Effectiveness and cost of recruitment strategies for a community-based randomised controlled trial among rainwater drinkers

<p>Abstract</p> <p>Background</p> <p>Community-based recruitment is challenging particularly if the sampling frame is not easily defined as in the case of people who drink rainwater. Strategies for contacting participants must be carefully considered to maximise generalisability and minimise bias of the results. This paper assesses the recruitment strategies for a 1-year double-blinded randomised trial on drinking untreated rainwater. The effectiveness of the recruitment strategies and associated costs are described.</p> <p>Methods</p> <p>Community recruitment of households from Adelaide, Australia occurred from February to July 2007 using four methods: electoral roll mail-out, approaches to schools and community groups, newspaper advertising, and other media involvement. Word of mouth communication was also assessed.</p> <p>Results</p> <p>A total of 810 callers were screened, with 53.5% eligible. Of those who were eligible and sent further information, 76.7% were willing to participate in the study and 75.1% were enrolled. The target for recruitment was 300 households, and this was achieved. The mail-out was the most effective method with respect to number of households randomised, while recruitment via schools had the highest yield (57.3%) and was the most cost effective when considering cost per household randomised (AUD$147.20). Yield and cost effectiveness were lowest for media advertising.</p> <p>Conclusion</p> <p>The use of electoral roll mail-out and advertising via schools were effective in reaching households using untreated rainwater for drinking. Employing multiple strategies enabled success in achieving the recruitment target. In countries where electoral roll extracts are available to researchers, this method is likely to have a high yield for recruitment into community-based epidemiological studies.</p

Bias in Online Freelance Marketplaces: Evidence from TaskRabbit and Fiverr

Online freelancing marketplaces have grown quickly in recent years. In theory, these sites offer workers the ability to earn money without the obligations and potential social biases associated with traditional employment frameworks. In this paper, we study whether two prominent online freelance marketplaces - TaskRabbit and Fiverr - are impacted by racial and gender bias. From these two platforms, we collect 13,500 worker profiles and gather information about workers' gender, race, customer reviews, ratings, and positions in search rankings. In both marketplaces, we find evidence of bias: we find that gender and race are significantly correlated with worker evaluations, which could harm the employment opportunities afforded to the workers. We hope that our study fuels more research on the presence and implications of discrimination in online environments

Mitochondrial dysfunction in a cell model of thyroid oncocytoma

The role of mitochondrial dysfunction in cancer has long been a subject of great interest. In this study, such dysfunction has been examined with regards to thyroid oncocytoma, a rare form of cancer, accounting for less than 5% of all thyroid cancers. A peculiar characteristic of thyroid oncocytic cells is the presence of an abnormally large number of mitochondria in the cytoplasm. Such mitochondrial hyperplasia has also been observed in cells derived from patients suffering from mitochondrial encephalomyopathies, where mutations in the mitochondrial DNA(mtDNA) encoding the respiratory complexes result in oxidative phosphorylation dysfunction. An increase in the number of mitochondria occurs in the latter in order to compensate for the respiratory deficiency. This fact spurred the investigation into the presence of analogous mutations in thyroid oncocytic cells. In this study, the only available cell model of thyroid oncocytoma was utilised, the XTC-1 cell line, established from an oncocytic thyroid metastasis to the breast. In order to assess the energetic efficiency of these cells, they were incubated in a medium lacking glucose and supplemented instead with galactose. When subjected to such conditions, glycolysis is effectively inhibited and the cells are forced to use the mitochondria for energy production. Cell viability experiments revealed that XTC-1 cells were unable to survive in galactose medium. This was in marked contrast to the TPC-1 control cell line, a thyroid tumour cell line which does not display the oncocytic phenotype. In agreement with these findings, subsequent experiments assessing the levels of cellular ATP over incubation time in galactose medium, showed a drastic and continual decrease in ATP levels only in the XTC-1 cell line. Furthermore, experiments on digitonin-permeabilised cells revealed that the respiratory dysfunction in the latter was due to a defect in complex I of the respiratory chain. Subsequent experiments using cybrids demonstrated that this defect could be attributed to the mitochondrially-encoded subunits of complex I as opposed to the nuclearencoded subunits. Confirmation came with mtDNA sequencing, which detected the presence of a novel mutation in the ND1 subunit of complex I. In addition, a mutation in the cytochrome b subunit of complex III of the respiratory chain was detected. The fact that XTC-1 cells are unable to survive when incubated in galactose medium is consistent with the fact that many cancers are largely dependent on glycolysis for energy production. Indeed, numerous studies have shown that glycolytic inhibitors are able to induce apoptosis in various cancer cell lines. Subsequent experiments were therefore performed in order to identify the mode of XTC-1 cell death when subjected to the metabolic stress imposed by the forced use of the mitochondria for energy production. Cell shrinkage and mitochondrial fragmentation were observed in the dying cells, which would indicate an apoptotic type of cell death. Analysis of additional parameters however revealed a lack of both DNA fragmentation and caspase activation, thus excluding a classical apoptotic type of cell death. Interestingly, cleavage of the actin component of the cytoskeleton was observed, implicating the action of proteases in this mode of cell demise. However, experiments employing protease inhibitors failed to identify the specific protease involved. It has been reported in the literature that overexpression of Bcl-2 is able to rescue cells presenting a respiratory deficiency. As the XTC-1 cell line is not only respiration-deficient but also exhibits a marked decrease in Bcl-2 expression, it is a perfect model with which to study the relationship between Bcl-2 and oxidative phosphorylation in respiratory-deficient cells. Contrary to the reported literature studies on various cell lines harbouring defects in the respiratory chain, Bcl-2 overexpression was not shown to increase cell survival or rescue the energetic dysfunction in XTC-1 cells. Interestingly however, it had a noticeable impact on cell adhesion and morphology. Whereas XTC-1 cells shrank and detached from the growth surface under conditions of metabolic stress, Bcl-2-overexpressing XTC-1 cells appeared much healthier and were up to 45% more adherent. The target of Bcl-2 in this setting appeared to be the actin cytoskeleton, as the cleavage observed in XTC-1 cells expressing only endogenous levels of Bcl-2, was inhibited in Bcl-2-overexpressing cells. Thus, although unable to rescue XTC-1 cells in terms of cell viability, Bcl-2 is somehow able to stabilise the cytoskeleton, resulting in modifications in cell morphology and adhesion. The mitochondrial respiratory deficiency observed in cancer cells is thought not only to cause an increased dependency on glycolysis but it is also thought to blunt cellular responses to anticancer agents. The effects of several therapeutic agents were thus assessed for their death-inducing ability in XTC-1 cells. Cell viability experiments clearly showed that the cells were more resistant to stimuli which generate reactive oxygen species (tert-butylhydroperoxide) and to mitochondrial calcium-mediated apoptotic stimuli (C6-ceramide), as opposed to stimuli inflicting DNA damage (cisplatin) and damage to protein kinases(staurosporine). Various studies in the literature have reported that the peroxisome proliferator-activated receptor-coactivator 1(PGC-1α), which plays a fundamental role in mitochondrial biogenesis, is also involved in protecting cells against apoptosis caused by the former two types of stimuli. In accordance with these observations, real-time PCR experiments showed that XTC-1 cells express higher mRNA levels of this coactivator than do the control cells, implicating its importance in drug resistance. In conclusion, this study has revealed that XTC-1 cells, like many cancer cell lines, are characterised by a reduced energetic efficiency due to mitochondrial dysfunction. Said dysfunction has been attributed to mutations in respiratory genes encoded by the mitochondrial genome. Although the mechanism of cell demise in conditions of metabolic stress is unclear, the potential of targeting thyroid oncocytic cancers using glycolytic inhibitors has been illustrated. In addition, the discovery of mtDNA mutations in XTC-1 cells has enabled the use of this cell line as a model with which to study the relationship between Bcl-2 overexpression and oxidative phosphorylation in cells harbouring mtDNA mutations and also to investigate the significance of such mutations in establishing resistance to apoptotic stimuli

Osteosynthetic improvement of osteoporotic bone: prevention surgery

A prior osteoporotic femoral neck fracture (FNF) doubles the risk of a second, contralateral hip fracture. Pharmacological prevention of osteoporotic fractures is cost-effective but medication compliance and persistence rates are suboptimal

Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element.

The transcription factor Nrf2, which normally exists in an inactive state as a consequence of binding to a cytoskeleton-associated protein Keap1, can be activated by redox-dependent stimuli. Alteration of the Nrf2-Keap1 interaction enables Nrf2 to translocate to the nucleus, bind to the antioxidant-responsive element (ARE) and initiate the transcription of genes coding for detoxifying enzymes and cytoprotective proteins. This response is also triggered by a class of electrophilic compounds including polyphenols and plant-derived constituents. Recently, the natural antioxidants curcumin and caffeic acid phenethyl ester (CAPE) have been identified as potent inducers of haem oxygenase-1 (HO-1), a redox-sensitive inducible protein that provides protection against various forms of stress. Here, we show that in renal epithelial cells both curcumin and CAPE stimulate the expression of Nrf2 in a concentration- and time-dependent manner. This effect was associated with a significant increase in HO-1 protein expression and haem oxygenase activity. From several lines of investigation we also report that curcumin (and, by inference, CAPE) stimulates ho-1 gene activity by promoting inactivation of the Nrf2-Keap1 complex, leading to increased Nrf2 binding to the resident ho-1 AREs. Moreover, using antibodies and specific inhibitors of the mitogen-activated protein kinase (MAPK) pathways, we provide data implicating p38 MAPK in curcumin-mediated ho-1 induction. Taken together, these results demonstrate that induction of HO-1 by curcumin and CAPE requires the activation of the Nrf2/ARE pathway

Conservative versus surgical treatment of osteogenesis imperfecta: a retrospective analysis of 29 patients

The aim of our study was to compare the surgical and conservative treatment of patients affected by fragility fractures and deformities of long bones in osteogenesis imperfecta (OI). Our series consisted of 29 consecutive OI patients treated at our Institute. The series comprised 14 females and 15 males of different ages. The mean age at the time of the first treatment was 8 years (median 6 years; SD ± 15; range 1 to 75). The mean follow-up was 88 months. The Sillence classification was used to classify OI. Fifteen patients were classified as Type I; five as Type III and nine as Type IV. A total number of 245 procedures were recorded. Of these, 147 were surgical (pinning; intramedullary nailing and plating) while 98 were conservative (cast, braces and bandages). Bisphosphonate use was a major variable in the study. Clinical charts and radiographic films were analyzed for complications (delayed union, nonunion, malunion, hardware loosening). We recorded 58 complications: 13 in Type I; 28 in Type III and 17 in Type IV OI. The rate of each complication was: 15/245 nonunions (6.1%), 14/245 delayed unions (5.7%), 14/245 malunions (5.7%) and 15/245 hardware loosenings (6.1%). We found no statistically significant differences between surgical and conservative treatments. Type III OI, which is a very crippling form of the disease, was associated with radiographically poorer results than the other types. In our analysis, the two groups were unbalanced and only five patients were treated with bisphosphonates. Nevertheless, bisphosphonate use can be considered a good adjuvant to both the conservative and surgical treatment of OI in order to reduce the rate of complication