Potential for natural and enhanced attenuation of sulphanilamide in a contaminated chalk aquifer

Understanding antibiotic biodegradation is important to the appreciation of their fate and removal from the environment. In this research an Isotope Ratio Mass Spectrometry (IRMS) method was developed to evaluate the extent of biodegradation of the antibiotic, sulphanilamide, in contaminated groundwater. Results indicted an enrichment in δ13C of 8.44‰ from − 26.56 (at the contaminant source) to − 18.12‰ (300 m downfield of the source). These results confirm reductions in sulphanilamide concentrations (from 650 to 10 mg/L) across the contaminant plume to be attributable to biodegradation (56%) vs. other natural attenuation processes, such as dilution or dispersion (42%). To understand the controls on sulphanilamide degradation ex-situ microcosms assessed the influence of sulphanilamide concentration, redox conditions and an alternative carbon source. Results indicated, high levels of anaerobic capacity (~ 50% mineralisation) to degrade sulphanilamide under high (263 mg/L), moderate (10 mg/L) and low (0.02 mg/L) substrate concentrations. The addition of electron acceptors; nitrate and sulphate, did not significantly enhance the capacity of the groundwater to anaerobically biodegrade sulphanilamide. Interestingly, where alternative carbon sources were present, the addition of nitrate and sulphate inhibited sulphanilamide biodegradation. These results suggest, under in-situ conditions, when a preferential carbon source was available for biodegradation, sulphanilamide could be acting as a nitrogen and/or sulphur source. These findings are important as they highlight sulphanilamide being used as a carbon and a putative nitrogen and sulphur source, under prevailing iron reducing conditions

Recruitment and retention of participants in a pragmatic randomized intervention trial at three community health clinics: Results and lessons learned

Background: Obesity and hypertension and their associated health complications disproportionately affect communities of color and people of lower socioeconomic status. Recruitment and retention of these populations in research trials, and retention in weight loss trials has been an ongoing challenge. Methods: Be Fit, Be Well was a pragmatic randomized weight loss and hypertension management trial of patients attending one of three community health centers in Boston, Massachusetts. Participants were asked to complete follow-up assessments every 6-months for two years. We describe challenges encountered and strategies implemented to recruit and retain trial participants over the 24-month intervention. We also identify baseline participant characteristics associated with retention status. Retention strategies included financial incentives, contact between assessment visits, building relationships with health center primary care providers (PCPs) and staff, and putting participant convenience first. Results: Active refusal rates were low with 130 of 2,631 patients refusing participation (4.9%). Of 474 eligible persons completing telephone screening, 365 (77.0%) completed their baseline visit and were randomized into the study. The study population was predominantly non-Hispanic Black (71.2%), female (68.5%) and reported annual household income of less than $35,000 (70.1%). Recruitment strategies included use of passive approval of potential participants by PCPs, use of part-time staff, and outsourcing calls to a call center. A total of 314 (86.0%) people completed the 24-month visit. Retention levels varied across study visits and intervention condition. Most participants completed three or more visits (69.6%), with 205 (56.2%) completing all four. At 24-months, lower retention was observed for males and the intervention condition. Retention strategies included building strong relationships with clinic staff, flexibility in overcoming participant barriers through use of taxi vouchers, night and weekend appointments, and keeping participants engaged via newsletters and social gatherings. Conclusion: We were able to retain 86.0% of participants at 24-months. Recruitment and retention of high percentages of racial/ethnic minorities and lower income samples is possible with planning, coordination with a trusted community setting and staff (e.g. community health centers and RAs), adaptability and building strong relationships. Trial registration Clinicaltrials.gov Identifier: NCT0066181

Early diagenetic vivianite [Fe-3(PO4)(2) center dot 8H(2)O] in a contaminated freshwater sediment and insights into zinc uptake: a mu-EXAFS, mu-XANES and Raman study

The sediments in the Salford Quays, a heavily-modified urban water body, contain high levels of organic matter, Fe, Zn and nutrients as a result of past contaminant inputs. Vivianite [Fe3(PO4)2 · 8H2O] has been observed to have precipitated within these sediments during early diagenesis as a result of the release of Fe and P to porewaters. These mineral grains are small (<100 μm) and micron-scale analysis techniques (SEM, electron microprobe, μ-EXAFS, μ-XANES and Raman) have been applied in this study to obtain information upon the structure of this vivianite and the nature of Zn uptake in the mineral. Petrographic observations, and elemental, X-ray diffraction and Raman spectroscopic analysis confirms the presence of vivianite. EXAFS model fitting of the FeK-edge spectra for individual vivianite grains produces Fe–O and Fe–P co-ordination numbers and bond lengths consistent with previous structural studies of vivianite (4O atoms at 1.99–2.05 Å; 2P atoms at 3.17–3.25 Å). One analysed grain displays evidence of a significant Fe3+ component, which is interpreted to have resulted from oxidation during sample handling and/or analysis. EXAFS modelling of the Zn K-edge data, together with linear combination XANES fitting of model compounds, indicates that Zn may be incorporated into the crystal structure of vivianite (4O atoms at 1.97 Å; 2P atoms at 3.17 Å). Low levels of Zn sulphate or Zn-sorbed goethite are also indicated from linear combination XANES fitting and to a limited extent, the EXAFS fitting, the origin of which may either be an oxidation artifact or the inclusion of Zn sulphate into the vivianite grains during precipitation. This study confirms that early diagenetic vivianite may act as a sink for Zn, and potentially other contaminants (e.g. As) during its formation and, therefore, forms an important component of metal cycling in contaminated sediments and waters. Furthermore, for the case of Zn, the EXAFS fits for Zn phosphate suggest this uptake is structural and not via surface adsorption

The mediating effect of task presentation on collaboration and children's acquisition of scientific reasoning

There has been considerable research concerning peer interaction and the acquisition of children's scientific reasoning. This study investigated differences in collaborative activity between pairs of children working around a computer with pairs of children working with physical apparatus and related any differences to the development of children's scientific reasoning. Children aged between 9 and 10 years old (48 boys and 48 girls) were placed into either same ability or mixed ability pairs according to their individual, pre-test performance on a scientific reasoning task. These pairs then worked on either a computer version or a physical version of Inhelder and Piaget's (1958) chemical combination task. Type of presentation was found to mediate the nature and type of collaborative activity. The mixed-ability pairs working around the computer talked proportionally more about the task and management of the task; had proportionally more transactive discussions and used the record more productively than children working with the physical apparatus. Type of presentation was also found to mediated children's learning. Children in same ability pairs who worked with the physical apparatus improved significantly more than same ability pairs who worked around the computer. These findings were partially predicted from a socio-cultural theory and show the importance of tools for mediating collaborative activity and collaborative learning

High Priority Research Needs for Gestational Diabetes Mellitus

Identification of unanswered research questions about the management of gestational diabetes mellitus (GDM) is necessary to focus future research endeavors. We developed a process for elucidating the highest priority research questions on GDM

Retinoic acid enhances skeletal muscle progenitor formation and bypasses inhibition by bone morphogenetic protein 4 but not dominant negative β-catenin

<p>Abstract</p> <p>Background</p> <p>Understanding stem cell differentiation is essential for the future design of cell therapies. While retinoic acid (RA) is the most potent small molecule enhancer of skeletal myogenesis in stem cells, the stage and mechanism of its function has not yet been elucidated. Further, the intersection of RA with other signalling pathways that stimulate or inhibit myogenesis (such as Wnt and BMP4, respectively) is unknown. Thus, the purpose of this study is to examine the molecular mechanisms by which RA enhances skeletal myogenesis and interacts with Wnt and BMP4 signalling during P19 or mouse embryonic stem (ES) cell differentiation.</p> <p>Results</p> <p>Treatment of P19 or mouse ES cells with low levels of RA led to an enhancement of skeletal myogenesis by upregulating the expression of the mesodermal marker, Wnt3a, the skeletal muscle progenitor factors Pax3 and Meox1, and the myogenic regulatory factors (MRFs) MyoD and myogenin. By chromatin immunoprecipitation, RA receptors (RARs) bound directly to regulatory regions in the Wnt3a, Pax3, and Meox1 genes and RA activated a β-catenin-responsive promoter in aggregated P19 cells. In the presence of a dominant negative β-catenin/engrailed repressor fusion protein, RA could not bypass the inhibition of skeletal myogenesis nor upregulate Meox1 or MyoD. Thus, RA functions both upstream and downstream of Wnt signalling. In contrast, it functions downstream of BMP4, as it abrogates BMP4 inhibition of myogenesis and Meox1, Pax3, and MyoD expression. Furthermore, RA downregulated BMP4 expression and upregulated the BMP4 inhibitor, Tob1. Finally, RA inhibited cardiomyogenesis but not in the presence of BMP4.</p> <p>Conclusion</p> <p>RA can enhance skeletal myogenesis in stem cells at the muscle specification/progenitor stage by activating RARs bound directly to mesoderm and skeletal muscle progenitor genes, activating β-catenin function and inhibiting bone morphogenetic protein (BMP) signalling. Thus, a signalling pathway can function at multiple levels to positively regulate a developmental program and can function by abrogating inhibitory pathways. Finally, since RA enhances skeletal muscle progenitor formation, it will be a valuable tool for designing future stem cell therapies.</p

Endothelin receptor antagonism does not prevent the development of in vivo glyceryl trinitrate tolerance in the rat

ABSTRACT There is evidence that increased endothelial production of endothelin-1 (ET-1) may contribute to glyceryl trinitrate (GTN) tolerance. We used the competitive ET A receptor antagonist ZD2574 to determine whether chronic ET A receptor blockade affected the biochemical and functional responses to GTN during the development of GTN tolerance in vivo. Tolerance induced using transdermal GTN patches resulted in a 5.3 Ϯ 1.2-fold increase in the EC 50 value for GTN relaxation in isolated aorta from GTN-tolerant rats. Coadministration of ZD2574 (100 mg kg Ϫ1 t.i.d. for 3 days) during tolerance induction had no effect on GTN-induced relaxation. This dose of ZD2574 markedly blunted the pressor response to ET-1, indicating effective blockade of ET A receptors, and also abolished the initial transient depressor response to ET-1, indicating that blockade of endothelial ET B receptors also occurred using this dosage regimen for ZD2574. Consistent with the relaxation data, coadministration of ZD2574 had no effect on the decrease in GTNinduced cGMP accumulation or on the decrease in GTN biotransformation that occurred in aortae from GTN-tolerant animals. Radioimmunoassay data indicated that the GTN tolerance induction protocol caused a 2.3 Ϯ 0.4-fold and a 2.2 Ϯ 0.5-fold increase in total tissue ET-1 levels in tolerant aorta and vena cava, respectively. These data suggest that chronic inhibition of ET receptors by ZD2574 was not sufficient to prevent or diminish the tolerance-inducing effects of GTN, and that the increase in ET-1 levels observed in tolerant tissues may occur as a consequence of the vascular changes that occur during chronic GTN exposure

Right at home: living with dementia and multi-morbidities

Dementia is recognised as the biggest health crisis of our time in terms of high personal and social costs and wider impact on health and social care systems. Increases in people living with dementia and multimorbidities presents critical challenges for homecare worldwide. Healthcare systems struggle to provide adequate home-care services, delivering limited care restricted to a single-condition focus. This study explored the experiences and expectations of homecare from the multiple perspectives of people living with dementia and multimorbidities and homecare workers providing support. Findings draw from qualitative semi-structured interviews with people with dementia (n=2), their partners (n=2), other partners or family carers (n=6) and homecare workers (n=26). Three themes are identified: (a) the preference for and value of home; (b) inadequate homecare provision and enhanced care-burden; (c) limited training and education. Despite continued calls for homecare investment, the focus on reduction in costs hides key questions and further dialogue required exploring how people with dementia can be supported to live independently and flourish at-home. This study considers these complex experiences and care requirements through the prism of disability and human rights frameworks. This paper concludes with consideration of more recent human social rights debate. We critically discuss what this may mean for people living with dementia and consider the implications for corequisite policy development to optimise available homecare support. Keywords: dementia, multimorbidities, homecare, independent-living, social right

ORIO (Online Resource for Integrative Omics): a web-based platform for rapid integration of next generation sequencing data

Abstract Established and emerging next generation sequencing (NGS)-based technologies allow for genome-wide interrogation of diverse biological processes. However, accessibility of NGS data remains a problem, and few user-friendly resources exist for integrative analysis of NGS data from different sources and experimental techniques. Here, we present Online Resource for Integrative Omics (ORIO; https://orio.niehs.nih.gov/), a web-based resource with an intuitive user interface for rapid analysis and integration of NGS data. To use ORIO, the user specifies NGS data of interest along with a list of genomic coordinates. Genomic coordinates may be biologically relevant features from a variety of sources, such as ChIP-seq peaks for a given protein or transcription start sites from known gene models. ORIO first iteratively finds read coverage values at each genomic feature for each NGS dataset. Data are then integrated using clustering-based approaches, giving hierarchical relationships across NGS datasets and separating individual genomic features into groups. In focusing its analysis on read coverage, ORIO makes limited assumptions about the analyzed data; this allows the tool to be applied across data from a variety of experiments and techniques. Results from analysis are presented in dynamic displays alongside user-controlled statistical tests, supporting rapid statistical validation of observed results. We emphasize the versatility of ORIO through diverse examples, ranging from NGS data quality control to characterization of enhancer regions and integration of gene expression information. Easily accessible on a public web server, we anticipate wide use of ORIO in genome-wide investigations by life scientists