Synthesis and Detection of Oxygen-18 Labeled Phosphate

Phosphorus (P) has only one stable isotope and therefore tracking P dynamics in ecosystems and inferring sources of P loading to water bodies have been difficult. Researchers have recently employed the natural abundance of the ratio of 18O/16O of phosphate to elucidate P dynamics. In addition, phosphate highly enriched in oxygen-18 also has potential to be an effective tool for tracking specific sources of P in the environment, but has so far been used sparingly, possibly due to unavailability of oxygen-18 labeled phosphate (OLP) and uncertainty in synthesis and detection. One objective of this research was to develop a simple procedure to synthesize highly enriched OLP. Synthesized OLP is made up of a collection of species that contain between zero and four oxygen-18 atoms and, as a result, the second objective of this research was to develop a method to detect and quantify each OLP species. OLP was synthesized by reacting either PCl5 or POCl3 with water enriched with 97 atom % oxygen-18 in ambient atmosphere under a fume hood. Unlike previous reports, we observed no loss of oxygen-18 enrichment during synthesis. Electrospray ionization mass spectrometertry (ESI-MS) was used to detect and quantify each species present in OLP. OLP synthesized from POCl3 contained 1.2% P18O16O3, 18.2% P18O216O2, 67.7% P18O316O, and 12.9% P18O4, and OLP synthesized from PCl5 contained 0.7% P16O4, 9.3% P18O316O, and 90.0% P18O4. We found that OLP can be synthesized using a simple procedure in ambient atmosphere without the loss of oxygen-18 enrichment and ESI-MS is an effective tool to detect and quantify OLP that sheds light on the dynamics of synthesis in ways that standard detection methods cannot

Reflections and Experiences of a Co-Researcher involved in a Renal Research Study

Background Patient and Public Involvement (PPI) is seen as a prerequisite for health research. However, current Patient and public involvement literature has noted a paucity of recording of patient and public involvement within research studies. There have been calls for more recordings and reflections, specifically on impact. Renal medicine has also had similar criticisms and any reflections on patient and public involvement has usually been from the viewpoint of the researcher. Roles of patient and public involvement can vary greatly from sitting on an Advisory Group to analysing data. Different PPI roles have been described within studies; one being a co-researcher. However, the role of the co-researcher is largely undefined and appears to vary from study to study. Methods The aims of this paper are to share one first time co-researcher's reflections on the impact of PPI within a mixed methods (non-clinical trial) renal research study. A retrospective, reflective approach was taken using data available to the co-researcher as part of the day-to-day research activity. Electronic correspondence and documents such as meeting notes, minutes, interview thematic analysis and comments on documents were re-examined. The co-researcher led on writing this paper. Results This paper offers a broad definition of the role of the co-researcher. The co-researcher reflects on undertaking and leading on the thematic analysis of interview transcripts, something she had not previously done before. The co-researcher identified a number of key themes; the differences in time and responsibility between being a coresearcher and an Advisory Group member; how the role evolved and involvement activities could match the co-researchers strengths (and the need for flexibility); the need for training and support and lastly, the time commitment. It was also noted that it is preferable that a co-researcher needs to be involved from the very beginning of the grant application. Conclusions The reflections, voices and views of those undertaking PPI has been largely underrepresented in the literature. The role of co-researcher was seen to be rewarding but demanding, requiring a large time commitment. It is hoped that the learning from sharing this experience will encourage others to undertake this role, and encourage researchers to reflect on the needs of those involved.Peer reviewedFinal Published versio

Growth inhibition of thyroid follicular cell-derived cancers by the opioid growth factor (OGF) - opioid growth factor receptor (OGFr) axis

<p>Abstract</p> <p>Background</p> <p>Carcinoma of the thyroid gland is an uncommon cancer, but the most frequent malignancy of the endocrine system. Most thyroid cancers are derived from the follicular cell. Follicular carcinoma (FTC) is considered more malignant than papillary thyroid carcinoma (PTC), and anaplastic thyroid cancer (ATC) is one of the most lethal human cancers. Opioid Growth Factor (OGF; chemical term - [Met⁵]-enkephalin) and its receptor, OGFr, form an inhibitory axis regulating cell proliferation. Both the peptide and receptor have been detected in a wide variety of cancers, and OGF is currently used clinically as a biotherapy for some non-thyroid neoplasias. This study addressed the question of whether the OGF-OGFr axis is present and functional in human thyroid follicular cell - derived cancer.</p> <p>Methods</p> <p>Utilizing human ATC (KAT-18), PTC (KTC-1), and FTC (WRO 82-1) cell lines, immunohistochemistry was employed to ascertain the presence and location of OGF and OGFr. The growth characteristics in the presence of OGF or the opioid antagonist naltrexone (NTX), and the specificity of opioid peptides for proliferation of ATC, were established in KAT-18 cells. Dependence on peptide and receptor were investigated using neutralization studies with antibodies and siRNA experiments, respectively. The mechanism of peptide action on DNA synthesis and cell survival was ascertained. The ubiquity of the OGF-OGFr axis in thyroid follicular cell-derived cancer was assessed in KTC-1 (PTC) and WRO 82-1 (FTC) tumor cells.</p> <p>Results</p> <p>OGF and OGFr were present in KAT-18 cells. Concentrations of 10^-6M OGF inhibited cell replication up to 30%, whereas NTX increased cell growth up to 35% relative to cultures treated with sterile water. OGF treatment reduced cell number by as much as 38% in KAT-18 ATC in a dose-dependent and receptor-mediated manner. OGF antibodies neutralized the inhibitory effects of OGF, and siRNA knockdown of OGFr negated growth inhibition by OGF. Cell survival was not altered by OGF, but DNA synthesis as recorded by BrdU incorporation was depressed by 28% in OGF-treated cultures compared to those exposed to sterile water. The OGF-OGFr axis was detected and functional in PTC (KTC-1) and FTC (WRO 82-1) cell lines.</p> <p>Conclusion</p> <p>These data suggest that OGF and OGFr are present in follicular-derived thyroid cancers, and that OGF serves in a tonically active inhibitory manner to maintain homeostasis of cell proliferation. These results may provide a biotherapeutic strategy in the treatment of these cancers.</p

Orthodontic tooth movement enhancing bony apposition in alveolar bony defect: a case report

Introduction: Prevalence of complications from orthognathic surgery is relatively low but if it happens it is vital to manage the post complication bony defect appropriately. Case Presentation: This case report describes a 20-year-old gentleman who suffered from a complication from a bimaxillary orthognathic surgery. A bone grafting was carried out to repair the bony defect from the surgery but it was unsuccessful. A non-invasive technique employing the use of very light orthodontic force with a laceback stainless steel ligature is described and a successful space closure with an improvement in the periodontal condition and bone apposition has been shown. Conclusion: This technique can be considered if orthodontic tooth movement is needed across a deficient alveolar ridge. © 2009 Hibino and Wong; licensee BioMed Central Ltd.published_or_final_versio

Cancer risks following diagnostic and therapeutic radiation exposure in children

The growing use of interventional and fluoroscopic imaging in children represents a tremendous benefit for the diagnosis and treatment of benign conditions. Along with the increasing use and complexity of these procedures comes concern about the cancer risk associated with ionizing radiation exposure to children. Children are considerably more sensitive to the carcinogenic effects of ionizing radiation than adults, and children have a longer life expectancy in which to express risk. Numerous epidemiologic cohort studies of childhood exposure to radiation for treatment of benign diseases have demonstrated radiation-related risks of cancer of the thyroid, breast, brain and skin, as well as leukemia. Many fewer studies have evaluated cancer risk following diagnostic radiation exposure in children. Although radiation dose for a single procedure might be low, pediatric patients often receive repeated examinations over time to evaluate their conditions, which could result in relatively high cumulative doses. Several cohort studies of girls and young women subjected to multiple diagnostic radiation exposures have been informative about increased mortality from breast cancer with increasing radiation dose, and case-control studies of childhood leukemia and postnatal diagnostic radiation exposure have suggested increased risks with an increasing number of examinations. Only two long-term follow-up studies of cancer following cardiac catheterization in childhood have been conducted, and neither reported an overall increased risk of cancer. Most cancers can be induced by radiation, and a linear dose-response has been noted for most solid cancers. Risks of radiation-related cancer are greatest for those exposed early in life, and these risks appear to persist throughout life

X-ray emission from isolated neutron stars

X-ray emission is a common feature of all varieties of isolated neutron stars (INS) and, thanks to the advent of sensitive instruments with good spectroscopic, timing, and imaging capabilities, X-ray observations have become an essential tool in the study of these objects. Non-thermal X-rays from young, energetic radio pulsars have been detected since the beginning of X-ray astronomy, and the long-sought thermal emission from cooling neutron star's surfaces can now be studied in detail in many pulsars spanning different ages, magnetic fields, and, possibly, surface compositions. In addition, other different manifestations of INS have been discovered with X-ray observations. These new classes of high-energy sources, comprising the nearby X-ray Dim Isolated Neutron Stars, the Central Compact Objects in supernova remnants, the Anomalous X-ray Pulsars, and the Soft Gamma-ray Repeaters, now add up to several tens of confirmed members, plus many candidates, and allow us to study a variety of phenomena unobservable in "standard'' radio pulsars.Comment: Chapter to be published in the book of proceedings of the 1st Sant Cugat Forum on Astrophysics, "ICREA Workshop on the high-energy emission from pulsars and their systems", held in April, 201

Sustainability of the whole-community project '10,000 Steps': a longitudinal study

<p>Abstract</p> <p>Background</p> <p>In the dissemination and implementation literature, there is a dearth of information on the sustainability of community-wide physical activity (PA) programs in general and of the '10,000 Steps' project in particular. This paper reports a longitudinal evaluation of organizational and individual sustainability indicators of '10,000 Steps'.</p> <p>Methods</p> <p>Among project adopters, department heads of 24 public services were surveyed 1.5 years after initially reported project implementation to assess continuation, institutionalization, sustained implementation of intervention components, and adaptations. Barriers and facilitators of project sustainability were explored. Citizens (<it>n </it>= 483) living near the adopting organizations were interviewed to measure maintenance of PA differences between citizens aware and unaware of '10,000 Steps'. Independent-samples <it>t</it>, Mann-Whitney <it>U</it>, and chi-square tests were used to compare organizations for representativeness and individual PA differences.</p> <p>Results</p> <p>Of all organizations, 50% continued '10,000 Steps' (mostly in cycles) and continuation was independent of organizational characteristics. Level of intervention institutionalization was low to moderate on evaluations of routinization and moderate for project saturation. The global implementation score (58%) remained stable and three of nine project components were continued by less than half of organizations (posters, street signs and variants, personalized contact). Considerable independent adaptations of the project were reported (e.g. campaign image). Citizens aware of '10,000 Steps' remained more active during leisure time than those unaware (227 ± 235 and 176 ± 198 min/week, respectively; <it>t </it>= -2.6; p < .05), and reported more household-related (464 ± 397 and 389 ± 346 min/week, respectively; <it>t </it>= -2.2; p < .05) and moderate-intensity-PA (664 ± 424 and 586 ± 408 min/week, respectively; <it>t </it>= -2.0; p < .05). Facilitators of project sustainability included an organizational leader supporting the project, availability of funding or external support, and ready-for-use materials with ample room for adaptation. Barriers included insufficient synchronization between regional and community policy levels and preference for other PA projects.</p> <p>Conclusions</p> <p>'10,000 Steps' could remain sustainable but design, organizational, and contextual barriers need consideration. Sustainability of '10,000 Steps' in organizations can occur in cycles rather than in ongoing projects. Future research should compare sustainability other whole-community PA projects with '10,000 Steps' to contrast sustainability of alternative models of whole-community PA projects. This would allow optimization of project elements and methods to support decisions of choice for practitioners.</p

Effects of non-steroidal anti-inflammatory drugs on cancer sites other than the colon and rectum: a meta-analysis

BACKGROUND: Observational studies have consistently shown that aspirin and non-steroidal anti-inflammatory drug (NSAID) use is associated with a close to 50% reduced risk of colorectal cancer. Studies assessing the effects of NSAIDs on other cancers have shown conflicting results. Therefore, we conducted a meta-analysis to evaluate the relationship between NSAID use and cancer other than colorectal. METHODS: We performed a search in Medline (from 1966 to 2002) and identified a total of 47 articles (13 cohort and 34 case-control studies). Overall estimates of the relative risk (RR) were calculated for each cancer site using random effects models. RESULTS: Aspirin use was associated with a reduced risk of cancer of the esophagus and the stomach (RR, 0.51; 95%CI (0.38–0.69), and 0.73; 95%CI (0.63–0.84)). Use of NSAIDs was similarly associated with a lower risk of esophageal and gastric cancers (RR,0.65; 95% CI(0.46–0.92) and RR,0.54; 95%CI (0.39–0.75)). Among other cancers, only the results obtained for breast cancer were fairly consistent in showing a slight reduced risk among NSAID and aspirin users (RR, 0.77; 95%CI (0.66–0.88), and RR, 0.77; 95%CI (0.69–0.86) respectively)). CONCLUSIONS: The results of this meta-analysis show that the potential chemopreventive role of NSAIDs in colorectal cancer might be extended to other gastrointestinal cancers such as esophagus and stomach. Further research is required to evaluate the role of NSAIDs at other cancers sites

BMP-2 Up-Regulates PTEN Expression and Induces Apoptosis of Pulmonary Artery Smooth Muscle Cells under Hypoxia

To investigate the role of bone morphogenetic protein 2 (BMP-2) in regulation of phosphatase and tensin homologue deleted on chromosome ten (PTEN) and apoptosis of pulmonary artery smooth muscle cells (PASMCs) under hypoxia.Normal human PASMCs were cultured in growth medium (GM) and treated with BMP-2 from 5-80 ng/ml under hypoxia (5% CO(2)+94% N(2)+1% O(2)) for 72 hours. Gene expression of PTEN, AKT-1 and AKT-2 were determined by quantitative RT-PCR (QRT-PCR). Protein expression levels of PTEN, AKT and phosph-AKT (pAKT) were determined. Apoptosis of PASMCs were determined by measuring activities of caspases-3, -8 and -9. siRNA-smad-4, bpV(HOpic) (PTEN inhibitor) and GW9662 (PPARγ antagonist) were used to determine the signalling pathways.Proliferation of PASMCs showed dose dependence of BMP-2, the lowest proliferation rate was achieved at 60 ng/ml concentration under hypoxia (82.2±2.8%). BMP-2 increased PTEN gene expression level, while AKT-1 and AKT-2 did not change. Consistently, the PTEN protein expression also showed dose dependence of BMP-2. AKT activity significantly reduced in BMP-2 treated PASMCs. Increased activities of caspase-3, -8 and -9 of PASMCs were found after cultured with BMP-2. PTEN expression remained unchanged when Smad-4 expression was inhibited by siRNA-Smad-4. bpV(HOpic) and GW9662 (PPARγ inhibitor) inhibited PTEN protein expression and recovered PASMCs proliferation rate.BMP-2 increased PTEN expression under hypoxia in a dose dependent pattern. BMP-2 reduced AKT activity and increased caspase activity of PASMCs under hypoxia. The increased PTEN expression may be mediated through PPARγ signalling pathway, instead of BMP/Smad signalling pathway