2008

Objectives

To analyse the effect of an organized, nationwide breast cancer screening programme on non-organized mammography activities in Hungary.

Setting

The nationwide dataset of the Hungarian National Health Insurance Fund Administration covering the years 2000-2005.

Methods

Data derived from the nationwide database of the Hungarian National Health Insurance Fund Administration. The study includes all women undergoing mammography before (2000-2001) and after (2002-2003/2004-2005) the introduction of organized screening.

Results

The number of women having non-organized (opportunistic/diagnostic) mammograms was around 250,000 in 2000-2001, but increased to 350,000 in 2005. In the age group 45-64 years in 2000-2001, only 27.4% of all women undergoing mammography were examined within locally-organized programmes. After the introduction of the nationwide programme, this percentage increased to 61.0% in 2002-2003, and 56.3% in 2004-2005. After the introduction of the nationwide organized programme (2002-2003), the proportion of organized screening mammographics remained among the highest in county Hajdú-Bihar (78.4%) and Zala (88.3%) and increased significantly in county Vas (87.7%).

Conclusion

The introduction of an organized nationwide screening programme in Hungary resulted in increases in the number of screening mammographics, and also of non-organized mammographics. Although the ratio of organized screening versus non-organized mammography changed in favour of screening mammographics, there are large within-country differences between counties.
Estimating the cumulative risk of a false-positive under a regimen involving various types of cancer screening tests
Authors: Baker Stuart G , Kramer Barnett S
Published: April 2008

Introduction

Objectives When evaluating screening for the early detection of cancer, it is important to estimate both harms and benefits. One common harm is a false-positive (FP), which is a positive screening result, perhaps followed by an invasive test, with no cancer detected on the diagnostic work-up or within a specified time period. An important goal is to estimate the risk of at least one FP, which we call the cumulative risk of an FP, if persons took a regimen of various screening tests, as is commonly recommended. The estimation is complicated because the data come from a study in which subjects are offered various screening tests in rounds with some missing tests in most subjects. Previous methods for estimating cumulative risk of FPs with a single type of test are not directly applicable, so a new approach was developed.

Methods

The tests were ordered by appearance, where the last test was either the first FP (analogous to a failure time) or the last test taken with no FPs having occurred on that test or previously (analogous to a censoring time). We applied a Kaplan-Meier approach for survival analysis with the innovation that the hazard for a first FP for a given test depends on the type of test and number of previous tests of that type which were taken.

Results

The method is illustrated with data from the screening arm of the randomized Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. With an FP defined as a diagnostic work-up in the absence of cancer (or advanced adenoma) within three years, the probability of at least one FP among 14 tests in men was 60.5% with 95% confidence interval of (59.3%, 61.6%).

Conclusion

A simple estimate is proposed for the probability of at least one FP if persons took a regimen of multiple screening tests of different types. The methodology is useful for summarizing the burden of multiphasic screening programmes.
The implementation of revised guidelines and the performance of a screening programme for congenital Hypothyroidism
Authors: Korada M , Kibirige M , Turner S , Day J , Johnstone H , Cheetham T
Published: April 2008

Objectives

To see whether revised screening standards and health-professional training are associated with changes in the performance of a neonatal screening programme for congenital hypothyroidism (CHT).

Methods

Screening data from the regional screening service in Durham and Newcastle, which covers north-east England and North Cumbria.

Setting

We assessed the timing of the different stages of the screening process leading up to the introduction of the revised guidelines between April 2004 and March 2005 (year 1) and afterwards between April 2005 and March 2006 (year 2) in all babies notified as having CHT. We also assessed the interval between sampling and specimen arrival in the laboratory at the beginning and end of year 2 in all babies screened.

Results

Twenty-three babies tested positive or borderline in year 1 and 18 babies in year 2. There was reduced variability in the overall time from birth to notification in year 2 versus year 1 ( P = 0.001). This reduction was a consequence of a reduced interval between sample collection and arrival in the laboratory ( P = 0.047) and for the laboratory to notify the positive test result ( P = 0.003). There was a reduction in the mean time from sampling to receipt by the laboratory in the 2997 babies screened in the final month compared with the 2498 babies screened in the first month of year 2 ( P = 0.01).

Conclusion

There was an improvement in neonatal screening programme performance around the time that revised neonatal screening guidelines were introduced. This highlights the importance of ongoing education and training for those involved in screening programmes.
Article Commentary: The English national screening programme for sight-threatening diabetic retinopathy
Authors: Scanlon P H
Published: April 2008

Objectives

The main objective of the national screening programme is to reduce the risk of sight loss among people with diabetes due to diabetic retinopathy (DR).

Methods

Offering two-field mydriatic digital photographic screening to all people with diabetes in England over the age of 12 years.

Stage of development

The programme is in its infancy, receiving the first year's annual reports from approximately 96 screening programmes, each of which have developed to offer screening to a minimum number of 12,000 people with diabetes, which would cover a population of 350,000 people with 3.4% diabetes prevalence. The national programme has commenced the External quality assurance (QA) programme in order to achieve and sustain the highest possible standards.

Potential benefits

England has a population of two million people with diabetes over the age of 12 and it is believed that there is a prevalence of blindness of 4200 and an annual incidence of blindness of 1280 people with diabetes. This programme has the potential to reduce the prevalence of blindness in England from 4200 people to 1000 people and a conservative estimate of reducing the annual incidence of DR blindness by one-third would save 427 people per annum from blindness. These figures are based on the UK certification of blindness but if World Health Organization (WHO) definitions are used the prevalence, incidence and potential reductions in blindness are much greater.
Vitamin D Receptor–Dependent 1α,25(OH)2 Vitamin D3–Induced Anti-Apoptotic PI3K/AKT Signaling in Osteoblasts
Authors: Zhang Xiaoyu , Zanello Laura P
Published: April 2008

Osteoblast apoptosis plays a crucial role in bone remodeling. Physiological doses of 1α,25(OH)2-vitamin D3 (1,25D) protect osteoblasts against apoptosis by means of mechanisms only partially understood. We studied activation of an Akt survival cascade downstream of 1,25D nongenomic stimulation of phosphatidylinositide-3′-kinase (PI3K) in osteoblastic cells. We measured a dose- and time-dependent 1,25D induction of Akt phosphorylation (p-Akt) in cultured osteoblastic cells. Maximal response was achieved with 10 nM 1,25D after 5 min. We found that staurosporine (STSP)-induced apoptosis was significantly reduced in 1,25D-pretreated osteoblasts. 1,25D prosurvival effects were abolished when cells were preincubated with inhibitors of PI3K activation. By means of siRNA silencing, we proved that 1,25D induction of p-Akt requires a classic vitamin D receptor (VDR) in osteoblasts. Furthermore, non-osteoblastic CV-1 cells transfected with an enhanced green fluorescent protein (EGFP)-VDR construct responded to 1,25D treatment with a rapid p-Akt response associated with increased cell survival not detected in native, nontransfected cells. We measured increased levels of p-Akt substrates p-Bad and p-FKHR and significantly reduced activity of caspases 8 and 3/7 after 1,25D treatment. In addition, 1,25D-induced protection against apoptosis was abolished when osteoblasts were preincubated with pertussis toxin. We conclude that anti-apoptotic effects of 1,25D in osteoblasts occur through nongenomic activation of a VDR/PI3K/Akt survival pathway that includes phosphorylation of multiple p-Akt substrates and reduction of caspase activities.
Randomized Controlled Trial of the Effects of Calcium With or Without Vitamin D on Bone Structure and Bone-Related Chemistry in Elderly Women With Vitamin D Insufficiency
Authors: Zhu Kun , Bruce David , Austin Nicole , Devine Amanda , Ebeling Peter R , Prince Richard L
Published: April 2008

There are few data on the relative effects of calcium supplementation with or without extra vitamin D on BMD in patients selected for low vitamin D status. The aim of this study is to evaluate the relative importance of vitamin D and calcium treatment on BMD and bone-related chemistry in elderly women with vitamin D insufficiency. Three hundred two elderly women (age, 77.2 ± 4.6 yr) with serum 25(OH)D concentrations <60 nM participated in a 1-yr randomized, double-blind, placebo-controlled trial. All subjects received 1000 mg calcium citrate per day with either 1000 IU ergocalciferol (vitamin D2) or identical placebo (control). The effects of time and time treatment interactions were evaluated by repeated-measures ANOVA. At baseline, calcium intake was 1100 mg/d, and 25(OH)D was 44.3 ± 12.9 nM; this increased in the vitamin D group by 34% but not the control group after 1 year (59.8 ± 13.8 versus 45.0 ± 13.3 nM, p < 0.001). Total hip and total body BMD increased significantly, and procollagen type I intact N-terminal propeptide (PINP) decreased during the study with no difference between the treatment groups (hip BMD change: vitamin D, +0.5%; control, +0.2%; total body BMD change: vitamin D, +0.4%; control, +0.4%; PINP change: vitamin D, −3.9%; placebo, −2.8%). Although the fasting plasma and urine calcium increased in both groups equally, there was no detectable change in serum PTH. The increase in 25(OH)D achieved with vitamin D supplementation had no extra effect on active fractional intestinal calcium absorption, which fell equally in both groups (vitamin D, −17.4%; control, −14.8%). In patients with a baseline calcium intake of 1100 mg/d and vitamin D insufficiency, vitamin D2 1000 IU for 1 year has no extra beneficial effect on bone structure, bone formation markers, or intestinal calcium absorption over an additional 1000 mg of calcium. Vitamin D supplementation adds no extra short-term skeletal benefit to calcium citrate supplementation even in women with vitamin D insufficiency.
Low Serum 25-Hydroxyvitamin D Levels Associated With Falls Among Japanese Community-Dwelling Elderly
Authors: Suzuki Takao , Kwon Jinhee , Kim Hunkyung , Shimada Hiroyuki , Yoshida Yuko , Iwasa Hajime , Yoshida Hideyo
Published: April 2008

Previous studies have shown that low serum 25-hydroxyvitamin D [25(OH)D] level is a risk factor for falls among the elderly in European and North American populations. We used a cross-sectional community-based survey to study the association of serum 25(OH)D level and falls among Japanese community-dwelling elderly. A total of 2957 elderly persons (950 men and 2007 women) 65–92 yr of age who participated in mass health examinations for the prevention of geriatric syndrome for the elderly underwent an interview, blood analysis, and physical performance testing. Experience of falls over the previous year was assessed in an interview. Physical performance tests of handgrip strength, stork standing time with the eyes open, and normal waking speed as risk factors for falls among the elderly were conducted. Serum albumin and 25(OH)D concentrations were analyzed. Mean 25(OH)D concentration was significantly lower in women than in men (p < 0.001). Women showed a significant decline of 25(OH)D level with increased age (p < 0.001). There was also a significant difference in the prevalence of 25(OH)D insufficiency [25(OH)D level < 20 ng/ml] between the sexes (p < 0.001). The rate of falls was significantly higher in the lowest quartile of 25(OH)D level in women (p = 0.02) and in women with 25(OH)D insufficiency (p = 0.001). Women also showed significant declines in all three fall-related physical performance tests. Multiple logistic regression analysis showed significant and independent associations between 25(OH)D level and experience of falls in women only (p = 0.01). Low 25(OH)D level was significantly associated with a high prevalence of falls in Japanese elderly women because of their inferior physical performance. Low serum 25(OH)D levels appear preventable and easily treated; there is an evident need for greater awareness to screen and thus prevent this condition.
Linkage Screen for BMD Phenotypes in Male and Female COP and DA Rat Strains
Authors: Koller Daniel L , Liu Lixiang , Alam Imranul , Sun Qiwei , Econs Michael J , Foroud Tatiana , Turner Charles H
Published: April 2008

Because particular inbred strains of experimental animals are informative for only a subset of the genes underlying variability in BMD, we undertook a genome screen to identify quantitative trait loci (QTLs) in 828 F2 progeny (405 males and 423 females) derived from the Copenhagen 2331 (COP) and dark agouti (DA) strains of rats. This screen was performed to complement our study in female Fischer 344 (F344) and Lewis (LEW) rats and to further delineate the factors underlying the complex genetic architecture of BMD in the rat model. Microsatellite genotyping was performed using markers at an average density of 20 cM. BMD was measured by pQCT and DXA. These data were analyzed in the R/qtl software to detect QTLs acting in both sexes as well as those having sex-specific effects. A QTL was detected in both sexes on chromosome 18 for midfemur volumetric BMD (vBMD; genome-wide, p < 0.01). On distal chromosome 1, a QTL was found for femur and vertebral aBMD as well as distal femur vBMD, and this QTL appears distinct from the proximal chromosome 1 QTL impacting BMD in our F344/LEW cross. Additional aBMD and vBMD QTLs and several sex-specific QTLs were also detected. These included a male-specific QTL (p < 0.01) on chromosome 8 and a female-specific QTL on chromosomes 7 and 14 (p < 0.01). Few of the QTLs identified showed overlap with the significant QTLs from the F344/LEW cross. These results confirm that the genetic influence on BMD in the rat model is quite complex and would seem to be influenced by a number of different genes, some of which have sex-specific effects.
BMD and Bone Geometry in Transtibial and Transfemoral Amputees
Authors: Sherk Vanessa D , Bemben Michael G , Bemben Debra A
Published: April 2008

Prolonged unloading of bone(s) in the residual limb after amputation may cause significant bone loss in the hip and distal bony end of the residual limb. The purpose of this study was to examine the effect of amputation on bone geometry, volumetric BMD (vBMD), and areal BMD (aBMD) by comparing the intact and residual limbs in unilateral transfemoral and transtibial amputees. Amputees (seven above-knee; seven below-knee) and two groups of nonamputee control subjects gave informed consent to participate in this study. aBMD of the dual proximal femur, lumbar spine, and total body was assessed using DXA. Bone geometry and vBMD were assessed at the distal ends of the residual limb and intact limb and at a comparable cross-sectional slice of the intact limb using pQCT (Stratec XCT 3000). There were no significant group differences in age, height, weight, physical activity, time as an amputee, hours wearing a prosthesis per day, or total body and lumbar spine BMD and BMC. There were significant side × group interactions for total hip, femoral neck, and trochanter BMD, with the amputated side having lower BMD, and differences being most severe in above-knee amputees. Total and cortical vBMD and area were significantly lower at the end of the residual limb compared with the similar slice of the intact limb for both above- and below-knee amputees. In conclusion, amputees exhibited large decrements in BMD, both at the hip and at the end of the residual limb, compared with the intact side. These lower BMD values put amputees, particularly the above-knee amputees, at increased risk for osteoporosis and fragility fractures in the hip.
Expression and Regulation of the Vitamin D Receptor in the Zebrafish, Danio rerio
Authors: Craig Theodore A , Sommer Stacy , Sussman Caroline R , Grande Joseph P , Kumar Rajiv
Published: April 2008

Vitamin D and vitamin D metabolites such as 25-hydroxyvitamin D and 1α,25-dihydroxyvitamin D [1α,25(OH)2D3] circulate in the serum of fish. The receptor for 1α,25(OH)2D3 (VDR) has previously been cloned from fish intestine, and ligand binding assays have shown the presence of the VDR in the gills, intestine, and liver of fish. Using immunohistochemical methods with specific antibodies against the VDR, we now report that the VDR is widely expressed in tissues of the adult male and female zebrafish, Danio rerio, specifically in epithelial cells of gills, tubular cells of the kidney, and absorptive cells in the intestine. Additionally, the VDR is expressed in the skin, the olfactory organ, the retina, brain, and spinal cord. Sertoli cells of the testis, oocytes, acinar cells of the pancreas, hepatocytes, and bile duct epithelial cells express substantial amounts of the receptor. Osteoblast-like cells and chondrocytes also express VDR. Preimmune serum and antiserum preadsorbed with Danio VDR protein fails to detect VDR in the same tissues. The VDR is also present in the developing eye, brain, and otic vesicle of 48- and 96-h postfertilization zebrafish embryos. Parenteral administration of 1α,25(OH)2D3 increases concentrations of VDR in intestinal epithelial cells but not in epithelial cells of the gills. Lithocholic acid, however, does not alter concentrations of VDR after parenteral administration. The data suggest that VDR is widely distributed in tissues of the zebrafish, D. rerio, and is likely to play important roles in epithelial transport, bone, and endocrine function. Furthermore, concentrations of the receptor seem to be regulated by its ligand, 1α,25-dihydroxyvitamin D but not by lithocholic acid. Zebrafish may serve as a useful model in which to assess the function of the VDR in diverse tissues.
Relationship of Blood Lead Levels to Incident Nonspine Fractures and Falls in Older Women: The Study of Osteoporotic Fractures
Authors: Khalil Naila , Cauley Jane A , Wilson John W , Talbott Evelyn O , Morrow Lisa , Hochberg Marc C , Hillier Teresa A , Muldoon Susan B , Cummings Steven R
Published: April 2008

Lead is stored in the skeleton and can serve as an endogenous source for many years. Lead may influence the risk of fracture, through direct effects on bone strength or indirectly by disturbing neuromuscular function and increasing the risk of falls. The objective of this analysis is to test the hypothesis that women with higher blood lead levels experience higher rates of falls and fracture. This was a prospective cohort study of 533 women 65–87 yr of age enrolled in the Study of Osteoporotic Fractures at two U.S. research centers (Baltimore, MD; Monongahela Valley, PA) from 1986 to 1988. Blood lead levels (in μg/dl) were measured in 1990–1991 by atomic absorption spectrophotometry and classified as “low” (≤3; lower 15th percentile, referent); “medium” (4–7); or “high” (≥8; upper 15th percentile). Total hip BMD was measured by DXA twice, 3.55 yr apart. Information on falls was collected every 4 mo for 4 yr. Incident nonspine fractures were identified and confirmed over 10 yr. Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% CI of fracture. Generalized estimating equations were used to calculate the incident rate ratio of falls (95% CI). The mean blood lead level was 5.3 ± 2.3 (SD) μg/dl (range, 1–21 μg/dl). Baseline BMD was 7% lower in total hip and 5% lower in femoral neck in the highest compared with lowest blood lead group (p < 0.02). Hip bone loss tended to be greater in the high lead group, but differences were not significant. In multivariable adjusted models, women with high blood lead levels had an increased risk of nonspine fracture (HR = 2.50; 95% CI = 1.25, 5.03; p trend = 0.016) and higher risk of falls (incident rate ratio = 1.62; 95% CI = 1.07, 2.45; p trend = 0.014) compared with women with lowest lead level. Blood lead levels are associated with an increased risk of falls and fractures, extending the negative health consequences of lead to include osteoporotic fractures.
Theoretical Implications of the Biomechanical Fracture Threshold
Authors: Keaveny Tony M , L Bouxsein Mary
Published: April 2008

Because of the dichotomous nature of a bone fracture, when Φ, the ratio of the applied impact force to the bone strength, is greater than a critical value—the biomechanical fracture threshold—fracture should occur. We sought to elucidate the conceptual implications of this biomechanical fracture threshold with application to hip fracture. We used data from the PaTH study, a 2-yr clinical trial in postmenopausal women treated with alendronate, PTH, or their combination. Outcomes included the force applied to the hip in a sideways fall as estimated from subject height and weight; femoral strength as determined by QCT-based finite element analysis; the load-to-strength ratio Φ; and total hip areal BMD from DXA. Results indicated that those with “very low” femoral strength (<2000 N) invariably had load-to-strength ratio Φ values well above the theoretical biomechanical fracture threshold (Φ = 1), but those with “moderately low” femoral strength (2000–4000 N) displayed Φ values both above and below the theoretical biomechanical fracture threshold. This finding implies that the risk of a hip fracture can be high in those with only moderately low BMD because femoral strength can be low relative to fall impact forces. The observed weak correlation between areal BMD and the load-to-strength ratio Φ (r2 = 0.14) suggests that consideration of the biomechanical fracture threshold may improve fracture risk assessment, particularly for those in the osteopenic range. Regarding treatment effects, only those subjects having load-to-strength ratio Φ values within a relatively narrow “transition zone” of ±20% of the assumed biomechanical fracture threshold at baseline were predicted to change fracture status during the trial. In theory, outcomes of fracture trials may be dominated by the responses of those within the “transition zone” at baseline, and treatment benefits in terms of fracture efficacy may depend the patient's baseline status with respect to the biomechanical fracture threshold. We conclude that consideration of the theoretical implications of the biomechanical fracture threshold may lead to new insights and advances in the assessment and treatment of osteoporosis.
Functional Adaptation to Loading of a Single Bone Is Neuronally Regulated and Involves Multiple Bones
Authors: Sample Susannah J , Behan Mary , Smith Lesley , Oldenhoff William E , Markel Mark D , Kalscheur Vicki L , Hao Zhengling , Miletic Vjekoslav , Muir Peter
Published: April 2008

Regulation of load-induced bone formation is considered a local phenomenon controlled by osteocytes, although it has also been hypothesized that functional adaptation may be neuronally regulated. The aim of this study was to examine bone formation in multiple bones, in response to loading of a single bone, and to determine whether adaptation may be neuronally regulated. Load-induced responses in the left and right ulnas and humeri were determined after loading of the right ulna in male Sprague-Dawley rats (69 ± 16 days of age). After a single period of loading at −760-, −2000-, or −3750-μϵ initial peak strain, rats were given calcein to label new bone formation. Bone formation and bone neuropeptide concentrations were determined at 10 days. In one group, temporary neuronal blocking was achieved by perineural anesthesia of the brachial plexus with bupivicaine during loading. We found right ulna loading induces adaptive responses in other bones in both thoracic limbs compared with Sham controls and that neuronal blocking during loading abrogated bone formation in the loaded ulna and other thoracic limb bones. Skeletal adaptation was more evident in distal long bones compared with proximal long bones. We also found that the single period of loading modulated bone neuropeptide concentrations persistently for 10 days. We conclude that functional adaptation to loading of a single bone in young rapidly growing rats is neuronally regulated and involves multiple bones. Persistent changes in bone neuropeptide concentrations after a single loading period suggest that plasticity exists in the innervation of bone.
Sodium and Bone Health: Impact of Moderately High and Low Salt Intakes on Calcium Metabolism in Postmenopausal Women
Authors: Teucher Birgit , Dainty Jack R , Spinks Caroline A , Majsak-Newman Gosia , Berry David J , Hoogewerff Jurian A , Foxall Robert J , Jakobsen Jette , Cashman Kevin D , Flynn Albert , Fairweather-Tait Susan J
Published: April 2008

High salt intake is a well-recognized risk factor for osteoporosis because it induces calciuria, but the effects of salt on calcium metabolism and the potential impact on bone health in postmenopausal women have not been fully characterized. This study investigated adaptive mechanisms in response to changes in salt and calcium intake in postmenopausal women. Eleven women completed a randomized cross-over trial consisting of four successive 5-wk periods of controlled dietary intervention, each separated by a minimum 4-wk washout. Moderately low and high calcium (518 versus 1284 mg) and salt (3.9 versus 11.2 g) diets, reflecting lower and upper intakes in postmenopausal women consuming a Western-style diet, were provided. Stable isotope labeling techniques were used to measure calcium absorption and excretion, compartmental modeling was undertaken to estimate bone calcium balance, and biomarkers of bone formation and resorption were measured in blood and urine. Moderately high salt intake (11.2 g/d) elicited a significant increase in urinary calcium excretion (p = 0.0008) and significantly affected bone calcium balance with the high calcium diet (p = 0.024). Efficiency of calcium absorption was higher after a period of moderately low calcium intake (p < 0.05) but was unaffected by salt intake. Salt was responsible for a significant change in bone calcium balance, from positive to negative, when consumed as part of a high calcium diet, but with a low calcium intake, the bone calcium balance was negative on both high and low salt diets.
The Influence of Cultural Background on Experiences and Beliefs about Traumatic Brain Injury and their Association with Outcome
Authors: Saltapidas Helen , Ponsford Jennie
Published: April 2008

The aim of the study was to compare beliefs and experiences of traumatic brain injury (TBI) in patients with TBI from the dominant English-speaking culture in Australia versus those from minority culturally and linguistically diverse (CALD) backgrounds and examine the relative influence of beliefs, acculturation, along with demographic and injury-related variables on outcome. The primary measures included the Illness Perception Questionnaire-Revised (IPQ-R), and the Craig Handicap Assessment and Reporting Technique (CHART). Participants were 70 individuals with mild to severe TBI, including 38 of English-speaking background (ESB) and 32 from CALD backgrounds. Although similar to the ESB participants in education, preinjury employment status, injury severity and experience of TBI, the CALD participants differed significantly from ESB participants on acculturation variables. CALD participants also experienced greater negative emotions and were less likely to have internal locus of control causal beliefs than ESB participants. Regression analyses indicated that describing one's value system as other than Australian, poorer understanding of TBI and greater negative emotional reactions, along with fewer years of education were associated with poorer outcomes on the CHART. Thus, in treating patients from different cultural backgrounds it is important for health professionals to understand beliefs about and responses to TBI, as they could potentially impact on coping, emotional adjustment and long-term outcome.